Chapter 18: In Vitro Developmental Models and Their Applications in Teratology Research

Identification and characterization of teratogenic liability is an area of safety assessment best addressed proactively. This is due to the considerable loss in investment in animals, time and funds when unexpected teratogenicity is conventionally identified. Typically these findings surface when embryo fetal development studies are conducted to support Phase II enrollment of women of childbearing potential into clinical trials, which is relatively late in drug development. Applying in vitro models for studying teratogenic mechanism or for screening developmental toxicity of compounds can facilitate proactive identification and characterization of teratogenic liability. Furthermore, use of such approaches aligns well with the 3R Perspective: to replace, reduce and refine the use of animals for research purposes. This chapter describes several relevant developmental models and reviews their application in teratology screening or mechanistic investigations, emphasizing assay refinement and high-throughput strategies for proactive safety assessment of compounds.