Teratogenic and reproductive effects of ethanol in Long‐Evans rats

Abstract
The effects of ethanol alone or ethanol and dieldrin given orally were investigated on the reproductive processes of female Long-Evans rats. Three studies were undertaken as follows: effects on reproduction (phase I), perinatal and postnatal effects (phase III) and teratological effects (phase II). Female Long-Evans rats were divided into 5 groups for all studies as follows: 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, 2 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. Microphthalmia and paralysis were the defects noted. Aspirin caused significant teratogenic effects and maternal deaths from gastrointestinal hemorrhage. Dieldrin 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 and soft tissue teratology. Aspirin (500 mg/kg) caused skeletal (cranial bone) defects and soft tissue anomalies in pups; Dieldrin was without untoward effects. Dams given a combination of Dieldrin and 0.4 ml ethanol/kg displayed increased embryolethality but no teratogenic effect was noted. The Long-Evans rat is a sensitive model for the induction of FAS at a dose level equivalent to 1 alcoholic drink/day in human females. The reported embryolethal effect of concommitant exposure to Dieldrin (an organochlorine insecticide) and ethanol deserves further evaluation.