Comparison of maternal and fetal toxic dose responses in mammals

The role of maternal toxicity in adverse developmental outcome and the importance of maternal toxicity as a factor in developmental risk assessment have received increasing attention in the recent literature. This paper reviews these concepts and some of the experimental approaches that have been used to assess their importance. The often non-parallel nature of maternal and fetal toxic dose response curves makes specific comparisons of maternal and fetal toxic doses quite difficult. The use of specific ratios of maternal to fetal toxic doses, such as the A/D ratio and the Relative Teratogenic Index is discussed, including some of the difficulties encountered in assigning such ratios, and a compilation of A/D ratios for compounds for which this ratio could be estimated in more than one mammalian species is included. Results of our studies on the fungicide, dinocap, for which the A/D ratio does not seem to be consistent across species, are briefly reviewed. Maternal toxicity is usually evaluated only on the basis of significant mortality, dose-related weight loss, or obvious external observations. Some examples of other more specific indications of maternal toxicity that may be involved in teratogenesis are presented.