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Offspring of mothers who consumed either 32, 19, 8, or 0% of their daily caloric intake in the form of ethanol during pregnancy were tested for passive avoidance. At 18 days of age, the number of trials to criterion and the within-group variability were direct functions of the amount of ethanol consumed by the mother during pregnancy. At 41--53 days of age, alcohol-treated pups still required more trials to criterion than controls and had faster speeds into the shock compartment on the first trial. When the progeny of mothers consuming either 35, 17, or 0% ethanol-derived calories during pregnancy were compared for conditioned taste aversion to a lithium chloride solution, a linear dose-response function was again evident. Animals in the alcohol-treated groups showed less suppression of drinking than controls. These investigations indicated that the effects of alcohol exposure in utero were manifested in behavioral outcomes involving response inhibition that were not correlated with the more familiar physical symptoms.

Behavioral/functionaI testing is a required segment of reproductive/developmental toxicity safety evaluations of pharmaceuticals to be marketed in the United Kingdom and Japan. Should the current momentum for mandating behavioral teratology testing continue, these evaluations may become required components of reproductive/developmental toxicity safety evaluations submitted to regulatory agencies of the United States. The selection of appropriate behavioral tests and the practical application of these tests in existing safety evaluations present an array of problems. Although there is a vast number of different types of behavioral tests, the specific methodologies of many of the tests are incompatible with standard endpoints of existing reproductive/developmental toxicity protocols. There are multiple inherent methodological and practical problems associated with the incorporation of behavioral tests into currently existing safety evaluations designed for regulatory review. These problems include relative time and cost effectiveness, interlaboratory and intralaboratory variability, test validity, and the interpretation of data.