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Applying a Tiered Risk-based Approach to Prioritizing Thousands of Chemicals for Further Evaluation: A Comparison of Current High Throughput Computational Approaches
Citation:
Nicolas, C., K. Mansouri, P. McMullen, M. Minto, R. Clewell, M. Yoon, M. Phillips, G. Patlewicz, J. Wambaugh, AND H. Clewell III. Applying a Tiered Risk-based Approach to Prioritizing Thousands of Chemicals for Further Evaluation: A Comparison of Current High Throughput Computational Approaches . Presented at SETAC High Throuthput Screening and Environmental Risk Assessment, Durham, NC, April 16 - 18, 2018. https://doi.org/10.23645/epacomptox.6946037
Impact/Purpose:
Here we present a case study on applying a risk-based approach to chemical prioritization based on an initial triage by ranking the ratios between ExpoCast high-throughput exposure estimates and Thresholds of Toxicological Concern (TTCs).
Description:
There is a need to prioritize thousands of environmental chemicals for further testing with the help of current computational technologies. Here we present a case study on applying a risk-based approach to chemical prioritization based on an initial triage by ranking the ratios between ExpoCast high-throughput exposure estimates and Thresholds of Toxicological Concern (TTCs). In order to first demonstrate the utility of TTCs for triage of environmentally relevant compounds, the following process was applied to 358 ToxCast compounds: 1) oral equivalent doses (OEDs) were calculated based on ToxCast bioactivity measurements and available metabolism data for estimating in vivo clearance, 2) TTC values were determined using the Cramer classification system, 3) OEDs and TTCs were then compared with available ExpoCast exposure estimates to determine their respective activity:exposure ratios. TTCs were lower than OEDs for 349 (97%) of ToxCast compounds, implying that TTCs can serve as a conservative estimate of hazard in the absence of chemical-specific data. A similar triage process was applied to a set of 45,000 chemicals whereby ratios between their ExpoCast exposure estimates and TTC values were evaluated. In order to ground-truth the results, we curated an ensemble of compounds with established points of departure (e.g., no observed adverse effect levels (NOAELs)). TTC values were lower than NOAELs for all 128 compounds that overlap with the chemical database and have published NOAEL values based on a daily oral exposure. This study demonstrated the utility of exploiting existing computational approaches as part of a tiered risk-based approach to prioritize thousands of chemicals for further analysis. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: Applying a Tiered Risk-based Approach to Prioritizing Thousands of Chemicals for Further Evaluation: A Comparison of Current High Throughput Computational Approaches
NICOLAS_EXPOSUREPRIORITIZATION_SOT2018_POSTER_CLEARED.PDF (PDF, NA pp, 2396.289 KB, about PDF)