Approaches to defining the relationship of maternal and developmental toxicity.

Maternal and developmental toxicities reported in the literature were examined in an attempt to define more clearly their relationship. Relationships were difficult to ascertain because maternal toxicity end points are not clearly defined, or even assessed, in every study. However, maternal toxicity accompanied by developmental toxicity is the most common outcome of in vivo testing. Approaches to define these associations have included assessment of acute maternal toxicity and teratogenicity; evaluation of maternal toxicity and its association to developmental toxicity in general, and to malformations, specifically; and examination of developmental variations, embryolethality, and altered growth. None has demonstrated an unequivocal relationship between specific maternal and developmental toxicities: Developmental disruption appears not to result unconditionally from maternal toxicity. Maternal "stress" appears to have some impact on development but resists further definition at this time. Variations in association may be due to the extent to which maternal homeostasis has been compromised. Several quantitative approaches to relating maternal toxicity and developmental toxicity in animal systems (ie, relative teratogenic index, adult/developmental toxicity ratio) may provide the most satisfactory means of evaluating developmental toxicity testing for assessment of hazard.