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Appendix D Food Codes for NHANES - OEHHA

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Scientific Review Panel Draft February, 2012<br />

extensive percutaneous metabolism when absorbed, and reducing the metabolic<br />

capabilities of skin samples will reduce dermal penetration of absorbed PAHs<br />

(Kao et al., 1985; Ng et al., 1992; Moody et al., 2009a).<br />

For metal salts, it has been postulated that low diffusion values through the<br />

stratum corneum in vitro are a result of skin shunts (e.g., hair follicles and sweat<br />

ducts) swelling shut upon hydration of skin samples (Tregear, 1966; Hostynek,<br />

2003). Skin shunts that bypass the stratum corneum are thought by some to be<br />

a significant absorption route <strong>for</strong> charged metals. For example, dermal<br />

absorption of nickel salts shows there is a surge in diffusion at the earliest stage,<br />

which then rapidly decreases towards steady state (Tanojo et al., 2001). The<br />

decrease in diffusion rate has been proposed to be a result of the skin tissue<br />

becoming hydrated, shutting down the skin shunts.<br />

A further potential limitation under in vitro conditions is that diffusing compounds<br />

must traverse the epidermis and the entire dermis in order to reach the receptor<br />

fluid. In vivo, the majority of the absorption into the cutaneous microcirculation is<br />

thought to occur in the upper dermis and the penetrant compounds may not have<br />

to diffuse across the entire thickness of the dermis. However, the bulk of the<br />

connective tissue in the dermis is often eliminated from the skin preparation by<br />

cutting the skin parallel to the skin surface with a dermatome (Poet and<br />

McDougal, 2002).<br />

In vivo studies are not without limitations. Dermally applied chemicals are often<br />

radiolabeled to facilitate quantification of the usually low absolute amounts of<br />

chemical dermally absorbed. In small mammals, a total accounting of all<br />

dermally absorbed radioactivity can be estimated from excreta, carcass, and site<br />

of skin absorption. However, in larger mammals measurements of radiotracer<br />

are quantified in excreta and measurements from intravenous, intramuscular, or<br />

oral dosing are applied as a correction <strong>for</strong> tissue absorbed chemical. The validity<br />

of this method depends on the underlying assumption that metabolism and<br />

disposition of the applied compound is route independent, and that the<br />

pharmacokinetic behavior of the intravenous and topical doses is similar (Kao,<br />

1990).<br />

F.2.8 Inter- and Intra-Species Specificity<br />

The variability in dermal absorption of chemicals among mammalian species has<br />

been investigated in vivo and in vitro. Bartek et al. (1972) suggest that the extent<br />

of in vivo uptake among animals follows the rank: rabbit > rat > pig ≈ monkey ≈<br />

humans, based on dermal absorption of benzoic acid, hydrocortisone,<br />

testosterone, caffeine, N-acetylcysteine, and butter yellow. However, the species<br />

ranking did not strictly hold <strong>for</strong> all chemicals, indicating not only species-specific<br />

differences but also chemical-specific differences.<br />

F-12

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