Behavioral teratogenic effect of methylmercury and d‐amphetamine: Meta‐analysis and power analysis of data from the collaborative behavioral teratology study of national center for toxicological research

Abstract

The data of the Collaborative Behavioral Teratology Study (CBTS) were analyzed. Population-effect sizes were estimated, in terms of confidence intervals, by meta-analysis. A treatment effect of methylmercury was clearly observed and a dose-response effect was also observed. On the other hand, no clear treatment effect was observed in the d-amphetamine study. The effect of auditory startle habituation was very large, although it was limited to the high-dose group in the methylmercury study. The effects observed for physical landmarks were, as a whole, somewhat larger than those for behavioral measures. There is no clear evidence for sex-related differences except for activity measures. A curious treatment effect that was not referred to in the CBTS report was observed: eye-opening day and incisor-eruption day were hastened by the treatment of methylmercury. Power analysis results showed that obtaining a statistically significant effect for these compounds is very difficult, suggesting that even though published papers reported the significant effect of these compounds there might have been many unpublished experiments that obtained nonsignificant effects. If one uses these compounds as positive controls, a very large sample size will be needed. No highly sensitive test that is reproducible across compounds or dose-levels was observed among tests employed in the CBTS.