Developmental Toxicity Hazard Assessment Without Animals: Pathways and Prospects
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Global efforts are underway to transition toxicological risk assessment away from vertebrate animal models, as exemplified by the announcement from the U.S. EPA administrator announcing their intent to virtually eliminate use or funding of vertebrate animal research within 15 years. The Lautenberg Chemical Safety for the 21st Century Act requires that new approach methodologies (NAMs) be developed and that NAMs should replace animal models only when they are deemed to provide information of equivalent or better scientific quality. This goal is perhaps most aspirational for developmental toxicity hazard assessment given the complex and dynamic nature of human pregnancy and embryofetal development. “Teratogen screens” have been developed and used for prioritization and mechanistic studies for decades. Now, new discoveries and technologies along with the urgency to reduce animal usage have emboldened the belief that replacement of animals for developmental toxicity hazard assessment and dose-response is within sight. NAMs that are based largely on in vitro data and in silico models provide a path forward to animal-free testing of the potential for developmental toxicity. This session will present the latest in NAMs, including cheminformatics and connectivity mapping, utility of transcriptomics for hazard assessment, advances in stem cell models, and data driven in silico models. Establishing scientific confidence in the reliability and relevance of NAMs requires comparisons to our current human and animal knowledge base, and automated tools to enhance literature searching and reference data curation/annotation will be discussed. The unifying theme of the session and the subsequent panel discussion will be to discuss breakthroughs, opportunities and challenges in NAMs for developmental toxicology, and how they can ultimately contribute to an animal-free system for developmental hazard identification and dose-response that is equivalent or better than the existing animal-based regulatory framework.