ESTIMATED MAGNITUDE OF BEHAVIORAL-EFFECTS OF PHENYTOIN IN RATS AND ITS REPRODUCIBILITY - A COLLABORATIVE BEHAVIORAL TERATOLOGY STUDY IN JAPAN

A collaborative study was conducted by 30 laboratories that participat ed in the Behavioral Teratology Meeting in Japan. Pregnant Sprague-Daw ley rats from four breeders were orally administrated 200 mg/kg of phe nytoin each day from day 10 to day 14 of gestation. The offspring were tested for behavioral teratogenic effects at various ages. The effect s were estimated in terms of common effect size, which should be very resistant to the variation inevitable in behavioral teratology results , and thus yield a different type of information from that reported in the usual behavioral teratology studies. The common effect size also gives information on the magnitude of the behavioral teratogenic effec ts that previous studies could not provide. A breeder difference in th e effect of phenytoin for several measures was found in terms of commo n effect size. The estimated phenytoin effect was found to be large en ough to be detected by using a sample size of 20 per group. As to repr oducibility of results, estimation by standard deviation across labora tories disclosed that there was almost no difference in magnitude betw een behavioral and nonbehavioral measures, indicating that much of the variation in behavioral teratology results of phenytoin might not be due to measurement error from behavioral tests but rather to the pheny toin effect itself administered via the mother. How seriously a single study is affected by uncontrollable variation of results was illustra ted by plotting the respective laboratory results on a dimension. A st andard practice in the interpretation of discrepancies among results o btained from single studies is criticized; it is pointed out that such interpretations rely on an optimistic assumption: that is, that resul ts obtained from single studies would be free from the usual variation of results found in behavioral teratogenic research.