DEVELOPMENTAL EFFECTS OF COMBINED EXPOSURE TO ETHANOL AND VITAMIN-A

The potential for ethanol (EtOH) to influence the developmental toxici ty of vitamin A was investigated. 11 groups of approximately 31 FDA-br ed Osborne-Mendel rats received either a control or isocaloric 6.4% Et OH liquid diet (containing 4000 IU vitamin A/litre) ad lib. The vehicl e control, EtOH and pair-fed (pair-fed against the EtOH group) groups received corn oil (the vehicle) by gavage. Vitamin A was administered by gavage without EtOH at 40,000, 80,000, 120,000 or 160,000 IU/kg dai ly. Vitamin A was administered by gavage at 10,000, 20,000, 40,000 or 80,000IU/kg with EtOH ad lib., daily throughout the study. Combined Et OH and vitamin A resulted in significant reductions in maternal diet c onsumption and body weight when doses of vitamin A were as low as 10,0 00 IU/kg. The most severe effects on overall (days 0-20) maternal body weight gain were observed in the groups receiving 120,000 or 160,000 IU vitamin A/kg alone or EtOH in combination with 80,000 IU vitamin A/ kg. The overall diet consumption (days 0-20) paralleled the overall we ight gain. In general, pups exposed to ethanol and vitamin A had a ten dency to weigh less than those exposed to vitamin A alone, but to weig h more than those exposed to EtOH alone. EtOH combined with vitamin A at 80,000 IU/kg resulted in an increased incidence of cleft palate rel ative to the vehicle control or either treatment alone. The incidence of exencephaly and protruding tongue was significantly greater in the group given vitamin A at 160,000 IU/kg, compared with the vehicle cont rol group. The most consistent statistically significant skeletal find ing in the groups receiving combined treatment was a treatment-related increased incidence of supernumerary ribs [14th rib (C7), 14th rib bu d (L1) and 15 ribs]. In addition, the incidence of misshapen zygomatic arch was also significantly increased in the group exposed to EtOH an d vitamin A at 80,000 IU/kg. The incidence of moderately enlarged rena l pelvis and severely enlarged ureter proximal to the kidney was incre ased in the group exposed to EtOH and vitamin A at 80,000 IU/kg relati ve to the vehicle control, or either treatment alone. Therefore, for s ome of the endpoints examined in this investigation, it would appear t hat ethanol potentiates the developmental effects of vitamin A.