Chemical mixtures, dermal interactions

Riviere JE, Brooks JD. 2007. Prediction of dermal absorption from complex chemical mixtures incorporation of vehicle effects and interactions into a QSPR framework. SAR QSAR Environ Res 18 31 -4. 

Our research program has focused on the effects of chemical mixture components on dermal absorption of select marker chemicals in the mixture (Qiao et al., 1996 Baynes, Brooks, Mumtaz, et al., 2002 Riviere et al., 2001,2003). As varied as these potential interactions may be, experimentally isolating them is difficult because of... 

When exposed to mixtures, chemicals in the exposure medium may affect each other s uptake by humans in a manner that is analogous to some of the bioavailability effects outlined here for environmental species. This was, for instance, shown for the neurotoxicity of EPN (O-ethyl-O-4-nitrophenyl phenylphosphono-thionate), which was enhanced by aliphatic hydrocarbons due in part to increased dermal absorption (Abou-Donia et al. 1985). It was also shown that dietary zinc inhibits some aspects of lead toxicity, which could in part be explained by decreasing dietary lead absorption (Cerklewski and Forbes 1976). Other examples of interactions of chemicals at the uptake phase in humans, which may in part be related to bioavailability interactions, are summarized in Table 1.3. 

Administration of zinc provides some protection against the testicular toxicity of di- -butyl phthalate exposure in rats (Cater et al. 1977). No other studies were located regarding the interaction of di- -butyl phthalate with other chemicals. Schulsinger and Mullgaard (1980) reported that humans exposed to a mixture of three phthalate esters, including di- -butyl phthalate, did not develop dermal sensitization, but since di- -butyl phthalate is negative for skin sensitization, these results shed little light on possible interactions. 

Beyond the pure physicochemical interactions described, there is increasing evidence that jet fuels themselves can alter skin structure, and it is probably by this additional mechanism that may be associated with increased dermal absorption of permethrin. These chemical-induced modifications in skin structure have been demonstrated by increased transepidermal water loss and significant dermatotoxicity at the macroscopic and molecular levels in skin (Monteiro-Riviere et al., 2001, 2004 McDougal and Rogers, 2004). It is therefore no surprise that chronic exposure to these mixtures of solvents can enhance jet fuel hydrocarbon absorption (Muhammad etal., 2004). This is characteristic for chronic dermal exposures to solvents and strongly suggests that military persormel are more likely to absorb hazardous chemicals across their skin if they are chronically exposed to jet fuels or solvrait-related chemicals. 

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