Use of Alternative Developmental Toxicity Assays to Assess Teratogenicity Potential of Pharmaceuticals

Abstract Teratogenic potential of human drugs is assessed in embryo-fetal development (EFD) studies in two species as per regulatory guidelines. In vitro developmental toxicity assays can be vital in early drug development efforts to distinguish teratogenic potential of drugs, while reducing animal use. Results from two developmental toxicity in vitro assays (rat whole embryo culture assay and mouse embryonic stem cell test), were evaluated for their ability to predict the teratogenic potential of 83 compounds with known EFD outcome in rats. With an integrated model, the sensitivity and specificity for teratogens and/or embryo-lethal drugs in the presence (89% and 54%, respectively) or absence (96% and 52%, respectively) of maternal toxicity were calculated. Based on these results, we propose that a battery of assays be used to screen for potential EFD toxicity and, in combination with reduced in vivo rat EFD studies, be a part of an integrated regulatory risk assessment.