Thresholds of toxicological concern

For most types of toxic effects (e.g., organ-specific, neurological, immunological, non-genotoxic carcinogenicity, reproductive, developmental), it is generally considered that there is a dose or 

The establishment of TTC is based on the analysis of the toxicological and stmctural data of a broad range of different substances. It might be used as a substitute for substance-specific information in situations where there are limited or no information on the toxicity of a given substance to which the human exposure is so low that undertaking toxicity studies is considered not warranted, because of the costs incurred in the use of animals, manpower, and laboratory resources as well as for animal welfare reasons. 

The threshold of toxicological concern (TTC) describes a level of toxicant exposure that represents negligible risk to human health or the environment. In some situations, this is also referred to as a de minimis level. Data-poor chemicals often are classified using TTC as a surrogate for definitive toxicity data [6]. Decision trees are often constructed using the original classifications by Cramer and co-woikers [33], which are as follows  

Over time the TTC principles have been vetted against a number of diverse datasets and differing opinions have been raised about the robusmess of the approach. 

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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]. 

BARLOW, S. M., KOZIANOWSKI, G., WURTZEN, G. and SCHLATTER, J. 2001. Threshold of toxicology concern for chemical substances present in the diet. Food Chem. Toxicol. 39 893-905. 

Finally, the concept of hormesis (Section 4.12), threshold of toxicological concern (Section 4.13), and probabilistic methods for effect assessment (Section 4.14) will be briefly addressed. 

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... 

Veenstra, G. and D. Kroese. 2005. Threshold of toxicological concern. A concept in toxicological risk assessment. Discussion Document, March 2005. RIP 3.3 SEGl-19. 

Thyroid-Releasing Hormone Toxic Substances Control Act Thyroid Stimulating Hormone Treatment Technique Threshold of Toxicological Concern Target-organ Toxicity dose Unscheduled DNA Synthesis Uncertainty Factor United Nations... 

Reactive chemicals are used to manufacture drugs and a proportion of these are geno-toxic. A draft guideline has been issued by the Europe and CHMP that seeks to control patient exposure to most genotoxic contaminants to below a Threshold of Toxicological concern of 1.5 xg/day. This is based on modelling data on known human carcinogens where such concentrations for specific compoimds would not be expected to increase human cancer above 1 per 10 exposed individuals. ... 

Delaney, F.J. (2007) An impact analysis of the application of the threshold of toxicological concern concept to pharmaceuticals. Regulatory Toxicology and Pharmacology, 49, 107-124. 

Kroes, R., Kleiner, J. and Renwick, A.G. (2005) The threshold of toxicological concern concept in risk assessment. Toxicol Sci, 86, 226-230. 

J. M.Z. and Crane, M. (2009) Thresholds of toxicological concern for endocrine active substances in the aquatic environment. Integr Environ Assess Manage, 6, 2-11. 

For example, the Threshold of Toxicological Concern concept has been proposed, which reduces the amount of toxicological data necessary and therefore reduces the number of animals used in the assessment of hazard. This uses a tiered approach and excludes certain kinds of chemicals such as dioxins and organophosphates. It also makes use of structural alerts and chemical classes to select out chemicals, which are likely to be of little toxicological concern (13). 

Other concepts used are ALARA (exposure as low as reasonable) or 7TC (threshold of toxicological concern) for insignificant low exposures. The ALARA principle intends to keep the exposure to substances at the lowest achievable level,... 

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... 

Fig. 5.7 Threshold levels and different structural classes used in the Threshold of Toxicological Concern principle (adapted from Cramer et al. (1978) and Kroes et al.

KROES, R., GALLI, C., MUNRO, I., SCHILTER, B., TRAN, L.-A., WALKER, R. and WURTZEN, G., 2000, Threshold of toxicological concern for chemical snbstances present in the diet a practical tool for assessing the need for toxicity testing. Food and Chemical Toxicity, 38, 255-312. 

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

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