Threshold of Toxicological Concern concept

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. 

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). 

Dolan, D., Naumann, B., Sargent, E., Maier, A., and Dourson, M. (2005). Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations. Regul Toxicol Pharmacol 43, 1-9. 

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. 

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. 

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,... 

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. 

Toxicological databases and the concept of thresholds of toxicological concern as used by the JECFA for the safety evaluation of flavouring agents - A. G. Renwick - Toxicology Letters 149(1-... 

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. 

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