Testtt
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Received: 11 October 2014, Revised: 12 January 2015, Accepted: 13 January 2015 Published online in Wiley Online Library: 23 March 2015
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: heavy metals; aluminium; cosmetics; natural cosmetics; law regulations; metal nanoparticles; concentrations; toxic effects;
topical action; systemic action
J. Appl. Toxicol. 2015; 35: 551–572                         Copyright © 2015 John Wiley & Sons, Ltd.
                                                                                                                         S. Borowska and M. M. Brzóska
         One of the groups of dangerous substances present in cos-                et al., 2003; Aguilar et al., 2008; Cao et al., 2010; Zhuang et al., 2014).
      metics are heavy metals, including particularly toxic elements such         Herbal medicines and dental amalgams are other sources of expo-
      as lead (Pb), cadmium (Cd), nickel (Ni), arsenic (As) and mercury           sure to toxic metals (Başgel and Erdemoğlu, 2006; Jallad and
      (Hg). Apart from these toxic trace metals, elements such as chro-           Espada-Jallad, 2008; Gasser et al., 2009; Sukender et al., 2012;
      mium (Cr), iron (Fe), copper (Cu) and cobalt (Co) – necessary, but          Oliveira et al., 2014). An important source of exposure to toxic
      dangerous when they occur in excessive amounts – may also be                metals is also cigarette smoking (Galazyn-Sidorczuk et al., 2008;
      present in cosmetics. In addition, some cosmetics contain alumin-           Ashraf, 2012). The repeated use of cosmetics containing toxic
      ium (Al), classified as a light metal. Owing to the harmfulness of          metals is an additional source of exposure to these elements
      metals to human health, their content in cosmetic products is               (Fig. 1), and the available literature provides evidence that in some
      prohibited or restricted by the regulations of some countries, but          cases cosmetic preparations may be a source of excessive amounts
      in many countries there are no regulations in this regard (OJEU,            of metals creating a danger for human health (Warley et al., 1968;
      2009). The European Regulations describe over 1200 various toxic            Chan et al., 2001; Soo et al., 2003; Guillard et al., 2004; CDC, 2005,
      substances whose presence are prohibited in cosmetic products.              2012a, 2013a; Özkaya et al., 2009; Li et al., 2010; Al-Dayel et al.,
      Among them, there are metals particularly dangerous for human               2011; Benz et al., 2011; Chakera et al., 2011; Lin et al., 2012;
      health such as Pb, Cd, As, Ni and Hg. Owing to the lack of uniform          Dickenson et al., 2013; Tang et al., 2013).
      legislation regarding toxic metals presence in cosmetics all over              Taking into account the growing use of cosmetics as well as the
      the world and the possibility of accidental contamination of cos-           reports on the presence of dangerous metals in the cosmetic prod-
      metic products with these elements, they are detected in various            ucts currently available worldwide and the cases of unfavourable
      types of currently commercially available cosmetics (colour                 health effects due to their presence in cosmetics, it was warranted
      cosmetics, face and body care products, hair cosmetics, herbal cos-         to pay special attention to problems related to metals occurrence
      metics, etc.), in some cases in dangerous concentrations (Amry              in these products. Thus, the present paper focused on this matter
      et al., 2011; Lin et al., 2012; Dickenson et al., 2013; Tang et al.,        including the sources, concentrations and allowed limits of metals
      2013). Although absorption of metals from cosmetics through                 content in various types of cosmetics, as well as the danger for hu-
      the skin is rather low (Filon et al., 2009), these elements may accu-       man health caused by these elements. This paper is a critical re-
      mulate in the skin and internal organs, where they can exert toxic          view of worldwide literature concerning this issue and it draws
      effects. Numerous cases of topical (mainly allergic contact                 attention to the fact that cosmetics usage may be an additional
      dermatitis) and systemic effects caused by exposure to metals               source of exposure to toxic metals, and that adverse effects some-
      present in cosmetics have been reported (Warley et al., 1968;               times noted after the application of cosmetics may be related to
      Waldron, 1979; Shaltout et al., 1981; Van Ketel and Liem, 1981;             the presence of metals in these products. The harmfulness of
      Goh et al., 1989; Zemba et al., 1992; Chan et al., 2001; Saxena             heavy metals and Al for humans is well known and widely reported
      et al., 2001; Soo et al., 2003; Guillard et al., 2004; CDC, 2005,           and numerous data show that these metals may create a risk for
      2012a, 2012b; Foulds, 2006; Tang et al., 2006, 2013; Held and               health even at low exposure (Guillard et al., 2004; Gump et al.,
      Bayerl, 2008; Özkaya et al., 2009; Li et al., 2010; Amry et al., 2011;      2011; Karagas et al., 2012; Sommar et al., 2013). However, until
      Benz et al., 2011; Chakera et al., 2011; Travassos et al., 2011; Lin        now no sufficient attention has been given to cosmetics as a po-
      et al., 2012; Dickenson et al., 2013).                                      tential source of exposure to metals. In order to underline that
         Owing to the common pollution of the natural environment by              the health problems related to metals presence in cosmetics are
      metals in developed countries and their numerous industrial appli-          still current, in this article we have presented all the contemporary
      cations people are exposed to them during the lifetime via food,            cases of topical effects and poisonings caused by metals coming
      water or air as well as from occupational sources (Fig. 1; Hengstler        from cosmetics which we were able to find in scientific literature
                                                                                  (Medline, Scopus, Elsevier, etc.) since the year 2000 up until now.
      wileyonlinelibrary.com/journal/jat                    Copyright © 2015 John Wiley & Sons, Ltd.                      J. Appl. Toxicol. 2015; 35: 551–572
Metals in cosmetics
   Compounds of some metals are used for purpose in the cos-                        the key melanin-forming enzyme (Hostynek, 2003), compounds of
metic industry, mainly as UV filters in face and body care products                 this metal are used on purpose in skin-lightening creams and thus
and pigments in coloured cosmetics. The law of the European                         the highest concentrations of this element are found in this type of
Union (EU) allows the presence of various pigments in cosmetics                     cosmetics (Weldon et al., 2000; Chan et al., 2001; Soo et al., 2003;
in a wide range of colours: white (Al, barium sulphate, bismuth                     Tang et al., 2006, 2013; Held and Bayerl, 2008; Özkaya et al., 2009;
chloride oxide, calcium carbonate, calcium sulphate, magnesium                      Li et al., 2010; Benz et al., 2011; Chakera et al., 2011; CDC, 2012b;
carbonate, silver, 4% silver nitrate – only for colouring eyelashes                 Dickenson et al., 2013).
and eyebrows, as well as titanium dioxide and zinc oxide – which                       Another source of metals may also be derivatives of crude oil
are rather more popular as UV filters), green [chromium (III) oxide,                such as mineral oils, paraffin, silicones and aliphatic hydrocarbons
chromium (III) hydroxide, cobalt aluminium oxide], brown (Cu,                       used in the production of many cosmetic preparations. These in-
gold – Au) and iron oxides in colours such as orange, red, yellow                   gredients by themselves are harmful to human health and in addi-
and black (Fig. 2; OJEU, 2009). This law allows the use of 25% tita-                tion they may contain metals such as Cd, As, Cr and Cu (Stigter
nium dioxide as an UV filter and silver chloride (in the concentra-                 et al., 2000).
tion of 0.004% in ready-to-use preparations) deposited on
titanium dioxide as a preservative in cosmetic products (OJEU,
2009). The EU law does not allow the presence of other metals or
                                                                                    Regulations on Metals Content in Cosmetics
their compounds which could be used as pigments owing to their                      Owing to metals harmfulness to human health, their use in
colours, for example lead oxide (yellow or red) and lead dioxide                    cosmetic products is prohibited or restricted by regulations of
(black; OJEU, 2009). As a result of using of metal-based pigments                   many countries. However, it is important to underline that per-
in colour cosmetics, metal concentrations (especially Pb, Cr, Fe)                   missible concentrations of metals are individually specified by
in preparations of this type are higher than in other cosmetic prod-                particular regulations and are different for various products and
ucts (Al-Saleh et al., 2009; Omolaoye et al., 2010; Al-Dayel et al.,                countries (MHLW, 2000; FDA, 2007, 2009, 2013, 2014; OJEU,
2011; Zakari et al., 2014). Because Hg inactivates tyrosinase, being                2009; HC-SC, 2012).
Figure 2. The Regulation No 1223/2009 of the European Parliament on metals and their compounds presence in cosmetics (OJEU, 2009). Ag, silver; Al, al-
uminium; As, arsenic; Au, gold; Cd, cadmium; Co, cobalt; Cr, chromium; Cu, copper; Hg, mercury; Ni, nickel; Sb, antimony; Se, selenium; Pb, lead; Tl, thallium; Zr,
zirconium.
                                                                                                                                                                      553
J. Appl. Toxicol. 2015; 35: 551–572                        Copyright © 2015 John Wiley & Sons, Ltd.                            wileyonlinelibrary.com/journal/jat
                                                                                                                     S. Borowska and M. M. Brzóska
         According to the Regulation No 1223/2009 of the European Par-          authors who determined metals in cosmetics and whose data
      liament and the Council, the presence of cosmetic products of             were used for the preparation of this review article, is the lack of
      metals particularly dangerous for human health, such as Cd, Pb,           certified cosmetic materials (Ciaralli et al., 1996; Al-Saleh et al.,
      As, Ni and Hg, is prohibited in the countries of the EU, with the ex-     2009; Atz and Pozebon, 2009; Omolaoye et al., 2010). That is why
      ception of some Hg compounds only (Fig. 2; OJEU, 2009). Other             reference materials other than cosmetic products are used by
      metals such as zinc (Zn), silver (Ag), and strontium (Sr) are allowed     some investigators to check the reliability of metal measurements
      with special restrictions (Fig. 2). According to this Regulation, alu-    in cosmetics (Sainio et al., 2000; Al-Dayel et al., 2011).
      minium zirconium chloride hydroxide complexes (AlxZr(OH)yClz)
      and aluminium zirconium chloride hydroxide glycine complexes
      can be used in antiperspirants in a concentration of 20% as anhy-         Metals in Colour Cosmetics
      drous aluminium zirconium chloride hydroxide and the antiperspi-
      rants containing aluminium complexes mentioned above cannot               The use of colour cosmetics by women is a very popular daily cus-
      be applied to irritated or damaged skin (OJEU, 2009). In addition,        tom all over the world (Mudholkar, 2012). These cosmetics are of-
      Al and some of its compounds are allowed to be used as                    ten left on the skin for a whole day and are repeatedly used.
      colourants in cosmetics (Fig. 2; OJEU, 2009). It is important to un-      Among the products that contain toxic metals, the most hazardous
      derline that according to the EU Regulation No 1223/2009 (article         seem to be preparations which are applied to the mucous mem-
      17) small quantities of non-intended prohibited substances, in-           branes, such as lipsticks and lip glosses (Gondal et al., 2010; Khalid
      cluding toxic metals, may be present in final cosmetic products           et al., 2013; Soares and Nascentes, 2013). In the case of cosmetics
      as technically unavoidable contaminations if these preparations           applied to the lips there is a risk of their direct oral ingestion with
      are safe for human health. Unfortunately, the safe levels of these        food when eating or by licking lips. Eye shadows and mascaras are
      technically unavoidable contaminations in cosmetics are not               applied to the periocular area of the face where the skin is the thin-
      described.                                                                nest, which enables easy absorption of various substances,
         In the USA, the Food and Drug Administration (FDA) has stated          including metals, from cosmetics into the blood (Pratchyapruit
      that lead acetate is safe for use in cosmetics that colour the hair       et al., 2007). Some impurities and intended ingredients of eye cos-
      and approved its use at the maximum content of 0.6% (w/v) Pb              metics can cause allergic reactions of the eyelids and eyes
      in the product (FDA, 2007, 2009). The FDA accepts the contami-            irritation.
      nation of lead acetate used as a colour additive with As and                  Metals may be absorbed from cosmetics through the conjunc-
      Hg at levels up to 3 and 1 mg kg-1, respectively (FDA, 2007).             tiva and during lacrimation. The thin epidermis of the eyelids
      The FDA limit for Pb in colour additives is 20 mg kg-1 (FDA,              may be mechanically broken during eye rubbing, enabling the
      2014). The highest acceptable level of Hg (as unavoidable contam-         penetration of pigments containing metals into the blood circula-
      ination) according to the FDA is 1 mg Hg kg-1, but when Hg                tion, so eye shadow should not be applied to broken skin (Sainio
      compounds are used on purpose as preservatives in cosmetics ap-           et al., 2000; Omolaoye et al., 2010). In addition, slow percutaneous
      plied to the periocular area the acceptable limit is 65 mg Hg kg-1        absorption of metals from cosmetics into the body through
      (FDA, 2013). Health Canada has established the maximum                    healthy skin is also possible (Omolaoye et al., 2010). Individuals
      acceptable limits of heavy metal concentrations in cosmetics at the       sensitized to metals, especially to Ni (van Ketel and Liem, 1981;
      following levels: Pb – 10 mg kg-1, Hg – 3 mg kg-1, Cd – 3 mg kg-1,        Goh et al., 1989; Zemba et al., 1992; Foulds, 2006; Travassos et al.,
      As – 3 mg kg-1 and antimony (Sb) – 5 mg kg-1 (HC-SC, 2012). In            2011), should completely avoid eye shadows because sensitizing
      Japan, the use of Cd and its compounds, as well as Hg and its             metals can occur as impurities in this sort of colour cosmetics
      compounds in cosmetics, is prohibited (MHLW, 2000). Apart from            (Table 1; van Ketel and Liem, 1981; Goh et al., 1989; Sainio et al.,
      the regulations in the EU, the USA and Canada, there are no               2000; Goossens, 2004). Ni is the main metallic allergen from
      precise regulations concerning limits of metals content in final          make-up. In dyes used in the manufacture of coloured cosmetics
      cosmetic products in other countries. Although, in spite of the lack      in Korea, metals which can cause contact allergy were detected
      of appropriate regulations in some countries, there exist data on         in the following concentrations: 0 – 19.5 mg Ni kg-1, 0.16 – 97.6
      these elements concentrations in cosmetics produced and used              mg Cr kg-1, 0 – 789.9 mg Fe kg-1, 0 – 6.6 mg Cu kg-1 and 0 –
      in these countries.                                                       177.9 mg Co kg-1 (Kang et al., 2006; Lee et al., 2008). In Nigeria,
         It seems important to emphasize that the fact that the usage of        the concentrations of metals in dyes used in the production of
      a metal for the production of cosmetics is prohibited does not            eye shadows were as follows: 6.11 – 55.0 mg Pb kg-1, 0 – 8.89
      mean that this element cannot be present in the final product in          mg Cd kg-1, 80.56 – 359.44 mg Ni kg-1, 0 – 150 mg Cr kg-1, 1.67 –
      a detectable amount. Even the most rigorous EU Regulation (OJEU,          136.67 mg Cu kg-1 and 15.0 – 253.33 mg Co kg-1 (Omolaoye
      2009) allows for the presence of trace amounts of prohibited heavy        et al., 2010).
      metals (as technically unavoidable contaminations). Thus, the con-            The available literature data show that metals, such as Pb, Cd,
      centrations of heavy metals in cosmetic products are more impor-          Ni, As, Hg, Cr, Co, Cu, Fe and Al are present in many types of
      tant than the mere fact of their presence. That is why it is necessary    colour cosmetics produced and used in various parts of the
      to monitor commercially available cosmetics regarding the con-            world (Table 1; Supplementary Table S1). Apart from the data
      centrations of metals, especially the most toxic trace elements, in       presented in Table 1, there is plenty of other information about
      order to recognize whether the concentrations are within the              the concentrations of toxic heavy metals in colour cosmetics;
      ranges of safe values. Highly advanced analytical methods (atomic         however, it is impossible to present all of them in one article
      absorption spectrometry – AAS and especially inductively coupled          and thus only the more recent and most important findings
      plasma mass spectrometry – ICP-MS) used nowadays in metal                 have been provided to emphasize that the problem of toxic
      analysis allow the detection of even trace amounts (part per mil-         metals presence in these products is still current. In addition,
      lion – ppm and part per billion – ppb) of metals (Atz and Pozebon,        based on the available literature we have created ranges of
      2009; Al-Qutob et al., 2013). The important issue raised by many          metal concentrations in colour cosmetics. These concentrations
554
      wileyonlinelibrary.com/journal/jat                  Copyright © 2015 John Wiley & Sons, Ltd.                    J. Appl. Toxicol. 2015; 35: 551–572
                                                 Table 1. Concentrations of heavy metals detected in colour cosmetics (mg kg-1) a
                                                 Eye shadows         0 – 202.06     0 – 55.59 0.02 – 359.44 0 – 11.1 0 – 0.74    0 – 11,900      2.2 – 300,000    0 – 99,000 0 – 258.33 (Sainio et al., 2000; Kang et al., 2006;
                                                                                                                                                                                        Lee et al., 2008; Al-Saleh et al., 2009;
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                                           555
                                                                                                                      S. Borowska and M. M. Brzóska
      range from 0 (undetectable values) up to 300.0 g Fe kg-1, 99.0 g          present in Europe was in most cases below 1 mg kg-1, and the
      Cu kg-1, 11.9 g Cr kg-1, 3.76 g Pb kg-1, 359.44 mg Ni kg-1, 258.33        maximum concentration of this metal observed in lipsticks and
      mg Co kg-1, 60.2 mg Cd kg-1, 0.74 mg Hg kg-1 and 50.0 g Al kg-1           lip glosses reached 3.75 mg kg-1 and 2.12 mg kg-1, respectively
      (Tables 1 and 2; Supplementary Tables S1–S4). Brandão et al.              (Piccini et al., 2013). In 2007, the FDA detected Pb in lipsticks rang-
      (2012) have noted the following concentrations of Pb in cosmetics         ing from 0.09 to 3.06 mg kg-1 (FDA, 2014) and in 2010 Frontier
      commonly used in South Africa: 7.4 ± 1.3 mg kg-1 in concealer,            Global Sciences under contract with the US FDA detected Pb in
      29 ± 9.2 mg kg-1 in lip liner, 17.3 ± 2.9 mg kg-1 in oil absorbent        this kind of products in more than twice higher concentrations
      powder, 15.8 ± 0.2 mg kg-1 in mascara, 4.7 – 11.7 mg kg-1 in lip          (0 – 7.19 mg kg-1; FDA, 2014).
      glosses, 0 – 73.1 mg kg-1 in lipsticks and 7.8 – 32.9 mg kg-1 in             Recently, a growing popularity of toy make-up has been ob-
      foundations. Adepoju-Bello et al. (2012) have found the follow-           served and toy cosmetics is widely available. However, these prod-
      ing toxic metals while evaluating 50 various cosmetics from               ucts can be potentially dangerous for children, including especially
      Nigeria, including lipsticks, lip glosses and skin-whitening              atopic children. The children’s skin is particularly thin, so it is very
      creams: As (0.006 – 0.31 mg kg-1), Cd (0.023 – 0.203 mg kg-1),            susceptible to external harmful factors (Brandão and Gontijo,
      Pb (0.017 – 0.9 mg kg-1), Hg (0.09 – 0.207 mg kg-1) and Ni                2012). Toy cosmetics are sold in kits such as eye shadows and lip-
      (0.032 – 0.105 mg kg-1). However, they have not provided                  sticks. Each product in the kit is a cosmetic product and should be
      any data on concentrations of these metals in particular                  compliant to the cosmetic directive. These products are often used
      categories of these products. Among cosmetics such as face                on children’s faces and usually stay on as long as real cosmetics. Ni,
      cleansers, lip polishes, nail paints, powders, styling gels and           Cr and Co were detected in these products and these metals were
      aloe facial scrubs from Nigeria Pb (0 – 0.17 mg kg-1), Cd                 present in the highest concentrations in toy eye shadows (Table 3;
      (0.01 – 0.09 mg kg-1), Ni (0 – 0.08 mg kg-1), Cr (0.01 – 0.47             Corazza et al., 2009; Contado and Pagnoni, 2012).
      mg kg-1), Fe (0.52 – 6.65 mg kg-1) and Cu (0.04 – 1.03 mg kg-1)              To sum up, metals were detected in different concentrations in
      were detected (Odukudu et al., 2014).                                     various types of colour cosmetics (Tables 1–3). Pb was detected in
         The highest concentration of Pb was found in shimmering and            the highest concentrations in lipsticks, reaching up to 3,76 g kg-1 in
      brown colours, whereas the lowest concentration was found in              a lipstick from Saudi Arabia (Table 1; Al-Saleh et al., 2009), whereas
      red colours of lipsticks from Saudi Arabia (Al-Saleh et al., 2009).       Ni, Cr, Fe, Cu, Co and Al were detected in high concentrations in
      Among the lipsticks from Pakistan, the highest concentrations of          eye shadows (Tables 1 and 2). In the eye shadows from Nigeria,
      heavy metals were found in dark brown and shocking pink colours           Ni was found in a concentration as high as 359.44 mg kg-1
      (Khalid et al., 2013). On the Brazilian market, the highest concentra-    (Omolaoye et al., 2010). Ni and Cr were also present in high con-
      tions of Pb were found in red lipsticks (Soares and Nascentes,            centrations in toy make-up products (Corazza et al., 2009; Contado
      2013). Lip glosses produced in the EU contained less Pb than lip-         and Pagnoni, 2012). Based on the available literature data, the con-
      sticks present on the European market, and this can be explained          centrations of metals in colour cosmetics can be set in the follow-
      by a lower content of pigments in lip glosses (Piccini et al., 2013).     ing order: Fe > Cu > Al > Cr > Pb > Ni > Co > Cd > As > Hg. As
      The Pb concentration in most of the lip colour products currently         can be seen from the presented data (Tables 1–3; Supplementary
Table 2. Concentrations of aluminium (Al) detected in various types of cosmetics (mg kg-1)
      wileyonlinelibrary.com/journal/jat                  Copyright © 2015 John Wiley & Sons, Ltd.                     J. Appl. Toxicol. 2015; 35: 551–572
Metals in cosmetics
Tables S1–S4), metals, whose usage is prohibited or restricted by           > Al (0 – 62.17 mg kg-1) > Ni (0 – 29.39 mg kg-1) > Cd (0 –
the EU law (OJEU, 2009) or other regulations (FDA, 2009, 2014;              28.73 mg kg-1) > Cu (0 – 18.95 mg kg-1) > Cr (0 – 6.29 mg kg-1).
HC-SC, 2012), were detected in excessive concentrations in com-             Detailed data on the concentrations of metals detected in the
mercially available colour cosmetics. Detailed data on the concen-          face and body care products produced in various countries are
trations of heavy metals detected in colour cosmetics produced in           presented in Table 2 and as the Supplementary Material (Supple-
various countries are presented as the Supplementary Material               mentary Tables S5 and S6).
(Supplementary Tables S1–S4).
J. Appl. Toxicol. 2015; 35: 551–572                   Copyright © 2015 John Wiley & Sons, Ltd.                    wileyonlinelibrary.com/journal/jat
                                           558
Table 4. Concentrations of heavy metals detected in face and body care products (mg kg-1) a
wileyonlinelibrary.com/journal/jat
                                                                                     0 – 41,600     0 – 5.05    0.01 – 18.45     0 – 65,133      0 – 4.3    0.53 – 2,469    0 – 18.95 0.22 – 0.25 (Chan et al., 2001; Sin and
                                                 skin-lightening, anti-freckles,                                                                                                                  Tsang, 2003; Ayenimo et al.,
                                                 anti-wrinkes, for acne,                                                                                                                          2010a, 2010b; Chauhan
                                                 medicated)                                                                                                                                       et al., 2010; McKelvey et al.,
                                                                                                                                                                                                  2011; Onwordi et al., 2011;
                                                                                                                                                                                                  Perkin Elmer, 2012; Adawe
                                                                                                                                                                                                  and Oberg, 2013; Al-Qutob
                                                                                                                                                                                                  et al., 2013; Cristuado et al.,
                                                                                                                                                                                                  2013; Ullah et al., 2013;
                                                                                                                                                                                                  Umar and Caleb, 2013)
                                                 Germicidal creams,                     -              -             -         204 – 4,770         -             -            -            -      (McKelvey et al., 2011)
                                                 soaps and balms
                                                 Body creams/lotions/milks           0 – 9.2        0 – 16.67      0 – 6.56         -         0.02 – 0.4         -          0 – 0.05       -       (Bocca et al., 2007; Cristuado
                                                                                                                                                                                                   et al., 2013; Orisakwe and
                                                                                                                                                                                                   Otaraku, 2013; Umar and
                                                                                                                                                                                                   Caleb, 2013)
                                                 Shaving creams                    0.66 – 0.72    0.01 – 0.02        -              -              -             -             -            -      (Chauhan et al., 2010)
                                                 Eye cleansers,                    8.06 – 213.6    0.3 – 3.88        -              -            0.28            -             -            -      (Nnorm et al., 2006;
                                                 cleansing oil                                                                                                                                     Hwang et al., 2009)
                                                 Emulsions                                             -             -              -                                          -            -      (Oyedeji et al., 2011)
enrich the skin with nutrients (Sukender et al., 2012). However, not
                                                                                                      (Abdel-Fattah and
                                                                                                      2010b; Umar and
                                                                                  References
                                                                                                      Caleb, 2013)
                                                                                                                                                                                                                                                                                                                                               toxic metals. Concentrations of metals in herbal cosmetics depend
                                                                                                                                                                          Detailed data on the concentrations of heavy metals detected in hair products produced in various countries are presented as the Supplementary Tables S7A and S7B.
                                                                                                                                                                                                                                                                                                                                               on the content of these unintended impurities in herbs. Herbal ma-
                                                                                                                                                                                                                                                                                                                                               terials that are used in cosmetics production should come from
                                                                                                                                                                                                                                                                                                                                               certificated ecological cultures or controlled wild crops. However,
                                                                                                                                                                                                                                                                                                                                               according to the EU Regulation No 1223/2009, small quantities of
                                                                                                                                                                                                                                                                                                                                               non-intended prohibited metals can be present in final cosmetic
                                                                                                                                                                                                                                                                                                                                               products as technically unavoidable contaminations (OJEU,
                                                                                                                                                      10.67 – 25.35
                                                                                                                                                                                                                                                                                                                                               2009). According to the WHO, the maximum allowed amounts of
                                                                                                                                      0.18 – 0.37
                                                                                                                                                            -
                                                                                                                        -
                                                                                                      -
                                                                                                                                      0.07 – 2.39
                                                                                                    0.57 – 0.67
                                                                                                                                                                                                                                                                                                                                               the production of colour cosmetics and face and body care prod-
                                                                                                                                                                                                                                                                                                                                               ucts in the following concentrations: As ≤ 3 mg kg-1, Pb ≤ 0.1 mg
                                                                                                                                                                                                                                                                                                                                               kg-1 and Hg ≤ 1 mg kg-1 [Final Report on the Safety Assessment
                                                                                                                                                                                                                                                                                                                                               of Hydrogenated Cottonseed Oil, Cottonseed (Gossypium) Oil, Cot-
                                                                                                                                                                                                                                                                                                                                               tonseed Acid, Cottonseed Glyceride, and Hydrogenated Cotton-
                                                                                                                                      27.97 – 154.2
                                                                                                    0.76 – 1.03
0.51 – 2.15
81.6 – 421
0.34 – 1.5
5 – 11
0.01 – 2.03
0.06 – 3.11
1.3 – 72
0.28 – 6.95
0.03 – 4.17
4.2 – 6.8
0 – 0.49
1.3 – 17.7
                                                                                                                                                                                                                                                                                                                                               are sometimes too high (Table 6). Unlike heavy metals, there is a
                                                                                                                                                         0.18
                                                                                  Pb
Shampoos
Hair dyes
J. Appl. Toxicol. 2015; 35: 551–572                                                                                                                              Copyright © 2015 John Wiley & Sons, Ltd.                                                                                                                                                                           wileyonlinelibrary.com/journal/jat
                                                                                                                          S. Borowska and M. M. Brzóska
        Table 6. Concentrations of heavy metals in raw plant material from Europe which can be used for pharmaceutical and cosmetic rea-
        sons (mg kg-1)
                                   Pb                 Cd                  Ni              As               Hg                       References
        Poland
        Nettle               1.1 – 7.23         0.06 – 0.27             1.49          0.09 – 0.24                        (Baranowska et al., 2002;
                                                                                                                         Fijałek et al., 2003)
        Chamomile                 8.08                0.3               1.17               -                -            (Baranowska et al., 2002)
        Turkey
        Nettle             1.59 – 4.8                 0.06           3.6 – 13.1            -                             (Başgel and Erdemoğlu, 2006;
                                                                                                            -            Tokalioğlu, 2012)
        Chamomile          0.06 – 0.72                0.44           1.8 – 3.68            -                             (Başgel and Erdemoğlu, 2006;
                                                                                                            -            Tokalioğlu, 2012)
        Horsetail                 -                   -                 4.73               -                             (Tokalioğlu, 2012)
                                                                                                            -
        Germany
        Nettle                 0 – 4,249.6         0 – 0.2                -                -              0 – 0.17       (Gasser et al., 2009)
        Horsetail              0 – 21.45           0 – 0.63               -                -              0 – 0.1        (Gasser et al., 2009)
        Bulgaria
        Chamomile          0.29 – 1.62          0.18 – 0.26               -           0.08 – 0.12           -            (Arpadjan et al., 2008)
                           Cr                        Fe              Cu               Co
        Poland
        Nettle                    -              56.2 - 266         7.26 - 13              -                             (Fijałek et al., 2003)
        Turkey
        Nettle               1.2 – 8.71          810 – 3,456         5.6 – 15.2       0.48 – 2.35                        (Başgel and Erdemoğlu, 2006;
                                                                                                                         Tokalioğlu, 2012)
        Chamomile          1.22 – 3.48         502.7 - 716         8.34 – 13.9        0.32 – 0.44                        (Başgel and Erdemoğlu, 2006;
                                                                                                                         Tokalioğlu, 2012)
        Horsetail                 1.02                804               8.59             0.43                            (Tokalioğlu, 2012)
        Pb, lead; Cd, cadmium; Ni, nickel; As, arsenic; Hg, mercury; Cr, chromium; Fe, iron; Cu, copper; Co, cobalt.
         Heavy metals, such as Cd, Pb, Ni, As, Hg, Cr, Fe, Cu and Co were           other seas (e.g. Adriatic Sea), cosmetic clays (Tateo et al., 2009; Otto
      also detected in numerous other raw materials which can be used               and Haydel, 2013) and talcum used especially in powders (Tables 2
      for the production of cosmetics considered as natural products, for           and 9; Supplementary Tables S8A, S8B and S9). These raw materials
      example in honey (Table 7; Roman, 2003; Borawska et al., 2012),               contain toxic metals in concentrations corresponding to their con-
      argan oil (Mohammed et al., 2013), and olive oil (Brkljača et al.,            centrations in the Earth’s upper crust. Toxic metals bound with the
      2013) as well as in citrus essential oils (lemon, mandarin, bergamot,         surface of natural clays can be exchanged with ions present in the
      and sweet orange oils; Table 8) often used as natural ingredients of          skin and can be absorbed through the skin (Tateo et al., 2009; Otto
      cosmetics and as aromatizing agents. Another raw materials con-               and Haydel, 2013). In cosmetic clays from Nigeria such as calabash
      taining metals and used in the production of cosmetics are Dead               stone (a mixture of aluminium silicate hydroxide, seashells, clay
      Sea muds used as an ingredient in body lotions, hand creams, fa-              mud, sand, wood ash and salt) and black antimony, metals such
      cial masks, soaps and shampoos as well as in healing muds from                as Pb, Cr, and Cd were detected (Table 9; Supplementary
Table 7. Concentrations of heavy metals detected in honey (which is one of often ingredients of natural cosmetics; mg kg-1)
        Origin               Pb                  Cd                    Ni                  As               Hg                       References
        Croatia         0.01 – 0.84             0 – 0.2                -                0 – 0.1            0 – 0.31        (Bilandžić et al., 2001)
        Greece               -               0.08 – 0.22               -                  -                  -             (Ioannidou et al., 2005)
        Italy            0.1 – 1.53          0.01 – 0.27               -                  -                  -             (Sanna et al., 2000)
        Spain              0 – 0.12             0 – 0.002              -                  -                  -             (Muñoz and Palmero, 2006)
        Turkey             0 – 0.06               -                  0 – 0.13             -                  -             (Silici et al., 2008)
                            Cr                    Fe                   Cu                 Co
        Croatia              -                    -               0.04 – 41.27            -                                (Bilandžić et al., 2001)
        Greece               -                    -                  0 – 0.48        0.01 – 0.09                           (Ioannidou et al., 2005)
        Italy                -                    -               0.19 – 2.98             -                                (Sanna et al., 2000)
        Turkey             0 – 0.01          1.12 – 12.9          0.01 – 0.04           0 – 0.03                           (Silici et al., 2008)
        Pb, lead; Cd, cadmium; Ni, nickel; As, arsenic; Hg, mercury; Cr, chromium; Fe, iron; Cu, copper; Co, cobalt.
560
      wileyonlinelibrary.com/journal/jat                      Copyright © 2015 John Wiley & Sons, Ltd.                     J. Appl. Toxicol. 2015; 35: 551–572
Metals in cosmetics
  Table 8. Mean concentrations of cadmium (Cd), lead (Pb) and                et al., 2011). Kohl is an ointment prepared by burning vegetable
  copper (Cu) determined in methanol extracts of citrus essential            fat and adding charcoal to the residue or a powder made from
  oils (mg kg-1) according to Pera et al. (2003)                             lead sulphide and ingredients added such as carbon, herbs,
                                                                             plant juices and vegetable ashes (Jallad and Espada-Jallad,
  Citrus essential oil kind            Cd            Pb            Cu        2008; Amry et al., 2011). Medicinally, kohl is used to stop bleed-
                                                                             ing and after circumcision for hygienic purposes (Al Mahroos
  Lemon                               0.002         0.10          0.02       and Faap, 1993; Al-Ashban et al., 2004). Mothers apply kohl to
                                                                             their children to protect them from the ’evil eye‘ (Hardy et al.,
  Mandarin                            0.002         0.17          0.27       2004; Hardy et al., 2006). Sometimes manufacturers of kohl give
                                                                             false information on the labels about many benefits connected
  Sweet orange                        0.008         0.08          0.07       with their product, e.g. that it is helpful in the treatment of all kinds
                                                                             of eye trouble (e.g. sore eyes, tears, reddishness, eye dirt and burn-
  Bergamot                            0.02          0.08          0.36       ing eyes); however, none of the ingredients present in samples of
                                                                             kohl have these properties (Hardy et al., 2006). The mean concen-
                                                                             trations of toxic metals in Nigerian local kohl were the following:
Tables S8A and S9). The mean concentrations of Pb and Cr in cal-             277,300 mg Pb kg-1, 2,256 mg Ni kg-1, 810 mg As kg-1, whereas
abash stone reached 5.13 ± 9.08 and 7.69 ± 4.41 mg kg-1 respec-              in kohl imported to Nigeria they reached 180,900 mg Pb kg-1,
tively, whereas the Cd concentration was below the limit of                  1,140 mg Ni kg-1 (1970–2690 mg Ni kg-1), 1630 mg As kg-1 and
detection. The concentrations of these metals in black antimony              7460 mg Cr kg-1 (3450–9270 mg Cr kg-1; Zakari et al., 2014). The
were 171.14 ± 5.85 mg Pb kg-1, 5.75 ± 3.33 mg Cr kg-1 and 0.53               mean Pb concentration in the imported kohl samples available
± 4.19 mg Cd kg-1 (Popoola et al., 2013). Another natural raw ma-            on the Nigerian market reached 178,366 ± 947 mg kg-1 and one-
terial used for cosmetics production, especially shimmering                  third out of the 15 evaluated samples contained this metal in the
lipsticks, which may contain heavy metals (mainly Pb), is Mica               concentration far beyond the recommended limit (20 mg kg-1),
(Al-Saleh et al., 2009) being a group of natural silicate minerals           while they were labelled as containing Pb below this limit. It is
(Al-Saleh et al., 2009; Volpe et al., 2012; Piccini et al., 2013).           important to underline that Pb concentrations declared by the
   Heavy metals were detected in excessive concentrations in                 producers on kohl labels were not in conformity with the actual
herbal cosmetic formulations of preparations sold on the Indian              content of this metal (Zakari et al., 2014). The Pb concentration in
market and in herbal (including antiseptic) soaps from Nigeria               kohl from Saudi Arabia was 141.2 ± 2.8 mg kg-1 (Haider et al.,
(Tables 9; Obi et al., 2006). It was found that alkalis used for the pro-    2012) and in that from Bangladesh it ranged from 89.8 ± 3.5 mg
duction of cheap soaps in Nigeria contain 0.02 mg Pb kg-1, 0.003             kg-1 to 146.1 ± 4.8 mg kg-1 (Haider et al., 2012).
mg Cd kg-1, 0.05–0.06 mg Ni kg-1, 0.02–0.04 mg Cr kg-1,
1.67–2.45 mg Cu kg-1 and 99.18–241.63 mg Fe kg-1 (Oluremi
Olabanji et al., 2012).
                                                                             Metal Nanoparticles in Cosmetic Products
   Henna is another traditional product that has been used over              In recent years, a growing popularity of nanocosmetics has been
the centuries for medical and cosmetic purposes in many parts                observed. These products contain one or more nanoscale ingredi-
of the world. Henna dye is obtained from the dried leaves of                 ents. The nanoscale version of ingredients provides better UV pro-
the Lawsonia inermis or Cassia obovata, which are powdered                   tection, deeper skin penetration, higher stability of active
and mixed with oil and water (Kang and Lee, 2006; Jallad and                 ingredients and long-lasting effects as well as increases the colour
Espada-Jallad, 2008). It is applied to the hair for the purpose of           and quality of finished products (Raj et al., 2012). In addition, some
hair dying and giving it a healthy and beautiful look (Jallad                nanoparticles (calcium carbonate or calcium phosphate) are capa-
and Espada-Jallad, 2008). This product is a substitute for chemical          ble of preventing allergenic metal ions penetration into the skin
hair dyes (Kang and Lee, 2006). Henna is also applied as tempo-              (by capturing them by means of cation exchange and remaining
rary paint-on-tattoos on hands and feet as an alternative to per-            on the surface of the skin, allowing them to be removed simply
manent tattoos (Kang and Lee, 2006; Jallad and Espada-Jallad,                by washing with water; Vemula et al., 2011).
2008). Henna preparations are fortified with mineral products                   Many different types of nanomaterials, including nanometals,
and various herbs in order to give it a stronger colour and to               are used in cosmetics. The usage of nanometals in cosmetics has
shorten the time of application (Kang and Lee, 2006; Jallad and              many advantages. Nanoparticles of Ag and Au have antibacterial
Espada-Jallad, 2008). These mineral products and herbs are                   properties and thus they are useful in face and body care products,
rich in Pb (Jallad and Espada-Jallad, 2008). The highest concen-             e.g. toothpastes or soaps (Raj et al., 2012; Ramakritinan et al., 2013).
trations of this metal are reaching values as high as 65.98 mg               Cu species-coated silica nanoparticles are used in some deodor-
kg-1 were found in henna from the United Arab Emirates (Table 9;             ants because this element placement on nanoparticles increases
Jallad and Espada-Jallad, 2008). Ni and Co present in henna mix-             the surface of Cu having antibacterial properties and neutralizing
tures provoke sensitization, which plays a role in the occurrence            odours (Singh et al., 2010). Nanoparticles of aluminium oxide are
of allergic contact dermatitis (Kang and Lee, 2006), whereas Pb is           used in mineral foundations and concealers owing to their proper-
absorbed through the skin ( Jallad and Espada-Jallad, 2008). A               ties of diffusing light and disguising wrinkles (FOE-Australia, 2014).
prolonged period of henna tattoos remaining on the skin facili-              Titanium dioxide and zinc oxide in the size range of 20 nm are
tates this action. Apart from heavy metals (Table 9), Al has also            used in sunscreen products as efficient UV filters (Raj et al., 2012).
been detected in henna (Table 2).                                            Popov et al. (2005) have suggested that titanium dioxide nanopar-
   The problem of natural cosmetics contamination with toxic                 ticles are more effective during the exposure to UVB (310 nm) than
metals also refers to kohl (surma) being one of the traditional prod-        to UVA (400 nm) because, as they have revealed, in the case of ex-
ucts used in Asia and Africa as eyeliner to darken the eyelids and as        posure to UVB, nanoparticles of titanium dioxide with diameters
mascara for the eyelashes (Tables 2 and 9; Hardy et al., 2006; Amry          56–62 nm effectively decreased the transmission of UVB through
                                                                                                                                                          561
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                                           562
Table 9. Concentrations of heavy metals detected in raw materials, natural cosmetics and cosmetics considered as natural products (mg kg-1) a
wileyonlinelibrary.com/journal/jat
                                                 Type of product                Pb               Cd              Ni              As            Hg             Cr          Fe        Cu            Co               References
                                                 Muds                       2.5 – 4.5       0.14 – 2.6        13 – 15         1.3 – 1.7         -          23 – 30         -       4 – 63      2.3 – 4.5    (Vreca and Dolenec,
                                                                                                                                                                                                            2005; Abdel-Fattah
                                                                                                                                                                                                            and Pingitore, 2009)
                                                 Cosmetics with            0.01 – 6.2          0 – 1.7      0.01 – 17       0.03 – 1.8          -         0.81 - 24        -       0 – 10        0–4        (Abdel-Fattah and
                                                 muds from                                                                                                                                                  Pingitore, 2009)
                                                 Dead Sea
                                                 Cosmetic clays            3.74 – 171.14     0.1 – 0.56          -               -              -         0.39 – 7.69      -         -            -         (Popoola et al., 2013)
                                                 Talcum                    0.24 – 20        0.01 – 2.1           -               -              -          0.2 – 30        -         -           0.7        (Chauhan et al., 2010;
                                                                                                                                                                                                            Nnorm, 2011; Gondal
                                                                                                                                                                                                            et al., 2012)
                                                 Henna                        2 – 65.98          -           2.5 – 83            -              -              -           -        7.75     2.96 – 3.54    (Tosti et al., 1991;
                                                                                                                                                                                                            Kang and Lee, 2006;
                                                                                                                                                                                                            Jallad and Espada-Jallad,
                                                                                                                                                                                                            2008)
                                                 Kohl                       3.2 – 1,219.4       0.94            1.01             -              -         0.08 – 9      1,272      302.2         0.72       (Malakootian et al., 2010;
                                                                                                                                                                                                            Gondal et al., 2013; Ullah
the skin up to 1%, whereas in the case of exposure to UVA, higher             It is important to emphasize that the current knowledge about
diameters of titanium dioxide nanoparticles were necessary to de-          the danger connected with the use of nanometals in cosmetics is
crease the transmission of UVA from 50% to 25%. Zinc oxide nano-           insufficient. This is related to methodological problems with
particles are effective UV filters in a broader spectrum of radiation,     nanometals determination on the one hand and the fact they have
including UVA (Mitchnick et al., 1999). Zinc oxide and titanium di-        not been used long enough for evaluation of the long-term effects
oxide from sunscreens were only present in the uppermost layer             of exposure to them, on the other hand. Further investigations
of the stratum corneum after 2 h of application so they are                should provide more information on whether nanoparticles of
considered to be relatively safe (Filipe et al., 2009). However,           metals are really safe for human health and give more advantages
Monteiro-Riviere et al. (2011) have revealed that damage to the            than hazards.
skin caused by UVB slightly increased the penetration of titanium
dioxide and zinc oxide nanoparticles through the skin. Ag and zinc
oxide nanoparticles are ingredients of chemically modified clays
                                                                           Absorption of Metals Through the Skin
because of their microbicidal activity against bacteria, fungi and vi-     Metals present in cosmetics may be accumulated in the skin or
ruses present on the skin (Otto and Haydel, 2013). Moreover, it has        absorbed by this route (Fig. 3). Elements such as Ni, Co and Cr
been revealed that 70-nm nanoparticles of calcium carbonate and            are accumulated in the stratum corneum and may cause allergic
calcium phosphate present in a glycerine emollient used on the             contact dermatitis (Larese et al., 2007; Filon et al., 2009), whereas
skin surface can reduce the skin’s exposure to Ni ions (Vemula             Hg, Pb, Cd and Al pass through the skin layers to blood vessels
et al., 2011).                                                             and are transported into various organs where they are accumu-
   Although using metal nanoparticles in cosmetology has many              lated and exert toxic effects (Stauber et al., 1994; Lansdown and
advantages, there may be risk factors for human health. Because            Sampson, 1996; Palmer et al., 2000; Sun et al., 2002; CDC, 2012b;
of their very small size, nanoparticles can penetrate the skin (partic-    Lin et al., 2012). Increased Pb, Cd, Hg and Al concentrations in
ularly if the skin is damaged) and easily gain access to the blood         the blood, urine or internal organs noted in individuals in whom
stream and they can be transported to various organs (Raj et al.,          the use of cosmetic products was the only source of excessive ex-
2012). People may inhale nanoparticles when they use                       posure to these metals confirm their absorption through the skin
nanomaterial products such as spray versions of sunscreens con-            (Warley et al., 1968; Shaltout et al., 1981; Al Mahroos and Faap,
taining nanoparticles of titanium dioxide (Raj et al., 2012). Topically    1993; Weldon et al., 2000; Chan et al., 2001; Soo et al., 2003; Guillard
applied nanoparticles of copper (II) oxide have been reported to in-       et al., 2004; CDC, 2005, 2012a, 2012b, 2013a; Tang et al., 2006, 2013;
duce inflammatory cytokine secretion and necrosis in human skin            Held and Bayerl, 2008; Özkaya et al., 2009; Al Naama et al., 2010; Li
organ culture (Cohen et al., 2013). In contrast to nanoparticles of        et al., 2010; Amry et al., 2011; Benz et al., 2011; Chakera et al., 2011;
copper (II) oxide, nanoparticles of Al probably have no cytotoxic          Lin et al., 2012; Dickenson et al., 2013). Although absorption of
activity. Monteiro-Riviere et al. (2010) have reported that exposure       these metals by the skin is less effective than by the gastrointesti-
to nanoparticles of Al (50 and 80 nm) in the concentrations of             nal tract or inhalation, some amounts of them may enter the body
0.0004–4.0 mg ml-1 for 24 h did not cause cytotoxicity in cultured         by this way as a result of the use of cosmetics.
human neonatal epidermal keratinocytes.                                        Hg enters the skin mainly through appendages such as hair fol-
   Results of experimental studies conducted in various animal             licles and sweat ducts (Guy et al., 1999; Palmer et al., 2000). Part of
models (Balasubramanyam et al., 2009; Prabhakar et al., 2012; Ze
et al., 2014) confirm toxicity of metal nanoparticles used in cosme-
tology and medicine. Prabhakar et al. (2012) have reported that
acute oral treatment with aluminium oxide (Al2O3) nanoparticles
(30 and 40 nm) in a single dose of 500, 1000 and 2000 mg kg-1 in-
duced oxidative stress in the liver, kidneys and brain of rats. The
administration of Al2O3 nanoparticles, in a dose-dependent man-
ner, decreased the concentration of reduced glutathione and the
activities of superoxide dismutase and glutathione reductase,
while increased activities of catalase and glutathione S-transferase,
and malondialdehyde concentration (a biomarker of lipid peroxi-
dation). The changes were different in various organs and
depended not only on the dose, but also on the size of the
nanoparticles. The Al2O3 nanoparticles-induced oxidative stress
in the liver contributed to the development of histopathological
changes in this organ such as dilated central vein and expanded
portal tract (hepatic artery, hepatic portal vein and bile duct).
Balasubramanyam et al. (2009) have revealed that exposure to al-
uminium oxide nanoparticles (30–40 nm, in the concentrations
of 500–2000 mg kg-1 body weight) caused genetic damages in
the bone marrow of rats. Inhalation of titanium dioxide nanoparti-
cles (in the concentrations of 2.5–10 mg kg-1 body weight) during
90 days caused accumulation of these nanoparticles in the brain of
mice, oxidative stress in the cells of the brain, overproliferation of
all glial cells, tissue necrosis, hippocampal cell apoptosis and           Figure 3. Schematic representation of metals accumulation in the skin
alterations in the expression of 249 known function genes (Ze              and their absorption by the skin. Al, aluminium; As, arsenic; Cd, cadmium;
et al., 2014).                                                             Cr, chromium; Hg, mercury; Ni, nickel; Pb, lead.
                                                                                                                                                        563
J. Appl. Toxicol. 2015; 35: 551–572                  Copyright © 2015 John Wiley & Sons, Ltd.                      wileyonlinelibrary.com/journal/jat
                                                                                                                        S. Borowska and M. M. Brzóska
      the amount of this element is reduced in the skin to the metallic           oxidized when suspended in synthetic sweat into Ni2+ and Co2+
      form and is accumulated in dermal tissues, which is seen as char-           ions that can permeate the skin, whereas Cr powder is not oxidized
      acteristic discolouration of the skin (Hg localized in the skin inacti-     and thus cannot permeate the skin. The impact of sweat on Ni and
      vates tyrosinase, which is the key melanine-forming enzyme; Chan            Co penetration by the skin and these elements retention in the
      et al., 2001; Hostynek, 2003). It has been revealed, using an in vitro      stratum corneum were confirmed by Sartorelli et al. (2012). They
      human skin model, that Hg is easily absorbed from popular skin-             have noted that in vitro percutaneous absorption of 63Ni (from
      lightening creams (Palmer et al., 2000). Application (without rub-          nickel chloride) and 57Co (from cobalt chloride) through the hu-
      bing) of 90 mg of skin-lightening cream (a typical amount of the            man skin during 24 h from application in water and artificial sweat
      cosmetic required to cover the exposed surface of the skin) con-            reached 0.23 ± 0.34% and 1.04 ± 0.64%, respectively, and 0.76 ±
      taining 290 μg Hg l-1 resulted in the concentration of 12 ± 1 μg            1.21% and 3.30 ± 2.65% respectively. The amounts of 63Ni and
      Hg l-1 in the receptor compartment (representing systemic absorp-           57
                                                                                    Co present in the stratum corneum reached 50.33 ± 19.91% and
      tion) after 3 h, whereas between the 18th and 24th hour the con-            27.62 ± 14.96%, respectively, in the case of application of these ele-
      centration increased up to 33 ± 9 μg l-1 (Palmer et al., 2000).             ments in water and 36.16 ± 9.30% and 41.30 ± 18.83%, respectively,
         Similarly to Hg, Pb is rapidly absorbed via skin appendages              when they were applied in artificial sweat (Sartorelli et al., 2012).
      (Stauber et al., 1994). It has been detected (using 204Pb isotope)             The percutaneous metal absorption is determined by many exo-
      that within 24 h almost 30% of the amount of lead nitrate applied           and endogenous factors. The first group involves the dose, vehicle,
      to the skin (4.4 mg) was absorbed (Stauber et al., 1994). Sun et al.        polarity, solubility, pH, frequency of application and the duration of
      (2002) have revealed Pb absorption by the skin from various com-            remaining on the skin as well as the temperature of the skin
      pounds of this metal (lead sulphate, lead oxide, lead powder and            (Palmer et al., 2000; Lin et al., 2012; Sartorelli et al., 2012; Otto
      lead stearate) applied to the dorsal side of the hand and the back          and Haydel, 2013). The main endogenous factors involve anatom-
      of Pb-battery workers based on an increased Pb concentration in             ical differences in skin properties, age (incomplete barrier function
      their blood.                                                                in infants and neonates, diminishing lipid surface and blood sup-
         Cd is absorbed well through the skin and is accumulated in the           ply, and transepidermal water loss in the elderly), skin health,
      liver and kidneys (Lansdown and Sampson, 1996). Moreover, Cd2+              and oxidation or reduction of metals in the skin (Hostynek, 2003).
      ions bind tightly to epidermal keratin (Guy et al., 1999). Lansdown         A very important factor influencing the efficiency of metal absorp-
      and Sampson (1996) have noted that after 10-day application of              tion via the skin is the place of cosmetic application. It is worth
      1% solution of cadmium chloride to the rat’s skin, the blood con-           underlining that the skin of the eyelids is the thinnest skin in the
      centration of this heavy metal reached 11.65 μg l-1, whereas its            body (Pratchyapruit et al., 2007), which enables easy absorption
      concentration in the liver and kidneys was 0.526 and 0.216 mg               of chemical substances, including metals, from eye make-up prod-
      kg-1, respectively, providing clear evidence of this heavy metal ab-        ucts. Moreover, dabbing a cosmetic in the skin facilitates metal ab-
      sorption via the skin. An average Cd concentration in the skin of           sorption (Lin et al., 2012). It is obvious that absorption of
      these animals reached 6 mg kg-1, confirming its accumulation in             xenobiotics via damaged skin is higher than through the intact
      the skin (Lansdown and Sampson, 1996).                                      skin (Lachenmeier, 2008; Pinneau et al., 2012). This also refers to
         It has been revealed that a single application to the human skin         metals (Filon et al., 2009). Filon et al. (2009) in in vitro permeation
      of aluminium chlorohydrate, used as the active ingredient in many           experiments, performed using Franz diffusion cells with intact
      antiperspirants, is not a significant contributor to the body burden        and damaged human skin, noted that Co and Ni powders (dis-
      of Al (Flarend et al., 2001). Flarend et al. (2001) have noted that only    persed in synthetic sweat at pH = 4.5 and applied to the outer sur-
      4.5 μg of Al (0.04%) in a woman and 2.6 μg (0.02%) in a man were            face of the skin for 24-h) permeate through the skin more easily
      absorbed during 6 days after a single application to the skin under         than Cr powder. Moreover, they have revealed that Co and Ni per-
      an occlusive bandage of 12.4 and 13.3 mg, respectively. Some                meation through the abraded skin barrier (3.6% and 1.27% of the
      amounts (1.9 μg in the woman and 1.1 μg in the man) of the metal            applied dose, respectively) was significantly higher compared with
      applied to the skin were eliminated in the urine during the 6-day           the intact skin (0.02% and 0.03% of the applied dose, respectively).
      period.                                                                     In the case of Cr, no significant difference in permeation through
         In the available literature, there are no in vivo data indicating        intact and damaged skin (0.03% and 0.01% of the applied dose, re-
      that Ni, Cr or Co can permeate through the skin into internal or-           spectively) was noted. Lower skin penetration by Cr powder than
      gans. These metals form deposits at deeper layers of the stratum            by Co and Ni powders may be explained with stronger binding
      corneum causing allergic contact dermatitis (van Ketel and Liem,            of Cr by the skin proteins (Filon et al., 2009).
      1981; Goh et al., 1989; Zemba et al., 1992; Saxena et al., 2001; Kang
      and Lee, 2006; Filon et al., 2009; Travassos et al., 2011). Ni binds
      mainly to carboxyl groups of keratin in epidermal and dermal tis-           Unfavourable Health Effects of Heavy Metals
      sue and penetrates the stratum corneum via diffusion through in-
      tercellular lipids (Guy et al., 1999). Cr (III) ions are unable to
                                                                                  Presence in Cosmetics
      penetrate biological membranes and are linked with epithelial               In the available literature, some cases of topical and systemic ef-
      and dermal tissues, forming stable complexes (Guy et al., 1999).            fects, related to the use of cosmetics containing heavy metals, in-
      Cr (VI) compounds such as chromate (CrO2-           4 ) and dichromate      cluding serious clinical cases, have been reported (Warley et al.,
      (Cr2O2-7 ) are rapidly taken up by cells through the anion transport        1968; Waldron, 1979; Shaltout et al., 1981; van Ketel and Liem,
      system (Guy et al., 1999). Cr (VI) applied to the skin is reduced to        1981; Goh et al., 1989; Zemba et al., 1992; Chan et al., 2001; Saxena
      Cr (III) ions during passage through the skin (Guy et al., 1999). It        et al., 2001; Soo et al., 2003; CDC, 2005, 2012a, 2012b; Foulds, 2006;
      has been revealed that metal absorption through the skin is closely         Tang et al., 2006, 2013; Held and Bayerl, 2008; Özkaya et al., 2009; Li
      related to the capacity of sweat to oxidize metals (Larese et al.,          et al., 2010; Amry et al., 2011; Benz et al., 2011; Chakera et al., 2011;
      2007). Larese et al. (2007), using the Franz diffusion cells with hu-       Travassos et al., 2011; Lin et al., 2012; Dickenson et al., 2013). Topi-
      man skin, demonstrated that metal powders of Ni and Co can be               cal effects such as various allergic reactions were caused mainly by
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      wileyonlinelibrary.com/journal/jat                    Copyright © 2015 John Wiley & Sons, Ltd.                     J. Appl. Toxicol. 2015; 35: 551–572
Metals in cosmetics
Ni and Fe present particularly in colour cosmetics (van Ketel and           the same product (especially in coloured cosmetics, for example
Liem, 1981; Goh et al., 1989; Zemba et al., 1992, Saxena et al.,            Ni and Cr in eye pencils; Table 1; Zemba et al., 1992). Kang and
2001; Foulds, 2006; Travassos et al., 2011), whereas especially             Lee (2006) noticed a case of allergic contact dermatitis after the
unfavourable effects, including internal organs damage, were re-            use of henna because of Ni, Co and p-phenylenediamine were
ported as a result of Hg or Pb presence (Warley et al., 1968;               present in this product. In most of the above-described cases of al-
Shaltout et al., 1981; , Al Mahroos and Faap, 1993; Weldon et al.,          lergy caused by the use of cosmetics containing metals (especially
2000; Chan et al., 2001; Soo et al., 2003; CDC, 2005, 2012a, 2012b,         Ni), the allergy to metals was confirmed by patch tests (van Ketel
2013a; Tang et al., 2006, 2013; Held and Bayerl, 2008; Özkaya               and Liem, 1981; Goh et al., 1989; Zemba et al., 1992; Saxena et al.,
et al., 2009; Al Naama et al., 2010; Li et al., 2010; Benz et al., 2011;    2001; Foulds, 2006; Kang and Lee, 2006; Travassos et al., 2011). Peo-
Chakera et al., 2011; Lin et al., 2012; Dickenson et al., 2013). In most    ple who know that they are allergic to metals should completely
cases, we did not find any information that the products                    avoid cosmetics containing metals such as Ni, Cr, Co or Fe. Thus,
responsible for the harmful effects had labels indicating the pres-         manufacturers should provide on packagings the information
ence of metals as ingredients. Only Özkaya et al. (2009) mentioned          about the presence and levels of these metals in the final products.
that one cream had the abbreviation ’precip blanc‘ on the label,               Cd and Cu present in cosmetics are other metals responsible for
which should suggest that this product contains Hg. None of the             unintended effects to the human body. A case of change of the
authors describing cases of poisoning and other unfavourable                hair colour into green after the use of henna containing Cu was ob-
health effects caused by metals from cosmetics provided informa-            served (Tosti et al., 1991). Severe eye keratitis after using kohl,
tion whether health authorities had removed these products from             which contained high amounts of Cd (6259 mg kg-1) and trace
the market and we cannot be sure if these products are still avail-         concentrations of Hg and thallium (Tl), has been reported in a
able or not.                                                                21-year-old woman (Amry et al., 2011).
   A few cases of allergic contact dermatitis caused by Ni from eye            Although Hg is widely known as a dangerous heavy metal
make-up products have been described (van Ketel and Liem, 1981;             (Karagas et al., 2012; Sommar et al., 2013) and some cases of poi-
Goh et al., 1989; Zemba et al., 1992). In one case, a woman suffered        sonings owing to the use of skin creams containing this element
from oedema and eczema of her eyelids after using for a few days            have been reported in the past (Karagas et al., 2012; Sommar
the eye shadows containing 15.9 mg Ni kg-1 and 4.5 mg Co kg-1.              et al., 2013), Hg-containing skin-lightening creams are still com-
Her problems disappeared after she had stopped using this prod-             monly used in many developing countries. Some women, espe-
uct. She had the same kind of skin problems in the past because of          cially from Africa, Asia or Mexico, often use such creams (Weldon
using an eye shadow of another brand (Goh et al., 1989). Another            et al., 2000; Soo et al., 2003; Tang et al., 2006, 2013; Chakera et al.,
woman was suffering from eyelid eczema for 13 months because                2011; CDC, 2012b). Using skin-lightening creams containing
of using an eye pencil containing 1.4 mg Ni kg-1 and 6.19 mg Cr             1762–30 000 mg Hg kg-1 resulted in an elevated concentration
kg-1. Her health problem disappeared after corticosteroids treat-           of Hg in hair (22.5 mg kg-1 vs. < 11.6 mg kg-1 in the family mem-
ment, but the eczema returned when she started to use this prod-            bers non-using these cosmetics; Chan et al., 2001), blood (26–233
uct again (Zemba et al., 1992). van Ketel and Liem (1981)                   nmol l-1 vs. its normal concentration < 30–50 nmol l-1 according
mentioned two women with eyelid dermatitis, one of whom also                to various authors; Chan et al., 2001; Soo et al., 2003; Chakera
had hand dermatitis. They considered Ni as a cause of these prob-           et al., 2011; Tang et al., 2013) and urine (316–2521 nmol per day
lems. The eye shadows used by these women contained 76 and 87               vs. normal concentration < 10–50 nmol per 24 h according to var-
mg Ni kg-1, whereas the mascara used by one of them contained               ious authors; Chan et al., 2001; Soo et al., 2003; Tang et al., 2013).
102 mg Ni kg-1. Allergic contact dermatitis, itching, erythema,             Using skin-lightening creams resulted in low back pain (Chan
moderate infiltration and scaling of both eyelids (symptoms last-           et al., 2001), sleep disorders, as well as in kidney damage mani-
ing 4 months) were also noticed in a woman from Belgium who                 fested by the oedema of this organ, stiffness of the glomerular pe-
used an eye pencil containing Ni in the concentration of 0.028              ripheral capillary loops, slight thickening of the glomerular
mg kg-1. These symptoms disappeared after stopping the use of               basement membrane, mild proliferation of mesangial cells and
this cosmetic, but they returned after she started to use this eye          matrix (Soo et al., 2003; Li et al., 2010), ankle swelling, frothy urine
pencil again (Travassos et al., 2011). Five cases of facial eczema          (Soo et al., 2003), proteinuria (Soo et al., 2003; Tang et al., 2006,
connected with using foundations containing iron oxide pigments             2013; Li et al., 2010), as well as peripheral and periorbital oedema
with trace amounts of Ni have been reported (Foulds, 2006). Ni was          (Chakera et al., 2011). In addition, systemic allergic dermatitis, ery-
also found in iron oxide brown pigments (1.9–250 mg kg-1) used              thema and itchy papulo-vesicular lesions 5–6 h after the applica-
for the production of eye cosmetics (van Ketel and Liem, 1981).             tion of the skin-lightening cream containing Hg have been
In addition, an incident of a 44-year-old woman with persistent             observed (Özkaya et al., 2009). Nephropathy was also reported in
eyelid allergic contact dermatitis (lasting for 10 months) caused           a woman exposed to Hg for 36 months from a hair dye who had
by 5% black iron oxide from a mascara has been noticed. Simulta-            the urinary concentration of this metal at the level of 27 μg l-1 (Li
neously the patch tests showed that she was also susceptible to             et al., 2010). Weldon et al. (2000) detected an elevated concentra-
lanolin present in this cosmetic (Saxena et al., 2001). However,            tion of Hg in the urine (mean 146.7 μg l-1; range 0 – 1,170 μg l-1;
her condition improved after she stopped using the mascara. An-             whereas the safe concentration is up to 20 μg l-1; CDC, 1990)
other allergen often present in coloured cosmetics is Cr (Zemba             among 330 lightening-cream users from Texas (USA).
et al., 1992; Sainio et al., 2000; Kang et al., 2006; Atz and Pozebon,         It is very important to underline that there exists strong and
2009; Al-Dayel et al., 2011). Chromium hydroxide green [Cr2O                well-confirmed evidence that using Hg-containing cosmetics
(OH)4] and chromium oxide green (Cr2O3) are added intentionally             may be a source of exposure to this metal of the family members
to eye shadows as colouring agents (Kang et al., 2006), which is ap-        non-using these products. The exposure may occur by the dermal
proved by EU regulations (OJEU, 2009). The threshold for allergic           route and through the gastrointestinal tract as well as by inhalation
reactivity to Cr (VI) is 5 mg l-1 (Kang et al., 2006). It should be em-     of Hg vapours (Held and Bayerl, 2008; CDC, 2012b). In the USA, a
phasized that metals causing allergic reactions may be present in           study was performed to establish a Hg concentration in the urine
                                                                                                                                                        565
J. Appl. Toxicol. 2015; 35: 551–572                   Copyright © 2015 John Wiley & Sons, Ltd.                     wileyonlinelibrary.com/journal/jat
                                                                                                                     S. Borowska and M. M. Brzóska
      of 22 members of 5 households where skin-lightening creams                et al., 2010; Lin et al., 2012; Goswami, 2013). The blood Pb concen-
      coming from Mexico were used (CDC, 2012b). Hg was detected                trations in 222 children from China having applied Pb powder for a
      in excessive amounts (≥5 μg g-1 creatinine) in the urine of 15 peo-       skin care purpose (as a folk remedy) ranged from 0.19 to 69.0 μg
      ple; however, only 10 of the 22 people declared the use of skin-          100 ml-1. The mean blood concentration of this heavy metal in
      lightening creams. Among the 15 people (9 users and 6 non-users           the entire group reached 18.1 μg 100 ml-1, whereas in regular
      of these creams), the Hg concentration in the urine ranged from           users, irregular users and non-users of this powder the concentra-
      26–317 μg g-1 of creatinine for users and from 20 to 276 μg g-1           tion was 32 μg 100 ml-1, 12 μg 100 ml-1 and 6 μg 100 ml-1, respec-
      of creatinine for non-users. Only in one user of these creams, the        tively (Lin et al., 2012). The final formulations (prepared by mixing
      Hg concentration in the urine was below 5 μg g-1 creatinine. High         lead monoxide – reddish powder with talcum powder) used for
      concentrations of Hg in the urine were also observed in young chil-       infants’ eczema and other skin problems in these children
      dren from families described above (up to 276 μg g-1 creatinine;          contained from 42 g Pb kg-1 to 623 g Pb kg-1 (Lin et al., 2012).
      CDC, 2012b). The non-specific symptoms of chronic Hg poisoning                The blood Pb concentrations in two twin children from the His-
      (numbness, tingling, dizziness, forgetfulness, headaches, and de-         panic community in the USA who used a yellow powder called
      pression) were observed in six users of these products. The results       ’litargirio‘ containing 790 g Pb kg-1 as an antiperspirant reached
      suggest that the 6 family members who had an increased Hg con-            14 μg 100 ml-1 and then increased (from June 2001 to May 2003)
      centration in the urine also were exposed to this metal from the          up to 42 μg 100 ml-1 for one of them and 15 μg 100 ml-1 in the
      bleaching creams. The concentration of Hg vapours in spot house-          other and then increased up to 26 μg 100 ml-1 (CDC, 2005). The
      hold locations (for example near items frequently touched                 Pb concentration in the blood of their female cousins aged 1 and
      by cream users or furniture where creams were stored) reached             5 years was 32 μg 100 ml-1 (from June 2002 to January 2003) and
      17 – 50 μg per m3 (CDC, 2012b). Cases of Hg poisonings from               then increased up to 44 μg 100 ml-1), and 24 μg 100 ml-1 and then
      skin-bleaching creams containing this element were also affirmed          increased up to 29 μg 100 ml-1, respectively (CDC, 2005). The youn-
      in two families who originated from the Kosovo–Albanian region            ger sister had not used litargirio, but she shared a bedroom with
      (Held and Bayerl, 2008). Elevated Hg concentrations in the urine          her sister (who used it regularly) and probably she ingested resi-
      were detected in a school survey in one of the sons of each family        dues of this product present on various surfaces through hand-
      and it was the reason for screening all members of these families.        to-mouth activity. The concentration of Pb in the blood of this girl
      The highest concentrations of Hg were found in females who had            decreased after her sister stopped using this product (CDC, 2005).
      used creams containing this element. One of them suffered from                In the available literature, we can found many cases of poison-
      chronic headaches and another lost weight and had high blood              ings caused by Pb from kohl (surma), which might be absorbed
      pressure. One of the male members of these families who did               through the conjunctiva, lacrimation, eye rubbing and finger suck-
      not use these creams suffered from concentration impairment               ing by children (Warley et al., 1968; Shaltout et al., 1981; Al Mahroos
      and gastrointestinal disorders. Because the women kept their              and Faap, 1993; Al Naama et al., 2010; CDC, 2012a, 2013a;
      creams in the fridges, the family members might be exposed to             Goswami, 2013). Many years ago, Warley et al. (1968) reported a
      this metal present in their diet (Held and Bayerl, 2008).                 case of Pb poisoning from kohl in a 3-year-old Indian boy (resident
         Particularly dangerous poisonings caused by Hg from cosmetics          in England) admitted to hospital with Pb encephalopathy. This
      were noted in children and pregnant women (Benz et al., 2011;             child had convulsions, Pb lines in the long bones and intestinal
      Dickenson et al., 2013). In a 4-year-old Iraqi girl, symptoms indicat-    opacities, suggesting ingestion of this heavy metal. The Pb concen-
      ing chronic intoxication with Hg such as clonic seizures, loss of ap-     tration in his blood was very high and reached 178 μg 100 ml-1.
      petite, and weight loss, weakness, dysthymia, impulsiveness,              The blood concentrations of this metal in his mother and a 5-
      itching rash in the palms, tachycardia, and hypertension, and hy-         year-old sibling were 65 μg 100 ml-1 and 72 μg 100 ml-1, respec-
      perintense lesions in the brain were observed after 3-month use           tively. The only source of the three subjects’ exposure to Pb was
      of this metal-containing skin-whitening cream. The concentrations         surma used by the mother for cosmetic reasons and in children
      of Hg in her blood and urine reached 32.5 and 41.1 μg l-1, respec-        for ’health‘ (Warley et al., 1968). Pb from kohl has also been consid-
      tively (Benz et al., 2011), whereas the safe level of Hg in urine has     ered as the cause of encephalopathy noted in Kuwait (Shaltout
      been considered to be < 20 μg per l-1 (CDC, 1990) and the highest         et al., 1981) and Bahrain children (Al Mahroos and Faap, 1993).
      acceptable concentration of this element in the blood is 6 μg l-1             Too high concentrations of Pb in the blood of children of two
      (Kuno et al., 2013). Using two different face creams, containing          families originating from Afghanistan and Nigeria were noticed
      21 and 30 g Hg kg-1, purchased from a pharmacy in Mexico by a             in USA as the result of using kohl or ’tiro‘ (a Nigerian cosmetic very
      woman who was in the third trimester of pregnancy resulted in a           similar to kohl used in Asia) to promote eye health or to protect the
      blood Hg concentration of 15.16 μg l-1 (Dickenson et al., 2013).          children from ’the evil eye‘ (CDC, 2012a, 2013a). Fortunately, de-
      The concentration of this element detected in her bathroom near           spite too high concentrations of Pb in the blood (reaching up to
      the jars of these face creams reached above 11 μg per m3                  33.5 μg 100 ml-1), they had no signs of Pb toxicity, because the
      (Dickenson et al., 2013), while its acceptable residential indoor air     chelation therapy was performed very quickly (CDC, 2012a,
      concentration is ≤ 0.5 μg per m3 (CDC, 1990).                             2013a). The content of Pb in the kohl used by the family originat-
         According to Centers for Disease Control and Prevention (CDC),         ing from Afghanistan reached 54% (CDC, 2013a), whereas this
      the acceptable Pb level in the blood of children is below 5 μg 100        metal content in the tiro used by the Nigerian family was 82.6%
      ml-1, whereas in adults from the general population (not working          (CDC, 2012a). The mean blood Pb concentration among 69 chil-
      in factory or other places where high concentrations of Pb are            dren in India whose parents applied kohl on their bodies (e.g. to
      present) the level is below 10 μg Pb 100 ml-1 (CDC, 2013b,                stop bleeding after a circumcision) was 29.6 ± 10.2 μg 100 ml-1
      2013c). Elevated Pb concentrations in the blood were reported in          (Goswami, 2013). On the labels of the surma packages it was not
      children and adults as a result of using cosmetic products contain-       mentioned that this product contained Pb; however, this metal
      ing this heavy metal (Warley et al., 1968; Shaltout et al., 1981; Al      was present in all collected samples in the concentrations ranging
      Mahroos and Faap, 1993; CDC, 2005, 2012a, 2013a; Al Naama                 from 0.64 to 32.13 mg kg-1 (Goswami, 2013). Al Naama et al. (2010)
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      wileyonlinelibrary.com/journal/jat                  Copyright © 2015 John Wiley & Sons, Ltd.                    J. Appl. Toxicol. 2015; 35: 551–572
Metals in cosmetics
have reported higher Pb concentrations in the blood of women                radiopaque particles in an ultrasound gel pad, simulating breast
from Iraq using kohl (13.91 ± 4.42 μg 100 ml-1) in comparison with          tissue. These particles were seen on a mammography, mimicking
their counterparts not using this product (9.88 ± 2.68 μg 100 ml-1).        microcalcifications whoses shape depends on the mode of appli-
   Many years ago a case of poisoning with Pb in a child from a hair        cation (solid, gel and roll-on) of the antiperspirants (Mesurolle
cosmetic used to darken hair was described. The concentration of            et al., 2014). The presence of radiopaque particles originating from
Pb in the blood of the 4-year-old girl was 1,360 μg l-1. The Environ-       antiperspirants in an ultrasound gel pad, simulating breast tissue,
mental Health Department discovered that the only source of Pb in           clearly shows that Al is accumulated in the breast tissue. Moreover,
her home was the product that her mother used to darken her hair.           some data indicate that Al is accumulated in high concentrations
The girl was in the habit of putting her fingers into cosmetic and          in nipple aspirate fluid present in the breast ducts of the people
licking them, and she suffered from Pb encephalopathy, head-                suffering from the breast cancer (Mannello et al., 2011) and in
aches, nausea and pale-grey colour of the skin (Waldron, 1979).             the human breast cyst fluid of the people suffering from gross
   The above-mentioned, well-documented reports on the                      cystic breast disease (Mannello et al., 2009). However, it is unclear
unfavourable effects related to metals presence in commercially             whether this metal found in the breast of the human who suffered
available cosmetics provide strong evidence that heavy metals               from breast cancer originated from antiperspirants.
present in these products may be dangerous.                                    The results of experiments conducted in recent years
                                                                            (Sappino et al., 2012; Darbre et al., 2013) confirmed the possibil-
                                                                            ity of Al participation in the development of cancer. Sappino
Danger for Health Created by Al Presence in                                 et al. (2012) revealed that aluminium chloride in concentrations
                                                                            of 10–300 μM (approximately 100 000-fold lower than those
Cosmetics                                                                   found in antiperspirants) acts as an activated oncogene in prolif-
As was mentioned previously, Al compounds may be present in                 erating primary human mammary epithelial cells because it in-
various types of cosmetic products, including antiperspirants, col-         duces genomic instability, DNA synthesis, senescence in
our cosmetics, creams and cosmetic emulsions, as well as in tradi-          proliferating primary human mammary epithelial cells and DNA
tional products and cosmetics containing minerals from the Dead             double-strand breaks, as well as it displays strong upregulation
Sea (Table 2). The use of these cosmetics is one of the sources of          of the p53/p21Waf1 pathway (a key mediator of growth arrest
exposure to Al, which is absorbed through the skin, and accumu-             and senescence) and it promotes anchorage-independent
lated in the organism as the result of repeated use of these prod-          growth in human mammary epithelial cells. Mutagenic action
ucts. Al is a metal characterized by high toxicity and under                was observed only in the cell line present in the human breast
prolonged exposure it accumulates in the bone tissue leading to             while it was not observed neither in bacteria nor in human
osteomalacia (Guillard et al., 2004) and in the brain contributing          keratinocytes, and it is strong evidence that Al has cancerogenic
to the development of Alzheimer’s disease and other neurodegen-             activity in human breasts (Sappino et al., 2012). Darbre et al.
erative disorders (Exley and Vickers, 2014).                                (2013) have noticed that Al can increase migratory and invasive
   Some literature data shows that Al presence in cosmetic prod-            properties of the human breast cancer cell line.
ucts may create a danger for human health (Guillard et al., 2004;
Sappino et al., 2012). Guillard et al. (2004) have provided clear evi-
dence of an unfavourable action of Al present in antiperspirants on
                                                                            Conclusions
the health of these products users. They have reported a case of            The numerous data presented in this review paper provide evi-
43-year-old woman suffering from hyperaluminemia, bone pain,                dence that heavy metals and the presence of Al and their too high
and extreme fatigue after using everyday for 4 years an antiperspi-         concentrations have been detected in cosmetics produced in var-
rant cream containing aluminium chlorohydrate. The woman ap-                ious countries, including countries with established strict law limi-
plied to each underarm about 1 g of the antiperspirant cream                tations on metals in cosmetics. The fact that nowadays people may
containing 20% of aluminium chlorohydrate (the authors did not              buy cosmetic products via the Internet or bring them from the
provide data about a brand of this product), what constituted a             countries without any specific regulations concerning the maxi-
daily dose of 0.108 g of Al(III), which over a 4-year period                mum levels of metals in cosmetics creates the risk of the use of
amounted to 157.3 g. The use of this antiperspirant was the only            contaminated cosmetic products even in countries with strict reg-
source of this woman’s exposure to Al. This element was detected            ulations on metals content in these products. Reported in the liter-
in her plasma and urine in concentrations of 3.88 ± 0.07 μmol l-1           ature are cases of allergic reactions and systemic actions caused by
(the normal concentration is < 0.37 μmol l-1) and 1.71 μmol per             heavy metals present in cosmetics together with the available data
24 h (the normal concentration is < 1.1 μmol per 24 h), respec-             on metal concentrations in cosmetics nowadays produced show
tively. When the woman has stopped using the antiperspirant,                that the risk of the unfavourable health effects due to metals pres-
the Al concentrations in the urine and plasma decreased and                 ence in the used cosmetics is still real. Thus, appropriate actions, in-
reached the reference levels (3 and 8 months later, respectively),          cluding especially the setting of limits of occurrence when they are
and then the bone pain and fatigue completely disappeared                   lacking until now as well as regular control of raw materials, condi-
(Guillard et al., 2004). This case clearly indicates that Al present in     tions of cosmetics production and the final products are necessary.
antiperspirants may be harmful for human health and that cessa-             This is particularly important because cosmetic products are used
tion of use of this cosmetic allows recovery.                               every day all over the world not only by women and men but also
   It is supposed that the presence of Al in antiperspirants can con-       by children and older people in who metal absorption via the skin
tribute to the development of breast cancer, especially of the up-          is facilitated and who are more susceptible to their toxic action.
per outer quadrant of the breast being a part of the body where             That is why cosmetics should be considered as a possible source
antiperspirants are applied (Darbre, 2003; Darbre, 2006; Mannello           of exposure to toxic metals and in the case of poisonings with
et al., 2009, 2011; Sappino et al., 2012; Darbre et al., 2013). Al-based    metals when the history of the case do not provide evidence of
complexes (used in antiperspirants as active ingredients) produce           exposure to metals from occupational and environmental
                                                                                                                                                        567
J. Appl. Toxicol. 2015; 35: 551–572                   Copyright © 2015 John Wiley & Sons, Ltd.                     wileyonlinelibrary.com/journal/jat
                                                                                                                                 S. Borowska and M. M. Brzóska
      conditions, cosmetics should be considered as possible causative                 Başgel S, Erdemoğlu SA. 2006. Determination of mineral and trace elements
      factors. It is necessary to make efforts to reduce dangerous metal                   in some medicinal herbs and their infusions consumed in Turkey. Sci.
                                                                                           Total Environ. 359: 82–89.
      concentrations in cosmetics with the aim to enhance the safety                   Benz MR, Lee SH, Kellner R, Döhlemann C, Berweck S. 2011. Hyperintense
      of these commonly used products.                                                     lesions in brain MRI after exposure to a mercuric chloride-containing
                                                                                           skin whitening cream. Eur. J. Pediatr. 170: 747–750.
                                                                                       Bilandžić N, Dokić M, Sedak M, Kolanović BS, Varenina I, Končrat A, Rudan N.
                                                                                           2001. Determination of trace elements in Croatian floral honey originat-
      Conflict of interest                                                                 ing from different region. Food Chem. 128: 1160–1164.
                                                                                       Bocca B, Forte G, Petrucci P, Cristuado A. 2007. Levels of nickel and other
      The authors declare that there are no conflicts of interest.                         potentially allergenic metals in Ni-tested commercial body creams.
                                                                                           J. Pharm. Biomed. Anal. 44: 1197–1202.
                                                                                       Borawska MH, Socha K, Soroczyńska J, Winiarska IM, Pełszyńska A.
                                                                                           2012. Ocena zawartości kadmu i ołowiu w naturalnych miodach
      References                                                                           pszczelich z regionu Podlasia. Bromat. Chem. Toksykol. 45:
      Abdel-Fattah A, Pingitore NE Jr. 2009. Low levels of toxic elements in Dead          775–779 (in Polish).
          Sea black mud and mud-derived cosmetic products. Environ. Geochem.           Brandão MHT, Gontijo B. 2012. Contact sensitivity to metals (chromium,
          Health 31: 487–492.                                                              cobalt and nickel) in childhood. An. Bras. Dermatol. 87: 269–276.
      Abdulla NN, Hamidi S, Younis MZ, Parkash J. 2013. Consumer awarness of           Brandão JD, Okonkwo OJ, Sekhula M, Raseleka RM. 2012. Concentrations of
          health risks of arsenic, cadmium, chromium and lead present in cos-              lead in cosmetics commonly used in South Africa. Toxicol. Environ.
          metic and personal care products in Dubai. J. Community Med. Health              Chem. 94: 70–77.
          Educ. 3: article 216.                                                        Brkljača M, Giljanovič J, Prkič A. 2013. Determination of metals in olive oil by
      Adawe A, Oberg C. 2013. Skin-lightening practices and mercury exposure in            electrothermal atomic absorption spectrometry: validation and uncer-
          the Somali community. Minn. Med. 96: 48–49.                                      tainty measurement. Anal. Lett. 46: 2912–2926.
      Adepoju-Bello AA, Oguntibeju OO, Adebisi RA, Okpala N, Coker HAB. 2012.          Cao H, Chen J, Zhang J, Zhang H, Qiao L, Men Y. 2010. Heavy metals in rice
          Evaluation of the concentration of toxic metals in cosmetic products in          and garden vegetables and their potential health risks to inhabitants in
          Nigeria. Afr. J. Biotechnol. 11: 16360–16364.                                    the vicinity of an industrial zone in Jiangsu, China 2010. J. Environ. Sci.
      Aguilar F, Autrup H, Barlow S, Castle L, Crebelli R, Dekant W, Engel KH,             (China) 22: 1792–1799.
          Gontard N, Gott D, Grilli S, Gürtler R, Larsen JC, Leclercq C, Leblanc JC,   CDC (Centers for Disease Control and Prevention). 1990. Epidemiologic
          Malcata FX, Mennes W, Milana MR, Pratt I, Rietjens I, Tobback P, Toldrá          notes and reports elemental mercury poisoning in a household – Ohio,
          F. 2008. Safety of aluminium from dietary intake. Scientific opinion of          1989. MMWR Morb. Mort. Wkly. Rep. 39: 424–425.
          the panel on food additives, flavourings, processing aids and food con-      CDC (Centers for Disease Control and Prevention). 2005. Lead poisoning as-
          tact materials (AFC). EFSA J.. 754: 1–34.                                        sociated with use of litargirio – Rhode Island, 2003. MMWR Morb. Mort.
      Al Mahroos F, Faap MD. 1993. Lead encephalopathy in a Bahraini infant.               Wkly. Rep. 54: 227–229.
          Bahrain Med. Bull. 15: 109–111.                                              CDC (Centers for Disease Control and Prevention). 2012a. Infant lead poi-
      Al Naama LM, Hassan MK, Hehdi JK, Al-Sadoon IO. 2010. Screening for                  soning associated with the use of tiro, an eye cosmetic from Nigeria –
          blood lead levels in Basrah, Southern Iraq. Qatar Med. J. 19: 43–47.             Boston, Massachusetts, 2011. MMWR Morb. Mort. Wkly. Rep. 61:
      Al-Ashban RM, Aslam M, Shah AH. 2004. Kohl (surma): a toxic traditional eye          574–576.
          cosmetic study in Saudi Arabia. Public Health 118: 292–298.                  CDC (Centers for Disease Control and Prevention). 2012b. Mercury exposure
      Al-Dayel O, Hefne J, Al-Ajyan T. 2011. Human exposure to heavy metals                among household users and nonusers of skin-lightening creams pro-
          from cosmetics. Orient. J. Chem. 27: 1–11.                                       duced in Mexico – California and Virginia, 2010. MMWR Morb. Mort.
      Al-Qutob MA, Alatrash HM, Abol-Ola S. 2013. Determination of different               Wkly. Rep. 61: 33–36.
          heavy metals concentrations in cosmetics purchased from the Palestin-        CDC (Centers for disease control and prevention). 2013a. Childhood lead
          ian markets by ICP/MS. AES Bioflux 5: 287–293.                                   exposure associated with the use of kajal, an eye cosmetic from Afghan-
      Al-Saleh I, Al-Enazi S, Shinwari N. 2009. Assessment of lead in cosmetic             istan – Albuquerque, New Mexico, 2013. MMWR Morb. Mort. Wkly. Rep.
          products. Regul. Toxicol. Pharmacol. 54: 105–113.                                62: 917–919.
      Amartey EO, Asumadu-Sakyi AB, Adjei CA, Quashie FK, Duodu GO, Bentil             CDC (Centers for disease control and prevention). 2013b. Standard surveil-
          NO. 2011. Determination of heavy metals concentration in hair po-                lance definitions and classifications. http://www.cdc.gov/nceh/lead/
          mades on the Ghanaian market using Atomic Absorption Spectrometry                data/definitions.htm [2 September 2014]
          Technique. Br. J. Pharmacol. Toxicol. 2: 192–198.                            CDC (Centers for disease control and prevention). 2013c. Very high blood
      Amry AM, Al-Saikhan F, Ayoubi A. 2011. Toxic effect of cadmium found in              lead levels among adults – United States, 2002 – 2011. MMWR Morb.
          eyeliner to the eye of 21 year old Saudi woman: A case report. Saudi             Mort. Wkly. Rep. 62: 967–971.
          Pharm. J. 19: 269–272.                                                       Chakera A, Lasserson D, Beck LH Jr. 2011. Membranous nephropathy after
      Arpadjan S, Çelik G, Taşkesen S, Güçer S. 2008. Arsenic, cadmium and lead in         use of UK-manufactured skin creams containing mercury. Q. J. Med.
          medicinal herbs and their fractionation. Food Chem. Toxicol. 46:                 104: 893–896.
          2871–2875.                                                                   Chan MHM, Chung RCK, Chan IHS, Lam CWK. 2001. An unusual case of mer-
      Ashraf MW. 2012. Levels of heavy metals in popular cigarette brands and              cury intoxication. Br. J. Dermatol. 144: 192–194.
          exposure to these metals via smoking. Sci. World J. 2012: article            Chauhan AS, Bhadauria R, Singh AK, Lodhi SS, Chaturvedi DK, Tomar VS.
          729430. DOI: 10.1100/2012/729430                                                 2010. Determination of lead and cadmium in cosmetic products.
      Atz VL, Pozebon D. 2009. Graphite furnace atomic absorption spectrometry             J. Chem. Pharm. Res. 2: 92–97.
          (GFAAS) methodology for trace element determination in eye shadow            Ciaralli L, Giordano S, Cassino A, Sepe A, Constantini S. 1996. Determination
          and lipstick. Atom. Spectrosc. 30: 82–91.                                        of chromium and nickel in commercial foam bath products by ETA-AAS.
      Ayenimo JG, Yusuf AM, Adekunle AS, Makinde OW. 2010a. Heavy metal ex-                Ann. Ist. Super. Sanita 32: 381–385.
          posure from personal care products. Bull. Environ. Contam. Toxicol. 84:      Cohen D, Soroka Y, Ma’or Z, Oron M, Portugal-Cohen M, Brégégère FM,
          8–14.                                                                            Berhanu D, Valsami-Jones E, Hai N, Milner Y. 2013. Evaluation of topically
      Ayenimo JG, Yusuf AM, Doherty WO, Ogunkule A. 2010b. Iron, lead and                  applied copper (II) oxide nanoparticle cytotoxicity in human skin organ
          nickel in selected consumer products in Nigeria: A potential public              culture. Toxicol. Vitro 27: 292–298.
          health concern. Toxicol. Environ. Chem. 92: 51–59.                           Contado C, Pagnoni A. 2012. A new strategy for pressed powder eye
      Balasubramanyam A, Sailaja N, Mahboob M, Rahman MF, Misra S, Hussain                 shadow analysis: allergenic metal ion content and particle size distribu-
          SM, Grover R. 2009. Evaluation of genotoxic effects of oral exposure to          tion. Sci. Total Environ. 432: 173–179.
          aluminium oxide nanomaterials in rat bone marrow. Mut. Res. 676:             Corazza M, Baldo F, Pagnoni A, Miscioscia R, Virgili A. 2009. Measurement of
          41–47.                                                                           nickel, cobalt and chromium in toy make-up by atomic absorption spec-
      Baranowska I, Srogi K, Włochowicz A, Szczepanik K. 2002. Determination of            troscopy. Acta Derm. Venereol. 89: 130–133.
          heavy metal contents in samples of medicinal herbs. Pol. J. Environ. Stud.   Cosmetic Ingredient Review Expert Panel. 2007. Final report on the safety
          11: 467–471.                                                                     assessment of Aloe Andongensis extract, Aloe Andongensis leaf juice,
568
      wileyonlinelibrary.com/journal/jat                        Copyright © 2015 John Wiley & Sons, Ltd.                          J. Appl. Toxicol. 2015; 35: 551–572
Metals in cosmetics
     Aloe Arborescens leaf extract, Aloe Arborescens leaf juice, Aloe                Goh CL, Ng SK, Kwok SF. 1989. Allergic contact dermatitis from nickel in an
     Arborescens leaf protoplasts, Aloe Barbadensis flower extract, Aloe                  eye pencil. Contact Dermatitis 20: 380–381.
     Barbadensis leaf, Aloe Barbadensis leaf extract, Aloe Barbadensis leaf          Gondal MA, Dastageer MA, Naqvi AA, Isab AA, Maganda YW. 2012. Detec-
     juice, Aloe Barbadensis leaf polysaccharides, Aloe Barbadensis leaf wa-              tion of toxic metals (lead and chromium) in talcum powder using laser
     ter, Aloe Ferox leaf extract, Aloe Ferox leaf juice, and Aloe Ferox leaf             induced breakdown spectroscopy. Appl. Optics 51: 7395–7401.
     juice extract. Int. J. Toxicol. 20: 1–50.                                       Gondal MA, Maganda YW, Dastageer MA, Al-Adel FF, Naqvi AA, Qahtan TF.
Cristuado A, D’Ilio S, Gallinella B, Mosca A, Majorani C, Violante N, Senofonte           2013. Development of a laser induced breakdown sensor for detecting
     O, Morronte A, Petrucci F. 2013. Use of potentially harmful skin-                    of carcinogenic chemicals in cosmetic products (conference paper).
     lightening products among immigrant women in Rome, Italy: a pilot                    High Capacity Optical Networks and Emerging/Enabling Technologies.
     study. Dermatology 226: 200–206. DOI: 10.1159/000348706                              HONET CNS 84–87.
Darbre PD. 2003. Underarm cosmetics and breast cancer. J. Appl. Toxicol. 23:         Gondal MA, Maganda YW, Dastageer MA, Al-Adel FF, Naqvi AA, Qahtan TF.
     89–95.                                                                               2014. Detection of carcinogenic chromium in synthetic hair dyes using
Darbre PD. 2006. Metalloestrogens: an emerging class of inorganic                         laser induced breakdown spectroscopy. Appl. Optics 53: 1636–1643.
     xenoestrogens with potential to add to the oestrogenic burden of the            Gondal MA, Seddiqi ZS, Nasr MM, Gondal B. 2010. Spectroscopic detection
     human breast. J. Appl. Toxicol. 26: 191–197.                                         of health hazardous contaminants in lipstick using laser induced break-
Darbre PD, Bakir A, Iskakova E. 2013. Effect of aluminium on migratory and                down spectroscopy. J. Hazard. Mater. 175: 726–732.
     invasive properties of MCF-7 human breast cancer cells in culture.              Goossens A. 2004. Contact allergic reactions on the eyes and the eyelids.
     J. Inorg. Biochem. 128: 245–249.                                                     Bull. Soc. Belge Ophthalmol. 292: 11–17.
Darbre PD, Harvey PW. 2014. Parabens can enable hallmarks and character-             Goswami K. 2013. Eye cosmetic „surma”: hidden threats of lead poisoning.
     istics of cancer in human breast epithelial cells: a review of the literature        Indian J. Clin. Biochem. 28: 71–73.
     with reference to new exposure data and regulatory status. J. Appl.             Guillard O, Fauconneau B, Olichon D, Dedieu G, Deloncle R. 2004.
     Toxicol. 34: 925–938.                                                                Hyperaluminemia in a woman using an aluminium-containing antiper-
Dickenson CA, Woodruff TJ, Stotland NE, Dobraca D, Das R. 2013. Elevated                  spirant for 4 years. Am. J. Med. 117: 956–959.
     mercury levels in pregnant woman linked to skin cream from Mexico.              Gump BB, Mackenzie JA, Bendinskas K, Morgan R, Dumas AK, Palmer CD,
     Am. J. Obstet. Gynecol. 209: e4–5.                                                   Parson PJ. 2011. Low-level Pb and cardiovascular responses to acute
Exley C, Vickers T. 2014. Elevated brain aluminium and early onset                        stress in children: the role of cardiac autonomic regulation. Neurotoxicol.
     Alzheimer’s disease in an individual pccupationally exposed to alumin-               Teratol. 33: 212–219.
     ium: a case report. J. Med. Case Rep. 8: 41.                                    Gunduz S, Akman S. 2013. Investigation of lead contents in lipsticks by solid
Faruruwa MD, Bartholomew SP. 2014. Study of heavy metal contents in fa-                   sampling high resolution continuum source electrothermal atomic ab-
     cial cosmetics obtained from open markets and superstores within                     sorption spectrometry. Regul. Toxicol. Pharmacol. 65: 34–37.
     Kaduna metropolis, Nigeria. Am. J. Chem. App. 1: 27–33.                         Guy RH, Hostýnek JJ, Hinz RS, Lorence CR. 1999. Metals and the Skin. Topical
Favaro PC, Bode P, De Nadai Fernandes EA. 2005. Trace elements in nail pol-               Effects and Systemic Absorption. Marcel Dekker: New York.
     ish as a source of contaminations of nail clippings when used in epide-         Haider AFMY, Lubna RS, Abedin KM. 2012. Elemental analyses and determi-
     miological studies. J. Radioanal. Nucl. Chem. 264: 61–65.                            nation of lead content in kohl (stone) by laser-induced breakdown spec-
FDA (Food and Drug Administration). 2007. CFR – Code of Federal Regula-                   troscopy. Appl. Spectrosc. 66: 420–425.
     tions title 21. Lead acetate. http://www.accessdata.fda.gov/scripts/cdrh/       Harada M, Nakachi S, Tasaka K, Sakashita S, Muta K, Yanagida K, Doi R, Kizaki
     cfdocs/cfCFR/CFRSearch.cfm?fr=73.2396 [21 July 2014].                                T, Ohno H. 2001. Wide use of skin-lightening soap may cause mercury
FDA (Food and Drug Administration). 2009. Product and ingredient safety:                  poisoning in Kenya. Sci. Total Environ. 269: 183–187.
     Hair dye products. http://www.fda.gov/Cosmetics/ProductandIngre                 Harcz P, Temmerman L, De Voghel S, Waegeneers N, Wilmart O, Vromman
     dientSafety/ProductInfor-mation/ucm143066.htm [20 December 2012]                     V, Schmit JF, Moons F, Van Peleghem S, De Saeger S, Schneider YJ,
FDA (Food and Drug Administration). 2013. CFR – Code of Federal Regula-                   Larondelle Y, Pussemier L. 2007. Contaminants in organically and con-
     tions Title 21. Use of mercury compounds in cosmetics including use as               ventionally produced Winter wheat (Triticum aestivum) in Belgium.
     skin bleaching agents in cosmetic preparations also regarded as drugs.               Food Addit. Contam. 24: 713–720.
     http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.              Hardy AD, Walton RI, Myers KA, Vaishnav R. 2006. Availability and chemical
     cfm?fr=700.13&SearchTerm=Mercury [21 July 2014]                                      composition of traditional eye cosmetics („kohls”) used in the United
FDA (Food and Drug Administration). 2014. Lipstick and lead: questions and                Arab Emirates of Dubai, Sharjah, Ajman, Umm Al-Quwaim, Ras Al-
     answers. http://www.fda.gov/Cosmetics?ProductsandIngredientSafety/                   Khaimah and Fujairah. J. Cosmet. Sci. 57: 107–125.
     ProductInformation/ucml137224.htm [10 April 2014]                               Hardy AD, Walton RI, Vaishnav R. 2004. Composition of eye cosmetics
Fijałek Z, Sołtyk K, Łozak A, Kominek A, Ostapczuk P. 2003. Determination of              (kohls) used in Cairo. J. Pharm. Biomed. Anal. 76: 225–233.
     some micro- and macroelements in preparations made from pepper-                 HC-SC (Health Canada-Santé Canada). 2012. Consumer product safety.
     mint and nettle leaves. Pharmazie 58: 480–482.                                       Guidance on heavy metal impurities in cosmetics. http://www.hc-sc.
Filipe P, Silva JN, Silva R, Cirne de Castro JL, Marques Gomes M, Alves LC,               gc.ca/cps-spc/pubs/indust/heavy_metals-metaux_lourds/index-eng.
     Santus R, Pinheiro T. 2009. Stratum corneum is an effective barier to                php [10 April 2014]
     TiO2 and ZnO nanoparticle percutaneous absorption. Skin Pharmacol.              Held B, Bayerl C. 2008. Chronic mercury intoxication in children of two fam-
     Physiol. 22: 266–275.                                                                ilies due to the cosmetic application of a mercury containing bleaching
Filon FL, D’Agostin F, Crosera M, Adami G, Bovenzi M, Maina G. 2009. In vitro             cream by the mothers. Akt. Dermatol. 34: 274–278 (in German).
     absorption of metal powders through intact and damaged human skin.              Hengstler JG, Bolm-Audorff U, Faldum A, Janssen K, Reifenrath M, Götthew
     Toxicol. Vitro 23: 574–579.                                                          W, Jung D, Mayer-Popken O, Fuchs J, Gebhard S, Bienfait G, Schlink K,
Final Report on the Safety Assessment of Hydrogenated Cottonseed Oil,                     Dietrich C, Faust D, Epe B, Oesch F. 2003. Occupational exposure to
     Cottonseed (Gossypium) Oil, Cottonseed Acid, Cottonseed Glyceride,                   heavy metals: DNA damage induction and DNA repair inhibition prove
     and Hydrogenated Cottonseed Glyceride. 2001. Int. J. Toxicol. 2: 21–29.              co-exposures to cadmium, cobalt and lead as more dangerous than
Flarend R, Bin T, Elmore D, Hem SL. 2001. A preliminary study of the dermal               hitherto expected. Carcinogenesis 24: 63–73.
     absorption of aluminium from antiperspirants using aluminium-26.                Hostynek JJ. 2003. Factors determining percutaneous metal absorption.
     Food Chem. Toxicol. 39: 163–168.                                                     Food Chem. Toxicol. 41: 327–345.
FOE-Australia. 2014. Beauty industry backs high risk small particles: Contro-        Hwang M, Yoon WK, Kim JY, Son BK, Yang SJ, Yun MO, Choi SS, Jang DD,
     versial nano-ingredients found in big name brands. www.                              Yoo TM. 2009. Safety assessment of chromium by exposure from cos-
     nanolawreport.com/uploads/file/FOE-Australia Cosmetics Report.pdf                    metic products. Arch. Pharm. Res. 32: 235–241.
     available 15 December 2014.                                                     Ioannidou MD, Zachariadis GA, Anthemidis AN, Stratis JA. 2005. Direct de-
Foulds IS. 2006. Facial eczema due to colour pigments in foundation                       termination of toxic trace metals in honey and sugars using inductively
     makeup in nickel sensitive patients. Contact Dermatitis 55: 11.                      coupled plasma atomic emission spectrometry. Talanta 65: 92–97.
Galazyn-Sidorczuk M, Brzóska MM, Moniuszko-Jakoniuk J. 2008. Estimation              Jallad KN, Espada-Jallad C. 2008. Lead exposure from the use of Lawsonia
     of Polish cigarettes contamination with cadmium and lead, and expo-                  inermis (henna) in temporary paint-on-tattooing and hair dying. Sci. To-
     sure to these metals via smoking. Environ. Monit. Assess. 137: 481–493.              tal Environ. 397: 244–250.
Gasser U, Klier B, Kühn AV, Steinhoff B. 2009. Current findings on the heavy         Kang IJ, Lee MH. 2006. Quantification of para-phenylenediamine and heavy
     metal content in herbal drugs. Pharmeur. Sci. Notes 1: 37–50.                        metals in henna dye. Contact Dermatitis 55: 26–29.
                                                                                                                                                                        569
J. Appl. Toxicol. 2015; 35: 551–572                          Copyright © 2015 John Wiley & Sons, Ltd.                           wileyonlinelibrary.com/journal/jat
                                                                                                                                    S. Borowska and M. M. Brzóska
      Kang EK, Lee S, Park JH, Joo KM, Jeong HJ, Chang IS. 2006. Determination of          Muñoz E, Palmero S. 2006. Determination of heavy metals in honey by po-
          hexavalent chromium in cosmetic products by ion chromatography                       tentiometric stripping analysis and using a continuous flow methodol-
          and postcolumn derivatization. Contact Dermatitis 54: 244–248.                       ogy. Food Chem. 94: 478–483.
      Karagas MR, Choi AL, Oken E, Horvat M, Schoeny R, Kamai E, Lowell W,                 Nnorm IC. 2011. Trace metals in cosmetic facial talcum powders marketed
          Grandjean P, Kerrick S. 2012. Evidence on human health effects of                    in Nigeria. Toxicol. Environ. Chem. 93: 1135–1148.
          low-level methylmercury exposure. Environ. Health Perspect. 120:                 Nnorm IC, Igwe JC, Oji-Nnorm CG. 2005. Trace metal contents of facial
          799–806.                                                                             (make-up) cosmetics commonly used in Nigeria. Afr. J. Biotechnol. 4:
      Khalid A, Bukhari IH, Riaz M, Rehman G, Ain QU, Bokhari TH, Rasool N, Zubair             1133–1138.
          M, Munir S. 2013. Determination of lead, cadmium, chromium and                   Nnorm IC, Osibanjo O, Eleke C. 2006. Evaluation of human exposure to lead
          nickel in different brands of lipsticks. IJBPAS 2: 1003–1009.                        and cadmium from some local Nigerian medicinal preparations. J. Appl.
      Kuno R, Roquettia MH, Beckerb K, Seiwertb M, Gouveiac N. 2013. Reference                 Sci. 6: 2907–2911.
          values for lead, cadmium and mercury in the blood of adults from the             Nourmoradi H, Foroghi M, Farhadkhani M, Dastjerdi MV. 2013. Assessment
          metropolitan area of Sao Paulo, Brazil. Int. J. Hyg. Environ. Health 216:            of lead and cadmium levels in frequently used cosmetic products in
          243–249.                                                                             Iran. J. Environ. Public Health 2012: article 962727.
      Lachenmeier DW. 2008. Safety evaluation of topical applications of ethanol           Obi E, Akunyili DN, Ekpo B, Orisakwe OE. 2006. Heavy metal hazards of Ni-
          on the skin and inside the oral cavity. J. Occup. Med. Toxicol. 3: article 26.       gerian herbal remedies. Sci. Total Environ. 369: 35–41.
      Laden K, Felger CB. 1988. Antiperspirants and Deodorants. Marcel Dekker:             Odukudu FB, Ayenimo JG, Adekunle AS, Yusuf AM, Mamba BB. 2014. Safety
          New York.                                                                            evaluation of heavy metals exposure from consumer products. Int. J.
      Lansdown ABG, Sampson B. 1996. Dermal toxicity and percutaneous ab-                      Consum. Stud. 38: 25–34.
          sorption of cadmium in rats and mice. Lab. Anim. Sci. 46: 549–554.               OJEC (Official Journal of the European Communities). 1993. Council
      Larese F, Gianpietro A, Venier M, Maina G, Renzi N. 2007. In vitro percutane-            Directive 93/35/EEC of 14 June 1993 amending for the sixth time
          ous absorption of metal compounds. Toxicol. Lett. 170: 49–56.                        Directive 76/768/EEC on the approximation of the laws of the
      Lee SM, Jeong HJ, Chang IS. 2008. Simultaneous determination of heavy                    Member States relating to cosmetic products. eur-lex.europa.
          metals in cosmetic products. J. Cosmet. Sci. 59: 441–448.                            eu/LexUriServ/LexUriServ.do?uri=OJ:L:1993:151:0032:0037:EN:PDF
      Li SJ, Zhang SH, Chen HP, Zeng CH, Zheng CX, Li LS, Liu ZH. 2010. Mercury-               [11 April 2014]
          induced membranous nephropathy: clinical and pathological features.              OJEU (Official Journal of the European Union). 2009. Regulation (EC) No
          Clin. J. Am. Soc. Nephrol. 5: 439–444.                                               1223/2009 of the European Parliament and of the Council of 30 Novem-
      Lin SH, Wang XR, Yu ITS, Tang WJ, Li J, Liu BY. 2012. Lead powder use for skin           ber 2009 on cosmetic products. eur-lex.europa.eu/LexUriServ/Lex
          care and elevated blood lead level among children in a Chinese rural                 UriServ.do?uri=OJ:L:2009:342:0059:0209:en:PDF [10 April 2014]
          area. J. Expo. Sci. Environ. Epidemiol. 22: 198–203.                             Oliveira MT, Constantino HV, Molina GO, Milioli E, Ghizoni JS, Pereira JR.
      Liu S, Hammond K, Rojas-Cheatham A. 2013. Concentrations and potential                   2014. Evaluation of mercury contamination in patients and water
          health risks of metal in lip products. Environ. Health Perspect. 121:                during amalgam removal. J. Contemp. Dent. Pract. 15: 165–168.
          705–710.                                                                         Oluremi Olabanji I, Ayodele Oluyemi E, Solomon Ajayi O. 2012. Metal anal-
      Malakootian M, Pourshaaban Mazandarani M, Hosseini H. 2010. Lead levels                  yses of ash derived alkalis from banana and plantain peels (Musa spp.)
          in powders of surma (kohl) in Kerman. J. Kerman Univ. Med. Sci. 17:                  in soap making. Afr. J. Biotechnol. 11: 16512–16518.
          167–174.                                                                         Omolaoye A, Uzairu A, Gimba CE. 2010. Heavy metals assessment of some
      Mannello F, Tonti GA, Medda V, Simone P, Darbre PD. 2011. Analysis of alu-               eye shadow products imported into Nigerian from China. Arch. Appl. Sci.
          minium content and iron homeostasis in nipple aspirate fluids from                   Res. 2: 76–84.
          healthy women and breast cancer-affected patients. J. Appl. Toxicol.             Onwordi CT, Onebunne OC, Dorcas WA, Ajani OI. 2011. Potentially toxic
          31: 262–269.                                                                         metals exposure from body creams sold in Lagos, Nigeria. Researcher
      Mannello F, Tonti GA, Darbre PD. 2009. Concentration of aluminium in                     3: 30–37.
          breast cyst fluids collected from women affected by gross cystic breast          Orisakwe OE, Otaraku JO. 2013. Metal concentrations in cosmetics com-
          disease. J. Appl. Toxicol. 29: 1–6.                                                  monly used in Nigeria. Sci. World J. DOI: 10.1155/2013/959637
      McKelvey W, Jeffery N, Clark N, Kass D, Parson PJ. 2011. Population-based            Otto CC, Haydel SE. 2013. Microbicidal clays: composition, activity,
          inorganic mercury biomonitoring and the identification of skin care                  mechanism of action, and therapeutic application. In Microbial
          products as a source of exposure in New York City. Environ. Health                   Pathogens and Strategies for Combating Them: Science, Technology
          Perspect. 119: 203–209.                                                              and Education, Méndez-Vilas A (ed). Formatex Research Center:
      Mesurolle B, Ceccarelli J, Karp I, Sun S, El-Khoury M. 2014. Effects of                  Badajoz; 2: 1169–1180.
          antiperspirant aluminium percent composition and mode of applica-                Oyedeji FO, Hassan GO, Adeleke BB. 2011. Hydroquinone and heavy
          tion on mock microcalcifications in mammography. Eur. J. Radiol. 83:                 metals levels in cosmetics marketed in Nigeria. Trends Appl. Sci. Res.
          279–282.                                                                             6: 622–639.
      MHLW. Ministry of Health Labor and Welfare Notification no. 331 of 2000.             Özkaya E, Mirzoyeva L, Ötkür B. 2009. Mercury-induced systemic allergic
          Japan. 2000. http://www.mhlw.go.jp/file/06-Seisakujouhou-11120000                    dermatitis caused by „white precipitate” in a skin lightening cream. Con-
          Iyakushokuhinkyoku/0000032704.pdf [18 August 2014]                                   tact Dermatitis 60: 61–63.
      Minocha R, Minocha SC. 2005. Effects of soil pH and aluminium on plant res-          Palmer RB, Godzin DA, McKinney PE. 2000. Transdermal kinetics of a mercu-
          piration. Advances in photosyntheis and respiration. Plant Respir. 18:               rous chloride beauty cream: an in vitro human skin analysis. Clin. Toxicol.
          159–176.                                                                             38: 701–707.
      Mitchnick MA, Fairhust D, Pinnell SR. 1999. Microfine zinc oxide (Z-cote) as a       Pera LL, Saitta M, Di Bella G, Dugo G. 2003. Simultaneous determina-
          photostable UVA/UVB sunblock agent. J. Am. Acad. Dermatol. 40: 85–90.                tion of Cd (II), Cu (II), Pb (II), and Zn (II) in citrus essential oils by
      Mohammed FA, Bchitou R, Boulmane M, Bouhaouss A, Guillaume D.                            derivative potentiometric stripping analysis. J. Agricult. Food Chem.
          2013. Modeling of the distribution of heavy metals and trace ele-                    51: 1125–1129.
          ments in argan forest soil and parts of argan tree. Nat. Prod. Commun.           Perkin Elmer. 2012. The determination of metals in cosmetics. http://www.
          8: 21–23.                                                                            perkinelmer.com/CMSResources/Images /44-132749APP_Metalsin Cos
      Monteiro-Riviere NA, Oldenburg SJ, Inman AO. 2010. Interactions of alumin-               meticsELANICP-MS.pdf [10 April 2014]
          ium nanoparticles with human epidermal keratinocytes. J. Appl. Toxicol.          Piccini P, Piecha M, Fortaner TS. 2013. European survey on the content of
          30: 276–285.                                                                         lead in lip products. J. Pharm. Biomed. Anal. 76: 225–233.
      Monteiro-Riviere NA, Wiench K, Landsiedel R, Schulte S, Inman AO, Riviere            Pinneau A, Guillard O, Fauconneau B, Favreau F, Marty MH, Gaudin A,
          JE. 2011. Safety evaluation of sunscreen formulations containing tita-               Vincent CM, Marrauld A, Marty JP. 2012. In vitro study of percutaneous
          nium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an                  absorption of aluminium from antiperspirants through human skin in
                                                                                                          TM
          in vitro and in vivo study. Toxicol. Sci. 123: 264–280.                              the Franz diffusion cell. J. Inorg. Biochem. 110: 21–26.
      Mousavi Z, Ziarati P, Shariatdoost A. 2013. Determination and safety assess-         Popoola OE, Bisi-Johnson MA, Abiodun A, Ibeh OS. 2013. Heavy metal con-
          ment of lead and cadmium in eye shadows purchased in local market                    tent and antimicrobial activities of some naturally occuring facial cos-
          Tehran. J. Environ. Anal. Toxicol. 3: article 193.                                   metics in Nigeria. IJS 15: 637–644.
      Mudholkar BS. 2012. Cosmetics consumption of females – a case study on               Popov AP, Ladermann J, Priezzhev AV, Myllylä R. 2005. Effect of size of TiO2
          girls students of S.R.T.M University, Nanded. IJRRBP 1: 94–97.                       nanoparticles embedded into stratum corneum on ultraviolet-A and
570
      wileyonlinelibrary.com/journal/jat                           Copyright © 2015 John Wiley & Sons, Ltd.                           J. Appl. Toxicol. 2015; 35: 551–572
Metals in cosmetics
     ultraviolet-B sun-blocking properties of the skin. J. Biomed. Opt. 10: arti-       mercury-containing skin lightening cream. Hong Kong Med. J. 12:
     cle 064037.                                                                        316–318.
Prabhakar PV, Reddy UA, Singh SP, Balasubramanyam A, Rahman MF, Indu                Tang HL, Mak YF, Chu KH, Lee W, Fung KS, Chan TYK, Tong KL. 2013. Mini-
     Kumari S, Agawane SB, Murty USN, Grower P, Mahboob M. 2012. Oxida-                 mal change disease caused by exposure to mercury-containing skin
     tive stress induced by aluminium oxide nanomaterials after acute oral              lightening cream: a report of 4 cases. Clin. Nephrol. 79: 326–329.
     treatment in Wistar rats. J. Appl. Toxicol. 32: 436–445.                       Tateo F, Ravaglioli A, Andreoli C, Bonina F, Coiro V, Degetto S, Giaretta A,
Pratchyapruit W, Kikuchi K, Gritiyarangasan P, Aiba S, Tagami H. 2007. Func-            Menconi Onisi A, Puglia C, Summa V. 2009. The in vitro percutaneous
     tional analyses of the eyelid skin constituting the most soft and smooth           migration of chemical elements from a thermal mud for healing use.
     area on the face: contribution of its remarkably large superficial                 Appl. Clay Sci. 44: 83–94.
     corneocytes to effective water-holding capacity of the stratum                 Tokalioğlu S. 2012. Determination of trace elements in commonly con-
     corneum. Skin Res. Technol. 13: 169–175.                                           sumed medicinal herbs by ICP-MS and multivariate analysis. Food Chem.
Raj S, Jose S, Sumod US, Sabitha M. 2012. Nanotechnology in cosmetics: op-              134: 2504–2508.
     portunities and challenges. J. Pharm. Bioallied Sci. 4: 186–193.               Tosti A, Mattioli D, Misciali C. 1991. Green hair caused by copper present in
Ramakritinan CM, Kaarunya E, Shankav S, Kumaraguru AK. 2013. Antibacte-                 cosmetic plant extracts. Dermatologica 182: 204–205.
     rial effects of Ag, Au and bimetallic (Ag-Au) nanoparticles synthesized        Travassos AR, Bruze M, Dahlim J, Goossens A. 2011. Allergic contact dermatitis
     from Red Algae. Solid State Phenom. 201: 211–230.                                  caused by nickel in a green eye pencil. Contact Dermatitis 65: 307–308.
Report for International Cooperation on Cosmetic Regulations (ICCR). 2011.          Ullah H, Noreen S, Fozia, Rehman A, Waseem A, Zubair S, Adnan M, Ahmad
     Principles for the handling of traces of impurities and or contaminants            I. 2013. Comparative study of heavy metals content in cosmetic prod-
     in cosmetic products. http://ec.europa.eu/consumers/sectors/cos-                   ucts of different countries marketed in Khyber Pakhtunkhwa, Pakistan.
     metics/files/pdf/iccr5_contaminants_en.pdf [10 April 2014]                         Arab. J. Chem.. DOI: 10.1016/j.arabic.2013.09.021
Roman A. 2003. Wpływ stanu toksykologicznego miodu na poziom                        Umar MA, Caleb H. 2013. Analysis of metals in some cosmetic products in
     kumulacji wybranych pierwiastków śladowych w organizmie pszczoły                   FCT – Abuja, Nigeria. Int. J. Res. Cosmet. Sci. 3: 14–18.
     miodnej (Apis mellifera L.). Acta Agrophys. 1: 295–300 (in Polish).            van Ketel WG, Liem DH. 1981. Eyelid dermatitis from nickel contaminated
Sah RC. 2012. The problem of lead in lipsticks in Nepal. CEPHED http://www.             cosmetics. Contact Dermatitis 7: 217.
     no-burn.org/downloads/CEPHED2012 LeadinLipstick-finalprint.pdf [11             Vemula PK, Anderson RR, Karp JM. 2011. Nanoparticles reduce nickel allergy
     April 2014]                                                                        by capturing metal ions. Nat. Nanotechnol. 6: 291–295.
Sainio EL, Jolanki R, Hakala E, Kanerva L. 2000. Metals and arsenic in eye          Volpe MG, Nazarro M, Coppola R, Rapuano F, Aquiro RP. 2012. Determina-
     shadows. Contact Dermatitis 42: 5–10.                                              tion and assessments of selected heavy metals in eye shadow cos-
Sanna G, Pilo MI, Piu PC, Tapparo A, Seeber R. 2000. Determination of heavy             metics from China, Italy and USA. Microchem. J. 101: 65–69.
     metals in honey by anodic stripping voltammetry at microelectrodes.            Vreca P, Dolenec T. 2005. Geochemical estimation of copper contamination
     Anal. Chim. Acta 415: 165–173.                                                     in the healing mud from Makirina Bay, central Adriatic. Environ. Int. 31:
Sappino AP, Buser R, Lesne L, Gimelli S, Béna F, Belin D, Mandriota SJ. 2012.           53–61.
     Aluminium chloride promotes anchorage-independent growth in hu-                Waldron HA. 1979. Lead poisoning from cosmetics. Lancet 2: 1070–1071.
     man mammary epithelial cells. J. Appl. Toxicol. 32: 233–243.                   Warley MA, Blackledge P, O’Gorman P. 1968. Lead poisoning from eye cos-
Sartorelli P, Montomoli L, Sisinni AG. 2012. Percutaneous penetration of                metic. Br. Med. J. 1: 117.
     metals and their effects on skin. Prevent. Res. 2: 158–164.                    Wei ZL, Rui YK, Shen L. 2008. Effects of hair dyeing on the heavy metals con-
Saxena M, Warshaw E, Ahmed DD. 2001. Eyelid allergic contact dermatitis to              tent in hair. Guang Pu Xue Guang Pu Fen Xi 28: 2187–2188 (in Chinese).
     black iron oxide. Am. J. Contact Dermatitis 12: 38–39.                         Weldon MM, Smolinski MS, Maroufi A, Hasty BW, Gillis DL, Boulanger LL,
Shaltout A, Yaish SA, Fernando N. 1981. Lead poisoning encephalopathy in                Balluz LS, Dutton RJ. 2000. Mercury poisoning associated with a Mexi-
     infants in Kuwait. Ann. Trop. Pediatr. 1: 209–215.                                 can beauty cream. West. J. Med. 173: 15–18.
Silici S, Uluozlu OD, Tuzen M, Soylak M. 2008. Assessment of trace element          World Health Organization. 2007. WHO Guidelines for Assessing Quality of
     in Rhododendron honeys of Black Sea Region,Turkey. J. Hazard. Mater.               Herbal Medicines with References to Contaminants and Residues. WHO,
     156: 612–618.                                                                      Geneva, Switzerland.
Sin KW, Tsang HF. 2003. Large-scale mercury exposure due to a cream cos-            Zakari IY, Sadiq AM, Nasiru R, Sadiq U. 2014. Radiological and toxic assess-
     metic: community-wide case series. Hong Kong Med. J. 9: 329–334.                   ment of Nigerian kohl as cosmetic compared with imported kohl cos-
Singh A, Krishna V, Angerhofer A, Do B, MacDonald G, Moudgil B. 2010. Cop-              metics. Res. J. Appl. Sci. Eng. Technol. 7: 2970–2975.
     per coated silica nanoparticles for odor removal. Langmuir 26:                 Ze Y, Hu R, Wang X, Sang X, Ze X, Li B, Su J, Wang Y, Guan N, Zhao X, Gui S,
     15837–15844.                                                                       Zhu L, Cheng Z, Cheng J, Sun Q, Wang L, Hong F. 2014. Neurotoxicity
Smart KE, Kilbum M, Schroeder M, Martin BG, Hawes C, Marsh JM, Grovenor                 and gene-expressed profile in brain-injured mice caused by exposure
     CR. 2009. Copper and calcium uptake in colored hair. J. Cosmet. Sci. 60:           to titanium dioxide nanoparticles. J. Biomed. Mater. Res. A 102:
     337–345.                                                                           470–478.
Soares AR, Nascentes CC. 2013. Development of a simple method for                   Zemba C, Romaguera C, Vilaplana J. 1992. Allergic contact dermatitis from
     the determination of lead in lipstick using alkaline solubilization                nickel in an eye pencil. Contact Dermatitis 27: 116.
     and graphite furnace atomic absorption spectrometry. Talanta 105:              Zhuang P, LuH, LZ, Zou B, McBride MB. 2014. Multiple exposure and effects
     272–277.                                                                           assessment of heavy metals in the population near mining area in
Sommar JN, Svensson MK, Björ BM, Elmståhl SI, Hallmans G, Lundh T, Schön                South China. PLoS One DOI: 10.1371/journal.pone.0094484
     SM, Skerfving S, Bergdahl IA. 2013. End-stage renal disease and low level
     exposure to lead, cadmium and mercury; a population-based, prospec-
     tive nested case-referent study in Sweden. Environ. Health 12: article 9.      Supporting Information
Soo YOY, Chow KM, Lam CWK, Lai FMM, Szeto CC, Chan MHM, Li PKT. 2003.
     A whitened face woman with nephrotic syndrome. Am. J. Kidney Dis. 41:          Additional supporting information may be found in the online ver-
     250–253.                                                                       sion of this article at the publisher’s web-site:
Stauber JL, Florence TM, Gulson BL, Dale LS. 1994. Percutaneous absorption
     of inorganic lead compounds. Sci. Total Environ. 145: 55–70.                   Table S1. Concentrations of heavy metals detected in colour eye
Stigter JB, De Haan HP, Guicherit R, Dekkers CP, Daane ML. 2000. Determi-           cosmetics produced in various countries (mg kg-1)
     nation of cadmium, zinc, copper, chromium, and arsenic in crude oil
     cargoes. Environ. Pollut. 107: 451–467.
Sukender K, Jaspreet S, Sneha D, Munish G. 2012. AAS estimation of heavy            Table S2. Concentrations of heavy metals detected in colour eye
     metals and trace elements in Indian herbal cosmetic preparations. Res. J.      cosmetics produced in various countries (mg kg-1)
     Chem. Sci. 2: 46–51.
Sun CC, Wong TT, Hwang YH, Chao KY, Jee SH, Wang JD. 2002. Percutane-
                                                                                    Table S3. Concentrations of heavy metals detected in colour lip
     ous absorption of inorganic lead compounds. AIHA J. 63: 641–646.
Tang HL, Chu KH, Mak YF, Lee W, Cheuk A, Yim KF, Fung KS, Chan HWH,                 cosmetics (lipsticks and lip glosses) produced in various countries
     Tong KL. 2006. Minimal change disease following exposure to                    (mg kg-1)
                                                                                                                                                                     571
J. Appl. Toxicol. 2015; 35: 551–572                          Copyright © 2015 John Wiley & Sons, Ltd.                         wileyonlinelibrary.com/journal/jat
                                                                                                              S. Borowska and M. M. Brzóska
      Table S4. Concentrations of metals detected in foundation            Table S8A. Concentrations of heavy metals detected in raw mate-
      creams, make-up bases, powders, nail polish and blushers pro-        rials, natural cosmetics and cosmetics considered as natural prod-
      duced in various countries (mg kg-1)                                 ucts (mg kg-1)
      Table S5. Concentrations of heavy metals detected in face and        Table S8B. Concentrations of heavy metals detected in raw mate-
      body care products (mg kg-1)                                         rials, natural cosmetics and cosmetics considered as natural prod-
                                                                           ucts (mg kg-1)
      Table S6 Concentrations of heavy metals detected in face and
      body care products (mg kg-1)                                         Table S9 Concentrations of heavy metals detected in raw material,
                                                                           natural cosmetics and cosmetics considered as natural products
      Table S7A. Concentrations of heavy metals detected in hair cos-      (mg kg-1)
      metics (mg kg-1)
wileyonlinelibrary.com/journal/jat Copyright © 2015 John Wiley & Sons, Ltd. J. Appl. Toxicol. 2015; 35: 551–572