https://tpx.sagepub.com/content/32/2_suppl/93.full.pdf

Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet

The threshold of toxicological concern (TTC) is a pragmatic risk assessment tool that is based on the principle of establishing a human exposure threshold value for all chemicals, below which there is a very low probability of an appreciable risk to human health. The concept that there are levels of exposure that do not cause adverse effects is inherent in setting acceptable daily intakes (ADIs) for chemicals with known toxicological profiles. The TTC principle extends this concept by proposing that a de minimis value can be identified for many chemicals, in the absence of a full toxicity database, based on their chemical structures and the known toxicity of chemicals which share similar structural characteristics. The establishment and application of widely accepted TTC values would benefit consumers, industry and regulators. By avoiding unnecessary toxicity testing and safety evaluations when human intakes are below such a threshold, application of the TTC approach would focus limited resources of time, cost, animal use and expertise on the testing and evaluation of substances with the greatest potential to pose risks to human health and thereby contribute to a reduction in the use of animals. An Expert Group of the European branch of the International Life Sciences Institute-ILSI Europe-has examined the TTC principle for its wider applicability in food safety evaluation. The Expert Group examined metabolism and accumulation, structural alerts, endocrine disrupting chemicals and specific endpoints, such as neurotoxicity, teratogenicity, developmental toxicity, allergenicity and immunotoxicity, and determined whether such properties or endpoints had to be taken into consideration specifically in a step-wise approach. The Expert Group concluded that the TTC principle can be applied for low concentrations in food of chemicals that lack toxicity data, provided that there is a sound intake estimate. The use of a decision tree to apply the TTC principle is proposed, and this paper describes the step-wise process in detail. Proteins, heavy metals and polyhalogenated-dibenzodioxins and related compounds were excluded from this approach. When assessing a chemical, a review of prior knowledge and context of use should always precede the use of the TTC decision tree. The initial step is the identification and evaluation of possible genotoxic and/or high potency carcinogens. Following this step, non-genotoxic substances are evaluated in a sequence of steps related to the concerns that would be associated with increasing intakes. For organophosphates a TTC of 18microg per person per day (0.3 microg/kg bw/day) is proposed, and when the compound is not an OP, the TTC values for the Cramer structural classes III, II and I, with their respective TTC levels (e.g. 1800, 540 and 90 microg per person per day; or 30, 9 and 1.5 microg/kg bw /day), would be applied sequentially. All other endpoints or properties were shown to have a distribution of no observed effect levels (NOELs) similar to the distribution of NOELs for general toxicity endpoints in Cramer classes I, II and III. The document was discussed with a wider audience during a workshop held in March 2003 (see list of workshop participants).

Structure-Based Thresholds of Toxicological Concern (TTC): Guidance for Application to Substances Present at Low Levels in the Diet

http://fragrancematerialsafetyresource.elsevier.com/sites/default/files/AB-1-Ford-Criteria_0.pdf

Criteria for development of a database for safety evaluation of fragrance ingredients.

This scientific opinion of EFSA deals with the criteria to be used for safety evaluation of a recycling process to produce recycled PET intended to be used for manufacture of materials and articles in contact with food. The principle of the evaluation is to apply the cleaning efficiency of a recycling technology or process, obtained from a challenge test with surrogate contaminants, to a reference contamination level for post consumer PET, conservatively set a 3 mg/kg PET for a contaminant resulting from possible misuse. The resulting residual concentration of each contaminant in recycled PET (Cres) is then compared to a modelled concentration in PET (Cmod). This Cmod is calculated using generally recognized conservative migration models such that the related migration does not give rise to a dietary exposure exceeding 0.0025 μg/kg bw/day, the human exposure threshold value for chemicals with structural alerts raising concern for potential genotoxicity, below which the risk to human health would be negligible. The default scenario, when the recycled PET is intended for general use, is that of an infant weighing 5 kg and consuming every day 0.75 l of water coming from a water bottle manufactured from 100% recycled PET. According to this scenario, it can be derived that the highest concentration of a substance in water that would ensure that the dietary exposure of 0.0025 µg/kg bw/day is not exceeded, is 0.017 μg/kg food. Taking into account that generally agreed diffusion modelling overestimates migration by at least 5 times, a calculated migration less than 0.1 µg/kg in food would satisfy the above criterion for the default exposure scenario. In the case of the other exposure scenarios for adults and toddlers, the relevant migration criterion will accordingly be 0.75 and 0.15 µg/kg food. Therefore if a recycling process is able to reduce an input reference contamination of 3 mg/kg PET to a Cres not higher than a Cmod corresponding to the relevant migration criterion, the potential dietary exposure cannot be higher than 0.0025 µg/kg bw/day and recycled PET manufactured with such recycling process is not considered of safety concern. The Panel considered appropriate that the proportion of PET from non-food consumer applications should be no more than 5% in the input to be recycled.

Scientific Opinion on the criteria to be used for safety evaluation of a mechanical recycling process to produce recycled PET intended to be used for manufacture of materials and articles in contact with food

Evaluation of certain food additives : sixty-fifth report of the Joint FAO/WHO Expert Committee on Food Additives

The theme of the 1987 Annual Meeting of the Society for Risk Analysis (Nov. 1987, Houston, TX), from which these essays were drawn, was Setting National Priorities. The theme reflects a concern with the conventional practice of isolating and individualizing risks, thereby ignoring the holistic asp

James J. Bonin

Papers

Risk Assessment in Setting National Priorities