Stage-dependent abnormalities induced by the fungicide triadimefon in the mouse☆

Aim of this work is the study of abnormalities induced by the triazole triadimefon (FON) administered to pregnant mice at E8, E9, E10, E11 or E12. Pregnant CD-1 mouse were gavaged with FON 500 mg/kg at the selected stages and sacrificed at term and fetuses morphologically examined and processed for visceral and skeletal analysis. Administration of FON on E8, E10-E12 resulted in fetuses with cleft palate (E8 39% and E12 24% representing the peak of sensitivity, in E8 fetuses associated to severe skull basis abnormalities). Other cranial malformations (fusions abnormalities or agenesis of bones) were observed in E8-E10 groups (E8 the most sensitive with 96% of malformed fetuses). Cardiovascular abnormalities were observed in a stage dependent manner at E8-E10 (22.2, 3.8, 7.8%). As far as craniofacial malformation is concerned, we propose that FON acts on two different stages, involved in early and late craniofacial formation.