Threshold of toxicological concern TTC

The platform includes different decision trees for the following endpoints the estimation of Threshold of Toxicological Concern (TTC), aquatic modes of action [44], skin and eye irritation and corrosion, mutagenicity and carcinogenicity [45], in vivo micronucleus assay, identification of Michael Acceptors and biodegradation potential [46]. 

Human Exposure Threshold of Toxicological Concern (TTC) Values... 

Barlow, S. 2005. Threshold of Toxicological Concern (TTC). A tool for assessing substances of unknown toxicity present at low levels in the diet. ILSI Europe Concise Monograph Series. Europe, Bmssels, Belgium ILSI. http //europe.ilsi.org/publications/Monographs/ThreshoIdToxicoIogicaIConcem.htm Barnes, D., G. Daston, J. Evans, et al. 1995. Benchmark dose workshop Criteria for use of a benchmark dose to estimate a reference dose. Regul. Toxicol. Pharmacol. 21 296-306. 

Kroes, R., A. Renwick, M. Cheeseman, et al. 2004. Structure-hased thresholds of toxicological concern (TTC) Guidance for application to substances present at low levels in the diet. Food Chem. Toxicol. 42 65-83. 

NCM. 2005. Threshold of toxicological concern TTC). Literature review and applicability. TemaNord 2005, 559, Copenhagen Nordic Council of Ministers http /www.norden.org/pub/miljo/miljo/sk/ TN2005559.pdf... 

Munro, I.C., Renwick, A.G., Danielewska-Nikiel, B. (2008) The threshold of toxicological concern (TTC) in risk assessment. Toxicology Letters 180 151-156. 

A protocol for risk assessment of unlisted migrants should be developed that is pragmatic, cost-effective and accepted by both industry and legislative authorities. In this protocol, exposure, toxicology and chemical analysis should be combined. A possible combination would be the approach described above of relating exposure to the threshold of toxicological concern (TTC) principle. This would determine the analytical boundaries for screening of... 

KROES, R., RENWICK, A.G., CHEESEMAN, M., KLEINER, I., MANGELSDORF, L, PIERSMA, A., SCHILTER, B., SCHLATTER, I., VAN SCHOTHORST, F., VOS, J.G. and WURTZEN, G., 2004, Stmctnre-based thresholds of toxicological concern (TTC) gnidance for application to snbstances present at low levels of diet. Food and Chemical Toxicity, 42, 65-83. 

Barlow S, (2005), Threshold of toxicological concern (TTC) a tool for assessing substances of unknown toxicity present in the diet, ILSI Monograph 2005. 

The Cramer classification scheme can be used to make a threshold of toxicological concern (TTC) estimation. TTC is a concept that aims to establish a level of exposure for all chemicals below which there would be no appreciable risk to human health the threshold is based on a statistical analysis of the toxicological data from a broad range of different and/or structurally related chemicals and on the extrapolation of the underlying animal data to a no-effect dose considered to represent a negligible risk to human health. 

The threshold of toxicological concern (TTC) concept has been developed to provide criteria for risk assessment decision-making in the absence of detailed information on chemicals. The approach involves estimating a tolerable human exposure value for all chemicals below which there is a very low probability of an appreciable risk to human health (Kroes et al. 2004, 2005), based on their chemical structures, compared to an extensive toxicity database. As utilized by U.S. FDA in their Threshold of Regulation procedure, structural alerts for high-potency carcinogenicity are included, to increase the assurance of safety. 

However, in such situations, a more scientifically accurate approach is to use methods such as risk based on surrogates or threshold of toxicological concern (TTC) to estimate the risk for chemicals lacking sufficient data, rather than modifying the approach to risk estimation for individual chemicals to account for otho-chemical exposures [e.g., see reviews by Kroes et al. (2005) and Dolan et al. (2005)]. 

The substances in this group that have been evaluated at this meeting and at the fifty-third and sixty-first meetings are predicted to be metabolized by a variety of metabolic pathways. Because of the diverse structures, there are few common metabolites. Examples are 3-(methylthio)propionic acid (from Nos 476 and 468) and thioacetic acid (from Nos 482, 483, 485 and 491). The combined intakes of substances with a common metabolite were below the relevant threshold of toxicological concern (TTC) value. 

Deichmann WB, Henschler D, Holmsted B et al (1986) What is there that is not poison A study of the Third Defense by Paracelsus. Arch Toxicol 58(4) 207-213. doi 10.1007/BE00297107 Dewhurst I, Renwick AG (2012) Evaluation of the threshold of toxicological concern (TTC)— challenges and approaches. Regul Toxicol Pharmacol 65(1) 168-177. doi 10.1016/j.yrtph. 2012.03.007... 

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