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.