SKIN ORGAN-CULTURE AS AN ALTERNATIVE TO IN-VIVO DERMATOTOXICITY TESTING

Various aspects of acute cutaneous toxicity were studied in a skin org an culture model. Chemicals were applied topically for four hours, aft er which cytotoxicity was assessed by measuring the conversion of the tetrazolium salt, MTT. The relationship between pKa and cytotoxicity w as investigated for a homologous series of benzoic acids. In this seri es, salicylic acid had the lowest pKa and proved to be the most toxic compound. Furthermore, the pH of the carrier solution was shown to inf luence the toxicity of chloroacetic acid and acetic acid in a differen t way. Using skin discs of both human and rabbit origin, we found that human skin was more resistant to toxicity induced by the irritants be nzalkonium chloride and formaldehyde. As an additional aspect of derma l toxicology, the percutaneous absorption of testosterone was studied. After topical application to rabbit skin discs, testosterone was abso rbed in a dose-dependent manner and concurrent metabolism was demonstr ated.