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This report contains the collective views of international groups of experts and does not necessarily represent
the decisions or the stated policy of the United Nations Environment Programme, the International Labour
Organization, or the World Health Organization.

Environmental Health Criteria 221

ZINC
First draft prepared by Drs B. Simon-Hettich and A. Wibbertmann, Fraunhofer Institute of Toxicology and
Aerosol Research, Hanover, Germany, Mr D. Wagner, Department of Health and Family Services, Canberra,
Australia, Dr L. Tomaska, Australia New Zealand Food Authority, Canberra, Australia, and Mr H. Malcolm,
Institute of Terrestrial Ecology, Monks Wood, England.

Published under the joint sponsorship of the United Nations Environment Programme, the International
Labour Organization, and the World Health Organization, and produced within the framework of the Inter-
Organization Programme for the Sound Management of Chemicals.

World Health Organization

Geneva, 2001

The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the
United Nations Environment Programme (UNEP), the International Labour Organization (ILO), and the
World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for
assessment of the risk to human health and the environment from exposure to chemicals, through
international peer-review processes, as a prerequisite for the promotion of chemical safety, and to provide
technical assistance in strengthening national capacities for the sound management of chemicals.

The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established
in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO, the United
Nations Industrial Development Organization, the United Nations Institute for Training and Research, and
the Organisation for Economic Co-operation and Development (Participating Organizations), following
recommendations made by the 1992 UN Conference on Environment and Development to strengthen
cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is to promote
coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to
achieve the sound management of chemicals in relation to human health and the environment.

WHO Library Cataloguing-in-Publication Data

Zinc.

(Environmental health criteria ; 221)

1.Zinc - analysis

2.Zinc - toxicity

3.Occupational exposure

4.Environmental exposure

5.Risk assessment I.Series

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ISBN 92 4 157221 3

(NLM Classification: QD 181.Z6)

ISSN 0250-863X

The World Health Organization welcomes requests for permission to reproduce or translate its publications,
in part or in full. Applications and enquiries should be addressed to the Office of Publications, World Health
Organization, Geneva, Switzerland, which will be glad to provide the latest information on any changes
made to the text, plans for new editions, and reprints and translations already available.

©World Health Organization 2001

Publications of the World Health Organization enjoy copyright protection in accordance with the provisions
of Protocol 2 of the Universal Copyright Convention. All rights reserved.

The designations employed and the presentation of the material in this publication do not imply the
expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization
concerning the legal status of any country, territory, city or area or of its authorities, or concerning the
delimitation of its frontiers or boundaries.

The mention of specific companies or of certain manufacturers’ products does not imply that they are
endorsed or recommended by the World Health Organization in preference to others of a similar nature that
are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by
initial capital letters.

CONTENTS
ENVIRONMENTAL HEALTH CRITERIA FOR ZINC

PREAMBLE
ABBREVIATIONS
1. SUMMARY AND CONCLUSIONS
1.1 Identity, and physical and chemical properties
1.2 Analytical methods

1.3 Sources of human and environmental exposure

1.4 Environmental transport, distribution and transformation
1.5 Environmental concentrations
1.5.1 Human intakes
1.6 Kinetics and metabolism in laboratory animals and humans
1.7 Effects on laboratory animals
1.8 Effects on humans
1.9 Effects on other organisms in the laboratory and field

1.10 Conclusions
1.10.1 Human health
1.10.2 Environment
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2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES,

AND ANALYTICAL METHODS
2.1 Identity
2.2 Physical and chemical properties
2.2.1 Zinc metal
2.2.2 Zinc compounds
2.3 Analytical methods

2.3.1 Introduction
2.3.2 Sampling and sample preparation
2.3.3 Separation and concentration
2.3.4 Detection and measurement
3. SOURCES OF HUMAN AND ENVIRONMENTAL
EXPOSURE
3.1 Natural occurrence
3.2 Anthropogenic sources
3.2.1 Production levels and processes
3.2.1.1 Production levels

3.2.1.2 Production processes

3.2.2 Uses
3.2.3 Emissions during production and use
3.2.3.1 Emissions to atmosphere
3.2.3.2 Emissions to aquatic environment

3.2.3.3 Emissions to soil

3.2.4 Emissions during combustion of coal and oil, and refuse
incineration
3.2.5 Zinc releases from diffuse sources

3.2.5.1 Releases from atmospheric zinc corrosion

3.2.5.2 Releases from sacrificial zinc anodes

3.2.5.3 Household zinc emissions

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND
TRANSFORMATION
4.1 Transport and distribution between media

4.1.1 Air

4.1.2 Water and sediment

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4.1.2.1 Fresh water

4.1.2.2 Seawater

4.1.2.3 Wastewater
4.1.2.4 Groundwater

4.1.2.5 Sediment
4.1.3 Soil

4.2 Bioavailability
4.2.1 Factors affecting bioavailability

4.2.2 Techniques for estimation

4.3 Biotransformation

4.3.1 Biodegradation

4.3.2 Bioaccumulation
4.3.2.1 Aquatic organisms

4.3.2.2 Terrestrial organisms

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1 Environmental levels

5.1.1 Air

5.1.2 Precipitation

5.1.3 Water
5.1.3.1 Fresh water

5.1.3.2 Seawater
5.1.4 Soil

5.1.5 Sediments and sewage sludge

5.1.6 Aquatic and terrestrial organisms

5.1.6.1 Aquatic plants and animals

5.1.6.2 Terrestrial plants and animals

5.2 General population exposure

5.2.1 Air
5.2.2 Food

5.2.3 Drinking-water
5.2.4 Miscellaneous exposures

5.3 Occupational levels

5.4 Total human intake from all sources
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5.4.1 General population

5.4.2 Bioavailability in mammalian systems

5.4.3 Occupational exposure

6. KINETICS AND METABOLISM IN MAMMALS

6.1 Absorption

6.1.1 Inhalation
6.1.1.1 Human studies

6.1.1.2 Animal studies

6.1.2 Oral

6.1.2.1 Human studies

6.1.2.2 Animal studies

6.1.3 Dermal

6.1.3.1 Human studies

6.1.3.2 Animal studies

6.2 Distribution
6.3 Excretion

6.4 Biological half-life

6.5 Zinc status and metabolic role in humans

6.5.1 Methods for assessment of zinc status in humans

6.5.1.1 Dietary methods to predict the proportion of the

population at risk of inadequate intakes of dietary zinc

6.5.1.2 Static tests of zinc status

6.5.1.3 Functional tests of zinc status

6.5.1.4 New approaches

6.5.2 Metabolic role

6.5.2.1 Zinc metalloenzymes

6.5.2.2 Metallothionein

6.5.2.3 Other metabolic functions of zinc

6.5.3 Human studies

6.5.3.1 Copper

7. EFFECTS ON LABORATORY MAMMALS AND IN VITRO

TEST SYSTEMS

7.1 Single exposure

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7.1.1 Lethality
7.1.2 Acute studies: summary of key findings

7.2 Short-term exposure

7.2.1 Oral exposure

7.2.2 Inhalation exposure

7.3 Long-term exposure

7.3.1 Oral exposure

7.4 Skin irritation

7.5 Reproductive toxicity, embryotoxicity and teratogenicity
7.6 Mutagenicity and related end-points

7.6.1 In vitro studies

7.6.2 In vivo studies
7.7 Carcinogenicity

7.8 Interactions with other metals

7.8.1 Zinc and copper
7.8.2 Zinc and other metals
7.9 Zinc deficiency in animals

8. EFFECTS ON HUMANS
8.1 Human dietary zinc requirements
8.1.1 Estimation of zinc requirements

8.2 Zinc deficiency

8.2.1 Clinical manifestations
8.2.2 Brain function
8.2.3 Immune function

8.2.4 Growth
8.2.5 Dermal effects
8.2.6 Reproduction

8.2.7 Carcinogenicity
8.3 Zinc toxicity: general population
8.3.1 Poisoning incidents
8.3.2 Dermal effects

8.3.3 Immune function

8.3.4 Reproduction
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8.3.5 Zinc-induced copper deficiency

8.3.5.1 Controlled human studies

8.3.5.2 Case reports
8.3.6 Serum lipids and cardiovascular disorders
8.4 Occupational exposure

8.4.1 Acute toxicity

8.4.2 Short-term exposure
8.4.3 Long-term exposure
8.4.4 Epidemiological studies

8.5 Subpopulations at special risk

8.5.1 Dialysis patients
8.5.2 People with diabetes

8.5.3 Hospital patients

8.5.4 Other populations
8.6 Interactions
8.6.1 Copper

8.6.2 Iron
8.6.3 Calcium
9. EFFECTS ON OTHER ORGANISMS IN THE
LABORATORY AND FIELD
9.1 Laboratory experiments
9.1.1 Microorganisms
9.1.1.1 Water

9.1.1.2 Soil
9.1.2 Aquatic organisms
9.1.2.1 Plants
9.1.2.2 Invertebrates and vertebrates

9.1.2.3 Effects on communities

9.1.3 Terrestrial organisms
9.1.3.1 Plants

9.1.3.2 Invertebrates
9.1.3.3 Vertebrates
9.2 Tolerance to zinc
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9.3 Interactions with other metals

10. EVALUATION OF HUMAN HEALTH RISKS AND

EFFECTS ON THE ENVIRONMENT
10.1 Homeostatic model

10.2 Evaluation of risks to human health

10.2.1 Exposure of general population
10.2.2 Occupational exposure
10.2.3 Risks of zinc deficiency

10.2.4 Risks of zinc excess

10.3 Evaluation of effects on the environment
10.3.1 Environmental risk assessment

10.3.2 Components of risk assessment for essential elements

10.3.3 Environmental risk assessment for zinc
10.3.3.1 Environmental concentrations
10.3.3.2 Overview of toxicity data

11. CONCLUSIONS AND RECOMMENDATIONS FOR

PROTECTION OF HUMAN HEALTH AND THE
ENVIRONMENT
11.1 Human health

11.2 Environment
12. RECOMMENDATIONS FOR FURTHER RESEARCH
12.1 Zinc status
12.2 Functional indices of zinc status

12.3 Interactions with other trace elements

12.4 Supplementation
12.5 Occupational medicine

12.6 The molecular mechanism

12.7 Environment
REFERENCES
RÉSUMÉ ET CONCLUSIONS

RESUMEN Y CONCLUSIONES

NOTE TO READERS OF THE CRITERIA

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MONOGRAPHS

Every effort has been made to present information in the criteria monographs as accurately as possible
without unduly delaying their publication. In the interest of all users of the Environmental Health Criteria
monographs, readers are requested to communicate any errors that may have occurred to the Director of the
International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland, in order that
they may be included in corrigenda.

***

A detailed data profile and a legal file can be obtained from the International Register of Potentially Toxic
Chemicals, Case postale 356, 1219 Châtelaine, Geneva, Switzerland (telephone no. + 41 22 - 9799111, fax
no. + 41 22 - 7973460, E-mail irptc@unep.ch).

***

This publication was made possible by grant number 5 U01 ES02617-15 from the National Institute of
Environmental Health Sciences, National Institutes of Health, USA, and by financial support from the
European Commission.

Environmental Health Criteria

PREAMBLE

Objectives

In 1973 the WHO Environmental Health Criteria Programme was initiated with the following objectives:

(i) to assess information on the relationship between exposure to environmental pollutants

and human health, and to provide guidelines for setting exposure limits;
(ii) to identify new or potential pollutants;
(iii) to identify gaps in knowledge concerning the health effects of pollutants;

(iv) to promote the harmonization of toxicological and epidemiological methods in order to

have internationally comparable results.

The first Environmental Health Criteria (EHC) monograph, on mercury, was published in 1976 and since that
time an ever-increasing number of assessments of chemicals and of physical effects have been produced. In
addition, many EHC monographs have been devoted to evaluating toxicological methodology, e.g. for
genetic, neurotoxic, teratogenic and nephrotoxic effects. Other publications have been concerned with
epidemiological guidelines, evaluation of short-term tests for carcinogens, biomarkers, effects on the elderly
and so forth.

Since its inauguration the EHC Programme has widened its scope, and the importance of environmental
effects, in addition to health effects, has been increasingly emphasized in the total evaluation of chemicals.

The original impetus for the Programme came from World Health Assembly resolutions and the
recommendations of the 1972 UN Conference on the Human Environment. Subsequently the work became
an integral part of the International Programme on Chemical Safety (IPCS), a cooperative programme of
UNEP, ILO and WHO. In this manner, with the strong support of the new partners, the importance of
occupational health and environmental effects was fully recognized. The EHC monographs have become
widely established, used and recognized throughout the world.

The recommendations of the 1992 UN Conference on Environment and Development and the subsequent
establishment of the Intergovernmental Forum on Chemical Safety with the priorities for action in the six
programme areas of Chapter 19, Agenda 21, all lend further weight to the need for EHC assessments of the
risks of chemicals.
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Scope

The criteria monographs are intended to provide critical reviews on the effect on human health and the
environment of chemicals and of combinations of chemicals and physical and biological agents. As such,
they include and review studies that are of direct relevance for the evaluation. However, they do not describe
every study carried out. Worldwide data are used and are quoted from original studies, not from abstracts or
reviews. Both published and unpublished reports are considered and it is incumbent on the authors to assess
all the articles cited in the references. Preference is always given to published data. Unpublished data are
used only when relevant published data are absent or when they are pivotal to the risk assessment. A detailed
policy statement is available that describes the procedures used for unpublished proprietary data so that this
information can be used in the evaluation without compromising its confidential nature (WHO (1999)
Guidelines for the Preparation of Environmental Health Criteria. PCS/99.9, Geneva, World Health
Organization).

In the evaluation of human health risks, sound human data, whenever available, are preferred to animal data.
Animal and in vitro studies provide support and are used mainly to supply evidence missing from human
studies. It is mandatory that research on human subjects is conducted in full accord with ethical principles,
including the provisions of the Helsinki Declaration.

The EHC monographs are intended to assist national and international authorities in making risk assessments
and subsequent risk management decisions. They represent a thorough evaluation of risks and are not, in any
sense, recommendations for regulation or standard setting. These latter are the exclusive purview of national
and regional governments.

Content

The layout of EHC monographs for chemicals is outlined below.

• Summary – a review of the salient facts and the risk evaluation of the chemical

• Identity – physical and chemical properties, analytical methods

• Sources of exposure

• Environmental transport, distribution and transformation

• Environmental levels and human exposure

• Kinetics and metabolism in laboratory animals and humans

• Effects on laboratory mammals and in vitro test systems

• Effects on humans

• Effects on other organisms in the laboratory and field

• Evaluation of human health risks and effects on the environment

• Conclusions and recommendations for protection of human health and the environment

• Further research

• Previous evaluations by international bodies, e.g. IARC, JECFA, JMPR

Selection of chemicals

Since the inception of the EHC Programme, the IPCS has organized meetings of scientists to establish lists of
priority chemicals for subsequent evaluation. Such meetings have been held in Ispra, Italy, 1980; Oxford,
United Kingdom, 1984; Berlin, Germany, 1987; and North Carolina, USA, 1995. The selection of chemicals
has been based on the following criteria: the existence of scientific evidence that the substance presents a
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hazard to human health and/or the environment; the possible use, persistence, accumulation or degradation of
the substance shows that there may be significant human or environmental exposure; the size and nature of
populations at risk (both human and other species) and risks for environment; international concern, i.e. the
substance is of major interest to several countries; adequate data on the hazards are available.

If an EHC monograph is proposed for a chemical not on the priority list, the IPCS Secretariat consults with
the Cooperating Organizations and all the Participating Institutions before embarking on the preparation of
the monograph.

Procedures

The order of procedures that result in the publication of an EHC monograph is shown in the flow chart on p.
xv. A designated staff member of IPCS, responsible for the scientific quality of the document, serves as
Responsible Officer (RO). The IPCS Editor is responsible for layout and language. The first draft, prepared
by consultants or, more usually, staff from an IPCS Participating Institution, is based initially on data
provided from the International Register of Potentially Toxic Chemicals, and reference data bases such as
Medline and Toxline.

The draft document, when received by the RO, may require an initial review by a small panel of experts to
determine its scientific quality and objectivity. Once the RO finds the document acceptable as a first draft, it
is distributed, in its unedited form, to well over 150 EHC contact points throughout the world who are asked
to comment on its completeness and accuracy and, where necessary, provide additional material. The contact
points, usually designated by governments, may be Participating Institutions, IPCS Focal Points, or
individual scientists known for their particular expertise. Generally some four months are allowed before the
comments are considered by the RO and author(s). A second draft incorporating comments received and
approved by the Director, IPCS, is then distributed to Task Group members, who carry out the peer review, at
least six weeks before their meeting.

The Task Group members serve as individual scientists, not as representatives of any organization,
government or industry. Their function is to evaluate the accuracy, significance and relevance of the
information in the document and to assess the health and environmental risks from exposure to the chemical.
A summary and recommendations for further research and improved safety aspects are also required. The
composition of the Task Group is dictated by the range of expertise required for the subject of the meeting
and by the need for a balanced geographical distribution.

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The three cooperating organizations of the IPCS recognize the important role played by nongovernmental
organizations. Representatives from relevant national and international associations may be invited to join
the Task Group as observers. Although observers may provide a valuable contribution to the process, they
can only speak at the invitation of the Chairperson. Observers do not participate in the final evaluation of the
chemical; this is the sole responsibility of the Task Group members. When the Task Group considers it to be
appropriate, it may meet in camera.

All individuals who as authors, consultants or advisers participate in the preparation of the EHC monograph
must, in addition to serving in their personal capacity as scientists, inform the RO if at any time a conflict of
interest, whether actual or potential, could be perceived in their work. They are required to sign a conflict of
interest statement. Such a procedure ensures the transparency and probity of the process.

When the Task Group has completed its review and the RO is satisfied as to the scientific correctness and
completeness of the document, it then goes for language editing, reference checking and preparation of
camera-ready copy. After approval by the Director, IPCS, the monograph is submitted to the WHO Office of
Publications for printing. At this time a copy of the final draft is sent to the Chairperson and Rapporteur of
the Task Group to check for any errors.

It is accepted that the following criteria should initiate the updating of an EHC monograph: new data are
available that would substantially change the evaluation; there is public concern for health or environmental
effects of the agent because of greater exposure; an appreciable time period has elapsed since the last
evaluation.

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All Participating Institutions are informed, through the EHC progress report, of the authors and institutions
proposed for the drafting of the documents. A comprehensive file of all comments received on drafts of each
EHC monograph is maintained and is available on request. The Chairpersons of Task Groups are briefed
before each meeting on their role and responsibility in ensuring that these rules are followed.

WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ZINC

Members

Dr H.E. Allen, Department of Civil and Environmental Engineering, University of Delaware, Newark,
Delaware, USA

Dr G. Batley, CSIRO Centre for Advanced Analytical Chemistry, Division of Coal and Energy Technology,
Lucas Heights Research Laboratories, Menai, Australia

Dr G. Cherian, Department of Pathology, University of Western Ontario, London, Ontario, Canada (Vice-
Chairman)

Dr G. Dixon, Department of Biology, University of Waterloo, Waterloo, Ontario, Canada

Professor W.H.O. Ernst, Vrije University, Amsterdam, the Netherlands

Professor R. Gibson, Department of Human Nutrition, University of Otago, Dunedin, New Zealand

Dr C.R. Janssen, University of Ghent, Laboratory for Biological Research in Aquatic Pollution, Ghent,
Belgium

Dr L.M. Klevay, US Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand
Forks, North Dakota, USA

Mr H. Malcom, Institute of Terrestrial Ecology, Monks Wood, Huntingdon, Cambridgeshire, United

Kingdom (Co-Rapporteur)

Dr L. Maltby, Department of Animal and Plant Sciences, School of Biological Sciences, University of
Sheffield, Sheffield, United Kingdom

Professor M.R. Moore, University of Queensland, National Research Centre for Environmental Toxicology,
Coopers Plains, Brisbane, Australia

Dr G. Nordberg, Department of Occupational and Environmental Medicine, Environmental Medicine Unit,

Umea University, Umea, Sweden

Dr H.H. Sandstead, University of Texas School of Medicine, Department of Preventive Medicine and
Community Health, Galveston, Texas, USA

Dr B. Simon-Hettich, Fraunhofer Institute of Toxicology and Aerosol Research, Hanover, Germany

Dr J.H.M. Temmink, Wageningen Agricultural University, Department of Toxicology, Wageningen,

Netherlands (Chairman)

Dr J. Vangronsveld, Limburgs University Centre, University Campus, Diepenbeek, Belgium

Dr D. Wagner, Chemicals Safety Unit, Human Services and Health, Canberra, Australia (Co-Rapporteur)

Observers/Representatives

Dr K. Bentley, Commonwealth Department of Health and Family Services, Canberra, Australia

Dr C. Boreiko, International Lead Zinc Research Organization, Inc., Research Triangle Park, North Carolina,
USA
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Dr P. Chapman, EVS Environment Consultants, Ltd., North Vancouver, Canada (Representing the
International Lead Zinc Research Organization)

Dr T.M. Florence, Centre for Environmental Health Sciences, Oyster Bay, New South Wales, Australia

Dr T.V. O’Donnell, University of Otago, Wellington South, New Zealand

Mr D. Sinclair, Pasminco Ltd., Melbourne, Victoria, Australia

Dr L. Tomaska, Australia New Zealand Food Authority, Canberra, Australian Capital Territory, Australia

Dr F. Van Assche, European Zinc Institute, Brussels, Belgium

Dr W.J.M. Van Tilborg, Rozendaal, Netherlands (Representing the European Chemical Industry Ecology and
Toxicology Centre)

Mr H. Waeterschoot, Union Minière, Brussels, Belgium (Representing the International Zinc Association)

Secretariat

Dr G.C. Becking, International Programme on Chemical Safety, World Health Organization, Interregional
Research Unit, Research Triangle Park, North Carolina, USA (Secretary)

Mr P. Callan, Environmental Health Policy, Department of Health and Family Services, Canberra, Australian
Capital Territory, Australia

Dr A. Langley, Hazardous Substances Section, South Australia Health Commission, Adelaide, South
Australia, Australia

Mr S. Mangas, Hazardous Substances Section, South Australian Health Commission, Adelaide, South
Australia, Australia

WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ZINC

A WHO Task Group on Environmental Health Criteria for Zinc met in McLaren Vale, Australia, from 16 to
20 September 1996. The meeting was sponsored by a consortium of Australian Commonwealth and State
Governments through a national steering committee chaired by Dr K. Bentley, Commonwealth Department
of Health and Family Services, Canberra. The meeting was co-hosted and organized by the South Australian
Health Commission, Dr A. Langley and Mr S. Mangas being responsible for the arrangements. Participants
were welcomed on behalf of the host organizations by Dr I. Calder, Director, Environmental Health Branch,
South Australian Health Commission. Dr G.C. Becking, IPCS, opened the meeting and, on behalf of the
Director, IPCS and the three cooperating organizations (UNEP/ILO/WHO), thanked the Australian
Commonwealth and State Governments for their funding of the Task Group as well as their financial and in-
kind support for the preparation of the first draft of the Environmental Health Criteria for Zinc. He thanked
the staff of the Hazardous Substances Section, South Australian Health Commission for their excellent work
in organizing the Task Group. The Task Group reviewed and revised the draft criteria monograph, and made
an evaluation of the risks to human health and the environment from exposure to zinc.

The first draft of this monograph was prepared by Dr B. Simon-Hettich and Dr A. Wibbertmann, Fraunhofer
Institute of Toxicology and Aerosol Research, Hanover, Germany; Mr D. Wagner, Commonwealth
Department of Health and Family Services, Canberra, Australia; Dr L. Tomaska, Australia New Zealand
Food Authority (ANZFA), Canberra, Australia, and Mr H. Malcolm, Institute of Terrestrial Ecology, Monks
Wood, United Kingdom. The draft reviewed by the Task Group, incorporating the comments received from
the IPCS Contact Points, was prepared through the cooperative efforts of the Commonwealth Department of
Health and Family Services, ANZFA, Institute of Terrestrial Ecology, and the Secretariat.

Dr G.C. Becking (IPCS Central Unit, Interregional Research Unit) and Ms S.M. Poole (Birmingham,
England) were responsible for the overall scientific content and technical editing, respectively, of this
monograph.

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The efforts of all who helped in the preparation and finalization of the monograph are gratefully
acknowledged.

ABBREVIATIONS

AAS atomic absorption spectroscopy

AES atomic emission spectroscopy

ASV anodic stripping voltametry

BAF bioaccumulation factor

BCF bioconcentration factor

CRIP cysteine-rich intestinal protein

CSV cathodic stripping voltametry

DNA deoxyribonucleic acid

DP-ASV differential pulse-anodic stripping voltametry

DTPA diethylenetriamine pentaacetic acid

dw dry weight
Eh redox potential

EC50 effective concentration, affecting 50% of test organisms

EDTA ethylenediaminetetraacetic acid

EPA Environmental Protection Agency (USA)

ESOD Cu, Zn erythrocyte superoxide dismutase

FAAS flame atomic absorption spectroscopy

GF-AAS graphite furnace atomic absorption spectroscopy

HDL high-density lipoprotein

ICP-AES inductively-coupled plasma-atomic emission spectroscopy

ICP-MS inductively-coupled plasma-mass spectrometry

Ig immunoglobulin
IGF insulin-like growth factor

LC50 lethal concentration killing 50% of test organisms

LDL low-density lipoprotein

LOEC lowest-observed-effective concentration

LT(50) lethal time(50) for specified concentration of chemical killing 50% of test
organisms
MS mass spectrometry

NAA neutron activation analysis

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NHANES National Health and Nutrition Examination Survey (USA)

NOEC no-observed-effect concentration

NOEL no-observed-effect level

RNA ribonucleic acid

SEM standard error of the mean

TFIIIA transcription factor IIIA

UV ultraviolet
XRF X-ray fluorescence

1. SUMMARY AND CONCLUSIONS

1.1 Identity, and physical and chemical properties
Zinc metal does not occur in the natural environment. It is present only in the divalent state Zn(II). Ionic zinc
is subject to solvation, and its solubility is pH and anion dependent. Zinc is a transition element and is able to
form complexes with a variety of organic ligands. Organometallic zinc compounds do not exist in the
environment.

1.2 Analytical methods

Because zinc is ubiquitous in the environment, special care is required during sampling, sample preparation
and analysis to avoid sample contamination. Sample preparation for solid samples typically involves
microwave-assisted mineralization with concentrated acids. For water samples, solvent extraction in the
presence of complexing agents and chelating resin separation have been used to preconcentrate zinc.

Inductively-coupled plasma atomic emission spectrometry (ICP-AES), graphite furnace atomic absorption
spectrometry (GF-AAS), anodic stripping voltammetry (ASV) and ICP-mass spectrometry (ICP-MS) are
commonly used instrumental techniques for zinc determination. For low-level analyses, GF-AAS, ASV and
ICP-MS are preferred.

With special care, zinc concentrations as low as 0.006 µg/litre and 0.01 mg/kg are detectable in water and
solid samples, respectively.

Speciation analyses in water require the application of separation techniques with any of the above methods
or use of the labile-bound discrimination offered by ASV.

1.3 Sources of human and environmental exposure

Most rocks and many minerals contain zinc in varying amounts. Commercially, sphalerite (ZnS) is the most
important ore mineral and the principal source of the metal for the zinc industry. In 1994, world metal
production of zinc was 7 089 000 tonnes and zinc metal consumption amounted to 6 895 000 tonnes.

Zinc is widely used as a protective coating of other metals, in dye casting and the construction industry, and
for alloys. Inorganic zinc compounds have various applications, e.g., for automotive equipment, storage and
dry cell batteries, and dental, medical and household applications. Organo-zinc compounds are used as
fungicides, topical antibiotics and lubricants.

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Zinc becomes malleable when heated to 100–150 °C and is then readily machined into shapes. It is capable
of reducing most other metal states and is therefore used as an electrode in dry cells and in hydrometallurgy.

The largest natural emission of zinc to water results from erosion. Natural inputs to air are mainly due to
igneous emissions and forest fires. Anthropogenic and natural sources are of a similar magnitude. The main
anthropogenic sources of zinc are mining, zinc production facilities, iron and steel production, corrosion of
galvanized structures, coal and fuel combustion, waste disposal and incineration, and the use of zinc-
containing fertilizers and pesticides.

1.4 Environmental transport, distribution and transformation

Zinc in the atmosphere is primarily bound to aerosol particles. The size of particle is determined by the
source of zinc emission. A major proportion of the zinc released from industrial processes is adsorbed on
particles that are small enough to be in the respirable range.

The transport and distribution of atmospheric zinc vary according to the size of particles and the properties of
the zinc compounds concerned. Zinc is removed from the atmosphere by dry and wet deposition. Zinc
adsorbed on particles with low densities and diameters can be transported over long distances.

The distribution and transport of zinc in water, sediment and soil are dependent upon the species of zinc
present and the characteristics of the environment. The solubility of zinc is primarily determined by pH. At
acidic pH values, zinc may be present in the aqueous phase in its ionic form. Zinc may precipitate at pH
values greater than 8.0. It may also form stable organic complexes, for example, with humic and fulvic acids.
The formation of such complexes can increase the mobility and/or solubility of zinc. Zinc is unlikely to be
leached from soil owing to its adsorption on clay and organic matter. Acidic soils and sandy soils with a low
organic content have a reduced capacity for zinc absorption.

Zinc is an essential element and in vivo levels are therefore regulated by most organisms. Zinc is not
biomagnified. The absorption of zinc by aquatic animals tends to be from water rather than food. Only
dissolved zinc tends to be bioavailable, and bioavailability depends on the physical and chemical
characteristics of the environment and biological processes. Consequently, environmental assessment must
be conducted on a site-specific basis.

1.5 Environmental concentrations

Zinc occurs ubiquitously in environmental and biological samples. Concentrations in soil sediments and
fresh water are strongly determined by local geological and anthropogenic influences and thus vary
substantially. Natural background total zinc concentrations are usually < 0.1–50 µg/litre in fresh water,
0.002- 0.1 µg/litre in seawater, 10–300 mg/kg dry weight (dw) in soils, up to 100 mg/kg dw in sediments,
and up to 300 ng/m3 in air. Increased levels can be attributed to natural occurrence of zinc-enriched ores, to
anthropogenic sources or to abiotic and biotic processes. In anthropogenically contaminated samples, zinc
levels of up to 4 mg/litre in water, 35 g/kg in soil, 15 µg/litre in estuarine water, and 8 µg/m3 in air are found.

Zinc concentrations in representative organisms during exposure to water-borne zinc are in the range 200–
2000 mg/kg.

Concentrations in plants and animals are higher near anthropogenic point sources of zinc contamination.
Interspecies variations in zinc content are considerable; intraspecies levels vary, for instance, with life stage,
sex, season, diet and age. Normal levels of zinc in most crops and pastures are in the range 10–100 mg/kg
dw. Some plants are zinc accumulators, but the extent of the accumulation in plant tissues varies with soil
and plant properties.

Only negligible quantities of zinc are inhaled from ambient air, but a broad range of exposures to dusts and
fumes of zinc and zinc compounds is possible in occupational settings.

1.5.1 Human intakes

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Estimated ranges of daily dietary intakes of total zinc are 5.6- 10 mg/day for infants and children aged 2
months–11 years, 12.3–13.0 mg/day for children aged 12–19 years, and 8.8- 14.4 mg/day for adults aged
20–50 years. Mean daily zinc intake from drinking-water is estimated to be < 0.2 mg/day.

Dietary reference values for zinc vary according to the dietary pattern of the country, assumptions on the
bioavailability of dietary zinc, and age, sex and physiological status. Dietary reference values range from 3.3
to 5.6 mg/day for infants aged 0–12 months, 3.8 to 10.0 mg/day for children aged 1–10 years, and 8.7 to 15
mg/day for adolescents aged 11–18 years. Adult values range from 6.7 to 15 mg/day for those aged 19–50
years, 7.3 to 15 mg/day during pregnancy, assuming diets of moderate zinc availability, and 11.7 to 19
mg/day during lactation, depending on the stage.

1.6 Kinetics and metabolism in laboratory animals and humans

For inhalation studies (nose only) in guinea-pigs, rats and rabbits, retention values of 5–20% in the lung were
observed after exposure to zinc oxide aerosols at a concentration of 5–12 mg/m3 for 3–6 h. The intestinal
absorption of zinc is controlled by a homeostatic mechanism which is not fully understood but is mainly
controlled by pancreatic and intestinal secretion and faecal excretion. Homeostasis may involve metal-
binding proteins such as metallothionein and cysteine-rich intestinal protein. Other unknown mechanisms
may also exist. The uptake from intestinal mucosa may involve both active and passive transport processes.
In animals, absorption can vary in the range 10–40% depending on nutritional status and other ligands in the
diet. Dermal absorption of zinc from zinc oxide and zinc chloride can occur and is increased in zinc
deficiency. Absorbed zinc is mainly deposited in muscle, bone, liver, pancreas, kidney and other organs. The
biological half-life of zinc is about 4–50 days in rats, depending on the administered dose, and about 280
days in humans.

1.7 Effects on laboratory animals

Acute oral toxicity in rodents exposed to zinc is low, with LD50 values in the range 30–600 mg/kg body
weight, depending on the zinc salt administered. Acute effects in rodents following inhalation or intratracheal
instillation of zinc compounds include respiratory distress, pulmonary oedema and infiltration of the lung by
leukocytes.

Toxic effects of zinc in rodents following short-term oral exposure include weakness, anorexia, anaemia,
diminished growth, loss of hair and lowered food utilization, as well as changes in the levels of liver and
serum enzymes, morphological and enzymatic changes in the brain, and histological and functional changes
in the kidney. The level at which zinc produces no adverse symptoms in rats has been set at about 160 mg/kg
body weight. Pancreatic changes were observed in calves exposed to high levels of dietary zinc. Short-term
inhalation exposure of guinea-pigs and rats to zinc oxide at concentrations of > 5.9 mg/m3 resulted in
inflammation and pulmonary damage.

Long-term oral exposure to zinc indicated the target organs of toxicity to be the haematopoietic system in
rats, ferrets and rabbits; the kidney in rats and ferrets; and the pancreas in mice and ferrets. The no-observed-
effect level (NOEL) with respect to growth and anaemia for zinc sulfate in the diet was reported to be < 100
mg/kg in rats. Increases in zinc concentrations in the bodies of experimental animals exposed to zinc are
accompanied by reduced levels of copper, suggesting that some of the signs of toxicity ascribed to exposure
to excess levels of zinc may be caused by zinc-induced copper deficiency. Moreover, studies have shown that
exposure to zinc alters the levels of other essential metals, including iron, in the bodies of exposed animals.
Some signs of toxicity observed in animals exposed to high levels of zinc can be alleviated by the addition of
copper or iron to the diet.

Very high levels of zinc are toxic to pregnant mice and hamsters. Rats exposed to zinc at 0.5% and 1% in the
diet for 5 months were unable to conceive until the zinc was withdrawn. High levels of zinc in the diet (2000
mg/kg) were also associated with an increase in resorptions and stillbirths in mice and rats; a finding also
observed in sheep and hamsters. Resorptions were increased in one study in which rats were exposed,
throughout the entire gestation period, to zinc at doses as low as 150 mg/kg. In another rat study, however, no
deleterious effects on the developing fetus were observed at doses of 500 mg/kg. Exposure of rats to dietary
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zinc levels of 4000 mg/kg post coitus was shown to interfere with the implantation of ova. Elevation of zinc
levels in rat pups exposed to zinc was accompanied by reductions in the levels of copper and iron.

Genotoxicity studies have been conducted in a variety of systems. Most of the findings have been negative,
but a few positive results have been reported.

Zinc deficiency in animals is characterized by reduction in growth, cell replication, adverse reproductive
effects, adverse developmental effects, which persist after weaning, and reduced immunoresponsiveness.

1.8 Effects on humans

Poisoning incidents with symptoms of gastrointestinal distress, nausea and diarrhoea have been reported
after a single or short-term exposure to concentrations of zinc in water or beverages of 1000- 2500 mg/litre.
Similar symptoms, occasionally leading to death, have been reported following the inadvertent intravenous
administration of large doses of zinc. Kidney dialysis patients exposed to zinc through the use of water stored
in galvanized units have developed symptoms of zinc toxicity that were reversible when the water was
subjected to activated carbon filtration.

A disproportionate intake of zinc in relation to copper has been shown to induce copper deficiency in
humans, resulting in increased copper requirements, increased copper excretion and impaired copper status.
Pharmacological intakes of zinc have been associated with effects ranging from leukopenia and/or
hypochromic microcytic anaemia to decreases in serum high-density lipoprotein concentrations. These
conditions were reversible upon discontinuation of zinc therapy together with copper supplementation.

The human health effects associated with zinc deficiency are numerous, and include neurosensory changes,
oligospermia, impaired neuropsychological functions, growth retardation, delayed wound healing, immune
disorders and dermatitis. These conditions are generally reversible when corrected by zinc supplementation.

There is no single, specific and sensitive biochemical index of zinc status. The most reliable method for
detecting deficiency is to show a positive response to zinc supplementation in controlled double-blind trials
(in the absence of other limiting nutrient deficiencies). This approach is time-consuming and often
impractical, however, and determination of a combination of dietary, biochemical and functional
physiological indices is generally preferred. Several concordant abnormal values are more reliable than a
single aberrant value in diagnosing a zinc deficiency state. The inclusion of functional physiological indices,
such as growth, taste acuity and dark adaptation with a biochemical test (e.g., plasma or hair zinc
concentration) allows the extent of the functional consequences of the zinc deficiency state to be assessed.

Inhalation exposure to zinc chloride following the military use of "smoke bombs" has resulted in effects that
include interstitial oedema, interstitial fibrosis, pneumonitis, bronchial mucosal oedema, ulceration and even
death under extreme exposure conditions in confined spaces. These effects are possibly attributable to the
hygroscopic and astringent nature of the particles released by such devices.

Occupational exposure to finely dispersed particulate matter formed when certain metals, including zinc, are
volatilized can lead to an acute illness termed "metal-fume fever", characterized by a variety of symptoms
including fever, chills, dyspnoea, nausea and fatigue. The condition is generally severe but transient, and
individuals tend to develop tolerance. Exposure of volunteers to zinc concentrations of 77–150 mg/m3 for
15–30 min gave rise to symptoms in some of the subjects, a marked dose-related inflammatory response with
increased polynuclear lymphocytes in broncheoalveolar lavage fluid, and a marked increase in cytokines.
Occupational asthma has been reported among those working with soft solder fluxes, but the evidence was
not sufficient to indicate a causative relationship. A rare case suggesting such a relationship has been
diagnosed recently in a worker from a hot-dip (zinc) galvanizing plant.

1.9 Effects on other organisms in the laboratory and field

Zinc is important in membrane stability, in over 300 enzymes, and in the metabolism of proteins and nucleic
acids. The adverse effects of zinc must be balanced against its essentiality. Zinc deficiency has been reported
in a wide variety of cultivated plants and animals, with severe effects on all stages of reproduction, growth
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and tissue proliferation. Zinc deficiencies in various crops have resulted in large crop losses worldwide. Zinc
deficiency is rare in aquatic organisms in the environment, but can be induced under experimental
conditions.

The toxicity of zinc can be influenced by both biotic and abiotic factors, such as organism age and size, prior
exposure, water hardness, pH, dissolved organic carbon and temperature. The integration of environmental
chemistry and toxicology has allowed a better prediction of the effects on organisms in the environment. This
has led to the now accepted view that the total concentration of an essential element such as zinc in an
environmental compartment is not, taken alone, a good predictor of its bioavailability.

Acute toxicity values of dissolved zinc to freshwater invertebrates range from 0.07 mg/litre for a water flea
to 575 mg/litre for an isopod. Acute toxicity values for marine invertebrates range from 0.097 mg/litre for a
mysid to 11.3 mg/litre for a grass shrimp. Acutely lethal concentrations for freshwater fish are in the range
0.066–2.6 mg/litre; the range for marine fish is 0.19–17.66 mg/litre.

Zinc has been shown to exert adverse reproductive, biochemical, physiological and behavioural effects on a
variety of aquatic organisms. Zinc concentrations of > 20 µg/litre have been shown to have adverse effects
on aquatic organisms. However, the toxicity of zinc to such organisms is influenced by many factors, such as
the temperature, hardness and pH of the water, and previous zinc exposure.

Zinc toxicity in plants generally causes disturbances in metabolism, which are different from those occurring
in zinc deficiency. The critical leaf tissue concentration of zinc for an effect on growth in most species is in
the range 200–300 mg/kg dw.

Field studies have revealed adverse effects on aquatic invertebrates, fish and terrestrial plants close to
sources of zinc contamination. Zinc tolerances in terrestrial plants, algae, microorganisms and invertebrates
have developed in the vicinity of areas with elevated zinc concentrations.

1.10 Conclusions
1.10.1 Human health

• There is a decreasing trend in anthropogenic zinc emissions.

• Many pre-1980 environmental samples, in particular in water samples, may have been
subject to contamination with zinc during sampling and analysis and, for this reason, zinc
concentration data for such samples should be viewed with extreme caution.
• In countries where staple diets are based on unrefined cereals and legumes, and intakes of
flesh foods are low, dietary strategies should be developed to improve the content and
bioavailability of zinc.
• Preparations intended to increase the zinc intake above that provided by the diet should not
contain zinc levels that exceed dietary reference values, and should contain sufficient
copper to ensure a ratio of zinc to copper of approximately 7, as is found in human milk.

• There is a need for better documentation of actual exposures to zinc oxide fume in
occupational settings. Workplace concentrations should not result in exposure levels as high
as those known to have given rise to inflammatory responses in the lungs of volunteers.

• The essential nature of zinc, together with its relatively low toxicity in humans and the
limited sources of human exposure, suggests that normal, healthy individuals not exposed to
zinc in the workplace are at potentially greater risk from the adverse effects associated with
zinc deficiency than from those associated with normal environmental exposure to zinc.

1.10.2 Environment

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• Zinc is an essential element in the environment. The possibility exists both for a deficiency
and for an excess of this metal. For this reason it is important that regulatory criteria for
zinc, while protecting against toxicity, are not set so low as to drive zinc levels into the
deficiency area.
• There are differences in the responses of organisms to deficiency and excess.

• Zinc bioavailability is affected by biotic and abiotic factors, for instance: organism age and
size, prior history of exposure, water hardness, pH, dissolved organic carbon and
temperature.

• The total concentration of an essential element such as zinc, alone, is not a good predictor
of its bioavailability or toxicity.

• There is a range of optimum concentrations for essential elements such as zinc.

• The toxicity of zinc will depend on environmental conditions and habitat types, thus any
risk assessment of the potential effects of zinc on organisms must take into account local
environmental conditions.

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES,

AND ANALYTICAL METHODS
Zinc is the twenty-fifth most abundant element. It is widely found in nature and makes up 0.02% by weight
of the earth’s crust (Budavari, 1989). Zinc normally appears dull grey owing to coating with an oxide or
basic carbonate. It is extremely rare to find zinc metal free in nature (Beliles, 1994).

Some zinc compounds, synonyms and formulae are given in Table 1.

Table 1. Chemical names, synonyms and formulae of elemental zinc and zinc compounds

Chemical name CAS registry number Formula Synonyms

Zinc 7440-66-6 Zn -

Zinc acetate 557-34-6 Zn(C2H3O2)2 -

Zinc arsenite 10326-24-6 Zn(AsO2)2 zinc meta-arsenite,

ZMA

Zinc bromide 7699-45-8 ZnBr2 -

Zinc carbonate 3486-35-9 ZnCO3 -

Zinc chloride 7646-85-7 ZnCl2 butter of zinc

Zinc cyanide 557-21-1 Zn(CN)2 -

Zinc diethyldithiocarbamate 14324-55-1 Zn[SC(S)N(C2H5)2]2 -

Zinc fluoride 7783-49-5 ZnF2 -

Zinc hexafluorosilicate 16871-71-9 ZnSiF6.6H2O zinc silicofluoride; zinc

fluosilicate

Zinc iodide 10139-47-6 ZnI2 -

Zi l t Z (C H O )
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Zinc laurate - Zn(C12H33O2)2 -

Zinc nitrate 7779-88-6 Zn(NO3)2 -

Zinc oleate 557-07-3 Zn(C17H33COO)2 -

Zinc oxide 1314-13-2 ZnO Chinese white; zinc

white; flowers of zinc;
philosopher's wool

Zinc permanganate 23414-72-4 Zn(MnO4)2.6H2O

Zinc peroxide 1314-22-3 ZnO2 zinc dioxide; zinc

superoxide; ZPO

Zinc-1,4-phenolsulfonate 127-82-2 Zn (SO3C6H4OH)2.8H2O p-

hydroxybenzenesulfonic
acid zinc salt; zinc
sulfophenate; zinc
sulfocarbolate

Zinc phosphate 7779-90-0 Zn3(PO4)2 zinc orthophosphate;

zinc phosphate, tribasic

Zinc phosphide 1314-84-7 Zn3P2 -

Zinc silicate 13597-65-4 Zn2SiO4 zinc orthosilicate

Zinc sulfate 7733-02-0 ZnSO4.7H2O white vitriol; white

copperas; zinc vitriol

Zinc sulfide 1314-98-3 ZnS wurtzite; sphalerite;

zinc blende

Zinc telluride 1315-11-3 ZnTe -

Zinc thiocyanate 557-42-6 Zn(SCN)2 zinc thodanide; zinc

sulfocyanate

Zinc dimethyldithiocarbamate 137-30-4 Zn(SCSNCH3CH3)2 Ziram

Zinc ethylene- 12122-67-7 Zn(CS2NHCH2)2 Zineb

bis(dithiocarbamate)

2.1 Identity
Pure zinc is bluish-white and lustrous when polished. It has the atomic number of 30 and the relative atomic
mass of 65.38, and belongs to group 2b and the fourth period of the periodic table. The configuration of the
outermost electrons is 3d104s2. Thus, its valence in chemical compounds is +2. In nature, zinc is a mixture of
five stable isotopes: 64Zn (49%), 66Zn (28%), 68Zn (19%), 67Zn (4.1%), and 70Zn (0.62%) (Budavari, 1989).
A further 19 radioactive isotopes (57Zn–63Zn, 65Zn, 68Zn–80Zn) are known; 65Zn is the most stable with a
half-life of 243.8 days, but most have very short half-lives (Lide, 1991).

2.2 Physical and chemical properties

2.2.1 Zinc metal
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Zinc possesses a low to intermediate hardness (Mohs’ hardness 2.5) and crystallizes in a distorted hexagonal
close-packed structure. Because of its density of 7.13 g/cm3, it is called a heavy metal. It has an electrical
conductivity of 28.3% of the international annealed copper standard (Kirk & Othmer, 1982). At ordinary
temperatures the metal is too brittle to roll, but it becomes malleable and ductile when heated to 100–150 ºC.
At temperatures of > 210 ºC, zinc becomes brittle and pulverizable, and, at higher temperatures, again soft
and malleable (Budavari, 1989; Beliles, 1994). Since zinc is very reactive, it reacts strongly with other
elements, such as oxygen, chlorine and sulfur, at elevated temperatures (Melin & Michaelis, 1983). Zinc has
reducing and also several transitional properties (see below).

The metal burns in air with a bluish-green flame. It is stable in dry air, but on exposure to moist air it
becomes covered with an adherent film of zinc oxide or basic carbonate (2ZnCO3·3Zn(OH)2), so isolating
the underlying metal and retarding further corrosion.

Zinc is amphoteric and dissolves in strong alkalis and mineral acids with evolution of hydrogen and soluble
zinc salts. Oxidizing agents or metal ions, e.g., Cu2+, Ni2+ and Co2+, accelerate the dissolution of zinc. Zinc
is capable of reducing most metals except aluminium and magnesium (E o(aq) Zn/Zn2+, 0.763 eV; Budavari,
1989).

In solution, four to six ligands can be coordinated with the zinc ion. Complexes are formed with polar
ligands, e.g., ammonia, amines, cyanide and halogen ions. Zinc is a reactive amphoteric metal. The
hydroxide is precipitated in alkaline solution, but with excess base, it redissolves to form "zincates", ZnO22-,
which are hydroxo complexes such as Me+[Zn(OH)3]-, Me2+[Zn(OH)4]2-and Me2+[Zn(OH)4(H2O)2]2-
(Budavari, 1989).

2.2.2 Zinc compounds

Zinc has a strong tendency to react with acidic, alkaline and inorganic compounds. Because of its amphoteric
properties, zinc forms a variety of salts, which are all nonconducting, nonmagnetic and white or colourless,
with the exception of those with a chromophore group, such as chromate. Some physical and chemical data
for zinc and selected zinc compounds are given in Table 2.

Table 2. Physical and chemical properties of zinc and some of its compoundsa

Chemical name Relative Melting Boiling Relative Crystalline Solubility

atomic/ point point density form
molecular (° C) (° C) (g/cm3)
mass (° C)

Zinc 65.38 419.58 907 7.14 (25) distorted soluble acid,

hexagonal close alkali; insoluble
packed H2O,

Zinc acetate 183.47 237 200b 1.735 monoclinic soluble H2O,

alcohol

Zinc bromide 225.19 394 690 4.201 (25) rhombic soluble H2O,
alcohol, ether

Zinc carbonate 125.39 300b ND 4.398 rhombohedral soluble acid,

alkali; slightly
soluble H2O

Zinc chloride 136.29 283 732 2.907 (25) hexagonal, soluble H2O,
deliquescent acid, acetone,
alcohol

Zinc fluoride 103.38 872 ca. 1500 4.95 (25)

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monoclinic or soluble HCl,

triclinic HNO3, NH4OH;
slightly soluble
H2O, aqueous
HF

Zinc 207.46 NDb ND 2.104 crystalline soluble H2O

hexafluorosilicate powder

Zinc hydroxide 99.39 125b ND 3.053 rhombic soluble acid,

alkali; very
slightly soluble
H2O

Zinc iodide 319.19 446 624b 4.736 (25) hexagonal soluble H2O,
alcohol, ether

Zinc nitrate, 297.48 36.4 105–131 2.065 (14) tetragonal soluble H2O,
hexahydrate (-H2O) alcohol

Zinc oxide 81.38 1975 ND 5.606 hexagonal soluble dilute

acetic acid,
alkali; insoluble
H2O, alcohol

Zinc phosphate 386.08 900 ND 3.998 (15) rhombic soluble acid,

NH4OH;
insoluble H2O,
alcohol

Zinc phosphide 258.09 > 420 1100 4.55 (13) tetragonal soluble benzene,
(sublimes CS2; insoluble
in H2) H2O, alcohol

Zinc sulfate 161.44 600b ND 3.54 (25) rhombic soluble H2O,

MeOH, glycerol

alpha-Zinc sulfide 97.44 1700 ± ND 3.98 hexagonal very soluble

20 alcohol;
insoluble acetic
acid

beta-Zinc sulfide 97.44 NDb ND 4.102 (25) cubic very soluble acid

a From: Lide (1991); ND = not determined.

b Decomposition.

Zinc oxide is a coarse white or greyish powder, odourless and with a bitter taste. It absorbs carbon dioxide
from the air and is soluble in acids and alkalis but insoluble in water and alcohol. The compound is used as a
pigment in paints and as an ultraviolet (UV) absorber in several products. It has the greatest UV absorption
of all commercial pigments (Lide, 1991). Its major use (see section 3.2.2) is as a vulcanizing agent in the
production of rubber products (Melin & Michaelis, 1983).

Zinc chloride, chlorate, sulfate and nitrate are readily soluble in water, whereas the oxide, carbonate,
phosphates, silicates, sulfides and organic complexes are practically insoluble in water, with the exception of
zinc diethyldithiocarbamate (Budavari, 1989).

Zinc halogenides are hygroscopic. Zinc chloride forms hydrates with 1.33–4 mol H2O and exerts a water-
extracting and condensing action on many organic compounds. Owing to the high polarizing effect, zinc
protolyses part of the water envelope and forms hydroxo complexes. Thus, concentrated zinc chloride

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solutions react like strong acids because of the formation of the acids H[ZnCl2OH] and H2[ZnCl2(OH)2]
(Giesler et al., 1983). Zinc chloride and fluoride have catalytic properties and are used in organic synthesis
and also in wood preservation and for antiseptic purposes (Budavari, 1989).

Zinc carbonate occurs naturally as zinc spar. When heated to 150 ºC, the compound decomposes into zinc
oxide and carbon dioxide. Basic zinc carbonate, zinc carbonate hydroxide, is known in variable composition
and is usually characterized as 3Zn(OH)2 2ZnCO3. It occurs as the mineral hydrozincite, a weathering
product of zinc spar.

Zinc sulfide is a white powder that appears in two different modifications: the hexagonal close packed alpha-
modification (wurtzite), the form preferred by the pigment industry (n » 2.37); and the cubic beta-
modification (sphalerite), which is substantially converted to wurtzite when heated to 725 ºC in the absence
of air. Because of its semiconducting and luminescent properties, zinc sulfide is used industrially as a
pigment and as phosphors in X-ray and television screens (Neumueller, 1983; Budavari, 1989).

Some organo-zinc compounds (diethyl zinc, diphenyl zinc) are sensitive to air and water. The lower alkyl
compounds are autoflammable when exposed to air.

Other organo-zinc compounds, such as zineb (zinc ethylene-bis(dithiocarbamate)) and ziram (zinc dimethyl-
dithiocarbamate), are used as agricultural fungicides (Neumueller, 1983).

2.3 Analytical methods

2.3.1 Introduction

Because zinc is ubiquitous in the environment, special care is required during sampling, sample preparation
and analysis to avoid sample contamination. Precautions must be taken to avoid contamination arising from
such sources as sampling apparatus, filtration equipment, and atmospheric exposure during collection and
analysis. Clean room conditions and sample handling using apparatus rigorously cleaned with acid by
operators wearing polyethylene gloves and appropriate lint-free clothing are desirable (Batley, 1989a). The
necessary detection limits for trace analysis are often affected by problems related to inadequate reagent
purity or contamination introduced during the course of the sampling and analytical manipulations. With
adequate care, however, zinc concentrations as low as 0.006 µg/litre in water and 0.1 mg/kg in solid samples
are detectable, using modern instrumental analysis techniques.

For many environmental samples, zinc concentrations are sufficiently high to obviate the need for the
precautions described above. Nevertheless, appropriate quality assurance during both sampling and analysis
is necessary to ensure confidence in the methods of analysis used and the subsequent data that they generate.

2.3.2 Sampling and sample preparation

The background concentrations of dissolved zinc in many natural water samples are frequently below 1
µg/litre. However, contamination leading to levels as high as 20 µg/litre is quite possible during sampling
and filtration of waters. Containers must be carefully selected and precleaned before use. Teflon containers
are preferable; polyethylene is acceptable and superior to Pyrex glass, but soda glass should be avoided
(Batley, 1989a). Precleaning is best carried out by prolonged soaking in 2 mol/litre nitric or hydrochloric
acids, although hot nitric acid has been used (Mart, 1979). The containers should be rinsed with distilled
water and thoroughly rinsed with sample before collection. The need for rigorous care with water sampling
has been elegantly demonstrated by Ahlers et al. (1990).

Water sample preservation is achieved by acidification to < pH 2, generally after filtration if dissolved metals
are being sought. For zinc speciation analysis, acidification is unacceptable, and storage at 4 °C minimizes
species transformations or losses. Similar constraints apply to biological fluids.

For ultratrace analysis, the use of a clean laboratory or at least a laminar flow work station is highly
recommended to avoid contamination from airborne particulates. Typical unfiltered urban room air may

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contain zinc at concentrations as high as 1 µg/m3 (Henkin, 1979). In general laboratory operations, care
should be taken to avoid galvanized laboratory fittings (especially retort stands and clamps), rubber materials
and powdered gloves, all of which contain zinc.

Contamination of soil and sediment samples, in which zinc concentrations may vary in the range 10–2000
mg/kg, is less of a problem. Where sediment samplers are likely to contaminate the sample, the outer sample
layers should be discarded and only those portions not in contact with contaminating surfaces should be
subsampled. Coring is usually carried out with PVC or Perspex tubes; where metal corers are used, it is usual
for them to have polyethylene or polycarbonate liners. Where sieving of samples is undertaken, stainless
steel or nylon sieves are unlikely to cause sample contamination.

If the measurement of zinc present in soils or sediments in specific mineral phases is required, the sample
should be frozen as soon as possible after collection and air excluded to avoid oxidation of metal sulfides and
transformation of chemical forms. When selective extractions are to be undertaken, the sample is thawed and
homogenized by mixing. An aliquot of the moist sample is then taken for analysis, with moisture content
being determined in replicate aliquots (Batley, 1989a).

Sampling of plant material from the field requires procedures that take into account a number of abiotic and
biotic factors (Quevauviller & Maier, 1994; Ernst, 1995). The former include climate, i.e., sampling before
or after rain and, in the case of roots, soil type. Biotic factors include age of material and the presence of
parasites (e.g., mildew) or mycorrhizal fungi.

For total zinc analysis, sample preparation involves drying at 110 °C followed by acid digestion. Total
mineralization requires a mixture of concentrated acids, e.g., nitric, hydrochloric and hydrofluoric acids, and
the digestion is performed on a hot plate in a heated block assembly or microwave oven. Microwave
digestion is being increasingly used to minimize sample contamination. The detection of acid-soluble metals,
as stipulated by US EPA method 200.8, uses only nitric and hydrochloric acids (Long & Martin, 1991).

Biological samples comprise aquatic and terrestrial organisms and may include human tissue, hair, sweat,
blood, urine and faeces. Again, care is required in the handling of samples to avoid contamination (Batley,
1989a), avoiding metal surfaces and using appropriately cleaned plastic containers. The method of sample
preparation depends to a large extent on sample type. Animal and human tissue samples are usually analysed
without drying, and wet weight concentrations are reported. In some instances freeze-drying has been
employed. Plant tissue samples have been dried at 110 °C, freeze-dried and, in some instances, ashed at 500
°C to facilitate dissolution. In recent years, however, it has been realized that temperature can have a
significant effect on the quality of plant material during drying and mineralization prior to analysis. Owing to
burning of carbohydrates, drying at 110 °C will diminish the real dry mass, leading to overestimation of the
zinc concentration. Ashing at 500 °C should be avoided as it causes loss of zinc as volatile compounds. Plant
samples are therefore now usually oven-dried at 80 °C for 48 h (Ernst, 1995; Rengel & Graham, 1995).
Freeze-drying remains an option, especially in zinc compartmentation studies.

Dissolution is usually undertaken by wet ashing with nitric acid, either on a hot plate or by microwave-
assisted digestion (White, 1988). The use of perchloric acid is generally avoided nowadays, and complete
decomposition of organic compounds is not required for most spectroscopic analysis techniques. For marine
organisms, hydrogen peroxide is usually added during the dissolution process. Tissue solubilizers such as
tetramethylammonium hydroxide or potassium hydroxide have been used for effective dissolution of
biological tissue samples (Martin et al., 1991).

Care should be taken in the acid dissolution of blood and urine samples, as frothing of natural surfactants in
the sample during digestion can lead to losses. Allowing the sample to stand overnight after the addition of
acid can often obviate this problem.

It should be noted that in all of the above analyses, care must be paid to the quality of acids and other
reagents used. For analysis of zinc at low concentrations, reagents of an appropriately high purity are
essential.

For air sampling with high-volume samplers, low-ash filters are required. Glass fibre filters are sources of
zinc contamination and membrane filters made of cellulose acetate or Teflon are preferred (Batley, 1989a).

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Samples are analysed after dissolution of particulates in nitric acid, although ashing has also been used
(NIOSH, 1984).

2.3.3 Separation and concentration

Given the low detection limits of modern analytical techniques, separation techniques, such as ion exchange
or solvent extraction, that preconcentrate zinc from solution, are less frequently used nowadays, although
they are required for ultratrace detection. Any additional sample manipulation, however, increases the
opportunity for sample contamination. A range of preconcentration techniques has been applied, but only
those currently in common use are discussed here.

Most appropriate is the use of the complexing agents ammonium pyrrolidine dithiocarbamate (APDC) or
diethyldithiocabamate (DDC) to extract zinc, using trichloroethane or chloroform as the solvent. Apte &
Gunn (1987) have described a micro solvent extraction procedure with analysis by graphite furnace atomic-
absorption spectrometry (GF-AAS); detection of zinc concentrations as low as 20 ng/litre in seawater and
other natural waters is possible.

Chelating resins have also been widely used for preconcentration. Chelex-100 or equivalent iminodiacetate
resins in the sodium or calcium forms effectively remove zinc from seawater or fresh waters at pH values
greater than 6. It should be noted that zinc associated with colloids will not be satisfactorily removed. The
use of immobilized 8-hydroxyquinoline, dithiocarbamates or other zinc-binding ligands has also been
reported. The former is incorporated in at least one in situ water sampler (Willie et al., 1983; Batley, 1989b).

In natural water systems, measurements typically involve either total zinc, dissolved zinc or some form of
zinc speciation analysis. Water quality criteria are frequently based on total analyses. Acidification of the
sample, with heating, is therefore used as a pretreatment option. Filtration through 0.45-µm membrane filters
provides the accepted means of separating particulate species, and a separate analysis can then be performed
on each phase. For speciation, the principal concern is for bioavailable species, and a range of procedures has
been applied, including ultrafiltration, dialysis, ligand exchange, chelating resin separations and
measurement techniques, such as anodic and cathodic stripping voltammetry (ASV and CSV) that
discriminate between labile and non-labile zinc. These have been comprehensively reviewed elsewhere
(Florence & Batley, 1980; Batley, 1989b; Apte & Batley, 1995).

2.3.4 Detection and measurement

For environmental and biological samples, the required detection limits necessitate the use of modern
instrumental methods of analysis. Traditional titrimetric and gravimetric methods are not sufficiently
sensitive. Spectrophotometric methods offer greater sensitivity, but are tedious and subject to numerous
interferences (Cherian & Gupta, 1992). A summary of analytical methods for zinc in various environmental
media is given in Table 3.

Table 3. Analytical methods for zinc

Sample Preparationa Analytical Limit of detection Reference

methodb

Atmospheric collection on membrane F-AAS 2.6 pg/litre Ottley & Harrison

particulates filter, ashing with HNO3 (1993)

Atmospheric polystyrene filter collection, NAA not given Zoller et al. (1974)
particulates pressed into pellets

Atmospheric cellulose filter collection NAA 0.4 pg/litre Amundson et al. (1992)
particulates

Water filtration, acidification FAAS 50 µg/litre Greenberg et al. (1992)

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Water APDC/MIBK extraction FAAS not given Greenberg et al. (1992)

Water filtration, acidification GF-AAS 0.1 µg/litre Greenberg et al. (1992)

Water filtration, acidification ICP-AES 2 µg/litre Greenberg et al. (1992)

Water filtration, acidification US ICP-MS 1.8 µg/litre Long & Martin (1991)
EPA Method 200.8

Water/seawater APDC/trichloroethane GF-AAS 0.02 µg/litre Apte et al. (1998)

extraction

Water/seawater acidification, ultraviolet DP-ASV 0.05 µg/litre Batley & Farrar (1978)
irradiation

Seawater APDC chelation CSV 0.006 µg/litre Van den Berg (1986)

Water/seawater chelating resin ICP-MS 0.05 µg/litre Sturgeon et al. (1981)

preconcentration

Water, leachates acidification XRF 5 mg/litre Cornjeo et al. (1994)

Soil, sediments US EPA Method 200.8 ICP-MS 0.7 mg/kg Long & Martin (1991)

Soil, sediments HCl/HNO3/HF microwave ICP-MS 0.7 mg/kgc Dale (unpublished data)
digestion

Biota (fish, oysters, HNO3/H2O2 microwave ICPA-ES 0.2 mg/kgc Martin et al. (1991)
mussels, etc.) digestion

Biota (fish, oysters, tetramethylammonium ICP-AES 0.2 mg/kgc Martin et al. (1991)
mussels, etc.) hydroxide dissolution, US
EPA Method 200.11

Biota (fish, oysters, homogenization, freeze- IDMS 1.5 ng absolute Waidmann et al. (1994)
mussels, etc.) drying, HNO3/H2O2
dissolution

Biological samples solid XRF 0.1 mg/kg Heckel (1995)

Plant material homogenization, digestion AAS/F- not given Harmens et al. (1993)
in HNO3/HCl in Teflon AAS
bomb

Food dry ashing, HNO3 /H2O2 ICP-MS not given Veillon & Patterson
digestion (isotope (1995)
dilution)

Food homogenization, freeze- ICP-AES 2 mg/kgc Copa-Rodriguez &

drying, acid microwave Basadre-Pampin (1994)
digestion

Blood serum dilution with HNO3/HCl ICP-AES 10–50 µg/litre Que Hee & Boyle
(1988)

Biological tissues, heating with HNO3 , Parr ICP-AES 10–50 µg/litre Que Hee & Boyle
whole blood, faeces bomb digestion, addition of (1988)
HClO4

Blood, plasma dilution with water GF-AAS 6 µg/litre Schmitt et al. (1993)

Human milk ultrafiltration GF-AAS 1.6 µg/litre Arnaud & Favier (1992)

Faeces drying digestion with F AAS not given Dastych (1990)

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Faeces drying, digestion with F-AAS not given Dastych (1990)
H2SO4/HClO4

Saliva - GF-AAS 0.4 µg/litre Henkin et al. (1975)

a APDC = ammonium pyrrolidine dithiocarbamate; MIBK = methyl isobutyl ketone; US EPA = United States
Environmental Protection Agency.

b CSV = cathodic stripping voltammetry; DP-ASV = differential pulse anodic stripping voltametry; F-AAS = flame
atomic-absorption spectrometry; GF-AAS = graphite furnace atomic-absorption spectrometry; ICP-AES =
inductively-coupled plasma atomic emission spectrometry; ICP-MS = inductively-coupled plasma mass
spectrometry; IDMS = isotope dilution studies; NAA = neutron activation analysis; XRF = X-ray fluorescence.

c Dependent upon the mass of sample taken and the dilution.

To achieve the necessary detection limits, spectrophotometric methods will usually require some form of
sample preconcentration. The achievable detection limit is frequently limited in practice by the purity of the
reagents used.

Instrumental techniques offer element-specific detection at low concentrations. The most common are atomic
absorption or emission spectrometry (AAS and AES), X-ray fluorescence (XRF), electroanalytical
techniques, such as polarography or stripping voltammetry, and neutron activation analysis.

XRF and other focused particle beam methods require solid samples. The detection limit for zinc by direct
microprobe analysis is only around 240 mg/kg (Kersten & Forstner, 1989). For liquid samples,
preconcentration by adsorption or complexation onto solid phases has been used. A relatively new XRF
procedure based on polarized X-rays has a detection limit for zinc of 0.1 mg/kg in biological materials
(Heckel, 1995).

Flame atomic absorption spectrometry (F-AAS) has for many years been the basis of the standard method for
determining zinc in waters (Hunt & Wilson, 1986). The method is very sensitive: for direct F-AAS analysis,
the instrumental detection limit is 5 µg/litre, although the optimal concentration range is 50–2000 µg/litre.
This can be further enhanced with preconcentration by complexation/solvent extraction or using solid-phase
adsorbents. GF-AAS offers improved detection limits for direct analysis, but is subject to matrix
interferences, particularly in saline waters (Slavin, 1984).

Inductively-coupled plasma atomic emission spectrometry (ICP-AES) is considerably more sensitive than F-
AAS, and detection of 2 µg/litre is possible by direct analysis (Greenberg et al., 1992), although with the
latest axial plasma instruments with ultrasonic nebulization, the limit is as low as 0.2 µg/litre. Calibration by
standard additions is essential. This technique offers adequate sensitivity for zinc in contaminated waters or
for acid digests of soil, sediment and biological samples. The multi-element capability offered by ICP-AES
is a considerable advantage over AAS methods.

ICP mass spectrometry (ICP-MS) offers excellent sensitivity. The instrumental detection limit for zinc in
fresh waters is 20 ng/litre using conventional nebulization systems. With aerosol desolvation devices, the
detection limit is about one order of magnitude better. However, these detection limits are not achievable
unless stringent procedures to avoid zinc contamination are implemented, including the use of ultrapure
reagents. A content of solids in excess of 0.1%, as in seawater samples, creates problems during
nebulization. These are best overcome by complexation and extraction of zinc as described earlier. The
technique is ideally suited to digests of soils, sediments and biological samples; the greater sensitivity means
that any difficulties due to a high content of solids are overcome by dilution. In addition, because of its mass
resolution, ICP-MS enables isotopic ratio analysis (67Zn/68Zn/70Zn) or isotope dilution studies using 65Zn
(Ward, 1987). Isotope tracers have been used to study zinc absorption following administration of the isotope
in food (Johnson, 1982; Watson et al., 1987).

Neutron activation analysis (NAA) is a useful technique for the non-destructive analysis of solid samples,
and requires a minimum of sample preparation (Fredrickson, 1989; Heydorn, 1995). Its main advantage is its
multi-element capability; the great disadvantage is its limited availability, and long analysis time. It has
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largely been superseded by ICP-MS, which offers a similar capability and is more widely available. For zinc,
the sensitivity of NAA is poor.

Of the electroanalytical techniques, polarography is rarely employed except for samples containing high zinc
concentrations (> 10 µg/litre), such as digests of ores. For ambient water concentrations, stripping
voltammetric techniques are essential. Differential-pulse ASV (DP-ASV) offers detection limits in natural
waters in the ng/litre range (Florence, 1989). An advantage of ASV is the in situ preconcentration achieved
during the accumulation step, which avoids the contamination problems associated with the greater sample
manipulation of other preconcentration techniques. A disadvantage is the potential interference from high
concentrations of natural organic compounds in some samples, which may adsorb to the mercury electrode
and limit zinc deposition. Although this is not a problem for most natural water samples, complete digestion
of biological samples or highly contaminated waters, to decompose interfering surface-active organic
compounds, is essential.

CSV has also been successfully applied to the detection of baseline concentrations of zinc in seawater (Van
den Berg, 1986). It requires the formation of a zinc complex with APDC, which can be accumulated at a
mercury electrode and stripped using a cathodic scan. CSV is best used with pristine samples, where
interference due to other metals or adsorbing ligands is less likely.

It should be noted that voltammetric techniques applied to water samples will only measure an operationally-
defined labile fraction unless the sample is pretreated by UV irradiation to destroy non-labile zinc
complexes, and acidification to dissociate zinc bound to natural colloids. This property can be an advantage
in speciation studies, where the ASV-labile concentration has been related to the zinc fraction that is
bioavailable (Florence & Batley, 1980; Florence, 1992).

New zinc-specific fluorophores have been developed to measure and visualize intracellular zinc. One of
these, Zinquin, has been successfully used in lymphoid, myeloid and hepatic cells to detect labile
intracellular zinc (Zalewski et al., 1993; Coyle et al., 1994), although the interaction between Zinquin and the
zinc-binding protein, metallothionein (see section 6.5.1.4) needs further study (Coyle et al., 1994).

In all analyses, the use of appropriate quality assurance procedures is required. In particular, standard
reference materials are essential. These are currently available for waters, sediments and soils, as well as for
plant and other biological materials.

3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1 Natural occurrence
Zinc is a chalcophilic element like copper and lead, and a trace constituent in most rocks. Zinc rarely occurs
naturally in its metallic state, but many minerals contain zinc as a major component from which the metal
may be economically recovered (Table 4). The mean zinc levels in soils and rocks usually increase in the
order: sand (10- 30 mg/kg), granitic rock (50 mg/kg), clay (95 mg/kg) and basalt (100 mg/kg) (Adriano,
1986; Malle, 1992). Sphalerite (ZnS) is the most important ore mineral and the principal source for zinc
production. Smithsonite (ZnCO3) and hemimorphite (Zn4(Si2O7) (OH)2·XH2O) were mined extensively
before the development of the froth-flotation process (Melin & Michaelis, 1983; Jolly, 1989). The main
impurities in zinc ores are iron (1–14%), cadmium (0.1–0.6%), and lead (0.1–2%), depending on the location
of the deposit (ATSDR, 1994).

Table 4. CAS chemical names and registry numbers, synonyms, trade names and molecular formula of
zinc oresa

Chemical name CAS registry Synonyms and trade Composition Formula

number names

Zinc oxide 1314-13-2 zincite 80.34% Zn, 19.66% ZnO

O

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Zinc phosphate 7779-90-0 hopeite 50.80% Zn, 33.16% Zn3(PO4)2.4H2O

O, 16.04% P

Zinc silicate 13597-65-4 willemite 58.68% Zn, 28.72% Zn2SiO4

O, 12.60% Si

Zinc sulfide 1314-98-3 sphalerite, wurtzite 67.09% Zn, 32.91% ZnS

S, up to 25% Fe

Zinc carbonate 3486-35-9 smithsonite, zincspar 52.14% Zn, 38.28% ZnCO3

O, 9.58% C

Hemimorphite - - 58.28% Zn Zn4(Si2O7)(OH)2·XH2O

Franklinite - - 15–25% ZnO, 10– (Zn, Fe, Mn).(FeMn)2O4

16% MnO

Hydrozincite - zinc bloom - Zn5(OH)6(CO3)2

Tetrahedrite - - 8–9% Zn (Cu,Zn)12Sb4S14

a Adapted from Neumueller (1983) and Melin & Michaelis (1983).

Natural levels of zinc in the soil environment can vary by three or four orders of magnitude. When ore-rich
areas are included in the analysis this variation is even greater (GSC, 1995). National Geochemical
Reconnaissance data of Canada have reported a mean value of 80 mg/kg for stream sediments with 10th and
90th percentile values of 40 mg/kg and 245 mg/kg, respectively (GSC, 1995). The 99th percentile value for
lake sediments was 1280 mg/kg with a maximum of > 20 000 mg/kg. Similar variations were noted in zinc
levels in agricultural soils and lake sediments.

As a result of weathering, soluble compounds of zinc are formed and may be released to water. US EPA
(1980) estimated the input of zinc to waters in the USA resulting from erosion of soil particles containing
natural traces of zinc to be 45 400 tonnes/year. The global flux of zinc to water through erosion has been
estimated at 915 000 tonnes/year (GSC, 1995). Zinc flux to the oceans from high temperature hydrothermal
fluids in mid-ocean ridges has been estimated to be of the order of 681 000 tonnes/year.

Global emissions to air are mainly due to windborne soil particles, igneous emissions and forest fires, and are
estimated to be 19 000 tonnes/year, 9600 tonnes/year and 7600 tonnes/year, respectively. Further natural
sources of zinc in air are biogenic emissions and seasalt sprays, with annual amounts calculated at 8100
tonnes and 440 tonnes, respectively (Nriagu, 1989).

Lantzy & Mackenzie (1979) calculated the natural continental and volcanic dust flux to be about 35 800
tonnes annually, based on the average zinc concentration in soils and andesites. Thus, total annual emissions
of zinc to air from natural sources are estimated at about 45 000 tonnes/year (Nriagu, 1989). Such estimates
of zinc may be low (Rasmussen, 1996), particularly those for zinc transferred by biogenic emissions and
from volcanic activity. Long-range dust flux has been estimated at 61–366 million tonnes/year (Pye, 1987).
Given an average zinc crustal abundance of 70 mg/kg (70 ppm), this yields up to 25 600 tonnes/year.
However, short-range, low-level dust transport can also be included and would increase the windblown dust
estimate to 5000 × 106 tonnes/year (Pye, 1987), corresponding to a zinc input of 350 000 tonnes/year. Given
such uncertainties in the database, it is very difficult to estimate a ratio of natural to anthropogenic emissions
for zinc.

3.2 Anthropogenic sources

3.2.1 Production levels and processes

3.2.1.1 Production levels

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Zinc ore (smithsonite) has been used for the production of brass since 1400. In Europe, the production of
elemental zinc started in 1743 (Melin & Michaelis, 1983).

World mine production of zinc was 7 140 000 tonnes in 1992 and 7 089 000 tonnes in 1994 (US Bureau of
Mines, 1994; ILZSG, 1995). Global zinc production and consumption are summarized in Table 5.

Secondary zinc production constitutes about 20–30% of current total zinc production (1.9 million tonnes in
1994). Taking the historical consumption and produce life cycles of recovered zinc products into account,
recovery rates have been estimated to be as high as 80% from zinc sheet and coated steels (EZI, 1996).

Table 5. Total zinc production and consumption in 1994 (thousand tonnes)a

Geographical area Mine production Zinc production Zinc consumption

Europe 1012 2510 2350

Canada 1008 693 148

Australia 971 323 161

China 755 975 577

Peru 682 158 69

USA 597 356 1191

Mexico 369 212 108

Other countries 1271 1862 2291

World total 6665 7089 6895

a From: ILZSG (1995). Total figures for 1995 were: mine production, 6939 ´ 103 tonnes; zinc production, 724 ´ 103
tonnes; and zinc consumption, 7354 ´ 103 tonnes (ILZSG, 1996).

3.2.1.2 Production processes

Zinc ore is mined from underground and open pit mines (approximately 62% underground, 14% open pit,
15% a combination, 9% unspecified) (MG, 1994). The mined ores usually contain zinc at levels of 4–8% and
are concentrated at the mine sites to levels of 40–60%. Unwanted impurities (gangue) and other impurities,
such as iron, cadmium and lead, which substitute for zinc in the mineral crystal structure, are removed by
flotation (Jolly, 1989).

The resulting fine-grained sphalerite concentrates contain 40- 60% zinc, 30% sulfur and a number of other
metals, in varying quantities, that are of economic significance as extractable by-products. All the world’s
cadmium (excluding recycles) and a large proportion of the germanium and gallium are extracted as by-
products of zinc production. Large quantities of sulfuric acid are also produced (UN ECE, 1979; Melin &
Michaelis, 1983). Concentrates are the raw materials for zinc smelting.

Zinc metallurgy can be divided into two basic processes: electrolytic refining, which comprised 83% of
primary production in 1993; and pyrometallurgical smelting (ILZSG, 1994).

In the conventional electrolytic process zinc concentrates are roasted to remove sulfur, as sulfur dioxide,
which is made into sulfonic acid. The resulting calcine (zinc oxide) is leached with spent electrolyte, the
solution is then purified and zinc is recovered by electrowinning. The process produces iron residues, such as

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goethite and jarosite, and gypsum. In an alternative electrolytic process, pressure leaching, concentrates are
treated directly with spent electrolyte under pressure to remove sulfur, iron and other impurities. The zinc
dissolves in the spent electrolyte and the solution is purified prior to recovery of zinc by electrowinning. This
process also produces iron residues and gypsum, and elemental sulfur as a marketable by-product.

In the pyrometallurgical process, concentrates are roasted to produce sinter, as a solid lump feed for the blast
furnace, and sulfur dioxide, which is made into sulfuric acid. Sinter and coke are charged to the imperial
smelting blast furnace, which produces metallic zinc and lead, and an iron-rich slag. The zinc is refined by
distillation in reflux columns.

Trade in zinc intermediate products (ash, drosses, skimmings and residues) represents an important source of
material for secondary zinc production. These products contribute up to 42% of the sources of zinc for
recycling purposes in western countries (Henstock, 1996). Recycling provides some 28% of the zinc metal
produced.

3.2.2 Uses
Zinc is the fourth most widely used metal in the world after iron, aluminium and copper. Table 6 shows the
applications of zinc in western Europe. An overview of the uses of zinc compounds is given in Table 7.

Table 6. Applications of zinc in western Europe (ILZSG, 1995)

Application Consumption (%)

Galvanizing 43

Brass 23

Alloys, other than brass 13

Wrought zinc 12

Pigments/chemicals 8

Othersa 1

a Including use of zinc in veterinary and human medicines, as a feed additive, and in cosmetics

(Bruère et al., 1990; EU, 1996).

Zinc is mainly used as a protective coating of other metals, such as iron and steel. Because the metal lacks strength, it is often
alloyed with other metals, e.g., aluminium, copper, titanium and magnesium, to impart a variety of properties. If zinc is the primary
constituent of the alloy, it is called a zinc-base alloy, mainly used for casting and for wrought applications. The zinc-copper-
titanium alloy has become the dominant wrought-zinc alloy because of its greater strength and dent resistance than other metals of
the same thickness (Beliles, 1994). Further important applications are in dye-casting, the construction industry, and other alloys
(brass, bronze). Zinc dust is a widely used catalyst; it is also used as a reducing and precipitating agent in organic and analytical
chemistry. Inorganic zinc compounds have various applications, e.g., for automotive equipment, storage and dry-cell batteries and
organ pipes. Zinc chloride, sulfide and sulfate have dental, medical and household applications. Zinc oxide is frequently used in
ointments, powders and other medical formulations. Zinc salts are used as solubilizing agents in pharmaceuticals (e.g., injectable
insulin) (Budavari, 1989). Organo-zinc compounds are used as fungicides, topical antibiotics and lubricants (Shamberger, 1979;
Sax & Lewis, 1987). Zinc soaps (zinc palmitate, stearate and oleate) are used as drying lubricants and dusting agents for rubber,
and as waterproofing agents for textiles, paper and concrete (Budavari, 1989). Zinc phosphide is highly poisonous owing to
liberation of phosphine gas; it is used in rat and mouse poisons (Bertholf, 1988).

Table 7. Some uses of zinc compoundsa

Zinc compound Uses

Zinc acetate medicine (astringent), timber preservative, textile dyeing

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Zinc antimonide thermoelectric devices

Zinc arsenate insecticide, timber preservative

Zinc arsenite insecticide, timber preservative

Zinc bacitracin antibacterial agent in ointments, suppositories

Zinc bromide photographic emulsions, rayon manufacture

Zinc caprylate fungicide

Zinc carbonate ceramics, fire-proofing agents, cosmetics, pharmaceuticals

(ointments, dusting powder), medicine (topical antiseptic)

Zinc chloride organic synthesis (catalyst and dehydrating agents),

fireproofing, soldering fluxes, electroplating, antiseptic
preparations, textiles (mordants, mercerizing agents),
adhesives, dental cements, medicine (astringent)

Zinc dibenzyldithiocarbamate accelerator for latex dispersions and cements

Zinc dichromate pigment

Zinc fluoride phosphors, ceramic glazes, timber preservation,

electroplating

Zinc fluorosilicate concrete hardener, laundry sour, preservative, mothproofing

agents

Zinc iodide medicine (topical antiseptic), analytical reagent

Zinc laurate paints, varnishes, rubber compound manufacture

Zinc linoleate paint drier, especially with cobalt and manganese soaps

Zinc oxide accelerator, rubber (reinforcing agent), ointments, paints

(pigment, mould-growth inhibitor), plastics (ultraviolet
absorber), feed additive, cosmetics, photoconductor,
piezoelectric devices

Zinc-1,4-phenol-sulfonate insecticide, medicine (antiseptic)

Zinc phosphate dental cements, phosphors, conversion coating of steel

Zinc phosphide rodenticide

Zinc propionate fungicide on adhesive tape

Zinc salicylate medicine (antiseptic)

Zinc stearate cosmetics, lacquers, ointments, lubricant, mould-release

agent, medicine (for dermatitis), dietary supplement

Zinc sulfate rayon manufacture, dietary supplement, mordant, timber

preservative, production of plastics

Zinc sulfide pigment, glass, ingredient of lithopone, phosphor in X-ray

and television screens, luminous paints, fungicide
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Zineb insecticide, fungicide

Ziram fungicide, rubber accelerator

a Adapted from: Sax & Lewis (1987) and Budavari (1989).

Zinc dialkyldithiocarbamates are used as accelerators for the vulcanization of rubber.

In agriculture, zinc-carrying fertilizers are by far the largest source of zinc. About 22 000 tonnes of zinc are used annually as
fertilizers in the USA (Adriano, 1986).

3.2.3 Emissions during production and use

Zinc emissions can be classified as follows: controlled emissions (e.g., point source emissions) from industrial processes; fugitive
emissions resulting from mining, handling or transport operations or from leakages from buildings and insufficient ventilation; and
diffuse emissions from the use of zinc-containing products (OSPARCOM, 1994; Van Assche, 1995). Zinc is released to the
atmosphere as dust and fumes from mining, zinc production facilities, processing of zinc-bearing raw materials, brass works, coal
and fuel combustion, waste incineration, and iron and steel production. However, refuse incineration, coal combustion, smelter
operations, and some metal-working industries constitute the major sources of zinc in air (ATSDR, 1994). More efficient emission
control technology and changes in zinc refining methods have resulted in decreases of emissions of 73% to air and 83% to water
during the period 1985- 1995 (Royal Belgian Federation of Non-Ferrous Metals, 1995). These data are confirmed by the results of
the US Toxics Release Inventory during the period 1988–1993.

Additionally, the use of zinc-containing chemical fertilizers and pesticides in agriculture, the application of sewage sludge and
manure to fields, and the disposal of zinc-bearing waste may increase zinc concentrations in soil (US EPA, 1980; Cleven et al.,
1993).

3.2.3.1 Emissions to atmosphere

During mining, atmospheric zinc loss is estimated to be 100 g per tonne of zinc mined, mostly from handling ores and concentrates
and from wind erosion of tailing piles (Lloyd & Showak, 1984). From stationary sources, average emissions of zinc to the
atmosphere of 151 000 tonnes/year are reported for 1969–1971 (Fishbein, 1981). Based on emission studies in western Europe,
USA, Canada and the former Soviet Union, total worldwide zinc emissions to air were estimated to be in the range 70 250–193
500 tonnes in 1983. Emissions from the non-ferrous metal industry account for the largest fraction of zinc emitted (50–70%).
Cement production accounted for 1780–17 800 tonnes/year and the use of phosphate fertilizers was stated to contribute 1370–6850
tonnes/year. Additionally, 1724–4783 tonnes/year were attributed to emissions from miscellaneous sources (Nriagu & Pacyna,
1988).

The above estimates are not generally descriptive of emissions from modern zinc production techniques. Emission factors for
industrial point sources have decreased significantly since the 1970s. For pyrometallurgical zinc production, Nriagu & Pacyna
(1988) used an emission factor of 100–180 kg of zinc for each tonne of metal produced. Currently, emission factors for releases to
air from pyrometallurgical processes do not exceed 0.7 kg per tonne of metal produced in western Europe (EZI, 1996). In addition,
industrial production patterns were erroneously estimated at the time these estimates were made. Nriagu & Pacyna (1988)
estimated that total world pyrometallurgical zinc production was 4.6 × 106 tonnes in 1983-1984. Given a total of 6.25 × 106 tonnes
of global zinc production, including about 1 × 106 tonnes of zinc from new scrap recycling for that period (ILZSG, 1995), 74% of
zinc production was considered to be by electrolytic processes. However, 80% of western world zinc production in 1984 was by
electrolytic refining and only 20% by non-electrolytic processes (ILZSG, 1994). Even if it is assumed that all zinc production
elsewhere (1.5 × 106 tonnes) was by pyrometallurgical technology, the proportion of zinc produced by this technology could not
have exceeded 2.4 × 106 tonnes, or 39%.

By 1993, 83% of zinc was being produced by electrolytic techniques (ILZSG, 1994). The emissions to air from hydrometallurgical
zinc production processes are currently 4–400 g of zinc per tonne produced (EZI, 1996). Taking present-day emission factors and
production methods into account, total zinc emissions to air from zinc production are likely to be about 2000 tonnes/year. This
contrasts with the estimates of 70 250–193 500 tonnes (for 1983- 1984) made by Nriagu & Pacyna (1988), but is in good
agreement with the data on controlled emissions in Europe (OSPARCOM, 1994).

Controlled emissions from point sources to air from the German non-ferrous industry were 16.2 tonnes/year in 1993-1994. Zinc
emissions of 47.7 tonnes were reported for the French zinc and lead industry in 1991. For the Netherlands, annual emissions of
zinc oxide from zinc production in 1990 amounted to 24 tonnes/year. From zinc production, zinc emissions of 58 tonnes were
reported for the United Kingdom in 1990 and 6 tonnes for Spain in 1992. For a combined zinc-copper-lead plant in Sweden, zinc
emissions to air amounted to 33 tonnes in 1990 (OSPARCOM, 1994). In the USA, industry data for stack/point source emissions
indicated a release of 387 tonnes in 1994 with fugitive emissions of 377 tonnes (TRI, 1995). Emissions of zinc from all industrial
sources in Canada in 1983 were 1410 tonnes compared to 151 000 tonnes in the period 1969–1971 (NPRI, 1994).

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The reduction of atmospheric zinc emissions for European countries near the North Sea over the time period 1985–1995 is
summarized in Table 8.

Table 8. Reduction of zinc emissions to air and surface waters in European countries in the period 1985–1995 after the
NORTHSEA Conference (OSPARCOM, 1994) a

Country Reduction of zinc emissions (%)

To air To water

Belgium 25b 5b

Germany 70 no data

Netherlands 25 25

Norway 75 37

Sweden 50 70

Switzerland 5 35

United Kingdom 5 no data

a All data are official country data. It must be emphasized that in some countries
strong reductions in emissions took place before the reference period 1985–
1995. For example, in Belgium the reduction of zinc emissions to water from
the non-ferrous metal industry during the period 1980–1985 was 65% (Royal
Belgian Federation of Non-Ferrous Metals, 1995).

b 1995 figures for Belgium: to air, reduction of 18%; to water, reduction of 32%
(VMM, 1996).

3.2.3.2 Emissions to aquatic environment

Anthropogenic inputs of zinc from mining and manufacturing processes (production of zinc, iron, chemicals,
pulp and paper, and petroleum products) into aquatic ecosystems are given as 33 000- 178 000 tonnes/year.
A further 15 000–81 000 tonnes/year originate from domestic waste water, 21 000–58 000 tonnes/year from
atmospheric fallout, and 2600–31 000 tonnes/year from the dumping of sewage sludge. Total worldwide
input was estimated to be 77 000–375 000 tonnes/year (Nriagu & Pacyna, 1988). In this study, the emission
factors for non-ferrous metals smelting and refining were 300–3000 g of zinc per tonne of metal produced. In
current zinc production, emission factors are 0.1–50 g of zinc per tonne of metal produced (EZI, 1996). US
EPA (1980) calculated that urban runoff accounts for approximately 5200 tonnes/year, and drainage from
inactive mines for 4060 tonnes/year. The German chemical industry and the Rotterdam harbour agreed to
reduce the annual zinc input into the river Rhine and its tributaries from 270 tonnes in 1995 to 100 tonnes in
2000 (VDI-Nachrichten, 1995).

For the North Sea, a total input of 28 000 tonnes of zinc was estimated for 1987 (Kersten et al., 1988)
compared to 15 190 tonnes in 1990 (riverine input, 6900 tonnes; dredgings and direct discharge, 5000
tonnes; atmospheric input, > 2700 tonnes; industrial waste, 440 tonnes; and sewage sludge, 150 tonnes)
(UBA, 1994). For the Baltic Sea, the following inputs were estimated for 1987: municipal input, 460 tonnes;
rivers, 6709 tonnes; industrial, 1765 tonnes; and atmosphere, 3200 tonnes (UBA, 1992). For German rivers,
an input of around 18 tonnes to the Baltic Sea was estimated for 1990 (UBA, 1994). A marked reduction of
industrial point source emissions has been observed in western Europe during the last decade, resulting in a
substantial decrease of the concentrations in surface water (Van Assche, 1995). Significant reductions are

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also evident from the US TRI database; discharges to surface waters were 386 tonnes in 1988 and only 30
tonnes in 1993 (TRI, 1993).

The recent general tendency for reduction of zinc emissions to the water, is illustrated by data reported by
European countries bordering or close to the North Sea (see Table 8). This general reduction is also reflected
in the decrease of zinc deposited in Greenland snow samples after the 1960s (Boutron et al., 1995).

3.2.3.3 Emissions to soil

On an annual basis, an estimated 1–3 million tonnes of zinc from mining and smelter operations are
discharged on land worldwide. An additional 689–2054 × 103 tonnes/year are released to soil from
anthropogenic activities: 260–1100 tonnes/year originate from the use of fertilizers and 49 000–135 000
tonnes/year from atmospheric fallout. However, a further significant source of zinc emissions to soil is
represented by zinc-containing wastes, such as agricultural and animal wastes, manure, sewage sludge and
fly ash, which contribute 640–1914 × 103 tonnes/year (Nriagu & Pacyna, 1988). On the basis of an average
zinc concentration of 60–470 mg/kg in chemical phosphate fertilizers and < 5 mg/kg in non-phosphate
fertilizers, and the consumption of commercial fertilizers, the total zinc input into soil from these fertilizers
was 745 tonnes in Germany in 1989. The zinc content of manure is given as 12.6–39 mg/kg (UBA, 1992). In
Australia, annual consumption of zinc in fertilizers ranged between 900 and 1700 tonnes (Mortvedt &
Gilkes, 1993). In the USA, zinc in fertilizer increased from 13 100 tonnes in 1967-1968 to 37 300 tonnes in
1984 (Mortvedt & Gilkes, 1993).

Nriagu & Pacyna (1988) estimated that zinc is discharged on land worldwide during mining and smelting
operations at a rate of approximately 310–620 ×103 tonnes/year in smelter in slags and wastes, and 194–620
× 103 tonnes/year in mine tailings. The vast majority of such discharges are non-dispersive and occur within
the mine or smelter site. Its physical and chemical properties, and the lack of availability of the zinc make it
difficult to envisage a large global impact of this material on the environment.

3.2.4 Emissions during combustion of coal and oil, and refuse incineration

Zinc concentrations in oil and coal average 0.25 mg/kg and 50 mg/kg, respectively (Bertine & Goldberg,
1971). On the basis of these data, the global emissions from oil and coal combustion to air were calculated
by Lantzy & Mackenzie (1979) to average 140 000 tonnes/year. For 1983, the releases of zinc to atmosphere
due to coal and oil combustion were calculated to be 2570- 19 630 tonnes/year and 532–3786 tonnes/year,
respectively. Estimated emissions from refuse incineration are in the range 2950- 8850 tonnes/year (Nriagu
& Pacyna, 1988).

3.2.5 Zinc releases from diffuse sources

Several categories of diffuse emissions can be relevant in terms of total environmental input of zinc: zinc
wash-off from metallic zinc surfaces exposed to atmospheric conditions (sacrificial zinc corrosion),
household emissions, emissions from agricultural practice (see section 3.2.3.3) and traffic, and atmospheric
emissions (see section 3.2.3.1).

3.2.5.1 Releases from atmospheric zinc corrosion

In air, acidifying factors, such as sulfur dioxide, nitric oxides and chlorides attack the zinc hydroxide-
carbonate layer on the surface of metallic zinc yielding soluble zinc compounds. Sulfur dioxide levels in
ambient air are particularly important in this respect. Chloride levels are significant but only at distances
smaller than 1.5 km from the seaside (Porter, 1995). Zinc is washed off slowly and forms a diffuse source of
zinc release to the environment. Corrosion is increased at pH levels of rain of < 4, corrosion at pH 4–7
amounts to less than 1 µm/year but increases six-fold at pH 3. It has been demonstrated that atmospheric
corrosion is strongly and linearly related to the sulfur dioxide levels in ambient air (Knotknova & Porter,
1994). An empirical formula for the reduction of the thickness of zinc layers is:

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Rate of zinc corrosion (µm/year) = 0.29 + 0.039 × [SO2] ([SO2] in µg/m3 in air)

Since the 1970s, ambient air sulfur dioxide levels have markedly decreased (Iversen et al., 1991). As a
consequence, corresponding zinc corrosion rates have also decreased. In Stockholm, for example, ambient
air sulfur dioxide levels and experimental zinc corrosion rates have decreased concomitantly by 94% and
73%, respectively (Knotknova & Porter, 1994).

The annual removal of zinc from exposed metal is estimated to be 3.6 µm in rural air, 3.8 µm in urban air,
4.3 µm in industrial air, and 4.5 µm in sea air (Boettcher, 1995). For European countries, annual corrosion
rates are estimated to be < 8 g/m2, 8–16 g/m2, and 16–28 g/m2 for rural, urban and industrialized areas,
respectively (Van Assche, 1995). A study by Knotkova et al. (1995) indicates that corrosion rates in Europe
are now about 1.1 µm/year, corresponding to a potential zinc wash-off of about 8 g/year per m2 of exposed
zinc surface. The highest corrosion rate reported by Knotkova et al. (1995) was 2.2 µm/year in an industrial
site (< 16 g/m2 of zinc surface). Similar corrosion rates have been observed in North America (Spence &
McHenry, 1994).

3.2.5.2 Releases from sacrificial zinc anodes

In order to protect steel structures from corrosion in the marine environment and in soils, sacrificial zinc
anodes are used, resulting in a slow release of zinc to the environment. Current releases to the marine
environment from European countries bordering or close to the North Sea are estimated at 1900 tonnes/year
(OSPARCOM, 1994).

3.2.5.3 Household zinc emissions

Some household zinc emissions are of natural origin, e.g., background levels in tap water and foodstuffs.
Others are of anthropogenic origin: from galvanized water pipes, cosmetics, pharmaceuticals, etc. In the
Netherlands, the zinc load from households was estimated to be 8.1 g per person per year, of which 53%
originated from food consumption (estimated from faeces), 25% from drinking-water, and 22% from
"consumer products" (Coppoolse et al., 1993).

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION

AND TRANSFORMATION
4.1 Transport and distribution between media
4.1.1 Air

Zinc in the atmosphere is primarily in the oxidized form in aerosols (Nriagu & Davidson, 1980). Zinc is
found on a particles of various sizes, the size being determined by the source of zinc emission. Waste
incinerators release small zinc-containing particles to the atmosphere, whereas wear of vehicle tyres
produces large particles (Sohn et al., 1989).

Zinc in urban and industrial areas, including metallurgical plants and brass/zinc production facilities, was
present on particles with diameters of up to 5 µm (Nriagu & Davidson, 1980). Dorn et al. (1976) reported
that 73% of the atmospheric zinc sampled from a farm near a lead smelter was in the form of particles
smaller than 4.7 µm (the upper limit of respirable particles), compared to 54% on a farm not affected by the
smelter. Zinc has been reported to be adsorbed to even larger particles from windblown soil and road dust.
Zinc bound to soil particulates may be transported to the atmosphere as wind-blown dust (Perwak et al.,
1980).

Anderson et al. (1988) examined atmospheric aerosol particles collected from Arizona. The aerosols
originated from the nearby urban area, the surrounding desert and several major copper smelters, which were
120 km from the sampling area. The particles containing zinc were divided into five groups: zinc sulfide,
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ferrous zinc, zinc phosphide, zinc chloride and metallic zinc. The authors suggested that the zinc sulfide
particles originated from the copper smelters, and that the zinc phosphide particles may have been emitted
during spray-painting of primer on steel, possibly from a construction site.

The proportion of zinc on atmospheric particulate matter collected from a rural area that was in water-soluble
form ranged from 12% to 48%, with a mean value of 26% (Lum et al., 1987). The proportion of zinc in the
dissolved fraction of rainwater collected from Rhode Island, USA ranged from 52% to 100% (Heaton et al.,
1990). Colin et al. (1990) reported zinc in rainwater collected in France. The geometric mean was 78 µg/litre
(1.20 µM) for total zinc and 3.25 µg/litre (0.05 µM) for insoluble zinc.

Zinc particles in the atmosphere are transported to soil and water by wet and dry deposition. These processes
are dependent upon particle size. Pacyna et al. (1989) derived a model which demonstrated that zinc
adsorbed on particles of low diameter and density can be transported through the atmosphere to regions in
Norway distant from their source in Central Europe. The dry deposition velocity for zinc was calculated to
be 0.5 cm/s. Analysis of Greenland snow samples shows a significant decrease in the atmospheric zinc
deposition over time. Between 1967 and 1989, the level decreased by a factor 2.5 (Boutron, 1991). More
extensive studies have shown a five-fold increase of zinc deposition in Greenland snow layers in the period
after the industrial revolution (from 1800 onwards), with a maximum during the 1960s followed by a
significant decrease of 40% between 1960 and 1990 (Boutron et al., 1995).

The deposition rate of airborne zinc downwind of an abandoned metalliferous mine complex was reported to
range from 3.10 ± 1.30 µg/cm2 per month at a site 10 m from the edge of the spoil tip, to 0.61 ± 0.14 µg/cm2
per month at a site 1000 m from the edge of the spoil tip (Roberts & Johnson, 1978).

Teraoka (1989) reported zinc concentrations in dry atmospheric fallout sampled in Japan to range from 290
to 790 mg/kg of ashed sample. Concentrations in bulk precipitations were 25–67 µg/litre.

Dasch & Wolff (1989) reported zinc concentrations in rain from Massachusetts, USA. The mean
concentration was calculated to be 3.7 ± 0.8 µg/litre. The enrichment factor (the degree of enrichment of an
element in the atmosphere compared to the relative abundance of that element in crustal material) was
calculated to be 110 ± 78. Enrichment factors have to be calculated and interpreted with care. The use of
simple enrichment ratios in a sample relative to average crustal abundance does not take into account the fact
that organic and inorganic enrichment processes cause trace metal levels to shift by orders of magnitude
(GSC, 1995). The source of zinc is therefore not entirely due to crustal material. Similar conclusions were
derived following analysis of atmospheric particles collected from near sea level in the North Atlantic, with
reported concentrations of 0.3- 27 ng/m3 (Duce et al., 1975).

4.1.2 Water and sediment

Zinc in water can be divided into seven classes (Florence, 1980):

• particulate matter (diameter > 450 nm)

• simple hydrated metal ion, e.g., Zn(H2O)62+ (diameter 0.8 nm)

• simple inorganic complexes, e.g., Zn(H2O)5Cl+, Zn(H2O)5OH+ (diameter 1 nm)

• simple organic complexes, e.g., Zn-citrate, Zn-glycinate (diameter 1–2 nm)

• stable inorganic complexes, e.g., ZnS, ZnCO3, Zn2SiO4 (diameter 1–2 nm)

• stable organic complexes, e.g., Zn-humate, Zn-cysteinate (diameter 2–4 nm)

• adsorbed on inorganic colloids, e.g., Zn2+Fe2O3, Zn2+SiO2 (diameter 100–500 nm)

• adsorbed on organic colloids, e.g., Zn2+-humic acid, Zn2+-organic detritus (diameter 100–
500 nm).
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Zinc compounds hydrolyse in solution to produce hydrated zinc ions, zinc hydroxide and hydrated zinc
oxides, which may precipitate. These reactions decrease the pH of the water, although the natural buffering
capacity of the water usually prevents any significant change (US DHHS, 1994).

Zinc is adsorbed strongly by ferric hydroxide in alkaline waters (Gadde & Laitinen, 1974). Zinc has also
been reported to be adsorbed on sulfides (Hem, 1972), silica (Huang et al., 1977), alumina (Huang et al.,
1977), manganese dioxide (Doshi et al., 1973), and humic acid (Guy & Chakrabarti, 1976).

The stability constant (logk) for zinc-fulvic acid complexes in lake water was reported to be 5.14 (Mantoura
& Riley, 1975).

Farrah & Pickering (1976) determined the adsorption of zinc to three clay minerals, kaolinite, illite and
montmorillonite. The adsorption capacity of the clays increased between pH 3.5 and pH 6.5. Under alkaline
conditions, zinc precipitated as hydroxy species, which adsorbed to the clay. At pH > 10.5 zinc returned to
solution as the zincate, although such a high pH is unlikely to exist in the environment. The attachment of the
hydroxy species was reported to be the controlling process for kaolinite and illite. The dominant controlling
mechanism in montmorillonite was ion exchange at the negative lattice sites.

Zinc sulfide is the most dominant form of zinc in anoxic sediments (Casas & Crecelius, 1994). Only the
uppermost sediments are oxic, and here zinc will primarily be associated with hydrous oxides of iron and
manganese as components of the clay fraction or as coatings on the surface of other minerals (US National
Academy of Sciences, 1977). In waters, zinc forms complexes with a variety of organic and inorganic
ligands (Callahan et al., 1979; US EPA, 1984). Up to 50% of the total zinc in acidic fresh waters is in a non-
colloidal inorganic form, such as zinc carbonate, zinc hydroxy carbonate or zinc silicate. In alkaline fresh
waters, most bound zinc is adsorbed to organic and inorganic colloidal particles.

Hydroxides and hydrous ions of iron and manganese are components of the clay fraction of sediments and
they also exist as coatings on the surface of other minerals (US National Academy of Sciences, 1977). When
these hydrous oxides are oxidized they may co-precipitate with zinc. As the precipitates form, they trap
various ions in their crystal lattice (Callahan et al., 1979).

Zinc is not directly affected by changes in redox potential (Eh), although the valencies and reactivities of the
ligands that react with zinc are (Callahan et al., 1979).

4.1.2.1 Fresh water

The pH of most fresh waters is in the range that is critical for the adsorption of heavy metals on particulates.
A change in pH of 0.5 can mean the difference between the majority of zinc being in an adsorbed or
desorbed form. Florence (1977) reported that zinc in several fresh waters at pH 6.0–6.1 was distributed
between labile ionic species and a stable inorganic form. The amount of zinc bound to organic colloids was
minor.

Elevated zinc concentrations were reported in water sampled from areas rich in ores (White & Driscoll,
1987). Organic material has an important role in the binding of zinc in fresh water, particularly at high pH
values (> 6.5). Spatial and temporal variations in the zinc concentration were reported to be minor. Peak
concentrations were reported during snowmelt, but were limited to meltwater in streams and at the lake
surface. Zinc did not appear to be retained in the lake. Transport of particulate-bound zinc to sediment
represented a minor flux. The authors suggested that long- and short-term variations in retention of zinc in
the lake due to surface water acidification may complicate quantitative interpretation of zinc deposition in
sediments.

4.1.2.2 Seawater

The chemical pathway of zinc is mainly determined by interactions with dissolved organic complexing
agents (Van den Berg et al., 1987). The dissolved zinc concentration throughout the Scheldt estuary
(Netherlands) was reported to vary according to the dissolved organic concentration. The proportion of
dissolved zinc determined to be in a labile form was 34–69%, owing to the low solubility of iron and
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competition for dissolved copper and zinc with organic complexing ligands. The concentration of these
ligands was calculated to be in the range 1.43–14.3 µg/litre (22–220 nM). The conditional stability constants
(logk values) of the zinc complexing ligands were calculated to be 8.6–10.6. The average product of ligand
concentrations and conditional stability constants (alpha coefficient) was 6 ´ 102.

Increases in the dissolved and suspended fractions of zinc in estuarine water were reported in the mixing
zone between fresh and brackish waters. The increases were attributed to the increased residence time of zinc
in the estuary compared to that in the fresh water. There was a five-fold increase in the amounts of leachable
zinc in sediments sampled from brackish waters compared with those in sediments from fresh waters. The
ratio of suspended zinc to leachable zinc was increased from 20% in fresh waters to 86% in brackish waters
(Grieve & Fletcher, 1977).

4.1.2.3 Wastewater

Patterson et al. (1977) demonstrated that zinc hydroxide precipitates at a faster rate from industrial
wastewaters than zinc carbonate. The minimum soluble zinc concentration reported was 0.25 mg/litre at pH
9.5. Treatment of the effluent with carbonate increased only the amount of dissolved solids. Optimization of
the zinc carbonate system with the use of denser sludges or better filtration methods provided no advantage
over the zinc hydroxide system.

Rudd et al. (1988) studied the forms of zinc in sewage sludges during chemical extraction and progressive
acidification treatment stages (pH values 4.0, 2.0 and 0.5). Fractionation profiles of samples from sequential
extraction demonstrated that the majority of zinc was associated with the tetrasodium pyrophosphate
(Na4P2O7) fraction, comprising 18–52% of the total zinc content. This fraction corresponds to organic and
some insoluble inorganic forms. The remaining zinc was evenly distributed between the ethylene diamine
tetra-acetic acid (EDTA) and nitric acid fractions. The potassium fluoride (KF) fraction accounted for 2–13%
of the total zinc, with less in the potassium nitrate (KNO3) fraction. The threshold for mobilization of zinc
was reported to approach pH 6.0. The majority of mobilizable metal was extracted at pH 2.0, with only slight
increases in the amount released at pH 0.5. Zinc was more easily extracted from raw sludges than from dried
forms of activated and digested sludges. The threshold for mobilization from liquid sludge samples was pH
4.0. Acidification of the sludge increased the proportion of zinc in an easily extractable form, e.g., from the
predominant Na4P2O7 fraction to KNO3-extractable and KF-extractable forms at pH 0.5.

4.1.2.4 Groundwater

Zinc solubility in groundwater increases with redox potential (Eh) value (Hermann & Neumann-Mahlkau,
1985; Pedroli et al., 1990). The solubility also increases with decreasing pH (Pedroli et al., 1990).

4.1.2.5 Sediment

There are two forms of sediment: suspended sediment and bed sediment. Zinc and other heavy metals are
highly partitioned to suspended sediment in the water column. Trefry & Presley (1971) calculated that 90%
of the zinc was carried in the particulate phase in a clean stretch of the Mississippi River; 40% was reported
for a contaminated river (Kopp & Kroner, 1968). Golimowski et al. (1990) reported ranges in distribution
constant Kd (the ratio of chemical concentration in the solid phase to the concentration in the liquid phase)
for three rivers in the Netherlands: 10 000–145 000 (Rhine), 10 000–190 000 (Waal) and 75 000–230 000
(Meuse).

Phosphates and iron hydroxides play an important role in the transfer of heavy metals from river water to
sediments (Houba et al., 1983). Deposition to the bottom of a water body occurs concurrently with a change
in the microenvironment. Organic matter reaching the bedded sediment is oxidized. Because oxygen and
nitrate are limited, sulfate is the most prevalent terminal electron receptor. Thus sediments tend to be sulfide-
rich. Sulfide reacts with transition metals such as zinc to form metal sulfide compounds of low solubility
(Allen et al., 1993).

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As bedded sediments change from a reduced to an oxidized state, greater amounts of zinc are mobilized and
released in soluble forms (US EPA, 1987). The pH controls the interaction of zinc with dissolved organic
carbon, a process which determines the bioavailability of zinc (Bourg & Darmendrail, 1992). Compared with
other physical processes, diffusive transport of zinc to and from the sediment pore water is negligible.

Sprenger et al. (1987) recorded the zinc concentrations in water and sediments sampled from six acidic lakes
in New Jersey, USA. Increased zinc concentrations were reported in the most acidic lakes. The active growth
of macrophytes in one of the lakes resulted in sediment with a high organic matter content, with the
subsequent retention of zinc.

In estuaries, desorption of zinc from sediments occurs with increasing salinity (Helz et al., 1975) owing to
the displacement of adsorbed zinc ions by alkali and alkaline earth cations, which are abundant in brackish
and saline waters (Callahan et al., 1979).

4.1.3 Soil
The major sources of zinc in soils are the zinc sulfide minerals, such as sphalerite and wurtzite, and to a
lesser extent minerals such as smithsonites (ZnCO3), willemite (Zn2SiO4), zincite (ZnO), zinkosite (ZnSO4)
franklinite (ZnFe2O4) and hopeite (Zn3(PO4)2· 4H2O).

Zinc in soil is distributed between the following fractions (Viets, 1962):

· dissolved in soil water

· exchangeably bound to soil particles

· bound to organic ligands

· occluded in secondary clay minerals and metal oxides/hydroxides

· present in primary minerals.

Only those fractions of zinc that are soluble or may be solubilized are available to plants (Brümmer, 1986).
Zinc undergoes reactions involving precipitation/dissolution, complexation/dissociation and
adsorption/desorption. These reactions and the resulting bioavailability of zinc will be controlled by the pH
and redox potential of the soil, the concentration of zinc ions and other ions in the soil solution, the nature
and number of adsorption sites associated with the solid phase of the soil, and the concentration of ligands
capable of forming organo-zinc complexes (Kiekens, 1995).

Under most conditions, the amount of zinc present in adsorbed soil fractions is much higher than the soluble
fraction that remains in the pore waters or soil solution. A change in any of the above factors will result in a
change in the overall equilibrium of the soil, with zinc transformed to different forms until a new equilibrium
is reached. Such equilibrium displacements may occur as a result of plant uptake, losses by leaching, zinc
input, changes in soil moisture content, changes in pH, mineralization of organic matter, and changes in the
redox status of the soil. The proportion of zinc in soil solution increases with decreasing pH. In high pH soils
(> 6.5), the chemistry of zinc is dominated by interactions with organic ligands.

Zinc forms complexes with chloride, phosphate, nitrate and sulfate. The complexes with sulfate and
phosphate are the most important with regard to total zinc in solution. Under neutral or alkaline conditions,
ZnHPO4 contributes to zinc in solution, although this depends on phosphate activity (Kiekens, 1995). The
formation of carbonates is also possible (Misra & Tiwari, 1966), and is probably an important factor in
explaining some of the retention of zinc at high pH values. Slow diffusion of zinc into soil reduces the
mobility and bioavailability of zinc (Brümmer, 1986).

Humic and fulvic acids are important for the speciation of zinc in soil and aquatic systems. For example, 60–
75% of zinc in soil solution has been reported to be bound by fulvates (Hodgson et al., 1966; Geering &
Hodgson, 1969). These acids are defined by solubility. Because fulvic acid is soluble, its chelates are mobile
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in the soil. Stability constants for zinc fulvates and humates have been reported by a number of investigators
(Courpron, 1967; Schnitzer & Skinner, 1967; Stevenson, 1991); they are dependent on pH. Because the acids
are mixtures, not pure chemicals, the stability constants are averages representing the extent of metal or
proton binding over the limited range of concentrations for the titration. Adequate descriptions of the metal
binding characteristics of these heterogeneous organic substances can be achieved using models
incorporating a number of discrete binding sites (Tipping, 1993) or a continuum of binding sites of varying
pK (Perdue & Lytle, 1983).

The selective adsorption of zinc and the occurrence of an adsorption/desorption hysteresis effect is controlled
by the following parameters (Kiekens, 1995):

• number of pH-dependent adsorption sites

• interactions with amorphous hydroxides

• affinity for the formation of organomineral complexes, and their stability

• formation of hydroxy complexes
• steric factors
• properties of zinc including: ionic radius, polarizability, thickness of the hydration sheet,
equivalent conductance, hydration enthalpy and entropy.

The observed hysteresis effect may have important practical consequences and applications. Addition of soil
additives such as lime (calcite), zeolite, hydroxyapatite, vermiculite, bentonite, beringite (a modified clay)
and other clay minerals, and other products, such as selective cation exchangers (e.g., polystyrene resins),
steel shots, Thomas basic slags and hydrous manganese oxide, can reduce the mobility of zinc and uptake of
plants cultivated in a contaminated soil (Van Assche & Jansen, 1978; Kiekens, 1986; Vangronsveld et al.,
1990, 1995a,b; Vangronsveld & Clijsters, 1992; Mench et al., 1994).

Soils high in clay or organic matter have higher zinc adsorption capacities than sandy soils with a low
organic content (Shuman, 1975). A further reduction in zinc adsorption capacity of sandy soils, compared to
soils with a high colloidal-size material content, was reported at low pH. Zinc accumulated in the organic
horizon (organic matter layer) of sandy soil, with low concentrations in the mineral horizons (mineral layers)
(Pedroli et al., 1990).

The mobility of zinc in soil increases at low soil pH under oxidizing conditions and at a lower cation
exchange capacity of soil (Tyler & McBride, 1982: Hermann & Neumann-Mahlkau, 1985). The dominant
species under anaerobic conditions is zinc sulfide, which is insoluble and so the mobility of zinc in anaerobic
soils is low (Kalbasi et al., 1978; Perwak et al., 1980).

Zinc can be readily displaced by calcium, which can be abundant in the soil solution (Van Bladel et al.,
1988). There is greater potential for leaching of zinc in light acidic soils, compared to soils with a high
organic matter or calcium carbonate content. MacLean (1974) studied the factors that determined the
extractability of zinc with diethylenetriamine-penta-acetic acid (DTPA), magnesium chloride or calcium
chloride in soils incubated with zinc solutions. The amount of zinc extracted increased with increasing rates
of added zinc and increasing amounts of added phosphorus. Extractable zinc was negatively correlated to the
soil organic matter content. Liming reduced the amount of extractable zinc in an acid soil. Pretreatment of
the soil with phosphate fertilizer also increased the amount of zinc extracted.

The distribution constant for zinc between soil and water (Kd) has been reported to vary from 0.1 to 8000
litres/kg (Baes & Sharp, 1983). Baes et al. (1984) reported an average Kd value of 40 litres/kg. Anderson &
Christensen (1988) reported a range of Kd values for zinc of 1–3540 litres/kg. The Kd value was strongly
related to pH, although the presence of extractable manganese oxides and hydroxides and the magnitude of
the anion exchange capacity were also important. Gerritse et al. (1982) reported Kd values in a variety of soil
types and sewage sludges: 70–100 litre/g for sandy loam soil; 2.1 and 3.2 litre/g for organic soil; 0.2–4 litre/g
for sandy soils; 60–90 litre/g for sewage sludge; and 3–4 litre/g for sewage sludge after aeration. Bunzl &
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Schimmack (1989) calculated the Kd value for zinc in the organic and mineral horizon of podzol forest soil.
The median values were 14 and 41 litre/kg , respectively. The organic-horizon Kd values were not
significantly correlated with pH.

Zinc supplementation of soils is achieved using sewage sludge or chemical fertilizers. Sanders & Adams
(1987) added sewage sludge to a clay loam and two sandy loam soils. The concentration of extractable zinc
increased rapidly at pH values below a threshold of 6.2–7.0, with less being extracted from the clay soil than
from the sandy soils. Sanders & El Kherbawy (1987) determined zinc adsorption equilibria in United
Kingdom soils that had similar textures and zinc concentrations but different pH values. Zinc was added to
the soils in the form of zinc nitrate or sewage sludge. There were no differences in the results obtained with
the different zinc treatments.

Mehrotra et al. (1989) studied the speciation of zinc in primary, secondary, digested and zinc-spiked sewage
sludge. They found that 50% of zinc was organically bound and there were no differences in the zinc
speciation or zinc loading of the different sludge types. Zinc added to the sludge is redistributed in a similar
fashion to existing zinc. It was concluded that the distribution pattern remains more or less the same whether
zinc is added during or after digestion. However, other studies have reported that zinc added to sludges after
digestion is more readily bioavailable than zinc added prior to digestion. Bloomfield & McGrath (1982)
determined the levels of extractable zinc in sludges to which zinc sulfate had been added either prior to or
following anaerobic digestion. All three extractants used (NH4OAc, HOAc and EDTA) removed zinc
adsorbed on pre-digested sludge more readily than those incorporated during the digestion process. Davis &
Carlton-Smith (1981) reported increased extractability of zinc in sewage sludges amended with soluble zinc
salts compared to those to which insoluble zinc sulfide was added. Speciation of heavy metals in sewage
sludge and sludge-amended soils has been reviewed by Lake et al. (1984).

Williams et al. (1984) determined the fate of zinc in soil amended annually for 6 years with sewage sludges,
one of which contained industrial waste. Zinc moved up to 10 cm below the area of sludge incorporation.
The ratios of DTPA-extracted zinc to nitric acid-extracted zinc were similar over the last 4 years and at all
soil depths. The availability of zinc was highest in the soils with the lowest pH.

4.2 Bioavailability
The bioavailable fraction (a physicochemical term) is the maximum fraction of the total zinc concentration
that can potentially be taken up by organisms, essentially over and above very stable forms of zinc. Uptake (a
biological-physiological term) refers to the fraction that is actually taken up by organisms. The term
"bioavailability" is used to describe the interaction in nature of physicochemical properties and physiological
factors. For instance, zinc in the aquatic environment interacts with binding agents in the aqueous phase and
similarly with biological receptors.

Knowledge of the bioavailable fraction is a critical requirement for risk assessment. Total concentrations in
the aquatic and soil environments alone, including food, are not useful for estimating bioavailability.

4.2.1 Factors affecting bioavailability

The most important physicochemical factors affecting bioavailability are: pH, dissolved organic carbon
(DOC), water hardness, competing ions, soluble ligands, and binding sites on solid phases (e.g., metal oxides
in suspended matter, sulfides in sediments and anaerobic soils) (Florence & Batley, 1980).

The most important physiological factors affecting bioavailability are: adsorption sites at the cell wall (type
and quantity), exudation of organic substances, protons, and gaseous substances (e.g., oxygen, carbon
dioxide) (Cakmak & Marschner, 1988; Bergman & Dorward-King, 1996).

The above physicochemical and physiological factors apply both to aquatic and to terrestrial ecosystems.
Bioavailability is determined on the basis of a combination of these factors as well as the kinetics of the
chemical and biological processes concerned.

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4.2.2 Techniques for estimation

There are currently two different approaches for estimating bioavailability: correlative (e.g., extractable
metals in the terrestrial environment, free metal ion in the aquatic environment; Campbell, 1995); and
predictive, which models bioavailability, for instance at gill surfaces (Bergman & Dorward-King, 1996).
These approaches need to be further developed and validated against bioassays. In particular, improved
analytical techniques are required to measure zinc speciation in environmental and biological compartments
(the latter related to human health). Extraction techniques are better developed in some areas than in others,
for instance they are particularly well developed to measure zinc deficiencies in agricultural soils (relative to
crop production) (Brennan et al., 1993). Leach tests, although they may provide a prediction of potential
environmental risk, do not accurately measure the bioavailable fraction.

4.3 Biotransformation
4.3.1 Biodegradation
Zinc is an element and therefore cannot be biodegraded, in contrast to zinc compounds. Some studies have
examined microbial or abiotic transformations of zinc compounds which can result in a change in zinc
speciation (Touvinen, 1988).

Biomethylation of zinc has not been observed.

Biological degradation of zinc complexes is necessary for the normal functioning of ecosystems to enable the
recycling of zinc from litter, faeces and dead organisms. In certain environments, bacteria as well as fungi are
able to oxidize zinc sulfide in ores, producing zinc sulfate which can be leached into solution (Ilyaletdinov et
al., 1977; Tuovinen, 1988).

4.3.2 Bioaccumulation

The concept of bioaccumulation was originally designed to determine the accumulation of a

substance/element in biota in comparison to its occurrence in an environmental compartment, i.e., water, soil
or sediment. The ratio between the concentration of a substance/element in biota and that in an
environmental compartment was defined as the bioconcentration factor (BCF). For example, for uptake from
water the BCF is a unitless value calculated by dividing the "steady state" wet tissue concentration of a
particular substance by its "steady state" water concentration. Bioaccumulation factors (BAFs) differ from
BCFs in that they assume uptake from water and accumulation from the diet.

In the case of zinc, the BCF is not useful for relating uptake to adverse effects, because it does not consider
physiological parameters (Canada/EU, 1996; Chapman et al., 1996). The fact that zinc, as an essential metal,
is naturally concentrated by living organisms means that the BCF for zinc bears no relationship to toxicity.
Bioaccumulation does not differentiate between zinc adsorbed to the outer surface of organisms, and the zinc
within organisms. Rapid bio-inactivation of zinc, for instance compartmentation into vacuoles, may result in
elevated BCFs with no difference in the health of the organism (Mathys, 1977). Further, the fact that many
organisms are capable of regulating internal zinc concentrations within certain limits means that these
organisms can stabilize internal concentrations against perturbations or high concentrations in the external
environment. Thus, zinc tissue concentrations do not necessarily reflect ambient concentrations and, in
contrast to lipophilic organic compounds, zinc BCFs cannot be considered to be constant ratios between
tissue concentrations and external water concentrations. Finally, an inverse relationship has been observed in
many biological organisms between the BCF and external water concentrations.

Accumulation of zinc to meet physiological requirements can be mistaken for trophic transfer. However, zinc
is not biomagnified (Beyer, 1986; Suedel et al., 1994).

4.3.2.1 Aquatic organisms

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In aquatic environments, organisms tend to have a high surface:volume ratio, which is necessary for
exchange processes (oxygen, carbon dioxide, nutrients). Exchange processes are enhanced by the
enlargement of the receptive tissues (e.g., gills in fish and some benthic organisms, and soft body surfaces in
some benthic organisms) and/or by enhancing water passage through the organism and/or its tissues. The
effect on the health of an organism of adsorbed zinc is different to that of incorporated intracellular zinc;
however, in most experiments and sampling procedures the impact of adsorption is not considered. Thus, for
instance, gelatinous algae such as Chlamydomonas spp. and Gloeococcus spp. are more zinc-insensitive than
other species (Foster, 1982). The presence of other organisms may diminish the adsorption of an element by
changes in its chemical speciation (Nakatsu & Hutchinson, 1988). The amount of zinc taken up by an
organism will strongly depend on the speciation of the metal in the environment. Within the organism the
metal can be compartmented in various ways, either being moved to sites of demand (sinks) or partly bio-
activated by storage in vacuoles in plants or, in the case of animals, excreted.

As a general rule in ecology, organisms, except cultivated ones, have had sufficient time to adapt to the
concentration of bioavailable elements in their ecosystem. However, interference by humans, causing a rapid
change in the concentration in the environment, can break down this adaptation. Diversity in niches is a
general ecological rule; active excretion of substance to modify bioavailability is a rising issue in modern
ecophysiology. In special situations, the life cycle of an organism may be adapted to seasonal changes in
element availability.

Aquatic organisms accumulate zinc from food and water. The relative importance of these sources varies
between species (Hare et al., 1991; Timmermans et al., 1992; Weeks & Rainbow, 1993).

The bioavailability of zinc in water is influenced by physicochemical and physiological factors (section 4.2).

In general, animals regulate their internal zinc concentrations. However, in some, such as barnacles, the
internal zinc concentration is a consequence of zinc storage in granules (Rainbow, 1987; Powell & White,
1990). The concentration at which zinc is homoeostatically regulated is species-specific (Larson & Hyland,
1987) and the external zinc concentration at which regulation breaks down depends on both intrinsic (e.g.,
species) and extrinsic (e.g., temperature) factors (Nugegoda & Rainbow, 1987).

Examples of the ranges of zinc concentrations that can be found in aquatic organisms are provided in Table
9. These ranges are not all-inclusive, are provided solely for information purposes, and do not necessarily
bear any relationship to toxicity, which is discussed in Chapter 9.

Table 9. Zinc concentrations in representative organisms during exposure to waterborne zinc

Species Duration Exposure Zinc Experimental Reference

of concentration concentration conditions
exposure in organism
(dry weight)

Gammarus pulex 3 days 2020 µg/litre 555 µg/g pH 7.7, temperature Xu & Pascoe
11 ° C, (1993)

15 days 410 µg/litre 213 µg/g hardness 109 mg/litre

CaCO3

Gammarus pulex 15 days 65 µg/litre 1502 µg/g pH 7.1, temperature Xu & Pascoe
10–12 ° C, hardness (1994)
319 µg/litre 2159 µg/g 108 mg/litre CaCO3

Daphnia magna 40 days 250 µg/litre 420 µg/g pH 7.8, temperature Memmert
19–22 ° C, total (1987)
hardness 2.2
mmol/litre

Chironomus riparius 28 days 900 µg/litre 880 µg/g temperature 20 ° C Timmermans et

al. (1992)

B h d i i 35 d 250 /lit 390 / H78 t t M t

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Brachydnanio rerio 35 days 250 µg/litre 390 µg/g pH 7.8, temperature Memmert
19–22 ° C, total (1987)
hardness = 2.2
mmol/litre

Littorina littorea 42 days 150.10-10 605 µg/g full strength seawater Mason (1988)
mol/litre

Orchestia 21 days 32 µg/litre 193 µg/g temperature 10 ° C, Weeks &

gammarellus salinity 33% Rainbow (1991)
1000 µg/litre 412 µg/g

Orchestia 21 days 32 µg/litre 202 µg/g temperature 10 ° C, Weeks &

mediterranae salinity 33% Rainbow (1991)
1000 µg/litre 324 µg/g

Carcinus maenas 21 days 2–316 µg/litre 82 µg/g temperature 10 ° C, Rainbow (1985)

salinity 33%

Palaemon elegans 21 days 2.5–100 76 µg/g (5 ° temperature 5–20 ° C, Nugegoda &

µg/litre C) salinity 32% Rainbow (1987)

90 µg/g
(20 ° C)

Fundulus heteroclitus 56 days 210 µg/litre 198 µg/g temperature 20–24 ° Sauer & Watabe
C, salinity 25% (1984)
7880 µg/litre 355 µg/g

4.3.2.2 Terrestrial organisms

Zinc taken up by plant roots is mainly in the form of Zn2+, although absorption of hydrated zinc, zinc
complexes and zinc organic chelates has also been reported (Kabata-Pendias & Pendias, 1984). Many factors
affect the bioavailability of zinc in soils, including total zinc content, pH, organic matter, adsorption site,
microbial activity and moisture content. Bioavailability is also determined by climatic conditions and
interactions between zinc and other macro- and micronutrients in soil and plants (Kiekens, 1995).
Determining factors can be summarized as follows (Kiekens, 1995):

• Highly leached acid soils may have low zinc levels.

• With increasing pH levels there is an increase in the adsorption of zinc by negatively
charged colloidal soil particles, with a subsequent decrease in the solubility of zinc.
• In soils with a low organic matter content, the availability of zinc is directly affected by the
content of organic complexing or chelating agents originating from decaying organic matter
or root exudates.
• Low temperatures and light intensities restrict root development and therefore zinc uptake.
• Reduced zinc uptake has been reported in soils with high phosphorus levels.

• Interactions with other minerals, such as iron, copper, nitrogen and calcium, also reduce
zinc uptake.

The factors listed above primarily affect the fraction of zinc in soil that has been immobilized by readily
reversible processes. Long-term bioavailability of zinc in soil is influenced by mineralization processes, such
as lattice penetration, which result in irreversible binding of zinc (Kiekens, 1995).

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The absorption of zinc by the lichen Usnea florida was found to follow the classical Langmuir adsorption
isotherm and was therefore reversible (Wainwright & Beckett, 1975). The log stability constant was
calculated to be 4.46, suggesting a stable association between the zinc ion and the binding site. Zinc binding
was dependent upon pH owing to competition between hydrogen ions and zinc for binding sites.

Falahi-Ardakani et al. (1987) reported uptake of zinc by broccoli, cabbage, lettuce, egg plant, pepper and
tomato grown in a medium enriched with composted sewage sludge. The uptake of zinc was calculated to be
4–10 mg per week.

Henry & Harrison (1992) studied the uptake of metals by turfgrass, tomatoes, lettuce and carrots grown in
different soils (control soil, soil amended with NPK fertilizer, compost, and a 1:1 soil-compost mixture). The
loading rates of zinc in the control soil, compost mixture and compost were 232, 239 and 245 kg/ha,
respectively. The order of uptake by plants was in the order lettuce > grass > carrots > tomatoes. Uptake
slopes for lettuce, grass and carrots grown in compost were higher for than those for plants grown in soil.
Zinc concentrations were higher in lettuce, carrots and grass grown in compost and the compost-soil mixture
than in plants grown in either the control or fertilized soils. The zinc concentrations in the tomatoes showed
no variation.

Singh & Låg (1976) grew barley (Hordeum vulgare) in soil sampled from an area near a zinc-smelting plant.
Initial zinc concentrations were 545–710 mg/kg. Zinc sulfate was added to the soils at concentrations of 0,
150, 300, 450 and 600 mg/kg. The zinc concentration in the barley increased with increasing total zinc
concentration in the soil. The proportion of soil zinc that was bioavailable to plants was reported to be
independent of the zinc application.

Increased uptake of zinc was reported for ryegrass (Lolium perenne) grown in sludge-amended soil: the zinc
concentration in grass exposed to the sludge was 7.5 times that in controls (Dudka & Chlopecka, 1990).

MacLean (1974) studied the uptake of zinc by maize (Zea mays), lettuce (Lactuca sativa) and alfalfa
((Medicago sativa) grown successively (for 6 weeks, 5 weeks and 16 weeks, respectively) in pots with soil of
varying zinc concentrations. The concentration of zinc in the plants increased with increasing soil zinc
concentration. Maize and lettuce grown in a soil pre-treated with phosphorus tended to have lower zinc
levels than those grown in soils without any pre-treatment. Increased zinc levels were also reported in plants
grown in soils with higher organic matter contents.

Jones (1983) grew lettuce (Lactuca sativa) and radish (Raphanus sativus) in soil collected from plots 10 m
and 90 m from a rusty galvanized steel electrical transmission (hydro) tower. The plants were harvested after
45 days. The zinc content was higher in soil sampled nearer the hydro tower. The plants grown in this soil
had the highest zinc concentrations; lettuce roots had significantly higher zinc levels than lettuce tops, while
radish tops had significantly higher zinc levels than radish roots. No differences between zinc levels in tops
and roots were reported for plants grown in the soil sampled 90 m from the tower.

Gintenreiter et al. (1993a) studied the bioaccumulation of zinc by gypsy moth (Lymantria dispar) larvae
following dietary exposure of first instar larvae to 100 or 500 mg/kg. Zinc concentrations in the first instar
larvae were similar at both exposure levels. The subsequent uptake of zinc was dependant upon exposure
concentration. An increase in larval zinc concentration was reported at the 500 mg/kg dose. At the 100
mg/kg dose and in the control larvae, a dose-related decrease in larval zinc concentrations was reported. The
highest zinc concentration factor was reported to be 3.5. The zinc concentration in larval faeces was reported
to be inversely related to the zinc concentration in the larvae. Zinc levels in the exuviae decreased with
successive larval stages, whereas constant zinc concentrations were reported for the head capsules in all
groups. The total amount of zinc in the larvae increased at every stage with the highest amount detected in
the pupae. However, the adult life stages tended to have less zinc.

A positive relationship between the zinc concentrations in the terrestrial amphipod (Arcitalitrus dorrieni) and
zinc concentration in its food was reported (Weeks, 1992). The mean zinc accumulation rate was calculated
to be 2.21 µg/g per day, which was calculated to be equivalent to 1.11% of the total body zinc per day.

Hames & Hopkin (1991) determined the assimilation of zinc in two species of woodlouse, Oniscus asellus
and Porcellio scaber fed for 115 h on leaves treated with zinc chloride. The mean zinc assimilation rate

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during the exposure period was 29.4% in O. asellus and 36.7% in P. scaber, with a significant (P < 0.001)
inter-species difference.

Hopkin & Martin (1985) studied the uptake of zinc by the spider Dysdera crocata exposed to zinc through its
diet of woodlice (P. scaber). Spiders fed on woodlice collected from the same site as themselves consumed
34.5% of the total zinc in the woodlice. Spiders fed on woodlice from an area contaminated with heavy
metals consumed 42.4% of the total zinc in the woodlice. There were no differences in zinc content of the
spiders fed on woodlice from their own site, and those spiders starved throughout the experiment. The
spiders were therefore able to excrete any excess absorbed zinc and did not assimilate it.

Lindqvist & Block, (1994) studied the excretion of zinc by the grasshopper Omocestus viridulus during
moulting. The grasshopper nymphs were fed grass leaves containing a known amount of radiolabelled zinc,
and the zinc contents of the grasshopper faeces, exuviae and carcasses were determined. The exuviae
accounted for only a minor part of excreted zinc. After rearing for 15 days, approximately 50% of the
ingested zinc remained in the grasshoppers.

Recio et al. (1988) studied the cellular distribution of zinc in slugs (Arion ater) exposed to dietary zinc. The
highest zinc concentration was reported in the lipofuscin material of the excretory cells. Zinc was also
detected in the perinuclear cytoplasm and the spherules of the calcium cells (low zinc exposures and short
exposure times only). The authors suggested that slugs could be used to indicate high levels of zinc in the
environment.

Simkiss & Watkins (1990) determined the factors that affect the uptake of zinc by the garden snail, Helix
aspersa. The snails were divided into four treatment groups, receiving an artificial diet (controls), antibiotics,
zinc nitrate at a concentration of 1.5 µmol/g in the artificial diet, or a diet supplemented with antibiotics and
zinc nitrate. Food consumption in the two groups fed a diet containing zinc was reported to be reduced to
about 38% of normal. However, the dry weights of snails from each group did not differ after exposure for
either 4 or 8 weeks. A direct linear relationship between soft body zinc content and dietary zinc consumed
was reported for the snails that were not fed antibiotics. The dietary intake was also correlated with the zinc
concentration of the digestive gland. The same was also evident in the snails fed antibiotics, although the
relationship was significantly different. In a second experiment it was reported that snails fed a bacterially
contaminated diet absorbed more zinc than snails fed a sterile diet.

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1 Environmental levels
In nature, zinc occurs only rarely in its metallic state and the vast majority of environmental samples contain
the element only in the form of zinc compounds. In the following text, therefore, zinc content relates to those
compounds.

5.1.1 Air

Zinc concentrations in air are summarized in Table 10. The proportion of zinc derived from anthropogenic
sources remains uncertain (see section 3.2). In air, zinc is primarily adsorbed to particulate matter, which is
expected to be short-lived in the atmosphere (Perwak et al., 1980). The mass median diameter for zinc-
containing particles in airborne dust is 1.5 µm for rural and urban sites (Lioy et al., 1978).

Table 10. Zinc concentrations in atmospheric particulate matter

Area Year Particle size Zinc concentration Reference

(µm) (ng/m3)

North Atlantic Ocean (various 1970–1972 >0.1 0.3–27 Duce et al. (1975)
sites)
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North Sea (various sites; 91 1988–1989 >0.5 74.6a (nd–611) Ottley & Harrison
samples) (1993)

North Sea, Helgoland 1985–1986 not given 32.8b (4.7–185) Kersten et al. (1988)

North Sea (various sites; 98 1988–1989 not given 41a (0.7–250) Chester & Bradshaw
samples) (1991)

North Sea (65 samples) 1980–1985 not given 67.4b (5.0–1460) Baeyens &
Dedeurwaerder (1991)

Baltic Sea (various sites; 17 1985 >0.1 26.6c (7.0–54.5) Haesaenen et al. (1990)
samples)

South Norway, Birkeness (160 1985–1986 not given 11d; 15a (<0.4–114) Amundsen et al. (1992)
samples)

Germany/Belgium, rural area not given 100–300 Cleven et al. (1993)

United Kingdom, rural area not given 41a (1.4–237) Yaaqub et al. (1991)

Netherlands, rural area 1984–1985 not given 30 van Daalen (1991)

Netherlands 65 Cleven et al. (1993)

Netherlands (4 sites) 1990 60–80 CCRX (1991)

1992 38–57 CCRX (1994)

USA, urban air 1973 MMD 0.58- 100–1700 Lee & Von Lehmden
1.79 (1973)

USA, San Francisco Bay Area 1970 not given 27–500 John et al. (1973)
(9 sites)

USA, New York City (1 site) 1972–1975 MMD: 1.5 330c (293–379) Lioy et al. (1978)

USA, cities (87 samples) <10–840 Schroeder et al. (1970)

USA, 19 cities (86 samples) not given not given 10–2400 Cole et al. (1984)

USA, Idaho (site near lead 1972 not given 4620c (270–15 700) Ragaini et al. (1977)
smelter)

Germany/Belgium, urban area 400–1000 Cleven et al. (1993)

Germany, industrial area (48 1983 not given 140–810 Lahmann (1987)
samples)

Germany, industrial area (35 1984 170–730 Lahmann (1987)

samples)

Belgium, Angleur 1986 9300 Cleven et al. (1993)

South-Holland, industrial area 1984–1985 not given 70 van Daalen (1991)

MMD = mass median diameter; nd = not detected

a Arithmetic mean.

b Mean.

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c Average.

d Median.

In general, zinc levels in urban and industrial areas are higher than in rural areas. Natural atmospheric zinc
levels due to weathering of soil are almost always less than 1000 ng/m3. Levels of 10- 300 ng/m3 are given
for background concentrations and up to 1000 ng/m3 for urban industrial areas. Zinc concentrations of 0.3-
27 ng/m3 were found over the Atlantic Ocean, < 0.4–300 ng/m3 in European rural areas, and 10–2400 ng/m3
in urban areas (see Table 10). For indoor air in an urban setting, zinc concentrations were in the range 0.1–
1.0 µg/m3 (Henkin, 1979).

Air zinc levels in Belgium have shown a decreasing trend. In 1989–1990, levels were 150–380 ng/m3 in
rural areas and small towns, 140–210 ng/m3 in large cities, and 500–1270 ng/m3 in industrial areas (IHE,
1991). By 1992–1993 levels had fallen to 70- 100, 100–170 and 390–1020 ng/m3 for the same locations
(VMM, 1994).

In the Netherlands, yearly average zinc levels in the air at four sampling sites varied between 60 ng/m3 and
80 ng/m3 in 1990 (CCRX, 1991). By 1992, the averages had decreased to 43–57 ng/m3 (CCRX, 1994). The
98th percentile of the daily values in 1992 was < 210 ng/m3 (CCRX, 1994).

5.1.2 Precipitation
Deposition of airborne zinc is strongly dependent on particle size and meteorological factors, primarily wind
speed and humidity. Wet deposition predominates with estimated values for zinc removal from air of 60–
90% (Ohnesorge & Wilhelm, 1991). In rainwater (North Sea, 21 samples), Baeyens et al. (1990) measured
average concentrations of dissolved zinc of 500 ± 500 g/litre. In rain sampled on a gas platform in the North
Sea, Peirson et al. (1973) found an average zinc level of 2000 µg/litre (includes dry deposition). The annual
wet deposition to the North Sea has been estimated to be in the range 14- 53 µg/cm2 (Peirson et al., 1973;
Dedeurwaerder et al., 1982; Baeyens et al., 1990).

The mean annual wet deposition of zinc in the Netherlands was determined to be 1.2 µg/cm2 in 1992
(CCRX, 1994).

In Germany, zinc levels in rain were 7–26 µg/litre in rural areas, 23 µg/litre in urban areas, and up to 90
µg/litre in urban industrial areas (Malle, 1992). Peirson et al. (1973) reported an annual average of 85 µg/litre
zinc in rain collected in the United Kingdom in 1971. In Nigeria (1976), rain was found to contain 130
µg/litre and annual total zinc deposition was calculated at 10 µg/cm2 (Beavington & Cawse, 1979).

Samples from Greenland snows analysed for their heavy metal contents showed a decrease in anthropogenic
zinc by a factor of about 2.5 during the period 1967–1989, which is stated to be a consequence of the
abatement policies for industrial emissions in the European Union and North America (Boutron et al., 1991).
The same authors have more recently reported a five-fold increase of zinc deposition in Greenland ice in the
period since the industrial revolution (from 1800 onwards) with a maximum during the 1960s followed by a
significant decrease (40%) between 1960 and 1990 (Boutron et al., 1995). However, not all studies have been
successful in detecting anthropogenic inputs of zinc distant from point source emissions. For example,
studies of the metal content of lake sediments in the Arctic have failed to detect any anthropogenic inputs
(Gubala et al., 1995).

5.1.3 Water

When interpreting the data on water concentration of zinc, it is necessary to be aware that the higher values
reported in early studies may be due to contamination of the samples.

Zinc concentrations in fresh waters depend significantly on local geological influences and anthropogenic
input. As a result of chemical weathering of minerals, soluble zinc compounds, such as zinc sulfate, are

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formed which may be transferred to surface waters especially at low pH levels (Perwak et al., 1980). Urban
runoff, mine drainage and municipal and industrial effluents can also make a considerable contribution to the
zinc load of surface water (US EPA, 1980).

In water, zinc is present primarily in the ionic form, but it has a strong tendency to adsorb to suspended
organic matter and clay minerals or to precipitate with iron or manganese oxides, resulting in zinc removal
from the water column and enrichment of sediments (Perwak et al., 1980). Dissolution of zinc increases at
low pH, low hardness and high temperature (Malle, 1992).

5.1.3.1 Fresh water

An overview of zinc concentrations in fresh water is given in Tables 11 and 12. In natural fresh water
concentrations rarely exceed 40 µg/litre (Spear, 1981); Bowen (1979) reported a medium background value
of 15 µg/litre, with a range of < 1–100 µg/litre. For various rivers worldwide, Holland (1978) reported
average values of 5–45 µg/litre. Higher average levels are associated with zinc-enriched ore deposits and
anthropogenic sources of pollution. The average zinc concentration of the river Rhine at Lobith was reduced
from 57 µg/litre in 1984 to 22 µg/litre in 1993 (see Table 11). Using an erosion model, the natural
background level has been estimated at 4 µg/litre (Van der Weijden & Middelburg, 1989), whereas Van
Tilborg & Van Assche (1995) have suggested that the natural concentration of zinc in the Rhine is about 10
µg/litre. The estimated zinc load of the Rhine decreased by 42% from 3600 tonnes/year in 1985 to 2 100
tonnes/year in 1990. In the Scheldt river at the Belgian-Netherlands border, total zinc concentration declined
from about 120 µg/litre in 1975 to approximately 50 µg/litre in 1989 (Goethals, 1991). The annual average
zinc concentration in United Kingdom rivers decreased from 42 µg/litre in 1978 to 22 µg/litre in 1992 (UK,
1994).

Table 11. Zinc concentrations in fresh water

Area Year pH Particle Zinc Reference

size concentration
(m m) (m g/litre)

Various rivers, worldwide 5–45a Holland (1978)

Canada, unpolluted rivers and lakes <40 Spear (1981)

USA, nationwide 0.5–10 US EPA (1987)

USA, ambient surface water stations 20b Eckel & Jacob

(1988)

Orinoco (9 samples, various sites) 1982 4.3–7.6 < 0.4 0.131 Shiller & Boyle
(1985)

9 Rivers in the Orinoco Basin (10 1982 4.3–7.6 < 0.4 0.02–1.77 Shiller & Boyle
samples) (1985)

Yangtze (mouth at low flow) 1981 < 0.4 0.077 Shiller & Boyle
(1987)

Amazon (mouth at high flow) 1976 6.7 < 0.4 0.249 Shiller & Boyle
(1987)
Amazon (mouth at low flow) 1982 7.5 < 0.4 0.02

15 Rivers in the Amazon Basin (26 1976 5.4–7.1 < 0.4 0.043–1.24 Shiller & Boyle
samples) (1985)

India, freshwater lake 200 Prahalad &

Seenayya (1989)

Huanghe (10 sites) 1986 8.21 < 0.45 65–327

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Zhang & Huang

(1993)

Rhine, at Lobith 1984 not 57a RIWA (1993)

given

Rhine, at Lobith (25 samples) 1993 7.1–7.9 22a, b (<15–38)

Ohio (9 samples; various sites) 1984 7.3–7.5 < 0.4 0.288–3.2 Shiller & Boyle
(1985)

16 Ohio tributaries (29 samples) 1984 6.9–8.1 < 0.4 0.072–4.32 Shiller & Boyle
(1985)

Mississippi (7 samples; 2 sites in 1982–1984 7.6–8.2 < 0.4 0.194a (0.11– Shiller & Boyle
Louisiana) 0.27) (1987)

St. Lawrence (10 m depth) 1975–1976 7.63 < 0.4 8.6a Yeats & Bewers
(1982)

Twelvemile Creek 1982 < 10 LaPerriere et al.

(1985)

Potomac River (3 sites) 1988 14–310 Hall et al. (1989)

Streams with current mining 29–882 LaPerriere et al.

(1985)

United Kingdom, River Ystwyth 1973–1975 170–880 Grimshaw et al.

(1976)

United Kingdom, Willow Brook, 1969–1971 7–8.5 < 0.45 320–1150c Solbé (1973)
polluted
(7 sites; 42 sampling occasions)

Spain, surface water near mine 1984 Gonzáles et al.

(1985)

– mine (5 samples): 12- 3925

– marshes near mine (16 samples): 7.5- 895

– stabilized sands (6 samples): 9.6- 23.8

a Average

b Median

Table 12. Dissolved and total zinc concentrations in fresh water

Location Value Measurement Reference

(m g/litre)

World 40 dissolved Spear (1981)

World 15 (0.2–100) total Bowen (1979)

World 5–45 total Holland (1978)

World 12–35 total Zuurdeeg (1992)

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World 0.6–17 total Zuurdeeg (1992)

Europe 5–43 total Zuurdeeg (1992)

Rhine 22 total RIWA (1993)

Rhine 4 total Van der Weijden & Middleburg

(1989)

Rhine 10 total Van Tilborg & Van Assche (1994)

Belgium 50 total Goethals (1991)

Alaska 10 total LaPerriere (1985)

Lake Pontchartrain <1 total Francis & Harrison (1988)

Ohio 0.065–0.65 dissolved Shiller & Boyle (1985)

Great Lakes 0.09–0.3 dissolved Nriagu et al. (1996)

Drainage from active and inactive mining areas may be a significant source of zinc in water. Waters in acidic mine tailing ponds in
Canada were found to contain an average zinc level of 900 µg/litre with a maximum value of 3300 µg/litre (Mann et al., 1989).
Gonzáles et al. (1985) reported zinc levels of up to 4 mg/litre in surface water collected near a mine. Elevated zinc levels of up to
175 µg/litre were found in Birch Creek, a heavily mined river, compared to <10 µg/litre in an unmined stream (LaPerriere et al.,
1985).

The natural background range (total zinc) based on a data set of 8000 analyses of clean streams for Northern European lowland
rivers is 5–43 µg/litre. Two data subsets are given by Zuurdeeg (1992) for clean rivers of the world (outside Europe): the first gives
a range of 12–35 µg/litre, and the second a range of 0.6–17 µg/litre (total zinc). The latter data set indicates the existence of areas
low in natural zinc.

Dissolved average zinc concentrations of the Great Lakes Superior, Erie and Ontario determined by ultraclean techniques were
0.09–0.3 µg/litre (Nriagu et al., 1996). A depletion of zinc in surface waters and an increase in concentration with depth were
observed. Similarly, Francis & Harrison (1988) reported zinc concentrations for lake Pontchartrain of < 1 µg/litre (total zinc). In
relatively undisturbed rivers of the Ohio valley, dissolved zinc concentrations of 0.06–0.6 µg/litre were measured by Shiller &
Boyle (1985).

The inadequacy of many zinc data for fresh waters is well illustrated in the study by Windom et al. (1991). Their results for
dissolved zinc obtained using clean sampling and analysis techniques were lower by 1–2 orders of magnitude than those obtained
in a national monitoring programme.

5.1.3.2 Seawater

Zinc concentrations in seawater are summarized in Table 13. Baseline levels in seawater are typically in the range 0.0005- 0.026
µg/litre (Sprague, 1986), with 0.002–0.1 µg/litre (US EPA, 1987; Yeats, 1988) in open ocean waters. Concentrations are lower at
the ocean surface than in deeper water (Bruland et al., 1978). Zinc correlates well with dissolved silicate concentrations (Yeats,
1988). In estuarine waters, anthropogenic inputs result in seafood concentrations with typical values of 1–15 µg/litre (Van den
Berg et al., 1987). Concentrations decrease in an offshore direction (Duinker & Nolting, 1982). It should be noted that many of the
data, particularly those reported prior to 1975, may be unreliable, if inadequate care was taken to avoid contamination during
sample collection and analysis. For example, older data for zinc in open ocean waters can be up to three orders of magnitude
higher than current values (Preston et al., 1973).

Table 13. Zinc concentrations in seawater

Area Year Sampling Zinc concentration Reference

depth (m g/litre)
(m)

Ocean, surface water 0.002–0.1 US EPA (1987)

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North-east Pacific Ocean, California 1977 0.2 0.0084 Bruland et al. (1978)
coast

100 0.08

1020 0.43

2500 0.61

North-east Pacific Ocean 1981 100 0.23 Yeats (1988)

1000 0.54

2500 0.60

3500 0.40

North Atlantic Ocean, Sargasso Sea 1984 20 0.065 Yeats (1988)

165 0.026

1000 0.092

1915 0.137

3715 0.124

North Sea, Southern Bight (128 1975 ³ 0.3 Duinker & Nolting
samples; < 0.45 m m (1982)

Skagerak 0.27–0.81 Kersten et al. (1988)

Western Mediterranean, coastal 0.001–0.002 Sprague (1986)

Western Mediterranean, estuary max. 0.01 Sprague (1986)

Western Mediterranean, near shore 0.0036 Sprague (1986)

Australia (polluted) 0.134 Sprague (1986)

USA, San Diego coastal 0.0005 Sprague (1986)

USA, San Diego harbour 0.0026 Sprague (1986)

United Kingdom, heavily polluted 0.026 Sprague (1986)

United Kingdom, polluted 0.007–0.012 Sprague (1986)

Pacific Ocean, Australia, New South 1995 surface < 0.04 Batley (1995)
Wales coast

5.1.4 Soil
Zinc concentrations in igneous and sedimentary rocks were reported to be 48–240 mg/kg for basaltic igneous rock, 5–140 mg/kg
for granitic igneous rock, 18–180 mg/kg for shales and clays, 34- 1500 mg/kg for black shales and 2–41 mg/kg for sandstones
(Thornton, 1996). Zinc levels in geochemically anomalous parent materials in the United Kingdom were found to be 1% and more
(Thornton, 1996).

Zinc levels in soils are given in Table 14. Zinc levels and speciation in soil may vary with the soil profile, especially in natural
ecosystems (see section 3.1). The mobility of zinc in soils is dependent on its speciation, the soil pH, and content of organic matter.

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For non-contaminated soils worldwide, Adriano (1986) reported average zinc concentrations of 40–90 mg/kg, with a minimum of
1 mg/kg and a maximum of 2000 mg/kg. Low levels are found in sandy soils (10–30 mg/kg), while high contents are found in
clays (95 mg/kg). Wet and dry deposition, the use of zinc compounds as fertilizers and the application of municipal sludges and
manure to cropland are considerable sources of zinc in soils (Chang et al., 1987).

Table 14. Zinc concentrations in soils

Area Zinc concentration Remarks Reference

(mg/kg dry weight)

Worldwide 10–300 > 2000 soils Swaine (1955)

Worldwide 90 (1–900) Bowen (1979)

Worldwide 50 Vinogradov (1959)

Worldwide 40 Berrow & Reaves (1984)

Worldwide 59.8a (1.5–2000) 7402 soils Ure & Berrow (1982)

Canada 74 (10–200) McKeague & Wolynetz (1980)

Canada, Ontario 47.6b (5–162) 296 soils; 0–15 Frank et al. (1976)
cm

USA 54 McKeague & Wolynetz (1980)

USA 5–264 (53, 50th 3045 soils Holmgren et al. (1993)

percentile)

307 soils series

Germany, rural area 85b 73 samples UBA (1994)

United Kingdom 77 (5–816) 748 samples Adriano (1986)

United Kingdom, Scotland 58a (<0.7–987) 725 samples Berrow & Reaves (1984)
from 83 soil
profiles

Ukraine, Poles'ye 14–95c Golovina et al. (1980)

USSR, Eastern European Plain 25–120 Vinogradov (1959)

China 100 (9–790) Liu et al. (1983)

Germany, Rhine-Main plain 3–30 Kauder (1987)

Germany, urban industrialized 311b 371 samples UBA (1994)

area

Germany, Harz, polluted area up to ca. 10 000 Aurand & Hoffmeister (1980)

USA, Ohio, soil treated with 107 Levine et al. (1989)

sewage sludge for 10 years

Electrical transmission tower 4 samples; 0–5 Jones & Burgess (1984)

(galvanized, corroded): cm

near tower 11 480a

1 m distance 10 431a
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1 m distance 10 431a

5 m distance 362a

10 m distance 160a

50 m distance 54a

United Kingdom, Scotland, 69–236a Eduljee et al. (1986)

vicinity of chemical waste
disposal facility

United Kingdom, Wales, zinc-lead 2923 Davies & Roberts (1975)

ore mine

USA, Palmerton, 2 zinc smelters: O2 horizon Beyer et al. (1985)

2 km downwind from smelter 24 000

10 km upwind of smelter 960

Peru, zinc smelter: Reif et al. (1989)

1 km distance 575

13 km distance 183

27 km distance 154

35–55 km distance 16–29

Zinc smelter for 50 years: 260 10–15 cm Hogan & Wotton (1984)

6 km distance 80

35 km distance

USA, Idaho, lead smelter 200–29 000 Ragaini et al. (1977)

United Kingdom, revegetated 1915–2160 1–8 cm Andrews et al. (1989)

mine tailings dam

USA, Idaho, reclaimed phosphate 443–1112c 10-15 sites; Hutchison & Wai (1979)
mine waste dumps 0–25 cm

a Mean

b Median
c Average

Zinc concentrations of up to 118 000 mg/kg are associated with industrial contamination (Eisler, 1993). Significant relationships were found between the
distance from smelters or roads and the levels of easily extractable zinc in soil, and the zinc content in herbage (Hogan & Wotton, 1984; Beyer et al., 1985;
Reif et al., 1989).

Old geological formations that have been extensively leached may have background concentrations of natural zinc in water that are one order of magnitude
below those of the mineral-rich European alluvial flow system.

In soil samples from gardens next to a zinc and lead ore mine in Wales (United Kingdom), average levels of 2923 mg/kg were found, compared to 94 mg/kg
in uncontaminated soils (Davies & Roberts, 1975).

Soil and vegetation in Palmerton, Philadelphia, USA were found to be highly contaminated with zinc by fumes escaping from two zinc smelters. Zinc
concentrations in the organic horizon (decomposed leaf litter) increased by regular gradations from a minimum of 67 mg/kg dw at a site 105 km west of the
smelters to a maximum of 35 000 mg/kg dw 1.2 km east of the smelters. At a depth of 0–15 cm, concentrations of about 10 000 mg/kg were measured (Beyer
et al., 1984, 1985; Beyer, 1988). Soil sampled at a distance of 1–40 km from the smelters showed that approximately 90% of the metal deposited on the soil
surface was retained in the top 15 cm of the soil profile (Buchauer, 1973). Soils (0–15 cm) from 40 gardens in rural areas at different distances from the

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smelters contained average zinc concentrations of 5830 mg/kg dw; background levels of 346 mg/kg dw and 311 mg/kg dw were reported (Chaney et
al.,1988; see Table 14).

In the Netherlands, reference values for agricultural soils have been related to soil types on the basis of the percentage by weight of clay (C) and organic
matter (H) according to the following equation:

Zn (mg/kg dw) = 50 + 1.5 (2C + H)

This relationship was based on a large data set of widely varying uncontaminated Netherlands soils. The derived values are regarded as ambient levels from
which no detrimental effects are expected. For a standard soil (C = 25% and H = 10%) the reference value is 140 mg/kg (Cleven et al., 1993).

5.1.5 Sediments and sewage sludge

The concentration of zinc and other metals in sediment spans at least three orders of magnitude. The concentration is related to particle size, mineralogy and
input sources. The biological effects of metals in sediment are not related to total concentrations (Allen, 1996). The binding of zinc by sulfide, organic matter
and metal oxides should be taken into account (Allen, 1996). Standards for metals should not be based on total concentration (Allen, 1996).

As a consequence of adsorption to organic substances and other inorganic minerals, zinc is precipitated from waters and thus enriched in sediments (Malle,
1992).

Zinc concentration in sediments from aquatic systems in northern Greece was 40 mg/kg dw (Sawidis et al., 1995). In the Elbe estuary, a median zinc
concentration of 1400 mg/kg (range 440- 2920 mg/kg; 60 samples, < 20-µm fraction) was observed in 1992; the background level was reported to be 95
mg/kg (Mueller & Furrer, 1994). The zinc concentration in the sediments of the Rhine harbour in Rotterdam amounted to 1900 mg/kg dw in 1980 (Cleven et
al., 1993). A time series in the same area showed a decrease in zinc content in this sediment of more than 50% between 1979 and 1986 (Malle, 1992). Zinc
levels in the Scheldt estuary at the Belgian-Netherlands border declined from 520 mg/kg dw in 1951 to 350 mg/kg dw and 229 mg/kg dw, respectively in
1971 and 1974 (Van Alsenoy et al., 1990). In sediments from the highly polluted river Vesdre (Belgium), mean zinc concentrations were 2920 mg/kg dw
(1629–4806 mg/kg dw; 26 samples) at a site located 6 km downstream from a zinc factory; 2 km upstream from the factory, the concentration was 1317
mg/kg dw (823–1666 mg/kg dw; 5 samples) (Houba et al., 1983). For the <20-µm fraction of sediments from the Wadden Sea, baseline levels of 100 mg/kg
dw were given (UBA, 1994). For the zinc concentrations in sediments in the upper layer (0–10 cm) from the Baltic Sea, average values of 180 mg/kg and
337 mg/kg, with maximum levels of up to 2290 mg/kg, were reported. Zinc levels in this layer were 1.5–10 times higher than in the next layer (10–20 cm)
(UBA, 1994).

Chaney et al. (1984) stated that the levels of zinc in composted sewage sludge vary between 101 and 49 000 mg/kg dw with a mean of 1700 mg/kg dw. A
compilation of more than 100 values from the literature gives a mean of 2420 mg/kg, while an analysis of 80 samples from sewage treatment plants (USA)
gives 6380 mg/kg dw (Dean & Smith, 1973; Ohnesorge & Wilhelm, 1991). Zinc contents of 2300 mg/kg dw and 2000–3000 mg/kg were reported for sewage
sludge from Switzerland and Germany, respectively (Ohnesorge & Wilhelm, 1991). Additionally, average zinc concentrations of 1480 mg/kg dw were
determined in Germany (Schweiger, 1984). Sewage sludge applied to arable land in Ohio, USA was found to contain zinc at a concentration of 866 mg/kg
dw (Levine et al., 1989). In the European Union, the maximum zinc concentration permitted in biosolids (sludge) for application to agricultural soils cannot
raise the zinc level above 300 mg/kg of dry soil (Berrow & Reaves, 1984).

5.1.6 Aquatic and terrestrial organisms

Zinc is present in all tissues of all organisms, as it is essential for growth. Concentrations are higher in organisms near anthropogenic point sources of zinc
pollution. Interspecies variations in zinc content are considerable; intraspecies levels also vary, for instance with life stage, sex and season. In general, zinc-
specific sites of accumulation in animals are bone, liver and kidney (Spear, 1981).

5.1.6.1 Aquatic plants and animals

For rooted aquatic plants and algae, zinc concentrations are generally in the range 20–120 mg/kg dw (Spear, 1981). Zinc concentrations of 38 and 90 mg/kg
dw were reported for marine phytoplankton and seaweeds, respectively (Young et al., 1980). In eelgrass (Zostera marina), zinc levels were found to increase
with age of leaf but were independent of the zinc load at the sampling site (Brix & Lyngby, 1982). Background levels in aquatic moss (Fontinalis squamosa)
were < 400 mg/kg dw, whereas moss from a contaminated river contained maximum concentrations of 2810 mg/kg dw (Young et al., 1980). Sawidis et al.
(1995) analysed aquatic macrophytes from aquatic systems in northern Greece for zinc metal concentrations. Levels of between 10.2 mg/kg and 145 mg/kg
dw were reported for Ceratophyllum demersum, Cladophora glomerata, Myriophyllum spicatum, and Potamogeton nodosus. Many species of algae in
Canadian mine tailing environments were found to have zinc contents of > 1000 mg/kg (Eisler, 1993).

Baseline zinc levels in invertebrates are in the range 50- 300 mg/kg dw (Spear, 1981). In molluscs, which are known to be good accumulators of trace
metals, concentrations may be elevated. In soft parts from mussels (Mytilus edulis), zinc ranged from 28 mg/kg dw (visceral mass) to 3410 mg/kg dw
(kidney). In scallops (Pecten sp.), zinc levels of 200 mg/kg dw were found in soft parts, but concentrations of up to 32 000 mg/kg dw and 120 000 mg/kg dw
were reported in kidney and kidney granules, respectively (Eisler, 1993). Luten et al. (1986) examined the zinc content of mussels from the North Sea, the
Wadden Sea, and three estuaries over the period 1979–1983. The median zinc content in mussels was 87–234 mg/kg dw. In the marine bivalve Macoma
balthica in the Westerschelde Estuary (Netherlands), zinc concentrations of 377–692 mg/kg dw were recorded; concentrations were higher in winter and
lower in summer (Bordin et al., 1992).

Bullfrogs (Rana catesbeiana) caught downstream from the source of mine tailings had markedly higher zinc levels in most tissues (Niethammer et al., 1985).

Spear (1981) reported background levels for fish usually ranging from 4 mg/kg to 20 mg/kg fresh weight (fw). In muscle of marine fish, such as the northern
anchovy (Engraulis mordax) and the Atlantic menhaden (Brevortia tyrannus), concentrations of up to 20- 25 mg/kg fw were measured (US National
Academy of Sciences, 1979). Schmitt & Brumbaugh (1990) reported results of a US national contaminant biomonitoring programme in which the
concentration of zinc in freshwater fish was measured. Zinc concentrations were highest in the common carp (Cyprinus carpio); maximum zinc
concentrations were 168.1 µg/g fw in 1978–1979, 109.2 µg/g fw in 1980–1981 and 118.4 µg/g fw in 1984. Maximum values for other common fish species
measured in the 1984 survey were 32.66 m g/g fw for channel catfish (Ictalurus punctatus), 24.39 µg/g fw for white sucker (Catostomus commersoni), 23.91
µg/g fw for large-scale sucker (Catostomus macrocheilus), 19.93 µg/g fw for largemouth bass (Micropterus salmoides) and 12.78 µg/g for lake trout
(Salvelinus namaycush). Lowest zinc levels are found in muscle, highest (5–10 times higher) in eggs, viscera and liver (Eisler, 1993; Stanners & Bourdeau,
1995). In Toronto Harbour, Ontario, Canada, various species of fish contain only slightly elevated zinc levels (36 mg/kg fw) in muscle tissues. In acidic lakes
near Sudbury (mining area), Canada, the zinc content of fish liver tissues is generally 1–2 orders of magnitude higher than in muscle tissues.

5.1.6.2 Terrestrial plants and animals

Studies have shown that the uptake of zinc by terrestrial plants is significantly increased at a low soil pH, but reduced when there is a high content of organic
matter (Jones & Burgess, 1984; Chaney et al., 1987). Normal levels of zinc in most crops and pastures range from 10 mg/kg to 100 mg/kg. Some plant
species are zinc accumulators, but the extent of the accumulation in plant tissues varies with soil properties, plant organ and tissue age.

Application of fertilizers (including sewage sludge) to soil increases the zinc concentration in plants (Mortvedt & Gilkes, 1993).

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Earthworms (various species) from uncontaminated soils were found to contain 120–650 mg/kg dw, from mining sites 200- 950 mg/kg dw, from industrial
sites 320–1600 mg/kg dw, and near galvanized towers 340–690 mg/kg dw (Beyer & Cromartie, 1987). For various species of moths, background loads of
140- 340 mg/kg dw were reported. Beetles (various species) were found to contain 470 mg/kg dw zinc, and zinc levels in caterpillars (Porthetria dispar)
averaged 170 mg/kg dw (Beyer et al., 1985)

Zinc concentrations in birds were found to range between 6.4 mg/kg fw in eggs (Pelicanus occidentalis) and 150 mg/kg fw in liver (Pandion haliaetus), but
the highest values, 250 mg/kg, fw were reported in the liver of the Californian condor (Gymnogyps californianus) (Wiemeyer et al., 1988).

For white-footed mouse (Peromyscus leucopus), short-tailed shrew (Blarina brevicauda) and different species of songbirds, background levels of 140, 200
and 120 mg/kg dw were reported, whereas in animals from a polluted area, concentrations were 190, 380 and 140 mg/kg dw, respectively (Beyer, 1988).
Andrews et al. (1989) reported tissue levels of 103 µg/kg dw (muscle) to 226 µg/kg dw (pelvic girdle) for the field vole (Microtus agrestis) and 126 µg/kg
dw (heart) to 547 µg/kg dw (femur) for the common shrew (Sorex araneus). The kidney of a white-tailed deer (Odocoileus virginianus) collected 4 km from
zinc smelters contained 600 mg/kg dw, well above the mean of 145 mg/kg detected in five deer collected at least 100 km from the smelters (Sileo & Beyer,
1985).

5.2 General population exposure

5.2.1 Air

Negligible quantities of zinc are inhaled in ambient air (approximately 0.7 µg/day) (Cleven et al., 1993). For urban room air, zinc concentrations range from
0.1 to 1.0 µg/m3 (Henkin, 1979). Harrison (1979) analysed dust samples collected in Lancaster, United Kingdom, for their metal content. The total zinc
levels detected were 1600 mg/kg in dust from car parks, 534 mg/kg in urban dust, 940 mg/kg in household dust, and 297 mg/kg in dust from rural roads. In
Germany, mean zinc concentrations of 496 mg/kg in household dust and 2.9 µg/m2 per day in dust deposition were reported (UBA, 1992).

Elevated amounts may be inhaled by people who work in facilities for smelting and refining zinc material or in coal mines, or who live near waste sites and
smelters. At zinc levels of 1 µg/m3, the general population would inhale about 20 µg/day.

5.2.2 Food

Zinc is an ubiquitous and essential element. For diets with moderate bioavailability of zinc, Sandstead et al. (1990) proposed the following daily dietary zinc
intakes as adequate: 3–5 mg for infants, 5–10 mg for children, 9–18 mg for adults, and 13–25 mg for pregnant or lactating females (Sandstead et al., 1990).
Similar values have been published by the US National Academy of Sciences (1989): 12–15 mg/day for adults, and 15–25 mg/day for pregnant or lactating
females. The mean dietary zinc intakes of women in industrialized countries are listed in Table 15.

Table 15. Dietary zinc intake of women in industrial countries

Country Age group in years Zinc Method Reference

(No. n) (mg/day)

Canada 30.0 ± 6.1 (n = 100) 10.1 ± 3.3 3-day diet record Gibson & Scythes
(1982)

USA (NHANES III) 20–29 (n = 838) 9.7 ± 0.28a single 24-h recall Alaimo et al. (1994)

USA (NHANES III) 20–29 (n = 838) 9.6 ± 0.26a single 24-h recall Alaimo et al. (1994)

Germany 25–34 8.9b 7-day protocol Van Dokkum (1995)

Germanyb 35–44 9.2b 7-day protocol Van Dokkum (1995)

United Kingdom 25–34 8.2 7-day weighed record Gregory et al. (1990)

United Kingdom 35–49 8.7 7-day weighed record Gregory et al. (1990)

Irelandb 25–40 (n = 122) 9.4 ± 3.3 7-day dietary history Van Dokkum (1995)

Netherlandsb 22–50 9.7 2-day diet record Van Dokkum (1995)

Sweden 30–79 (n = 60) 8.0 24-h duplicate diet Van Dokkum (1995)
composites

New Zealand 25–44 9.0 ± 6.0 single 24-h recall LIZ (1992)

Australia 18–60+ 11.2 semiquantitative Baghurst et al. (1991)

food-frequency
questionnaire

a SEM = standard error of the mean

b Data compiled by Van Dokkum (1995).

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The zinc content of some foods is shown in Table 16. Zinc levels of 10–150 mg/kg of fresh edible portion are found in vegetables, with values as high as 550 mg/kg in mongo beans. In
general, meat, eggs and dairy products contain more zinc than plants; liver is a particularly rich zinc source, with average values of 44–84 mg/kg of edible portion. High zinc levels are also
found in wheat and rye germ, yeast and oysters; white sugar and pome and citrus fruits provide among the lowest, usually with < 1 mg/kg of fresh edible portion (Adriano, 1986; Scherz et
al., 1986).

Information on the concentration, distribution and variation of zinc in the 234 food items comprising the US Food and Drug Administration’s Total Diet Survey from 1982 to 1991 has
recently been published (Pennington & Young, 1991; Pennington et al., 1995). Major food group sources of zinc (> 10% of daily intake) were identified as meat, mixed dishes and ready-to-
eat cereals. Zinc contents in foods were presented as mean and median values per 100 g and per serving portion. Zinc intakes (mg/day) in the period 1982–1989 ranged from 8.7 to 9.7
mg/day for women aged 60–65 and 25–30 years, respectively; comparable estimates for men were 12.9 and 16.4 mg/day.

Table 16. Zinc concentrations in some foodstuffsa

Food Zinc concentration

(mg/kg of edible portion)

Meat

Beef 31.7 (25.9–42.1)

Mutton 31

Pork 19 (14–62)

Liver 44 (sheep)–84 (calf)

Kidney 3.7 (pig)–28 (sheep)

Poultry

Chicken 08.5

Chicken liver 32

Turkey 20 (17–23)

Chicken eggs 8–20

Fish and seafood

Sea fish 5 (haddock)–14 (anchovy)

Freshwater fish 4.8 (trout)–12 (eel)

Oysters 65–1600

Shrimps 23.1

Dairy products

Butter 2.3

Cow's milk 3.8

Milk powder 21

Cheese 11–106

Fruit

Apple 1.2 (0.4–2.2)

Banana 2.2

Fig 2.5
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Stone fruits 0.2 (peach)–1.5 (cherry)

Berries 0.8 (grape)–2.5 (cranberry)

Exotic fruits 0.8 (mandarin)–9 (guava)

Nuts 5 (coconut)–48 (cashew nut)

Vegetables

Vegetable fruits 10–30

Leaves, stems, flowers 13 (rhubarb)–140 (onions)

Roots and tubers 2.7 (potato)–170 (taro)

Legumes and oilseeds 124 (chickpea)–550 (mungo bean)

Carrot 6.4 (1.8–21)

Tomato 2.4 (0–2.5)

Lettuce, cabbage 2.2 (1.6–15)

Mushroom 3.9 (2.8–5)

Cereal products

Whole grain 13 (rye)–45 (oats)

Flour 7.7 (rye)–34 (wheat wholemeal)

Germs 120 (wheat)–208 (rye)

Rye bread 8.6 (5.9–12)

Wheat bread 5 (2–8)

Wheat wholemeal bread 21

Corn flakes 3

Rolled oats 44 (35–69)

Brewer's yeast 80

Pasta 16 (10–22)

a From: Scherz et al. (1986).

In areas highly polluted with zinc, accumulation by plants, especially leafy vegetables, may occur. Machholz & Lewerenz (1989) reported zinc concentrations of 301 mg/kg for
contaminated lettuce compared to 77 mg/kg in uncontaminated lettuce. In other crops, baseline zinc levels of 0.4–35 mg/kg were found, but in contaminated samples levels of 4–400 mg/kg
were measured (Fiedler & Roesler, 1988).

Food processing can alter the zinc content of food and usually results in a decrease. For example, the zinc content of spinach is reduced by about 20% during freezing and thawing (Kampe,
1986); during the milling of wheat flour, up to 80% of zinc is removed. Increased zinc contents in acidic foods attributed to storage in galvanized zinc containers has been reported (Halsted
et al., 1974).

5.2.3 Drinking-water
Zinc concentrations in drinking-water have been reported as follows: Canada, 10–750 µg/litre (Meranger et al., 1981); Netherlands, 20–400 µg/litre (Zoeteman, 1978); and in other
European countries, from 2 µg/litre in Bordeaux, France to 688 µg/litre in Frankfurt, Germany (Zoeteman, 1978). In general, concentrations of 1–2 mg/litre, rarely up to 5 mg/litre, may
occur in water after passage of corrosive water through galvanized pipes or after standing in galvanized pipes, especially in combination with elevated chloride and sulfate concentrations
(Hoell et al., 1986). On the basis of taste, such water would be considered of extremely poor quality for drinking (WHO, 1996a).

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In USA, drinking-water from 35 areas (100–110 samples) was found to contain zinc concentrations of 0.025–1447 µg/litre zinc (Greathouse & Osborne, 1980). Median concentrations in
water from galvanized pipes were about 10 times higher than those in water from copper pipes; for homes older than 5 years, reported values were 547 µg/litre and 70 µg/litre, respectively
(Sharrett et al., 1982a,b).

5.2.4 Miscellaneous exposures

Intentional consumption of large doses of zinc supplements in excess of dietary intake and chronic treatment of patients with drugs containing zinc salts, e.g., injectable insulin, may result
in high-level zinc exposure (Bruni et al., 1986). People with copper deficiency are at particular risk. Zinc exposure may also occur after extensive application of zinc-containing powder or
ointments to wounds (Seeger & Neumann, 1985).

5.3 Occupational levels

Occupational exposure to dusts and fumes of metallic zinc and zinc compounds occurs during production of zinc (e.g., mining, smelting) and zinc compounds, and during their use. Many
countries regulate workplace levels of zinc oxide fume and dust at levels between 5 and 10 mg/m3 (ILO, 1991) to prevent adverse respiratory effects and metal-fume fever.

Size distribution and chemical composition of condensation aerosol particles generated in metallurgical plants in Germany during high-temperature processes were studied by Reiter &
Poetzl (1985). Zinc concentrations detected during smelting of iron from scrap in induction furnaces averaged 0.190–0.287 mg/m3 (main particle size 0.3–0.4 µm); during sprays and hot-
dip galvanizing of tubes, 0.101 and 0.076 mg/m3 (main particle size > 0.09 µm) or 0.067 and 0.122 mg/m3 (main particle size 0.3–0.4 µm); and during the electrolytical production of
aluminium, 0.6 µg/m3.

A zinc concentration of 0.540 mg/m3 (range 0.110–0.800 mg/m3) was measured in the breathing zone during welding of painted unalloyed steel in large rooms without local exhaust
ventilation in Netherlands industries (Van der Wal, 1990). During decorative chrome plating, Lindberg et al. (1985) found zinc levels of 2.2- 1.3 mg/m3 in air. A collective of 35 workers
(Germany) was exposed to 2.2 mg/m3 zinc oxide in the breathing zone during welding of coated and uncoated steel (Zschiesche, 1988). Gun metal founders were exposed to a mean
concentration of zinc oxide fumes of 0.680 mg/m3 (Murata et al., 1987).

Personal breathing zone samples collected throughout the production area of a brass foundry (USA) for 7 employees contained zinc concentrations (time-weighted average) ranging from 4
µg/m3 to 0.732 mg/m3 depending on the working area (Clark et al., 1992). In a plant using zinc stearate releasing agent (USA), area samples were collected from lathe operators, a steam
autoclave operator, and three areas near these operators. The total zinc concentrations ranged from 2 µg/m3 to 0.120 mg/m3 (Letts et al., 1991).

Zinc oxide concentrations were monitored at a non-ferrous foundry for three different job classifications from 1989 to 1990. The respirable fraction of personal air samples showed levels of
1.4 mg/m3 for assistant caster-top, 1.34 mg/m3 for assistant caster-pit, 0.896 mg/m3 for caster, and 1.240 mg/m3 for all casting positions; maximum values were 3.830 mg/m3, 6.230 mg/m3,
5.590 mg/m3 and 6.230 mg/m3, respectively. However, only 35% of the total collected zinc oxide was respirable. Total zinc oxide concentrations of up to 20.2 mg/m3 were measured for
caster positions (Cohen & Powers, 1994).

Borroni et al. (1986) measured zinc concentrations in the plating room of an electromechanical factory (Italy) before and after reorganization. Before reorganization, zinc concentrations
were 39 µg/m3 in the anticorrosive treatment plant, 0.388 mg/m3 in the zinc barrel plating area, and 0.693 mg/m3 in the zinc rack plating area; after reorganization the levels were 0.021,
0.003 and 0.009 mg/m3, respectively. Dust exposure levels monitored during catalyst handling (loading and unloading) in the chemical industry (France) ranged from 0.210 to 2.18 mg/m3
(mean values 0.400- 1.29 mg/m3) (Hery et al., 1991).

Airborne samples in a Philadelphia waste incinerator plant (USA) contained zinc at a level of 1.2 mg/m3 in the personal breathing zone. With area sampling, the level was 0.0028 mg/m3
(Bresnitz et al., 1992).

In Sweden, the average 8-h exposure of 12 painters to zinc from various water-based paints was reported to be < 0.001–0.080 mg/m3 (mean 0.020 mg/m3) (Wieslander et al., 1994).

5.4 Total human intake from all sources

5.4.1 General population
For humans, the most important route of exposure to zinc is through the ingestion of food. The dietary intakes of zinc in several countries are summarized in Table 17. Daily dietary intake
ranges from 4.7 to 18.6 mg/day. Low zinc intakes have been reported for populations in Papua New Guinea, while intakes of zinc from vegetarian diets in India have been reported to be as
high as 16 mg/day (WHO, 1996b). The major food sources of dietary zinc for adult women are outlined in Table 18.

Table 17. Estimated mean dietary intakes of zinc

Country Zinc intake Reference

(mg/day)

Australia adult males (18–60+ years) 12.8

adult females (18–60+ years) 11.2

Germany adults (25–34 years) 8.9 Van Dokkum (1995)

adults (35–44 years) 9.2

adults (45–54 years) 9.2

Germany children (4–9 years) 5.3 Laryea et al. (1995)

India 8.0 Pfannhauser (1988)

16.1 Adriano (1986)

Netherlands male children (4–10 years) 7.7 Van Dokkum (1995)

female children (4–10) years) 7.1

adult males (22–50 years) 12.1

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adult females (22–50 years) 9.7

New Zealand adult females (15–65+ years) 9 LIZ (1992)

adult males (15–65+ years) 13

Ireland male children (8–12 years) 10.1 Van Dokkum (1995)

female children (8–12 years) 8.9

adult males (25–40 years) 14.4

adult females (25–40 years) 9.4

United adult males 10.5–11.6 Gregory et al. (1990)

Kingdom
adult females 8.3–8.5

children (1.5–4.5 years) 4.3–4.8

USA adults (20–80+ years) 8.8–12.4 Pennington et al. (1995);

Alaimo et al. (1994)
infants (2–11 months) 6.0

children (3–11 years) 8.0–10.0

children (12–19 years) 12.3–13.0

USA (1994) infants 5.6–6.3 Sandstead & Smith (1996)

adult males 12.3–13.3

adult females 8.4–8.9

Table 18. Major food sources of dietary zinc for adult women

Study Bread and Meats, Vegetables Milk and Fats, Reference

cereal eggs, and fruit dairy sugars,
products legumes, products beverages,
nuts and alcohol
seeds

Canada. Women in 19.0 43.0 12.5 23.7 1.7 Gibson & Scythes
1982 aged 30.0 ± 6.1 (1982)
years

USA. Women in 1986 22.5 51.3 8.1 14.2 4.4 Moser-Veillon

(NFCS, CSF11 Report (1990)
No. 86-3)

Germany. Women 21.0b 18.0a ? 24.0 ? Van Dokkum

(National Food (1995)
consumption
Survey,1985–1988)

United Kingdom. 28.0 36.0a ? 15.0 ? Gregory et al.

Women aged 16–64 (1990)
years (n = 2200)

Ireland 12–24b 35–49a 5–9c 9–20 ? Van Dokkum

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35 9 5 9
Adults >18 years (1995)
(n = 676) plus

children 8–18 years

(n = 538)

Netherlands Women 16b 28.0a ? 28.0 ? Van Dokkum

(National Food (1995)
Consumption Survey in
1987–1988)

New Zealand. Women 17.0 45.4d 1.5 13.2 < 20.5 Pickston et al.
aged 23–50 years (1985)
(Market Basket Survey
based on 8.4 MJ energy
intake)

Australia. National 12.3e 13.3 ? 15.5f ? Baghurst et al.

sample of women aged (1991)
18–60+ years (n = 763)

a Meat only

b Bread only
c Potatoes only
d Meat, fish and eggs

e Bread and breakfast cereal

f Milk and cheese only.

The zinc requirement is mainly met by consumption of meat in omnivorous diets, or unrefined cereals, legumes and nuts diet patterns that are mostly vegetarian. High zinc concentrations are also found in seafood, especially
oysters, whereas fruits and vegetables contain relatively low zinc concentrations. Absorption of dietary zinc is estimated to range from < 15% to 55%, depending on the composition of the diet; absorption is facilitated by foods
containing animal protein.

5.4.2 Bioavailability in mammalian systems

"Bioavailability" is the term used to refer to the proportion of the external dose of a compound (in this case zinc) that is actually absorbed by living organisms. In pharmacology and nutrition, the proportion utilized is also
included. For mammalian systems, nutrient intakes calculated for food composition data or determined by direct chemical analysis represent the external dose. For most studies, the amount actually absorbed and utilized by the
body (i.e., the internal dose) is much lower than the administered dose. Although there are certain common aspects of bioavailability, as discussed in section 4.2, there are various other factors that can affect the bioavailability
of zinc in mammals (Table 19). These include the chemical form of the nutrient (speciation), the composition of the food ingested (e.g., fibre and phytic acid content), the body stores of the nutrient and related chemicals, the
physiological status of the organism, and nutrient and nutrient–dietary interactions (WHO, 1996b).

Bioavailability from foods of plant origin is impaired by inositol phosphate (phytate), and possibly components of dietary fibre, increased levels of calcium in the presence of phytate, and certain metals, if consumed at high
levels as dietary supplements (Sandstead, 1981) (see section 6.1.2.1).

Mean daily intake of zinc from drinking-water is estimated to be < 0.01 mg/day (Cleven et al., 1993), but may be higher due to water treatment or zinc leaching from transmission and distribution pipes, especially at low pH. A
study in Seattle (USA) revealed zinc levels of 2 mg/litre in standing and 1.2 mg/litre in running water from galvanized pipes and 0.44 and 0.16 mg/litre in standing and running water from copper pipes, respectively (Sharrett et
al., 1982b). Where drinking-water is drawn from systems with corroded fittings, galvanized piping or private wells, it can provide up to 10% of the daily zinc intake (0.5–1 mg/day) (WHO, 1996a). However, in general, this
source provides only a small part (< 0.1 mg/day) of the total oral intake.

In conclusion, the total intake of zinc from all environmental sources by the general adult population varies between 4.7 and 16 mg/day. In most circumstances, over 95% of this comes from food, with negligible amounts from
air, and between <1% and 10% from drinking-water. Comparison of the recommended daily intakes (section 5.2.2) and the lower intakes shown in Table 17 indicates that the risk of zinc deficiency is a worldwide public health
concern (see section 8.3.5).

Table 19. Factors affecting the bioavailability of zinc in the diet for mammals

Factor Major food

Extrinsic

Diet chemical form of element in diet presence of competitive antagonism

between ions (e.g. Cu–Zn; Cd–Zn; Fe–Zn; Ca–Zn; Mg–Zn)
antagonistic ligands: decrease in gastrointestinal lumen solubility of zinc
(products of Maillard browning; lignin; casein phosphopeptides; ethanol;
inositol hexaphosphates, i.e., phytate)
ligands that enhance zinc absorption (e.g. citrate; histidine; cysteine;
picolinic acid)

Intestinal lumen pH and redox state

Intrinsic

Genetic influences inhibitor condition: inborn absorption errors (e.g. acrodermatitis

enteropathica)
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Age infants: poor postnatal regulation of zinc absorption

elderly: reduced efficiency of zinc absorption with age

Metabolic function enhancer conditions: growth in infancy, childhood; pregnancy and

lactation

Homeostatic enhancers: feedback stimulation of absorption in deficiency

regulation inhibitors: decreased absorption when excess amounts are available and
nutritional status is normal (mechanism unclear: possibly
metallothionein)
adaptation to low zinc intake and existing low zinc status by increasing
absorption of exogenous zinc and conserving endogenous zinc

Physiological stress intestinal malabsorption syndromes

Disease

5.4.3 Occupational exposure

Levels of zinc in the diverse facilities worldwide that manufacture, utilize or repair zinc and zinc compounds vary widely (see section 5.3) and are largely dependent upon the quality of industrial hygiene practices. It is thus
difficult to estimate with certainty the exposure of workers globally. In the non-ferrous metal industries, where levels of zinc can be high (0.8–1.3 mg/m3), workers may inhale an amount of zinc about equivalent to that taken
orally by food (see Table 17). However, it is the level of zinc on respirable particulates and absorption from the lung that will determine the amount absorbed (see Chapter 6). In most other industries in developed countries, the
intake of zinc by workers will be lower (< 10 µg to 5 mg per shift).

6. KINETICS AND METABOLISM IN MAMMALS

6.1 Absorption
6.1.1 Inhalation

6.1.1.1 Human studies

While quantitative data on the absorption of zinc following inhalation exposures were not determined, the increased zinc levels demonstrated in plasma, blood and urine of occupationally exposed workers indicated that
absorption from the pulmonary tract does occur (Hamdi, 1969; Trevisan et al., 1982).

6.1.1.2 Animal studies

Gordon et al. (1992) exposed guinea-pigs, rats and rabbits (nose-only) to zinc oxide aerosols at concentrations of 4.3–11.3 mg/m3 for 3 h and guinea-pigs for 6 h. Particle mass median diameter was 0.17 µm. Retention values
were 19.8% and 11.5% in rabbits, and 4.7% in the lungs of guinea-pigs and rats.

6.1.2 Oral

6.1.2.1 Human studies

In humans, the absorption of zinc in the diet ranges widely. Bioavailability can be affected by abnormalities in the gastrointestinal tract, in transport ligands or in substances that interfere with zinc absorption. A decreased
absorption was noted for elderly subjects. Bioavailability also depends on the amount of zinc ingested or the amount and kind of food eaten (Sandstroem & Cederblad, 1980; Aamodt et al., 1982, 1983; Istfan et al., 1983; Seal &
Heaton, 1983; Bunker et al., 1984, 1987; Wada et al., 1985; Hunt et al., 1987, 1991; Sandstroem & Abrahamson, 1989; Sandstroem & Sandberg, 1992).

A significantly reduced absorption of zinc in humans and laboratory animals was observed after oral uptake of phytate (from grain and vegetable components) owing to the formation of insoluble zinc-phytate-complexes in the
upper gastrointestinal tract (O’Dell & Savage, 1960; Oberleas et al., 1962; Reinhold et al., 1973, 1976; Davies & Nightingale, 1975; Solomons et al., 1979; Loennerdal et al., 1984; Turnland et al., 1984; Sandstroem et al., 1987;
Ferguson et al., 1989; Ruz et al., 1991; Sandstroem & Sandberg, 1992). In a study with human volunteers, the absorption of zinc decreased with increasing gastric pH (Sturniolo et al., 1991). Other components that have been
shown to reduce the availability of zinc are binding to casein and its phosphopeptides as a result of tryptic or chymotryptic digestion. Maillard products, dairy products such as milk or cheese, and interactions with calcium in the
diet, coffee or orange juice (Pécoud et al., 1975; Walravens & Hambidge, 1976; Spencer et al., 1979; 1992; Harzer & Kauer, 1982; Flanagan et al., 1985; Lykken et al., 1986). The availability of zinc from diets rich in foods
prepared from unrefined cereals tends to be poor owing to the content of phytate, fibre and lignin (Prasad et al., 1963a; Reinhold et al., 1973, 1976; Pécoud et al., 1975; Solomons et al., 1979).

The mechanism and control of zinc absorption from the intestine has not yet been fully elucidated, although absorption is known to be regulated homoeostatically, and depends on the pool of zinc in the body and the amount of
zinc ingested. In humans and laboratory animals, increased uptake is associated with decreased absorption and increased excretion. Persons with adequate nutritional levels of zinc absorb approximately 20–30% of all ingested
zinc, while greater proportions of dietary zinc are absorbed in zinc-deficient subjects if presented in a bioavailable form. Both a passive, unsaturable pathway and an active, saturable carrier-mediated process are involved. At
low luminal zinc concentrations the binding of zinc is to specific sites, whereas at higher concentrations a non-specific binding occurs (Smith et al., 1978; Davies, 1980; Smith & Cousins, 1980; Flanagan et al., 1983; Istfan et
al., 1983; Menard & Cousins, 1983; Cousins, 1989; Lee et al., 1989b; Oestreicher & Cousins, 1989; Tacnet et al., 1990; Gunshin et al., 1991; Hempe & Cousins, 1991, 1992).

In a study with human volunteers, most of the zinc in a zinc acetate solution (0.1 mmol/litre) administered by intestinal perfusion was absorbed from the jejunum, followed by the duodenum and the ileum (357, 230 or 84
nmol/litre per min per 40 cm respectively). The absorption showed a linear increase at concentrations of 0.1- 1.8 mmol/litre (Lee et al., 1989b).

6.1.2.2 Animal studies

Metallothionein and a low-molecular-mass zinc-binding protein, cysteine-rich intestinal protein (CRIP), which was isolated from intestinal mucosa of rats, play an important role in the gastrointestinal absorption of zinc. Like
several other metals, zinc can rapidly induce metallothionein production in intestinal mucosal cells, liver, pancreas, kidney and lungs; in the intestine in particular, binding to metallothionein leads to retention of zinc and may so
prevent absorption of excess zinc into the body (Richards & Cousins, 1975, 1976; Hall et al., 1979; Foulkes & McMullen, 1987; Bremner & Beattie, 1990; Rojas et al., 1995). In rats, a direct correlation between dietary zinc
intake and the binding of zinc to mucosal metallothionein was observed following administration of 30–900 mg/kg (Hall et al., 1979). In rats fed a low-zinc diet, more zinc was associated with CRIP and lesser amounts were
bound to metallothionein (40% compared to 4%), while with a high-zinc diet lesser amounts were associated with CRIP and most zinc was bound to metallothionein (14% compared to 52–59%) (Hempe & Cousins, 1991,
1992).

In the rat, the major site of zinc absorption was shown to be the duodenum followed by the more distal portions of the small intestine; absorption was rapid. Only minimal amounts were absorbed from the stomach, caecum and
colon (Methfessel & Spencer, 1973; Davies, 1980).

6.1.3 Dermal

6.1.3.1 Human studies

An increase in serum zinc levels was observed in 8 burn patients treated with adhesive zinc-tape (zinc oxide content 7.5 ± 0.05 g/100 g dw); the maximum value (28.3 µmol/litre) was reached within 3–18 days of treatment
(Hallmans, 1977).

The mean release rate of zinc to normal skin to which a zinc oxide (25%) medicated occlusive dressing was applied was 5 µg/cm2 per hour. After 48 h of treatment, a 6- to 14-fold increase in zinc concentration in the epidermis
was noted. The zinc flux was found to increase with decreasing pH (Ågren, 1990). The transport of zinc through intact human skin was enhanced by gum rosin (Ågren, 1991).

6.1.3.2 Animal studies

After topical application of zinc chloride (as 65Zn) at a concentration of 0.005–4.87 mol/litre to guinea-pigs at pH values in the range 1.8–6.1, the loss of radioactivity in most cases was < 1% within 5 h; at a concentration of
0.08 mol/litre at pH 1.8 only, an increased loss of radioactivity (1–3% within 5 h) was observed. An increase of radioactivity in liver, kidney, intestine and faeces was noted (Skog & Wahlberg, 1964).

Two applications of zinc were administered to rabbits (3 per group) as zinc oxide, zinc omadine, zinc sulfate or zinc undecylenate. Each application provided 2.5 mg of zinc containing 5 µCi of 65Zn. The animals were killed 6
or 24 h after the second application. All the zinc compounds were absorbed equally after one or two applications. The 65Zn retention on excised skin blocks ranged from 3% to 65% of the applied dose. 65Zn was located mostly

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in the keratogenous zone of the hair shaft and in the subcutaneous muscle layer (Kapur et al., 1974).

Keen & Hurley (1977) studied the effect of topical application of zinc chloride in female Sprague-Dawley rats (5–7 per group). Four groups were fed a zinc-deficient diet for 24 h. Half of the animals were treated during this
period with a topical application of oil saturated with zinc chloride, for the full 24 h in one group, and for the last 8 h in the other. Plasma zinc levels in rats receiving zinc supplementation for 8 h were similar to those of the
control group (114 µg/100 ml), while levels in rats receiving zinc supplementation for 24 h were significantly increased (182 µg/100 ml).

In a comparative study with zinc oxide and zinc sulfate in rats with full-thickness skin excision, the application of zinc oxide resulted in a sustained delivery of zinc ions, while zinc sulfate delivered zinc ions rapidly, resulting in
decreasing wound-tissue zinc levels. About 450 µg of zinc (12% of the initial dose) was delivered to each wound from the zinc oxide dressing and about 650 µg of zinc (65% of the initial dose) from the zinc sulfate dressing
over a 48-h treatment period (Ågren et al., 1991).

6.2 Distribution
Zinc is one of the most abundant trace metals in humans and is found in all tissues and all body fluids. The total zinc content of the human body (70 kg) is in the range 1.5–3 g. Most of this is found in muscle (» 60%), bone (»
30%), skin and hair (» 8%), liver (» 5%) and gastrointestinal tract and pancreas (» 3%). In all other organ systems, the zinc content is < 1% (Wastney et al., 1986; Aggett, 1994). After ingestion, zinc in humans is initially
transported to the liver and then distributed throughout the body (Aamodt et al., 1979). Glucocorticoids have been shown to enhance the uptake of zinc to liver cells in vitro (Failla & Cousins, 1978). Interleukin-1 and ACTH
also cause increased liver uptake of zinc (Sandstead, 1981; Hambidge et al., 1986). Glutathione may be involved in the release of zinc from intracellular protein ligands and its transfer to the blood by forming complexes in the
mucosa, which pass by passive diffusion across basolateral membranes (Foulkes, 1993).

The highest concentrations of zinc in humans were found in liver, kidney, pancreas, prostate and eye (Forsséen, 1972; Yukawa et al., 1980; Hambidge et al., 1986). Zinc is also present in plasma, erythrocytes and leukocytes. In
healthy subjects, the normal plasma zinc concentration is @ 1 mg/litre (Spencer et al., 1965; Juergensen & Behne, 1977; Whitehouse et al., 1982; Ohno et al., 1985). Zinc is mostly bound to albumin (60–80%) and to a lesser
extent to a -2-macroglobulin and transferrin (Prasad & Oberleas, 1970; Giroux et al., 1976; Smith & Cousins, 1980; Wastney et al., 1986; Bentley & Grubb, 1991).

After oral uptake in humans, peak levels in plasma are reached within 3 h (Nève et al., 1991; Sturniolo et al., 1991). An excess of dietary zinc in humans and animals resulted in high concentrations accumulated in kidneys,
liver, pancreas and bone (Allen et al., 1983; Bentley & Grubb, 1991; Schiffer et al., 1991). As shown by Giugliano & Millward (1984) in a study with zinc-deficient rats, a redistribution of zinc from bone mainly into muscle
may occur; the authors described a marked increase in muscle zinc with a similar loss from bone.

Placental transfer of zinc in pregnant ewes has also been demonstrated (James et al., 1966 ). In an isolated perfused single-cotyledon human term placental model, the normal zinc transfer was shown to be slow. Only up to 3%
of maternal zinc reaches the fetal compartment in 2 h (Beer et al., 1992). The uptake of zinc in the placenta seems to involve a potassium-dependent zinc transport mechanism, as shown in studies with microvilli isolated from
human term placenta (Aslam & McArdle, 1992). Baseline values for zinc were measured in parenchyma, membrane and cord from placental tissue taken from 23, 24 and 22 healthy pregnant women, respectively. Ranges
reported were: parenchyma, 12.8–89.9 µg/g dry tissue; membrane, 21.4–80.3 µg/g dry tissue; and cord, 13.7- 97.2 µg/g dry tissue (Centeno et al., 1996).

6.3 Excretion
In humans, most ingested zinc is eliminated in the the faeces (5- 10 mg/day), and comprises unabsorbed zinc and endogenous zinc from bile, pancreatic fluid and intestinal mucosa cells. In humans and animals, a considerable
amount of zinc is excreted into the small intestine through pancreaticobiliary secretion (Davies, 1980; Matseshe et al., 1980; Johnson & Evans, 1982). In rats, biliary zinc excretion seems to be a glutathione-dependent process;
glutathione probably acts as a carrier molecule (Alexander et al., 1981). Human pancreatic secretions contain zinc levels of 0.5–5 µg/ml (Hambidge et al., 1986). As shown by Spencer et al. (1965), up to 18% of an intravenous
dose of radiolabelled zinc was excreted into the intestine within 45 days. In a study by Matseshe et al. (1980) in healthy volunteers, zinc was recovered from the duodenum at levels greater than the dose ingested.

Zinc is also reabsorbed from the intestine. In a study with ligated duodenal and ileal loops of rats, approximately 35% of zinc secreted into the gut lumen was reabsorbed (Davies & Nightingale, 1975). In humans, a mean
reabsorption of 70% of the administered dose (45 mg of zinc as zinc sulfate) was demonstrated by Nève et al. (1991).

Yokoi et al. (1994) measured the disappearance of zinc from blood after an injection of isotope in women with normal (> 20 µg/litre) and low (< 20 µg/litre) levels of ferritin. The disappearance of zinc from blood in women
with low ferritin was accelerated in the range usually found in subjects with zinc deficiency. This confirmed the early studies of Prasad (1963).

Rats fed a diet supplemented with zinc oxide at a rate of @ 96- 672 mg/kg per day (1200–8400 ppm) for 21 days (Ansari et al., 1976) or @ 48 mg/kg per day (600 ppm) for 7–42 days (Ansari et al., 1975) showed a linear
increase in excretion in the faeces with an increase in dietary intake.

In healthy humans, only small amounts (» 0.5 mg/day) are excreted via urine (Halsted et al., 1974; Elinder et al., 1978). In patients with taste and smell dysfunction given zinc sulfate at a rate of 8–13 mg/day for 290–440 days
followed by an additional 100 mg/day over the next 112–440 days, a 188% increase in daily renal excretion with only a 37% increase in plasma zinc was observed; this was possibly due to an increase in filtration and/or
decreased reabsorption in the kidney (Babcock et al., 1982). In zinc clearance studies in anaesthetized dogs, proximal secretion and distal reabsorption in the nephron was described (Abu-Hamdan et al., 1981).

Hohnadel et al. (1973) reported that zinc concentrations in cell-free sweat from healthy human subjects averaged 0.50 mg/litre (range 0.13–1.46 mg/litre) in 33 men and 1.25 mg/litre (range 0.53- 2.62 mg/litre) in 15 healthy
women. Zinc in sweat appeared to be related to the level of dietary zinc in three studies in male volunteers (Milne et al., 1983), with whole body sweat losses averaging 0.49 mg/day when zinc intakes averaged 8.3 mg/day,
compared with losses of 0.29 mg/day (range 0.18–0.38 mg/day) with a zinc intake of 3.6 mg/day, and 0.62 mg/day (0.46 and 0.77 mg/day in two studies) when zinc intake was 33.7 mg/day

6.4 Biological half-life

After oral, intravenous or intraperitoneal application, equilibrium is quickly achieved between plasma zinc and a rapidly changing non-plasma pool, probably located within the liver (Fairweather-Tait et al., 1993). In humans,
the liver is the organ of highest initial zinc uptake, and with a slow turnover (Spencer et al., 1965). A kinetic two-compartment model can be applied for the estimation of the rapid initial flow of zinc out of the plasma to the
liver following administration of radiolabelled zinc (Foster et al., 1979; Aamodt et al., 1979). After intravenous injection of 65Zn, the average biological half-life of zinc in the smaller compartment was 12.5 days and the
turnover of the larger compartment averaged 322 days (Spencer et al., 1965). In another human isotope study, the estimated half-life was approximately 280 days (Wastney et al., 1986).

In the rat, the biological half-life of 65Zn decreased with an increase in dietary zinc (5 mg/kg, 52 days; 160 mg/kg, 4 days) (Coppen & Davies, 1987).

6.5 Zinc status and metabolic role in humans

6.5.1 Methods for assessment of zinc status in humans

Diagnosis of zinc deficiency in humans is hampered by the lack of a single, specific and sensitive biochemical index of zinc status. A large number of indices have been proposed, but many are fraught with problems that affect
their use and interpretation. At present, the most reliable method for diagnosing marginal zinc deficiency in humans is a positive response to zinc supplementation. Such an approach is time-consuming; it necessitates good
compliance with follow-up visits, making it impractical for community studies. Consequently, dietary and/or static and functional biochemical and physiological functional indices are frequently used to evaluate zinc status.
However, some of these indices are affected by biological and technical factors other than depleted body stores of zinc, which may confound the interpretation of the result. The potential impact of these confounding factors
should be taken into account by standardizing sample collection and analytical procedures.

6.5.1.1 Dietary methods to predict the proportion of the population at risk of inadequate intakes of dietary zinc

A quantitative dietary assessment method designed to measure the quantity of foods consumed by an individual over more than one day must be used to calculate the proportion of the population at risk of inadequate intakes of
dietary zinc. The number of days required depends on the day-to-day variation in zinc intakes for the population group under study. Suitable methods include recalls and records and, in some circumstances, semi-quantitative
food frequency questionnaires. A detailed description of these methods can be found in Gibson (1990). Energy, nutrient and antinutrient intakes can be calculated from the quantitative food consumption data using food
composition tables or a nutrient data bank. Alternatively, chemical analyses of representative samples of staple foods collected from the study area can be performed.

The adequacy of the zinc intakes can then be evaluated by comparison with an appropriate set of tables of recommended nutrient intakes for the population group under study. Several such tables are available; they are discussed
in detail in Gibson (1990). For studies in developing countries, the newly revised requirement estimates for zinc set by WHO (1996b) can be used. Because the adequacy of dietary zinc depends on both its amount and
bioavailability in the diet, however, an estimate of the bioavailability of zinc in the diets under study is also required for this evaluation. Direct measurements of the bioavailability of zinc in the plant-based diets consumed in
many developing countries are limited; some have been made using metabolic studies or stable isotope techniques (WHO, 1996b). The zinc absorption data have been used by WHO (1996b) to develop a model for classifying
diets as having high, moderate and low zinc bioavailability. The model is based on the dietary content of animal and/or fish protein calcium (< 1 or > 1 g/day), and phytate/zinc molar ratios (< 5, 5–15 or > 15) per day.

Once the bioavailability of the zinc in the diets has been estimated, the zinc intakes can be evaluated, preferably using the probability approach, which attempts to assess more reliably the risk of nutrient inadequacy both for an
individual and for the population. The method predicts the number of persons within a group with nutrient intakes below their own requirements and provides an estimate of the population at risk, or the prevalence of inadequate
intakes. For the individual, the method estimates the relative probability that the zinc intake does not meet his or her actual requirement (Anderson et al., 1982).

Probability estimates for risk of zinc deficiency do not identify actual individuals in the population who are deficient or define the severity of the zinc inadequacy, however. Such information can only be obtained when the
dietary intake data are combined with biochemical and functional physiological indices of zinc status. This is especially important in developing countries, where the coexistence of many other multifaceted health problems
often confounds the diagnosis of zinc deficiency.

6.5.1.2 Static tests of zinc status

Static tests measure the total quantity of zinc in various accessible tissues and body fluids, such as blood or some of its components, urine, hair or nails. Ideally, the tissue or fluid selected should reflect total body content of
zinc, or at least the size of the body pool most sensitive to zinc depletion. Unfortunately, the tissues containing the most zinc (i.e., bone and muscle) are not readily accessible for human studies, and their zinc content is not
measurably reduced, even in severe zinc deficiency. Consequently, the choice of biopsy materials for static tests is based primarily on their accessibility, convenience and ethical acceptability (Aggett, 1991).

Serum/plasma

Serum/plasma zinc is the most widely used index of zinc status in humans. Only a small proportion (< 1%) of body zinc circulates in plasma. Hence, plasma zinc does not necessarily reflect total body zinc content.
Nevertheless, in persons with severe zinc deficiency, serum/plasma zinc concentrations are usually low (Arakawa et al., 1976; Hess et al., 1977; Prasad et al., 1978a; Gordon et al., 1982; Baer & King, 1984). Concentrations
return to normal following zinc supplementation.

Serum/plasma zinc concentrations are not useful for detecting mild zinc deficiency states, when values are often within the normal range (Milne et al., 1987; Gibson et al., 1989a; Ruz et al., 1991). Serum/plasma zinc is also not
very specific. Concentrations are modified by a number of non-nutritional factors, some of which (e.g., acute infection, inflammation and stress) decrease levels by inducing hepatic uptake of zinc (Beisel et al., 1976). During
periods of rapid tissue synthesis, pregnancy and use of oral contraceptive agents, serum zinc levels are also decreased (Swanson et al., 1983; Breskin et al., 1983; King, 1986). Chronic disease states associated with
hypoalbuminaemia also induce low serum zinc; zinc circulates in serum bound principally to albumin.

Serum/plasma zinc concentrations are also affected by haemolysis: erythrocytes have a high zinc content. Haemolysis may be particularly important in cases of zinc deficiency, when red cell fragility is increased (Bettger et al.,
1978). In addition, blood samples should be taken under carefully controlled conditions standardized with respect to time of day, fed or fasted state, position of the subject during blood collection, refrigeration of blood samples

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and length of time prior to the separation of serum/plasma; all these factors influence serum/plasma zinc concentrations (Markowitz et al., 1985; Wallock et al., 1993; Tamura et al., 1994).

Blood samples for zinc analysis must also be taken carefully to avoid contamination from sources such as preservatives, evacuated tubes, rubber stoppers and anticoagulants. Certain anticoagulants (e.g., citrate, oxalate and
EDTA) efficiently chelate metallic ions; if these agents are used, plasma zinc values will be lower than if zinc-free heparin is used. The cut-off point generally used to assess risk of zinc deficiency for both plasma and serum
values is < 10.71 µmol/litre (< 70 µg/dlitre), a value approximately two standard deviations below the adult mean. This value may only be appropriate for morning fasting blood samples. For nonfasting morning, and for
afternoon samples, lower cut-off points of < 9.95 µmol/litre (< 65 µg/dlitre) and < 9.18 µmol/litre (< 60 µg/dlitre), respectively, have been recommended.

Erythrocytes

Relatively few investigators have used erythrocytes as a biopsy material for assessing zinc status because the analysis is difficult and the response during experimentally induced zinc depletion–repletion studies has been
equivocal (Prasad et al., 1978a; Baer & King, 1984; Ruz et al., 1992). The half-life of erythrocytes is quite long (120 days), so that erythrocyte zinc concentrations will not reflect recent changes in body zinc stores.

Zinc uptake by erythrocytes is influenced by many other factors, including protein intake, stress and endotoxins (Chesters & Will, 1978). Age-related changes in erythrocyte zinc in infants and children (Nishi, 1980) and
adolescent females have been reported (Kenney et al., 1984).

Leukocytes

Leukocytes have a shorter half-life than erythrocytes and should therefore reflect changes in zinc status over a shorter time-period. They also contain up to 25 times more zinc than erythrocytes. Concentrations of zinc in mixed
leukocytes and specific cellular types (e.g., neutrophils and lymphocytes) have been examined as potential indices of zinc status in humans. Some investigators (Prasad & Cossack, 1982) but not all (Milne et al., 1985; Ruz et
al., 1992) have suggested that they are more reliable as indices of zinc status than plasma zinc. Relatively large volumes of blood are required, and isolation of the leukocytes and their subsequent analysis is lengthy and
technically difficult, limiting the use of these indices, especially for infants and young children.

Milne et al. (1985) have emphasized that the zinc content of leukocytes is a function of the type of separation used; contamination with zinc from the anticoagulant, reagents, the density gradient system or erythrocytes and
platelets may occur. Changes in the relative proportions of leukocyte subsets with physiological state (e.g., pregnancy) and haematological disorders (Aggett, 1991) must also be taken into account in the interpretation of the
results. Finally, comparison of results between different studies is difficult because no consensus exists as to how to express zinc concentrations in the cell types (Thompson, 1991).

Urine

Depletion of body zinc stores causes a reduction in urinary zinc excretion (Hess et al., 1977; Ruz et al., 1991), often before any detectable changes in serum/plasma zinc concentrations (Baer & King, 1984). Supplementation
with high (100 mg) but not moderate (50 mg) zinc intakes increases urinary zinc excretion (Verus & Samman, 1994). Several factors can affect urinary zinc concentrations, however, making interpretation of the results difficult.
For example, despite the presence of zinc deficiency in sickle-cell anaemia, hyperzincuria occurs (Prasad, 1985). Hyperzincuria is also present in disorders such as cirrhosis of the liver and diabetes mellitus, after injury, burns
and acute starvation, in certain renal diseases and infections, and after treatment with chlorothiazide. Hypertensive patients on long-term therapy with chlorothiazide may therefore be vulnerable to zinc deficiency (Prasad,
1983). The measurement of zinc in urine is therefore helpful for diagnosing zinc deficiency only in apparently healthy persons. Zinc levels in the urine usually range from 300 to 600 µg per day. In general, 24-h urine collections
are preferred because diurnal variation in urinary zinc excretion occurs.

Hair

The use of hair zinc concentrations as an index of zinc status has been controversial (Hambidge, 1982). Available evidence suggests that low zinc concentrations in hair samples collected during infancy and childhood probably
reflect a chronic suboptimal zinc status when the confounding effect of severe protein-energy malnutrition is absent (Hambidge et al., 1972a; Gibson, 1980; Smit Vanderkooy & Gibson, 1987; Gibson et al., 1989b). Hair zinc
cannot be used in cases of very severe malnutrition and/or severe zinc deficiency, when the rate of growth of the hair shaft is often diminished. In such cases, hair zinc concentrations may be normal or even high (Erten et al.,
1978; Bradfield & Hambidge, 1980).

Low hair zinc concentrations have been reported in infants and children with impaired linear growth (Hambidge et al., 1972; Walravens & Hambidge, 1976; Buzina et al., 1980; Walravens et al., 1983; Smit Vanderkooy &
Gibson, 1987; Gibson et al., 1989b; Ferguson et al., 1989) and taste acuity (Hambidge et al., 1972; Gibson et al., 1989a; Cavan et al., 1993), two clinical features of mild zinc deficiency in children. Moreover, in some of these
studies, the low hair zinc concentrations have been related to low availability of dietary zinc (MacDonald et al., 1982; Ferguson et al., 1989; Cavan et al., 1993). In some but not all of these cases of suboptimal zinc status, hair
zinc concentrations have increased in response to zinc supplementation. The discrepancies may arise from variations in the dose, duration of zinc supplementation, and confounding effects of season on hair zinc concentrations.
Periods of 6 weeks or less are probably too short for a response, since hair zinc reflects only chronic changes in zinc status (Greger & Geissler, 1978; Lane et al., 1982). Unfortunately, when studies are made over a longer term,
seasonal changes in hair zinc concentrations must also be taken into account when interpreting the results (Hambidge et al., 1979; Gibson et al., 1989a).

Standardized procedures for sampling, washing and analysing hair samples are essential in all studies. Variations in hair zinc concentrations with hair colour, hair beauty treatments, season, sex, age, anatomical site of sampling
(scalp or pubic), and rate of hair growth have been described (Hambidge, 1982; Taylor, 1986; Klevay, 1987; Gibson et al., 1989b). The effects of these possible confounding factors must be considered in the interpretation of
hair zinc concentrations.

Many investigators have failed to find any positive correlations between the zinc content of hair and serum/plasma zinc concentrations (Klevay, 1970; Lane et al., 1982; Gibson et al., 1989b). These findings are not unexpected.
The zinc content of the hair shaft reflects the quantity of zinc available to the hair follicles over an earlier time interval. Positive correlations between hair zinc concentrations and serum zinc are only observed in chronic, severe
zinc deficiency in the absence of confounding factors.

Clinical signs of marginal zinc deficiency in childhood, such as impaired growth, poor appetite and reduced taste acuity, are usually associated with hair zinc concentrations of less than 70 µg/g (1.07 µmol/g) (Hambidge et al.,
1972; Smit Vanderkooy & Gibson, 1987) Therefore, this value is frequently used as the cut-off point for hair zinc concentrations indicative of suboptimal zinc status in children. The validity of hair zinc as a chronic index of
suboptimal zinc status in adults is less certain, and further studies are required.

Saliva

Zinc concentrations in mixed saliva, parotid saliva, salivary sediment and salivary supernatant have all been investigated, but their use as indices of zinc status is equivocal (Greger & Sickles, 1979; Freeland-Graves et al., 1981;
Lane et al., 1982; Baer & King, 1984).

6.5.1.3 Functional tests of zinc status

Functional tests measure changes in the activities of certain enzymes or blood components that are dependent on zinc. Alternatively, physiological functions dependent on zinc, such as growth, taste acuity and immune
competence, can be assessed. Such tests have greater biological significance than static biochemical tests because they measure the extent of the functional consequences of zinc deficiency. Nevertheless, because functional
physiological tests are not very specific, they must always be interpreted in combination with a biochemical test.

Zinc-dependent enzymes

Over 300 zinc metallo-enzymes have been identified. They vary in their response to zinc deficiency, depending on the tissues examined, their affinity to zinc, and rate of turnover of the enzyme (Cousins, 1986). The activity of
serum alkaline phosphatase is the most widely used to assess zinc status (Adeniyi & Heaton, 1980), although its response has been inconsistent in humans (Ishizaka et al., 1981; Nanji & Anderson, 1983; Baer et al., 1985;
Weismann & Hoyer, 1985; Milne et al., 1987). In general, activity is reduced in severe zinc deficiency states (Kasarskis & Schuna, 1980; Sachdev et al., 1990) but this parameter is probably not sensitive enough for detecting
mild zinc deficiency (Walravens & Hambidge, 1976; Walravens et al., 1983, 1989; Ruz et al., 1991). Response of the enzyme during zinc supplementation studies has been inconsistent (Hambidge et al., 1983; Walravens et al.,
1983; Weismann & Hoyer, 1985; Gibson et al., 1989b. Measurements of alkaline phosphatase activity in neutrophils (Prasad, 1983, 1985), leukocytes (Baer et al., 1985; Schilirò et al., 1987), erythrocytes (Samman et al., 1996)
and red cell membranes (Ruz et al., 1992) have also been investigated as indices of body zinc status in humans. Although some promising results have been obtained, more studies are needed before any definitive conclusions
can be reached.

Other zinc metallo-enzymes that have been investigated as indices of zinc status in humans include alpha-amino-laevulinic acid dehydratase in erythrocytes (Faraji & Swendseid, 1983; Baer et al., 1985), angiotensin-1-
converting enzyme (Reeves & O’Dell, 1985; Ruz et al., 1992), alpha-d-mannosidase in serum/plasma (Apgar & Fitzgerald, 1985) and nucleoside phosphorylase in whole, lysed cells (Prasad & Rabbani, 1981; Ballester &
Prasad, 1983). To date, there is no universally accepted zinc-dependent enzyme that can be used to assess marginal zinc deficiency in humans.

Taste acuity tests

Diminished taste acuity (hypogeusia) is a feature of marginal zinc deficiency in children (Hambidge et al., 1972: Buzina et al., 1980; Gibson et al., 1989a,b; Cavan et al., 1993) and adults (Wright et al., 1981; Henkin, 1984).
Several methods for testing taste acuity have been used (Desor & Maller, 1975; Bartoshuk, 1978). In studies of Canadian and Guatemalan children, significant inverse relationships between the detection threshold for salt and
hair zinc concentrations were noted (Gibson et al., 1989a,b; Cavan et al., 1993). These results suggest that impaired taste acuity can be used as a functional test of suboptimal zinc nutriture in children, in conjunction with a
biochemical index of zinc status.

Growth

Impairments in ponderal and linear growth are characteristic features of mild zinc deficiency in infancy and childhood. Some of the double-blind studies in infants and children (Ronaghy et al, 1974; Walravens & Hambidge,
1976; Walravens et al., 1983, 1989, 1992; Castillo-Duran et al., 1987; Gibson et al., 1989a) but not all (Ronaghy et al., 1974; Udomkesmalee et al., 1992; Cavan et al., 1993; Bates et al., 1993) have demonstrated significant
improvements in weight and/or length or height in the zinc supplemented group compared to those receiving a placebo. In some cases, these changes have been observed only in the males. Possible reasons for failure of studies
to show an efficacious effect of zinc on growth may include the presence of other limiting deficiencies and binding ligands in diets, which lower bioavailability of the zinc supplement, the form and level of the dose given, and
the duration of the study period.

Until recently, a period of 6 months has been said to be the minimum interval for the provision of reliable growth data. For shorter intervals, measurement errors were too large in relation to the mean increments. Recently,
however, it has been shown that increments in knee height measured using a device developed by Spender et al. (1989) can be accurately assessed over 60 days, and possibly even over a 28-day period. Using this instrument,
future studies may measure knee height to monitor growth over a shorter time interval. The efficacy of this technique has been shown in controlled repletion trials in children (Sandstead et al., 1998).

6.5.1.4 New approaches

Plasma metallothionein concentrations have been suggested as a useful indicator of poor zinc status (King 1990). Metallothionein appears to play a role in zinc absorption, inter-organ zinc transport and tissue detoxification
(Grider et al., 1990; King, 1990). Levels fall in zinc depletion and deficiency as a result of impaired synthesis. Specificity is poor: levels are also affected by iron deficiency, diurnal rhythm and acute infection. Metallothionein
in erythrocytes appears to be much less responsive to stress and infection than in plasma, and may provide a useful index of zinc status in infancy and childhood.

Serum thymulin has also been assessed as a potential index of zinc status; thymulin is a zinc metallopeptide, the activity of which falls in mild zinc deficiency (King, 1990). Serum insulin-like growth factor (IGF), a peptide of
low molecular weight regulated by growth hormone, nutrition and insulin, is also affected by zinc status (Cossack, 1986). Zinc-deficient rats showed a reduced growth rate, which was associated with a significantly lower serum
IGF and with growth hormone receptor genes (McNall et al., 1995). Zinc repletion of Vietnamese children was followed by enhanced growth and increased serum concentrations of IGF-1 (Ninh et al., 1996).

Based on the essentiality of zinc for alcohol dehydrogenase, ethanol metabolism has been examined as a functional test of zinc status. Ethanol tolerance was shown to be impaired in women fed a diet marginal in zinc (Milne et
al., 1987).

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The essentiality of zinc for the activity of retinol reductase was first demonstrated in rats (Huber & Gershoff, 1975). Based on these findings, zinc was shown to be essential for human dark adaptation (Morrison et al., 1978).
Retinol reductase is required for the regeneration of rhodopsin from retinol, a reaction essential for normal rod function, which in turn is responsible for dark adaptation. More recently, Udomkesmalee et al. (1992) successfully
used the dark adaptation test for assessing the response to zinc repletion in schoolchildren in north-eastern Thailand. The test is not appropriate for pre-school children who are too young to perform it accurately. Age influences
dark adaptation and must be taken into account when interpreting test results.

The essentiality of zinc for brain function was established in laboratory animals (Sandstead, 1985). Studies in men showed that intakes of 1–4 mg of zinc daily for intervals of 35 days impaired neuromotor and cognitive
function (Penland, 1991). Observations in children showed that zinc repletion improved neuromotor and cognitive function (Penland et al., 1997).

6.5.2 Metabolic role

Zinc is an essential trace element in all biological systems studied, and health disorders as a result of zinc deficiency have been well documented in humans and animals (Prasad, 1966, 1976, 1988, 1993; Sandstead, 1982c;
Hambidge et al., 1986). The metabolic changes underlying human zinc deficiencies are incompletely understood (Hambidge, 1989); it is known, however, that zinc has a fundamental role in the structure and function of
numerous proteins, including metalloenzymes, transcription factors and hormone receptors. The widespread role of zinc in metabolism is underscored by the occurrence of zinc in all tissues, organs and fluids of the human body
(see section 6.2). Chapters 7 and 8 provide further information on the effects of zinc deficiencies in animals and humans respectively.

6.5.2.1 Zinc metalloenzymes

Many zinc metalloenzymes have been identified in humans and other mammals since the first report in 1940 of a zinc metalloenzyme, carbonic anhydrase, purified from ox erythrocytes (Keilin & Mann, 1940). The number of
zinc metalloenzymes identified in all phyla is now reported to exceed 300 (Vallee & Auld, 1990a; Coleman, 1992), and the list encompasses all major enzyme classes (Vallee & Auld, 1990b). A summary of the metabolic role of
major classes of zinc-containing enzymes has been given by Walsh et al. (1994). Information on some zinc metalloenzymes that have been widely studied in humans and other mammals has also been summarized by Vallee &
Falchuk (1993).

Zinc metalloenzymes contain stoichiometric amounts of zinc, which may serve a functional and/or structural role, depending on the particular enzyme. In its functional role, zinc is considered to be located at the active site in
many enzymes, and to participate directly in the catalytic process. Indirect evidence of a role of zinc in catalysis has been provided for many enzymes by the reversible inhibition or abolition of enzyme activity by metal
chelating agents in vitro. In a structural role, zinc may stabilize protein structure or influence protein folding. In a comparison of the 12 zinc metalloenzymes for which the structures have been determined by X-ray
crystallography, Vallee & Auld (1990a,b) noted that, at each catalytic site, zinc is generally coordinated by three amino acid residues, most commonly histidines, and a water molecule, whereas at structural sites zinc is
coordinated by four cysteine residues. The water molecule at catalytic sites has a critical role in the catalytic process (Vallee & Auld, 1990b).

DNA and RNA polymerases

DNA polymerases purified from the bacterium Escherichia coli and nuclei of the sea urchin Strongylocentrotus franciscanus have been reported to contain about 2 and 4 gram-atoms of zinc per mole of polymerase, respectively
(Slater et al., 1971). Activity of DNA polymerase from each source was inhibited by the metal-chelator ortho-phenanthroline (Slater et al., 1971). However, Wu & Wu (1987) suggested that the use of this agent may be
misleading, as it can form a complex with DNA that prevents the polymerase activity of DNA polymerase. The DNA polymerase of E. coli may retain its polymerase activity in the absence of stoichiometric amounts of zinc,
indicating that zinc may have another role in the bacterium.

Eukaryotic RNA polymerases I, II and III are involved in the synthesis of ribosomal, messenger and transfer RNAs, respectively. The DNA-dependent RNA polymerases I (Falchuk et al., 1977), II (Falchuk et al., 1976) and III
(Wandzilak & Benson, 1977) of the unicellular eukaryote Euglena gracilis have all been shown to be zinc metalloenzymes, each binding about 2 gram-atoms of zinc per mole of protein, with enzyme activity being reversibly
inhibited by a variety of metal-chelating agents.

Zinc transcription factors

A comparatively recent development in the study of zinc metabolism has been the elucidation of the potential role of zinc in many protein transcription factors. This development was initiated by the demonstration that
transcription factor IIIA (TFIIIA), isolated from Xenopus laevis oocytes, is a zinc metalloprotein and requires zinc for specific binding to DNA (Hanas et al., 1983). Examination of the amino acid sequence of Xenopus TFIIIA
revealed a repeated structural domain, termed the "zinc finger", which has been postulated to bind zinc and interact with DNA. The TFIIIA type of zinc finger is a compact globular structure containing a single zinc atom,
coordinated by 2 cysteine and 2 histidine residues (Lee et al., 1989a) The zinc atom maintains the finger structure (Frankel et al., 1987), and the zinc finger binds in the major groove of DNA, wrapping partly around the double
helix (Pavletich & Pabo, 1991).

The zinc finger motif first characterized in TFIIIA has subsequently been identified in the cDNA sequences of numerous transcription factors, although in only a few instances has the presence of zinc been confirmed
analytically (Vallee & Auld, 1990a). The zinc finger proteins include a substantial number of human proteins (Berg, 1990; South & Summers, 1990).

Steroid hormone receptors have also been identified as a group of transcription factors in which zinc may play an important role in DNA binding. These receptors are located in the cytoplasm or nucleus. Upon binding to the
respective hormone, the activated receptor also binds to a DNA element known as the hormone response element, and modulates gene transcription (Tsai & O’Malley, 1994). The DNA-binding domains of the oestrogen receptor
(Schwabe et al., 1990) and the glucocorticoid receptor (Freedman et al., 1988) have been shown to contain zinc-binding sites at which two zinc ions are each coordinated by four cysteine residues, and the DNA-binding site is
located between and attached to the two zinc complexes. This structural arrangement differs significantly from that of the TFIIIA type of zinc finger (Pavletich & Pabo, 1991), and has been termed the "zinc twist" (Vallee et al.,
1991). Zinc is required for the proper folding of the complex into its active structure (Freedman et al., 1988), which binds with DNA (Luisi et al., 1991). The conservation of structural amino acids among the DNA-binding
steroid receptors (Evans, 1988) suggests that all members of the steroid receptor superfamily may have a similar zinc-containing structure for DNA recognition (Freedman et al., 1988; Schwabe et al., 1990).

6.5.2.2 Metallothionein

Metallothioneins (MT) are a group of low-molecular-weight (6000-dalton) metalloproteins with many proposed biological functions but no known enzymatic activity (Hamer, 1986). In mammals they occur in four structurally
similar isoforms (MT-1,-2, -3 and -4) with several distinct features: a very high cysteine content (30%) of 20 cysteine residues in the total of 61 amino acids (Kissling & Kagi, 1977), and a high zinc and/or cadmium-binding
ratio of about 7 gram-atoms of zinc and/or cadmium per mole of protein (Pulido et al., 1966). They bind metals through mercaptide bonds with a tetrathiolate motif by terminal and bridging cysteine ligands, similar to those
found in zinc transcription factors (Berg & Shi, 1996). In addition, metallothioneins contains two distinct adamantine-like metal-binding clusters with three and four metal ions, respectively (Furey et al., 1986; Messerle et al.,
1990; Robbins et al., 1991). MT-1 and MT-2 are the major isoforms and are found at low basal levels in most adult tissues, especially liver, kidney and pancreas. MT-3 and MT-4 have organ-specific expression; MT-3 is
expressed specifically in brain and MT-4 is expressed in stratified squamous epithelium of tongue, cornea, intestine and stomach. High concentrations of MT-1 and MT-2 are found in fetal and neonatal livers, certain
proliferating cells and human tumour cells, and they have been localized in the nucleus of these cells (Cherian, 1994). Metallothionein synthesis is induced by various chemicals, including metals, such as zinc, copper, cadmium
and mercury, cytokines and stress conditions. The regulation of induced synthesis is at the transcriptional level by both cis- and trans-acting elements, which involve metal regulatory elements and transcription factors (Palmiter
et al., 1993).

The exact physiological role of metallothionein is unclear and suggested functions include detoxification of heavy metals, zinc and copper homeostasis, scavenging of free radicals, zinc storage, and its exchange to other zinc
proteins or enzymes (Zeng et al., 1991). Metallothionein is the major zinc- and copper-binding protein in fetal human liver. It is also involved in the altered zinc homeostasis during inflammation and is increased in the liver in
response to cytokines and the stress hormone response, leading to hepatic zinc accumulation (Philcox et al., 1995). The induction of metallothionein synthesis can protect animals and cultured cells from some metal toxicity and
free radical injury. In addition, recent studies in transgenic mice showed that metallothionein-null mice are very susceptible to cadmium toxicity (Michalska & Choo, 1993; Masters et al., 1994), and embryonic cells from these
mice are extremely sensitive to metal toxicity (Lazo et al., 1995). For discussions of the potential roles for metallothionein see Hamer (1986) and Bremner & Beattie (1990).

6.5.2.3 Other metabolic functions of zinc

For example purposes, the role of zinc in two metabolic functions is outlined below.

Hormone storage

Zinc may play a role in the synthesis and storage of insulin. Insulin forms insoluble zinc-insulin crystals (Adams et al., 1969), and is stored in crystalline form in granules of the beta-islet cells of the pancreas following synthesis
from its soluble precursor, proinsulin (Grant et al., 1972). Grant et al. (1972) showed that at low zinc concentrations in vitro, insulin and proinsulin form soluble hexamers, whereas at high concentrations insulin, but not
proinsulin, forms a precipitate. Yip (1971) found that pancreatic zinc (Zn2+) minimized the degradation of bovine insulin by a purified pancreatic protease in vitro.

Cunningham et al. (1990) proposed that the dimerization of human growth hormone by zinc may prolong the hormone’s storage life in the secretory granules of the anterior pituitary. It was shown that zinc (Zn2+) induces the
dimerization of human growth hormone, and retards its denaturation by guanidine-HCl in vitro (Cunningham et al., 1990).

Neurotransmission

There is some evidence that zinc may influence neurotransmission in the central nervous system, particularly in relation to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Westbrook & Mayer (1987)
demonstrated that zinc (Zn2+) is a potent antagonist of the excitatory neurotransmitter N-methyl-d-aspartate (NMDA) and GABA in cultured mouse hippocampal neurons. The non-competitive antagonism of NMDA suggested
that the NMDA receptor channel contains a third binding site, in addition to Mg2+ and glycine (Westbrook & Mayer, 1987). Xie & Smart (1991) found that the naturally occurring, spontaneous giant depolarizing potentials
(GDPs) in hippocampal neurons in brain slices from young postnatal rats could be inhibited by specific chelation of endogenous zinc, and that GDPs could be induced in adult brain slices by bath application of zinc. It was
proposed that GDPs are generated by an inhibitory action of zinc on pre- and postsynaptic GABAB receptors (Xie & Smart, 1991).

6.5.3 Human studies

6.5.3.1 Copper

Impaired copper nutriture in humans has been noted following the chronic, elevated intake of zinc. These effects are reported in section 8.3.5.

7. EFFECTS ON LABORATORY MAMMALS AND

IN VITRO TEST SYSTEMS
7.1 Single exposure
7.1.1 Lethality
In a study to determine the acute toxicity of four zinc compounds (acetate, nitrate, chloride and sulfate) administered by the oral or intraperitoneal route to male Swiss mice and male Sprague Dawley rats (Table 20), the majority
of deaths occurred during the first 48 h. The clinical and physical signs of toxicity included miosis, conjunctivitis, decreased food and water consumption, haemorrhage and haematosis in the tail. These effects were reported to
diminish with time, indicating rapid elimination of zinc from the body. The acute toxicity of zinc varied with the zinc salt used, and ranged from 237 to 623 mg/kg in rats and from 86 to 605 mg/kg in mice after oral

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administration; the acute toxicity following an intraperitoneal dose ranged from 28 to 73 mg/kg in rats and from 32 to 115 mg/kg in mice (Domingo et al., 1988). LC50 values following inhalation exposure to zinc chloride were
11 800 mg/min per m3 in mice (Schenker et al., 1981) and 2000 mg/m3 in rats (Karlsson et al., 1991).

7.1.2 Acute studies: summary of key findings

Zinc chloride can produce significant lung damage in rats when instilled directly into the lung; zinc oxide, by contrast, does not produce lung damage even when administered at relatively high concentrations. This is possibly
due to the respective solubilities of the two compounds: zinc chloride is readily soluble in water whereas zinc oxide is not. Zinc chloride induces intra-alveolar oedema which closely resembles the effects of inhaled zinc
oxide/hexachloroethane smoke in experimental animals. (Zinc oxide/hexachloroethane when burned produces zinc chloride with a residue of zinc oxide.) The oedema correlates with increased levels of protein in the lavage
fluid fraction, which represents a plasma exudate. Onset is very rapid, with the greatest effects generally being noted within 3 days when high doses are used. The condition was found to regress between days 3 and 7. Key
findings from these studies are summarized in Table 21.

Table 20. Acute lethal dose toxicity of various zinc compounds in rats and mice: LD50 values (mg/kg)a

Compound Route of administration

Rats Mice

Oral Intraperitoneal Oral Intraperitoneal

Zinc acetate 794 162 287 108

as zinc: 237 48 86 32

Zinc nitrate 1330 133 926 110

as zinc: 293 39 204 32

Zinc chloride 1100 58 1260 91

as zinc: 528 28 605 44

Zinc sulfate 1710 200 926 316

as zinc: 623 73 337 115

a Animals were observed for 14 days.

From: Domingo et al. (1988).

Table 21. Key findings from acute studies in experimental animals

Species Exposure Compound Effects Reference

Rats (male) inhalation, 1 h zinc oxide/ 11/40 deaths, Brown et al.

0, 11, 580 mg/min/m3 hexachloroethane pulmonary oedema (1990)

Rats (male) intratracheal 0, 2.5 mg/kg zinc chloride respiratory distress, Brown et al.
alveolitis, (1990)
parenchymal
scarring

Guinea-pigs and inhalation (nose only), 3 h zinc oxide (median inflammatory Gordon et al.
rats 2.5, 5 mg/m3 diameter 0.06 m m) changes in the lung (1992)
at both levels of
exposure

Guinea-pigs aerosol, 3 h 0, 7.8 mg/m3 zinc oxide (projected decrease in the lung Lam et al. (1982)
(male, Hartley) area diameter 0.05 m volume capacity
m)

Rats (male, intratracheal 0.3 mg/kg zinc oxide, zinc elevated alveolar Richards et al.
Porton Wistar) chloride surface protein (1989)
levels with zinc
chloride exposure
only

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Rats (male, intratracheal 0, 0.25, 0.5, 1, zinc oxide, zinc intra-alveolar Richards et al.
Porton Wistar) 2, 4, 5 mg/kg chloride oedema at doses (1989)
above 0.5 mg/kg

Rats (male, inhalation 2.5 mg/kg zinc chloride pulmonary oedema Richards et al.
Porton Wistar) (1989)

Sheep (weaner) drench 3 g zinc 14/100 deaths, Allen et al. (1986)

oedema of
abomasum and
duodenum,
fibrosing
pancreatitis

Rabbits (New inhalation 0, 0.6, 0.81 g/m3 hexachloroethane/zinc acute inflammation Marrs et al. (1983)
Zealand) of lungs,
pulmonary oedema
at both doses

7.2 Short-term exposure

7.2.1 Oral exposure
Reduced growth rates, reduced body weights and anaemia were observed in a number of rat studies and also in a mouse and a sheep study, following high oral or dietary intakes of zinc (Van Reen, 1953; Maita et al., 1981; Allen
et al., 1983; Zaporowska & Wasilewski, 1992). Copper deficiency induced by high doses of zinc, was implicated in these effects, as copper supplementation reversed the zinc-induced anaemia (Smith & Larson 1946).

Exposure to high doses of zinc was associated with pancreatic atrophy and histological changes in kidneys, accompanied by changes in kidney function in rats, mice and sheep (Maita et al., 1981; Allen et al., 1983; Llobet et al.,
1988). Changes in the liver, including decreased activities of cytochrome P450 and liver catalase, and decreased de novo synthesis of high-density lipoprotein, were seen in rats exposed to high levels of zinc (Van Reen, 1953;
Woo, 1983; Cho et al., 1989). Minor degenerative changes in the brain, accompanied by elevated neurosecretion and increased activity in the neurohypophysis were seen in rats exposed intragastrically to zinc oxide for 10 days
at 100 mg/day (Kozik, 1981).

Key findings from these studies are summarized in Table 22.

Table 22. Key findings from short-term exposure studies in experimental animals

Species Exposure Compound Effects Reference

Mice 0.6 g/kg of diet for 4 zinc sulfate no adverse effects on immune Schiffer et al.
weeks responsiveness (1991)

Mice, rats 0, 300, 3000, 30 000 m zinc sulfate NOEL for both species was set at Maita et al. (1981)
g/g diet for 13 weeks 3000 m g/kg; retarded growth,
anaemia and pancreatic atrophy at
3000 m g/kg level

Rats 0, 0.5, 1% of diet for zinc oxide death at 1% level; reduced body Van Reen (1953)
15 days weight, reduced fat content of the
liver and impaired bone
development at both doses

Rats 500–700 mg/100 g zinc in zinc growth reduction, reduced levels Van Reen (1953)
diet for 4–5 weeks carbonate of liver catalase and cytochrome
oxidase activity, effects reversed
by copper supplement

Rats 100 mg/day zinc oxide elevated neurosecretion in Kozik (1981)

intragastrically for 10 hypothalamus, increased release of
days antidiuretic hormone in
neurohypophysis

Rats 100 mg/day zinc oxide morphological and histoenzymic Kozik (1981)
intragastrically for 10 changes in the brain
days

Rats 0, 0.12 mg/ml zinc as zinc decreased body weight, anaemia Zaporowska &
drinking-water for 4 chloride and increased lymphocyte count Wasilewski (1992)
weeks

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Rats 0, 160, 320, 640 zinc acetate no effect on weight gain or on red Llobet et al.
mg/kg body blood cells, histological changes (1988)
weight/day for 3 in kidneys and increased
months concentrations of urea and
creatinine in plasma at 640 mg/kg
body weight per day

Rats 0, 0.7, 1% in diet for 4 zinc carbonate subnormal growth, anaemia and Smith & Larson
weeks reproductive failure at both dose (1946)
levels, anaemia reversed by
copper supplement, growth
retardation reversed by liver
extract supplement

7.2.2 Inhalation exposure

Guinea-pigs (3 per group) were given 1, 2 or 3 consecutive, daily, 3-hour, nose-only exposures to freshly generated zinc oxide particles with a projected area diameter of 0.05 µm at concentrations of 0, 2.3, 5.9 or 12.1 mg/m3.
Exposure to zinc oxide at 5.9 or 12.1 mg/m3 was associated with increased protein and neutrophils and increased activities of beta-glucuronidase, acid phosphatase, alkaline phosphatase, lactate dehydrogenase and angiotensin-
converting enzyme in lavage fluid. These increases were concentration-dependent, were detected after the second exposure, and generally increased after the third exposure. Significant morphological changes observed at
concentrations of 5.9 or 12.1 mg/m3 consisted of inflammation and type 2 pneumocyte hyperplasia in the proximal alveolar ducts. No evidence of inflammation was present in animals exposed to zinc oxide at 2.3 mg/m3. It was
concluded that exposure of guinea-pigs to ultrafine atmospheric zinc oxide at concentrations of 5.9 or 12.1 mg/m3 causes significant pulmonary damage. Detection of injury was stated to correlate well with pulmonary lavage
fluid changes (Conner et al., 1988).

Male Hartley guinea-pigs exposed to zinc oxide at a concentration of 7 mg/m3 for 3 h/day for 5 consecutive days showed pulmonary impairment (as measured by lung oedema, lung volume carbon monoxide diffusing capacity
and pulmonary mechanics). Exposures at 2.7 mg/m3 using the same time frame did not cause pulmonary impairment (Lam et al., 1988). A single exposure at 8 mg/m3 was also without effect (Lam et al., 1982). Guinea-pigs
exposed to zinc oxide at a concentration of 5 mg/m3 for 3 h/day for 6 consecutive days showed significant reductions in vital capacity, functional residual capacity, alveolar volume, and lung volume carbon monoxide diffusing
capacity following the last exposure, which had not returned to normal values by 72 h, although increases to flow resistance and decreases in compliance and total lung capacity did return to normal (Lam et al., 1985)

Key findings from these studies are summarized in Table 23.

Table 23. Key findings from repeated dose inhalation studies in guinea-pigs

Species Exposure Compound Effects Reference

Guinea-pigs (male 0, 2.3, 5.9 or 12.1 zinc oxide inflammation and hyperplasia Conner et al.
Hartley, 3 per mg/m3, 3 h/day for (projected area of the lung at 5.9 and 12.1 (1988)
group) 1, 2 or 3 days diameter 0.05 µm) mg/m3 after the second
exposure; NOEL, 2.3 mg/m3

Guinea-pigs (male 0, 2.7or 7 mg/m3, 3 zinc oxide (median oedema, decrease in total lung Lam et al.
Hartley, 5–8 per h/day for 5 days diameter 0.05 µm) capacity and diffusing capacity (1988)
group) for CO at 7 mg/m3, oedema; no
effects observed at 2.7 mg/m3

Guinea-pigs (male 0 or 5 mg/m3, 3 zinc oxide inflammation, decrease in vital Lam et al.
Hartley, 18–38 per h/day for 6 days (projected area capacity, functional residual (1985)
group) (nose only) diameter 0.05 µm) capacity, total lung capacity and
diffusing capacity for CO

7.3 Long-term exposure

The long-term studies on the effects of zinc vary in quality and tend to be limited in their usefulness in determining chronic toxicity in animals, as the study design generally does not lend itself to elucidation of dose-related
effects. The available studies do, however, provide some information on target organ toxicity resulting from zinc exposure. Key findings from these studies are summarized in Table 24.

Table 24. Key findings from long-term exposure studies in experimental animals

Species Exposure Compound Effects Reference

Rats 0, 0.1, 0.5 or 1% in zinc carbonate reduction of growth at 1% and Sutton & Nelson
diet for up to 39 indications of anaemia in the 0.5 (1937)
weeks and 1% groups

Rats 0, 100, 500 or 1000 zinc sulfate minimal monitoring; no effect on Hagan et al. (1953)
µg/g in diet for 21 growth and no anaemia; dose–
months related decrease in
myeloid/erythrocyte ratio in all
treated groups; enlarged kidneys
at 500 and 1000 µg/g in all male
groups; NOEL, <100 µg/g

Mice 0 5 g/litre in zinc sulfate pancreatic hypertrophy pituitary Aughey et al

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Mice 0.5 g/litre in zinc sulfate pancreatic hypertrophy, pituitary Aughey et al.
drinking-water for 14 gland hypertrophy (1977)
months

Dogs 200 mg/kg body zinc sulfate emesis, 1/4 deaths, hypochromic Hagan et al. (1953)
weight per day in diet anaemia, hyperplastic bone
reduced to 50 mg/kg marrow
body weight/day by
week 35

Rabbits 5 mg/g in diet for 22 zinc carbonate no effects on growth, decrease in Bentley & Grubb
weeks haemoglobin and serum copper (1991)
concentrations

Mink 0, 500, 1000 or 1500 zinc sulfate no effect on body weights, Aulerich et al.
mg/kg for 144 days haematological parameters or (1991)
survival; no histological lesions in
liver, pancreas or kidney; NOEL,
1500 mg/kg

Ferrets 0, 500, 1500 or 3000 zinc oxide body weight loss, reduced food Straube et al.
mg/kg for up to 6 intake and death at 3000 mg/kg (1980)
months on days 9–13 and at 1500 mg/kg
on days 7–21; diffuse nephrosis
and active haemopoiesis in bone
marrow and spleen in the 3000
and 1500 mg/kg groups;
pancreatitis in one animal in each
group at 3000 and 1500 mg/kg;
no toxicity observed at 500 mg/kg
except some evidence of effect on
red blood cells

Mice, rats 0, 1.2, 12 or 120 zinc in smoke no effect on body weight; Marrs et al. (1988)
mg/m3 air for 1 h/day, produced by increase in mortality in mice at
5 days per week for ignition of zinc 120 mg/m3; macrophage
20 weeks oxide/ infiltration of the lung in rats and
hexachloroethane mice at the highest dose;
significant increase in the
frequency of alveologenic
carcinoma in high dose mice
Note: carbon tetrachloride may be
present in smoke

7.3.1 Oral exposure

Osborne-Mendel rats (4 per sex per group) were fed diets containing zinc sulfate at 0, 100, 500 and 1000 µg/g for 21 months. While only minimal monitoring of toxic effects was carried out, it was reported that food intake,
body weights, haemoglobin values, and erythrocyte, leukocyte and differential counts were unaffected by the treatment. Microcytosis coupled with polychromasia or hyperchromia appeared at 16 months in rats receiving the
highest dose and at 17 months in the other zinc-treated groups. However, it was stated that the erythrocyte count returned to normal later in the study (time not specified). Counts of the bone marrow smears taken at autopsy
revealed a dose-related decrease in the myeloid:erythrocyte ratio in all of the treated groups. The kidneys of male rats in the 500 and 1000 µg/g groups were enlarged and an increased incidence of nephritis was seen in male, but
not female, rats (Hagan et al., 1953).

In a chronic study (Aughey et al., 1977), C3H mice were administered zinc sulfate in the drinking-water at a concentration of 0.5 g/litre for 14 months. Control and zinc-treated mice were removed from the colony in groups of
five per sex, usually at monthly intervals, for estimation of plasma zinc, glucose and insulin, tissue zinc, and histological, histochemical and electron microscopy examinations. Plasma zinc increased to a plateau at levels about
1.5- 2 times those in controls within the first 30 days. Levels of zinc in the liver, spleen and skin remained unchanged. The pancreatic islet cells in treated mice were hypertrophied and contained an increased number of
secretory granules; however, plasma glucose and insulin levels remained comparable to those in control animals. Hypertrophy of the pituitary gland, suggestive of a pituitary feedback effect, was also observed.

Adult and juvenile mink (3 per sex per group) were fed diets supplemented with zinc as zinc sulfate at 0, 500, 1000 or 1500 mg/kg for 144 days. No adverse effects on food consumption, body weight gains, haematological
parameters, fur quality or survival were observed. Zinc concentrations in the liver, kidneys and pancreas increased in direct proportion to the zinc content of the diet. No histological lesions indicative of zinc toxicity were
detected in the liver, kidneys or pancreas (Aulerich et al., 1991).

Ferrets (3–5 per group) were fed diets containing zinc administered as zinc oxide at 0, 500, 1500 or 3000 mg/kg for up to 6 months. The three ferrets in the 3000 mg/kg group lost a significant amount of their body weights, had
greatly reduced food intakes, and died or were killed in extremis between days 9 and 13 of the dosing period. The ferrets exposed to 1500 mg/kg zinc were killed at 7–21 days, by which time they presented with poor condition,
weight loss and up to 80% reduction in food intake. Histological examination of the three animals from the 3000 mg/kg group and the four animals from the 1500 mg/kg group revealed diffuse nephrosis and active
haematopoiesis in the bone marrow and the extramedullary area of the spleen. One animal from each dose group had acute pancreatitis. Haematograms indicated a severe but responding macrocytic hypochromic anaemia, with
high reticulocyte counts in the two highest dose groups. In the liver and kidneys of treated animals, the zinc concentration was significantly increased and the copper concentration was lower than control values. These changes
were associated with a high concentration of iron in the liver. Increased incidences of elevated serum urea and blood glucose concentrations and decreased serum ceruloplasmin oxidase activity were observed at the two highest
doses, and protein, blood, glucose and bilirubin were present in the urine. None of the ferrets given zinc at 500 mg/kg in the diet developed clinical signs. These animals were killed on days 48, 138 and 191 respectively; they
showed signs of extramedullary haematopoiesis in the spleen and slight increases in kidney zinc concentration and decreases in liver copper concentration. Although the number of animals used was small, given the lack of
dose–response studies, the threshold of zinc toxicity in ferrets was proposed to be between 500 and 1500 mg/kg, with the kidney identified as the target organ of toxicity in this species (Straube et al., 1980).

The consequences of copper deficiency may be relevant to some of the effects noted in studies using elevated zinc levels. The occurrence of anaemia in animals receiving high doses of zinc is generally attributed to induction of
copper deficiency. Some otherwise unexplained effects of high doses of zinc may also be secondary to impaired copper utilization. Relevant studies are described in section 7.8.

7.4 Skin irritation

Zinc chloride, applied daily as a 1% aqueous solution in an open patch test for 5 days, was severely irritant in rabbits, guinea-pigs and mice, inducing epidermal hyperplasia and ulceration. Aqueous zinc acetate (20%) was
slightly less irritant. Zinc oxide (20% suspension in dilute Tween 800), zinc sulfate (1% aqueous solution) and zinc pyrithione (20% suspension) were mildly irritant, and induced a marginal epidermal hyperplasia and increased

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hair growth. Zinc undecylenate (20% suspension) was not irritant. Epidermal irritancy was related to the interaction of zinc with epidermal keratin (Lansdown, 1991).

7.5 Reproductive toxicity, embryotoxicity and teratogenicity

The available studies are limited in their usefulness in determining the reproductive and developmental effects of zinc owing to poor study design and inadequate reporting, although they do provide an indication of the effects
of zinc exposure. Key findings from these studies are summarized in Table 25.

Table 25. Key findings from studies on reproduction, embryotoxicity and teratogenicity in experimental animals

Species Exposure Compound Effects Reference

Mice 2000 mg/kg until zinc carbonate in second generation mice exposed Mulhern et al.
mating at 6 weeks of throughout gestation/lactation and (1986)
age, then in various after weaning, elevated levels of
combinations during zinc in bones, decreased blood
gestation/lactation and copper levels, signs of anaemia and
after weaning; second reduced body weights; alopaecia at 5
generation killed at 8 weeks, reversed at 8 weeks
weeks

Mice 0, 12.5, 20.5 or 25 zinc chloride increases in skeletal defect Chang et al.
mg/kg body weight incidence, usually ripple ribs; effects (1977)
i.p. on days 8, 9, 10 or were dose-related and seen at all
11 of gestation dose levels; no soft tissue anomalies
attributed to zinc; greatest effect at
20.5 mg/kg on day 10 of gestation,
causing 4/10 deaths

Mouse 100 µmol/litre in vitro zinc 40% increase in cell death at 1-cell Vidal &
embryos for 24 h at the 1-, 2-, stage; embryo development affected Hidalgo (1993)
4- and 8-cell stage more in early than late stages;
relevance to fetal development
uncertain

Rats 0, 0.1%, 0.5% or 1% zinc carbonate reproduction adversely affected in Sutton &
in diet for 39 weeks the 0.5% group: all second litters Nelson (1937)
and during pregnancy dead, no further pregnancies
thereafter; no pregnancy achieved in
the 1% group; anaemia in 0.5% and
1% groups; anaemia and sterility
reversed in 0.5% group but sterility
remained the 1% group when zinc
removed from diet

Rats 0, 4 or 500 mg/kg in zinc chloride testicular cell development Evenson et al.
diet for 8 weeks to examined only: excess zinc had no (1993)
weanlings. effect

Rats 0, 500, 1000 or 2000 not given significant decrease in total number O’Dell (1968)
µg/g diet during of pups born and increased
pregnancy percentage of stillbirths at 2000
µg/g; no increase in the incidence of
malformations

Rats 0 or 150 mg/kg in diet zinc sulfate effects on fetus assessed on day 18: Kumar (1976)
throughout gestation incidence of resorption significantly
increased in treated animals

Rats 0, 0.25 or 0.5% in diet zinc oxide maternal body weight, gestation Ketcheson et al.
during gestation and period and viable pups/litter were (1969)
14 days of lactation unattested at either dose level at
birth or on day 14; no malformations
observed in any pup; dose-related
reduction in pup body weight; some
changes in iron and copper
distribution in newborn pups at both
treatment levels

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Rats 500 mg/kg in diet zinc carbonate no effect on maternal haematocrits; Uriu-Hare et al.
during gestation no effects on litter numbers, (1989)
viability, implantation sites, fetal
length and weight, placental weights
or incidence of resorptions; no
increase in the incidence of
malformations or skeletal
ossification

Rats 4000 mg/kg, 18 days zinc sulfate incidence of conception reduced; no Pal & Pal
post coitus increase in stillbirths or (1987)
malformations in exposed groups

In a study in mice (Mulhern et al., 1986), female weanling C57BL/6J mice were fed diets containing zinc as zinc carbonate at a concentration of 2000 mg/kg until they were mated at 6 weeks of age. The dams and offspring
were distributed into 10 different dietary groups, exposing the second generation to various combinations during gestation, lactation and postweaning development. Second-generation mice were killed at 8 weeks of age.
Second-generation mice exposed to high doses of zinc throughout the gestation, lactation and postweaning period had elevated levels of zinc in their bones, decreased blood copper levels, lowered haematocrit values and
reduced body weights. Mice in this group began to lose fur at 2–4 weeks of age, with severe alopecia developing at 5 weeks of age, accompanied by thinner than normal skin. The fur grew back by 8 weeks of age, albeit lighter
in colour.

The feeding of low (4 mg/kg of diet), normal (12 mg/kg) and high (500 mg/kg) levels of zinc as zinc chloride to weanling Sprague-Dawley rats (10 males per group) for 8 weeks indicated that a diet deficient in zinc is
associated with a significant deviation in the ratio of testicular cell types present in the testes, including a reduction in the numbers of cells in S phase and total haploid cells. In rats fed zinc-deficient diets, about 50% of
epididymal spermatozoa had a significant decrease in resistance to DNA denaturation in situ. Excess zinc in the diet had no effect on rat testicular cell development as defined by sperm resistance to DNA denaturation,
distribution of testicular cell types and sperm chromatin structure integrity (Evenson et al., 1993).

A diet supplemented with zinc (source not identified) at 0, 500, 1000 and 2000 µg/g, and with adequate levels of copper (10 µg/g) was administered to pregnant rats (strain and number not given). There was a significant
decrease in the total number of pups born and an increase in the percentage of stillbirths at the highest dose of zinc, but no effect on the survival of offspring allowed to nurse for 1 week. The data were reported to indicate that
the incidence of hydrocephalus was increased in rat embryos of zinc-treated dams. However, there was no obvious correlation between dose and the incidence of hydrocephalic fetuses associated with the treatment: 0.1% in
controls, 0.2% in the 500 µg/g group, 0.7% in the 1000 µg/g group, and 0.1% in the 2000 µg/g group (O’Dell, 1968).

Pregnant rats (10–12 per group, strain not identified) were fed a diet supplemented with zinc sulfate (150 µg/g) throughout the entire gestation period. On day 18 of pregnancy, the incidence of resorptions in pregnant rats
increased from 2/101 implantation sites in the 12 control rats (2 females affected) to 11/116 implantations in the supplemented rats (8 females affected) This difference was statistically significant, indicating that even
moderately high levels of zinc in the diet of rats may be associated with harmful effects on pregnancy (Kumar, 1976).

Diets high in zinc (0.2 and 0.5%), added as zinc oxide, were fed to pregnant albino rats (10 per group) for the entire period of gestation and for the first 14 days of lactation. The zinc content of the basal diet was 9 mg/kg. Four
pups from each litter were killed at birth and the remaining pups were killed and examined on day 14 of lactation. Maternal body weights, food intake, gestation period and the number of viable young per litter were unaffected
by the increased zinc levels in the diet, either at birth or on day 14 of lactation. Two dams fed 0.5% zinc had stillborn litters containing oedematous pups. Four stillborn pups were born to dams fed 0.2% zinc (number of dams
not given); these pups were not oedematous. Anatomical malformations were not observed in any pup. The body weights of the newborn and 14-day-old pups in the 0.5% group were significantly reduced whereas the size of
newborn pups, but not the 14-day-old pups from the 0.2% group were significantly greater than pups from dams fed the basal diet. The dry liver weights of pups at birth were unaffected by the zinc treatment but were
significantly reduced in day-14 pups in the 0.5% group. Total zinc in newborn pups and day-14 weanlings was elevated in a dose-related manner in pups from the dams exposed to 0.2% and 0.5% zinc. Bodies (viscera removed)
of newborn and day-14 pups from mothers fed the zinc diets contained significantly lower total iron than those from mothers receiving the basal diet: the reduction was dose-dependent. In contrast, the livers of newborns from
zinc-treated dams contained significantly elevated total iron than the basal diet pups. These changes in liver iron levels were not observed in day-14 pups. Total copper in the whole animal and body (viscera removed) of the
newborn rats was not altered by the treatment. However, liver copper levels were significantly lower only in the newborns of mothers fed 0.5% zinc. After 14 days, total copper was significantly lower in the whole animal, liver
and body (viscera removed) of pups from dams fed both zinc diets; this reduction was dose-dependent. Livers of dams fed excess zinc contained elevated zinc and reduced iron and copper levels (Ketcheson et al., 1969).
Another study reported no resorption in Sprague-Dawley rats receiving 0.5% zinc as zinc carbonate in the diet (Kinnamon, 1963).

Pregnant Sprague Dawley rats (8 per group) were exposed to basal (24.4 mg/kg of diet) or high levels of zinc (500 mg/kg) in the diet, supplemented as zinc carbonate, for the duration of the gestation period. Ingestion of high
zinc levels had no effect on maternal food intake or on body weight throughout the pregnancy. Maternal haematocrits on gestational day 20 were similar in the basal and high-zinc groups. High dietary zinc levels had no effect
on litter numbers, litter viability, implantation sites, fetal lengths and weights, placental weights or number of resorptions. There was no significant increase in the incidence of malformations associated with high zinc exposure
or in the ossification of the fetal skeleton. Zinc, copper and iron content of the maternal liver, and maternal kidney weights in the basal and high-zinc groups remained comparable. Plasma of dams exposed to the high-zinc diet
contained significantly increased zinc levels and significantly decreased iron levels, whereas copper levels remained similar to those found in rats fed the basal diet. The absolute concentrations of zinc bound to albumin and
alpha2-macroglobulin proteins were significantly increased in the high-zinc group as were maternal liver metallothionein concentrations (Uriu-Hare et al., 1989).

Exposure of Charles Foster rats (12 per group) to diets containing zinc as zinc sulfate at a concentration of 4000 mg/kg reduced the incidence of conception in females treated for 18 days post coitus, indicating that high zinc
intake interferes with implantation of fertilized ova. However, exposure to this level of zinc 21–26 days before mating and throughout gestation for 18 days did not affect the incidence of conception. This apparently
contradictory finding was interpreted to be due to an adaptation to zinc feeding, which is known to decrease the body burden of zinc. No stillborn or malformed fetuses were observed in zinc-treated animals in either study (Pal
& Pal, 1987).

7.6 Mutagenicity and related end-points

Genotoxicity studies conducted in a variety of test systems have failed to provide evidence that zinc is mutagenic. However, there are indications of some weak clastogenic effects following zinc exposure. The findings from
genotoxicity studies are detailed below and are summarized in Table 26.

Table 26. Genotoxicity studies with zinc

Test Zinc source doses Concentrations Results Reference

of zinc

Non-mammalian systems

Prokaryotes

Gene mutation

Salmonella typhimurium (TA102) zinc sulfate 10–1000 - (no S9) Marzin & Vo
nmol/litre per (1985)
plate

S. typhimurium (TA98, TA100, zinc acetate 50–7200 m - (with and without Thompson et al.
TA1535, TA1537, TA1538) g/plate S9) (1989)

zinc 2,4- 400 m g/plate + (with and

pentanedione without S9)

S. typhimurium (TA98, TA1538) zinc sulfate up to 3600 m - (with and without Gocke et al.
g/plate S9) (1981)

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S. typhimurium (TA98, TA100, zinc oxide/ - (with and without Karlsson et al.
TA1535, TA1537, TA1538) hexachloroethane S9) (1991)
smoke

S. typhimurium (TA98, TA100, zinc chloride 0.05 mol/litre - Nishioka (1975)

TA1535, TA1537)
zinc chloride not given - Kada et al.
(1980)

Bacillus subtilis H17, M45 zinc chloride 0.4 mmol/litre - Rossman et al.
(1987)

Escherichia microscreen assay zinc chloride 0.4 mmol/litre - Rossman et al.

(1987)

lambda prophage induction Trp+ zinc chloride 0.4 mmol/litre - Rossman et al.
reversion comutagenesis (1987)

Fidelity of DNA synthesis zinc sulfate 0.2 mmol/litre - Miyaki et al.

(1977)

DNA polymerase zinc chloride 0.4 mmol/litre - Sirover & Loeb

(1976)

Plants

Chromosomal aberrations

Vicia faba zinc sulfate 0.1% solution + Herich (1969)

Insects

Sex-linked recessive lethal test zinc sulfate 5 mmol/litre - Gocke et al.

(1981)

Sex-linked recessive lethal test zinc chloride 0.247 mg/ml of + Carpenter & Ray
food (1969)

Dominant lethal test zinc chloride 0.247 mg/ml of +

food

Mammalian systems

In vitro animal cells

Gene mutation

mouse lymphoma zinc chloride 0.12–12.13 m - Amacher &

g/ml Paillet (1980)

mouse lymphoma zinc acetate 0–13 m g/ml and + (with and Thompson et al.
4.2–42 m g/ml without S9) (1989)

Chromosomal aberration

Chinese hamster ovary cells zinc acetate 25–45 m g/ml + (with and Thompson et al.
and 45–80 m without S9) (1989)
g/ml

Cell transformation

Syrian hamster embryo cells zinc chloride 0–20 m g/ml -

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DiPaolo & Casto

(1979)

enhancement of cell transformation zinc sulfate 0.05–0.6 +/- Casto et al.

mmol/litre (1979)

enhancement of cell transformation zinc chloride 0.05–0.6 +/-

mmol/litre

Unscheduled DNA synthesis

rat hepatocytes zinc acetate 10–1000 m g/ml - Thompson et al.

(1989)
rat hepatocytes zinc 2,4- 10–1000 m g/ml -
pentanedione

In vitro human cells

Chromosomal aberration

human lymphocytes zinc chloride 3 × 10-4 – 3 × + Deknudt &

10-5 mol/litre Deminatti
(1978)

In vivo animal

Sister chromatid exchange

sheep bone marrow cell emission dust 32 g/day + Bires et al.

(1995)

rat bone marrow zinc chloride 240 mg/kg + Kowalska-

Wochna et al.
(1988)

Micronucleus test

mouse zinc sulfate 0.1- 0.3 - Gocke et al.

mmol/litre per (1981)
kg

mouse zinc 0.1 ml smoke - Karlsson et al.

oxide/hexachloro condensate (1991)
ethane smoke

Chromosomal aberration

rat bone marrow zinc oxide 0.5- 1 mg/m3 + Voroshilin et al.

(1978)

mouse zinc chloride 15 g/kg - Vilkina et al.

(1978)

mouse bone marrow zinc chloride 0.5% zinc for 1 - Deknudt &
month Gerber (1979)

mouse bone marrow zinc chloride 0- 15 mg/kg + Gupta et al.

(1991)

rat bone marrow zinc chloride 240 mg/kg for + Kowalska-

14 days Wochna et al.
(1988)

sheep bone marrow cell emission dust 32 g/day - Bires et al.

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p g y
(1995)

Dominant lethal mutation

mouse zinc chloride 15 mg/kg - Vilkina et al.

(1978)

In vivo human

Chromosomal aberration zinc smelter dust + Bauchinger et al.

cadmium (1976)

plant fumes/dust - Deknudt &

Leonard (1975)

7.6.1 In vitro studies

Exposure to zinc does not increase mutation frequencies in the majority of bacterial or mammalian cell culture test systems (Nishioka, 1975; Amacher & Paillet, 1980; Kada et al., 1980; Gocke et al., 1981; Marzin & Vo, 1985;
Rossman et al., 1987; Thompson et al., 1989; Karlsson et al., 1991). However, gene mutation effects following exposure to zinc were observed in the TK+/-mouse lymphoma and Chinese hamster ovary cells in vitro cytogenetic
assays (Thompson et al., 1989), and chromosomal effects were obtained in human lymphocyte cultures (Deknudt & Deminatti, 1978). Zinc chloride did not induce mutations at the thymidine kinase locus in L5178Y mouse
lymphoma cells (Amacher & Paillet, 1980) and did not induce mispairing between nucleic acid bases in vitro (Murray & Flessel, 1976).

Zinc sulfate inhibited the activity of DNA polymerase-1 activity in vitro, but had no effect on the fidelity of DNA synthesis in an assay measuring misincorporation of nucleotides into the new strand of DNA (Sirover & Loeb,
1976; Miyaki et al., 1977). Zinc chloride at concentrations of up to 20 µg/ml did not cause morphological transformation of Syrian hamster embryo cells in vitro (Di Paolo & Casto, 1979); however, zinc chloride and zinc sulfate
gave equivocal results in an in vitro test for the capacity of these metal salts to enhance viral transformation of Syrian hamster embryo cells, producing enhancement in 3/6 and 3/7 trials respectively (Casto et al., 1979).
Exposure to zinc had no effect on the induction of unscheduled DNA synthesis in primary cultures of rat hepatocytes (Thompson et al., 1989).

7.6.2 In vivo studies

The induction of chromosome aberrations has been studied in bone marrow cells harvested from animals exposed to elevated levels of zinc. Taken as a whole, studies of this end-point yield equivocal and sometimes
contradictory results—a likely reflection of inter-study differences in routes, levels and duration of zinc exposure, the nature of lesions scored (gaps compared to more accepted structural alterations) and great variability in the
technical rigour of individual studies. Increased aberrations have been reported in rats after inhalation exposure (zinc oxide at 0.5–1.0 mg/m3 for 5 months; Voroshilin et al., 1978), in rats after oral exposure (zinc chloride in
water at 249 mg/litre for 14 days; Kowalska-Wochna et al., 1988) and in mice after multiple intraperitoneal injections of zinc chloride (at 2–5 mg/kg body weight; Gupta et al., 1991). In contrast, other studies have produced
negative findings, for example, after intraperitoneal injection of mice (zinc chloride at 15 mg/kg body weight; Vilkina et al., 1978), or have suggested that the induction of aberrations is contingent upon concomitant calcium
deficiency. Those studies do not provide compelling evidence for significant clastogenic activity. Negative results have also been reported in the mouse micronucleus test (intraperitoneal injection of zinc sulfate; Gocke et al.,
1981). Negative micronucleus test results are consistent with a lack of significant clastogenic activity.

There was no increase in the frequency of dominant lethal mutation in germ cells of mice injected by the intraperitoneal route with zinc chloride at 15 mg/kg body weight (Vilkina et al., 1978).

Zinc sulfate (5 mmol/litre), which is an almost-lethal dose) fed to adult Drosophila melanogaster did not increase the incidence of sex-linked recessive lethal mutations when tested in three successive broods (Gocke et al.,
1981). In contrast, zinc chloride fed to adult D. melanogaster at 0.247 mg/ml significantly increased the incidence of dominant lethal mutations and sex-linked recessive lethal mutations in treated flies (Carpenter & Ray, 1969).

7.7 Carcinogenicity
No adequate experimental evidence has been found to indicate that zinc salts administered orally or parenterally are tumorigenic.

Deficiency and supplements of zinc can have an influence on carcinogenesis, possibly as a result of the influence of zinc on cell growth (Petering et al., 1967; Barr & Harris, 1973; Phillips & Sheridan, 1976; Rath et al., 1991),
although zinc has also been reported to inhibit tumour induction (Kasprzak et al., 1988). Zinc has been demonstrated to inhibit the mutagenic action of some genotoxic carcinogens (Francis et al., 1988; Leonard & Gerber, 1989)
but has also been shown to be co-carcinogenic in other studies (Wallenius et al., 1979).

7.8 Interactions with other metals

In general, zinc shows a low toxicity to animals, but at high exposure levels it can interact with other trace elements, especially copper, resulting in toxicity, which is usually due to depletion of these elements, and leading to
nutritional deficiencies. It has been postulated (Hill & Matrone, 1970) that elements with similar properties will act antagonistically to each other biologically, as a result of their competition for binding sites on proteins that
require metals as cofactors. The interaction of zinc with other metals, such as copper, iron and calcium, has been reviewed in some detail elsewhere (Walsh et al., 1994; Bremner & Beattie, 1995).

7.8.1 Zinc and copper

Copper deficiency induced by excess zinc intake in experimental animals is manifested by reduced copper concentrations in liver, serum and heart, and decreased activities of copper metalloenzymes (Duncan et al., 1953; Van
Reen, 1953; Cox & Harris, 1960; L’Abbe & Fischer, 1984).

Excessive zinc intake has been shown to inhibit intestinal absorption, hepatic accumulation and placental transfer of copper, as well as to induce clinical and biochemical signs of copper deficiency (Campbell & Mills, 1974;
Bremner et al., 1976; Hall et al., 1979; L’Abbe & Fischer, 1984). Results of an isotope experiment suggest that zinc interferes with copper metabolism by decreasing utilization and increasing excretion of copper in the rat, but
has little effect on copper absorption (Magee & Matrone, 1960). High levels of zinc in the diet have been shown to induce de novo synthesis of metallothionein in a dose-related fashion. It has been suggested that the induced
metallothionein sequesters copper, reducing its bioavailability (Hall et al., 1979). Animals deficient in copper are infertile (Mertz, 1987). Richmond (1992) decreased the mortality of pups delivered of copper-deficient dams by
injection of oxytocin at term. Atrophy of the exocrine pancreas in copper deficiency (Alvarez et al., 1989) may be secondary to vascular changes (Weaver, 1989). Allen et al. (1982) found that copper-deficient rats responded
poorly to injection of thyrotropin-releasing hormone. Deficient, non-anaemic rats at 24 °C became hypothermic with, inter alia, decreased concentration of triiodothyronine in plasma. Mice deficient in copper (Lynch & Klevay,
1992) have a bleeding tendency characterized, inter alia, by increased activated partial thromboplastin time, prothrombin time.

Findings of infertility, thyroid abnormalities, pancreatic changes, coagulation defects and bone pathology in experiments using increasingly high doses of zinc may impair copper utilization. Characterization of the copper
contents of diets and the copper levels in organs is important in understanding the relevance of these effects. If the effects of high doses of zinc are not accompanied by decreased copper in target organs, it seems likely that the
they are related to zinc intoxication.

In a study designed to measure the level of zinc at which copper metabolism begins to be affected, Wistar rats (10 per group) were fed diets containing zinc as zinc sulfate at 0, 15, 30, 60, 120 or 240 mg/kg. Ceruloplasmin
activity is significantly reduced at doses of 30 mg/kg and greater, and the number of rats with extremely low ceruloplasmin activity increases with increased zinc levels in the diet. The level of zinc at which 50% of animals
would have abnormally low ceruloplasmin activity was calculated to be 125–129 mg/kg. Liver superoxide dismutase and heart cytochrome c oxidase activities were significantly reduced at 120 and 240 mg/kg respectively, as
compared to controls (L’Abbe & Fischer, 1984).

Mink (11 females and 3 males per group) were exposed to a basal diet or to a diet supplemented with zinc as zinc oxide at 1000 µg/g throughout the mating, gestation and lactation periods. The basal diet contained zinc at 20.2
µg/g and copper at 3.1 µg/g. Supplementation of the basal diet with zinc had no significant effect on the body, liver, spleen or kidney weights of the adult female mink. No significant differences from control females were seen
in the haematological parameters measured. Clinical signs consistent with copper deficiency (alopecia, anaemia or achromotrichia) were not observed in the adult mink. All females on the basal diet whelped, but only 8 females
on the zinc-supplemented diets produced offspring. The body weights of male kits born to dams consuming the zinc supplemented diet were significantly lower than those of controls at 12 weeks of age. No significant
differences were noted in erythrocyte or leukocyte count, haemoglobin concentration, mean corpuscular haemoglobin concentration, mean corpuscular volume or the leukocyte differential count between the zinc-treated and
control kits bled at 8 weeks of age. There was a significant decrease in haematocrit value in the zinc-exposed kits. The T-cell mitogenic response was significantly reduced in the zinc-treated mink kits; however, the
immunosuppression was reversible, as a normal response was seen approximately 14 weeks after the kits were weaned and placed on basal diets. In 3- to 4-week-old kits, whelped and nursed by females, that were fed a zinc-
supplemented diet, greying of the fur developed around the eyes, ears, jaws and genitals, with a concomitant hair loss and dermatosis in these areas. The condition was stated to be consistent with copper deficiency; it spread
over much of the body within a few weeks and persisted for several weeks after the kits were removed from the supplemented diets (Bleavins et al., 1983).

Pregnant sheep (5–12 per group) were fed diets containing zinc as zinc sulfate at 0, 30, 150 and 750 mg/kg for approximately 110 days. The diet contained copper at 2.5 mg/kg. Food consumption, weight gain and efficiency of
food utilization were reduced in ewes in the 750-mg dose group. The reduction in feed intake began within 10 days of the beginning of the treatment. Some 20 days prior to parturition, copper status in the highest dose group
was severely depressed, with reductions in plasma copper, ceruloplasmin and amine oxidase activity when compared to the group on the basal diet. The concentration of zinc in plasma was greatly increased in the 750 mg dose
group only. Reproductive performance was severely impaired in the highest dose group, with increased incidence of non-viable lambs, defined as lambs which were aborted, stillborn or died within 7 days of birth. The cause of
death in these lambs was not determined. Lambs born alive in the high dose group were weak, did not suckle, displayed ataxia and died following convulsions within 48 h of birth. Of 20 lambs conceived in the high-dose group,
only one survived longer than 5 weeks. Two findings common to all non-viable lambs from the high-dose group were high tissue zinc concentrations and low tissue copper concentrations; radiographs of these lambs revealed
arrested growth in the long bones. Addition of copper (10 mg/kg of diet) to another group of pregnant sheep fed diets containing zinc at 750 mg/kg, prevented the development of copper deficiency, but failed to prevent the
adverse effect of high zinc on weight gain, feed consumption, efficiency of feed utilization and lamb viability. The doses of zinc in pregnant ewes were calculated to be 20 mg/kg body weight per day at the start of the study,
declining to 10 mg/kg per day with reduced food intake. It was postulated that the reduced viability of lambs may have been due to fetal malnutrition caused by the reduced maternal food intake and food utilization, or
alternatively to direct toxicity of zinc to the fetus (Campbell & Mills, 1979).

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The reverse interaction, namely the effect of copper on zinc status, is less clear. Excessive copper can affect zinc metabolism in some species, but zinc absorption does not appear to be seriously affected. The intestinal
absorption of zinc in the rat was decreased by 20% when the dietary copper level was increased from 3 to 24 mg/kg, with no further decreases seen at copper levels of 300 mg/kg (Hall et al., 1979). However, there is some
evidence for competition and/or inhibition of copper or zinc uptake into intestinal cells when the luminal concentration of the respective metal is very high (Oestreicher & Cousins, 1985).

7.8.2 Zinc and other metals

High levels of zinc (0.5–1%) fed to rats have been shown to interfere directly with iron metabolism (Magee & Matrone, 1960). The occurrence of hypochromic, macrocytic anaemia in rats following the ingestion of excessive
zinc and the reversal of this anaemia by iron supplementation demonstrate the interaction between iron and zinc (Cox & Harris, 1960; Magee & Matrone, 1960). Zinc intoxication affects iron metabolism by increasing the iron
turnover, decreasing the life span of erythrocytes and decreasing the hepatic accumulation of iron as ferritin (Settlemire & Matrone, 1967a,b).

Zinc appears to be a less effective inhibitor of iron absorption than iron is of zinc absorption. In iron-deficient mice and rats, the oral absorption of zinc is greatly increased, which has been interpreted to indicate a shared
transport pathway (Pollack et al., 1965; Forth & Rummel, 1973; Hamilton et al., 1978). Iron absorption and distribution is altered by zinc deficiency. A marked increase in iron and a decrease in zinc concentration in various
organs, such as the liver, bone, pancreas and testes, have been observed in zinc-deficient animals in comparison to pair-fed controls. These changes are reversed following zinc supplementation (Prasad et al., 1967; Prasad et al.,
1969; Petering et al., 1971).

Excess dietary zinc administered to pregnant rats and also to weanling and adult rats lowers the tissue iron content of the treated animals (Duncan et al., 1953; Cox & Harris, 1960; Magee & Matrone, 1960; Cox et al., 1969). In
another study, reduced tissue iron and copper levels in weanling rats and reductions in calcium and phosphorus deposition in bones of young rats were observed following feeding with excess zinc (Sadasivan, 1951). High levels
of dietary zinc have been also been shown to interfere with the metabolism of calcium and to increase total calcium and concentrations of calcium in the liver, but to decrease these levels in the body of exposed fetuses (Cox et
al., 1969). Elevated magnesium concentrations (mg/kg) but not total magnesium content were detected in the liver and body of fetuses from mothers fed excess zinc (Cox et al., 1969).

Interaction between zinc and cadmium in animals has been reviewed elsewhere (IPCS, 1993). Supplementation with zinc has been shown to prevent the teratogenic and carcinogenic effects of cadmium: the induction of severe
facial abnormalities in hamster embryos induced by cadmium (2–4 mg/kg administered intravenously) was prevented by the simultaneous administration of zinc (as zinc sulfate at 992 mg/kg) (Ferm & Carpenter, 1968); and the
induction of interstitial cell tumours in rats and mice was prevented by concurrent zinc supplementation (Gunn et al., 1963).

7.9 Zinc deficiency in animals

Zinc is essential for DNA replication, RNA polymerases, protein synthesis and many metabolic processes. All cell replication, protein synthesis and growth processes are partially dependent upon zinc. Systemic depletion of
this element therefore inevitably leads to deleterious effects.

The essentiality of zinc for growth has been described elsewhere (Todd et al., 1934; Hove et al., 1937; Hove et al., 1938). In experimental animals, restriction of zinc in the diet leads to an immediate decline in plasma zinc
levels, followed by a loss of appetite and poor growth, which are evident within a few days of zinc depletion. Further symptoms can include dermatitis, alopecia and testicular atrophy (Macapinlac et al., 1966, 1968; Chesters &
Quarterman, 1970; Wallwork et al., 1981). Zinc deficiency in experimental animals is characterized by rash, alopecia, hyperkeratosis, parakeratosis and hypopigmentation (O’Dell et al., 1959; Oberleas et al., 1962). In monkeys,
as the deficiency progresses, animals stand in a hunched position, have an unsteady gait and unkempt fur, become emaciated and eventually die (Macapinlac et al., 1967; Sandstead et al., 1978; Swenerton & Hurley, 1980). It
has been observed that the healing of wounds is retarded in zinc-deficient rats and that healing can be accelerated with zinc supplementation (Sandstead et al., 1970).

Zinc deficiency has an adverse effect on the pancreas of experimental animals. In vitro assays in pancreatic preparations from rats fed a zinc-deficient diet showed a marked impairment of the insulin response to glucose , which
was directly proportional to the degree of zinc deficiency (Huber & Gershoff, 1973; Jhala & Baly, 1991). Plasma insulin levels in response to glucose injection were decreased in obese but not in lean rats fed a zinc-deficient
diet over 8 weeks (Zwick et al., 1991). Additionally, a markedly zinc-deficient diet in rats produced a significant reduction in the total pancreatic content of zinc within 2 days and was associated with a more than 50% reduction
in the activity of gamma-glutamyl hydrolase (an indicator of pancreatic activity) in pancreatic tissue (Canton & Cremin, 1990). Rapid loss of pancreatic carboxypeptidase activity has been demonstrated under similar conditions
(Mills et al., 1967).

Zinc deficiency has been shown to be correlated with a diminished activity of some enzymes. The level of a serum enzyme alkaline phosphatase decreased in zinc-deficient animals and increased with zinc replenishment
(Sadasivan, 1952; Van Reen, 1953). It has been postulated that the promoter region of the gene for intestinal alkaline phosphatases contains a metal-responsive element, and that zinc deficiency leads to suboptimal transcription
of this type of enzyme (Stuart et al., 1985; Millan, 1987). Zinc deficiency has also been reported to impair the activity of intracellular hepatic enzymes. The biotransformation of some pharmacological agents was reduced in
zinc-deficient rats and was also associated with a decrease in the cytochrome P450 content of microsomes (Becking & Morrison, 1970).

Serum lipid concentrations were shown to be lower than normal in zinc-deficient rats, and this was postulated to be caused by the impairment of intestinal absorption of lipids by zinc deficiency (Koo et al., 1987).

Adverse reproductive effects were seen in rats when their diets were low in zinc (Hurley & Swenerton, 1966; Hurley & Shrader, 1974). Spermatogenesis was shown to be arrested in weanling rats and the germinal epithelium of
the testes was atrophic (Barney et al., 1968). The menstrual cycle of rats (Apgar, 1970) and monkeys (Swenerton & Hurley, 1980) was also reported to be impaired, and ovarian follicular development appeared to be retarded
(see also Evenson et al., 1993 for another study in rats).

Zinc deficiency is lethal or injurious to the embryos and fetuses of experimental animals. Evidence indicates that adequate levels of zinc are essential for conception (Swenerton & Hurley, 1980), blastula development and
implantation (Hurley & Shrader, 1974), organogenesis (Blamberg et al., 1960; Kienholz et al., 1961; Hurley & Swenerton, 1966), fetal growth (McKenzie et al., 1975; Fosmire et al., 1977), prenatal survival (Hurley &
Swenerton, 1966) and parturition (Apgar, 1973). Severe zinc deficiency results in high fetal resorption, with malformation of the skeleton, nervous system and viscera found in most of the surviving fetuses (Hurley &
Swenerton, 1966; Hurley et al., 1971; Hurley & Shrader, 1972). Impaired synthesis and/or metabolism of DNA is postulated to cause these abnormalities (Swenerton et al., 1969; Dreosti et al., 1972; Dreosti & Hurley, 1975).

Zinc deficiency impairs development of the brain and has been shown to cause long-term behavioural consequences in rats. Evidence for the essentiality of zinc for the maturation of brain was provided by studies in rats (Hurley
& Swenerton, 1966; Warkany & Petering, 1972), which demonstrated a variety of malformations in the brains of offspring that had been deprived of zinc early in gestation. Inhibition of DNA synthesis in neural crest cells is
postulated to be one of the causes of such malformations (Swenerton et al., 1969). Zinc-deprived 10-day-old suckling rats showed suppression of incorporation of thymidine into their DNA (Sandstead et al., 1972). The
cerebellum of a 21-day-old rat showed histological evidence of retarded maturation (Buell et al., 1977), and impaired division and migration of external granular cell neurons (Dvergsten et al., 1983; Dvergsten et al., 1984). The
long-term functional significance of zinc deficiency in the fetus and neonate was studied in rats deprived of zinc during late gestation and/or suckling. Severe maternal deprivation (zinc at < 1 mg/kg in the diet) on days 14–20 of
gestation caused stunting and a decrease in brain cell number in fetuses (McKenzie et al., 1975). Nutritionally rehabilitated offspring subsequently showed active avoidance of shock and an increased aggressive response to
shock (Halas et al., 1975, 1976, 1977). Severe maternal zinc deprivation throughout nursing impaired growth of suckling pups and subsequently increased errors by nutritionally rehabilitated offspring in maze tests (Lokken et
al., 1973; Halas et al., 1983). Reference to or long-term memory of shock on days 18- 21 of nursing was also impaired (Halas et al., 1979). In rats that were mildly zinc-deprived during gestation and lactation (zinc at 10 mg/kg)
where there was only a minimum effect on the growth of pups, it was subsequently revealed that the zinc-rehabilitated offspring had deficits in working memory (Halas et al., 1986). Maternal zinc deprivation of rhesus monkeys
throughout most of the third trimester (Sandstead et al., 1978) and throughout gestation and lactation (Golub et al., 1985) caused acrodermatitis in the dam and subsequent reduction of exploration and play in infants during
weaning. Later study of these animals found impaired ability to solve complex learning sets at 300 and 700, but not at 1000 days (Strobel & Sandstead, 1984).

Immune function was shown to be adversely affected by zinc deficiency. Calves with an inborn error in zinc absorption display thymic hypoplasia, an increased susceptibility to infection, growth failure, diarrhoea, dermatitis
and death. Treatment with zinc can prevent and cure the illness (Brummerstedt et al., 1977). However, it may be difficult to separate immune deficiency from malnutrition in this case. In rats and mice, zinc deficiency was
reported to impair the growth of the thymus and to retard both cellular and humoral immunity (Fraker et al., 1978; Luecke et al., 1978; Fernandes et al., 1979; Pekarek et al., 1979; Lennard, 1980). Mice fed diets deficient in
zinc for 30 days developed thymic atrophy, had markedly depleted numbers of lymphocytes and macrophages in the spleen, and showed a markedly reduced ability to produce antibody-mediated responses to T-cell dependent
and T-cell independent antigens. Delayed-type hypersensitivity responses, cell-mediated responses to tumour antigens and the function of natural killer cells were also significantly reduced (Fraker et al., 1978, 1986; Fernandes
et al., 1979). However, in another study, it was shown that the ability of lymphocytes to proliferate and to produce interleukins and mitogenic-stimulated antibody responses was normal in zinc-deficient mice (Cook-Mills &
Fraker, 1993). The reasons for this discrepancy are unclear, but mitogenic responses are a less reliable indicator of immune reactivity than antigen-specific responses. It has been established that, although the T-cell:B-cell ratio
is unaffected, the total number of lymphocytes is significantly reduced in zinc-deficient mice (King & Fraker, 1991). The incidence of oesophageal tumours induced by methylbenzylnitrosamine (MBN) was higher in rats fed
diets low in zinc, at 3 mg/kg compared to rats fed diets containing 60 mg/kg (Fong et al., 1978). This effect may arise through the oesophageal epithelium being damaged by zinc deficiency, making it sensitive to MBN and/or
its activated metabolite (Fong et al., 1984). The mechanism appears to be via the activation of a specific cytochrome P450 by zinc deficiency, with a resultant increase in MBN-induced formation of O6-methylguanine in
oesophageal DNA (Barch & Fox, 1987). Studies investigating the effect of dietary zinc deficiency in oesophageal carcinogenesis are reported in section 8.3.7.

8. EFFECTS ON HUMANS
In the general population, essential elements have a range of acceptable exposures at which there are no untoward effects. Below this range there is the potential for effects associated with deficiency, and above it, effects
associated with toxicity. The curve describing this concept of acceptable intake is shown in Chapter 10 (Fig. 1). As zinc is an essential component in a multiplicity of enzymatic reactions (see section 6.5.2), there is a need to
define the range of acceptable intake to provide for biological requirements that balance the consequences of deficit and excess. In the position of balance, there is homeostasis, with optimum health. An additional factor is the
consequence of interactions of zinc with other elements, which can introduce a toxicity mediated by zinc excess (Hill & Matrone, 1970). In this Chapter, the effects associated with zinc deficiency are described, along with the
adverse effects associated with zinc excess, including those mediated by interaction with other elements.

8.1 Human dietary zinc requirements

8.1.1 Estimation of zinc requirements
There are inherent difficulties in estimating zinc requirements for humans, with a number of physiological, dietary and environmental factors affecting various populations. Estimates have been made using metabolic balance
studies, in which zinc intake was compared with zinc excretion in the urine and faeces (Sandstead, 1984, 1985; Sandstead et al., 1990), and using additional factorial calculations that account for the zinc required for growth,
losses (including zinc lost in sweat, shed hair and skin, semen and milk) and bioavailability (Sandstead, 1973; King & Turnlund, 1989). Growing infants, children, growing adolescents, and pregnant and lactating mothers
require more zinc per kilogram of body weight than do mature adults (WHO, 1996b). The factorial estimates for zinc requirements are outlined in Tables 27 and 28.

Table 27. Provisional dietary requirements for zinc in relation to estimates of retention, losses and availabilitya

Age Peak Urinary Sweat Total Intake necessary (mg) in daily diet for
daily excretion excretion required available zinc content of
retention (mg) (mg) (mg)
(mg) 10% 20% 40%

Infants

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0-4 months 0.35 0.4 0.5 1.25 12.5 6.3 3.1

5-12 months 0.2 0.4 0.5 1.1 11.0 5.5 2.8

Males

1-10 years 0.2 0.4 1.0 1.6 16.0 8.0 4.0

11-17 years 0.8 0.5 1.5 2.8 28.0 14.0 7.0

18+ years 0.2 0.5 1.5 2.2 22.0 11.0 5.5

Females

1-9 years 0.15 0.4 1.0 1.55 15.5 7.8 3.9

10-13 years 0.65 0.5 1.5 2.65 26.5 13.3 6.6

14-16 years 0.2 0.5 1.5 2.2 22.0 11.0 5.5

17+ years 0.2 0.5 1.5 2.2 22.0 11.0 5.5

Pregnant women

0-20 weeks 0.55 0.5 1.5 2.55 25.5 12.8 6.4

20-30 weeks 0.9 0.5 1.5 2.9 29.0 14.5 7.3

30-40 weeks 1.0 0.5 1.5 3.0 30.0 15.0 7.5

Lactating 3.45 0.5 1.5 5.45 54.5 27.3 13.7

women

a WHO, 1973. The above estimates were based on the assumption that the fat-free tissue concentration of zinc in
humans is approximately 30 µg/g. This figure is equivalent to 2.0 g of zinc in the soft tissues of an adult male and
1.2 g in the soft tissues of an adult female, as determined from lean body mass. The zinc requirement at various
ages was determined from the change in lean body mass with age. Bone zinc was not included in these
calculations, because zinc in bone is relatively sequestered from the metabolically active pool of body zinc. The
zinc content of sweat is based on an assumed zinc surface loss of 1 mg/litre. The estimated requirement for
lactation is based on a zinc content in milk of 5 mg/litre and a daily milk secretion of 650 ml. The urinary excretion
of zinc is based on reported levels.

A major factor affecting zinc requirements is the variation in the percentage absorption of zinc from differing dietary sources; this is discussed in section 6.1.2.

Table 28. Dietary reference values for zinc (mg/day)

Age United Kingdoma USA RDAb WHOc European

DRId
LNRI EAR RNI

Infants

0–3 months 2.6 3.3 4.0 5.0

4–6 months 2.6 3.3 4.0 5.0

7–12 months 3.0 3.8 5.0 5.0 5.6 4.0

1–3 years 3.0 3.8 5.0 10.0 5.5 4.0

4–6 years 4.0 5.0 6.5 10.0 6.5 6.0

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7–10 years 4.0 5.4 7.0 10.0 7.5 7.0

Males

11–14 years 5.3 7.0 9.0 15.0 12.1 9.0

15–18 years 5.5 7.3 9.5 15.0 13.1 9.5

19–50+ years 5.5 7.3 9.5 15.0 9.4 9.5

Females

11–14 years 5.3 7.0 9.0 12.0 10.3 9.0

15–18 years 4.0 5.5 7.0 12.0 10.2 7.0

19–50+ years 4.0 5.5 7.0 12.0 6.5 7.1

Pregnancy c c c 15.0 7.3–13.3 b

Lactation

0–4 months 19.0 12.7 +5.0

4+ months 16 11.7 +5.0

DRI = dietary reference intake; EAR = estimated average requirement;

LNRI = lower reference nutrient intake; RDA = recommended daily allowance; RNI = recommended nutrient intake

a UK (1991).

b US National Academy of Sciences (1989).

c WHO (1996b); normative requirement for diet of moderate zinc availability

d EU (1993); no increment.

The effects of dietary supplementation on humans have recently been reviewed (Gibson, 1994). Tables 29, 30 and 31 provide a summary, taken from this review, of the effects of
supplementation in infants, children and lactating women.

Methods for the assessment of zinc status in humans are discussed in section 6.5.1.

Table 29. Double-blind zinc supplementation studies in infants

Country Subjects and Mean plasma zinc levels (µmol/litre) Growth effects Reference
treatment and other
Zinc Control responses
supplementation

Start End Start End

USA 68 normal healthy 119 110 improved weight Walravens

full-term male infants and length in &
at birth; studied for 6 males only Hambidge
months double-blind (1976)
study; formula with
zinc at 1.8 mg/litre or
5.8 mg/litre

France 57 normal healthy improved weight Walravens

infants at 5.4 months gain; improved et al.
old, studied for 3 length in males (1992)
months double-blind only
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study; zinc at 5
mg/day (25) or
placebo (32)

USA 50 failure-to-thrive 10.7 9.8 10.7 10.4 improved weight Walravens

infants, 8–27 months especially in et al.
old, studied for 6 males;. tendency (1989)
months randomized to increased
double-blind trial, pair activity of serum
matched; zinc at 5.7 alkaline phosphate
mg/day as syrup (25) in zinc group
or placebo (25)

Chile 32 marasmic infants, 14.7 15.6 16.1 15.6 weight-for-length Castillo-

7–8 months old, effect; decrease in Duran et al.
studied for 90 days percentage of (1987)
randomized double- anergic infants;
blind trial; zinc at 2 increase in serum
mg/kg daily in IgA in zinc group
solution (16) or
placebo (16)

Chile 39 severely 19.4 18.6 23.4 18.0 linear length Schlesinger

malnourished infants effect; improved et al.
studied for 104 days immune function (1993)
double blind trial;
zinc at 1.9 mg/kg (19)
or 0.35 mg/kg in daily
formula (20)

Bangladesh 60 severely 8.2 18.5 7.9 10.6 improved weight Khanum et

malnourished infants gain and weight al. (1988)
–60 months old for length
studied or 3 weeks
rice-based diet ad lib
with vitamins and
minerals; zinc at 10
mg/kg daily if < 6 kg
or 50 mg/day if > 6 kg
as zinc sulfate; non-
supplemented group
(30)

Bangladesh 65 children with AD improved length Roy et al.

and 152 with PD 3–24 gain in AD group, (1992)
months old and in PD with <
supplemented for 2 90% weight/age
weeks followed for 2 and 90%
or 3 months in a height/age;
double-blind reduced no. of
randomized study episodes of
after supplementation diarrhoea in AD
for 2 weeks with zinc and PD groups
at 15 mg /kg daily or and attack rate of
placebo respiratory tract
infections in AD
group only

AD = acute diarrhoea; PD = persistent diarrhoea; SGA = small for gestational age

Table 30. Double-blind zinc supplementation studies in children

Reference
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Country, Subjects and Dietary Mean plasma zinc levels Growth effects
date treatment zinc (µmol/litre) and other
intake responses
(mg) Zinc Control
supplementation

Start End Start End

Egypt 90 growth- 14 1- 7 19- 11- 13- no weight or Carter et al.

1965–1966 retarded 2 7 3 height effects; (1969)
schoolboys, no difference in
11–18 years sexual
old studied for maturation; no
5.5 months effect on serum
randomized alkaline
trial; zinc at 14 phosphatase
mg (30) or
placebo (30);
capsules given
at school

Iran 60 growth- 12 17- 2 14- 11- 14- no weight or Ronaghy et al.

1967–1968 retarded 7 6 1 height effects; (1968)
schoolboys, difference in
12–18 years sexual
old, studied for maturation
17 months (5
months trial, 7
months rest, 5
months trial);
first 5 months,
28 mg of zinc
(20), 67 mg of
iron (20) or
placebo (20);
second 5
months, micro-
nutrients (20),
micronutrients
+ 40 mg of
zinc (20) or
placebo (20);
capsules given
at school

Iran 50 growth- 12 8- 2 10- 10- 10- weight and Ronaghy et al.

1969–1971 retarded 2 5 7 height effects; (1974)
schoolboys, 13 difference in
years old, bone age;
studied for 17 tendency for
months (5 faster sexual
months trial, 7 development;
months rest, 5 no effect on
months trial) serum alkaline
non- phosphatase
randomized
trial; micro-
nutrients (20),
micronutrients
+ 40 mg of
zinc (20) or
placebo (10);
capsules given
at school

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USA, 40 growth- 4- 6 10- 7 10- 11- 11- height effect Walravens et

Colorado retarded, low- 8 3 3 (especially in al. (1983)
zinc-status boys); increase
children, 2–6 in appetite
years old,
studied for 1
year
randomized
pair-matched
trial; zinc at 10
mg/day (20) or
placebo (20);
syrup given by
parents at
home

Canada 60 growth- 6- 4 15- 6 16- 16- 16- height effect Gibson et al.
1986 retarded boys, 2 5 4 only in subjects (1989b)
5–7 years old, with low hair
studied for 12 zinc (<1.68
months µmol/g);
randomized increase in
pair-matched appetite
trial; zinc at 10 perceived by
mg/day (30) or parents
with placebo
(30); fruit juice
drink given by
parents at
home

Thailand 133 children, 4.3 13.2 19.0 13.2 14.3 no weight or Udomkesmalee
1989–1990 6–13 years old, height effects; et al. (1992)
with increase in
suboptimal serum alkaline
zinc and phosphatase
vitamin A activity;
nutriture improved dark
studied for 6 adaptation;
months improved
randomized conjunctival
pair-matched integrity
trial; zinc at 25
mg/day (33),
vitamin A
(33), vitamin
A + zinc (32)
or with
placebo (35);
capsules taken
on school days

Gambia 109 apparently no weight or Bates et al.

1989–1990 healthy height effects; (1993)
children, 0.5–3 increase in arm
years old, circumference;
studied for 15 less malaria;
months improved
randomized intestinal
group-matched permeability
trial; 70 mg of
zinc (55) or
placebo (54);
drink given

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twice a week
at clinic

Guatemala 162 10 14.2 16.2 14.4 14.9 no weight or Cavan et al.

1989 schoolchildren, height effects; (1993)
6–8 years old, increase in
studied for 25 triceps skinfold;
weeks smaller
randomized decrease in mid-
pair-matched arm
trial; circumference;
micronutrients no increase in
(82), micro- serum alkaline
nutrients + phosphatase
zinc at 10
mg/day (80);
chewable
tablet given at
school on
weekdays

Chile 46 short- no weight Castillo-Duran

1991 stature effect; height et al. (1995)
schoolchildren, effect in males
6–12 years old, only; no
consuming difference in
diets providing plasma zinc
50–60% of
normal daily
zinc intake,
studied for 12
months
randomized
study; zinc at
10 mg/day or
placebo

Chile 1993 98 healthy pre- height effect in Ruz et al.

school children males; trend (1997)
studied for 14 towards
months zinc at improved
10 mg/day or immune
placebo function and
reduced
giardiasis

Table 31. Double-blind zinc supplementation studies in lactating women

Country Subjects and treatment Dietary Response Reference

zinc intake
(mg)

USA, 53 middle-income lactating women, 12.2 decreased fall in Krebs et al. (1985)
Colorado studied for varying durations up to 9 milk zinc levels
months controlled trial; zinc at 15 mg/day
(14), placebo (39) or control (8); tablets
taken at home

USA, 49 middle-income mothers studied for 11.2 higher milk zinc Karra et al. (1986)
Indiana first 6 months of lactation controlled trial; levels
micronutrients (25) or micronutrients +

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zinc at 25 mg/day (24); different

commercial supplements taken at home

USA, 40 middle-income women studied for 12 no effect on milk Moser-Veillon &

Maryland first 6 months of lactation randomized zinc levels Reynolds (1990)
double-blind trial; micronutrients (20) or
micronutrients + zinc at 25 mg/day (20);
tablets taken at home

8.2 Zinc deficiency

8.2.1 Clinical manifestations
Cases of severe zinc deficiency are now rare, but mild deficiency during periods of rapid growth, pregnancy, synthesis of new tissue, and in persons consuming plant-based diets, is not
uncommon. Zinc deficiency also occurs in the presence of certain disease states such as malabsorption syndromes, renal and hepatic diseases, and in association with burns and alcoholism.
Two genetic disorders, acrodermatitis enteropathica and sickle-cell disease, are associated with suboptimal zinc status.

The first cases of human zinc deficiency were reported in the Middle East among adolescent dwarves in the 1960s (section 8.2.4). Since those first reports, mild zinc deficiency has been
reported in infants and younger children living both in developing and in industrialized countries.

The health effects associated with zinc deficiency in humans have been extensively reviewed (Prasad, 1988; Aggett, 1989; Clegg et al., 1989; Hambidge, 1989; Keen & Hurley, 1989; Walsh
et al., 1994). Zinc deficiency has been classified into three syndromes (Henkin & Aamodt, 1983): acute, chronic and subacute zinc deficiency. The clinical symptoms range from
neurosensory changes, oligospermia in males, decreased thymulin activity, decreased interleukin-2 production, hypogeusia and impaired neuropsychological functions (Prasad, 1988;
Penland, 1991) in mild or marginal deficiency, through to growth retardation, male hypogonadism, and delayed wound healing with moderate deficiency, and alopecia, mental disturbances,
cell-mediated immune disorders and pustular dermatitis in patients with severe zinc deficiency (Prasad, 1988). These conditions are generally reversible when the deficiency is corrected by
zinc supplementation.

8.2.2 Brain function

In an experimental study (Henkin et al., 1975b) in which severe, acute zinc deficiency was induced in eight patients with scleroderma by treatment with large doses of oral histidine, severe
zincuria was produced, and plasma zinc levels decreased from 60–105 µg/dl to 40–60 µg/dl. Signs of zinc deficiency included anorexia, dysosmia, ataxia, tremor, loss of memory, impaired
higher intellectual processes, paranoid ideation and receptive aphasia. Treatment with zinc by mouth improved signs within 24 h.

The effects of less severe zinc deficiency are less easily characterized and include reduced growth and impaired immune function (WHO, 1996b). In a study in which 14 men were fed diets
providing zinc at a rate of 1, 2, 3, 4 or 10 mg/day for periods of 35 days in a 7-month study (Johnson et al., 1993), impaired neuromotor and cognitive function was observed (Penland,
1991), with significant decreases in sensory motor, attention, visual memory and spatial and perceptual tasks.

8.2.3 Immune function

In patients suffering from acrodermatitis enteropathica — a rare genetic defect affecting the assimilation of zinc — an increased incidence of secondary infections is seen, and T-cell
numbers, thymic hormone levels and T-cell mediated cellular and humoral immunities are deficient (Aggett, 1989). Similar changes have been noted in other patients with zinc deficiency
and with sickle-cell anaemia (Fraker et al., 1986; Endre et al., 1990), and patients with suboptimal zinc intakes have been reported to be at greater risk of infection and disease (Bogden et
al., 1987). In an experimental study in which male volunteers with experimentally induced mild zinc deficiency had decreased interleukin-2 activity, a decreased T4+:T8+ ratio and
increased T101 cells and serum immunoglobulin (Ig), these changes were corrected upon zinc repletion (Prasad et al., 1988). Immune function related to zinc deficiency has been reviewed
by Keen & Gershwin (1990). It has been suggested that zinc may act as an antiviral agent. Possible mechanisms by which this could be achieved are inhibition of virus protein coat synthesis
and prevention of virus entry into the cell (Korant & Butterworth, 1976; Prasad, 1996).

8.2.4 Growth
Growth retardation and hypogonadism were reported in adolescents in the Middle East, and these effects were believed to be related to inadequate dietary zinc intake (Prasad et al., 1961,
1963b). The principal features of this syndrome were growth failure and delayed sexual maturation, giving 16- to 18-year-olds a physical appearance resembling that of prepubertal 9-year-
olds, commonly associated with hepatosplenomegaly and iron deficiency. Zinc deficiency appears to be a major contributing factor in this syndrome. Administration of zinc, along with a
balanced diet, produced accelerated growth, and enlargement of the penis and testes in males, and of breasts in females; a well-balanced diet alone was not followed by rapid improvement
(Prasad et al., 1963a; Sandstead et al., 1967; Halsted et al., 1972). A subsequent series of zinc supplementation studies in Iran gave mixed results (Ronaghy et al., 1974; Mahloudji et al.,
1975): there was a clear stimulation of growth after supplementation, but no significant stimulation of gonadal development (Ronaghy et al., 1974). Supplementation with zinc plus iron did
not stimulate growth (Mahloudji et al., 1975).

Details of more recent double-blind zinc supplementation studies conducted on infants and children are reviewed in Gibson (1994).

8.2.5 Dermal effects

Severe zinc deficiency resulting from total parenteral nutrition without zinc (Arakawa et al., 1976; Kay et al., 1976), and in patients suffering from acrodermatitis enteropathica (Aggett,
1989) leads to dermatological effects, including erythematous scaling eruptions in the naso-labial and retro-auricular folds, with the dermatitis extending to the trunk and becoming
exudative upon continued zinc deficiency (total parenteral nutrition), and bullous pustular dermatitis of the extremities and the oral, anal and genital areas, combined with paronychia and
generalized alopecia (acrodermatitis enteropathica).

8.2.6 Reproduction
An association between low serum zinc levels and reproduction was made when one of 83 infants in a series of studies (Jameson, 1976) showed a congenital cardiac malformation, with a
ventricular septum defect and coarctation of the aorta. The infant’s mother had shown the lowest serum zinc level (12.2 µmol/litre) in the 13th week of gestation, but all other laboratory
findings were normal. In women with complications such as abnormal labour or atonic bleeding, serum zinc concentrations had been significantly reduced during early pregnancy.
Additionally, of 316 pregnancies, a high proportion (60%) of the women who gave birth to infants with congenital defects had shown low serum zinc concentrations in the first trimester.

In a study in which 450 women were followed during and after pregnancy (Mukherjee et al., 1984), plasma zinc was reported to be an indicator of feto-maternal complications, including
fetal distress and maternal infections, for those women in the lowest quartile for plasma zinc. In a study in low-income women, there was a significantly higher prevalence of low birth
weight in the infants of mothers in the lowest quartile for plasma zinc at 16 weeks gestation than in those born to the other mothers (Neggers et al., 1990).

Studies to examine whether maternal zinc status is a useful predictor of pregnancy outcome have produced mixed results. Scholl et al. (1993), in a cohort study of pregnant girls and women
of low socioeconomic status, reported that low dietary intakes of zinc (< 6.0 mg/day) were associated with increased risk of low-birth-weight infants, after controlling for energy intake and
other variables known to influence outcome. Some studies (including Hunt et al., 1984; Cherry et al., 1989; Goldenberg et al., 1995), but not all double-blind supplementation trials have
provided further support for this suggestion. In a study by Tamura & Goldenberg (1996) of 580 indigent African-American pregnant women, those randomly assigned to a zinc-
supplemented group (25 mg of zinc daily as zinc sulfate) at 19.2 weeks of gestation had infants with a significantly higher birth weight (126 g; P = 0.03) and head circumference (0.4 cm; P
= 0.04) than infants born to mothers in the placebo group. The results suggested that, by increasing the zinc intakes of pregnant women with suboptimal zinc nutriture, pregnancy outcomes
could be improved. Recent reviews of this subject appear in Gibson (1994) and Tamura & Goldenberg (1996), and a summary of some of these findings is provided in Table 32.

Table 32. Zinc supplementation studies in pregnant women

Country, date Subjects Treatment Responses References

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Dietary
zinc
intake (mg)

United 494 middle-class randomized double- 9 no effect on birth Mahomed et

Kingdom women studied for last blind trial; zinc at 20 weight; no al. (1989)
1985–1986 4 months of mg/day (246) or differences in
pregnancy placebo (248); leukocyte zinc
capsules taken at
home

USA, 556 low-income randomized double- 30 no effect on birth Cherry et al.

New Orleans adolescent women blind trial; zinc at 30 weight; reduced (1989)
studied for last 3 mg/day (268) or rates of pre-
months of pregnancy placebo (288); tablets maturity and
taken at home neonatal
morbidity

USA, 138 Hispanic randomized double- 9–8 no effect on birth Hunt et al.
Los Angeles teenagers studied for blind trial; weight (1995)
1981–1982 last 4 months of micronutrients (68) or
pregnancy micronutrients + zinc
at 20 mg/day (70);
capsules taken at
home

USA, 213 Hispanic low- randomized double- 9–3 no effect on birth Hunt et al.
Los Angeles income women blind trial; weight; reduced (1995)
enrolled at gestation micronutrients (106) incidence of
age < 27 weeks or micronutrients + pregnancy-
zinc at 20 mg/day induced
(107) hypertension

United 56 pregnant women at randomized double- 22.5 lower incidence Simmer et

Kingdom risk of small-for- blind trial; zinc at of Intra-uterine al. (1991)
gestational age infants 22.5 mg/day (30) or growth
studied for last 15–25 placebo (26) retardation;
weeks of pregnancy reduction in
induced labours
and Caesarean
sections

USA 46 pregnant middle- double-blind study; 11 no effect on birth Hambidge et

income women zinc at 15 mg/day (10) weight; no other al. (1983)
studied for 7–9 or placebo (36); tablet effects observed
months taken 2 h after dinner

8.2.7 Carcinogenicity
In a study in Chinese men aged between 45 and 75 years, the zinc levels in serum and hair were lower in those patients with oesophageal cancer (Lin et al., 1977). The results of these
studies do not provide evidence for any causal relationship between low plasma/serum zinc levels and an increased incidence of cancer in humans. Similarly, in another study by Lipman et
al. (1987), mean plasma zinc and mean plasma vitamin A in the 21 oesophageal cancer patients were significantly lower than in the 17 patients with oesophagitis, or the 12 normal controls.
However, there were no differences in oesophageal zinc content between the cancerous tissue and adjacent normal tissue, the oesophagitis tissue and adjacent normal tissue, and normal
oesophageal tissue.

8.3 Zinc toxicity: general population

8.3.1 Poisoning incidents
A number of reports outline the effect of acute exposure to zinc in humans. However, these reports are generally old and poorly documented, with inadequate characterization of the actual
exposure levels, although some estimates of exposure have been made. For example, high concentrations of zinc in drinks (up to 2500 mg/litre) have been linked with effects such as severe
abdominal cramping, diarrhoea, tenesmus, bloody stools, nausea, and vomiting in 300 people, and symptoms of dryness of the mouth, nausea, vomiting and diarrhoea in more than 40
people (Brown et al., 1964). The amount of zinc ingested was estimated to be approximately 325–650 mg. Lethargy, along with drowsiness, unsteady gait, and increased serum lipase and
amylase levels, was seen in an individual who had ingested 12 g of elemental zinc, equivalent to 150 mg/kg body weight, resulting in increases in blood zinc concentrations (Murphy, 1970).
No gastrointestinal distress was reported and chelation therapy was effective in achieving clinical improvement and reducing blood zinc levels. Severe local burns, metabolic acidosis,
hepatic damage, hyperamylasaemia, lethargy and hypertension resulting from the ingestion of zinc chloride/ammonium chloride soldering flux were reported in a 16-month-old boy who
developed pancreatic exocrine insufficiency 5 months later (Knapp et al., 1994).

Excess hepatic copper and zinc levels in a small number of Cree and Ojibwa-Cree children were associated with severe chronic cholestatic liver disease progressing to end-stage biliary
cirrhosis in these children (Phillips et al., 1996). It was postulated that the effects might have been due to an inborn error of metal metabolism, secondary dietary or environmental factors, or

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genetic factors. Zinc and copper also appeared to be accumulated in transplanted livers, but these findings were not quantitative and there were no detectable histological effects following
transplantation. There were no data to indicate that any exposure to excess zinc had occurred in these children.

8.3.2 Dermal effects

Contact dermatitis has been reported following use of shampoos containing zinc pyrithione (Nigam et al., 1988). The specific etiological role for zinc was not clear, and the dermal
application of zinc as zinc oxide has not been associated with any adverse dermal effects in humans.

8.3.3 Immune function

An adverse lymphocytic response was reported in 11 healthy adult men who ingested 150 mg of elemental zinc twice a day for 6 weeks; the subjects also showed a reduction in the
lymphocytic stimulation response to phytohaemagglutinin (up to 70% reduction at 6 weeks), chemotaxis (50% reduction) and phagocytosis of bacteria by polymorphonuclear leukocytes
(50% reduction). There were no control groups in this study and the copper status of the subjects was not measured. The absolute number of lymphocytes and the proportions of T- and B-
cells were not altered. However, the measurement of immune status conducted in vitro may not be a true reflection of the immune responses in the subjects, in whom a two-fold elevation in
serum zinc was measured (Chandra, 1984).

Conversely, when 103 apparently healthy elderly subjects were randomly assigned to one of three treatments and given supplementary daily doses of placebo, or 15 or 100 mg of zinc for 3
months, none of the treatments significantly altered delayed dermal hypersensitivity to a panel of seven recall antigens or in vitro lymphocyte proliferative responses to mitogens and
antigens. A modest increase in plasma zinc was not accompanied by a decrease in plasma copper levels (Bogden et al., 1988). Subjects also received a daily supplement of 2 mg of copper
above dietary intake.

Phagocytic fungicidal capacity was evaluated in a double-blind study in which marasmic infants received formula fortified with zinc and iron at 15 mg/litre for up to 105 days, with a mean
daily zinc intake of 1.9 mg/kg (Schlesinger et al., 1993). A decrease in the number of infants whose monocyte phagocytic activity was above the median was observed after 60 days of zinc
supplementation (63% upon admission compared to 32% after 60 days; P < 0.05). There was also a decrease in the number of infants whose monocyte fungicidal activity was above the
median after 105 days of zinc supplementation (61% upon admission compared to 39% after 105 days; P < 0.04). The number and duration of impetigo episodes were greater in the group
of infants fed the zinc-supplemented formula (1.31 ± 1.1 infectious episodes/infant compared to 0.55 ± 0.8 in controls).

However, in another study in marasmic infants (Castillo-Duran et al., 1987) in which 16 subjects received a daily elemental zinc supplement as zinc acetate of 2 mg/kg and 16 subjects
received a placebo for 90 days, the incidence of infection, especially pyoderma, was significantly decreased in the zinc-supplemented group (3/16 in the supplemented group compared to
10/16 in controls; P < 0.025). The proportion of anergic infants decreased (from 50% to 25% between days 0 and 90) and serum IgA increased significantly (from 81 ± 32 to 111 ± 26
mg/100 ml) only in the zinc-supplemented group.

8.3.4 Reproduction
Dietary supplementation with zinc at a rate of 20 mg/day did not result in adverse effects on pregnancy progress or outcomes in healthy pregnant women in a number of large, controlled
trials (Hunt et al., 1984; Kynast & Saling, 1986; Mahomed et al., 1989). In a double-blind trial in low-income pregnant adolescents thought to be at risk for poor zinc nutriture,
supplementation with zinc at 30 mg/day did not result in adverse pregnancy outcomes (Cherry et al., 1989). Of the women, one-third received the zinc for the first trimester and the
remainder from the second trimester. Similarly, dietary supplementation for the last 15–25 weeks of pregnancy with 22.5 mg/day to women at risk of delivering a small-for-gestational-age
baby did not result in adverse reproductive effects (Simmer et al., 1991).

When seven pregnant women with low serum zinc levels (< 11.5 µmol/litre) were given a zinc supplement of 90 mg/day for the last 13–25 weeks of pregnancy, no adverse effects were
associated with the supplementation (Jameson, 1976). In a follow-up study (Jameson, 1982) in which 133 women with low serum zinc levels (< 10 µmol/litre) were randomly assigned zinc
supplementation at 45 mg/day or no supplementation, no adverse effects were associated with zinc supplementation, and serum copper levels were unaffected.

8.3.5 Zinc-induced copper deficiency

Elevated intakes of zinc have been shown to induce copper deficiency in humans (Prasad et al., 1978a; Fischer et al., 1984; Hoffman et al., 1988). The level of intestinal metallothionein
may be important in the development of this zinc-induced hypocupraemia. As metallothionein has a greater affinity for copper than zinc, and zinc induces high levels of metallothionein in
the intestinal mucosa (Richards & Cousins, 1975), the proposed mechanism for this copper deficiency is a reduction in copper absorption followed by sequestration of copper in a stable
copper-metallothionein complex, which is returned to the intestinal lumen by the desquamation of the intestinal mucosal cells (Richards & Cousins, 1976a; Fischer et al., 1983). Balance
studies indicate that, as the amount of zinc in the diet increases, so does the amount of dietary copper required, so that persons on a diet high in zinc may have an increased risk of copper
deficiency (Sandstead, 1982b). The ingestion of zinc at levels near the recommended daily allowance of 15 mg (see section 5.2.2) may result in increased copper requirements, increased
copper excretion, impaired copper status, or reduced copper retention (Greger et al., 1978a,b,c; Burke et al., 1981; Festa et al., 1985). The effect of dietary zinc on copper utilization depends
markedly on the amount of dietary copper and the copper status of the individual (see section 8.3.5.1).

8.3.5.1 Controlled human studies

In a study in which adolescent females received dietary copper at a rate of 1.2 mg/day, faecal copper excretion was increased by approximately 14% (0.9 compared to 0.79 mg/day) in
subjects receiving zinc at 14.7 mg/day compared with those fed 11.5 mg/day during 10-day periods (Greger et al., 1978c), with all subjects in positive copper balance. The standard error in
the estimate for zinc was 2.18 mg/day. In another study in adolescent females, no increased copper excretion was reported in subjects given dietary zinc at 7.4 or 13.4 mg/day and copper at
2.8 mg/day for 18 days, again with all subjects in positive copper balance (Greger et al., 1978b). Other studies are cited in Table 33.

Table 33. Summary of effects of zinc on copper homeostasis in humansa

Copper Subjects, Zinc dose Effects Described Reference

intake duration (mg/day) health effects
(mg/day)

1.2 adolescents 14.7 increase in faecal copper Greger et al.

10 days excretion; positive copper (1987c)
balance

2.8 adolescents 7.4 or no effect on copper Greger et al.

(females) 18 days 13.4 excretion; positive copper (1978b)
balance; copper intake 2.8
mg/day

2.0 healthy adult 9.5 or no effect on faecal copper Colin et al.

females 12 days 19.9 excretion; positive copper (1983)
balance; copper intake 2
mg/day

2.0 adult females 8 or 24 no effect on copper Taper et al.

12 days excretion; negative copper (1980)
balance; copper intake 2
mg/day

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2.6 adult males 1.8–18.5 no effect on serum copper none Festa et al.
0.5 weeks concentration; sudden (1985)
increase in zinc intake
from 4–8 mg/day to 18.5
mg/day resulted in a
temporary increase in
faecal copper excretion

2.33 elderly adults 7.8 or reduced copper retention none Burke et al.
(5 male, 6 female) 23.26 and increased faecal (1981)
30 days copper excretion at higher
zinc dose compared with
lower dose; most subjects
in positive copper balance

a The interpretation of studies is difficult because in many supplemental studies the total intake of diet and
supplement of zinc is not given.

A group of 18 female volunteers participated in a 10-week, single-blind dietary supplementation study designed to investigate the effect of zinc
supplementation on iron, copper and zinc status. When subjects were given zinc at 50 mg/day (administered as two gelatin tablets daily, each containing 25
mg of zinc as zinc gluconate), there was a significant reduction (P < 0.05) compared with pretreatment levels in serum ferritin (23%), haematocrit (4%) and
erythrocyte copper,zinc-superoxide dismutase (ESOD; 47%). Serum zinc was increased by approximately 25% (P < 0.01), but there were no changes in
serum ceruloplasmin or haemoglobin. When subjects received iron at 50 mg/day in addition to the zinc, similar reductions in ESOD were observed (47%),
while there were increases in serum ferritin (25%) and serum zinc (21%); there were no changes in haemoglobin, haematocrit or ceruloplasmin (Yadrick et
al., 1989). No indication of dietary intake of zinc or copper was noted in this study.

The effects of zinc supplementation on the copper status of two groups of healthy adult men were investigated for 6 weeks. A test group containing half of
the subjects received 25 mg of elemental zinc as zinc gluconate twice daily in gelatin capsules (50 mg/day), while the control group received placebo
capsules (Fischer et al., 1984). No significant differences in plasma copper levels or ferroxidase activities were observed between the groups. Increases in
plasma zinc (approximately 20%) and decreases in ESOD (approximately 20%) were observed in the zinc-supplemented group, the differences becoming
statistically significantly (P < 0.05) in week 6 of the study. No indication of dietary intake of zinc or copper was noted in this study.

In a 12-week, double-blind cross-over study (Samman & Roberts, 1988), 47 healthy adult volunteers received 50 mg of elemental zinc (as 220 mg of zinc
sulfate) or placebo, in a capsule, three times a day for 6 weeks. The zinc supplementation resulted in reductions in the ferroxidase activity of serum
ceruloplasmin (from 13.0 to 11.3 U/ml), and ESOD activity (from 2184 to 1672 U/g of haemoglobin), but only in females. The change in plasma zinc levels
was greater in females (8.4 ± 1.5 µmol/litre) than males (5.5 ± 1.1 µmol/litre), and no changes were reported in plasma copper or haematocrit. No indication
of dietary intake of zinc or copper was noted in this study.

A study of five men and six women aged 56–83 years showed that zinc intakes of about 23 mg daily (about 6 mg from the diet and 17 mg from zinc sulfate
given in a beverage consumed at breakfast) significantly lowered retention of copper (about 1 mg from the diet and 1.3 mg from copper sulfate given in the
breakfast beverage) compared to copper retention when the diet plus zinc sulfate in the beverage provided 7.8 mg of zinc daily (Burke et al., 1981). When the
amount of copper lost in sweat (>0.3 mg daily) is considered in the interpretation of the data (Jacob et al., 1979; Milne et al., 1983), it is evident that intakes
of 23 mg of zinc daily placed the subjects at risk of negative copper retention. A zinc:copper ratio of about 10 had an adverse effect on copper retention that
was not evident with a ratio of about 3.5. Of note in this study is that the increased intake of zinc was from a zinc sulfate supplement.

8.3.5.2 Case reports

In case studies, effects associated with long-term, excessive zinc intakes (ranging from 150 mg/day to 1–2 g/day) have included sideroblastic anaemia,
hypochromic microcytic anaemia, leukopenia, lymphadenopathy, neutropenia, hypocupraemia and hypoferraemia. Patients recovered to normal blood
patterns after cessation of zinc intake with or without copper supplementation (Porter et al., 1977; Prasad et al., 1978b; Hoffman et al., 1988; Simon et al.,
1988; Broun et al., 1990; Forman et al., 1990; Gyorffy & Chan, 1992; Ramadurai et al., 1993).

8.3.6 Serum lipids and cardiovascular disorders

Following the induction of hypercholesterolaemia in rats by administration of a high ratio of ingested zinc to copper (Klevay, 1973) and the identification of
an association between the mortality rate for coronary heart disease and the zinc:copper ratio in cows’ milk in 47 cities in the USA (Klevay, 1975), it was
hypothesized that the zinc:copper ratio has important influences on processes related to coronary heart disease (Klevay, 1975, 1980, 1983).

As a partial investigation of these concepts, a number of studies have been conducted to examine the effects of zinc intake on blood lipid levels. The lowest
dose of zinc that affects lipid metabolism is ill-defined, but it was approximately twice the US recommended daily allowance. Doses of zinc of 50–300 mg in
excess of dietary amounts generally have potentially harmful effects on lipid metabolism.

Effects resulting from zinc-induced copper deficiency are discussed in section 8.3.5.

In a 12-week, double-blind study in adult males, subjects received daily a placebo tablet (n = 9), or tablets containing 50 (n = 13) or 75 (n = 9) mg of
elemental zinc, as zinc gluconate. Dietary analysis revealed that subjects in the 75 mg group consumed significantly less total fat, saturated fatty acids and
protein than those in the other groups. Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol
and triglycerides were not affected by zinc supplementation. Serum high-density lipoprotein (HDL) cholesterol was significantly decreased (P < 0.05) at zinc
doses of 75 mg/day (reductions of 11% and 15% at weeks 6 and 12, respectively) and 50 mg/day (15% at week 12) compared with placebo, and was also
lower than baseline values (P < 0.05) at weeks 6, 8 and 12 at 75 mg/day (reductions of 13%, 15% and 13%, respectively) and week 12 at 50 mg/day (11%).
Serum copper levels did not change with zinc supplementation (Black et al., 1988). The dietary intake of nutrients including copper and zinc were monitored
throughout the study.

A study was conducted to investigate the relationship between level of exercise, zinc supplementation, and serum HDL cholesterol in men and women over
the age of 60 years (Goodwin et al., 1985). There was a significant positive correlation between levels of exercise and serum HDL cholesterol in the 180
subjects not supplemented with zinc (r = 0.26; P = 0.005), but not for those subjects taking supplemental zinc. Following discontinuation of zinc
supplementation (24 mg/day; median 17–52 mg/day), there was a significant increase in HDL cholesterol levels (2.0 mg/100 ml; approximately 4%; P =
0.04) after 8 weeks in 22 subjects. This change was positively correlated with the level of exercise of the subjects. The authors noted that in young runners,
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HDL is unchanged by zinc administered at 50 mg/day for 8 weeks. They suggested that age and sex differences may be important in the relationship between
zinc and lipid metabolism in humans, but no data were provided to support this hypothesis.

Reiser et al. (1985) described a diet mainly of conventional food but low in copper, and containing an amount of fructose similar to that consumed by many
Americans. The effects of this diet on more than 20 male subjects have been described in a number of papers (Reiser et al., 1985, 1987; Bhathena et al.,
1986; Holbrook et al., 1989). Prominent among these effects were decreased plasma encephalins and dyslipidaemia characterized by decreased HDL
cholesterol and increased LDL cholesterol. The experiment was interrupted because of fear of adverse cardiac effects. Evidence of copper deficiency
assessed by traditional means was minimal, but included decreased activity of ESOD.

In a study in which 12 healthy male subjects received 440 mg of zinc sulfate (160 mg of elemental zinc) daily for 5 weeks, HDL cholesterol levels decreased
to 25% below baseline values (30.1 compared with 40.5 mg/100 ml; P = 0.0001), while total cholesterol, triglyceride and LDL cholesterol levels remained
unchanged (Hooper et al., 1980). No indication of dietary intake of zinc or copper was noted in this study.

When 11 healthy male subjects ingested 150 mg of elemental zinc twice a day, serum HDL concentrations decreased significantly compared with baseline
values after 4 weeks (20% reduction; P < 0.01) and 6 weeks (30% reduction; P < 0.001), while LDL levels increased slightly (by 10–15% at 4–6 weeks; P <
0.05); however, this study lacked a placebo control (Chandra, 1984). Dietary zinc estimates were made using 24-h dietary recall interviews.

Not all studies show that zinc supplementation affects serum HDL levels. In a double-blind, cross-over trial involving 26 women and 21 men, the diets of
healthy volunteers were supplemented with zinc at a rate of 150 mg/day for 6 weeks. Plasma total cholesterol and HDL levels remained unchanged in both
sexes, while in women only, the LDL level decreased by 9%. There was also a trend for HDL to be redistributed in women, with slight increases in HDL2
and slight decreases in HDL3 (Samman & Roberts, 1988). When groups of eight women were given dietary supplementation of zinc at doses of 0, 15, 50 or
100 mg/day for 2 months, a transient 8% decrease in HDL cholesterol was seen at 4 weeks at the highest zinc level, but no uniform or sustained response of
plasma cholesterol or HDL cholesterol was observed (Freeland-Graves et al., 1980). Records of the dietary nutrients, including zinc and copper, were
obtained from the 3-day dietary records kept throughout this study.

8.4 Occupational exposure

8.4.1 Acute toxicity

Inhalation exposure to zinc chloride following the military use of "smoke bombs" has been reported to result in various effects, including interstitial oedema,
interstitial fibrosis, pneumonitis, bronchial mucosal oedema and ulceration, and changes in the mucous membrane of the larynx and trachea (Pare & Sandler,
1954; Johnson & Stonehill, 1961; Milliken et al., 1963; Schenker et al., 1981; Matarese & Matthews, 1986). Acute injury has been associated with mortality
under extreme exposure conditions, sometimes attributed to the effects upon the respiratory tract mucosa due to the hygroscopic and astringent nature of the
zinc chloride particles released by such devices (Evans, 1945; Milliken et al., 1963; Hjortso et al., 1988; Homma et al., 1992).

8.4.2 Short-term exposure

The term "metal-fume fever" describes an acute industrial illness characterized by a variety of symptoms, including fever, chills, dyspnoea, muscle soreness,
nausea and fatigue, which occur in workers following the inhalation of finely dispersed particulate matter formed when certain metals are volatilized. The
oxides of a number of metals, including zinc, can cause this acute, reversible syndrome (Drinker et al., 1927a–d; Rohrs, 1957; Doig & Challen, 1964;
Gordon et al., 1992). The description of the effects has been cited extensively, and the condition has variously been called brassfounder’s ague, zinc chills,
zinc fever, Spelter’s shakes and metal shakes (Batchelor et al., 1926; McCord & Friedlander, 1926; Mueller & Seger, 1985; Blanc et al., 1991).

Metal-fume fever is common in welders who work on various types of non-ferrous metals or ferrous metals alloyed with or coated with other metals. Zinc
fume from galvanized coatings is a common cause. While the disease is generally short, transient and severe, serious complications are not common and
individuals tend to develop a tolerance (Drinker et al., 1927a–d). Symptoms might occasionally be followed by pulmonary oedema or pneumonia (Doig &
Challen, 1964). The size of the ultrafine zinc oxide particles appears to be critical in the development of the syndrome, with the particles needing to be small
enough to reach the alveoli when inhaled (Brown, 1988). Recent studies in humans following occupational exposure to zinc oxide fumes have demonstrated
some changes in pulmonary function and/or radiological abnormalities, which are reversible following cessation of exposure.

A cross-sectional analysis, conducted on spirometric lung-function parameters in zinc welders, non-welders with exposure to welding fumes and control
subjects (Marquart et al., 1989), revealed no differences in lung function between groups, and changes in lung function over five consecutive work shifts
were not related to the exposure level. The highest measured concentrations of welding fumes were 5.1 and 8.0 mg/m3 for an 8-h time-weighted average.

In a study designed to examine the pathogenesis of metal-fume fever in humans (Blanc et al., 1991), 14 subjects welded galvanized mild steel over a period
of 15–30 min in special environmental exposure chambers, with controlled ventilation, humidity and temperature, designed to produce an exposure level in
excess of 10 mg/m3 over 15 min. The mean cumulative exposure to zinc oxide for the 14 participants was reported to be 2.3 ± 1.7 g/min per m3 (range 0.6–
5.1 g/min per m3), resulting in a range of mean exposure levels of 77–153 mg/m3, and a minimum exposure of 20–40 mg/m3, depending upon whether
duration was 15 or 30 min. Pulmonary function and airway responsiveness were measured after 1 h (n = 14), 6 h (n = 5) and 20 h (n = 9), while
bronchoalveolar lavage was conducted 8 h or 22 h after welding. A marked, dose-dependent inflammatory response was observed in the lungs, with a
positive correlation between cumulative zinc exposure and polymorphonuclear leukocyte count in bronchoalveolar lavage fluid at early (r = 0.93; P < 0.05)
and late (r = 0.87; P < 0.01) follow-up. The proportion of polymorphonuclear leukocytes in the late follow-up sample, 37% (range 19–63%), was increased
compared with the early follow-up figure of 9% (2–21%). There was only a minimal effect on pulmonary function, and no statistically significant correlation
was observed between cumulative zinc exposure and pulmonary function. In the late follow-up group, the four participants with the highest cumulative
exposures (> 3.5 g/min per m3) all had myalgia. Two of the participants (with exposure of > 5 g/min per m3, i.e., approximately 150 mg/m3) also had fever
(38 °C).

In a subsequent paper (Blanc et al., 1993), further information from the same subjects was reported together with additional data from a total of 23 volunteers
adding a 3-h post-exposure time-point for bronchoalveolar lavage fluid (zinc exposure 1.8 ± 0.2 mg/m3). Increased concentration of tumour necrosis factor
(TNF) in bronchoalveolar lavage fluid was prominent at 3 h, and less marked at 8 h or 22 h after exposure, exhibiting a statistically significant exposure–
response relationship to airborne zinc at each time-point (P < 0.05). There were also significant changes in the concentrations of interleukin-6 and
interleukin-8, but not of interleukin-1. The findings are consistent with a role of these cytokines in the pathogenesis of the inflammatory changes in metal-
fume fever. Although these short-term exposures (15–30 min) were to zinc concentrations well above 10 mg/m3, it should be noted that they do not exceed
an 8-h time-weighted average of 5 mg/m3 if recalculated to an 8-h time interval; however, it is unlikely that an acute reaction of the type observed would
occur if the same cumulative exposures were given over 8 h.

A number of case reports have demonstrated the acute effects of zinc fume inhalation in occupational settings. Reversible clinical signs and radiological
effects, including aches and pains, dyspnoea, dry cough, lethargy, neutrophil leukocytosis, pyrexia, and widespread abnormality of both lung fields, with
multiple nodules measuring 3–4 mm and becoming confluent and ill-defined in some areas, were seen when an individual was exposed to zinc fumes in a
shipyard over a 3-week period (Brown, 1988). A systemic reaction and a self-limiting response in the periphery of the lung were reported when a patient
with a clinical history of recurring zinc fume fever underwent experimental welding exposures of 1 h using zinc-coated tubing (Vogelmeier et al., 1987). An
acute lung reaction was also seen in an individual working with heated zinc who experienced chills, muscle ache and dyspnoea; radiographic examination
revealed diffuse nodular infiltrates, which cleared after 10 days away from the job (Malo et al., 1990).

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8.4.3 Long-term exposure

The complex environment encountered by workers in galvanizing and metal plating plants results in exposure to a variety of compounds, including zinc and
zinc compounds.

A causal association between the exposure to zinc and any occupational asthma is difficult to establish. Occasional cases of occupational asthma have been
reported among workers using soft solder fluxes containing ammonium chloride and zinc chloride. A causative relationship with zinc could not be
concluded. The most suggestive case was a subject who developed asthma symptoms 2.5 years after being employed at a plant where metals were galvanized
in heated zinc (Malo et al., 1993). Positive immediate skin tests to zinc sulfate at concentrations of 1 and 10 mg/ml were obtained, although no specific IgE
antibodies to zinc were observed. An immediate asthmatic reaction was elicited after the subject inhaled nebulized zinc sulfate at a concentration of 10
mg/ml for 6 min.

The exposure of groups of volunteers to a polydisperse aerosol of zinc ammonium sulfate in an environmental control chamber at a nominal concentration of
20 µg/m3 produced minimal or no short-term respiratory effects, even in subjects diagnosed as asthmatics prior to the study (Linn et al., 1981).

8.4.4 Epidemiological studies

In general, well-conducted epidemiological studies in the workplace with adequate characterization of zinc exposure values are lacking, and there are
inadequate data available to make an association between occupational exposure to zinc and disease states.

8.5 Subpopulations at special risk

8.5.1 Dialysis patients

Acute zinc toxicity has been reported in patients following kidney dialysis (Gallery et al., 1972; Petrie & Row, 1977). A patient who, for home dialysis, used
rainwater draining from a painted galvanized iron roof, which had been stored in a galvanized iron tank, developed severe nausea and vomiting within 2 h of
starting the procedure, with similar symptoms at subsequent dialyses. The tank water contained zinc at a concentration of 625 µg/100 ml. The patient’s
plasma and red cell zinc concentrations were 700 and 3500 µg/100 ml, respectively, haemoglobin was 3.5 g/100 ml, and a blood film showed moderate
polychromatophilia; 6 weeks after rehospitalization, plasma zinc was still moderately raised. Intercurrent hospital dialyses were uneventful, and subsequent
deionization of the patient’s home water supply resulted in asymptomatic dialyses (Gallery et al., 1972). The use of water drawn through galvanized iron
piping resulted in a fall in the haemoglobin levels of two home dialysis patients; these effects were eliminated after the installation of carbon filtration of the
dialysis water (Petrie & Row, 1977). Severe anaemia was also seen in 9/10 patients dialysed in a hospital dialysis unit, following the installation of a new
galvanized iron water softener in the dialysate water supply system. The dialysate contained zinc at a concentration of 4.89 µmol/litre (32 µg/100 ml). The
installation of an activated carbon filter in the system reduced the zinc concentration to < 0.15 µmol/litre (< 1 µg/100 ml), resulting in a rise in haemoglobin
levels in the patients towards previous values (Petrie & Row, 1977).

8.5.2 People with diabetes

Non-infective furunculoid skin lesions were reported in an insulin-dependent diabetic subject, apparently induced by the zinc acetate component of an
intermediate-acting insulin preparation. This rare complication of insulin therapy was attributed to a reparative granulomatous phase arising from tissue
damage caused by the zinc in the preparation (Jordaan & Sandler, 1989; Sandler & Jordaan, 1989). In two patients using insulin preparations containing zinc,
pruritic, erythematous, papular lesions were observed at the injection site. Intradermal skin tests for zinc were positive in both patients. Zinc-free insulin did
not produce any allergic reactions in the patients (Feinglos & Jegasothy, 1979).

8.5.3 Hospital patients

An elderly woman died after she received 46 mmol (7.4 g) of zinc sulfate intravenously over 60 h, owing to a prescribing error; her serum zinc concentration
was 640 µmol/litre (4184 µg/100 ml). Zinc intoxication was characterized by hypotension, pulmonary oedema, diarrhoea, vomiting, jaundice and oliguria
(Brocks et al., 1977). In another incident, seven hospital patients undergoing intravenous feeding with fluid containing elemental zinc at a concentration of
227 µg/100 ml were inadvertently given fluid containing 10 times that amount (2270 µg/100 ml) for 26–60 days. Mortality was high (5/7). While the clinical
manifestation of the zinc overdose was hyperamylasaemia (unaccompanied by clinical signs of pancreatitis), the authors concluded that all deaths had
resulted from septic complications already present before the appearance of this symptom (Faintuch et al., 1978).

To investigate the effects of zinc administration on the healing of chronic leg ulcers, a double-blind trial was conducted in 27 subjects; 13 patients received
200 mg of zinc sulfate three times a day (approximately 135 mg of elemental zinc daily) for 18 weeks, while 14 patients received placebo. No signs of
toxicity associated with the zinc treatment were reported in the study (Hallbook & Lanner, 1972). Similarly, in another study investigating the effect of oral
zinc treatment on leg ulcers, no clinical signs of toxicity were reported in 18 patients administered 220 mg of zinc sulfate three times daily (approximately
150 mg of elemental zinc daily) for 16–26 weeks (Greaves & Skillen, 1970). Mild diarrhoea was reported in 3/52 patients receiving three daily doses of 220
mg of zinc sulfate for up to 71 days (Husain, 1969), while diarrhoea was reported in 6/16 geriatric patients receiving a similar zinc dose for 24 weeks
(Czerwinski et al., 1974).

8.5.4 Other populations

No adverse effects were observed as a result of ingestion of 300- 1200 mg of zinc sulfate heptahydrate daily for 3 years or 150 mg of zinc as zinc acetate
daily for several weeks to 2 years by Wilson disease patients (Hoogenraad et al., 1979, 1983, 1984; Brewer et al., 1983, Hill et al., 1987), doses of zinc of 1–
2 mg/kg daily by infants and children with acrodermatitis enteropathica (Hambidge & Walravens, 1982), and 68–102 mg of zinc daily during pregnancy by a
woman with acrodermatitis enteropathica (Jones & Peters, 1981). Few long-term studies of the effects of high oral zinc in healthy adults have been reported.
In 11 female and 13 male patients with Wilson disease, the administration of 50 mg of elemental zinc as zinc acetate three times a day for about 2 years
resulted in a decrease in total cholesterol of about 10% in both sexes and a reduction of HDL cholesterol of about 20% in male patients. The authors
concluded that the coronary heart disease risk factor was not changed significantly in either sex (Brewer et al., 1991).

Recently, a controlled, randomized double-blind study showed that oral zinc therapy, 100 mg of zinc sulfate twice daily taken with food, significantly
reduced visual loss in individuals with macular degeneration (Newsome et al., 1988).

8.6 Interactions
8.6.1 Copper

Impaired copper nutriture in humans has been noted following chronic elevated intake of zinc; these effects are reported in section 8.3.5.

8.6.2 Iron
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The effect of inorganic zinc on the absorption of inorganic iron from a solution was investigated in two studies in healthy male volunteers (Crofton et al.,
1989). Simultaneous administration of 344 µmol of zinc had no effect on the absorption of 842 µmol of radiolabelled iron (59Fe) in the first study, based
upon the area under the plasma iron concentration–time curve at 3 h and 6 h, the whole body retention of 59Fe, and plasma content of 59Fe. However, the
authors noted a reduction in 4/9 subjects of the areas under the curve at 3 h and 6 h for iron, and suggested that there was a trend (not statistically significant)
for zinc to inhibit the intestinal absorption of iron. The second study was conducted without a radiolabel, and the results indicated that the simultaneous
administration of iron with zinc at molar ratios of 1:1 (421 µmol) and 2.5:1 (1048 µmol) significantly reduced increments in the concentrations of iron in the
plasma.

In a study described in section 8.3.5.1, in which women were supplemented with zinc at 50 mg/day for 10 weeks, competitive interactions between iron and
zinc were suggested by the authors (Yadrick et al., 1989). Serum ferritin, the level of which is proportional to tissue iron stores, was reduced following zinc
supplementation alone, but when iron at 50 mg/day was administered together with the zinc, serum zinc and serum ferritin increased.

In human subjects, the presence of inorganic iron in solution with ionic zinc at molar ratios of between 2:1 and 3:1 resulted in significant inhibition of zinc
absorption (Solomons & Jacob, 1981; Solomons et al., 1983; Valberg et al., 1984; Sandstroem et al., 1985), while the presence of haem iron in the same
molar excess did not inhibit the absorption of zinc (Solomons & Jacob, 1981). In healthy, non-pregnant woman, a progressive decrease in plasma zinc was
seen as the ratio of iron to zinc was increased from 0.1 to 3.1, while the intake of zinc remained constant at 25 mg (Solomons & Jacob, 1981).

In studies in which iron was given with food, no inhibitory effect on zinc uptake was observed when the iron intake was not unusually high. The
consumption of 54 mg of "organic" zinc in oysters with 100 mg of ferrous iron did not alter plasma uptake of zinc (Solomons & Jacob, 1981). Neither the
addition of ferrous iron (at an iron:zinc ratio of 25) to a composite meal containing 2.6 mg of zinc (Sandstroem et al., 1985), nor the consumption of turkey
meat containing 4 mg of zinc with ferric iron (17 or 34 mg) (Valberg et al., 1984) significantly changed the absorption of zinc. No effects of iron-fortified
infant foods on zinc absorption of zinc from natural sources were demonstrated in adults or children (Fairweather-Tait, 1995) or in healthy infants given an
iron supplement (30 mg of iron as ferrous sulfate) before a meal. However, dietary supplementation with large amounts of iron may impair zinc absorption,
and this was observed in four human volunteers fed a zinc-deficient (zinc at 3.5 mg/day), protein-based, semisynthetic soy diet for 4 months (Prasad et al.,
1978a); the two subjects receiving 130 mg of iron daily displayed a more rapid reduction in plasma zinc than did the two volunteers fed 20.3 mg of iron
daily.

The effect of iron on zinc absorption may depend upon zinc status. For example, serum copper or zinc levels were not affected in healthy infants who were
fed a zinc-sufficient diet supplemented with 30 mg of iron as ferrous fumarate daily given 30 min before a meal (Yip et al., 1985).

Three pregnant women, whose daily diets were supplemented with iron at rates of 100 mg/day or more, had lower plasma zinc than other pregnant women
whose iron supplementation was less than 100 mg/day (Campbell-Brown et al., 1985), and daily multivitamin supplements containing 60–65 mg of iron
inhibited zinc absorption in first-trimester pregnant women, compared with pregnant women receiving no iron supplementation, or with iron supplementation
of less than 30 mg/day (Breskin et al., 1983). It is not known whether the iron supplements in these studies were taken in the presence or absence of food.

8.6.3 Calcium

Human subjects with a constant zinc intake of 14.5 mg/day and calcium intakes of 200–2000 mg/day showed no changes in zinc absorption (Spencer et al.,
1983). Conversely, the intake of high zinc levels (140 mg/day) reduced calcium absorption in men with low calcium intakes (200 mg/day) but calcium
absorption was not affected when calcium intake was 800 mg/day (Spencer et al., 1987).

9. EFFECTS ON OTHER ORGANISMS IN THE

LABORATORY AND FIELD
Zinc is an essential micronutrient in all biota owing to its involvement in many physiological processes. It is essential in the maintenance of plasma
membrane stability (Bettger & O’Dell, 1981; Cakmak & Marschner, 1988), in the activation of more than 300 enzymes, in transcription factors and in
hormone receptors (see section 6.5.2).

Generally, organisms growing in natural terrestrial environments do not show symptoms of zinc deficiency. However, species introduced by humans into the
environment may show these deficiencies. Zinc toxicity is observed in organisms exposed to anthropogenic zinc enrichment (Ernst, 1972) and in crops
grown in naturally enriched environments (Chaney, 1993). More often than toxicity, zinc deficiency is reported from environments where humans have
grown plants that are not adapted and/or have not been properly selected, ranging from crops and pastures in Australia (Donald & Prescott, 1975), Africa
(Cottenie et al., 1981), Asia (Katyal & Ponnamperuma, 1974) and North America (Lingle & Holmberg, 1957), to fruit trees (SSSA, 1990) and forest trees.
Application of various types of zinc fertilizers to soil or onto leaves can help to overcome these problems (Takkar & Walker, 1993). Another approach is to
increase the zinc efficiency of cultivated plant species (El Bassam et al., 1990). Animals fed or feeding on zinc-deficient plants will also show symptoms of
zinc deficiency (Blamberg et al., 1960, Elinder & Piscator, 1979).

Nutritional zinc deficiency is relatively rare for aquatic organisms. A possible exception may be the low zinc environments that characterize open oceans.
Extremely low concentrations of zinc, iron and copper have been observed in open oceans and it has been suggested that these are rate limiting for
phytoplankton growth (Anderson et al., 1978; Reuter & Morel, 1981; Bruland, 1993). In most other circumstances, organisms appear to have developed
appropriate physiological mechanisms to ensure adequate uptake of zinc from the concentrations present in their native environment. Organisms not capable
of doing this would of course have disappeared from a particular ecosystem. Information concerning zinc deficiency in aquatic organisms must thus be
obtained primarily from laboratory experiments. There are several reports of zinc deficiency under experimental conditions in protozoa (Falchuk, 1988),
algae (Vymazal, 1986), daphnids (Keating & Caffrey, 1989), fish (Spry et al., 1988) and amphibians (Herkovits et al., 1989). White & Rainbow (1985)
calculated theoretical estimates for the minimum metabolic requirements of zinc in molluscs and crustaceans. Enzymatic requirements for zinc in both
groups were estimated to be 34.5 mg/kg dw. The possession of haemocyanin as a respiratory pigment adds a further non-enzymatic metabolic requirement of
58.3 mg/kg for certain gastropod molluscs and 36.3 mg/kg for some crustaceans such as decapods. However, Depledge (1989) recalculated the amount of
zinc required by decapod crustaceans to be 67.9 mg/kg dw.

9.1 Laboratory experiments

Many experiments performed in laboratories give insufficient information on the speciation of zinc, especially when zinc is added to a medium rich in
complexing agents such as sewage sludge and agar (for example, Codina et al., 1993). In the case of soils, there is a lack of information on the time period
between the zinc application and the start of the experiments, i.e., the time necessary for an equilibrium to be reached between the metal application and the
soil solution (Spurgeon & Hopkin, 1996). The lack of this information adversely affects the reliability and utility of toxicity determinations. A similarly
inadequate procedure is followed in many experiments with animals in which zinc added to the feed is only adsorbed, whereas in the natural situation it is
processed by the organism and incorporated into organic compounds. The difference between adsorbed and metabolically processed zinc has clearly been
shown in experiments with Japanese quail fed spinach and lettuce (McKenna et al., 1992).

To be useful, toxicity testing requires, at a minimum, the following information: actual exposure concentrations (nominal concentrations are unacceptable);
acceptable control results (i.e., an acceptably low level of mortalities and/or effects); physicochemical conditions (at a minimum, temperature, pH, dissolved

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oxygen and hardness); and a concentration–response relationship. Studies that met these criteria are so indicated where appropriate in the text and tables that
follow.

9.1.1 Microorganisms

9.1.1.1 Water

Studies on the effect of zinc on microorganisms in the aquatic environment generally measure either growth or survival. However, the zinc concentrations
added in these tests are often too high to be of environmental relevance (Codina et al., 1993, 50–432 mg/litre; Tijero et al., 1991, 200–600 mg/litre). Values
for the EC50 (the concentration producing effects in 50% of the tested organisms) and LC50 (the concentration killing 50% of the tested organisms) in other
experiments varied in a species-specific manner (Table 34).

Table 34. Zinc toxicity (LC50 or EC50 values in mg/litre) for microorganisms in the aquatic environment

Species Duration of LC50 Reference

exposure (h)

Drepanomonas revoluta 24 0.25 Madoni et al. (1994)

Spirostomum teres 24 0.67 Madoni et al. (1994)

Blepharisma americanum 24 1.05 Madoni et al. (1994)

Tetrahymena pyriformis 56 5.77 Carter & Cameron (1973)

Tetrahymena pyriformis 8 < 1.00 Chapman & Dunlop (1981)

Zoogloea ramigera 24 approximately Norberg & Molin (1983)

3.0a

Euplotes patella 24 50.0 Madoni et al. (1992)

a EC50

9.1.1.2 Soil

Laboratory experiments are often carried out without equilibrium between the added zinc and the soil, which is a critical drawback in short-term experiments
(< 3 weeks). Three parameters of microbial activities in soil have been studied: mineralization of macronutrients (N, S); soil respiration as a parameter of the
mineralization of organic compounds; and general soil activity (dehydrogenase). Microbial activity is less affected by zinc in soils rich in organic materials
than in sandy and loamy soils (this situation was found for N-mineralization (Doelman & Haanstra, 1984), soil respiration (Frostegård et al., 1993) and
dehydrogenase activity (Rogers & Li, 1985). These results can be explained by differences in zinc speciation.

More recent literature confirms the importance of organic matter in reducing the effects of zinc in microbial processes, such as the breakdown of glutamic
acid, and phosphatase activity. Increasing exposure time lowers the EC50 value (Table 35).

Table 35. Impact of zinc (mg/kg) on nitrogen mineralization in relation to soil types

Process Duration EC50 Reference

Sand Sandy loam Silty loam Clay

Urease 6 weeks 420 480 1030 1780 Doelman & Haanstra

(1986)
18 months 230 110 – 90

Nitrification – – 100a – ca. 80 Wilson (1977)

1000

a No-observed-effect concentration.

9.1.2 Aquatic organisms

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9.1.2.1 Plants

Acute toxicity of zinc is often determined in short-term experiments of 24–96 h (Table 36). In the case of unicellular algae, these experiments cover 1–4 cell-
division cycles. EC50 values range from 0.058 to 10 mg/litre (nominal concentration) in a species-specific manner. The toxicity of zinc depends on the
external concentration, the zinc speciation, and the pH and hardness of the water (Starodub et al., 1987, Stauber & Florence, 1989). Aquatic macrophytes are
generally insensitive to zinc.

Table 36. Toxicity of zinc to algae and aquatic plants in static conditionsa

Organism Temp Zinc Hardness Parameter End-point EC50 Reference

(° C) compound (CaCO3 (mg/litre)
tested mg/litre)

Unicellular algae: freshwater

Green algae

Chlorella vulgaris 15.5 sulfate n.g. 96-h EC50 culture growth 2.4 (n) Rachlin &
Farran
(1974)

Scenedesmus 20 sulfate n.g. 24-h EC50 photosynthesis > 0.225 Starodub

quadricauda (n) et al.
(1987)

Selenastrum 25 zinc 16 72-h EC50 culture growth 0.15 van

capricornutum powder (m,d) Woensel
(1994)

NOEC culture growth 0.05 van

(m,d) Woensel
(1994)

Selenastrum 25 oxide 16 72-h EC50 culture growth 0.17 van

capricornutum (m,d) Ginneken
(1994)

NOEC culture growth 0.03 van

(m,d) Ginneken
(1994)

Diatoms

Navicula incerta 19 chloride n.g. 9-h EC50 culture growth 10.0 (n) Rachlin et
al. (1983)

Unicellular algae: marine

Marine diatoms

Asterionella 23 sulfate n.g. 72-h EC50 culture growth 0.058 (n) Fisher &
japonica Jones
(1981)

Nitzschia 15.5 sulfate n.g. 96-h EC50 culture growth 0.271 (n) Rosko &
closterium Rachlin
(1975)

Nitzschia 21 chloride n.g. 96-h EC50 culture growth 0.065 (n) Stauber &
closterium Florence
(1990)

Macrophytes: freshwater

Acute toxicity

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Elodea canadensis 24 sulfate 10 24-h EC50 photosynthetic 8.1 (n) Brown &
(segments) O2 Rattigan
(1979)

Prolonged tests

Elodea canadensis n.g. sulfate n.g. 28-d EC50 plant damage 22.5 (n) Brown &
Rattigan
(1979)

Lemna minor n.g. sulfate n.g. 28-d EC50 plant damage 67.7 (n) Brown &
Rattigan
(1979)

Lemna minor 25– chloride n.g. 7-d EC50 frond growth 10 (n) Dirilgen &
28 inhibition Inel
(1994)

Elodea nuttallii 21 sulfate n.g. 14 d no toxic 32.7 (n) Van der

symptoms Werff &
Pruyt

Callitriche 21 sulfate n.g. 28 d no toxic 32.7 (n) (1982)

platycarpa symptoms

Callitriche 21 sulfate n.g. 73 d no toxic 0.654 (n) Van der

platycarpa symptoms Werff &
Pruyt

Spirodela 21 sulfate n.g. 73 d no effects 0.654 (n) (1982)

polyrhiza observed

Lemna gibba 21 sulfate n.g. 73 d no effects 0.654 (n) Van der

observed Werff &
Pruyt
(1982)

d = measurements expressed as dissolved zinc; m = measured concentrations; n = nominal concentrations; n.g. = not
given

a Many of the older test results should be regarded with caution because the assays were carried out in culture
media containing complexing agents like EDTA, which could affect the bioavailability of zinc. Crucial
information concerning physicochemical factors such as hardness, DOC and DO is lacking in most of the papers.

Most of the data for unicellular algae were obtained using culture media as the assay solutions. These results should be used with
caution, since complexing agents, e.g., EDTA in the culture media, may reduce zinc bioavailability and lower its toxicity (Stauber,
1995). Crucial information with respect to physicochemical parameters (e.g., water hardness, dissolved organic carbon, dissolved
oxygen) is not generally provided in most of the cited references.

Acute toxicity values tend to be lower for marine unicellular algae than for freshwater species. Only one set of experiments
satisfies the ideal criteria as previously specified. In these tests, no-observed-effect concentrations, obtained under standardized test
conditions (OECD 201 algae growth-inhibition test) for Selenastrum capricornutum, ranged between 30 µg/litre and 50 µg/litre
(measured as dissolved concentration; hardness 16 mg/litre, CaCO3).

Floating aquatic plants can take up zinc by the roots and shoots (the lower surface with water contact). Zinc uptake is governed not
only by the zinc concentration in the water but also by evapotranspiration, which is not taken into account in most experiments
with duckweed (Lemna minor) (Hutchinson & Czyrska, 1975; Brown & Rattigan, 1979; Dirilgen & Inel, 1994). EC50 values vary
from 10 to 67.7 mg/litre depending on the test period and conditions. Submerged aquatic plants, e.g., pondweeds (Elodea sp.), are
more sensitive than floating aquatic plants (Brown & Rattigan, 1979).

Permanent high exposure to zinc gives rise to the selection of zinc-tolerant genotypes, e.g., Lemna minor (Van Steveninck et al.,
1990) which detoxifies zinc as zinc phytate in vacuoles, and in several algal species (Say et al., 1977; Harding & Whitton, 1981).

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Zinc tolerance in plants and other organisms is discussed further in section 9.2.

9.1.2.2 Invertebrates and vertebrates

Information on the acute toxicity of zinc to freshwater and marine invertebrates is summarized in Tables 37 and 38, respectively,
and to freshwater and marine fish is summarized in Tables 39 and 40, respectively. Studies that meet the criteria specified above so
indicated in these tables.

Table 37 (a) Toxicity of zinc to freshwater invertebratesa

Organism Size/age Stat/flow Temp Hardness pH

(oC) (mg/litre)

Snail eggs stat 17 50 7.6

Amnicola sp. eggs stat 17 50 7.6

adult stat 17 50 7.6

adult stat 17 50 7.6

Mollusc <2 mm stat 10

Ancylus fluviatilis >3 mm stat 10

Annelid <4 mg stat 10

Erpobdella oculata >15 mg stat 10

Bristle worm stat 17 50 7.6

Nais sp. stat 17 50 7.6

Water flea stat 17–19 44–53 7.4–8.2

Daphnia magna stat 17–19 44–53 7.4–8.2

<48 h stat 175 6.0

<24 h stat 20 6.5

<24 h stat 20 6.5

<24 h stat 45 7.2–7.4

<24 h stat* 20

stat

D. pulex <24 h stat 45 7.2–7.4

Ceriodaphnia dubia stat 25

C. reticulata <24 h stat 45 7.2–7.4

D. hyalina 1.27 mm stat 10 7.2

D. lumholtzi stat* 28.5 200 7.9

stat* 28.5 200 7.9

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Moina irrasa <24 h stat 20 <5 8.0

M. macrocopa stat* 24–27 6.5

Copepod Cyclops 1.27 mm stat 10 7.2

abyssorum

Eudiaptomus padanus 1.27 mm stat 10 7.2

Parastenocaris adult stat 10.5 10* 6.8

germanica
adult stat 10.5 6.8

Amphipod stat 17 50 7.6

Gammarus sp.
stat 17 50 7.6

Crangonyx 4 mm stat 13 50 6.75

pseudogracilis
4 mm stat 13 50 6.75

Isopod 7 mm stat 13 50 6.75

Asellus aquaticus

Ostracod stat* 28.5 200 7.9

Cypris subglobosa stat* 28.5 200 7.9

Harpacticoid adult stat 21 7 7.8

Nitocra spinipes

Rotifer juvenile stat 20 36.2 7.3

Brachionus calyciflorus
stat 25

Midge stat 17 50 7.6

Chironomus sp.
stat 17 50 7.6

C. tentans 3rd instar stat 13 25 6.3

Caddis fly stat 17 50 7.6

Unidentified
stat 17 50 7.6

Damsel fly stat 17 50 7.6

Unidentified
stat 17 50 7.6

Table 37 (b) Toxicity of zinc to freshwater invertebratesa

Organism Zinc compound Parameter Concentration Reference

tested (mg/litre)

Snail 24-h LC50 28.1 (m) Rehwoldt et al. (1973)

Amnicola sp. 96-h LC50 20.2 (m)

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24-h LC50 16.8 (m) Rehwoldt et al. (1973)

96-h LC50 14 (m)

Mollusc sulfate 96-h LC50 3.2 (n) Willis (1988)

Ancylus fluviatilis sulfate 96-h LC50 4.5 (n) Willis (1988)

Annelid sulfate 96-h LC50 2.05 (n) Willis (1989)

Erpobdella oculata sulfate 96-h LC50 8.8 (n) Willis (1989)

Bristle worm 24-h LC50 21.2 (m) Rehwoldt et al. (1973)

Nais sp. 96-h LC50 18.4 (m)

Water flea chloride 48-h EC50 0.1 (n) Biesinger & Christensen
(1972)
Daphnia magna chloride 48-h EC50 0.28 (n)

sulfate 48-h LC50 0.24 (n) LeBlanc (1982)

sulfate 48-h LC50 0.151 (n) Oikari et al. (1992)

sulfate 48-h LC50 0.244 (n, hw) Oikari et al. (1992)

48-h LC50 0.068 (n) Mount & Norberg (1984)

sulfate 48-h LC50 0.75 (n) Arambasic et al. (1995)

bromide 48-h LC50 1.22 (m) Magliette et al. (1995)

D. pulex 48-h LC50 0.107 (n) Mount & Norberg (1984)

Ceriodaphnia dubia bromide 48-h LC50 0.50 (m) Magliette et al. (1995)

C. reticulata 48-h LC50 0.076 (n) Mount & Norberg (1984)

D. hyalina sulfate 48-h LC50 0.04 (n) Baudouin & Scoppa

(1974)

D. lumholtzi 48-h LC50 2.29 (n) Vardia et al. (1988)

96-h LC50 0.44 (n)

Moina irrasa chloride 48-h LC50 0.059 (n) Zou & Bu (1994)

M. macrocopa sulfate 48-h LC50 1.17 (n) Wong (1992)

Copepod Cyclops sulfate 48-h LC50 5.5 (n) Baudouin & Scoppa
abyssorum (1974)

Eudiaptomus padanus sulfate 48-h-LC50 0.50 (n) Baudouin & Scoppa

(1974)

Parastenocaris sulfate 48-h LC50 4.5 (m) Notenboom et al. (1992)

germanica
sulfate 96-h LC50 1.7 (m)

Amphipod 24-h LC50 10.2 (m) Rehwoldt et al. (1973)

Gammarus sp.
96 h LC 81( )
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96-h LC50 8.1 (m)

Crangonyx sulfate 48-h LC50 121 (n) Martin & Holdich (1986)
pseudogracilis
sulfate 96-h LC50 19.8 (n)

Isopod sulfate 96-h LC50 18.2 (n)

Asellus aquaticus

Ostracod 48-h LC50 34.99 (n) Vardia et al. (1988)

Cypris subglobosa 96-h LC50 8.35 (n) Vardia et al. (1988)

Harpacticoid sulfate 96-h LC50 4.3 (n) Lindén et al. (1979)

Nitocra spinipes

Rotifer chloride 24-h LC50 1.32 (n) Couillard et al. (1989)

Brachionus calyciflorus
24-h LC50 1.3 (n) Snell et al. (1991)

Midge 24-h LC50 21.5 (m) Rehwoldt et al. (1973)

Chironomus sp.
96-h LC50 18.2 (m)

C. tentans sulfate 48-h EC50 8.2 (n) Khangarot & Ray (1989)

Caddis fly 24-h LC50 62.6 (m) Rehwoldt et al. (1973)

Unidentified
96-h LC50 58.1 (m)

Damsel fly 24-h LC50 32 (m) Rehwoldt et al. (1973)

Unidentified
96-h LC50 26.2 (m)

hw = humic water; m = measured concentrations; n = nominal concentrations; stat = static conditions (water
unchanged for duration of test); stat* = static renewal conditions (water changed at regular intervals)

a EC50 values based on immobilization; hardness expressed as mg/litre O3.

Table 38 (a) Toxicity of zinc to marine invertebratesa

Organism Size/age Stat/flow Temp Salinity pH

(oC) (%)

Starfish 11.2 g stat 20 20 7.8

Asterias forbesi

American oyster embryo stat 26 25

Crassostrea virginica

Mussel stat 12 7
Mytilus edulis

M. edulis planulatus stat 20.6 34 8.0

flow 17.6 7.8

juvenile stat* 20 25

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Bay scallop
Argopecten irradians

Surf clam juvenile stat* 20 25

Spisula solidissima

Soft-shell clam 4.6 g stat 20 20 7.8

Mya arenaria

Squid larvae stat 8.6 30 8.1

Loligo opalescens

Cabezon larvae stat 8.3 27 7.9

Scorpaenichthys
marmoratus

Eastern mud snail 0.4 g stat 20 20 7.8

Nassarius obsoletus

Amphipod 0.06 g stat 20.5 34.5 7.9

Allorchestes compressa

Harpacticoid copepod
Nitocra spinipes
Ragworm 7.6 g stat 20 20 7.8
Nereis virens

Sandworm 0.33 g stat 18.7 34.2 7.9

Neanthes vaalii

Dungeness crab larvae stat 8.5 30 8.1

Cancer magister

Fiddler crab 24–29 mm stat 29 25

Uca annulipes
24–29 mm stat 29 25

U. triangularis 24–29 mm stat 29 25

24–29 mm stat 29 25

Hermit crab 0.5 g stat 20 20 7.8

Pagurus longicarpus

Grapsid crab 1.44 g stat 19.6 34.2 8.1

Paragrapsus
quadridentatus

Crab zoeae stat* 25–27 35

Portunus pelagicus

P. sanguinolentus zoeae stat* 25–27 35

Charybdis feriatus zoeae stat* 25–27 35

Copepod stat 22 38
Tisbe holothuriae

Grass shrimp juvenile stat* 20 10

Palaemonetes pugio

Shrimp 0.28 g stat 19.5 35.5 7.8

Palaemon sp.
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Mysid juvenile stat 13–15.5 34–36

Holmesimysis costata
juvenile stat* 13–16 34–40

Prawn 30–50 mm stat* 27.5 7.5

Metapenaeus dobsoni
30–50 mm stat* 27.5 7.5

Table 38 (b) Toxicity of zinc to marine invertebratesa

Organism Zinc salt Parameter Concentration Reference

(mg/litre)

Starfish chloride 96-h LC50 39 (n) Eisler & Hennekey

Asterias forbesi (1977)

American oyster chloride 48-h LC50 0.31 (n) Calabrese et al.

Crassostrea virginica (1973)

Mussel chloride 24-h LC50 20.8 (n) Hietanen et al. (1988)

Mytilus edulis

M. edulis planulatus chloride 96-h LC50 2.5 (m) Ahsanullah (1976)

chloride 96-h LC50 3.6 (m) Ahsanullah (1976)

Bay scallop chloride 96-h LC50 2.25 (n) Nelson et al. (1988)
Argopecten irradians

Surf clam chloride 96-h LC50 2.95 (n) Nelson et al. (1988)
Spisula solidissima

Soft-shell clam chloride 96-h LC50 7.7 (n) Eisler & Hennekey
Mya arenaria (1977)

Squid chloride 96-h LC50 >1.92 (m) Dinnel et al. (1989)

Loligo opalescens

Cabezon chloride 96-h LC50 0.191 (m) Dinnel et al. (1989)

Scorpaenichthys marmoratus

Eastern mud snail chloride 96-h LC50 50 (n) Eisler & Hennekey
Nassarius obsoletus (1977)

Amphipod chloride 96-h LC50 0.58 (m) Ahsanullah (1976)

Allorchestes compressa

Harpacticoid copepod chloride 96-h LC50 0.85 (n) Bengtsson &

Nitocra spinipes Bergström (1987)
chloride 96-h LC50 1.3 (n)

sulfate 96-h LC50 2.4 (n) Bengtsson &

sulfate 96-h LC50 2.8 (n) Bergström (1987)

Ragworm chloride 96-h LC50 8.1 (n) Eisler & Hennekey

Nereis virens (1977)

Sandworm chloride 96-h LC50 5.5 (m) Ahsanullah (1976)

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50 ( ) ( )
Neanthes vaalii

Dungeness crab chloride 96-h LC50 0.586 (m) Dinnel et al. (1989)
Cancer magister

Fiddler crab sulfate 96-h LC50 31.9 (n) Devi (1987)

Uca annulipes
sulfate 96-h LC50 77 (n) Devi (1987)
(polluted)

U. triangularis sulfate 96-h LC50 39.1 (n) Devi (1987)

sulfate 96-h-LC50 66.4 (n) Devi (1987)

(polluted)

Hermit crab chloride 96h LC50 0.4 (n) Eisler & Hennekey
Pagurus longicarpus (1977)

Grapsid crab chloride 96-h LC50 11 (m) Ahsanullah (1976)

Paragrapsus quadridentatus

Crab chloride 48-h LC50 0.56–0.77 (n) Greenwood &

Portunus pelagicus Fielder (1983)

P. sanguinolentus chloride 48-h LC50 0.62 (n) Greenwood &

Charybdis feriatus chloride 48-h LC50 0.96 (n) Fielder (1983)

Copepod sulfate 48-h LC50 0.62 (n) Verriopoulos &

Tisbe holothuriae Dimas (1988)

Grass shrimp chloride 48-h LC50 11.3 (m) Burton & Fisher
Palaemonetes pugio (1990)

Shrimp chloride 96-h LC50 9.5 (m) Ahsanullah (1976)

Palaemon sp.

Mysid sulfate 48-h LC50 0.458 (m) Martin et al. (1989)

Holmesimysis costata
sulfate 96-h LC50 0.097 (m) Martin et al. (1989)

Prawn sulfate 48-h LC50 3 (n) Sivadasan et al.

Metapenaeus dobsoni (1986)
sulfate 96-h LC50 0.84 (n)

flow = flow-through conditions (zinc concentration in water continuously maintained); m = measured

concentrations; n = nominal concentrations; stat = static conditions (water unchanged for duration of test);
stat* = static renewal conditions (water changed at regular intervals)

a EC50 values based on immobilization; hardness expressed as mg/litre O3.

Table 39 (a) Toxicity (96-h LC50) of zinc to freshwater fisha

Organism Size/age Stat/flow Temp Hardness

(oC) (mg/litre)

Chinook salmon 1.03 g stat 12 211

Oncorhynchus
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tshawytscha juvenile flow 11–13 20–21

alevin flow 12 23

swim-up flow 12 23

parr flow 12 23

smolt flow 12 23

Coho salmon alevin stat 12 41

O. kisutch
0.47 g stat 12 41

0.63 g stat 12 41

2.7 kg flow 14 25

Rainbow trout alevin stat 12 41

O. mykiss
0.60 g stat 12 41

juvenile flow

alevin flow 12 23

swim-up flow 12 23

parr flow 12 23

smolt flow 12 23

2.7 kg flow 10 83

juvenile flow 15 26

juvenile flow 15 333

25–70 g flow 12.7 137

160–290 g flow 12.9 143

Cutthroat trout 0.6 g stat 10 38

Salmo clarki
0.9 g stat 15 43

0.9 g stat 10 40

1.0 g stat 10 40

1.0 g stat 10 38

1.0 g stat 5 38

Fathead minnow 79 mg flow 25 220

Pimephales promelas
1–2 g stat 25 20

1–2 g stat 25 360

1–2 g stat 25 20

1–2 g stat 15 20
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Arctic grayling fry stat 12 41

Thymallus arcticus
alevin stat 12 41

0.20 g stat 12 41

0.85 g stat 12 41

Bluegill 1–2 g stat 25 20

Lepomis macrochirus
1–2 g stat 25 360

1–2 g stat 15 20

Pumpkinseed stat 28 55
Lepomis gibbosus

Banded killifish stat 28 55

Fundulus diaphanus

Striped bass stat 28 55

Roccus saxatilis

White perch stat 28 55

Roccus americanus

American eel stat 28 55

Anguilla rostrata

Carp stat 28 55
Cyprinus carpio
3.2 cm stat* 15

6.0 cm stat* 15

47–62 mm stat* 15 19

Goldfish 1–2 g stat 25 20

Carassius auratus

Guppy 0.1–0.2 g stat 25 20

Poecilia reticulata

Flagfish juvenile flow 25 44

Jordanella floridae

Channelfish 500 mg stat 4

Nuria denricus

Tilapia subadult stat 9.3 20–22

Tilapia zilli
subadult stat 25 20–22

Catfish subadult stat 9.3 20–22

Clarius lazera
subadult stat 25 20–22

Table 39 (b) Toxicity (96-h LC50) of zinc to freshwater fisha

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Organism pH Zinc salt Concentration Reference
(mg/litre)

Chinook salmon 7.4–8.3 chloride 1.27 (n) Hamilton & Buhl

Oncorhynchus (47.3%) (1990)
tshawytscha
7.1–7.2 sulfate 0.084 (m) Finlayson & Verrue
(1982)

7.1 >0.66 (n) Chapman (1978b)

7.1 0.097 (n) Chapman (1978b)

7.1 0.46 (n) Chapman (1978b)

7.1 0.7 (n) Chapman (1978b)

Coho salmon 7.1–8.0 chloride 0.73 (n) Buhl & Hamilton

O. kisutch (1990)

7.1–8.0 chloride 0.82 (n) Buhl & Hamilton

(1990)

7.1–8.0 chloride 1.81 (n) Buhl & Hamilton

(1990)

7.4 chloride 0.91 (n) Chapman & Stevens

(1978)

Rainbow trout 7.1–8.0 chloride 2.17 (n) Buhl & Hamilton

O. mykiss (1990)

7.1–8.0 chloride 0.17 (n) Buhl & Hamilton

(1990)

6.4–8.3 acetate 0.550 (m) Hale (1977)

7.1 0.815 (n) Chapman (1978b)

7.1 0.093 (n) Chapman (1978b)

7.1 0.136 (n) Chapman (1978b)

7.1 >0.651 (n) Chapman (1978b)

7.45 chloride 1.76 (n) Chapman & Stevens

(1978)

6.8 sulfate 0.43 (n) Sinley et al. (1974)

7.8 sulfate 7.21 (n) Sinley et al. (1974)

7.3 sulfate 2.6 (m) Meisner & Quan Hum

7.1 sulfate 2.4 (m) (1987)

Cutthroat trout 7.5 sulfate 0.152 Mayer & Ellersieck

Salmo clarki (1986)

7.5 sulfate 0.600 Mayer & Ellersieck

(1986)

7.8 sulfate 0.130 Mayer & Ellersieck

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y
(1986)

8.5 sulfate 0.061 Mayer & Ellersieck

(1986)

6.5 sulfate 0.100 Mayer & Ellersieck

(1986)

7.5 sulfate 0.074 Mayer & Ellersieck

(1986)

Fathead minnow 7.8 sulfate 2.61 (n) Broderius & Smith

Pimephales promelas (1979)

7.5 sulfate 0.77–0.96 (n) Pickering & Henderson

8.2 sulfate 33.4 (n) (1966)

7.5 acetate 0.88 (n) Pickering & Henderson

7.5 2.33 and (1966)

2.55 (n)

Arctic grayling 7.1–8.0 chloride 0.32 (n) Buhl & Hamilton

Thymallus arcticus (1990)

7.1–8.0 chloride 2.92 (n) Buhl & Hamilton

(1990)

7.1–8.0 chloride 0.14 (n) Buhl & Hamilton

(1990)

7.1–8.0 chloride 0.17 (n) Buhl & Hamilton

(1990)

Bluegill 7.5 sulfate 4.85–5.82 (n) Pickering &

Lepomis macrochirus
8.2 sulfate 40.9 (n) Henderson

7.5 6.44 (n) (1966)

Pumpkinseed 8.0 20.1 (m) Rehwoldt et al. (1972)

Lepomis gibbosus

Banded killifish 8.0 19.2 (m) Rehwoldt et al. (1972)

Fundulus diaphanus

Striped bass 8.0 6.8 (m) Rehwoldt et al. (1972)

Roccus saxatilis

White perch 8.0 14.4 (m) Rehwoldt et al. (1972)

Roccus americanus

American eel 8.0 14.5 (m) Rehwoldt et al. (1972)

Anguilla rostrata

Carp 8.0 7.8 (m) Rehwoldt et al. (1972)

Cyprinus carpio
7.1 sulfate 0.45–1.34 (n) Alam & Maughan
(1992)

71 lf t 1 64 2 25 ( ) Al &M h
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7.1 sulfate 1.64–2.25 (n) Alam & Maughan
(1992)

6.3 sulfate 3.12 (n) Khangarot et al. (1983)

Goldfish 7.5 sulfate 6.44 (n) Pickering & Henderson

Carassius auratus (1966)

Guppy 7.5 sulfate 1.27 (n) Pickering & Henderson

Poecilia reticulata (1966)

Flagfish 7.1–7.8 sulfate 1.5 (n) Spehar (1976)

Jordanella floridae

Channelfish 6.1 6.06 (n) Abbasi & Soni (1986)

Nuria denricus

Tilapia 6.7 sulfate 33 (n) Hilmy et al. (1987)

Tilapia zilli
6.7 sulfate 13 (n) Hilmy et al. (1987)

Catfish 6.7 sulfate 52 (n) Hilmy et al. (1987)

Clarius lazera
6.7 sulfate 26 (n) Hilmy et al. (1987)

flow = flow-through conditions (zinc concentration in water continuously maintained); m = measured

concentrations; n = nominal concentrations; stat = static conditions (water unchanged for duration of test);
stat* = static renewal conditions (water changed at regular intervals)

a Hardness expressed as CaCO3 in mg/litre.

Table 40 (a) Toxicity of zinc to marine fish

Organism Size/age Stat/flow Temp Salinity pH

(oC) (%)

Chinook salmon 2.6 g stat 11–13 brackish 7.6–8.1

Oncorhynchus tshawytscha

Atheriniform fish 0.03–0.1 g flow 26–27 14

Rivulus marmoratus

Mummichog 0.02–0.1 g flow 26–27 14

Fundulus heteroclitus
juvenile stat* 20 10

1.3 g stat 20 20 7.8

Grey mullet 0.87 g flow 12 34.6 7.7

Chelon labrosus

English sole larvae stat 12

Parophrys vetulus

Bleak 8 cm stat 10 7 7.8

Alburnus alburnus
8 cm stat 10 7 7.8

Tidewater silverside larvae stat 25 20

Menidia peninsulae

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Spot adult stat 26 25

Leiostomus xanthurus

Table 40 (b) Toxicity of zinc to marine fish

Organism Zinc salt Parameter Concentration Reference

(mg/litre)

Chinook salmon chloride 96-h LC50 2.88 (n) Hamilton & Buhl
Oncorhynchus tshawytscha (47.3%) (1990)

Atheriniform fish 96-h LC50 119.3–176.6 Lin & Dunson (1993)

Rivulus marmoratus

Mummichog 96-h LC50 129.5 (n) Lin & Dunson (1993)

Fundulus heteroclitus
chloride 48-h LC50 96.5 (m) Burton & Fisher
(1990)

chloride 96-h LC50 60 (n) Eisler & Hennekey

(1977)

Grey mullet nitrate 96-h LC50 21.5 (m) Taylor et al. (1985)
Chelon labrosus

English sole sulfate 96-h LC50 14.5 (n) Shenker & Cherr
Parophrys vetulus (1990)

Bleak chloride 96-h LC50 32 (n) Lindén et al. (1979)

Alburnus alburnus
sulfate 96-h LC50 41.9 (n) Lindén et al. (1979)

Tidewater silverside sulfate 9-6h LC50 5.6 (n) Mayer (1987)

Menidia peninsulae

Spot sulfate 96-h LC50 38 (n) Mayer (1987)

Leiostomus xanthurus

flow = flow-through conditions (zinc concentration in water continuously maintained); m = measured

concentrations; n = nominal concentrations; stat = static conditions (water unchanged for duration of test);
stat* = static renewal conditions (water changed at regular intervals)

The toxicity of zinc can be influenced both by intrinsic and by extrinsic factors. Numerous studies with
aquatic animals have demonstrated that zinc toxicity decreases with increasing water hardness (Sinley et al.,
1974; Bradley & Sprague, 1985; Winner & Gauss, 1986; Paulauskis & Winner, 1988; Everall et al., 1989)
and decreasing temperature (McLusky & Hagerman, 1987; Hilmy et al., 1987; Zou & Bu, 1994). However,
Berglind & Dave (1984) reported that, hardness over the range 50–300 mg/litre, CaCO3, had no significant
effect on the toxicity of zinc to daphnids. Similarly, Rehwoldt et al. (1972) found no effect of temperature
(15–28 °C) on the toxicity of zinc to freshwater fish. Smith & Heath (1979) reported that the effect of
temperature on zinc toxicity was species specific. While increased temperature resulted in an increase in
toxicity of zinc to goldfish (Carassius auratus) and bluegill (Lepomis macrochinus), it had no effect on the
toxicity of zinc to golden shiners (Notemigonus crysoleucas) or rainbow trout (Oncorhynchus mykiss).

Zinc toxicity is also influenced by water pH and salinity, although the dose–response relationship is not
necessarily monotonic (McLusky & Hagerman, 1987; Meinel & Krause, 1988; Reader et al., 1989).
Notenboom et al. (1992) found no effect of reducing dissolved oxygen concentration (5.4 mg/litre to 0.1
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mg/litre) on the toxicity of zinc to the copepod, Parastenocanis germanica. Paulauskis & Winner (1988)
reported that the toxicity of zinc to Daphnia magna decreased with increasing concentrations of humic acids.

Bengsston (1974a) reported that yearling minnow (Phoxinus phoxinus) were more sensitive to zinc than
adults, and Naylor et al. (1990) reported that juvenile Gammarus pulex and Asellus aquaticus were more
sensitive than large adults. However, other studies have found little effect of organism age on zinc toxicity
(Martin et al., 1989; Collyard et al., 1994).

Acute and short-term toxicity

Of the studies reported in Table 37, the results from five freshwater crustaceans meet the minimal data
requirements. For four species the LC50 values for zinc at 48–96 h range from 0.5 to 10 mg/litre; Asellus
aquaticus was less sensitive to zinc (194- 575 mg/litre). Other acute toxicity test results reported range from
0.04 to 2.29 mg/litre zinc for daphnids (Daphnia, Ceriodaphnia and Moina) to 28.1 and 62.6 mg/litre for a
snail species and a caddisfly, respectively.

Acute toxicity results for eight marine invertebrate species were acceptable, in accordance with the minimal
data requirements (Table 38). The 96-h LC50 values for four species (including cabezon, amphipod, crab and
mysid species) ranged from 0.191 to 0.586 mg/litre; those for the remaining species ranged from 2.5 to 11.3
mg/litre. Other results ranged from 0.31 (American oyster) to 77 mg/litre (fiddler crab).

Dinnel et al. (1989) reported on short-term zinc toxicity tests with the early life stages of echinoderms.
Threshold values (EC50) for the purple sea urchin (Strongylocentrotus purpuratus) were 23 and 262 µg/litre
for embryo development (120 h) and gamete fertilization (80 min), respectively. Using the latter end-point,
these authors also report EC50 values of 383 and 28 µg/litre for the green sea urchin (S. droebachiensis) and
the sand dollar (Dendraster excentricus).

Baird et al. (1991) found that the 48-h EC50 for zinc for different clones of Daphnia magna ranged from 0.76
to 1.83 mg/litre. Hietanen et al. (1988) exposed the common mussel Mytilus edulis to increased zinc
concentrations in brackish water (salinity 7%) at a temperature of 12 °C. The 24-h EC50 values, based on an
increased opening response and on byssal attachment, were found to be 1.35 and 0.64 mg/litre respectively.
Kraak et al. (1994a) calculated the 48-h EC50, based on filtration rate, to be 1.35 mg/litre for the zebra
mussel (Dreissena polymorpha). The no-observed-effect concentration (NOEC) for the same parameter was
0.19 mg/litre.

Acute zinc toxicity data for two species of freshwater fish met the minimal requirements (Table 39). The 96-
h LC50 values for Oncorhynchus tshawytscha and O. mykiss were 1.27 and 2.6 mg/litre, respectively. Other
results for freshwater fish ranged from 0.061 to 52 mg/litre.

Data on three marine fish species were acceptable (Table 40). The 96-h LC50 values ranged from 21.5
mg/litre for grey mullet (Chelon labrosus) to 176.6 mg/litre for Rivulus marmoratus. A 96-h LC50 range of
2.88 to 129.5 mg/litre was found in the other reported data.

Norberg & Mount (1985) calculated the 7-day LC50 for the fathead minnow (Pimephales promelas) to be
0.238 mg/litre in Lake Superior water (hardness 48 mg/litre, CaCO3). No zinc-induced growth inhibition was
observed at 0.18 mg/litre but survival was significantly lower at that concentration. The maximum
acceptable toxicant concentration was estimated to be 0.125 mg/litre. Magliette et al. (1995) exposed larval
fathead minnow (Pimephales promelas) to zinc bromide in 7-day static renewal tests. The 7-day LC50 and
EC50 (growth), based on measured concentrations, were 0.78 and 0.76 mg/litre respectively. The lowest-
observed-effect concentration (LOEC) for growth was 0.63 mg/litre.

Reader et al. (1989) found that mortality in brown trout (Salmo trutta) exposed to zinc at a concentration of
281 µg/litre at pH 6.5 in soft water (calcium 22 µmol/litre) remained low during 30-day exposures, while in
fish exposed to 0.316 mg/litre at pH 4.5, mortality was greater than 80%.

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Mount et al. (1994) fed rainbow trout (Oncorhynchus mykiss) on a brine shrimp (Artemia sp.) diet containing
zinc at concentrations of 920, 930 or 1900 mg/kg dw for up to 60 days. No significant mortality or effect of
zinc on growth was observed during the experiment. Spry et al. (1988) fed rainbow trout (O. mykiss) on a
purified diet containing zinc concentrations of 1, 90 and 590 mg/kg, which ranged from deficient to
excessive. Fish were simultaneously exposed to zinc concentrations in water of up to 0.5 mg/litre for 16
weeks. There was no significant difference in the physical condition of fish in any treatment compared with
controls.

Chronic and long-term toxicity

Data that meet the selection criteria are presented in Table 41 for freshwater invertebrates and in Table 42 for
freshwater fish. No data are presented for marine and estuarine species. Table 41 contains data for four
invertebrate species, two crustaceans, an insect and a snail, tested under a variety of experimental conditions
and in waters of different pH (6.9–8.39), hardness (15–197 mg/litre, CaCO3) and humic acid concentration.
The threshold zinc concentrations range from 25 to 225 µg/litre (both values for D. magna) and clearly
illustrate the influence of water hardness and humic acid concentration on zinc toxicity.

Table 41 (a) Long-term and chronic toxicity to freshwater invertebratesa

Species Life End-point pH Hardness Humic acid

stage/age (mg/litre) (mg/litre)

Water flea < 24 h survival (LC50) 7.74 45.3 –

Daphnia magna
production of 7.74 45.3 –

young (EC50)

production of 8.39 51.9 –

young (MATC) 8.32 101.8 –

8.29 197 –

8.29 197 1.5

8.39 51.9 1.5

Ceriodaphnia dubia < 24 h production of 8 97.6 –

young (MATC) 113.6

182

Midge eggs survival (LC50) 7.5 46.8 –

Tanytarsus dissimilis

Snail adults eggs per capsule 6.9 15–15.3 –

Ancylus fluviatilis (NOEC–LOEC)

Table 41 (b) Long-term and chronic toxicity to freshwater invertebratesa

Species Temp Duration Threshold Reference

(° C) (days) (zinc in
µg/litre)

18 21 158

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Water flea Biesinger &

18 21 102
Daphnia magna Christensen (1972)

20 50 25 Paulauskis & Winner

(1988)
20 50 87.5

20 50 175 Paulauskis & Winner

(1988)
20 50 225

20 50 100

Ceriodaphnia dubia 25 7 22 Belanger & Cherry

(1990a)
71

71

Midge 22 10 36.8 Anderson et al. (1980)

Tanytarsus dissimilis

Snail – 31 105–187 Willis (1988)

Ancylus fluviatilis

LOEC = lowest-observed-effect concentration; MATC = maximum acceptable toxicant contamination;

NOEC = no-observed-effect concentration

a Measured zinc concentrations were ± 15% at nominal concentrations.

Table 42 (a) Long-term and chronic toxicity to freshwater fish

Species Life stage/ End-point pH Hardness Humic acid

age (mg/litre) (mg/litre)

Brachydanio rerio embryo- hatchability 7.5 100 –

larval (NOEC)

Phoxinus phoxinus yearling growth 7.5 (3.9 dH; –

(MATC) alkalinity; 64
mg/litre)

Oncorhyncus mykiss yearling growth and 7.3 374 –

(45 g) hypoglycaemia
(MATC)

Pimephales promelas males avoidance 8.1 318 –

(4.6 g) (MATC)

P. promelas full life cycle critical end-point 7–8 46 –

(MATC)

O. nerka adult survival, fertility, 7.2 35 –

embryo– fecundity, growth,
juvenile osmoregulation,
acclimation
(MATC)

Salvelinus fontinalis 7.0–7.7 45 –

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3-generation all life-cycle

life-cycle parameters (egg
fragility was
critical end-point)
(MATC)

Table 42 (b) Long-term and chronic toxicity to freshwater fish

Species Temp Duration Threshold Reference

(° C) (days) (µg zinc/litre

Brachydanio rerio 25 16 500 Dave et al. (1987)

Phoxinus phoxinus 12 150 80.6 Bengtsson (1974a)

Oncorhyncus mykiss 10 100 763 Watson & McKeown

(1976)

Pimephales promelas 20 7.5 130.5 Korver & Sprague (1989)

P. promelas 25 154 106 Benoit & Holcombe (1978)

O. nerka 9–14 21 months 164.6 Chapman (1978a)

Salvelinus fontinalis 9 3 generations 852 Holcombe et al. (1979)

MATC = maximum acceptable toxicant contamination ; NOEC = no-observed-effect concentration

With respect to freshwater fish (Table 42), there are primary chronic toxicity data for six species covering
water hardness ranging from 35 to 374 mg/litre, CaCO3. For water hardness of > 100 mg/litre, CaCO3, all
NOECs are > 500 mg/litre, except in one behavioural study (Korver & Sprague, 1989), which reported a
NOEC of 60 mg/litre. For studies in which water hardness was < 100 mg/litre, CaCO3, all NOECs were < 50
mg/litre.

Freshwater studies

Farris et al. (1989) studied growth and cellulase activity in the Asiatic clam (Corbicula sp.) during a 30-day
exposure to zinc sulfate concentrations ranging from 0.034 to 1.1 mg/litre. The cellulase index declined
following weight and shell loss between days 20 and 30 at the lower dose and by day 30 the growth rate was
only 50% of controls. At the higher dose, animals did not grow after 5 days and had a rapidly declining
cellulase index; 50% of the clams at this exposure concentration died.

Münzinger & Guarducci (1988) exposed the freshwater snail Biomphalaria glabrata to increased zinc
concentrations (0.5 to > 5.0 mg/litre) for 33 days. At a zinc concentration of 1.5 mg/litre, 60% of young
snails and 20% of adults died; at concentrations of > 3.0 mg/litre no snails survived. Egg capsules were
produced at zinc concentrations of up to 1.5 mg/litre. The number of eggs per capsule and the fecundity of
the molluscs were significantly reduced by zinc exposure.

Mirenda (1986) calculated the 2-week LC50 for zinc for the crayfish (Orconectes virilis) to be 84 mg/litre in
soft water (26 mg/litre, CaCO3). Bodar et al. (1989) exposed parthenogenetic eggs of Daphnia magna to zinc
concentrations of 10, 50 and 100 mg/litre. Exposure at 10 and 50 mg/litre had no significant effect on death
rates in the six early life stages. There was no effect of zinc on survival, even at the highest exposure
concentration, during developmental stages 1 and 2 (these stages take about half of the development time
from egg to juvenile). The toxicity of zinc at 100 mg/litre was exerted during stages 3–6. Winner (1981)
studied the toxicity of zinc to Daphnia magna in lifetime exposure tests. Zinc caused a significant reduction
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in body length of primiparous animals and longevity at concentrations of > 0.1 mg/litre; however, mean
brood sizes of animals reared at 0.2 mg/litre were not significantly different from those of control animals.
Winner & Gauss (1986) found that an increase in water hardness from 52 to 102 mg/litre (CaCO3) resulted in
a significant reduction in zinc toxicity as estimated from survival curves over a 50-day exposure to zinc at
0.125 mg/litre. The addition of humic acid (1.5 mg/litre) to soft water (52 mg/litre, CaCO3) significantly
increased survival.

Paulauskis & Winner (1988) studied the effect of zinc on the brood size of Daphnia magna in chronic (50-
day) toxicity tests. An increase in water hardness from 50 to 200 mg/litre (CaCO3), and the addition of
humic acid (1.5 mg/litre) significantly reduced the toxic effect of zinc on brood size. NOEC values were 0.1
and 0.025 mg/litre in soft water with and without humic acid and 0.225 and 0.175 mg/litre in hard water with
and without humic acid, respectively.

Belanger & Cherry (1990) exposed Ceriodaphnia dubia to zinc in reproductive toxicity tests at three pH
levels (6, 8 and 9) in three different surface waters from Virginia and Louisiana, USA. In New River water
(hardness, 97.6 mg/litre, CaCO3) significant reproductive impairment, as measured by the number of young
per female, was found at a zinc concentration of 0.025 mg/litre at pH 6 and 8, while in Amy Bayou water
(hardness, 113.6 mg/litre, CaCO3) significant reproductive impairment was noted at 0.1 mg/litre.
Reproductive impairment was found at 0.05 mg/litre in Clinch River water at pH levels of 6 and 9 but not 8.

Biesinger & Christensen (1972) exposed Daphnia magna to zinc chloride for 3 weeks. The 3-week LC50 was
0.16 mg/litre; the 3-week EC50, based on reproductive impairment, was 0.10 mg/litre. Enserink et al. (1991)
calculated the 21-day LC50 for Daphnia magna to be 0.84 mg/litre in Lake Ijssel water (background zinc
concentration < 0.01 mg/litre; hardness, 225 mg/litre, CaCO3). An EC50 based on population growth was
0.57 mg/litre. Münzinger & Monicelli (1991) carried out 21-day tests on Daphnia magna at added zinc
concentrations of 0.05, 0.10 or 0.15 mg/litre in lake water (total zinc < 6 µg/litre). No significant effects on
survival or reproduction were reported at the two lower concentrations. At 0.15 mg/litre, mortality was 80%,
the number of progeny was reduced by more than 50%, and primiparous individuals were significantly
smaller and produced significantly fewer eggs.

Wong (1993) studied the effect of zinc on the longevity and reproduction of the cladoceran Moina
macrocopa reared in aquarium water with a zinc content of less than 1 µg/litre. A significant reduction in
survival was observed at < 0.5 mg/litre within 1 day. The LT50 (time taken for 50% of animals to die) was
reduced by more than 2 days at a zinc concentration of > 0.45 mg/litre and the average life span was reduced
by more than 50% at > 0.70 mg/litre compared to controls. The net reproductive rate decreased abruptly at
0.7 mg/litre.

Maltby & Naylor (1990) exposed Gammarus pulex to zinc concentrations of 0.1, 0.3 or 0.5 mg/litre in 7-day
tests. Zinc had no significant effect on either the number or size of offspring released from the current brood
or on the number of offspring released from the subsequent brood, incubated under non-stressed conditions.
The metal did cause a significant reduction in the size of offspring released from the subsequent brood and a
positive correlation between zinc concentration and the number of broods aborted.

Anderson et al. (1980) calculated a 10-day LC50 for zinc for the midge Tanytarsus dissimilis reared in
unfiltered Lake Superior water (background zinc concentration 5.1 µg/litre) to be 0.037 mg/litre. The midges
were exposed to zinc during embryogenesis, hatching and larval development to the 2nd or 3rd instar. In
flow-through life-cycle tests with caddisfly (Clistoronia magnifica), the highest zinc concentration tested, 5.2
mg/litre, had no significant effect on any life stage (Nebeker et al., 1984).

Dave et al. (1987) reported the results of a ring test of the 16-day embryo-larval toxicity test on zebrafish
(Brachydanio rerio) using zinc sulfate as the toxicant. Hatching time delay was found to be the most
sensitive parameter, with an NOEC of 0.5 mg/litre. Dawson et al. (1988) studied the effect of zinc on fathead
minnow (Pimephales promelas) and South African clawed toad (Xenopus laevis) in embryo-larval assays.
Static renewal tests were conducted for 6 days with minnow embryos to allow for hatching to take place and
for 4 days with toad embryos. LC50 values were found to be 3.6 mg/litre for fathead minnows and 34.5
mg/litre for toad embryos. EC50 values, based on malformation, were 0.8 and 3.6 mg/litre for the two
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species, respectively; the minimum concentrations that significantly inhibited growth were 0.6 and 4.2
mg/litre, respectively.

Sayer et al. (1989) exposed yolk-sac fry of brown trout (Salmo trutta) to zinc concentrations of 4.9, 9.8 and
19.5 µg/litre (75, 150 and 300 nmol/litre) at pH 4.5 and calcium concentrations of 20 or 200 µmol for 30
days. Mortalities were high (70–100%) at the lower calcium concentration for all three zinc concentrations.
No deaths or significant effects on mineral uptake were observed for zinc at the higher calcium exposure.

Bengtsson (1974a) exposed both yearling and adult minnows (Phoxinus phoxinus) to zinc as zinc nitrate in
freshwater (< 0.02 mg/litre) over a 150-day period. Yearlings were the most sensitive, with growth
significantly reduced at 0.13 mg/litre. Suppressed growth was associated with reduced feeding activity.

Chapman (1978a) studied the chronic toxicity of zinc to sockeye salmon (Oncorhynchus nerka) in a 22-
month adult-to-smolt toxicity test. Fish were exposed to zinc concentrations ranging from 30 to 242 µg/litre
in well-water (background zinc concentration 2 µg/litre; hardness, 35 mg/litre, CaCO3). No adverse effects
on survival, fertility, fecundity, growth or the subsequent survival of smolts transferred to seawater were
observed.

Spehar (1976) exposed flagfish (Jordanella floridae) to zinc concentrations ranging from 28 to 267 µg/litre
during a complete life-cycle test in untreated Lake Superior water (background zinc concentration 10
µg/litre; hardness, 44 mg/litre, CaCO3). The 30-day survival of larvae previously exposed to zinc as embryos
was significantly reduced at 267 µg/litre, while growth (100 days) was significantly reduced at 139 µg/litre.
Reproduction was unaffected at zinc concentrations of up to 139 µg/litre. In a second experiment, fish were
not exposed as embryos and significant reductions were observed in survival at 85 µg/litre after 30 days. The
growth of female fish (100 days) was significantly reduced at 51 µg/litre. It should be noted that background
zinc concentrations were less than 1 µg/litre in the second experiment. Spehar et al. (1978) found that
cadmium (4.3–8.5 µg/litre) did not influence the mode of action of zinc under the same experimental
conditions. The joint action of the toxicants on survival was little different from the toxicity of zinc alone.

Benoit & Holcombe (1978) carried out fathead minnow (Pimephales promelas) life-cycle tests in Lake
Superior water (mean total zinc 2 µg/litre) at total zinc concentrations ranging from 44 to 577 µg/litre. The
most sensitive parameters were egg adhesiveness and fragility, which were significantly affected at 145
µg/litre but not at 78 µg/litre. Hatchability and survival of larvae were significantly reduced, and deformities
at hatching significantly increased at > 295 µg/litre.

Holcombe et al. (1979) found no significant harmful effects on brook trout (Salvelinus fontinalis) exposed to
zinc concentrations ranging from 2.6 (control) to 534 µg/litre for three generations in Lake Superior water. In
a second experiment, a zinc concentration of 1368 µg/litre significantly reduced both the survival of embryos
and 12-week-old larvae.

Kumar & Pant (1984) studied the toxic effects of zinc on the gonads of the fish Puntius conchonius exposed
to one-third of the 96-h LC50 for zinc (which is 33.26 mg/litre) for up to 4 months. Male fish showed dilation
in the testicular blood capillaries with necrosis and disintegration of the seminiferous tubules. Significant
atresia in the ovary and damage to younger oocytes was found in female fish.

Watson & McKeown (1976) exposed yearling rainbow trout (Oncorhynchus mykiss) to zinc concentrations
ranging from < 0.1 (control) to 1.12 mg/litre for up to 63 days. Growth was significantly inhibited at 1.12
mg/litre. Significant hyperglycaemia was found at all zinc exposure concentrations after 7 days but the
condition remained significant by the end of the experiment only at 1.12 mg/litre.

Nemcsók et al. (1984) found that zinc chloride (1, 10 or 50 mg/litre) did not decrease acetylcholinesterase
activity in serum, brain, heart or muscle of common carp (Cyprinus carpio) exposed for 2 h.

Korver & Sprague (1989) analysed the ability of male fathead minnows (Pimephales promelas) to avoid zinc
concentrations ranging from 0.02 (control) to 13.5 mg/litre for up to 180 min. The LOEC was found to be
0.284 mg/litre; however, when fish were exposed in the presence of a shelter, the LOEC was 1.83 mg/litre.

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Bengtsson (1974b) studied the effect of zinc on the ability of minnows (Phoxinus phoxinus) to compensate
for a rotating water mass. Fish were exposed for approximately 100 days and significant adverse effects were
found at 0.06 mg/litre for under yearlings, 0.16 mg/litre for yearlings and 0.2 mg/litre for adults.

Seawater studies

Calabrese et al. (1973) exposed eggs of American oyster (Crassostrea virginica) from within one hour of
fertilization for 42- 48 h to zinc chloride under static conditions (26 °C; salinity 25%). An EC50 based on
embryonic development was calculated to be 0.31 mg/litre. In similar tests, Calabrese & Nelson (1974)
found the EC50 for the hard clam (Mercenaria mercenaria) to be 0.166 mg/litre. Calabrese et al. (1977)
found the 8–10 day LC50 and an EC50, based on growth, for hard clam larvae (Mercenaria mercenaria) to be
195.4 and 61.6 µg/litre, respectively, when tested in natural seawater. The values do not include the
background zinc concentration of 17.7 µg/litre. Strömgren (1982) studied the effects of zinc on growth of the
common mussel Mytilus edulis in tests of 10–22 days. Zinc concentrations ranging from 0.01 to 0.20 mg/litre
were added to local seawater (background zinc concentration 5 µg/litre). Significant reductions in growth
were observed at 0.01 mg/litre; an EC50 of 0.06 mg/litre was calculated for days 2–6.

Hunt & Anderson (1989) exposed the red abalone Haliotis rufescens to increased zinc concentrations in
natural seawater. A 48-h EC50, based on larval development, and a 9-day EC50, based on metamorphosis,
were found to be 0.068 and 0.050 mg/litre, respectively; NOEC values for the two parameters were 0.037
and 0.019 mg/litre, respectively.

Dinnel et al. (1989) exposed the purple sea urchin (Strongylocentrotus purpuratus), green sea urchin
(Strongylocentrotus droebachiensis) and red sea urchin (Strongylocentrotus franciscanus) to zinc in 120-h
sperm/fertilization tests. The sand dollar (Dendraster excentricus) was exposed to zinc in a 72-h test. EC50
values were found to be 0.26, 0.38, 0.31 and 0.028 mg/litre in the sperm test for the four species,
respectively.

Reish & Carr (1978) found that the reproduction of the polychaetous annelids Ctenodrillus serratus and
Ophryotrocha diadema was significantly inhibited at zinc concentrations of > 0.5 mg/litre in 21-day tests.

Bengtsson & Bergström (1987) found that the 13-day EC50, based on fecundity, for the harpacticoid copepod
Nitocra spinipes ranged from 0.17 to 0.43 mg/litre. There was no significant effect of salinity, which ranged
from 7% to 25%.

Price & Uglow (1979) found the LT50 for the marine shrimp Crangon crangon to be 130 h at a zinc
concentration of 14.4 mg/litre. When the test was carried out on various moult stages, LT50 values were 64,
140 and 152 h for the post-moult, inter-moult and pre-moult stages respectively.

Macdonald et al. (1988) exposed embryos of yellow crab (Cancer anthonyi) to zinc in 7-day tests. Zinc
concentrations of > 0.1 mg/litre significantly reduced survival. Hatching of embryos and larval survival were
significantly reduced at 0.01 mg/litre; no embryos hatched at zinc concentrations of >1.0 mg/litre.

Redpath & Davenport (1988) reported that the pumping rate in the common mussel (Mytilus edulis)
decreased with increasing zinc concentration and stopped completely at zinc concentrations in the range
0.47–0.86 mg/litre.

Weeks (1993) found a significant reduction in the feeding rate of the talitrid amphipod Orchestia
gammarellus at dietary zinc concentrations ranging from 63 to 458 mg/kg during 48-h tests. However, no
significant effect was found in 20-day exposures.

Somasundaram et al. (1984a) exposed the Atlantic herring (Clupea harengus) to zinc concentrations ranging
from 0.1 to 6 mg/litre for up to 408 h. Zinc concentrations of > 2 mg/litre significantly decreased total egg
and yolk volumes throughout the study. At zinc concentrations of 0.1, 0.5 and 2.0 mg/litre, the development
rate of eggs was faster than controls but at 6 mg/litre the rate was slower.

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Somasundaram et al. (1984b) incubated eggs of Atlantic herring (Clupea harengus) at four zinc
concentrations (0.5, 2.0, 6.0 and 12.0 mg/litre). The ultrastructural changes in the trunk muscle tissue of
larvae hatched from the eggs were examined by morphometric analysis. The mean relative volumes of
mitochondria, sarcoplasmic reticulum and muscle fibre were significantly increased and the surface:volume
ratio of the mitochondrial cristae was significantly reduced. The ultrastructural changes in brain cells of
larvae were also examined (Somasundaram et al., 1984c). All zinc exposures caused significant swelling of
the nuclear membranes and rough endoplasmic reticulum, an increase in intracellular spaces and a decrease
in the relative volumes of mitochondria. Somasundaram et al. (1985) studied the ultrastructural changes in
the posterior gut and pronephric ducts of the herring larvae. Significant changes were observed only at zinc
concentrations of 6.0 and 12.0 mg/litre; the endoplasmic reticulum, perinuclear space and mitochondria were
swollen and there was a reduction in the surface:volume ratio of the mitochondrial cristae. At the highest
zinc concentration, the posterior gut cells showed signs of necrosis. Examination of the epidermal structure
revealed more vesicles and intracellular spaces in the epidermal cells, swollen mitochondria and signs of
necrosis at zinc concentrations of 6.0 or 12.0 mg/litre (Somasundaram, 1985).

9.1.2.3 Effects on communities

Mesocosms

Belanger et al. (1986) exposed the Asiatic clam (Corbicula sp.) to zinc concentrations ranging from 0.025 to
1 mg/litre for 30 days in outdoor artificial stream systems. Background total zinc concentrations ranged from
0.02 to 0.094 mg/litre. Zinc concentrations of > 0.05 mg/litre significantly reduced weight gain between days
20 and 30. Exposures to zinc at 1 mg/litre resulted in mortality of 10- 50% by day 30.

Genter et al. (1988) added zinc at a concentration of 0.5 mg/litre to a flow-through stream mesocosm and
studied the effects on an established periphyton community for 30 days. Seven diatoms and a coccoid green
alga were significantly inhibited by zinc exposure. The algal total biovolume-density was reduced to < 5% of
control levels by zinc from days 5–30. Zinc addition reduced protozoan numbers by more than 50%.

Marshall et al. (1983) conducted in situ experiments in Lake Michigan (background zinc concentration ~ 1
µg/litre) to determine the responses of the plankton community to added zinc for 2 weeks. Total zinc
concentrations of 17.1 µg/litre significantly reduced chlorophyll a, primary productivity, dissolved oxygen,
specific zooplankton populations and zooplankton species diversity.

Niederlehner & Cairns (1993) studied the effect of zinc on a naturally-derived periphyton community
collected from a 195-ha lake (pH 7.1; hardness, 12.6 mg/litre; background zinc concentration 13.3 µg/litre).
Toxicity tests with added zinc at concentrations of 73 and 172 µg/litre were carried out in dechlorinated tap
water (pH 7.78; hardness, 73.8 mg/litre; zinc 1.3 µg/litre) for 21 days. Species richness was significantly
impaired at the higher zinc exposure; primary production and community respiration were impaired at both
zinc concentrations. The community was then exposed to pH levels ranging from 3 to 4.5 for 48 h. The pH
stress significantly reduced species richness from the initial levels in controls and at both zinc
concentrations. No significant differences between zinc treatments were observed at pH < 4.0.

Colwell et al. (1989) studied the effect of zinc on epilithic communities in artificial streams. Zinc
concentrations of 0.05 and 1 mg/litre were added to the streams (background zinc concentration 0.02
mg/litre). After 30 days, greater biomass and lower protein:carbohydrate ratios were evident in epilithon
exposed to the highest zinc concentration compared to the controls. Metal-tolerant populations had replaced
metal-sensitive organisms by the end of the experiment at the higher zinc exposure.

Kiffney & Clements (1994) exposed benthic macroinvertebrate communities from two different sites to zinc
(130 µg/litre) for 7 days. The background zinc concentrations at the two collection sites and in the artificial
stream were below detection limits. Significant effects were observed at the community and population level
following the addition of zinc. Specifically, mayflies from both sites were sensitive to zinc, but the
magnitude of the response varied between sites. The results indicated that benthic macroinvertebrate
communities from different stream orders may vary in sensitivity to zinc.

Field observations

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Etxeberria et al. (1994) reported that increasing environmental levels of bioavailable zinc are associated with
enlarged digestive lysosomes in mussels.

Solbé (1977) found that macroinvertebrates and fish were adversely affected by effluent from a steel works
entering a hard water stream that had its source in the neighbouring limestone hills. The observed
concentration of dissolved zinc in the river was 25 mg/litre; ammonia was the only other contaminant found
at concentrations toxic to aquatic life, and it was quickly oxidized.

Graham et al. (1986) found increased mortality of rainbow trout (Oncorhynchus mykiss) at zinc-
contaminated sites on the Molonglo River, New South Wales, Australia when compared with non-
contaminated sites on the same river. Zinc concentrations of up to 2.32 mg/litre in the water and 1016 mg/kg
dw in gill tissue were reported. The authors concluded that the concentrations of copper measured in the
water were not sufficiently high to be lethal to the fish, although copper could have acted synergistically with
zinc.

Hogstrand et al. (1989) reported that hepatic levels and metallothionein in perch (Perca fluviatilis) caught
downstream from a brass works in Sweden reflected the water concentration of zinc (0.56–59 µg/litre). A
significant correlation was found between hepatic zinc and metallothionein levels.

Clements & Kiffney (1995) examined benthic macroinvertebrate community responses to heavy metals at 33
sites in six Colorado streams (USA) in which zinc concentrations ranged from 2 to 691 µg/litre. The number
of taxa and species richness of mayflies (Ephemeroptera), and the abundance of most mayfly and stonefly
taxa were significantly reduced at sites where the zinc concentration exceeded the hardness-based criterion .

Van Tilborg (1996) reported on a freshwater stream in Belgium (the Kleine Nete) which contained total zinc
at an average of 60 µg/litre (range <20–140 µg/litre). According to the Belgian Biotic Index, this stream has
a high quality ecosystem.

9.1.3 Terrestrial organisms

9.1.3.1 Plants

Geochemical differences in zinc concentrations in soils and autonomic selection processes during the
evolution of plants result in a great variation in zinc demand and zinc content between plant species and
between plant genotypes of the same species. As a general rule, plants from environments poor in zinc are
characterized by low zinc concentrations, those from zinc-enriched environments by high concentrations
(Ernst, 1996). Within each ecosystem, biodiversity can only be maintained if species differ in their various
ecological niches; zinc-demand is one variable. There is no convincing explanation as to why certain plant
species have a higher uptake rate and accumulation pattern of zinc than others, although one possible reason
may be to develop a defence against herbivores by accumulating high metal levels (Ernst et al., 1990). A
great variation of zinc content is well known in forest ecosystems growing on soils with a normal zinc
content. This variation is due to a number of factors including changes in the degree of infestation with
endomycorrhizal fungi during a growing season and changes in ectomycorrhizal partners during the life
history of the plant. When comparing zinc-sensitive and zinc-tolerant genotypes, it was found that, in zinc-
tolerant genotypes only, the rapid compartmentation of zinc in the vacuole is one reason for an increased
demand for zinc (Mathys, 1977). Zinc-activated enzymes, such as carbonic anhydrase, therefore reach the
same activity in tolerant plants at higher external zinc concentrations than in zinc-sensitive plants. This
response pattern has to be interpreted as a decrease in zinc efficiency in zinc-tolerant plants given the same
level of zinc uptake by both genotypes (Harmens et al., 1993a). Zinc tolerance in plants is coded by only two
major genes (Schat et al., 1996). Whether these genes are related to the zinc-efficiency genes reported from
soybean varieties (Hartwig et al., 1991) remains to be investigated.

Therefore critical zinc levels cannot be established by analysing only the zinc content of leaves or other plant
tissues; it is necessary to test the zinc demand of the plant genotype, its potential for physiological flexibility
(allocation and retranslocation) (Ernst, 1995), siderophore exudation (Von Wirén et al., 1996), and cellular
zinc compartmentation. The aim should be to establish the range of effects on the physiological processes
under consideration from no effect up to 100% effect.

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Toxicity to plants grown hydroponically and in soil

All such experiments involve acute toxicity, defined as toxicity over less than one life cycle in duration (seed
to seed: cereals, rape, trees) or a harvest cycle (spinach, lettuce, cabbage). Zinc toxicity is first expressed in
reduced root growth, a parameter that is used routinely in testing zinc-resistance in plants (Antonovics et al.,
1971; Wainwright & Woolhouse, 1977; Schat et al., 1996). In higher plants the toxicity of zinc increases with
exposure time, and therefore increasing zinc concentration in the plant and translocation from root to shoot
(Mitchell & Fretz, 1977; Rauser, 1978; Dijkshoorn et al., 1979; Davies, 1993; Sheppard et al., 1993).

Zinc toxicity affects general physiological processes, e.g., transpiration, respiration and photosynthesis, and
plant development in general can be visibly inhibited. Stunted growth, leaf epinasty and chlorosis of the
younger leaves are striking symptoms of strong zinc toxicity. However, at lower degrees of zinc toxicity,
these visible symptoms are less pronounced or can even be absent, whereas at the cellular level several
processes are affected, owing to increases in local metal concentrations. Several mechanisms of metal action
at the physiological and biochemical level have been described (for a review see Chaney, 1993;
Vangronsveld & Clijsters, 1994), ranging from disturbance of cell division (Powell et al., 1986a,b; Davies et
al., 1991) and ion balance (Ernst, 1996) to inhibition of photosynthesis (Van Assche & Clijsters, 1986). In
Phaseolus vulgaris, growth inhibition and stress enzyme induction were both observed to occur when exactly
the same internal zinc concentration was exceeded (Van Assche et al., 1988).

The critical leaf tissue concentration of zinc at which growth is affected was found for many plant species to
be between 200 and 300 mg/kg dry matter (Davis & Beckett, 1978; Van Assche et al., 1988; Balsberg
Påhlsson, 1989; Vangronsveld & Clijsters, 1992; Mench et al., 1994; Marschner, 1995). However, zinc
phytotoxicity in leaves can depend to a large extent on the plant species, the age of the leaf and other factors,
such as exposure period and exposure concentration.

Evaluations of phytotoxicity of zinc-polluted substrata are generally made by chemical analysis of the
substratum itself. These results give rise to misinterpretations since availability of zinc to plants in and
consequently metal uptake from the substratum are functions of the chemical form of the element in the soil,
several soil parameters (e.g., pH, organic matter content, soil type) and plant species. Moreover, soils are
frequently contaminated by a mixture of metals. Each of these materials separately can be phytotoxic, or they
can interact in a synergistic, antagonistic or cumulative way (Beckett & Davis, 1978) (see section 9.3). The
physiological and metabolic responses of test plants can be considered as a biological criterion for the total
phytotoxic effect, since they are the result of the interactions of the metals present in the soil with other soil
factors (biotic or abiotic) and with the plant. Phytotoxicity responses of test plants grown under controlled
environmental conditions only reflect further the interference with metabolic processes of metals assimilated
through the roots. Morphological responses (e.g., root growth, stem elongation, leaf expansion, biomass) and
physiological and biochemical parameters (respiration, photosynthesis, capacities of enzymes and isozyme
patterns, but not phytochelatin levels) can be used for the evaluation of phytotoxicity (Van Assche &
Clijsters, 1990; Vangronsveld & Clijsters, 1992; Harmens et al., 1993b) (Tables 43- 44).

Table 43. Impact of zinc-enriched sewage sludge added to non-dried sassafras sandy loam on crop
plants (after Chaney, 1993)

Crop species Yield as % of control Geometric mean of Chlorosisa

zinc shoot
(mg/kg dry weight)

Red fescue 17.2 965 1.8

Tall fescue 69.8 1060 1.7

Canadian blue grass 16.4 898 2.3

Cyperus 33.6 580 3.1

Barley 57.6 1060 1.4

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Soybean 11.4 1140 4.2

Lettuce 1.2 3620 4.6

a Range of 1–5 with 5 being severe chlorosis.

Table 44. Acute toxicity of zinc to plants grown in hydroponic culture or soil

Plant species Exposure End-point Toxicity Parameter Reference

data
Concentration Time
(mg/litre) (days)

Hydroponic culture 0–450 16 biomass, NOEC 8.3–27.2 mg/litre Davis &

Hordeum vulgare concentration Beckett
168–460 mg/kg dw (1978)

LD100 150–800 mg/litre

1000–8000 mg/kg
dw

Phaseolus vulgaris 0.975–26 4 biomass, NOEC 0.975 mg/litre Rauser

starch (1978)
content EC50 26 mg/litre

Phaseolus vulgaris 0–1990 16 primary leaf NOEC 189–266 mg/kg dw Van

physiology Assche et
and zinc EC50 500 mg/kg dw al. (1988)
concentration (for shoot length)

Allium cepa 6.5–65 2 root length NOEC 6.5 mg/litre Arambasic

et al.
EC50 25.9 mg/litre (1995)

Lepidium sativum 65–164 2 root length NOEC 65 mg/litre Arambasic

et al.
EC50 547 mg/litre (1995)

Lolium perenne 0–30 14 root length NOEC < 0.1 mg/litre Wong &
Bradshaw
EC50 1.6 mg/litre (1982)

Festuca rubra 0–0.2 4 mitosis Powell et

al. (1986a)
zinc-sensitive EC17 0.2 mg/litre

zinc-tolerant +NOEC 0.2mg/litre

Acer rubrum 0–0.4 78 root growth, EC50 0.05 mg/litre Mitchell &
zinc content Fretz
zinc root 2190 mg/kg dw (1977)

zinc leaf 381 mg/kg dw

Picea abies 0–0.4 66 root growth, EC50 0.2 mg/litre Mitchell &
zinc content Fretz
zinc root 4125 mg/kg dw (1977)

i 1440 /k d
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zinc 1440 mg/kg dw
needle

Pinus strobus 0–0.4 78 root growth, EC50 0.2 mg/litre Mitchell &
zinc content Fretz
zinc root 9375 mg/kg (1977)

zinc 1005 mg/kg

needle

Soil

Acer rubrum 0–165 mg/kg root growth, NOEC 165 mg/kg in soil Mitchell &
pH 6.7 zinc content Fretz
zinc root 618 mg/kg dw (1977)

zinc leaf 209 mg/kg dw

Picea abies 0–165 mg/kg root growth, NOEC 165 mg/kg in soil Mitchell &
pH 6.7 zinc content Fretz
zinc root 615 mg/kg dw (1977)

zinc 127 mg/kg dw

needle

Pinus strobus 0–165 mg/kg root growth, +NOEC 165 mg/kg in soil Mitchell &
pH 6.7 zinc content Fretz
zinc root 1430 mg/kg (1977)

zinc 314 mg/kg

needle

Plantago lanceolata 9.5–614 mg/kg 6 zinc content EC50 >1010 mg/kg in Dijkshoorn
pH 4.4, 4% weeks leaf et al.
organic matter (1979)

Trifolium repens 9.5–614 mg/kg 6 zinc content EC50 800 mg/kg leaf Dijkshoorn
pH 4.4, 4% weeks et al.
organic matter (1979)

Lolium perenne 9.5–614 mg/kg 6 zinc content EC50 500- 600 mg/kg Dijkshoorn
pH 4.4, 4% weeks leaf et al.
organic (1979)

matter

NOEC = no-observed-effect concentration; dw = dry weight

Concentrations of zinc that are subtoxic or non-toxic to plants may have metabolic effects higher up the food
chain. The disappearance of herbivorous insects on zinc-tolerant plants is one example of differences in
species-specific tolerances (Ernst et al., 1990). Similarly, the zinc-content of zinc-efficient plants may be
insufficient for optimum performance of herbivorous animals and humana, especially if all the cellular zinc
is present in a form which is not readily bioavailable.

9.1.3.2 Invertebrates

Haight et al. (1982) calculated 24-h, 48-h and 72-h LC50 values for zinc of 82, 39.4 and 20 mg/litre (added
as zinc sulfate to the growth medium), respectively, for juvenile free-living nematodes (Panagrellus silusiae)
and 255, 95.1 and 47.5 mg/litre for adults.
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Neuhauser et al. (1985) exposed earthworms (Eisenia fetida) to zinc in contact and artificial soil toxicity
tests. In 48-h contact tests LC50 values were 13 µg/cm2 for zinc acetate, 12 µg/cm2 for zinc chloride, 10
µg/cm2 for zinc nitrate and 13 µg/cm2 for zinc sulfate. There were no significant differences between the
toxicities of the different zinc salts. In an artificial soil test, the 2-week LC50 was found to be 662 mg/kg.
Spurgeon et al. (1994) reported the 14-day LC50 for E. fetida to be 1010 mg/kg. The 56-day LC50 and NOEC
were 745 and 289 mg/kg respectively; the EC50 and NOEC based on cocoon production were 276 and 199
mg/kg respectively.

Neuhauser et al. (1984) exposed earthworms (E. fetida) to zinc concentrations of 1000, 2500, 5000 and 10
000 mg/kg of manure (dry weight) for 6 weeks. Zinc at > 5000 mg/kg significantly reduced growth and
cocoon production. Similar results were obtained with four different zinc salts (acetate, chloride, nitrate and
sulfate). The growth rate and reproduction had returned to normal after a subsequent 6-week period without
zinc. Malecki et al. (1982) exposed earthworms (E. fetida) to six different zinc salts for 8 weeks. Significant
reductions in cocoon production were observed at zinc carbonate and sulfate concentrations of 500 mg/kg
dw. A zinc concentration of 2000 mg/kg adversely affected reproduction (acetate, chloride and nitrate) and
growth (chloride, nitrate and sulfate). Zinc oxide significantly affected both growth and reproduction at 4000
mg/kg. Zinc carbonate did not adversely affect growth at the highest exposure (40 000 mg/kg). Long-term
studies (20 weeks) with zinc acetate revealed significant reductions in cocoon production at 5000 mg/kg. Van
Gestel et al. (1993) exposed earthworms (E. andrei) to zinc as zinc chloride at concentrations in dry artificial
soil of 100–1000 mg/kg. Zinc significantly reduced reproduction at soil concentrations of 560 and 1000
mg/kg and induced the production of malformed cocoons. EC50 values for the effect of zinc on cocoon
production and the number of juveniles per worm per week were 659 and 512 mg/kg dry soil, respectively.
At the end of a 3-week recovery period, reproduction had returned to normal.

Marigomez et al. (1986) fed terrestrial slugs (Arion ater) for 27 days on a diet containing zinc concentrations
ranging from 10 to 1000 mg/kg. No treatment-related effect on mortality was observed. Zinc concentrations
of 1000 mg/kg significantly reduced feeding activity and growth.

Beyer & Anderson (1985) fed woodlice (Porcellio scaber) for 64 weeks on soil litter containing zinc at
concentrations of up to 12 800 mg/kg. Soil litter containing > 1600 mg/kg had adverse effects on
reproduction; adult survival was reduced at > 6400 mg/kg. Woodlice fed diets containing up to 20 000 mg/kg
for 8 weeks showed decreased survival at concentrations of > 5000 mg/kg (Beyer et al., 1984).

9.1.3.3 Vertebrates

High dietary levels of zinc are frequently fed to poultry to force moulting and reduce egg deposition
(Hussein et al., 1988). Stahl et al. (1990) fed hens on a diet containing zinc at concentrations of 48, 228 or
2028 mg/kg for 12 or 44 weeks. Zinc treatments had no effect on overall egg production, feed conversion,
feed consumption, hatchability, or progeny growth to the age of 3 weeks. Zinc levels were elevated in eggs
from hens fed the diet containing 2028 mg/kg, but chick performance and tissue zinc content were unaffected
by maternal zinc nutritional status. Stahl et al. (1989) fed chicks on a diet containing zinc at 37 (control), 100
or 2000 mg/kg for 21 days. There were no zinc-related deaths; at the highest exposure growth rate was
decreased, anaemia was evident, tissue copper and iron decreased and tissue zinc increased.

Japanese quail (Coturnix coturnix japonica) fed a diet containing zinc (as zinc oxide) at 15 000 mg/kg for 7
days showed significant reductions in body weight. Egg production approached zero on day 3, eggshell
breaking strength was reduced and moulting was induced (Hussein et al., 1988).

Dewar et al. (1983) fed 2-week-old chicks on a diet containing zinc at 74 (controls), 2000, 4000 or 6000
mg/kg for 4 weeks. High mortality was noted at the highest dose; all groups receiving zinc-supplemented
food showed an increased incidence of gizzard and pancreatic lesions. Similar results were found when 1-
day-old chicks were fed a diet containing zinc at 1000, 2000 or 4000 mg/kg for 4 weeks and when hens were
fed diets containing 10 000 or 20 000 mg/kg for only 4 days. No lesions were found in hens exposed for 4
days to 10 000 mg/kg followed by 28 days on a control diet. Dean et al. (1991) fed day-old male chicks a
diet containing zinc at 73 (controls) or 5280 mg/kg for 4 weeks. The zinc-supplemented feed significantly
decreased body weight but did not affect food consumption compared with controls. Serum cholesterol,
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thyroxine and triiodothyronine levels were significantly reduced; serum growth hormone was significantly
reduced but had recovered by the end of the experiment.

Gasaway & Buss (1972) maintained young mallard duck (Anas platyrhynchos) on a diet containing zinc
concentrations ranging from 3000 to 12 000 mg/kg for 60 days. Food intake and body weight showed
decreases as the level of zinc in the diet increased. Zinc caused reductions in pancreas and gonad weight in
relation to body weight. The ratio of adrenals and kidney to body weight increased significantly. No
significant changes in the liver:body weight ratios were observed. In ducks exposed to zinc there was partial
paralysis of the legs, diarrhoea and weight loss within 10 days; severe paralysis was noted in some ducks
within 20 days. Slight anaemia was found after 30 days but by day 45 extreme anaemia was observed in
most of the exposed birds. High mortality was noted in all groups during the 60-day experiment with only 2
of the 45 exposed ducks surviving the whole time period. Zinc toxicosis consisted of paralysis of the legs,
high concentrations of zinc in pancreas and kidney, and yellowish-red kidneys.

Zinc poisoning of birds has been reported as a result of the ingestion of zinc, for instance, from wire mesh
cages (Van der Zee et al., 1985; Reece et al., 1986). Grandy et al. (1968) dosed mallard ducks (A.
platyrhynchos) orally with eight No. 6 zinc shot and observed them for 30 days: three of the 15 birds died
within the observation period. The average weight loss among surviving birds was 22%, significantly more
than in control birds. Only three of the mallards dosed retained the zinc shot until the end of the study. Signs
of intoxication in order of increasing severity were stumbling, an inability to run, complete loss of muscular
control of the legs, loss of swimming ability and spasmodic wing movements. However, it should be noted
that the zinc pellets were found not to be pure zinc but contained 92% zinc, 0.16% lead, a trace of iron and
7% not determined. French et al. (1987) dosed mallard ducks with five or ten No. 6 zinc shot (99.9% purity)
and observed the birds for 28 days. Observation during the experimental period, post-mortem examination
and histopathological examination revealed no effects of zinc on the dosed birds.

Mammals can also die from ingestion of zinc. Straube & Walden (1981) reported that 20 of 25 ferrets
(Mustela putorius furo) being used in an experiment died of renal failure after eating raw meat that was
accidentally contaminated with zinc from the wire cages. Zinc poisoning was diagnosed after autopsy and
laboratory investigation.

Straube et al. (1980) fed ferrets (M. putorius furo) on a basal diet (zinc content 27 mg/kg) with zinc
supplements of 500, 1500 or 3000 mg/kg for up to 6 months. The ferrets fed the two highest concentrations
showed severe signs of toxicity between weeks 1 and 2, with the animals at the highest exposure dying
within 2 weeks. Lesions included diffuse nephrosis, haemorrhages in the intestine and severe macrocytic
hypochromic anaemia.

Bleavins et al. (1983) fed mink (M. vison) on a diet supplemented with zinc at 500 mg/kg for 2.5 months. No
clinical signs of zinc toxicity were observed and the zinc supplement was increased to 1000 mg/kg. Again,
no signs of zinc toxicity were observed; however, the offspring of zinc-treated females showed
achromotrichia, alopecia, lymphopenia and a reduced rate of growth suggesting copper deficiency, although
other signs of this latter condition (anaemia and neurotropenia) were not observed. Aulerich et al. (1991) fed
adult and kit male and female mink on a basal diet (zinc content 40 mg/kg) supplemented with zinc at 500,
1000 or 1500 mg/kg for 144 days. No marked adverse effects on food consumption, body weight gains,
haematological parameters, fur quality or survival were observed. Histopathological examination of the liver,
kidneys and pancreas did not reveal any lesions indicative of zinc toxicosis.

Racey & Swift (1986) housed pipistrelle bats (Pipistrellus pipistrellus) in roosting cages treated with zinc
octoate. The pregnant female bats (three groups of 10), collected from nursery roosts, were trained to feed on
mealworms before transfer to the experimental cages. The cages were metal, lined with plywood and painted
with zinc octoate as a solution in white spirit at 0.5 litre/m2 and containing 8% zinc as metal (as
recommended by the manufacturers), or with white spirit. Treatment of the wood was conducted 2 months
before introduction of the bats into the cages. During the course of the 142-day experiment, there were 2
deaths in the zinc ocoate group, 2 in the white spirit control group and 3 in the untreated control group.

9.2 Tolerance to zinc

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Tolerance to zinc (and other metals) has been documented in a wide variety of plants and animals. Tolerance
may occur in two ways (Miller & Hendricks, 1996): through acclimatization at some early stage in the life
cycle, or through natural selection. The latter process is heritable, the former is not. However, as noted by
Bervoets et al. (1996), few studies have discriminated even the effects of acclimatization on metal uptake or
toxicity. Some key studies that have done so are detailed below.

Free-living fungi, as well as those associated in mycorrhiza with higher plants (vesicular-arbuscular
mycorrhiza, ectomycorrhiza), have enhanced zinc resistance in zinc-enriched soils (Colpaert & Van Assche,
1992; Gadd, 1993). All tested actinomycetes and non-spore forming bacteria isolated from a site
contaminated with metals were zinc tolerant, growing normally in media containing zinc concentrations of
39–130 mg/litre (600–2000 µmol/litre) (Jordan & Lechevalier, 1975). Shehata & Whitton (1981) reported
that blue-green algae are often frequent in waters with very high levels of zinc, and laboratory assays have
shown that these algae are much more resistant to zinc than most isolates from sites lacking zinc enrichment.
Hornor & Hilt (1985) determined the distribution of zinc-tolerant bacteria from three stream sites containing
high (3125 µg/litre), medium (291 µg/litre) and low (109 µg/litre) concentrations of zinc. Zinc tolerance was
estimated by the ability of bacteria to grow on media amended with zinc (4–512 mg/litre). The presence of
zinc-tolerant bacteria was correlated with the degree of heavy metal contamination. Zinc concentrations
ranging from 4 to 16 mg/litre were stimulatory to growth of bacteria from contaminated sites while
concentrations of 4 mg/litre were inhibitory to bacteria from the control site.

Antonovics et al. (1971) reviewed metal tolerance in plants and found several examples of plant
communities that show high tolerance to zinc. Most of the studies that relate to zinc tolerance are associated
with soils enriched with zinc either naturally or by metal mining activity. All plants growing for a long time
on zinc-enriched soils have evolved a zinc resistance regardless of whether they are fungi, mosses, ferns or
angiosperms. Shaw (1990) noted that the development of metal tolerance in plants is among the best
observed examples of evolution related to natural and anthropogenic stress.

Acclimatization and adaptation to zinc have been demonstrated by Miller & Hendricks (1996) for
Chironomus riparius. Other examples of zinc resistance in aquatic organisms are provided by Klerks & Weis
(1987), Klerks & Levinton (1989) and Klerks (1990).

Pre-exposure of rainbow trout to zinc at a concentration of 2 mg/litre for more than 5 days significantly
decreased the acute toxicity of the metal (Bradley & Sprague, 1985). Anadu et al. (1989) found that
acclimatization to a zinc concentration of 50 µg/litre increased the tolerance of juvenile rainbow trout by a
factor of 3–5. Maximum tolerance was achieved within 7 days with no further change noted after 2–3 weeks.
Further studies revealed that there was no increase in tolerance after acclimatization periods of less than 3
days. Tolerance to zinc was rapidly lost following return to control water, with almost complete reversion to
control tolerance after only 7 days. Hobson & Birge (1989) found that tolerance to zinc in 96-h acute toxicity
tests increased significantly after 14 days of exposure to zinc at 0.6 mg/litre but decreased significantly
following exposure to 1.8 mg/litre for 7 and 14 days. After 21 days of pre-exposure to 0.6 or 1.8 mg/litre
there was no significant effect on acute toxicity compared with controls. The authors found no correlation
between changes in tolerance and observed changes in metallothionein-like proteins. Hogstrand & Wood
(1995) reported that acclimatization to zinc in rainbow trout adapted to fresh water can develop without any
detectable increase in zinc accumulation in the gills or liver. Acclimatization to zinc does not necessarily
involve induction of metallothionein. The inhibition of the calcium influx by zinc is mainly competitive in its
nature, and persists during chronic exposure, indicating that zinc and calcium compete for the same uptake
sites. Zinc-adapted fish have a decreased rate of zinc influx compared to controls. The authors therefore
speculated that fish are able to regulate the uptake of zinc separately from calcium so that, in zinc-adapted
fish, zinc influx can be markedly reduced without altering the influx of calcium.

Joosse et al. (1984) found that a tolerant population of the terrestrial woodlouse (Porcellio scaber) from a
contaminated site regulated its body content of zinc at a higher level than a control population. Another
population of P. scaber collected from a zinc-contaminated area was found to be adapted to high zinc and
cadmium concentrations (Van Capelleveen, 1987). However, individuals from the contaminated site
produced larger quantities of metalloproteins and showed lower growth efficiencies and drought resistance
than individuals from a control site.

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Differences in assimilation rates for zinc in two populations of centipede (Lithobius variegatus) were found
to be related to the degree of contamination of the site from which the population was collected (Hopkin &
Martin, 1984). Centipedes from a contaminated site survived longer than those from an uncontaminated site
when both populations were fed on woodlice hepatopancreas with high concentrations of metals. A review of
resistance in terrestrial invertebrates is provided by Posthuma & Van Straalen (1993).

9.3 Interactions with other metals

Zinc can behave antagonistically in combination with copper (Ahsanullah et al., 1988; Vranken et al., 1988;
Kraak et al., 1994b) and synergistically with lead or iron alone or in combination (Ahsanullah et al., 1988;
Konar & Mullick, 1993), and with mercury or nickel (Vranken et al., 1988). Zinc and cadmium can show
additive toxicity (Negilski et al., 1981; Kraak et al., 1994b). Metal interactions can vary, however, depending
on physicochemical conditions. For instance, Tomasik et al. (1995) found that zinc toxicity in soft water (50
mg/litre, CaCO3) was lowered by magnesium and molybdenum and increased by cobalt or selenium.
However, in hard water (100 mg/litre, CaCO3) zinc was either inhibited by all metals (at a concentration of 1
mg/litre) or there was a weak synergism (at 0.5 mg/litre). Similarly, Biesinger et al. (1986) found that
different zinc concentrations resulted in different interactions (with cadmium and mercury).

10. EVALUATION OF HUMAN HEALTH RISKS

AND EFFECTS ON THE ENVIRONMENT
10.1 Homeostatic model
Zinc is an essential trace element that can cause symptoms of deficiency and can be toxic when exposures
exceed physiological needs. This relationship is described by a homeostatic model that takes the form of a U-
shaped curve; the arms of the curve express risk of deficiency or excess, with the portion of the curve
between the arms expressing the range of exposure (intake) that is related to optimal function (good health)
(Fig. 1). The relationship between intake and health is affected by physiological factors (homeostasis) and by
extrinsic factors that affect the availability of zinc for absorption and utilization or that interfere with the
metabolism of zinc and biochemical processes that require zinc. In nature these relationships are not
necessarily symmetrical.

The homeostatic model defines the principle of an acceptable range of exposures for an essential trace
element like zinc. In the acceptable range, zinc, which is necessary for various metabolic processes,
embryonic development, cellular differentiation and cell proliferation, provides the substrates for expression
of the genetic potential of the individual, i.e., optimum growth, health, reproduction and development.
Environmental levels of zinc providing exposures or intakes within the acceptable range do not produce
adverse effects among the general human population or the environment. However, there are individuals or
groups with imbalances in relation to other trace elements, or with disorders in homeostatic mechanisms that
experience effects, of either deficiency or toxicity, from exposures within the acceptable range. These
disorders may be acquired or of genetic origin.

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10.2 Evaluation of risks to human health

People are exposed to zinc primarily from food, although oral exposure can become excessive through non-
dietary sources. Certain occupational exposures can be hazardous.

10.2.1 Exposure of general population

The estimated average daily dietary zinc intakes range from 5.6 to 13 mg/day in infants and children from 2
months up to 19 years and from 8.8 to 14.4 mg/day in adults aged 20–50 years. Flesh foods (i.e., meat,
poultry, fish and other seafood) are rich sources of readily available zinc, while fruits and vegetables contain
relatively low zinc concentrations. For omnivorous adults, more than one-third of dietary zinc can be
provided by flesh foods, whereas for vegetarians, plant-based foods are the major dietary source. Mean daily
intake of zinc from drinking-water is estimated to be < 0.2 mg/day.

Intakes via dermal and inhalation routes are generally insignificant in the general population. Consumption
of dietary supplements of zinc as well as prolonged treatment with pharmaceuticals containing zinc may
result in high exposure to zinc.

The absorption of zinc from diets based on solid foods generally ranges from < 15% to 55% (about 20–30%
from an omnivorous diet), depending on the composition of the diet, as well as the nutritional (especially in
relation to zinc), physiological and health status of the individual. When major dietary zinc sources are
unrefined cereals, nuts and legumes, absorption is low, owing primarily to the inhibitory effect on zinc
absorption of phytate and, to a lesser extent, Maillard browning products and dietary fibre.

The major excretory route for ingested zinc is via the faeces.

10.2.2 Occupational exposure

Occupational exposure to dusts and fumes of zinc and zinc compounds can occur in a variety of settings in
which zinc is produced, or in which zinc and zinc-containing materials are used. Typical airborne exposures
observed include 0.19–0.29 mg/m3 during the smelting of zinc-containing iron scrap, 0.90–6.2 mg/m3 at
non-ferrous foundries and 0.076–0.101 mg/m3 in hot-dip galvanizing facilities. Far higher exposures are
possible during particular job activities, such as welding of zinc-coated steels in the absence of appropriate
respiratory protection and/or fume extraction engineering controls.

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Occupational exposure to high levels of zinc oxide and/or non-ferrous metals is associated with metal-fume
fever. This is usually a short-term, self-limiting syndrome, characterized by fever and chills. Induction of
metal-fume fever is most common with ultra-fine particles capable of deep lung penetration under conditions
of exposure. Studies on volunteers conducted under short-term exposure conditions (77–153 mg/m3 for 15–
30 min) have detected pulmonary inflammation responses (including cytokine induction) which are
consistent with manifestations of metal-fume fever and support an immunological etiology for this acute
reversible syndrome.

Based on the available information, it is not possible to define a no-effect level for pulmonary inflammation
from exposure to zinc oxide fume.

10.2.3 Risks of zinc deficiency

Zinc is an ubiquitous and essential element. Dietary reference values for zinc for adults range from 6 to 15
mg/day (depending upon the bioavailability factor used). However, large numbers of people are believed to
ingest insufficient bioavailable zinc. The effects of zinc deficiency are well documented and may be severe.
They include impaired neuropsychological functions, oligospermia, growth retardation, impaired
reproduction, immune disorders, dermatitis and impaired wound healing. Most of these effects are treatable
with adequate amounts of zinc.

Because of the lack of data on zinc kinetics and inadequate measures of internal dose, there is limited
understanding of how site-specific zinc concentration relates to manifestations of deficiency (or excess). The
estimated absolute absorbed amount of zinc for adults is 2.5 mg daily. This implies a dietary need at 20%
bioavailability of 12.5 mg daily. As bioavailability increases, the amount needed in the diet will decrease.

10.2.4 Risks of zinc excess

Toxic effects in humans are most obvious from accidental or occupational inhalation exposure to high
concentrations of zinc compounds, such as from smoke bombs, or metal-fume fever. Modern occupational
health and safety measures can significantly reduce potential exposure. Intentional or accidental ingestion of
large amounts of zinc leads to gastrointestinal effects, such as abdominal pain, vomiting and diarrhoea. In the
case of long-term intakes of large amounts of zinc at pharmacological doses (150–2000 mg/day), the effects
(sideroblastic anaemia, leukopenia and hypochromic microcytic anaemia) are reversible upon
discontinuation of zinc therapy and/or repletion of copper status, and are largely attributed to zinc-induced
copper deficiency.

High levels of zinc may disrupt the homeostasis of other essential elements. For example, in adults, subtle
effects of zinc on copper utilization may occur at doses of zinc near the recommended level of intake of 15
mg/day and up to about 50 mg/day. Copper requirements may be increased and copper utilization may be
impaired with changes in clinical chemistry parameters, but these effects are not consistent and depend
largely upon the dietary intake of copper. Distortion of lipoprotein metabolism and concentrations associated
with large doses of zinc are inferred to be a result of impaired copper utilization. In groups with adequate
copper intake, no adverse effects, with the exception of reduced copper retention, have been seen at daily
zinc intakes of < 50 mg/day.

There is no convincing evidence that excess zinc plays an etiological role in human carcinogenesis. The
weight of evidence supports the conclusion that zinc is not genotoxic or teratogenic. At high concentrations
zinc can be cytotoxic.

10.3 Evaluation of effects on the environment

10.3.1 Environmental risk assessment
The science of performing environmental risk assessments has evolved rapidly in recent years with
standardized techniques being adopted in both the USA and Europe (US EPA, 1992 and OECD, 1995). The

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key components of environmental risk assessment are: problem formulation, analysis, and risk
characterization.

Problem formulation (i.e., hazard identification) consists of identifying and defining the risk problem,
assessing the population, community or ecosystem at risk, establishing the model for evaluating the potential
for risk, and selecting the biological end-points and environmental media to be analysed. The analysis phase
consists of assessments of exposure and effects. The exposure assessment involves detailed studies to
characterize the spatial and temporal concentrations of the chemical of interest. Effects assessment involves a
series of standardized laboratory and, in some cases, field studies, and is performed to evaluate the dose–
response curve for selected toxic end-points and species of interest. In the risk characterization phase, the
exposure and effects data are integrated, the potential for co-occurrence of organism and contaminant is
determined, and a conclusion is drawn about the potential for risk. The risk statement can be made in terms
of a probability statement, frequency or time effects are expected to occur, or number of species to be
affected. Risk is assessed by determination of the adequacy of the margin of safety between effects and
exposure concentrations and expert judgement is typically used to determine the acceptability of the
perceived margin of safety. General consensus exists that the larger the margin of safety the lower is the
environmental risk. Margins of safety of < 1.0 are usually indicative of a higher potential for risk and may
require further evaluation.

10.3.2 Components of risk assessment for essential elements

For essential elements, the principal components of risk assessment are exposure and effects assessments.
Environmental exposure has been assessed by reviewing the fate (transport, distribution and behaviour) of
the element from the point of release into and through the environmental compartments of air, water
soil/sediment and biota. Effects assessment involves toxicity tests conducted on representative species of the
trophic levels in the ecological community of interest, including algae and plants (primary producers),
aquatic and terrestrial invertebrates (secondary producers) and fish and terrestrial animals (consumers).

For essential micronutrients, a lower limit exists below which deficiency will occur as illustrated in Fig. 1.
This well-established concept is applicable at both the population and the community level. Deficiency as
well as toxicity must therefore be considered when assessing environmental risk Within the homeostatic
zone, organisms regulate their uptake and/or compartmentation of zinc to maintain optimal life conditions
without any stress occurring. Outside this zone, adaptation may occur.

There is a diversity of habitat types in both aquatic and terrestrial environments with different optimal
concentration ranges. Because zinc is ubiquitous, it is unlikely, except in some terrestrial regions, particularly
agricultural regions where zinc concentrations are very low or where antagonistic nutrient interactions occur,
that deficiency in the environment will be a significant issue. However, the use of large safety factors in
procedures to limit exposures to below toxic levels might result in target concentrations below essential
levels.

One of the key questions in ecotoxicology is the extent to which laboratory tests under controlled conditions
are predictive of effects that will be seen in the environment. Traditional toxicity testing has, in the past,
focused on the acute and chronic effects of chemicals on the life stages of aquatic and terrestrial organisms.
The integration of environmental chemistry and toxicology has allowed a better prediction of the effects of
metals on organisms in the environment. This has led to the now accepted view that the total concentration of
an essential element such as zinc in an environmental compartment is not a good predictor of its
bioavailability (section 4.2). Since site-specific parameters control the bioavailability of essential elements,
these parameters must be included in the risk assessment.

Organisms may also develop tolerance on a local scale by acclimatization (physiological behaviour) and
adaptation (genetic changes) towards higher as well as lower concentrations. Because of such tolerance, the
test-derived toxicity values may be lower or higher than the values for the same species from an adapted
population.

10.3.3 Environmental risk assessment for zinc

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There are limited data available for performing a detailed assessment of the potential risk for zinc for each
environmental medium (air, water, soil, sediment). The largest data set is reported for the aquatic
environment. The aim of this section is to provide an evaluation of the available biological effects and
exposure data for various organisms and media consistent with this risk paradigm, and describe ranges of
concentrations for which the potential for risk increases.

10.3.3.1 Environmental concentrations

Zinc is released to the environment from natural and anthropogenic sources. On a global scale, emissions
from these sources are similar in magnitude. However, on a local scale anthropogenic sources may dominate.

The fate of zinc in the environment is largely determined by sorption processes. Zinc bioavailability is
determined by a set of physicochemical and biological parameters as discussed in Chapter 4. Zinc occurs
ubiquitously in environmental samples, although the concentration is determined by several factors, such as
the local geological and anthropogenic influences. Natural background total zinc concentrations are as
follows:

air up to 300 ng/m3

fresh water < 0.1–50 µg/litre

seawater < 0.002–0.1 µg/litre

sediments up to 100 mg/kg dw

soil 10–300 mg/kg dw

Higher zinc concentrations can be attributed to anthropogenic contamination, although natural processes
(both abiotic and biotic) can contribute to localized high zinc concentrations. Total zinc concentrations in
fresh and estuarine waters have been reported to be up to 3900 and 15 µg/litre, respectively. Zinc
concentrations of up to 35 000 mg/kg dw have been reported in soil. In mineralized areas these values can be
exceeded.

10.3.3.2 Overview of toxicity data

The toxicity of zinc to aquatic organisms is affected by factors such as temperature, hardness, pH and
dissolved organic carbon. Overall the data are very variable (see chapter 9). Table 45 summarizes minimum
effects threshold data. Only data that met the acceptability criteria given in chapter 9 are included. It should
be noted that none of the aquatic plant toxicity data contained in chapter 9 met those criteria. Thus, aquatic
plants are not included in the table. A dissolved zinc concentration of 20 µg/litre has been shown to have
adverse effects on freshwater organisms in soft water (hardness < 100 mg/litre, CaCO3). In hard water
(hardness > 100 mg/litre, CaCO3), adverse effects have been reported at dissolved zinc concentrations of 90
µg/litre. In the marine environment, dissolved zinc concentrations of 100 µg/litre have been shown to have
adverse effects. Zinc deficiency in aquatic organisms in the open ocean has been reported.

The toxicity of zinc to terrestrial organisms is similarly dependent upon its bioavailability, which in turn is
determined by various factors such as the speciation of zinc, and the physicochemical and biological
characteristics of the soil. The bioavailable fraction of zinc in soil has been calculated to range from < 1% to
10% of the total zinc concentration. Zinc has to be in a soluble form to be taken up by plants. Plants may also
take up zinc that is deposited on the surface of leaves following aerial deposition or application of fertilizer.
Symptoms of zinc toxicity in plants differ from those of zinc deficiency, with coralloid rather than extended
roots and curled rather than mottled leaves. In the case of zinc toxicity, zinc replaces other metals (e.g., iron,
manganese) in the active centres of enzymes (e.g., hydrolases and haem enzymes).

Table 45. Minimum thresholds for adverse effects of dissolved zinc on aquatic organisms

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Concentration of dissolved Effects in fresh waters Effects in marine waters

zinc (µg/litre)

20–50 chronic effects on

cladocerans in soft watera

50–100 chronic effects on acute effects on mysids

cladocerans in hard water;
acute effects on cladocerans
in soft water; acute and
chronic effects on fish in soft
water; chronic effects on
freshwater insects

100–200 acute effects on algae; acute acute effects on fish

effects on cladocerans in hard
water; chronic effects on fish
in hard water; chronic effects
on molluscs

200–1000 acute effects on amphipods;

acute effects on decapods

1000–10000 acute effects on molluscs; acute effects on polychaetes;

acute effects on copepods; acute effects on molluscs
acute effects on amphipods;
acute effects on fish in hard
water

a For the purposes of this document, soft water is defined as having a hardness (CaCO3) of < 100 mg/litre, hard water as having a
hardness of > 100 mg/litre.

Among terrestrial invertebrates, earthworms (Eisenia andrei) and woodlice (Porcellio scaber) show adverse
effects on reproduction starting at total zinc concentrations of 560 and 1600 mg/kg dw, respectively. For
terrestrial vertebrates, only data on zinc toxicity through dietary zinc intake are available (see section
9.1.3.3).

The adverse effects of zinc must be balanced against its essentiality. Zinc is important in enzymes, in the
metabolism of proteins and nucleic acids, and in the stabilization of biological membranes. Zinc deficiency
has been reported in a wide variety of agricultural plants and animals with severe effects on all stages of
reproduction, growth and tissue proliferation. An evaluation of zinc must therefore take into account the
adverse effects of low zinc concentrations as well as those attributed to excess zinc. There are ranges of
optimal concentrations for essential elements such as zinc, which are dependent upon species and habitat.
The setting of an absolute toxic threshold value or minimum toxic concentration is not appropriate for such a
chemical. Any risk assessment of the potential effects of zinc on organisms must also take into account the
local environmental conditions.

11. CONCLUSIONS AND RECOMMENDATIONS FOR

PROTECTION OF HUMAN HEALTH
AND THE ENVIRONMENT
11.1 Human health
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• There is a decreasing trend in anthropogenic zinc emissions.

• Many pre-1980 environmental samples, in particular in water samples, may have been
subject to contamination with zinc during sampling and analysis and, for this reason, zinc
concentration data for such samples should be viewed with extreme caution.

• In countries where staple diets are based on unrefined cereals and legumes, and intakes of
flesh foods are low, dietary strategies should be developed to improve the content and
bioavailability of zinc.

• Preparations intended to increase the zinc intake above that provided by the diet should not
contain zinc levels that exceed dietary reference values, and should contain sufficient
copper to ensure a ratio of zinc to copper of approximately 7, as is found in human milk.
• There is a need for better documentation of actual exposures to zinc oxide fume in
occupational settings. Workplace concentrations should not result in exposure levels as
high as those known to have given rise to inflammatory responses in the lungs of
volunteers.

• The essential nature of zinc, together with its relatively low toxicity in humans and the
limited sources of human exposure, suggests that normal, healthy individuals not exposed
to zinc in the workplace are at potentially greater risk from the adverse effects associated
with zinc deficiency than from those associated with normal environmental exposure to
zinc.

11.2 Environment
• Zinc is an essential element in the environment. The possibility exists both for a deficiency
and for an excess of this metal. For this reason it is important that regulatory criteria for
zinc, while protecting against toxicity, are not set so low as to drive zinc levels into the
deficiency area.

• There are differences in the responses of organisms to deficiency and excess.

• Zinc bioavailability is affected by biotic and abiotic factors, e.g., organism age and size,
prior history of exposure, water hardness, pH, dissolved organic carbon and temperature.

• The total concentration of an essential element such as zinc, alone, is not a good predictor
of its bioavailability or toxicity.

• There is a range of optimum concentrations for essential elements such as zinc.

• The toxicity of zinc will depend on environmental conditions and habitat types. Thus any
risk assessment of the potential effects of zinc on organisms must take into account local
environmental conditions.

12. RECOMMENDATIONS FOR FURTHER RESEARCH

12.1 Zinc status
There is a need to improve techniques to assess zinc status. Current methods such as measurements of serum,
plasma and leukocyte zinc concentrations are insufficient. Newer approaches for consideration might include
the use of zinc kinetics as related to function, or the identification of enzymes that are dependent on zinc and
whose changes reflect zinc status as it relates to function.

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12.2 Functional indices of zinc status

There is a need for functional indices of zinc status to be measured before and after treatment, and in the
absence of other limiting nutrients. Areas of interest include immune function, neuropsychology, dark
adaptation, ethanol tolerance, intestinal permeability, and growth and body composition.

12.3 Interactions with other trace elements

Zinc homeostasis requires much clearer definition in respect of both its individual role, and the concurrent
role of other ions which may be affected by zinc deficiency or excess. In particular, biological effects at
various ratios of zinc and copper require further investigation. Specifically, attention needs to be given to
life-cycle issues in which the relationships between concentrations of the metals in organs such as the liver
should be related to the dietary ratios of these same metals. It is also important to determine whether the
biological end-point is a matter of clinical significance. Data defining the amount of zinc that might interfere
with copper utilization in infants, children and pregnant women are needed. The zinc:copper ratio has been
shown to induce dyslipidaemias, and studies on the cardiovascular consequences of these conditions need
further investigation.

12.4 Supplementation
As excess zinc impairs utilization of copper and other trace elements, research on the potential benefits of
adding copper and/or iron to oral zinc preparations is needed.

12.5 Occupational medicine

There is a need to define the NOEL for zinc exposure in occupational medicine.

12.6 The molecular mechanism

Data on zinc transport by proteins, both into and out of the cell, are poorly developed. Further studies on zinc
homeostasis and the role of metal-binding proteins (including metallothionein) are required.

12.7 Environment
Work is required to develop and standardize procedures for toxicity testing in terrestrial organisms.

Work is required to understand the homeostatic abilities of sensitive indicator organisms, and to determine
the boundaries of the optimal range for different species in different habitat types.

Techniques for measuring and predicting bioavailability in different media, including robust analytical
methods for measuring speciation, need to be developed, improved and validated against bioassays.

Important data gaps have been identified including, in particular, chronic marine toxicity data and toxicity
data for terrestrial plants.

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RESUME ET CONCLUSIONS
1. Identité , propriétés physiques et chimiques
Le zinc n'existe pas à l'état métallique dans la nature. Il n'est présent qu'à l'état divalent (Zn II). L'ion zinc
peut être solvaté; sa solubilité dépend du pH et de l'anion. Le zinc est un élément de transition capable de
former des complexes avec divers ligandes organiques. Les composés organozinciques n'existent pas dans la
nature.

2. Méthodes d'analyse
Le zinc étant très répandu dans l'environnement , il faut un soin particulier pour effectuer les prélèvements
ainsi que pour préparer et analyser les échantillons afin d'éviter toute contamination. Dans le cas des
échantillons solides on a le plus souvent recours à une minéralisation par des acides concentrés assistée par
traitement microonde. Dans le cas d'échantillons d'eau, on peut commencer par concentrer le zinc au moyen
d'une extraction par solvant en présence d'agents complexants ou d'une séparation sur résine chélatante.

Pour le dosage du zinc, on a couramment recours aux méthodes instrumentales suivantes: spectrométrie
d'emission atomique à source plasma à couplage inductif, spectrométrie d'absorption atomique avec four à
électrodes de graphite, voltamétrie par redissolution anodique et spectrométrie de masse à source plasma à
couplage inductif. Pour le dosage des faibles quantités on donne la préférence à la spectrométrie d'absorption
atomique avec four à électrodes de graphite, à la voltamétrie par redissolution anodique et à la spectrométrie
de masse avec source plasma à couplage inductif.

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En opérant de manière minutieuse, on parvient à doser le zinc jusqu'à des concentrations de 0,006 µg/litre
dans l'eau et de 0,01 mg/kg dans les échantillons solides.

Pour la recherche et le dosage des diverses espèces chimiques présentes dans l'eau (ou spéciation), il faut
mettre en oeuvre l'une ou l'autre des techniques de séparation indiquées plus haut ou recourir à la
différenciation des espèces labiles que permet la voltamétrie par redissolution anodique.

3. Sources d'exposition humaine et environnementale

La plupart des roches et de nombreux minéraux renferment du zinc. Sur le plan commercial, le minerai le
plus important est la sphalérite ou blende (ZnS), qui constitue la principale source de zinc pour l'industrie. En
1994, la production mondiale de zinc a été de 7 089 000 tonnes et la consommation de zinc métallique a
atteint 6 895 000 tonnes.

Le zinc est largement utilisé pour la protection d'autres métaux (zingage, galvanisation), en moulage sous
pression, dans le BTP et pour la confection d'alliages divers. Les dérivés minéraux du zinc ont des
applications diverses, notamment dans la fabrication d'équipements automobiles, d'accumulateurs et de piles
sèches ou encore dans le domaine dentaire, médical ou pour la confection d'objets ménagers. On utilise les
organozinciques comme fongicides,comme antibiotiques pour applications locales et comme lubrifiants.

Vers 100 à 150 °C, le zinc devient malléable et il est alors facile de le travailler. Comme il est capable de
réduire la plupart des ions d'autres métaux, on l'emploie pour la confection d'électrodes dans les piles sèches
ainsi qu'en hydrométallurgie.

La majeure partie du zinc naturellement présent dans l'eau y est amenée par l'érosion. Le zinc présent dans
l'atmosphère par suite de processus naturels provient d'émissions ignées et de feux de forêt. Les émissions
d'origine humaine sont du même ordre de grandeur. Les principales sources de zinc dues aux activités
humaines sont l'extraction du minerai, la production de zinc, la production de fer et d'acier, la corrosion des
structures galvanisées, la combustion du charbon et de carburants divers, l'élimination et l'incinération des
déchets et enfin l'utilisation d'engrais et de pesticides à base de zinc.

4. Transport, distribution et transformation dans l'environnement

Le zinc présent dans l'atmosphère est en majeure partie fixé à des particules d'aérosols. La granulométrie de
ces particules dépend de la source qui les émet. Une importante proportion du zinc libéré lors de divers
processus industriels est adsorbée sur des particules suffisamment petites pour être respirables.

Le transport et la distribution du zinc atmosphérique varient en fonction de la granulométrie des particules et

des propriétés des composés en cause. Le zinc s'élimine de l'atmosphère en se déposant par voie humide ou
par voie sèche. Le zinc adsorbé sur des particules de faible densité et de petit diamètre peut être en revanche
transporté sur de grandes distances.

La distribution et le transport du zinc dans l'eau, les sédiments et le sol dépendent de l'espèce chimique en
cause et des caractéristiques de l'environnement. C'est le pH qui détermine principalement la solubilité du
zinc. Si le pH est acide, le zinc peut être présent dans l'eau sous forme ionique. Si par contre le pH est
supérieur à 8,0, il peut y avoir précipitation du zinc. Il peut également former des complexes organique
stables, par exemple avec les acides humiques et fulviques. La formation de ces complexes augmente la
mobilité et la solubilité du zinc. Comme il est adsorbé sur les argiles et les matières organiques, il peu
probable qu'il puisse se détacher du sol par lessivage. Les sols acides et sablonneux à faible teneur en
matières organiques ne sont guère capables de retenir le zinc.

Le zinc est un élément essentiel et sa concentration in vivo est donc régulée chez la plupart des êtres vivants.
Les animaux aquatiques ont tendance à le prélever dans l'eau plutôt que dans leur nourriture. Pour être
biodisponible, le zinc doit obligatoirement être en solution et sa biodisponibilité dépend des caractéristiques
physiques et chimiques de l'environnement et des processus biologiques. Toute évaluation d'ordre écologique
doit donc se faire site par site.

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5. Concentrations dans l'environnement

Le caractère ubiquitaire du zinc le fait se retrouver dans un peu tous les échantillons d'origine biologique ou
environnementale. Sa concentration dans les sédiments et dans l'eau douce est fortement influencée par les
conditions géologiques et anthropogéniques locales et elle varie donc dans de larges proportions. La
concentration totale naturelle du zinc se situe en général autour de < 0,1- 50 µg /litre dans les eaux douces,
de 0,002- 0,1 µg/litre dans l'eau de mer, de 10- 300 mg/kg (poids sec) dans les sols; elle peut aller jusqu'à
300 mg/ kg (poids sec) dans les sédiments et jusqu'à 300 ng/m3 dans l'air. Des concentrations plus élevées
peuvent être attribuées à la présence naturelle de minerais enrichis en zinc, à des sources anthropogéniques
ou encore à des processus biotiques ou abiotiques. Les échantillons dont la teneur en zinc s'explique par la
présence de sources anthropogéniques, peuvent en contenir jusqu'à 4 mg/litre (eau), 35 g/kg (sol), 15 µg/litre
(eaux estuarielles) ou 8 µg/m3 (air).

Chez les organismes représentatifs, on observe des concentrations de zinc comprises entre 200 et 2000 mg/kg
en cas d'exposition au zinc présent dans l'eau.

Chez les végétaux et les animaux, la teneur en zinc est plus élevée à proximité des sources de pollution
anthropogéniques. Les variations de teneur sont importantes d'une espèce à l'autre; la teneur peut varier, par
exemple, en fonction du stade évolutif, du sexe, de la saison, du régime alimentaire et de l'âge. Dans la
plupart des cultures et des pâturages, la concentration normale du zinc se situe dans la fourchette 10- 100
mg/kg de poids sec. Certaines plantes accumulent le zinc, mais dans une proportion qui dépend de la nature
du sol et des caractéristiques de la plante.

La quantité de zinc inhalée avec l'air ambiant est négligeable, mais sur les lieux de travail, l'exposition aux
poussières et vapeurs contenant du zinc peut varier dans d'importantes proportions.

5.1 Apport chez l'Homme

On estime que l'apport de zinc total d'origine alimentaire est de 5,6 à 10 mg par jour pour les nourrissons et
les enfants de 2 mois à 11 ans, de 12,3 à 13,0 mg par jour pour les jeunes de 12 à 19 ans et de 8,8 à 14,4 mg
par jour pour les adultes de 20 à 50 ans. L'apport journalier moyen par l'eau de boisson est estimé à moins de
0,2 mg.

Les valeurs de référence pour l'apport de zinc d'origine alimentaire varient en fonction des habitudes
alimentaires du pays, des hypothèse formulées au sujet de la biodisponibilité du zinc présent dans les
aliments et également de l'âge, du sexe et de l'état physiologique des sujets. Ces valeurs se situent dans les
fourchettes suivantes: 3,3 à 5,6 mg par jour pour les nourrissons de 0 à 12 mois, 3,8 à 10,0 mg par jour pour
les enfants de 1 à 10 ans et 8,7 à 15 mg par jour pour les adolescents de 11 à 18 ans. Pour les adultes, les
valeurs vont de 6,7 à 15 mg par jour dans la tranche d'âge 19- 50 ans, à 7,3- 15 mg par jour chez la femme
enceinte- en supposant un régime alimentaire offrant une biodisponibilité moyenne- et à 11,7- 19 mg par
jour chez la mère allaitante, selon le stade.

6. Cinétique et métabolisme chez l'Homme et les animaux de laboratoire

Des études portant sur l'exposition au zinc par la voie respiratoire (par le nez uniquement) de cobayes, de rats
et de lapins ont montré que le taux de rétention pulmonaire était de 5 à 20% après exposition à des aérosols
d'oxyde de zinc à la concentration de 5- 12 mg/m3 pendant 3 à 6 heures. Dans l'intestin, l'absorption du zinc
s'effectue selon un mécanisme homéostatique qui n'est pas encore complètement élucidé, mais qui est sous la
dépendance des sécrétions pancréatiques et intestinales ainsi que de l'excrétion par la voie fécale. Il est
possible que cette homéostase fasse intervenir des métalloprotéines comme la métallothionéine et la protéine
intestinale riche en cystéine. D'autres mécanismes de nature inconnue peuvent également être à l'oeuvre. Au
niveau de la muqueuse intestinale, la résorption peut se faire par transport actif ou passif. Chez l'animal, la
résorption du zinc peut osciller entre 10 et 40%, selon l'état nutritionnel et la présence d'autres ligandes dans
l'alimentation. La résorption du zinc par la voie percutanée peut s'opérer en présence d'oxyde ou de chlorure
de zinc et elle augmente en cas de carence zincique. Une fois absorbé, le zinc se dépose principalement dans

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les muscles, les os, le foie, le pancréas, les reins et d'autres organes. La demi-vie biologique du zinc est de 4
à 50 jours chez le rat, selon la dose administrée, et elle est d'environ 280 jours chez l'Homme.

7. Effets sur les animaux de laboratoire

Le zinc a une faible toxicité aiguë pour les rongeurs, la valeur de la DL50 allant de 30 à 600 mg/kg de poids
corporel, en fonction de la nature du sel de zinc administré. Aprés inhalation ou instillation intratrachéenne
de composés du zinc, on a observé des effets aigus tels qu'une détresse respiratoire, un oedème pulmonaire et
une infiltration leucocytaire du parenchyme pulmonaire.

Chez des rongeurs brièvement exposés par voie orale à des composés du zinc, on peut observer les effets
toxiques suivants : faiblesse, anorexie, anémie, ralentissement de la croissance, dépilation, moindre
assimilation des aliments ainsi qu'une modification du taux des enzymes hépatiques et sériques, des
anomalies morphologiques et enzymatiques dans l'encéphale et des anomalies histologiques et fonctionnelles
au niveau rénal. Le seuil d'apparition des effets indésirables a été fixé à environ 160 mg/kg p.c. chez le rat.
Chez des veaux exposés à une forte concentration de zinc dans leur alimentation, on a observé des anomalies
pancréatiques. Une exposition de brève durée par la voie respiratoire à des concentrations d'oxyde de zinc >
5,9 mg/m3 a provoqué une inflammation et des lésions pulmonaires chez des cobayes et des rats.

Une exposition de longue durée par voie orale à des dérivés du zinc a permis de constater que les organes
cibles de l'action toxique de cet élément sont le système hémopoïétique chez le rat, le furet et le lapin; le rein
chez le rat et le furet, et le pancréas chez la souris et le furet. La dose sans effet observable (NOEL)- en
prenant en compte l'effet sur la croissance et l'anémie imputables à la présence de sulfate de zinc dans
l'alimentation- a été trouvée inférieure à 100 mg/kg chez le rat. Chez les animaux de laboratoire exposés au
zinc, on peut observer que l'augmentation de la concentration de cet élément dans l'organisme s'accompagne
d'une diminution de la concentration du cuivre, ce qui incite à penser que certains signes de toxicité attribués
à une exposition excessive au zinc pourraient en fait s'expliquer par une carence cuprique provoquée par le
zinc. Par ailleurs, certaines études montrent que l'exposition au zinc modifie la concentration d'autres métaux
essentiels dans l'organisme des animaux exposés, notamment celle du fer. De fait, certains signes de toxicité
observés chez des animaux exposés à de fortes concentrations de zinc peuvent être atténués par l'adjonction
de cuivre ou de fer à l'alimentation.

A très forte dose, le zinc est toxique pour la souris et le hamster gravides. Des rats qui avaient reçu pendant 5
mois une alimentation contenant soit 0,5%, soit 1% de zinc, se sont révélés incapables de se reproduire
jusqu'à ce que le zinc soit retiré de leur nourriture. Chez des souris et des rats, on a également constaté qu'une
forte teneur en zinc de l'alimentation (2000 mg/kg) s'accompagnait d'une augmentation des résorptions et des
mortinaissances; ces effets ont été aussi observés chez des moutons et des hamsters. Dans une étude au cours
de laquelle des rats avaient été exposés, pendant toute la durée de la gestation, à des doses de zinc ne
dépassant pas 150 mg/kg, on a également constaté une augmentation du nombre de résorptions. Toutefois,
dans une autre étude portant également sur des rats, on n'a pas observé d'effets délétères sur le foetus en
développement à la dose de 500 mg/kg. Chez des rats, l'administration après le coït d'une nourriture
contenant 4000 mg de zinc par kg, a empêché l'implantation des ovules. Chez des ratons exposés à des
composés du zinc, l'élévation de la concentration de cet élément s'accompagnait d'une réduction de celle du
fer et du cuivre.

Des études de génotoxicité ont été effectuées sur divers systèmes. Si la plupart des résultats se sont révélés
négatifs, quelques-uns ont tout de même été positifs.

Chez l'animal, une carence en zinc se caractérise par une moindre croissance, une perturbation de la
réplication cellulaire, des effets indésirables sur la reproduction et sur le développement - ces derniers
persistant après le sevrage- et une diminution des réponses immunitaires.

8. Effets sur l'Homme

Après exposition unique ou brièvement réitérée à de l'eau ou à des boissons contenant 1000 à 2500 mg de
zinc par litre, des symptômes d'intoxication consistant en débâcle gastrointestinale, nausées et diarrhée se
sont manifesté. Des symptômes analogues, mais qui ont parfois abouti à la mort ont été signalés après
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administration accidentelle de fortes doses de zinc par voie intraveineuse. Chez des insuffisants rénaux en
dialyse, on a constaté l'apparition de symptômes d'une intoxication par le zinc due à l'utilisation d'eau
conservée dans des réservoirs galvanisés. Ces symptômes étaient réversibles puisqu'ils ont disparu lorsque
l'eau a été filtrée sur charbon actif.

Chez l'Homme, lorsqu'il y a disproportion entre l'apport de zinc et celui de cuivre, il en résulte une carence
cuprique qui accroît les besoins de cuivre, en augmente l'excrétion et en rend le bilan déficitaire. On a
observé divers effets consécutifs à des apports de zinc d'origine pharmacologique, effets qui vont d'une
leucopénie et d'une anémie microcytaire hypochrome à une diminution du taux sérique des lipoprotéines de
haute densité. Ces anomalies disparaissent lorsque cesse l'apport zincique avec supplémentation cuprique
concomitante.

Chez l'Homme, les effets d'une carence en zinc sont nombreux et se traduisent notamment par les anomalies
suivantes: troubles neurosensoriels, oligospermie, altération des fonctions neuropsychologiques, retard de
croissance, allongement de la durée de cicatrisation, troubles de l'immunité et dermatite. Ces troubles sont
généralement réversibles et cèdent à une supplémentation zincique.

Il n'existe pas d'indice biochimique du bilan zincique qui soit à la fois spécifique et sensible. La méthode la
plus fiable pour diagnostiquer une carence en zinc consiste à chercher à mettre en évidence une réaction
positive à une supplémentation zincique dans le cadre d'un essai contrôlé en double insu (en l'absence
d'autres carences en nutriments limitants). Cette méthode est longue et souvent impraticable, aussi préfère-t-
on généralement recourir à un ensemble d'indices alimentaires, biochimiques et physiologiques. Plusieurs
valeurs anormales concordantes sont plus fiables qu'une seule valeur aberrante pour diagnostiquer une
carence en zinc. En faisant appel à des indices physiologiques fonctionnels comme la croissance, le sens du
goût et l'adaptation à l'obscurité et en les complétant par une épreuve biochimique (par exemple, le dosage du
zinc dans le plasma ou les cheveux) on perçoit mieux les conséquences fonctionnelles de la carence que l'on
s'efforce de déterminer.

L'exposition par la voie respiratoire au chlorure de zinc contenu dans les bombes fumigènes utilisées par les
forces armées a produit les effets suivants: oedème et fibrose interstitiels, pneumonie, oedème de la
muqueuse bronchique, ulcérations et même mort en cas d'extrême exposition dans un espace confiné. Ces
effets pourraient s'expliquer par la nature hygroscopique et astringente des particules libérées par ces
dispositifs.

L'exposition professionnelle aux particules finement dispersées qui se forment lorsque certains métaux, dont
le zinc, sont volatilisés, peut conduire à une pathologie aiguë qui porte le nom de « fièvre des fondeurs ».
Elle se caractérise par des symptômes divers au nombre desquels de la fièvre, des frissons, de la nausée et de
la fatigue. C'est une affection généralement grave mais passagère et les sujets ont tendance à acquérir une
tolérance. En exposant des volontaires à des concentrations de zinc de 77 à 150 mg/m3 pendant 15 à 30
minutes, on a pu observer chez certains d'entre eux les symptômes suivants: une réaction inflammatoire
marquée liée à la dose avec augmentation du nombre de polynucléaires dans le liquide de lavage
bronchoalvéolaire et un accroissement sensible des cytokines. On a signalé des cas d'asthme professionnel
chez des ouvriers travaillant avec des fondants pour soudure tendre, mais les données sont insuffisantes pour
qu'on puisse invoquer une relation de cause à effet. Un cas rare incitant à penser à une telle relation a été
récemment observé: il s'agissait d'un ouvrier travaillant dans un atelier de galvanisation par trempage dans
des bains de zinc fondu.

9. Effets sur les autres êtres vivants au laboratoire et dans leur milieu naturel
Le zinc joue un rôle important dans la stabilité de la membrane cellulaire, dans plus de 300 enzymes et dans
le métabolisme des protéines et des acides nucléiques. Il faut faire la part entre les effets indésirables du zinc
et son caractère d'élément essentiel. Des carences en zinc ont été observées chez toutes sortes de plantes
cultivées et d'animaux, avec de graves effets à tous les stades de la reproduction, de la croissance et de la
prolifération tissulaire. Un peu partout dans le monde, les carences en zinc touchant diverses cultures ont
pour effet d'importantes pertes au niveau des récoltes. Dans l'environnement aquatique, les carences en zinc
sont rares, mais on peut les provoquer expérimentalement.

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Des facteurs biotiques ou abiotiques tels que l'âge et la taille de l'organisme en cause, une exposition
antérieure éventuelle, la dureté de l'eau, le pH, la teneur en carbone organique dissous ou la température
peuvent influer sur la toxicité du zinc. Une approche écochimique et écotoxicologique intégrée a permis une
meilleure prévision des effets du zinc sur les êtres vivants dans leur milieu naturel. La conséquence en a été
que l'on admet désormais que la concentration totale d'un élément essentiel comme le zinc dans tel ou tel
compartiment de l'environnement ne peut, à elle seule, suffire pour prévoir correctement sa biodisponibilité.

En ce qui concerne les invertébrés d'eau douce on a obtenu, pour le zinc en solution, des valeurs de la
toxicité aiguë qui vont de 0,07 mg/litre chez la daphnie à 575 mg/litre chez une espèce d'isopode. Dans le cas
des invertébrés marins, les valeurs obtenues vont de 0,097 mg/litre pour une espèce de mysidé à 11,3 mg
/litre pour une espèce de crevette. Les concentrations létales en exposition instantanée pour les poissons
d'eau douce se situent entre 0,066 et 2,6 mg/litre; pour les poissons de mer, elles sont comprises entre 0,19 et
17,66 mg/litre.

On a montré que le zinc a des effets génésiques, biochimiques, physiologiques et comportementaux

indésirables sur divers organismes aquatiques. Ces effets indésirables se manifestent à partir de 20 µg/litre.
Cependant, la toxicité du zinc pour ces organismes dépend d'un grand nombre de facteurs comme la
température, la dureté et le pH de l'eau ainsi que des expositions antérieures éventuelle à cet élément.

D'une façon générale, les effets toxiques du zinc sur les végétaux se traduisent par des troubles métaboliques
différents de ceux que l'on observe en cas de carence zincique. Dans le tissu foliaire de la plupart des espèces
végétales, une concentration de zinc de l'ordre de 200- 300 mg/kg de poids sec constitue un seuil critique
pour la croissance.

Les études effectuées sur le terrain montrent que les invertébrés aquatiques, les poissons et les végétaux
terrestres qui vivent à proximité de sources de pollution zincique en subissent les effets nocifs. Toutefois, les
végétaux terrestres, les algues, les microorganismes et les invertébrés qui vivent non loin des zones fortement
polluées par le zinc, ont acquis une tolérance à cet élément.

10. Conclusions
10.1 Santé humaine

• Les émissions de zinc dues à l'activité humaine ont tendance à diminuer.

• Il est possible qu'un grand nombre d'échantillons - notamment des échantillons d'eau -
prélevés avant 1980 aient été contaminés par du zinc lors des prélèvements et de l'analyse et
c'est pourquoi la plus grande prudence s'impose concernant les valeurs de la concentration.
• Dans les pays où l'alimentation de base est constituée de légumineuses et de céréales non
raffinées et où la consommation de produits carnés est faible, il faudrait élaborer des
stratégies pour accroître la teneur en zinc des aliments et la biodisponibilité de cet élément.

• Les préparations qui sont destinées à augmenter l'apport de zinc au-delà de l'apport
alimentaire ne doivent pas avoir une teneur en zinc supérieure à la teneur de référence et
contenir en outre suffisamment de cuivre pour que le rapport Zn/Cu soit d'environ 7,
comme dans le lait humain.
• Il faudrait que l'exposition réelle aux vapeurs d'oxyde de zinc sur les lieux de travail soit
mieux documentée. La concentration en oxyde de zinc ne devrait pas y entraîner une
exposition aussi intense que celle qui provoque une réaction inflammatoire pulmonaire chez
des volontaires.
• Etant donné que le zinc est un élément essentiel, qu'il est relativement peu toxique pour
l'Homme et que les sources d'exposition humaine sont limitées, il apparaît que pour des
sujets en bonne santé qui ne sont pas professionnellement exposés à cet élément, le risque
d'une carence zincique est potentiellement plus important que celui qui découle de
l'exposition ordinaire dans l'environnement.
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10.2 Environnement

• Le zinc est un élément essentiel. Il peut y avoir carence ou au contraire excès de ce métal.
C'est pourquoi il importe que la réglementation relative au zinc, tout en assurant une
protection contre ses effets toxiques, n'impose pas des teneurs trop faibles qui pourraient
entraîner une carence zincique.

• Il existe des différences dans les réactions à une carence zincique ou à un excès de zinc.
• La biodisponibilité du zinc dépend d'un certain nombre de facteurs biotiques ou abiotiques
comme par exemple l'âge et la taille de l'organisme en cause, l'éventualité d'une exposition
antérieure, la dureté de l'eau, le pH, la teneur en carbone organique dissous et la
température.

• La concentration totale d'un élément essentiel tel que le zinc, ne permet pas à elle seule,
d'en prévoir correctement la biodisponibilité ou la toxicité.

• Pour des éléments essentiels comme le zinc, il existe une fourchette de concentration
optimale.

• La toxicité du zinc dépend des conditions environnementales et de la nature des biotopes,

de sorte que toute évaluation du risque relative aux effets potentiels de cet élément sur les
êtres vivants doit tenir compte de l'écologie locale.

RESUMEN Y CONCLUSIONES
1. Identidad y propiedades físicas y químicas
El zinc metálico no se encuentra de forma natural en el medio ambiente. Está presente sólo en estado
divalente como Zn (II). El zinc iónico sufre solvatación, dependiendo su solubilidad del pH y de la
concentración de aniones. El zinc es un elemento de transición y puede formar complejos con diversos
ligandos orgánicos. En la naturaleza no existen compuestos organometálicos de zinc.

2. Métodos analíticos
Debido a la ubicuidad del zinc en el medio ambiente, hay que prestar especial atención durante el muestreo,
la preparación y el análisis de las muestras para evitar su contaminación. La preparación de muestras a partir
de material sólido normalmente requiere la mineralización con ácidos concentrados y con la ayuda de
microondas. Para las muestras acuosas, se ha utilizado la extracción con disolventes en presencia de
sustancias capaces de formar iones complejos y la separación mediante resinas quelantes para conseguir una
concentración previa del zinc.

Las técnicas instrumentales normalmente utilizadas para la determinación del zinc son: espectrometría de
emisión atómica de plasma con acoplamiento inductivo, espectrometría de absorción atómica en horno de
grafito, voltametría de arranque anódico y espectrometría de masas de plasma con acoplamiento inductivo.
Para el análisis de concentraciones bajas se utilizan la espectrometría de absorción atómica en horno de
grafito, la voltametría de arranque anódico y la espectrometría de masas de plasma con acoplamiento
inductivo.

Prestando especial atención se pueden detectar concentraciones muy bajas, de hasta 0,006 µg/litro y 0,01
mg/kg en muestras acuosas y sólidas, respectivamente.

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Los análisis de especiación en agua requieren la aplicación de técnicas de separación con cualquiera de los
métodos antes mencionados o la separación de enlaces lábiles mediante voltametría de arranque anódico.

3. Fuentes de exposición humana y ambiental

La mayoría de las rocas y muchos minerales contienen zinc en cantidades variables. Desde el punto de vista
comercial, la esfalerita (SZn) es el mineral más importante y la fuente principal del metal para la industria
del zinc. En 1994, la producción de zinc metálico en todo el mundo fue de 7 089 000 toneladas y su consumo
de 6 895 000 toneladas.

El zinc se utiliza ampliamente como revestimiento protector de otros metales, en la fundición de color y en la
industria de la construcción, así como para aleaciones. Los compuestos de zinc inorgánico tienen varias
aplicaciones, por ejemplo de equipamiento para el automóvil, baterías de acumuladores y pilas secas y
aplicaciones dentales, médicas y domésticas. Los compuestos orgánicos de zinc se utilizan como fungicidas,
antibióticos tópicos y lubrificantes.

El zinc se convierte en maleable cuando se calienta a 100- 150 °C y entonces se moldea fácilmente para
darle distintas formas. Es capaz de reducir la mayoría de los otros estados metálicos y, por consiguiente, se
utiliza como electrodo en pilas secas y en hidrometalurgia.

La emisión natural más importante de zinc al agua procede de la erosión. Las aportaciones naturales al aire
se deben fundamentalmente a emisiones ígneas y a incendios forestales. Las fuentes antropogénicas y
naturales son de una magnitud semejante. Las principales fuentes antropogénicas de zinc son la extracción,
las instalaciones de producción de zinc, la producción de hierro y acero, la corrosión de estructuras
galvanizadas, la combustión de carbón y otros combustibles, la eliminación e incineración de desechos y el
uso de fertilizantes y plaguicidas con zinc.

4. Transporte, distribución y transformación en el medio ambiente

El zinc se encuentra en la atmósfera fundamentalmente unido a partículas de aerosol. El tamaño de la
partícula depende de la fuente de emisión del zinc. Una proporción importante del zinc que se libera en los
procesos industriales se adsorbe sobre partículas suficientemente pequeñas para quedar en la gama
respirable.

El transporte y la distribución del zinc atmosférico varían en función del tamaño de las partículas y de las
propiedades de los compuestos de zinc correspondientes. El zinc se elimina de la atmósfera mediante
deposición seca y húmeda. El zinc que se adsorbe sobre partículas con densidad y diámetro bajos puede
recorrer largas distancias.

La distribución y el transporte del zinc en el agua, los sedimentos y el suelo dependen de las especies de zinc
presentes y de las características del medio ambiente. La solubilidad del zinc está en función sobre todo del
pH. Con valores de pH ácido, el zinc puede estar presente en la fase acuosa en su forma iónica. A un pH
superior a 8 puede precipitar. También puede formar complejos orgánicos estables, por ejemplo con los
ácidos húmico y fúlvico. La formación de estos compuestos puede aumentar la movilidad y/o la solubilidad
del zinc. No es probable la lixiviación del zinc a partir del suelo, debido a su adsorción sobre la arcilla y la
materia orgánica. Los suelos ácidos y los arenosos con un contenido orgánico bajo tienen menos capacidad
de absorción.

El zinc es un elemento esencial, por lo que la mayoría de los organismos regulan sus niveles in vivo. El zinc
no se bioamplifica. Los animales acuáticos lo absorben del agua más que de los alimentos. Sólo el zinc
disuelto tiende a estar biodisponible, dependiendo dicha biodisponibilidad de las características físicas y
químicas del medio ambiente y de los procesos geológicos. En consecuencia, la evaluación en el medio
ambiente se debe realizar de manera específica para cada lugar.

5. Concentraciones en el medio ambiente

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El zinc se encuentra en todas partes en muestras del medio ambiente y biológicas. Sus concentraciones en los
sedimentos del suelo y en el agua dulce dependen en gran medida de influencias geológicas y antropogénicas
locales, de manera que son muy variables. La concentración natural total de fondo de zinc suele ser <0,1- 50
µg/litro en el agua dulce, 0,002- 0,1 µg/litro en el agua marina, 10- 300 mg/kg de peso seco en el suelo,
hasta 100 mg/kg de peso seco en los sedimentos y hasta 300 ng/m3 en el aire. Se pueden atribuir niveles
superiores a la presencia natural de minerales con concentraciones elevadas de zinc, a fuentes antropogénicas
o a procesos abióticos y bióticos. En muestras con contaminación de origen antropogénico, se obtienen
concentraciones de zinc de hasta 4 mg/litro en el agua, 35 g/kg en el suelo, 15 µg/litro en el agua de estuarios
y 8 µg/m3 en el aire.

Su concentración en organismos representativos durante la exposición al zinc presente en el agua es del

orden de 200- 2000 mg/kg.

Las concentraciones en plantas y animales son más altas cerca de fuentes puntuales antropogénicas de
contaminación por zinc. Las variaciones interespecíficas en cuanto al contenido de zinc son considerables;
los niveles intraespecíficos varían, por ejemplo, con la fase de la vida, el sexo, la estación, la alimentación y
la edad. Las concentraciones normales de zinc en la mayor parte de los cultivos y pastos son del orden de
10- 100 mg/kg de peso seco. Algunas plantas acumulan zinc, pero la magnitud de la acumulación en los
tejidos vegetales varía con las características del suelo y de la propia planta.

Sólo se inhalan cantidades insignificantes de zinc del aire ambiente, pero es posible la exposición a una gran
variedad de tipos de polvo y de vapor de zinc y sus compuestos en el entorno ocupacional.

5.1 Ingesta humana

La gama estimada de ingesta diaria total de zinc con los alimentos es de 5,6- 10 mg/día para los lactantes y
los niños de edades comprendidas entre los dos meses y los 11 años, de 12,3- 13,0 mg/día para los niños de
12- 19 años y de 8,8- 14,4 mg/día para los adultos de 20- 50 años. La ingesta diaria media de zinc con el
agua de bebida se estima en <0,2 mg/día.

Los valores de referencia del zinc en los alimentos varían según los hábitos alimentarios del país, las
hipótesis sobre la biodisponibilidad del zinc en los alimentos y la edad, el sexo y las condiciones fisiológicas.
Los valores de referencia en los alimentos oscilan entre 3,3 y 5,6 mg/día para los lactantes de 0- 12 meses,
entre 3,8 y 10,0 mg/día para niños de 1- 10 años y entre 8,7 y 15 mg/día para los adolescentes de 11- 18
años. Para los adultos, los valores varían entre 6,7 y 15 mg/día para las edades de 19- 50 años, entre 7,3 y 15
mg/día durante la gestación, suponiendo un consumo de alimentos con una disponibilidad moderada de zinc,
y entre 11,7 y 19 mg/día durante la lactación, dependiendo de la fase.

6. Cinética y metabolismo en animales de laboratorio y en el ser

humano
En estudios de inhalación (solamente nasal) realizados con cobayas, ratas y conejos se observaron valores de
retención del 5%- 20% en el pulmón tras la exposición a aerosoles de óxido de zinc a una concentración de
5- 12 mg/m3 durante 3- 6 horas. La absorción intestinal del zinc está regulada por un mecanismo
homeostático que no se conoce del todo, pero que depende fundamentalmente de la secreción pancreática e
intestinal y de la excreción fecal. En la homeostasis pueden intervenir proteínas fijadoras de metales, como
por ejemplo la metalotioneína y una proteína intestinal rica en cisteína. También pueden existir otros
mecanismos desconocidos. La absorción a partir de la mucosa intestinal puede entrañar procesos de
transporte tanto activo como pasivo. En los animales, la absorción puede variar en la gama del 10%- 40% en
función de su situación nutricional y de la presencia de otros ligandos en los alimentos. Se puede producir
absorción cutánea de zinc a partir del óxido y el cloruro de zinc, siendo mayor en casos de deficiencia de
zinc. El zinc absorbido se deposita principalmente en los músculos, los huesos, el hígado, el páncreas, el
riñón y otros órganos. La semivida biológica del zinc es de unos 4- 50 días en la rata, en función de la dosis
administrada, y de unos 280 días en las personas.

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7. Efectos en los animales de laboratorio

La toxicidad aguda por vía oral en roedores expuestos al zinc es baja, con valores de la DL50 del orden de
30- 600 mg/kg de peso corporal, en función de la sal de zinc administrada. Entre los efectos agudos en
roedores tras la inhalación o la instilación intratraqueal de compuestos de zinc figuran trastornos
respiratorios, edema pulmonar e infiltración de leucocitos en los pulmones.

Los efectos tóxicos del zinc para los roedores tras una exposición breve por vía oral incluyen debilidad,
anorexia, anemia, disminución del crecimiento, pérdida de pelo y una utilización menor de los alimentos, así
como cambios en las concentraciones de las enzimas del hígado y el suero, cambios morfológicos y
enzimáticos en el cerebro y cambios histológicos y funcionales en el riñón. La concentración a la cual el zinc
no produce síntomas adversos en los roedores se ha establecido en unos 160 mg/kg de peso corporal en las
ratas. Se observaron cambios pancreáticos en crías expuestas a concentraciones altas de zinc en los
alimentos. La exposición breve por inhalación de cobayas y ratas a concentraciones de óxido de zinc >5,9
mg/m3 provocó inflamación y daño pulmonar.

La exposición prolongada por vía oral al zinc puso de manifiesto que los órganos destinatarios de la
toxicidad eran en ratas, hurones y conejos el sistema hematopoyético; en ratas y ratones el riñón; y en ratones
y hurones el páncreas. Se notificó una concentración sin efectos observados (NOEL) con respecto al
crecimiento y la anemia para el sulfato de zinc en los alimentos < 100 mg/kg en la rata. Al aumentar la
concentración de zinc en el organismo de animales experimentales expuestos a él se produce una reducción
de la concentración de cobre, lo que parece indicar que algunos de los signos de toxicidad atribuidos a la
exposición a concentraciones excesivas de zinc podrían deberse a una deficiencia de cobre inducida por el
zinc. Además, diversos estudios han puesto de manifiesto que la exposición al zinc altera las concentraciones
de otros metales esenciales en el organismo de los animales expuestos, incluido el hierro. Algunos signos de
toxicidad observados en los animales expuestos a concentraciones elevadas de zinc se pueden atenuar
añadiendo cobre o hierro a los alimentos.

Las concentraciones muy altas de zinc son tóxicas para los ratones y los hámsteres en gestación. Las ratas
expuestas a un 0,5% y un 1% de zinc en los alimentos durante cinco meses no pudieron concebir hasta que se
suprimió el zinc de su alimentación. Las concentraciones altas de zinc en los alimentos (2000 mg/kg) se
asociaron también con un aumento de las resorciones y de los casos de muerte prenatal en ratones y ratas;
este resultado también se ha observado en ovejas y hámsteres. Las resorciones aumentaron en un estudio en
el cual las ratas estuvieron expuestas durante todo el período de la gestación a concentraciones bajas de zinc,
de apenas 150 mg/kg. Sin embargo, en otro estudio con ratas no se observaron efectos perjudiciales sobre el
desarrollo del feto a dosis de 500 mg/kg. Se comprobó que la exposición después del coito de ratas a
concentraciones de zinc de 4000 mg/kg en los alimentos interfería con la implantación del óvulo. El aumento
de la concentración de zinc en crías de ratas expuestas a él provocó una reducción de las concentraciones de
cobre y de hierro.

Se han realizado estudios de genotoxicidad en diversos sistemas. La mayoría de los resultados han sido
negativos, pero se han notificado algunos positivos.

La deficiencia de zinc en los animales se caracteriza por una reducción del crecimiento y de la replicación
celular, efectos reproductivos adversos y efectos adversos en el desarrollo, que persisten tras el destete, así
como una disminución de la respuesta inmunitaria.

8. Efectos en el ser humano

Se han notificado incidentes de intoxicación con síntomas de malestar gastrointestinal, náuseas y diarrea tras
una exposición única o breve a concentraciones de zinc en el agua o en bebidas de 1000- 2500 mg/litro. Se
han descrito síntomas semejantes, que ocasionalmente provocan la muerte, tras la administración intravenosa
inadvertida de grandes dosis de zinc. En pacientes de diálisis renal expuestos al zinc mediante el uso de agua
almacenada en compartimentos galvanizados se han observado síntomas de toxicidad del zinc que fueron
reversibles al filtrar el agua por carbón activado.

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Se demostrado que una ingesta desproporcionada de zinc en relación con el cobre induce deficiencia de
cobre en las personas, provocando un aumento de la necesidad de cobre, mayor excreción de cobre y una
situación de deficiencia de cobre. La ingesta farmacológica de zinc se ha asociado con efectos que van desde
la leucopenia y/o la anemia microcítica hipocrómica hasta la disminución de la concentración de
lipoproteínas de alta densidad en el suero. Estas condiciones fueron reversibles al interrumpir la terapia de
zinc y administrar un suplemento de cobre.

Los efectos en la salud humana asociados con la deficiencia de zinc son numerosos y entre ellos figuran
cambios neurosensoriales, oligospermia, alteración de las funciones neurosicológicas, retraso del
crecimiento, retraso de la cicatrización de las heridas, trastornos inmunitarios y dermatitis. Estas condiciones
generalmente son reversibles cuando se corrigen con la administración de zinc suplementario.

No hay un índice bioquímico único, específico y sensible de la situación con respecto al zinc. El método más
fidedigno para detectar su deficiencia es observar una respuesta positiva a un suplemento de zinc en ensayos
doble ciego controlados (en ausencia de otras deficiencias limitantes de nutrientes). Sin embargo, este
método es lento y con frecuencia poco práctico y en general se prefiere la determinación de una combinación
de índices alimentarios, bioquímicos y fisiológicos funcionales. Varios valores anormales concordantes son
más fidedignos que un valor aislado anómalo en el diagnóstico de un estado de deficiencia de zinc. La
inclusión de índices fisiológicos funcionales, como el crecimiento, la agudeza degustativa y la adaptación a
la oscuridad con una prueba bioquímica (por ejemplo, la concentración de zinc en el plasma o en el pelo),
permite evaluar el alcance de las consecuencias funcionales de la situación de deficiencia de zinc.

La exposición al cloruro de zinc por inhalación tras el uso militar de "bombas de humo" produjo efectos
como edema intersticial, fibrosis intersticial, neumonitis, edema de la mucosa bronquial, ulceración e incluso
la muerte en condiciones extremas de exposición en espacios cerrados. Estos efectos posiblemente son
atribuibles al carácter higroscópico y astringente de las partículas liberadas por tales dispositivos.

La exposición ocupacional a la materia particulada finamente dispersa que se forma cuando se volatilizan
ciertos metales, entre ellos el zinc, puede provocar una enfermedad aguda denominada "fiebre de los
fundidores", caracterizada por diversos síntomas, como por ejemplo fiebre, escalofríos, disnea, náuseas y
fatiga. El trastorno es generalmente grave pero transitorio, y las personas tienden a adquirir tolerancia. La
exposición de voluntarios a concentraciones de zinc de 77- 150 mg/m3 durante 15- 30 minutos dio lugar a
un aumento de los síntomas en algunos de ellos, una acusada respuesta inflamatoria relacionada con la dosis,
con aumento de los linfocitos polinucleares en el fluido de lavado bronquioalveolar, y un aumento acentuado
de la citoquinesis. Se ha notificado asma ocupacional en personas que trabajan con fundentes para soldadura
blanda, pero las pruebas no fueron suficientes para indicar una relación causal. Hace poco se ha
diagnosticado un caso raro que parece indicar una relación de ese tipo en un trabajador de una instalación de
galvanización por inmersión en caliente (zinc).

9. Efectos sobre otros organismos en el laboratorio y sobre el terreno

El zinc es importante para la estabilidad de las membranas, en más de 300 enzimas y en el metabolismo de
las proteínas y los ácidos nucleicos. Hay que encontrar un equilibrio entre los efectos adversos del zinc y su
carácter esencial. Se ha notificado deficiencia de zinc en una amplia variedad de plantas cultivadas y
animales, con efectos graves en todas las fases de la reproducción, el crecimiento y la proliferación tisular.
Las deficiencias de zinc en diversos cultivos han producido pérdidas importantes en todo el mundo. La
deficiencia de zinc es rara en los organismos acuáticos del medio ambiente, pero se puede inducir en
condiciones experimentales.

En la toxicidad del zinc pueden influir factores tanto bióticos como abióticos, como la edad y el tamaño del
organismo, la exposición anterior, la dureza del agua, el pH, el carbono orgánico disuelto y la temperatura.
La integración de la química y la toxicología en el medio ambiente ha permitido predecir mejor los efectos
en los organismos presentes en él. Esto ha llevado al punto de vista actualmente aceptado de que la
concentración total de un elemento esencial como el zinc en un compartimento del medio ambiente no es,
considerada de manera aislada, un buen indicador de su biodisponibilidad.

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Los valores de la toxicidad aguda del zinc disuelto para los invertebrados de agua dulce oscilan entre 0,07
mg/litro para la pulga de agua y 575 mg/litro para un isópodo. Los valores de la toxicidad aguda para los
invertebrados marinos varían entre 0,097 mg/litro para un mísido y 11,3 mg/litro para el camarón de fangal.
La concentración letal aguda para los peces de agua dulce es del orden de 0,066- 2,6 mg/litro; la gama para
los peces marinos es de 0,19- 17,66 mg/litro.

Se ha demostrado que el zinc tiene efectos reproductivos, bioquímicos, fisiológicos y de comportamiento

adversos en diversos organismos acuáticos. Se ha puesto de manifiesto que las concentraciones de zinc >20
µg/litro tienen efectos adversos en los organismos acuáticos. Sin embargo, la toxicidad del zinc para tales
organismos depende de numerosos factores, por ejemplo la temperatura, la dureza y el pH del agua y la
exposición anterior al zinc.

En general, la toxicidad del zinc en las plantas provoca trastornos en el metabolismo que son diferentes de
los que produce su deficiencia. La concentración crítica de zinc en el tejido foliar para un efecto sobre el
crecimiento varía en la mayoría de las especies de 200 a 300 mg/kg de peso seco.

En estudios sobre el terreno se han detectado efectos adversos en los invertebrados acuáticos, los peces y las
plantas terrestres en las cercanías de fuentes de contaminación por zinc. Se ha observado la aparición de
tolerancia al zinc en plantas terrestres, algas, microorganismos e invertebrados de las cercanías de zonas con
concentraciones elevadas de zinc.

10. Conclusiones
10.1 Salud humana

• Hay una tendencia decreciente en las emisiones antropogénicas de zinc.

• Muchas de las muestras del medio ambiente tomadas antes de 1980, en particular las
muestras de agua, pueden haber experimentado una contaminación por zinc durante el
muestreo y el análisis, por lo que habría que tomar con precaución extremada los datos
sobre la concentración de zinc en esas muestras.
• En los países donde los alimentos básicos consisten en cereales y legumbres no refinados y
la ingesta de alimentos frescos es baja, se deberían formular estrategias alimentarias para
mejorar el contenido y la biodisponibilidad de zinc.

• Las preparaciones orientadas a aumentar la ingesta de zinc por encima de la proporcionada

mediante los alimentos no deberían contener concentraciones de zinc que superasen los
valores de referencia para la alimentación y deberían contener una concentración
suficiente de cobre para garantizar una razón zinc:cobre aproximada de 7, como en la
leche humana.
• Es necesario documentar mejor las exposiciones reales al humo de óxido de zinc en el
entorno ocupacional. Las concentraciones en el lugar de trabajo no deberían producir
niveles de exposición tan altos como los que se sabe que dieron lugar a respuestas
inflamatorias en los pulmones de los voluntarios.

• La naturaleza esencial del zinc, junto con su toxicidad relativamente baja para el ser
humano y las fuentes limitadas de exposición humana, parecen indicar que las personas
normales sanas no expuestas al zinc en el lugar de trabajo tienen potencialmente un riesgo
de sufrir los efectos adversos asociados con la deficiencia de zinc superior al que
acompaña a una exposición normal al zinc en el medio ambiente.

10.2 Medio ambiente

• El zinc es un elemento esencial. Existe la posibilidad tanto de una deficiencia como de un

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7.3.2019 Zinc (EHC 221, 2001)

exceso de este metal. Por este motivo, es importante que los criterios de reglamentación
del zinc, al mismo tiempo que protegen de la toxicidad, no se establezcan en un nivel tan
bajo que pueda llevar a la deficiencia.
• Hay diferencias en las respuestas a la deficiencia y al exceso.

• La biodisponibilidad del zinc depende de factores bióticos y abióticos, por ejemplo: la

edad y el tamaño de los organismos, el historial anterior de exposición, la dureza del agua,
el pH, el carbono orgánico disuelto y la temperatura.

• La concentración total de un elemento esencial como el zinc por sí sola no es un buen

indicador de su biodisponibilidad o toxicidad.

• Hay una gama de concentraciones óptimas para los elementos esenciales como el zinc.
• La toxicidad del zinc dependerá de las condiciones ecológicas y de los tipos de hábitat, de
manera que en cualquier evaluación del riesgo de los efectos potenciales del zinc en los
organismos se deben tener en cuenta las condiciones del medio ambiente local.

See Also:
Toxicological Abbreviations
Zinc (WHO Food Additives Series 17)
ZINC (JECFA Evaluation)
Zinc (UKPID)

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