Comparison of penetration and metabolism of [3H]diacetoxyscirpenol, [3H]verrucarin A and [3H]T-2 toxin in skin.
The purpose of this research was to determine the rate of cutaneous penetration and metabolism of [3H]diacetoxyscirpenol (DAS) and [3H]verrucarin A (VCA) and compare these values to previously determined values for [3H]T-2 toxin (T-2), to compare the cutaneous penetration and metabolism of DAS in human and guinea-pig skin, and to compare the effects of dose and of two vehicles, methanol and dimethylsulphoxide (DMSO), on penetration rates. DAS or VCA was applied to the epidermal surface of excised skin, and the receptor fluid bathing the dermal surface was sampled periodically for 48 hr. Whether the applied dose (581 ng/cm2) was dissolved in methanol or DMSO, the rate of penetration through human skin was lower for VCA than for DAS or T-2, the rates for the two latter compounds being similar at this dose. Metabolism of DAS occurred during penetration through excised human skin and did not occur in the receptor fluid as a result of enzymes leaching out of the skin. VCA appeared to be metabolized by human skin, but this conclusion is tentative because of the relative instability of this compound. DAS penetrated significantly (P less than 0.05) faster through excised guinea-pig skin than through human skin. Metabolism of DAS was greater in human skin than in guinea-pig skin. When compared with methanol, DMSO increased the penetration of DAS and VCA by factors of between 7 and 52. At the low dose (79 ng/cm2) DAS penetrated human and guinea-pig skin significantly (P less than 0.05) faster than T-2 using either vehicle.
D000328:Adult; D000368:Aged; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D012717:Sesquiterpenes / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D013045:Species Specificity; D013605:T-2 Toxin / Q000378:metabolism* / Q000633:toxicity; D014255:Trichothecenes / Q000378:metabolism* / Q000633:toxicity; D014316:Tritium
D007509:Irritants; D012717:Sesquiterpenes; D014255:Trichothecenes; D014316:Tritium; D013605:T-2 Toxin; C005348:muconomycin A; C001809:diacetoxyscirpenol; D004121:Dimethyl Sulfoxide