Teratogenic and reproductive effects of ethanol in Long‐Evans rats

Abstract

The effects of ethanol alone or ethanol and dieidrin given orally were investigated on the reproductive processes of female Long‐Evans rats. Three studies were undertaken: effects on reproduction (phase I), perinatal and postnatal effects (phase III), and teratological effects (phase II). Female Long‐Evans rats were divided into five groups for all studies: group I‐distilled water; group II—corn oil; group III—4 mg Dieldrin/kg; group IV‐500 mg aspirin/kg; and group V‐0.4 ml ethanol/kg. For phase II, two additional groups were added to the experimental design: group VI‐4.0 ml ethanol/kg and group VII—4 mg Dieldrin/kg and 0.4 ml ethanol/kg. In the phase I study, ethanol produced a significant increase in the number of malformed pups at birth: micro‐phthalmia and paralysis were the defects noted. Aspirin caused significant teratogenic effects as well as maternal deaths from gastrointestinal hemorrhage. Dieidrin alone caused no adverse effects. In the phase III study, except for maternal toxicity among aspirin‐dosed dams, no adverse findings were elicited. In the phase II study, 0.4 ml ethanol/kg induced a significant increase in the frequency of soft tissue malformations such as microphthalmia and hydronephrosis. A 10‐fold increase in the ethanol dosage (4.0 ml/kg), caused embryolethality as well as soft tissue teratology. Aspirin (500 mg/kg) caused skeletal (cranial bone) defects and soft tissue anomalies in pups; Dieidrin was without untoward effects. Dams given a combination of Dieidrin and 0.4 ml ethanol/kg displayed increased embryolethality but no teratogenic effect was noted. These results suggest that the Long‐Evans rat is a sensitive model for the induction of FAS at a dose level equivalent to one alcoholic drink per day in human females. The reported embryolethal effect of concommitant exposure to Dieidrin (an organochlorine pesticide) and ethanol deserves further evaluation.