Comparison of percutaneous absorption and metabolism of di-n-butylphthalate in various species. 2010

Dominique Beydon, and Jean-Paul Payan, and Marie-Christine Grandclaude
Institut National de Recherche et de Sécurité, Département Polluants et Santé, Rue du Morvan, Vandoeuvre Cedex, France. dominique.beydon@inrs.fr

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.

UI MeSH Term Description Entries
D008812 Mice, Hairless Mutant strains of mice that produce little or no hair. Hairless Mice,Mice, Inbred HRS,Mice, hr,Hairless Mouse,Mice, HRS,Mouse, HRS,Mouse, Inbred HRS,HRS Mice,HRS Mice, Inbred,HRS Mouse,HRS Mouse, Inbred,Inbred HRS Mice,Inbred HRS Mouse,Mouse, Hairless
D010968 Plasticizers Materials incorporated mechanically in plastics (usually PVC) to increase flexibility, workability or distensibility; due to the non-chemical inclusion, plasticizers leach out from the plastic and are found in body fluids and the general environment. Plasticizer
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002265 Carboxylic Ester Hydrolases Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion. Carboxylesterases,Ester Hydrolases, Carboxylic,Hydrolases, Carboxylic Ester
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003993 Dibutyl Phthalate A plasticizer used in most plastics and found in water, air, soil, plants and animals. It may have some adverse effects with long-term exposure. Butyl Phthalate,Di-n-Butyl Phthalate,Di n Butyl Phthalate,Phthalate, Butyl,Phthalate, Di-n-Butyl,Phthalate, Dibutyl
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004817 Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).
D004950 Esterases Any member of the class of enzymes that catalyze the cleavage of an ester bond and result in the addition of water to the resulting molecules. Esterase
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea

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