In vivo and in vitro skin absorption of lipophilic compounds, dibutyl phthalate, farnesol and geraniol in the hairless guinea pig.
The relationship between in vitro and in vivo skin absorption of lipophilic cosmetic ingredients (dibutyl phthalate (DBP, Log K(ow) 4.45) farnesol (Log K(ow) 5.77) and geraniol (Log K(ow) 3.56) from an oil in water emulsion was investigated in the hairless guinea pig. In vivo absorption of DBP, farnesol and geraniol 24h after dermal application was 62.0+ 2.0, 39.8+ 2.5, and 15.1+ 1.8% of the applied dose %AD) respectively. In vitro absorption was measured at 24 and 72 h by using flow through diffusion cells (0.64 cm(2) with a receptor fluid consisting of HHBSS+4% BSA. In vitro studies of DBP, farnesol and geraniol absorption over 24h found 27.1+ 1.9, 43.5+ 3.3 and 45.9+ 3.2%AD in receptor fluid, respectively, and over 72 h found 59.9+ 3.2, 77.5+ 7.1 and 49.0+ 6.3%AD, respectively. We found that the amount of DBP absorbed in vivo after 24h closely agreed with the amount of DBP found in the receptor fluid in vitro after 72 h. In contrast, the amount of topically applied farnesol absorbed in vivo after 24h was similar to the amount of farnesol found in receptor fluid in vitro after 24h. A direct comparison between the in vivo absorption of geraniol and the in vitro absorption at 24 and 72 h was not meaningful due to the rapid evaporation of geraniol from the skin. Our in vitro results suggest that lipophilic chemicals initially form a reservoir in skin, and the material in the reservoir may ultimately diffuse out of the skin into the receptor fluid within 72 h. Our results also demonstrate the utility of in vivo studies for resolving questions about the fate of lipophilic chemicals remaining in skin after in vitro absorption studies.
Food and chemical toxicology an international journal published for the British Industrial Biological Research Association