Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides

The present study investigated whether a mixture of low doses of five environmentally relevant endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse developmental toxicity effects in rats. In rat dams, a significant increase in gestation length was seen, while in male offspring increased nipple retention and increased incidence and severity of genital malformations were observed. Severe mixture effects on gestation length, nipple retention and genital malformations were seen at dose levels where the individual pesticides caused no or smaller effects when given alone. Generally, the mixture effect predictions based on dose-additivity were in good agreement with the observed effects. The results indicate that there is a need for modification of risk assessment procedures for pesticides, in order to take account of the mixture effects and cumulative intake, because of the potentially serious impact of mixed exposure on development and reproduction in humans.

► Developmental exposure to a mixture of endocrine disrupting pesticides. ► Adverse effects on gestation length in dams. ► Increased number of nipples and incidence of genital malformations in male rat. ► Mix effect predictions based on dose-additivity in agreement with observed effects. ► In vitro data (AR reporter gene, H295R) gave good indications of the in vivo effects.