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Use of Threshold of Toxicological Concern (TTC) with High Throughput Exposure Predictions as a Risk-Based Screening Approach of Several Thousand Commodity Chemicals (SOT Poster)
Citation:
Becker, R., J. Wambaugh, G. Tier, S. Felter, AND T. Simon. Use of Threshold of Toxicological Concern (TTC) with High Throughput Exposure Predictions as a Risk-Based Screening Approach of Several Thousand Commodity Chemicals (SOT Poster). Presented at SOT, New Orleans, LA, March 13 - 17, 2016. https://doi.org/10.23645/epacomptox.5155954
Impact/Purpose:
Poster presentation at the 2016 SOT annual meeting on Use of the TTC approach to prioritize commodity chemicals
Description:
Although progress has been made with HTS (high throughput screening) in profiling biological activity (e.g., EPA’s ToxCast™), challenges arise interpreting HTS results in the context of adversity & converting HTS assay concentrations to equivalent human doses for the broad domain of commodity chemicals. Here, we propose using TTC as a risk screening method to evaluate exposure ranges derived from NHANES for 7968 chemicals. Because the well-established TTC approach uses hazard values derived from in vivo toxicity data, relevance to adverse effects is robust. We compared the conservative TTC (non-cancer) value of 90 μg/day (1.5 μg/kg/day) (Kroes et al., Fd Chem Toxicol, 2004) to quantitative exposure predictions of the upper 95% credible interval (UCI) of median daily exposures for 7968 chemicals in 10 different demographic groups (Wambaugh et al., Environ Sci Technol. 48:12760-7, 2014). Results indicate: (1) none of the median values of credible interval of exposure for any chemical in any demographic group was above the TTC; & (2) fewer than 5% of chemicals had an UCI that exceeded the TTC for any group. However, these median exposure predictions do not cover highly exposed (e.g., occupational) populations. Additionally, we propose an expanded risk-based screening workflow that comprises a TTC decision tree that includes screening compounds for structural alerts for DNA reactivity, OPs & carbamates as well as a comparison with bioactivity-based margins of exposure (Wetmore et al., Toxicol. Sci., 2015). This TTC risk-based screening approach may be useful in a modernized TSCA as the first step in risk-based prioritization. Subsequent steps for substances not deprioritized by this TTC method could include analysis using HTS bioactivity/mechanistic screening, read-across as part of integrated testing or exposure refinement. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: Use of Threshold of Toxicological Concern (TTC) with High Throughput Exposure Predictions as a Risk-Based Screening Approach of Several Thousand Commodity Chemicals (SOT Poster)
TTC EXPOSURE POSTER 7 MARCH 2016 FINAL.PDF (PDF, NA pp, 565.226 KB, about PDF)
SOT ABSTRACT TTC AND HTEXPOSURE 6 OCT 2015_CLEAN.PDF (PDF, NA pp, 100.126 KB, about PDF)