Threshold of Toxicological Concern (TTC)

ILSI Europe Concise Monograph

Humans are exposed to thousands of chemicals whether naturally occurring or man-made. The human diet, for example, contains innumerable low molecular weight, organic compounds that could, at some level of intake, represent a risk to human health. Extensive toxicity studies, utilising many animals, are necessary to evaluate the safety of chemicals applied in food or to establish if contaminants to which humans are exposed may cause harm.

The Threshold of Toxicological Concern (TTC) as described in this Monograph is a principle that refers to the establishment of a generic human exposure threshold value for (groups of) chemicals below which there would be no appreciable risk to human health. The concept proposes that such a value can be identified for many chemicals, including those of unknown toxicity when considering their chemical structures. Evidently the establishment of a more widely accepted TTC would benefit consumers, industry and regulators. For example, there is an ongoing concern that humans are exposed to a diverse array of chemicals and there is a demand to evaluate large numbers of chemicals. At the same time there exists a strong pressure to reduce our reliance on animal experimentation and to rely increasingly on in vitro and in silico data. Use of the TTC principle would eliminate the necessity of extensive toxicity testing and safety evaluations when human intakes of a chemical are below a certain level of concern, would focus limited resources of time, funding, animal use and expertise on the testing and evaluation of substances with greater potential to pose risks to human health and would considerably contribute to a reduction in the use of animals.

In addition, the principle may be applied to the assessment of chemicals in sectors of health risk assessment other than food and could moreover be further developed for environmental risk assessment. For example, application of the TTC principle could also be extended to other categories of chemical use such as cosmetics and consumer products. In this case, of course, appropriate methodologies should be developed to allow for route to route extrapolation and to assess combined multi-route exposure. In addition, the TTC principle can be used to indicate analytical data needs (as, for example, it is used in the USA for indirect food additives), or for setting priorities among chemicals for levels of “inherent concern”.

In addition, since the principle is based on safety evaluations relating to daily intake throughout life, the approach may further be used in the assessment of impurities present in compounds, for contaminants at large, and as a science-based approach to indicate potentially acceptable concentrations of chemicals present in nature, which could be utilised in the application of the precautionary principle. An International Life Sciences Institute (ILSI) – Europe expert group has examined this TTC principle for its applicability to food safety evaluation.

This monograph describes the history and development of the principle and its application to chemicals in food that humans are exposed to at low levels.

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