Last Update: 4 November 2017
Part II
Chemical Toxicology M
1 TOXIC CHEMICALS IN THE ENVIRONMENT
There are a number of chemicals in the environment. Some of these are toxic and the rest non-toxic.
The toxic chemicals are discharged by industries into air, water and soil. They get into the human food chain
from the environment. Once they enter our biological system they disturb the biochemical processes, leading
in some cases to fatal results. Chemical toxicology is the science of the study of toxic chemicals and their
modes of action.
The list of toxic chemicals is very long. It is intriguing that even now there are many cases where one
is not sure whether a particular chemical compound is toxic or not. Some useful and important chemicals are
being controlled rigorously as their non-toxicity has not been proved. There are valid confusions in respect
of elements; where will the line be drawn between the 'essential limit' and 'toxic limit'? Such sub-division
(toxic essential) is artificial and can be misleading. Many metals listed as environmental hazards are
essential dietary trace elements required for normal growth and development of animals and human beings.
These elements are Al, Sb, As, Ba, Be, Bi, Cd, Co, Cu, Cc, In, Pb, Hg, Mo, Ag, Te, Tl, Sn, Ti, W, U and Zn.
Schwartz used the term concentration window to draw the arbitrary lines of demarcation:
(a) essential at trace level for sustenance of life processes,
(b) deficient at lower level than (a) causing metabolic disorder,
(c) toxic at higher level than (a) causing adverse effects.
Even the well-known toxic elements As, Pb and Cd are required in trace quantities for the growth of
animals. The so-called biologically inert Al causes brain damage, bone disease and anemia in patients
subjected to haemodialysis using water containing 100-1000 parts per
billion of Al (This is the normal dose of Al in drinking water where alum is used in water-treatment plants).
Toxic substances may be classified according to their function and effects, such as mutagens, carcinogens,
etc., or food additions, etc., or heavy metals, metal carbonyls, organochlorine compounds, etc.
According to the International Register of Potentially Toxic Chemicals of the United Nations
Environment Programme, there are four million known chemicals in the world today and another 30,000
new compounds are added to the list every year. Among these, 60,000 to 70,000 chemicals are commonly
used. Apart from their benefit to increasing production, living standards and health, many of them are
potentially toxic.
Toxic Chemicals in Air
As a matter of fact, thousands of chemicals presumably pose the problems of health hazards so that it is
necessary to exercise strict control on those which offer the most serious threats during manufacture and
handling. In 1978 the U.S. Environmental Protection Agency, Occupational Safety and Health
Administration, and Consumer Product Safely Commission listed 24 extremely hazardous substances in the
atmosphere:
Acrylonitrile, As, asbestos, benzene, Be, Cd, chlorinated solvents, chlorofluorocarbons, chromates, coke
oven emissions, diethylstilbestrol, dibromochloropropane, ethylene dibromide, ethyline oxide, Pb, Hg,
nitrosoamines, O3, polybrominated biphenyls, polychlorinated biphenyls, radiation, SO2, vinyl chloride and
toxic waste disposal emissions and Icachatcs.
Toxic Elements in Water
A list of toxic trace elements found in natural waters and waste waters is tabulated in Table 1. Some of these
are essential at low levels, serving as nutrients for animal and plant life, but are toxic at higher levels.
K. Schwartz, Clinic Chemistry and Chemical Toxicology of Metals p. 3, Elsevier (1977): Cited in G-S.
Fell, "Mewls in the Environment 2", Chem, Britain, 167 323
(1980).
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Table 1 Toxic trace elements in natural water and waste water
Elements Sources Effects and significance
Arsenic Mining by-product, pesticides, Toxic, possibly carcinogenic
chemical waste
Cadmium Industrial discharge, mining waste, Replaces zinc biochemically, causes
metal pitting, water pipes high blood pressure, kidney damage,
destruction of testicular tissue and red
blood cells, toxicity to aquatic biota
Beryllium Coal, nuclear power and space Acute and chrome toxicity, possibly
industries carcinogenic
Boron Coal, detergent formulations, Toxic to some plants
industrial wastes
Chromium Metal plating, cooling tower water Essential trace elements; possibly
additive (chromate) normally found as carcinogenic as Cr (VI)
Cr (VI) in polluted water
Copper Metal pitting, industrial and domestic Essential trace elements, not very toxic
waste, mining, mineral leaching to animals, toxic to plants and algae al
moderate levels
Fluorine Natural geological sources, industrial Prevents tooth decay at about 1 mg/l,
(Fluoride waste, water additive causes mottled teeth and bone damage
ion) at about 5 mg/1
Lead Industry, mining, plumbing, coal, Toxic (anaemia, kidney disease,
gasoline nervous disorder), wild-life destroyed
Manganese Mining industrial waste, acid mine Relatively non-toxic to animals, toxic to
drainage, microbial action on plants at higher levels, stains materials
manganese minerals at low pE (bothroom fixtures and clothing)
Mercury Industrial waste, mining, pesticides, Highly toxic
coal
Molybdenum Industrial waste, natural sources Possibly toxic to animals, essential for
plants
Selenium Natural geological sources, sulphur, Essential at low levels but toxic at
coal higher levels
Zinc Industrial waste, metal plating, Essential in many metalloenzymes,
plumbing toxic to plants at higher levels
Pesticides in Water
The water bodies contain a large number of pesticides, primarily from the drainage of agricultural
land. These pesticides belong to two major groups of chlorinated hydrocarbons and organic phosphates, the
latter group being more biodegradable.
2 IMPACT OF TOXIC CHEMICALS ON ENZYMES
In general, toxic chemicals attack the active sites of enzymes, inhibiting essential enzyme function.
Heavy metal ions, in particular, e.g. Hg2+, Pb3+ and Cd2+ act as effective enzyme inhibitors. They have
affinity for sulphur containing ligands e.g.: SCH3 andSH in methionine and cysteine amino acids, which
are part of the enzyme structure:
Metalloenzymes contain metals in their structures. Their action is inhibited when one metal ion of a
metalloenzyme is replaced by another metal ion of similar size and charge. Thus, Zn2+ in some
metalloenzymes is substituted by Cd2+ which leads to cadmium toxicity. The enzymes inhibited by Cd2+
include adenosine triphosphate, alcohol dehydrogenase, amylase, carbonic amylase, peptidase activity in
carboxypeptidase, and glutamic-oxaloacctic transminase. Pb2+ inhibits acetylcholenesterase, alkaline
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phosphatase, adenosine triphosphates, carbonic anhydrase, cy-tochrome oxidase, and some of the key
enzymes in the synthesis of heme.
The biochemical effects of some typical toxic substances are discussed in the following sections.
3 BIOCHEMICAL EFFECTS OF ARSENIC
Arsenic commonly occurs in insecticides, fungicides and herbicides. Among its compounds, those of
As(III) are the most toxic.
As(III) exerts its toxic action by attackingSH groups of an enzyme, thereby inhibiting enzyme action.
The enzymes which generate cellular energy in the citric acid cycle arc adversely affected. The
inhibitory action is based on inactivation of pyruvate dehydrogenase by complexation with As(III), whereby
the generation of ATP is prevented.
By virtue of its chemical similarity to P, As
interferes with some biochemical processes involving
P. This is observed in the biochemical generation of
the key energy-yielding substance, ATP (adenosine
triphosphate). An important step in ATP generation is
the enzymatic synthesis of 1, 3-diphosphoglycerate
from glyceraldehyde 3-phosphate. Arsenite interferes
by producing l-areseno-3-phosphoglyceratc instead of
1, 3-diphosphoglycertc. Phosphorylation is replaced by
arsenolysis which consists of spontaneous hydrolysis
10 3-phosphoglyccrate and arsenate.
Arsenic (III) compounds at high concentrations
coagulate proteins, possibly by attacking the sulphur
bonds maintaining the secondary and tertiary
structures of proteins.
The three major biochemical actions of As
are coagulation of proteins, complexation
with coenzymes and uncoupling of
phosphyrylation.
The general antidotes for As
poisoning are chemicals havingSH groups
capable of bonding to As(III), e.g., 2,3-
dimcrcaptopropanol (BAL).
4 BIOCHEMICAL EFFECTS OF
CADMIUM
Cd occurs in nature in association
with zinc minerals. Growing plants acquire
Zn and they also take up and concentrate Cd
with the same biochemical setup. The
outbreak of Cd poisoning occurred in Japan in the form of itai itai or "Ouch ouch" disease. Many people
suffered from this disease in which their bones became fragile. At high levels, Cd causes kidney problems,
anemia and bone marrow disorders.
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Fig. 1 Metabolism of cadmium
The major portion of Cd ingested
into our body is trapped in the kidneys
and eliminated. A small fraction is bound
most effectively by the body proteins,
metallothionein, present in the kidneys,
while the rest is stored in the body and
gradually accumulates with age. When
excessive amounts of Cd2+ are ingested,
it replaces Zn2+ at key enzymatic sites,
causing metabolic disorders.
5 BIOCHEMICAL EFFECTS
OF LEAD
Lead is a relatively abundant
metal in nature, occurring in lead
minerals. In the atmosphere is relatively
more abundant than other heavy metals. By far the major source of airborne Pb is the combustion of leaded
petrol/ gasoline. Pb is added in the form of tetraalkyl lead, primarily Pb(CH8)4 and Pb(C2H5)4, together with
the scavengers 1,2-dichloroethane and 1, 2-dibromoethane. In common with other particulate pollutants, Pb
is removed from the atmosphere by wet and dry deposition processes. As a result, street dusts and roadside
soils become enriched with Pb, with concentrations typically of the order 1000-4000 mg kg-' on busy streets.
It may be noted that most of the Pb intake by a typical city dweller is from diet (about 200-300 g per day),
air and water adding a further 10-15 g per day each. Of this total intake, 200 g of Pb is excreted while 25
g is stored in the bones each day.
Fig. 2 Daily lead balance for a city resident
The major biochemical effect of Pb is its interference
with heme synthesis, which leads to hematological damage. Pb
inhibits several of the key enzymes involved in the overall
process of heme synthesis whereby the metabolic
intermediates accumulate. One such intermediate is delta-
amino levulinic acid. An important phase of heme synthesis is
the conversion of delta-aminolevulinic acid to
prophobilinogen:
Pb inhibits the ALA-dehydrase enzyme (I) so that it
cannot proceed further to form (II) prophobilinogen.
The overall effect is the disruption of the synthesis of
haemoglobin as well as other respiratory pigments,
such as cytochromes, which require heme. Finally, Pb
does not permit utilization of O2 and glucose for life-
sustaining energy production. This interference can be
detected at a head level in the blood of about 0.3 ppm.
The detection of (I) provides a sensitive test for Pb in
the body. At higher levels of Pb in the blood (>0.8
ppm) there will be symptoms of anaemia due to the
deficiency of haemoglobin. Elevated Pb levels (>0.5-
0.8 ppm) in the blood cause kidney dysfunction and
finally brain damage.
Due to the chemical analogy of Pb2+ with Ca2+, bones act as repositories for Pb accumulated by the
body. Subsequently, this Pb may be remobilized along with phosphates from the bones which exert a toxic
effect when transported to soft issues.
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Lead poisoning can be cured by
treatment with chelating agents which
strongly bind Pb2+. Thus, calcium chelate in
solution is fed to the victim of lead
poisoning; Pb2+ displaces Ca2+ from the
chelate and the resulting Pb2+ chelate is
rapidly excreted in the urine. Three typical
Pb chelates are shown below.
5.6 BIOCHEMICAL EFFECTS OF
MERCURY
Minamata Incident* Mercury is a
well-known toxic metal which came to
limelight only after the incidence of
Minamata Disease in 1953-60 in Japan. At
Minamata Bay in Japan more than 100 people lost their lives and many thousands were permanently
paralyzed from eating mercury-contaminated fish. In a particular village facing the Bay (population 1100)
15% of the villagers were either killed or permanently crippled. Genetic defects are observed in some 50
babies whose mothers had consumed the contaminated fish from the Bay. The sea fish in the Bay were
found to contain 27-102 ppm of Hg in the form of methyl mercury. The source of Hg was the effluent
discharged into the Bay from a vinyl chloride plant, Minamata Chemical Company. The Hg was
deposited on the bottom of the Bay and remained there since 1950s.
In the long history of water pollution, the Minamata incident was unique. The mystery of the
existence of methyl mercury in sea fish was baffling first since the source was inorganic mercury compound
discharged into the Bay by the Minamata Chemical Plant. The missing link between inorganic mercury in
Bay water and methyl mercury in sea fish was bridged only after extensive research since the 1950s. This is
the first known case where the natural bioaccumulation (in fish) of a toxic material (methyl mercury) killed
hundred people and genetically damaged a large population (see next section).
The fate of Hg was traced by measuring some 300 Hg concentrations in the surface sediments in
Yatsushiro sea (outside the Bay) during 1970-85. Twenty four sampling stations were set up to collect
samples at the same location every year. The dispersion of Hg from the Bay was documented: on the
average, 3.7 tonnes of Hg was transported outside from the Bay every year. The total Hg concentration in
the Bay water ranged from 125 ng L-1 (0.125 ppb) at the centre of the Bay to 22 ng L-1 (0.022 ppb) near the
exit to Yatsushiro sea. The amount of organic Hg ranged from 1.8 to 5.5 ng L-1 in the Bay water while the
total Hg in Yatsushiro sea water was 16-25 ng L-1 (25-40 km. from effluent point) in 1985. A
decontamination project ($ 400 million project) in 1984 dredged about one million cubic metres of
contaminated sediment having Hg > 25 ppm and dramatically decreased the flow of Hg from ihe Bay to the
sea and protected the environment of the Tatsushiro sea for years to come. The clean-up operation was
evident from decrease in Hg concentration in Bay and sea water in 1985 which were considered reasonable
for inland waters.
* A. Kudo and S. Miyahara, A Case HistoryMinamata Mercury Pollution in Japan,
Water Sci. Tech. 23,283-290 (1991).
The Minamata incident was followed by a more tragic report of Hg
poisoning from Iraq in 1972 where 450 villagers died after eating wheat
which had been dusted with a mercury-containing pesticide. These two tragic
events boosted the awareness of Hg as a pollutant so that it was studied more
extensively than any other toxic element.
In nature, Hg occurs as a trace component of many minerals, conti-
nental rocks containing an average of about 80 parts per billion of Hg. The
principal ore is Cinnabar, Hg. Fossil fuels, coal and lignite contain about 100
parts per billion of Hg. The natural abundance in soil is 0.1 parts per million.
Hg finds a wide variety of applications. The largest consumer is the
chlor-alkali industry which manufactures Cl2 and NaOH by an electrolytic
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process using Hg electrodes. The second largest consumption of Hg is in the production of electrical
apparatus, e.g. Hg vapour lamp, electrical switches, Hg batteries etc. The third largest consumer is the
agricultural industry using a large number of fungicides for seed dressings. Some typical compounds of this
category are:
The impact of seed dressing is enormous since it is applied to a large volume of seed, which is
subsequently sowed over millions of acres, thereby causing a widespread dispersal of Hg compounds.
Furthermore, Hg undergoes translocation in plants and animals and then finds its way into the human food
chain.
Hg enters the environment mainly through human activities, as above. Sewage effluent sometimes
contains up to 10 times the level of Hg in natural water (0.001-0.0001 ppm). Once Hg is absorbed on
sediments of water bodies and streams, it is slowly released into the water and constitutes a reservoir which
is likely to cause chromic pollution long after the original source of Hg is removed. Natural addition of Hg
to the oceans is about 5000 tonnes per annum, and a further 5000 tonnes is added via human activities.
Toxic Effects
The toxicity of Hg depends on its chemical species as shown in Table 2.
Table 2 Chemical species of mercury
Species Chemical and biochemical properties
Hg Elemental mercury: Relatively inert and nontoxic; vapour highly toxic when
inhaled.
2 Mercurous ion: Insoluble as chloride; low toxicity.
Hg 2
Hg2+ Mercuric ion: Toxic but not easily transported across biological membranes.
RHg+ Organomercurials: Highly toxic, particularly CH3Hg+ (methyl mercury); causes
irreversible nerve and brain damage; easily transported across biological
membranes; stored in fat tissue.
R2Hg Diorganomercurials: Low toxicity but can be convened to RHg+ in acidic medium.
HgS Mercuric sulfide: Highly insoluble and non-toxic; trapped in soil in this form.
Elemental Hg is fairly inert and non-toxic. If swallowed, it is excreted without serious damage. It has
a fairly high vapour pressure and so the vapour, if inhaled, is quite toxic. Hence Hg should be handled only
in well-ventilated areas and spills should be cleaned up as quickly as possible. Hg vapour, when inhaled,
enters the brain through the blood stream, leading to severe damage of the central nervous system.
Hg 22 forms an insoluble chloride with chloride ions. As our stomachs contain a fairly high
concentration of chloride, Hg 22 is not toxic. Hg2+ (mercuric ion) however, is fairly toxic. Because of its
high affinity for Sulphur atoms, it easily attaches itself to the
sulphurcontaining amino acids of proteins. It also forms
bonds with haemoglobin and serum albumin, both of which
contain sulphydryl groups. This ion, however, does not travel
across biological membranes and hence does not get access
into biological cells.
The most toxic species are the organomercurials,
particularly CH3Hg+ (methyl mercury), which are soluble in
fat, the lipid fraction of membranes, and brain tissue. The
covalent Hg-C bond is not easily disrupted and the alkyl
mercury is retained in cells for prolonged periods of time.
The most dangerous aspect is the ability of RHg+ to move
through the placental barrier and enter foetal tissues.
Attachment of Hg to cell membranes is likely to
inhibit active transport of sugars across the membranes and
allow the passage of K to the membrane. In case of brain
cells, this will result in energy deficiency in the cell and
disorders in the transmission of nerve impulses. This will
explain why babies born to mothers subjected to methyl
mercury poisoning suffer from irreversible damage to the
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central nervous system, including cerebral palsy, mental retardation and convulsions. Methyl mercury
poisoning also leads to segregation of chromosomes, chromosome breakage in cells and inhibited cell
division. All the symptoms of mercury poisoning set in at blood levels of 0.5 ppm of CH3Hg+.
Biological Methylation: Amplification in Food Chain
The Minamata Chemical Company
discharged Hg into Minamata Bay, but the
fish in the Bay were found to contain
CH3Hg+. This missing link was filled up
by subsequent research. Hg or its salts can
be converted to methyl mercury by anaerobic methane-synthesizing bacteria in water. This conversion is
facilitated by Co(III)-containing vitamin B]2coenzyme. A CH3 -group bonded to Co(III) on the coenzyme is
transferred enzymatically by methyl cobalamin to Hg2+, yielding CH3Hg+ or (CH3)2Hg:
An acidic medium promotes the conversion of dimethyl mercury to methyl mercury which is soluble
in water. It is methyl mercury which enters the food chain through plankton, and is concentrated by fish by a
factor 103 or more as it passes up the food chain, as shown in Fig. 3.
The Hg concentration builds up at each level of the food chain. This is valid even in uncontaminated
waters. Hg has always been part of our environment and Hg cycles existed long before any industry
developed. Large fish of ancient ages, preserved in some museums, have been found to contain significant
level of Hg. However, Hg pollution considerably enhances the Hg concentration in each level of the food
chain.
Soon after the Minamata disaster, it was reported that fresh-water fish from lake Erie and the St
Chair showed high levels of Hg(0.1-3.5 ppm), in the form of
Fig. 3 Propagation of mercury in food chain
methyl mercury in their living tissues. As a result,
important commercial fisheries in those areas were closed
down.
Remedial measures
Further environmental pollution by Hg can be prevented by adopting the following measures, as
recommended by the Environmental Protection Agencies of USA and Sweden:
1. All chlor-alkali plants must stop using Hg electrodes and switch to new technology.
2. All alkyl mercury pesticides must be banned.
3. All other mercurial pesticides must be restricted to some selected areas.
It should be noted that the already contaminated sediments of rivers and lakes will continue to yield
highly toxic CH3Hg+ into the waters for many years to come. In Sweden, pilot experiments were undertaken
for decontamination of sediments by covering the bottom sediments with fresh, finely divided materials
having high absorption capabilities and, alternatively, by burying the sediments under inorganic inert
materials.
7 BIOCHEMICAL EFFECTS OF CARBON MONOXTOE
The sources of CO are described in Ch. 6. The global atmosphere has a toad of approximately 530
million tones of CO, with an average residence of 36 to 110 days.
CO attacks haemoglobin and displaces O2 to form carboxy-haemoglobin. The reaction has an
equilibrium constant of approximately 210:
The carboxyhaemoglobin is a stronger complex so that the net result is reduction in the blood's
capacity for carrying O2.
The initial effect of CO poisoning is loss of awareness and judgment, which are responsible for many
automobile accidents. With increasing exposure to higher levels of CO, various metabolic disorders will
occur, ending in death, as shown in Table 5.3.
CO poisoning can be cured by exposing the affected person to fresh O2, whereby the reverse reaction
occurs:
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Traffic policemen on duty at busy street crossings during heavy traffic rush hours are advised to use
oxygen tanks in developed countries.
Table 3 Effects of continuous exposure to various levels of carbon monoxide
CO level, % conversion of Effects on humans
ppm O2Hb to COHb
10 2 Impairment of judgment and visual perception
100 15 Headache, dizziness, weariness
250 32 Loss of consciousness
750 60 Death after several hours
1000 66 Rapid death
8 BIOCHEMICAL EFFECTS OF NITROGEN OXIDES
Nitric oxide, NO, is less toxic than the dioxide, NO2. Like CO, it forms bonds with haemoglobin and
reduces O2 transport efficiency. In polluted air, NO is present at a much lower concentration than CO, so
that the effect on haemoglobin is much less.
NO2 is more harmful to human health. The effect of exposure to various levels of NO2 is shown in
Table 5.4.
Table 4 Effect of Exposure to various levels of NO2 on human health
Level of NO2, Duration of exposure Effects on human health
ppm
50-100 Up to 1 hour Inflammation of lung tissue for 6-8 weeks
150-200 Bronchiolitis fibrosa obligerans fatal result within
3-5 weeks of exposure
500 or more 2-10 days Death
Inhalation of NO2-containing gases from burning celluloid and nitrocellulose film lead to death. Two
people died and five were injured when there was accidental release of liquid N0 2 while loading into a Titan
II intercontinental missile at Rock, Kansas on August 24,1978. Liquid NO 2 was used in these rockets as an
oxidant for N2H4 fuel.
The biochemical mechanisms of NO2 toxicity are not clear. Probably some cellular enzyme systems
are susceptible to disruption by NO2, including catalase and lactic dehydrogenase. A possible antidote is
antioxidant vitamin E.
5.9 BIOCHEMICAL EFFECTS OF SULPHUR DIOXIDE
Sulphur dioxide is responsible for air pollution incidents, including fatalities in several countries, as
listed in Table 5.5.
Table 5.5 Sulphur dioxide poisoning cases
Year Place/Country Remarks-Effects
December- Meuse River Thermal inversion trapped SO2 38 ppm level 60
1930 Valley, Belgium deaths several cattle killed
October, Donora, Pennsyl- 40% population affected 20 deaths 2 ppm SO2
1948 vania, USA
December, London Temperature inversion smog 1.3 ppm SO2 approx.
1952 3500-4000 deaths in excess of normal
January, London 0.4 ppm SO, 180-200 deaths, majority victims (60%) in
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1956; the age group 70+years
December,
1957
The primary effect of SO2 is on the respiratory tract, causing irritation and increasing airway
resistance. It appears that most individuals experience irritation at SO2 levels of 5 ppm and above. Some
sensitive individuals even suffer irritation at 1-2 ppm SO2, and sometimes experiences severe bronchial
spasms on exposure to 5-10 ppm SO2. The symptoms of irritation are constriction of the air pathways
(respiratory tract) with corresponding increases in resistance to air flow during breathing.
The most widespread disaster due to SO2 occurs when it is a accompanied by smoke. This
combination occurs during temperature inversion smog conditions. In London (December 5-9,1952) heavy
smog conditions prevailed for five days at a stretch which took toll of 4000 deaths above the normal. The
peak SO2 concentration was 1.3 ppm and smoke, 4 mg m-3. The causes of death were bronchitis, pneumonia
and allied respiratory troubles. Similar smog conditions recurred in December 1962 but the number of
deaths was 700. The lower death rates was due to less smoke due to enforcement of the Clean Air Act, in
1962.
SO2 is deemed by public health authorities to be the most serious air pollutant, in spite of the fact that
20 ppm it causes no harm and becomes fatal only at 500 ppm. The reason for such concern is the way it
affects the aged population, particularly those who suffer from diseases of the respiratory and cardiovascular
systems. These aged people are highly susceptible to prolonged exposure to SO2 at elevated levels
characteristic of air pollution disasters.
Effect on Plants
SO2 is injurious to plants. Exposure to high levels of the gas causes destruction of leaf tissue (leaf
necrosis) and damage of the edges of leaves and the areas between leaf veins. Chronic exposure to SO2 leads
to chlorosis, i.e. bleaching or yellowing of the normally green portions of leaves. As relative humidity
increases, plant injury also is enhanced. Such injury becomes maximum when the stomata (small openings
in surface tissue which provide for interchange of gases with the atmosphere) are open, i.e. during daytime.
It is known that long-term low-level exposures to SO2 are more dangerous for crops than short-term high
dose exposures.
SO2 causes acid rains (Ch. 6) which also damage plants, besides, aquatic lives in rivers and lakes.
10 BIOCHEMICAL EFFECTS OF OZONE AND PAN
Both ozone and peroxyacetyl nitrate (PAN) are products of photochemical smog.
the former being the major product These are harmful to plants, animals and human beings.
Both O2 and PAN cause irritation of the eyes and respiratory tracts of human beings. Exposure to 50
ppm of O3 for several hours will lead to mortality due to pulmonary edema, i.e. accumulation of fluid in the
lungs. At lower levels, O3 brings about nonlethal accumulation of fluid in the lungs and damage to lung
capillaries. Young animals and humans are more susceptible to these toxic effects than older subjects.
The biochemical effects of O3 and PAN appear mostly to arise from the generation of free radicals.
The sulphydril groups (-SH) on enzymes are vulnerable to attack by these oxidants. These -SH groups are
oxidized by O3 and PAN and also acetylated by the latter. Among the sulphur-containing amino acids,
cysteine is strongly attacked by PAN
The enzymes inactivated by photochemical oxidants include isocitric dehydrogenase, malic
dehydrogenase and glucose-6-phosphate dehydrogenase. These enzymes are involved in the citric acid cycle
and in the degradation of glucose yielding cellular energy. It is also known that these oxidants inhibit the
activity of enzymes which synthesize cellulose and lipids in plants.
11 BIOCHEMICAL EFFECTS OF CYANIDE
Cyanide occurs in seeds of fruits such as apples, apricots cherries peaches and plums. Cyanide in plants is
bonded to glycoside (sugar) called amygdalin, and is released by enzymatic or acidic hydrolysis, (e.g. in the
stomach).
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Cyanide enters the environment from many sources. HCN is employed as a fumigating agent to
destroy rodents in grain bins, buildings and the holds of ships. Cyanide is used in various chemical syntheses
in electroplating and metal-cleaning industries.
Cyanide exerts its toxic action by inhibiting oxidative enzymes from mediating the process by which
O2 is utilized to complete the production of ATP in the mitochondria. In the first step, cyanide binds to
ferricytochrome oxidase, an iron-containing metalloprotein (abbreviated as Fe(lII)-oxid below) which is
reduced by glucose to Fe(II)-oxid ferrous cytochrome oxidase. The latter transfers the electrons to O (Step
II). The important products are the energetic ATP:
Cyanide interferes with step I
above by forming a bond with Fe (III)-
oxid, which is thereby inactivated so
that the reaction in step II, the energy-
producing process, is prevented.
Furthermore, CN-forms complexes
with other hematin compounds.
Cyanide poisoning can be treated by intravenous administration of NaNO2 or by inhalation of
amylnitrite. The reaction sequences are:
(a) NO2 oxidizes haemoglobin HbFe(II) to methemoglobin, HbFe(III) which is ineffective in carrying O 2
to tissues:
HbFe(II) HbFe(III) (11)
NO2
This reaction accounts for the toxic effect of NO2 which results in oxygen deficiency and sometimes death.
(b) HbFe(III) binds to CN, thereby releasing CN from the cyanide complex of ferricy tohrome oxidase,
Fe(III)-oxid:
HbFe(III) + Fe(III)-oxidCNHbFe(III)CN+ Fe(IIQ-oxid (12)
(c) Further treatment with S2O32 causes elimination of the cyanide:
HbFe(III) CN+ S2O32 SCN + HbFe(III) + SO32 (13)
This reaction is catalyzed by the enzyme rhodanase or mitochondrial sulphur transfers.
12 BIOCHEMICAL EFFECTS OF PESTICIDES
The list of pesticides as water pollutants is given in Ch. 3. From the viewpoint of public health, the
biochemistry of pesticides is of considerable significance. Biochemical processes constitute the major
mechanism by which pesticides in the environment are degraded and detoxified.
Among the pesticides, the biological action of DDT on the environment has been most extensively
studied. The central nervous system is the target of DDT, like many other insecticides. DDT dissolves in
lipid (fat) tissue and accumulates in the fatty membrane surrounding nerve cells. This is likely to lead to
interference with the transmission of nerve cells. The net result is disruption of the central nervous system
killing the target insect.
While DDT is fairly stable and persists in the environment, the other groupsorganophosphates and
carbamatesdegrade quite rapidly in
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the environment The latter react with O2 and H2O, undergoing decomposition within a few days in the
environment The products are not toxic.
Mode of Action of Insecticides
The mechanism by which chlorinated
hydrocarbons exert their toxic effects on
organisms is rot known with certainty. It is
presumed that they Dissolve in the fatty
membrane surrounding nerve fibre and interfere
with the transport of ions in and out of the fibre.
This leads to nerve impulse transmission which in
turn results in tremors, convulsions and death.
The pesticides probably inhibit a vital
enzyme, acetylcholinesterase as shown in Fig. 4.
Acetylcholine is a neurotransmitter it triggers
nerve cells. The space between nerve cells, called
a synapse, contains both acetylcholine and the enzyme acetylcholinesterase, which decomposes
acetylcholine and prevents the nerve cell from firing. This occurs in two steps A(l) and (2).
In the
first step the
enzyme acts
upon the
acetylcholine
forming an
intermediate
molecule,
the
acetylenzyme and one of the products, cho-line. In the next step the acetylenzyme is decomposed by H2O to
form CH3COOH and the enzyme is regenerated.
An organophosphate insecticide can mimic acetylcholine and induce the formation of a phosphoryl
enzyme. The rate of the reacton is determined by the rate of displacement of the x group from the
phosphorus atom by the enzyme. The breakdown of this intermediate is much slower (Step 2) than that of
the acetyl enzyme in A(2).
Fig. 5.4 (C) Acetylcholinesterase inhibition by carbamate insecticide
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Reactions under 5.4(B) and (C) proceed similarly. The phosphoryl and carbaryl enzymes, in B(l) and
C(l), build up and the level of the active enzyme decreases. The acetylcholine is no longer decomposed
rapidly enough and the nerve sorts firing in an uncontrollable manner, with the result that the organism
(insect/pest) is quickly killed.
DDT in Food Chain
As mentioned above, DDT is a persistent chemical. Once introduced into the environment, it keeps
circulating for many years.
It is interesting to note the manner in which DDT accumulates in the food chain. Plankton in
river/sea water contains about 0.04 ppm DDT. The clams that consume plankton concentrate it ten times, i.e.
they contain about 0.4 ppm DDT. From clams, to fish which feed on the clams, to fish eating birds, the DDT
level builds up from 0.4 to 2.1 and up to 75.5 ppm.
Fig. 5 Accumulation of DDT in aquatic food chain (in ppm)
DDT, the first pesticide to be introduced during World War n, found widespread agricultural use and
saved millions of lives through malaria control programmes. Its discoverer, the Swiss chemist Paul Miller,
won the Noble Peace Prize in 1948/ In spite of its tremendous service to humanity, DDT was banned in
USA because of concern about its long-term health effects. Although DDT does not act on the human
nervous system in the same way it does on insects, it stays in human bodies for a long time and its long-term
effects on humans are not known with certainty. The potential long-term effects of a chemical stored in body
fat compelled the US Environmental Protection Agency to ban DDT. In developing countries, however, it is
still in use, particularly in those regions where malaria is still endemic.
It is a well-known fact that many species of hunting birds, particularly those having high levels of
DDT, are threatened with extinction. Their eggs have shells which are too thin and fragile probably because
of interference with the hormones which control calcium deposition.
Methyl Isocyanate (MIC)
Methyl isocyanate, CH3NCO (MIC), is the raw material for the production of carbamate pesticide. It
is a volatile liquid, b.p. 43-45C, extremely hygroscopic and, therefore, stored in moisture-free refrigerated
tanks.
MIC is synthesized by the reaction of primary amine with phosgene, COC1 2. The intermediate
product is decomposed by heating with lime:
MIC is always associated with unreacted phosgene, COCl2 to the extent of 2%. The TLV (threshold limiting
value) for MIC is 0.02 ppm and for COC12, 0.1 ppm. Workers exposed to MIC suffer from chest tightness
and breathing troubles due to irritation of the respiratory tract Since it is accompanied by COCl 2, the
combined effect becomes fatal within 24 hours for most victims. Phosgene is a deadly gas, used as a poison
gas during World War I. Immediate symptoms of phosgene poisoning are bronchospasms, coughing,
constriction and pain in the chest. 80% of the victims die in the first 24 hours and those surviving usually die
from bronchopneumonia.
According to the findings of the World Health Organization some 750,000 people are poisoned by
pesticides every year, resulting in some 14.000 deaths. Developing countries account for only 30% of the
pesticide consumption, but share more than 60% of the casualties (Jan Husinans, Director of International
Register of Potentially Toxic Chemicals of UNEP, Nairobi, January 18,1985).
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13 CARCINOGENS
The term carcinogens means a group of chemicals which cause cancer in animals and humans. The
carcinogens affect DNA, preventing it from giving the necessary directions for the synthesis of substances
which control cell growth. Table 5.6 gives a list of carcinogens to which workers uiust not be exposed, as
established from studies of cancer-susceptible mice or mutagenicity in bacteria, as per recommendations of
the US Occupational Safety and Health Administration.
Table 5.6 Carcinogens to which workers should not be exposed
Compounds Uses Hazards
Chemical analysis May cause bladder cancer
Anti-oxidant, dye manufacture,
colour film manufacture
Plastic curing agent
Ion-exchange resin manufacture Usually contaminated with
carcinogenic bis (chloro-methyl) ether
Dye manufacture Known carcinogen
Ion-exchange resin manufacture Causes lung cancer
Dye manufacture, reagent Causes bladder cancer
Manufacture of dyes, rubber, Causes bladder cancer
plastics, printing ink
Paper and textile treating plastics Known carcinogen Suspected human
manufacture carcinogen
Polyvinyl chloride plastics Causes liver cancer
(PVC) manufacture
Industrial solvent, grain Causes stomach, spleen, lung cancer
fumigant and gasoline additive
for lead scavenging -74 x 106 kg
are lost to environment each year
Besides, the above chemicals, polycyclic aromatic hydrocarbons deserve special mention. Typical
examples are benzo (-) pyrene, chrysene and benzofluoranthene.
All professional chemists are required to possess a basic concept of chemical toxicology and remain
fully conscious of the chemical hazards of toxic chemicals.
QUESTIONS
1. Give a list of toxic chemicals in the environment. Indicate their sources and toxic actions. From this
list, prepare a short list of such chemicals in order of their toxicity.
2. Explain, with examples, the effect of toxic chemicals on enzymes.
3. Enumerate the biochemical effects of the following substances with particular reference to their
sources, species and pathways in the environment and impact on humans: (a) Arsenic (b) Mercury
(c) Lead
4. Explain the biochemical effects of:
(a) Carbon monoxide
(b) Nitrogen oxides
(c) Sulphur dioxide
(d) Cyanide
and suggest antidotes for each.
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