Teratologic Evaluation of Diethylene Glycol Dimethyl Ether (CAS No. 111-96-6) Administered to New Zealand White Rabbits on Gestational Days 6 through 19

摘要

Diethylene glycol dimethyl ether (DYME), a widely used organic solvent, is structurally related to several compounds which produce reproductive and developmental toxicity, including teratogenicity in laboratory animals. In the present study, DYME (0, 25, 50, 100 or 175 mg/kg/day) was administered by gavage in distilled water to timed-pregnant New Zealand White (NZW) rabbits (15-22 dams/group) during major organogenesis (gestational days (gd) 6-19) based on preliminary range-finding studies. In conclusion, exposure of NZW rabbits to diethylene glycol dimethyl ether at 25 mg/kg/day during major organogenesis produced no adverse maternal or developmental effects. Doses of 50 and 100 mg/kg/day were associated with adverse developmental effects, but did not produce distinctive evidence of maternal toxicity. The incidence of adverse developmental effects was further increased at a dose associated with increased maternal mortality (e.g., 175 mg/kg/day). The principal manifestations of developmental toxicity were increased resorptions and a higher incidence of major malformations among surviving fetuses.