T. Tachibana et al., ESTIMATED MAGNITUDE OF BEHAVIORAL-EFFECTS OF PHENYTOIN IN RATS AND ITS REPRODUCIBILITY - A COLLABORATIVE BEHAVIORAL TERATOLOGY STUDY IN JAPAN, Physiology & behavior, 60(3), 1996, pp. 941-952
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.