You are here:
Mining and Modeling ToxCast/Tox21 data for developmental toxicity
Citation:
Knudsen, T. Mining and Modeling ToxCast/Tox21 data for developmental toxicity. Presented at Society of Toxicology annual meeting, Baltimore, MD, March 10 - 14, 2019. https://doi.org/10.23645/epacomptox.7836980
Impact/Purpose:
Session proposal abstract for SOT 2019. This presentation will highlight some of the challenges for science and technology development in determining the applicability domain of high-throughput data from ToxCast/Tox21 in support of developmental hazard identification and characterization.
Description:
Synthetic reconstruction of embryonic development can provide in silico models that can be used to translate in vitro data from new alternative methods into critical phenomena for developmental toxicity. Computational methods are uniquely positioned to capture this connectivity and provide a mechanistic approach to AOP elucidation and toxicological assessment with less reliance on animal testing. In ToxCast, for example, approximately 1 in 6 chemicals of 1065 tested give an exposure-based prediction of teratogenicity in a human stem-cell based assay. Mining these data for broader relationships to in vitro bioactivity profiles, together with modeling specific correlations to molecular pathways and cellular processes that drive human embryology and development, can be used in a defined approach to testing and assessment. This presentation will highlight some of the challenges for science and technology development in determining the applicability domain of high-throughput data from ToxCast/Tox21 in support of developmental hazard identification and characterization. Progress in translating these large datasets into human-predictive models of developmental toxicity will be demonstrated utilizing case studies tying the in vitro data and in silico models to fundamental principles of teratogenesis. This work does not reflect EPA policy.
URLs/Downloads:
DOI: Mining and Modeling ToxCast/Tox21 data for developmental toxicity
KNUDSEN_SOT_2019_DEVTOX_M.PDF (PDF, NA pp, 3647.013 KB, about PDF)