Dermal Absorption Models in Toxicology and Pharmacology. Riviere, JE, ed., Boca Raton, FL: Taylor & Francis, 2005 Aug; :177-190
Although considerable progress has been made toward estimating the steady-state absorption rates of organic compounds applied to skin as aqueous solutions (Kasting et al., 1992; Potts and Guy, 1992; Wilschut et al., 1995; Johnson et al., 1997), less is known regarding the absorption of chemicals through skin under other conditions. In particular, the absorption of compounds, either volatile or nonvolatile, applied to skin neat or from volatile solvents is poorly understood. The problem is of great importance in risk assessment for both environmental and occupational chemical hazards, health and personal care products, and chemical warfare agents. This chapter focuses on the skin absorption of volatile chemicals, using fine fragrance ingredients as an example. These materials have been the subject of recent investigations in my laboratory (Kasting and Saiyasombati, 2001, 2003a, 2003b, 2004a, 2004b). For fine fragrances as well as many other fragranced consumer products, the chief concern in risk assessment is usually the potential for eliciting allergic contact dermatitis, otherwise known as skin sensitization (Robinson et al., 2000; Basketter, 1998; Kimber et al., 1999). The risk is usually assessed using a variety of tools, including structural-alert computer programs (Sanderson and Earnshaw, 1991), animal skin sensitization databases (Basketter et al., 2000), and human repeat insult patch tests (Basketter, 1998). Few, if any, additional animal studies are conducted on cosmetic products or ingredients given the zero animal use guidelines that have been adopted by the cosmetic and personal care industries. Consequently, there is a clear need to make accurate predictions from in silico models prior to exposing human subjects via a human repeat insult patch test (HRIPT) or a product introduction onto the market. A second aspect of risk assessment for fragranced products concerns systemic levels achieved by a combination of dermal absorption and inhalation. The hazards associated with each ingredient are carefully evaluated and controlled by a combination of exposure assessment plus intrinsic toxicity assessment (Gerberick and Robinson, 2000). Because most absorption occurs via the dermal route (caused by high dilution of the vapor into room air), skin absorption provides the link between these two areas. Absorption models should therefore attempt to answer the questions, What fraction of a topically applied dose will be absorbed? and How rapidly will this occur? For fragrance ingredients, a conservative but widely used approach is to assume 100% absorption (Robinson et al., 2000). There appear to be no widely used guidelines regarding absorption rates. The method described in this chapter represents a step toward tightening the risk assessment process for volatile compounds. It is simple to use and has been calibrated for fragrance ingredients (Kasting and Saiyasombati, 2001, 2003a, 2003b, 2004a, 2004b). Based on these data and the analysis described below, the method allows the estimation of percentage absorption and absorption rate to within a factor of two for commonly encountered fragrance ingredients. Research is under way to refine the method and extend its range of use to other chemical classes (Bhatt and Kasting, 2003).