Evaluation of monkey skin as a model for in vitro percutaneous penetration and metabolism of [3H]T-2 toxin in human skin.
Discs of abdominal skin (obtained from humans and hybrid monkeys at autopsy) were mounted on diffusion cells. The epidermal surfaces were dosed with [3H]T-2 dissolved in dimethyl sulfoxide (DMSO). The rate of [3H]T-2 penetration (expressed as ng/cm2/hr) through human skin was 0.38 +/- 0.10 and 3.85 +/- 0.96 (means +/- 95% confidence limit) when dosed with 74 and 582 ng/cm2, respectively. [3H]T-2 penetrated through monkey skin at the rate of 0.37 +/- 0.14, 0.80 +/- 0.43, 4.13 +/- 1.71, and 6.55 +/- 3.45 when dosed with 70, 155, 555 and 1063 ng/cm2, respectively. Analysis of the receptor fluid bathing human skin revealed 15% of the radioactivity was associated with T-2, 71% with HT-2 toxin (HT-2), and 6.3% with an unknown metabolite more polar than HT-2. The radioactivity in the receptor fluid bathing monkey skin was associated with T-2 (87%) and HT-2 (1.0%). The results are consistent with the hypothesis that metabolism of T-2 occurred during penetration through the excised skin and did not occur in the receptor fluid due to enzymes leaching out of the skin. These findings indicate that excised monkey skin is a good model for T-2 penetration through human skin when DMSO is the vehicle, but that dermal metabolism of T-2 is different in these two species.
D000818:Animals; D001711:Biotransformation; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008251:Macaca; D008954:Models, Biological; D012717:Sesquiterpenes / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013045:Species Specificity; D013605:T-2 Toxin / Q000378:metabolism* / Q000633:toxicity
D012717:Sesquiterpenes; D013605:T-2 Toxin; D004121:Dimethyl Sulfoxide