Comparison of in vivo and in vitro percutaneous absorption of T-2 toxin in guinea pigs.
The fate and distribution of T-2 were examined in 6 guinea pigs. T-2 (1.2 micrograms/cm2), in methanol or DMSO, was painted onto the shaved backs of guinea pigs, a screen barrier was applied, urine and feces were collected daily and the guinea pigs were killed after 48 hr. Disks of skin (lateral to the in vivo site of application) were excised from the guinea pigs and used for in vitro penetration studies with static diffusion cells. Skin excised from 6 additional guinea pigs was used for penetration studies with flow-through diffusion cells. For in vitro studies, T-2 dissolved in methanol or DMSO was applied to the epidermal surfaces and the appearance of penetrant in receptor fluid bathing the dermal surfaces was monitored for 48 hr. Metabolism of T-2 was measured by using thin layer radiochromatography to identify metabolites. In the in vivo study, mean cutaneous absorption (n = 3) after 48 hr (expressed as per cent dose) was 22.5 and 51.9 for the methanol and DMSO groups, respectively. In vitro cutaneous penetration for static diffusion cells was 3.9 and 38.4 for the methanol and DMSO groups. For flow-through diffusion cells, mean penetration (n = 9) was 14.6 and 42.6 for the methanol and DMSO groups. Urinary metabolites of T-2 were T-2 triol, 3' OH-HT-2, T-2 tetraol, the glucuronide conjugate of HT-2 and several more polar metabolites. The main metabolite of T-2 in the receptor fluid bathing the dermal surfaces of excised skin was HT-2.
Department of Pharmacal Sciences, School of Pharmacy, Auburn University, Alabama 36849.
B W
BW
Kemppainen
J G
JG
Page
R T
RT
Riley
D000818:Animals; D004058:Diffusion; D004121:Dimethyl Sulfoxide; D005243:Feces / Q000032:analysis; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D000432:Methanol; D014677:Pharmaceutical Vehicles; D012717:Sesquiterpenes / Q000493:pharmacokinetics*; D012869:Skin Absorption; D013605:T-2 Toxin / Q000493:pharmacokinetics* / Q000652:urine
D014677:Pharmaceutical Vehicles; D012717:Sesquiterpenes; D013605:T-2 Toxin; D000432:Methanol; D004121:Dimethyl Sulfoxide