**3. Metallokinetics and metallodynamics within the body**

The absorption, distribution, metabolism, excretion and interaction of heavy metals with bodily systems are complex processes that are not yet fully understood. This is even more complex when considering that some cosmetics are applied and rinsed shortly after (such as toothpastes, shampoos and conditioners and cleansers), others are applied and allowed for a few minutes to hours (such as body creams, lotions and facial makeup) and those that are applied and remain in contact with the skin for several hours (such as nail polish and hair dyes). The kinetics and dynamics of metals present in these cosmetic products, vary significantly in their fate and their extent of effects [21].

With the application of cosmetic products, the mode of entry of heavy metals in the body is via dermal or topical application. These metals may have either topical and/or systemic effects in humans [22]. At the site of application, heavy metals may accumulate in the stratum corneum causing local effects, that may be exhibited as allergic contact dermatitis associated with an excess of a metal (such as Ni, cobalt and chromium) at the site [23, 24] because of their binding to keratin [22]. In the case of Ni, this metal has a high affinity to the histidine component of the filaggrin in the stratum corneum [25]. Although, the mechanism by which heavy metals damage the skin is not yet fully understood, it is believed that this may be provoked by the formation of free radicals and/or by an inflammatory effect [26]. It was discovered that metals may accumulate with repeated application of contaminated cosmetics. Consequently, such areas would serve as reservoirs and hence lead to long-term exposure of the individual to the metal, even when such cosmetics are no longer applied [27]. The exposure of the skin to heavy metals may extend the dermal inflammation to the systemic system [26]. Ni can only penetrate and reach the general circulation, when damage is provoked by other metals [28]. Other metals such as Hg, Pb and Cd may enter the general circulation through the skin layers and transported to various organs within the body [29, 30]. This permeation can occur via sweat glands and hair follicles. Besides direct contact, oral ingestion of heavy metals may occur by the application of cosmetic products either to the lips (e.g., lipstick, lip gloss and lip balms) or within the buccal cavity (toothpastes, mouthwashes and breathe sprays) or by hand to mouth transfer of any cosmetic applied to any body part [31]. Thinner facial skin is more permeable than skin elsewhere [32]. Several studies show that certain heavy metals (such as Pb, Hg and Cd) found in topical cosmetics are found in high concentrations in the blood, urine and internal organs of individuals who use cosmetics when compared to individuals who do not [33–40]. Cosmetics that are applied directly to the skin may contain moisturizing agents that increase skin

permeation that may allow the entry of xenobiotics, to which some heavy metals may be bound, into the general circulation [41]. Apart from the binding of heavy metals to exogenous substances [42], these may also bind to endogenous biological molecules, hence replacing the beneficial metals. These metals may bind to several functional groups such as the amine, carboxylic and thiol function groups present in several proteins, some of which have functional roles (such as enzymes), while others have structural roles (such as collagen, keratin, actin and myosin). These metals can also bind to nucleic acids which may lead to defective DNA and RNA synthesis that may result in carcinogenesis. The application of underarm products has been hypothetically associated with the possibility of breast cancer [43]. Therefore, heavy metals provoke several toxic effects at the cellular and molecular levels [44, 45].

Several authors reported the presence of heavy metals in cosmetic products. This review gives an insight into the presence and effects of the most notorious and underestimated heavy metals in cosmetics products. The metals under discussion are lead, cadmium, nickel, mercury and arsenic.
