Contaminant mixtures and reproductive health: Developmental toxicity effects in rats after mixed exposure to environmentally relevant endocrine disrupting chemicals, with focus on effects in females

Thepresent study investigatedwhether amixtureof lowdosesoffiveenvironmentally relevant endocrinedisrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, wouldcause adverse developmental toxicity effects in rats. In rat dams, a significant increase in gestation lengthwas seen,while inmale offspring increased nipple retention and increased incidence and severity of geni-talmalformationswere observed. Severemixture effects on gestation length, nipple retention and genitalmalformationswere seen at dose levelswhere the individual pesticides causedno or smaller effectswhengiven alone. Generally, the mixture effect predictions based on dose-additivity were in good agreementwith the observed effects. The results indicate that there is a need for modification of risk assessmentprocedures for pesticides, in order to take account of the mixture effects and cumulative intake, becauseof the potentially serious impact of mixed exposure on development and reproduction in humans.© 2012 Elsevier Inc. All rights reserved.