Abstract
Alternative developmental toxicity assays are used by pharmaceutical companies to detect the teratogenic potential of human drugs. These methods are intended to reduce, refine, or replace (3Rs) animal use in nonclinical embryo-fetal developmental toxicity testing. Screening methods (e.g., rodent whole embryo culture, embryonic stem cells, and zebrafish) are powerful tools to identify hazards; they also provide unique mechanistic insights that improve our understanding of developmental toxicology. By improving the sophistication of these models over the past two decades, the field of developmental and reproductive toxicology has been preparing to meet the increased need for enhanced developmental toxicity testing in drug discovery and development. Interest in these tools has been further amplified since the International Conference on Harmonisation (ICH) indicated that it will address the use of in vitro, ex vivo, and non-mammalian developmental toxicity assays for regulatory purposes in the upcoming revisions to the ICH S5(R2) guideline. Moreover, alternative assays combined with newer technologies such as high-content imaging, automated embryo handling, and functional genomics may expedite testing of pharmaceuticals for teratogenic liabilities while also increasing the informational content of these screens. To illustrate the potential of alternative developmental toxicity assays, some examples of modern methods as well as modifications to enhance these methods in the future are highlighted.
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References
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Green, M.L., Gamse, J.T., Brannen, K.C. (2016). Alternative Methods Used to Assess Potential Embryo-Fetal Developmental Risk of Pharmaceuticals. In: Faqi, A. (eds) Developmental and Reproductive Toxicology. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/7653_2016_67
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