**4.4 Mercury**

Mercury is one of the heavy metals that is widely used in cosmetic formulations. Although, mercury is known as a shiny, silvery, dense liquid, it may occur in various inorganic and organic compounds. In the inorganic form, such as ammoniated Hg, it is used for its skin lightening properties, whereas in the organic form, such as phenyl mercuric and ethyl mercuric salts, it is used as a preservative in mascaras and eye makeup cleansing products [90, 109]. After dermal application, Hg penetrates through the skin via the hair follicles and sweat glands [29, 96]. During this process, part of the Hg is reduced to the metallic form that accumulates in the skin tissue. Hg blocks tyrosinase in situ, inhibiting the melanin-forming enzyme [110], hence its use in skin-lightening creams [22]. Only one study mentioned that cream had the abbreviation 'precip blanc' on the label, which should suggest that this product contains Hg [36]. Systemically, Hg may exhibit a range of signs which include vomiting, nausea and kidney damage, central nervous sytstem effect which include irritability, tremors, weakness, nervousness, fatigue and memory loss. It may affect also the sensorial systems, that is, loss in hearing, taste and vision. Finally, high Hg content may lead to death [111, 112]. In some instances, following dermal absorption and systemic uptake, Hg may induce autoimmune glomerulonephritis. Studies reveal significant accumulation of mercury in several organs and body fluids, such as hair (22.5 ppm, twice that in non-cosmetic users), blood (up to 233 nmol/l, more than four times than that in non-cosmetic users] and urine (up to 2531 nmol/day, fifty times more than that in non-cosmetic users) [39, 91, 113, 114].

Mercury is a metallic element that is naturally occurring in the environment and its compounds are the most common form that exists naturally in the environment. Due to its ubiquity, several authorities issued limitations for Hg use. For instance, the FDA restricts its use and is regulated in cosmetic products. The FDA allows a maximum level of 1 ppm of Hg in mercury-contaminated lead acetate when used as a colour in cosmetics [10]. Within the European Union, mercury and its compounds are not allowed in cosmetics, whereas phenyl mercuric salts are only allowed as preservatives in eye care products at a maximum allowable level of 70 ppm [5] whereas in the US it is allowed up to a level of 65 ppm by weight [10]. Health Canada allows a maximum Hg content of 1 ppm in cosmetics [11].

The main emphasis of analysis by researchers was conducted on skin-lightening creams due to their interaction with melanin metabolism. Very few studies report levels below the 3 ppm threshold [15, 53, 70] (**Tables 1**–**3**). Other studies reveal values up to 126,000 ppm [61, 89–93]. Although, in some lipstick products, the Hg content was below the detection limit [58, 61, 62], some of these same studies and others reveal contents up to 80 ppm [63]. The status of Hg contamination in eye cosmetic products varies significantly with levels of up to 181 pm in eye shadows [58, 62], 67.42 ppm in eyebrow pencils [58, 62, 63] but levels of up to 0.002 ppm in mascaras [58]. Apart from the make-up foundation where levels of Hg reach a maximum level of 60.77 ppm [63], other face products contain minimal amounts of Hg, such as face creams (0.09 ± 0.37 ppm [62]), sunblock creams (0.41 ± 1.21 ppm [62]) and face paints (<0.004 ppm [69]). In some studies, it was reported that the content of Hg in hair products is below the detection limit [62] whereas in other studies, it reached a maximum of 90.32 ppm [63, 83]. Body care products such as body lotions and cleansers contain varied amounts of Hg [62], with products from the first group with contents up to 47.5 ppm [61]. In some beauty creams, the Hg level reached a

maximum of 124.8 ppm [83]. The presence of mercury in toothpaste has not been widely investigated, but in two studies, the Hg level was reported to reach a maximum of 13.14 ppm [81, 83].

As can be concluded from these studies, Hg is one of the least detected heavy metals in most cosmetics [22], but not in skin-lightening products. Mercury is found intentionally in face and skin care products rather than in products for purely cosmetic use. Apart from skin-lightening properties, Hg compounds are claimed to reduce and remove freckles, treat acne, and prevent and remove wrinkles [22].

#### **4.5 Arsenic**

Arsenic is a metalloid that is present ubiquitously as a major contaminant in the environment. Although, it is redox inactive, its target functional groups are sulfydryl groups on proteins which may lead to the depletion of glutathione [115], an essential antioxidant of an amino acid origin, which prevents damage of cellular components caused by radicals and heavy metals. On long-term dermal exposure, As can cause hyperpigmentation and keratosis *in situ*, but systemically it may lead to carcinogenesis and vascular diseases [115, 116]. Though considered as a less significant contaminant in cosmetics than other heavy metals, authorities sought to establish limits for its presence in cosmetic products due to long-term exposure. The problem with As contamination goes beyond the legal cosmetic products placed on the market. It has been found in high quantities in cosmetic products from the underground market [58]. As with Hg, the FDA established a limit for As (up to 3 ppm) for lead acetate, as a colorant, contaminated with this metalloid [10]. This acceptable maximum limit goes also under the general limits set by Health Canada for all cosmetics [11]. Arsenic and its salts are prohibited in any cosmetic product within the EU [5].

In general, several studies reveal that As is not a significant contaminant and levels of this metalloid rarely exceed the 3 ppm limit (**Tables 1**–**3**). In lipsticks, although most studies report a level of up to 0.34 ppm [62, 63], a study reported a maximum level of 6.931 ppm of As [58]. In eye cosmetics, the maximum permissible limit is rarely exceeded. In general, eye shadows, eyebrow pencils and mascaras do not contain As levels more than 3.704, 2.071 and 1.656 ppm, respectively [58, 62, 63]. However, in a study, it was reported that in kohl, there was an alarming presence of As (810–1630 ppm). Kohl is an ancient eye cosmetic still used nowadays [75]. The danger with kohl is not solely because of its use as a cosmetic but there are claims that falsely indicating its use for the treatment of eye conditions. Apart from the presence of As in kohl, other face cosmetics, such as foundations and creams contain minimal quantities of As, reported as up to 1.0 and 0.171 ppm, respectively [62, 63]. Less commonly used products include face paints particularly used by opera actors in China. Levels of As reach a maximum of 25 ppm [79]. Shampoos, conditioners and dyes used on the hair contain low As concentrations (<0.71 ppm) [62, 63, 94]. Likewise, in a study, the As content for cleansers and sunblocks does not exceed 0.010 ppm [62] but higher levels were reported for body lotions (1.543 ppm) [83]. There are some concerns with skin-lightening creams as some exceed the 3 ppm threshold [53, 89] and other creams with levels up to 10.74 ppm [83]. In some toothpaste, the As content was 26.94 ppm [83]. Most likely, As is present as a contaminant with other heavy metals used for this purpose. In spite of these findings, As is one of those elements that is rarely found in cosmetics [22]. However, its presence may raise concerns particularly in legal products that are used on a long-term basis and in illegal cosmetic products on the underground market.
