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Evaluating Potential Refinements to Existing Threshold of Toxicological Concern Values for Environmentally-Relevant Chemicals
Citation:
Nelms, M., P. Pradeep, AND G. Patlewicz. Evaluating Potential Refinements to Existing Threshold of Toxicological Concern Values for Environmentally-Relevant Chemicals. Presented at Society of Toxicology annual meeting, Baltimore, MD, March 10 - 14, 2019. https://doi.org/10.23645/epacomptox.7874660
Impact/Purpose:
For chemicals where neither in vivo and in vitro studies are available, one approach being considered is a Threshold of Toxicological Concern (TTC)-to-Exposure ratio. The TTC approach has established different levels of human exposure below which there is expected to be a low probability of risk to human health. We profiled 12,116 unique discrete chemicals present in the ToxVal database into their respective TTC categories using the Kroes (2004) TTC module within the Toxtree tool. Abstract for presentation at Society of Toxicology annual meeting in March 2019.
Description:
The Toxic Substances Control Act mandates the US EPA to perform risk-based prioritization of chemicals in commerce and then, for high-priority substances, develop risk evaluations that integrate toxicity data with exposure information. For chemicals where neither in vivo and in vitro studies are available, one approach being considered is a Threshold of Toxicological Concern (TTC)-to-Exposure ratio. The TTC approach has established different levels of human exposure below which there is expected to be a low probability of risk to human health. Within the TTC paradigm, a chemical is assigned to a specific class based upon an evaluation of the chemical structure. In this study, we derived TTC values based on oral (sub)chronic No Observable (Adverse) Effect Level (NO(A)EL) data from the US EPA’s Toxicity Values (ToxVal) database and compared them with published TTC values. We profiled 12,116 unique discrete chemicals present in the ToxVal database into their respective TTC categories using the Kroes et al (2004) TTC module within the Toxtree tool. Of these chemicals, 1800 (14.9%) were not considered appropriate for TTC based on exclusion criteria and were removed. The remaining chemicals were assigned to one of the five TTC classes (Cramer structural class I, II, III, containing alerts for genotoxicity and acetylcholinesterase inhibitors [AChEI]). We calculated TTC values for chemicals in Cramer I and III categories as 0.0134 mg/kg bw/day and 0.00199 mg/kg bw/day, respectively. Due to a lack of data we were unable to calculate a TTC value for Cramer Class II chemicals. The TTC value for the Class I chemicals calculated in this study is more conservative than that of Munro et al (1996) who identified a TTC value of 0.03 mg/kg bw/day for Class I chemicals. This increased conservatism was also observed when comparing the 50th percentile NO(A)EL values between our study (0.659 mg/kg bw/day) with that of Munro et al (1996) (1.16 mg/kg bw/day). The Class III chemicals in both datasets had the same 50th percentile NO(A)EL value (0.09 mg/kg bw/day). The difference in TTC values from those calculated by Munro et al (1996) could be attributed to a difference in dataset composition as Munro et al (1996) contained a number of food additives in comparison to the ToxVal dataset, which typically comprised food-use pesticide active ingredients. This abstract does not necessarily reflect US EPA policy.
URLs/Downloads:
DOI: Evaluating Potential Refinements to Existing Threshold of Toxicological Concern Values for Environmentally-Relevant Chemicals
NELMS_SOT_2019_FINAL_04032019.PDF (PDF, NA pp, 763.625 KB, about PDF)