Challenges and opportunities for risk assessment and decision-making when using new approach methods for developmental neurotoxicity
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The rapidly expanding battery of developmental neurotoxicity (DNT) new approach methods (NAM) offers both an exciting opportunity and a challenge for risk assessors and regulatory decision makers. In vivo mammalian toxicology studies have historically provided the basis for hazard conclusions in health assessments. Concerted efforts to develop a battery of DNT NAMs has focused on evaluating key neurodevelopmental processes, including cell proliferation, differentiation, synaptogenesis, and signaling to better understand target chemical effects on neurodevelopment. Compared to the current in vivo approaches, such in vitro methodology may significantly reduce the ethical and practical limitations in terms of animal use, testing throughput, and costs. However, in using a battery of tests there can sometimes be heterogeneity in results when testing across a range of cell lines, alternative models, and endpoints. The interpretation of this heterogeneity is an important consideration in making “hit” calls and determining what levels of change are biologically meaningful. This session will explore tradeoffs that occur with respect to time, cost, and uncertainties and how characterizing model variability is critical for interpretation of DNT assays. Attendees will learn how NAMs approaches are currently utilized in different sectors to support decision making, and what steps are needed to further improve the methodology, possibly adapt regulatory systems and build confidence in the broader application of NAMs from screening to supporting decision-making processes.