Application of the threshold of toxicological concern (TTC) in the evaluation of drinking water contact chemicals

AbstractThe Threshold of Toxicological Concern (TTC) is an approach for assessing the safety of chemicals with low levels of exposure for which limited toxicology data are available. The original TTC criteria were derived for oral exposures from a distributional analysis of a dataset of 613 chemicals that identified 5th percentile no observed effect level (NOEL) values grouped within three tiers of compounds having specific structural functional groups and/or toxic potencies known as Cramer I, II and III classifications. Subsequent assessments of the TTC approach have established current thresholds to be scientifically robust. While the TTC has gained acknowledgment and acceptance by many regulatory agencies and organizations, use of the TTC approach in evaluating drinking water chemicals has been limited. To apply the TTC concept to drinking water chemicals, an exposure-based approach that incorporates the current weight of evidence for the target chemical is presented. Such an approach provides a comparative point of departure to the 5th percentile TTC NOEL using existing data, while conserving the allocation of toxicological resources for quantitative risk assessment to chemicals with greater exposure or toxicity. This approach will be considered for incorporation into NSF/ANSI/CAN 600, a health effects standard used in the safety evaluation of chemicals present in drinking water from drinking water contact additives and materials certified to NSF/ANSI/CAN 60 and 61, respectively.Keywords: Threshold of toxicological concern (TTC)drinking waterrisk assessmentqualitativeuncertainty factorscomparative point of departure (cPOD)NSF/ANSI/CAN 600 AcknowledgmentsThe views expressed in this article are those of the authors and do not necessarily represent the views or policies of the MI Department of Environment, Great Lakes, and Energy.The authors would like to thank the members of the NSF Health Advisory Board and the Joint Peer Review Steering Committee for their peer review and guidance during the development of this TTC process.Disclosure statementThe authors declare that they have no competing interests.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.