In vitro percutaneous penetration and metabolism of [3H]T-2 toxin: comparison of human, rabbit, guinea pig and rat

The purpose of this research was to determine which species of laboratory animal provided the best approximation of in vitro percutaneous penetration and metabolism of T-2 in humans. The [3H]T-2 which penetrated discs of skin after 48 hr (expressed as per cent of dose, 581 ng/cm2) was 1.0, 1.4, 2.8 and 9.7% for the human, rabbit, guinea pig and rat when the vehicle was methanol. The penetration was 29.2, 19.6, 51.9 and 52.6% for the human, rabbit, guinea pig and rat when the vehicle was DMSO. When 2 concentrations were compared, 79 ng/cm2 and 581 ng/cm2 (the vehicle was methanol), the higher dose caused a significant (P less than 0.05) increase in the per cent of dose which penetrated human and guinea pig skin. Metabolism was extensive in the human, rabbit, and rat, with the main metabolite being HT-2 toxin. Previous studies comparing human to monkey indicated penetration in these 2 species was different when methanol was the vehicle. This study indicates that the rabbit provides the best approximation of human skin, both in terms of penetration kinetics and metabolic activity.