THE ROAD TO EMBRYOLOGICALLY BASED DOSE-RESPONSE MODELS

The goal of researchers working in the area of developmental toxicolog y is to prevent adverse reproductive outcomes (early pregnancy loss, b irth defects, reduced birth weight, and altered functional development ) in humans due to exposures to environmental contaminants, therapeuti c drugs, and other factors. To best achieve that goal, it is important that relevant information be gathered and assimilated in the risk ass essment process. One of the major challenges of improved risk assessme nt is to better use all pertinent biological and mechanistic informati on. This may be done qualitatively (e.g., demonstrating that the exper imental model is not appropriate for extrapolation purposes); semiquan titatively (using information to reduce the degree of uncertainty pres ent under default extrapolation procedures), or quantitatively (formal ly describing the relationships between exposure and adverse outcome i n mathematical forms, including components that directly reflect indiv idual steps in the overall progression of toxicity). In this paper we review the recent advances in the risk assessment process for developm ental toxicants and hypothesize on future directions that may revoluti onize our thinking in this area. The road to these changes sometimes a ppears to be a well-mapped course on a relatively smooth surface; at o ther times the path is bumpy and obscure, while at still other times i t is only a wish in the eye of the engineer to cross an uncharted and rugged environment.