Comparative in vitro-in vivo percutaneous absorption of the pesticide propoxur

In vitro and in vivo skin absorption of the pesticide propoxur (2-isopropox yphenyl N-methyl carbamate, commercially Baygon(TM) and Unden(TM); log Po/w 1.56, MW 209.2) was investigated. In vivo studies were performed in rats a nd human volunteers, applying the test compound to the dorsal skin and the volar aspect of the forearm, respectively. In vitro experiments were carrie d out in static diffusion cells using viable full-thickness skin membranes (rat and human), non-viable epidermal membranes (rat and human) and a perfu sed-pig-ear model. Percutaneous penetration of propoxur in human volunteers was measured by analysis of its metabolite (2-isopropoxyphenol) in blood a nd urine; in all other studies radiolabeled propoxur ([ring-U-C-14]propoxur ) was used. In order to allow for direct comparison, experimental condition s were standardized with respect to dose (150 mug propoxur per cm(2)), vehi cle (60% aqueous ethanol) and exposure time (4 h). In human volunteers, it was found that approximately 6% of the applied dose was excreted via the ur ine after 24 h, while the potential absorbed dose (amount applied minus amo unt washed off) was 23 mug/cm(2). In rats these values were 21% and 88 mug/ cm(2), respectively. Data obtained in vitro were almost always higher than those obtained in human volunteers. The most accurate in vitro prediction o f the human in vivo percutaneous absorption of propoxur was obtained on the basis of the potential absorbed dose. The absorbed dose and the maximal fl ux in viable full-thickness skin membranes correlated reasonably well with the human in vivo situation (maximal overestimation by a factor of 3). Epid ermal membranes overestimated the human in vivo data up to a factor of 8, b ut the species-differences observed in vivo were reflected correctly in thi s model. The data generated in the perfused-pig-ear model were generally in termediate between viable skin membranes and epidermal membranes.