The effects of flurochloridone exposure during pregnancy on maternal and fetal development

Flurochloridone (FLC) was classified as "May cause harm to the unborn child" by the European Food Safety Authority (EFSA). Because of the potential for occupational exposure to FLC, and the lack of reported maternal and fetal data, we investigated the effects of FLC on sex hormones, toxicokinetics, and maternal well-being, as well as fetal development. Thirty-two pregnant Sprague-Dawley rats were divided into four groups: a vehicle control group and three FLC-treated groups (3, 10, and 30 mg/kg, respectively). FLC was administered to the dams via oral gavage from gestation day (GD) 0 to GD 20. Six dams in each group were used for toxicokinetic evaluations. Cesarean sections were performed on GD 21. Additionally, blood samples were collected for hormone analysis. We found that pregnancy decreased the clearance rate and increased the absorption of FLC in rats. In the 30-mg/kg group, FLC significantly reduced maternal heart weight and decreased testosterone and progesterone levels with no adverse effect on maternal fertility. FLC had no adverse effect on visceral development, but caused a significant increase in incomplete ossification of the fetal sternum in the 30-mg/kg group. In the present study, the no-observed-adverse-effect level (NOAEL) of FLC on embryo-fetal development was estimated to be 10 mg/kg/day.