Comparison of percutaneous absorption and metabolism of di-n-butylphthalate in various species.
An ex vivo study of the percutaneous absorption of di-n-butylphthalate (DBP) showed that DBP was completely hydrolysed by esterases during penetration through rat skin. Fluxes were dependent on the esterase activity in the skin. The aim of this study was to determine the nature of the esterases involved in the hydrolysis of DBP in the skin. The relation between the percutaneous absorption of DBP and the epidermis/dermis esterase activity was determined in human, rat, rabbit, guinea-pig and mouse skin. An animal model was tested to estimate the human percutaneous absorption of lipophilic ester substances such as DBP. The nature of the esterases was determined by inhibition study in epidermis and dermis homogenates. A topical application of neat [(14)C]-DBP was used to determine ex vivo fluxes. Monobutylphthalate (MBP) levels in each skin layer were determined by high-performance-liquid-chromatography (HPLC). DBP was mainly hydrolysed by skin carboxyesterases for the all studied species. Unlike MBP levels in the skin, epidermis or whole skin esterase activity was not related to the DBP fluxes (hairless rat>hairy rat>hairless mouse=rabbit>guinea-pig>human) of all studied species. Therefore prediction of the results in the human being by extrapolation from animal data should be done carefully.
Beydon
Dominique
D
Institut National de Recherche et de Sécurité, Département Polluants et Santé, Rue du Morvan, Vandoeuvre Cedex, France. dominique.beydon@inrs.fr
Payan
Jean-Paul
JP
Grandclaude
Marie-Christine
MC
D000818:Animals; D001711:Biotransformation; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors; D002851:Chromatography, High Pressure Liquid; D020405:Dermis / Q000201:enzymology; D003993:Dibutyl Phthalate / Q000493:pharmacokinetics* / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000201:enzymology; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D010968:Plasticizers; D011817:Rabbits; D051381:Rats; D054772:Rats, Hairless; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000033:anatomy & histology / Q000166:cytology / Q000201:enzymology; D012869:Skin Absorption / Q000502:physiology*; D013045:Species Specificity
D004791:Enzyme Inhibitors; D010968:Plasticizers; D003993:Dibutyl Phthalate; D004950:Esterases; D002265:Carboxylic Ester Hydrolases