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.