Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation

Critical Reviews in Toxicology
Alan BoobisHeli M Hollnagel

Abstract

The threshold of toxicological concern (TTC) approach is a resource-effective de minimis method for the safety assessment of chemicals, based on distributional analysis of the results of a large number of toxicological studies. It is being increasingly used to screen and prioritize substances with low exposure for which there is little or no toxicological information. The first step in the approach is the identification of substances that may be DNA-reactive mutagens, to which the lowest TTC value is applied. This TTC value was based on the analysis of the cancer potency database and involved a number of assumptions that no longer reflect the state-of-the-science and some of which were not as transparent as they could have been. Hence, review and updating of the database is proposed, using inclusion and exclusion criteria reflecting current knowledge. A strategy for the selection of appropriate substances for TTC determination, based on consideration of weight of evidence for genotoxicity and carcinogenicity is outlined. Identification of substances that are carcinogenic by a DNA-reactive mutagenic mode of action and those that clearly act by a non-genotoxic mode of action will enable the protectiveness to be determined of both...Continue Reading

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Oct 30, 2018·Toxicological Research·Takehiko Nohmi
Mar 13, 2020·Critical Reviews in Toxicology·Nigel J GooderhamSean V Taylor
Sep 25, 2019·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Benoit SchilterAlan Boobis
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Jul 25, 2021·Regulatory Toxicology and Pharmacology : RTP·Abhijit S VichareBrinda Mahadevan

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