Recent assessments of the status of developmental toxicology by the regulatory and scientific communities have identified a need to apply structure-activity relationships to existing test strategies. In past efforts, the principal investigator has developed a statistical structure-activity (SAR) model of teratogenicity based on the literature on frank malformations in mammals. This model is being used to estimate the probability of malformations for chemicals which have not been tested. The purpose of the proposed research is to improve on the prior work by assembling a more coherent and detailed data base of developmental effects and developing SAR models of related sets of chemicals, chemicals with common pharmacologic activity, and common biochemical activity. The data base and the SAR models derived from it would materially enhance the armamentarium of industrial toxicologists, hygienists and regulators in pinpointing exposures of concern. The estimates of developmental toxicity potential could also lead to more focused developmental effects testing of potentially harmful chemicals. The proposed research could also lead to a reduction in the number of animals used in reproductive effects testing. A few SAR models will be developed under the Phase I grant, the data base assemply will be limited to about 500 chemicals.
