Dermal Absorption Models in Toxicology and Pharmacology. Riviere, JE, ed., Boca Raton, FL: Taylor & Francis, 2005 Aug; :283-303
Drug and chemical dermal absorption typically involves experiments conducted using single chemicals, making the mechanisms of absorption extensively studied (the subject of most chapters in most risk assessment profiles and mathematical models of single chemicals. A primary route of occupational and to toxic chemicals is through the skin; however, such exposures chemical mixtures. In fact, the effects of coadministered extent of absorption of a topically applied systemic toxicant may determine whether toxicity is ever realized. This dichotomy between the availability of data and absorption models based on single chemicals with field exposure scenarios dominated complex mixtures deserves further attention. It is axiomatic that, for a topically applied chemical to exert systemic toxicity, absorption across the dermal barrier is required. For a topically applied compound to be absorbed into the skin, it must first pass through the stratum corneum, continue through the epidermal layers, and penetrate into the dermis, where absorption the dermal microcirculation becomes the portal for systemic exposure. For a chemical with direct toxicity to the skin, systemic absorption is not required as the cells could be any of those comprising the epidermis or dermis. The application of risk assessment to dermal absorption by U.S. regulatory agencies (U.S. Environmental Protection Agency [EPA], Occupational Safety Health Administration [OSHA], Agency for Toxic Substances and Disease Registry [ATSDR]) is varied and highly dependent on available data (Poet and McDougal, 2002; EPA, 1995, 2000). A similar concern over lack of data exists for overall assessment of chemical mixtures (Bogert et al., 2001; Pohl et al., 1997; EPA, 1988). The congressional Commission on Risk Assessment and Risk Management (CRARM, 1997) recommended moving beyond individual chemical assessments and focusing on the broader issue of toxicity of chemical mixtures. Current approaches are based on assigning toxicological equivalent units to similar chemical congeners (e.g., dioxins) or assessing toxicity after exposure to the complete mixture. Ideally, dose response curves of individual components of a mixture should characterized and then a "'no interaction" hypothesis tested (Bogert et al., 2001.) With complex mixtures of hundreds of components, this approach borders impossible. Importantly, interactions that involve modulation of absorption, and systemic bioavailability, have not been addressed.