Antifungal triazoles induce malformations in vitro

Triazole-derivatives are antimycotics used in agriculture as well as in cli nical and veterinary therapy. The aim of the present work is the in vitro c omparative study of the teratogenic activity of triazole (the parental comp ound), flusilazole (an agricultural triazole mono-derivative fungicide), an d fluconazole (a clinically used bis-triazole derivative). Rat embryos, 9.5 days old ( I to 3 somites) were exposed in vitro to triazole 500 to 5000 m uM, flusilazole 3.125 to 250 muM, or fluconazole 62.5 to 500 muM. After 48 h in culture, the embryos were morphologically examined and processed for h istologic and biochemical analysis. Flusilazole and fluconazole showed similar teratogenic effects (abnormaliti es at the branchial apparatus level and cell death at the level of the bran chial mesenchyme) at concentration levels of 6.25 muM and higher for flusil azole and of 125 muM and higher for fluconazole. By contrast, only slight d evelopmental retardation and blood discoloration were observed at the highe st concentrations of triazole, suggesting no teratogenic activity for the t riazole group. (C) 2001 Elsevier Science Inc. All rights reserved.