Criteria for judging the relative toxicity of chemicals from developmental toxicity data: a workshop summary

In summary, participants of this workshop confirmed that many criteria need to be considered when interpreting the results of developmental toxicity studies. All aspects of developmental toxicity are of interest, but their importance to the consideration varies along the continuum from hazard detection to risk estimation. As with many other manifestations of toxicity, potential developmental risk to humans is a function of exposure and developmental toxicity, the latter reflecting the inherent potential of a substance to cause an adverse effect under some defined condition. All of the criteria discussed in this workshop were considered to be of some importance in characterizing the developmental toxicity of a substance, their relative importance being a function of the question under consideration. Proper interpretation of developmental toxicity data, which must include prenatal as well as postnatal observations to be considered complete, should take into account the differential toxicity to the mother and the conceptus, the nature of the developmental toxicity observed, and the consistency of response between species. The proximity of human exposure levels to dose levels that are developmentally toxic in animals is a major determinant of the potential for hazard to humans. Mechanistic and pharmacokinetic knowledge can modulate interpretation of descriptive data and refine the prediction of human hazard. Recognizing that in vitro studies will never completely recapitulate the results of in vivo studies, the committee to update the "Smith list" will move forward taking the discussions of this workshop into account.