Threshold of toxicological concern (TTC) in food safety assessment.

The threshold of toxicological concern (TTC) is a principle which refers to the possibility of establishing a human exposure threshold value for all chemicals, below which there is no appreciable risk to human health. The concept that exposure thresholds can be identified for individual chemicals in the diet is already widely embodied in practice of many regulatory bodies in setting acceptable daily intakes (ADIs) for chemicals whose toxicological profile is known. However, the TTC concept goes further than this in proposing that a de minimis value can be identified for many chemicals, including those of unknown toxicity, taking the chemical structure into consideration. This concept forms the scientific basis of the US Food and Drug Administration (FDA) '1995 Threshold of Regulation' for indirect food additives. The TTC principle has also been adopted by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in its evaluations of flavouring substances. The establishment of a more widely accepted TTC would benefit consumers, industry and regulators. In precluding extensive toxicity testing and safety evaluations when human intakes are below such a threshold, TTC would focus limited resources of time, cost, animal use and expertise on the testing and evaluation of substances with greater potential to pose risks to human health and contribute to a reduction in the use of animals. An International Life Sciences Institute (ILSI)-Europe expert group has examined this TTC principle, which was based on general toxicity endpoints (including carcinogenicity), for its applicability in food safety evaluation. In addition, the group examined specific endpoints, such as neurotoxicity, immunotoxicity and developmental toxicity. The results of the expert group's considerations including the development of a guideline to apply the principle are discussed.