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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

Adverse Outcome Pathway for Embryonic Vascular Development

Work to identify alternative methods for developmental toxicity testing has focused on understanding and predicting disruption of key mechanisms in embryonic and fetal development. AOPs provide a useful framework for integrating the evidence derived from in silico and in vitro systems to inform chemical hazard characterization. An ongoing collaboration between NICEATM and EPA has built and applied an AOP for developmental toxicity through a mode of action linked to embryonic vascular disruption. A 2019 publication (Saili et al. 2019) reviewed the model for quantitative prediction of developmental vascular toxicity from ToxCast HTS data and compared the HTS results to functional vascular development assays in complex cell systems, virtual tissues, and small model organisms. Results increased confidence in the capacity to predict adverse developmental outcomes from HTS in vitro data and model computational dynamics for in silico reconstruction of developmental systems biology.