Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: an in vitro study with benzo(a)pyrene and testosterone
Because viable skin possesses enzyme activities, including those involved in the metabolism of xenobiotics, the extent to which cutaneous metabolism may influence the percutaneous fate of topically applied chemicals in the skin was examined in mammalian skin maintained as short-term organ cultures. Skin samples from mouse, rat, rabbit, guinea pig, marmoset, and man were examined. The results from studies with benzo(a)pyrene (BP) and testosterone showed that, in all species, metabolic viability was a major factor involved in the in vitro skin permeation of surface-applied chemicals. Permeation was accompanied by extensive cutaneous first pass metabolism; both parent compounds and a full spectrum of metabolites were found in the receptor fluid from viable skin preparations. However, in previously frozen nonviable skin preparations, essentially only unchanged parent compounds were detected in the receptor fluid. Permeation of BP and testosterone was highest in mouse skin, and significant species variations in the metabolite profiles were observed. Studies with mouse skin also demonstrated that induction of cutaneous drug-metabolizing enzymes can result in a two- to threefold increase in the in vitro permeation of topical BP, and a significant reduction in permeation was observed when KCN was added to the perfusion medium. These results indicate that diffusional and metabolic processes are intimately involved in the percutaneous fate of surface-applied chemicals. The relative importance of these processes is dependent upon the physicochemical properties of the compounds and the metabolic capabilities of the skin toward the compounds in question. Furthermore, these findings suggest that meaningful in vitro studies on skin absorption should consider both diffusion and cutaneous biotransformation of the applied compound.
- Research Organization:
- Oak Ridge National Lab., TN
- OSTI ID:
- 5941091
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Vol. 3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZOPYRENE
SKIN ABSORPTION
TESTOSTERONE
BIOCHEMICAL REACTION KINETICS
DIFFUSION
FREEZING
GLUCOSE
GUINEA PIGS
IN VITRO
METABOLISM
METABOLITES
MICE
RABBITS
RATS
TRITIUM COMPOUNDS
ABSORPTION
ALDEHYDES
ANDROGENS
ANDROSTANES
ANIMALS
AROMATICS
CARBOHYDRATES
CONDENSED AROMATICS
HEXOSES
HORMONES
HYDROCARBONS
HYDROXY COMPOUNDS
KETONES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MONOSACCHARIDES
ORGANIC COMPOUNDS
REACTION KINETICS
RODENTS
SACCHARIDES
STEROID HORMONES
STEROIDS
UPTAKE
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)