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20190925 - Exploring potential refinements to existing Threshold of Toxicological Concern Values for environmentally-relevant chemicals (ASCCT)
Citation:
Nelms, M., P. Pradeep, AND G. Patlewicz. 20190925 - Exploring potential refinements to existing Threshold of Toxicological Concern Values for environmentally-relevant chemicals (ASCCT). American Society for Cellular and Computational Toxicology (ASCCT) annual meeting, Gaithersburg, MD, September 25 - 26, 2019. https://doi.org/10.23645/epacomptox.11349746
Impact/Purpose:
Abstract and poster for the American Society for Cellular and Computational Toxicology (ASCCT) annual meeting in September 2019. The 8th annual conference theme is 'Computational Toxicology: Peeking into the Clouds while Keeping our Feet on Solid Ground'.
Description:
The US EPA are mandated by the Toxic Substances Control Act (TSCA) to perform risk-based prioritisation of chemicals and, for high-priority substances, integrate toxicity and exposure information to develop risk evaluations. One approach under consideration for chemicals with limited chemical-specific toxicity data is a Threshold of Toxicological Concern (TTC)-to-Exposure ratio. Within the TTC paradigm, a chemical is assigned to a specific class based upon an evaluation of chemical structure. Here, TTC values derived using (sub)chronic NO(A)EL data from EPA’s Toxicity Values database (ToxValDB) were compared with published TTC values from Munro et al (1996). Toxtree was utilised to assign 4554 chemicals with structural information to their respective TTC category: Cramer structural class I, II, III, containing genotoxicity alert, or acetylcholinesterase inhibitor. 114 (2.5%) chemicals were deemed to be not appropriate for TTC. Similar TTC values were derived from ToxValDB compared to the TTC values from Munro: Cramer I (37.3 compared to 30 µg/kg-day), Cramer II (34.6 compared to 9 µg/kg-day), and Cramer III (3.9 compared to 1.5 µg/kg-day). For Cramer classes I and II, the 5th percentile values were not statistically different between the two datasets; whereas, the class III values were different. Chemical features of the two class III datasets were evaluated to account for differences in TTC values. The TTC values derived by Munro et al (1996) were substantiated by the expanded dataset in ToxValDB, reaffirming the utility of TTC as a promising tool in a risk-based prioritisation approach. This abstract does not necessarily reflect EPA policy.
URLs/Downloads:
DOI: 20190925 - Exploring potential refinements to existing Threshold of Toxicological Concern Values for environmentally-relevant chemicals (ASCCT)
NELMS_ASCCT_2019_V2.PDF (PDF, NA pp, 653.973 KB, about PDF)