Di(2-ethylhexyl) adipate (DEHA) induced developmental toxicity but not antiandrogenic effects in pre- and postnatally exposed Wistar rats

Di(2-ethylhexyl) adipate (DEHA) has replaced the phthalates in thin plasticized polyvinyl chloride films used for food packaging, mainly because some phthalates induce testis toxicity and antiandrogenic effects. A dose-range finding study followed by a dose–response/effect study in Wistar rats investigated whether pre- and postnatal DEHA doses of 0, 800, or 1200 mg/kg/day body weight and doses of 0, 200, 400, or 800 mg/kg/day (main study) elicited developmental toxicity including antiandrogenic effects. In the main study, DEHA induced a prolonged gestation period (800 mg/kg/day) and a dose-related increase in postnatal death (400 and 800 mg/kg/day). DEHA also induced a permanent decrease in offspring body weight (800 mg/kg/day). No antiandrogenic endpoints were affected. We conclude that DEHA induced developmental toxicity and the NOAEL is 200 mg/kg. DEHA did not induce antiandrogenic effects similar to those of di(2-ethylhexyl) phthalate even though the chemical structures have similarities and the two chemicals have a common metabolite.