Increasing numbers of substances present at low and very low concentrations in food and feed are now detectable due to improved analytical methods. However, for many such substances there are little or no toxicological data available. There is an increased need to assess the potential health significance of these previously undetectable trace substances but it is not always possible to generate toxicological data on every single substance found in the diet.
The Threshold of Toxicological Concern (TTC) approach has been developed to qualitatively assess the risk of low-level substances in the diet. It can be used for an initial assessment of a substance to determine whether a comprehensive risk assessment is required. It is an important science-based approach for prioritising assessment of those chemicals with low-level exposures that require more data over those that can be presumed to present no appreciable human health risk.
June 2019 – EFSA published new guidance on use of threshold of toxicological concern (TTC) approach in food safety assessment. The document takes into account the latest scientific developments in the field and was finalised following a public consultation with EFSA’s stakeholders. It is intended to help guide EFSA’s scientists in the use of the TTC approach as a screening and prioritisation tool for the safety assessment of chemicals, when hazard (toxicological) data are incomplete and human exposure can be estimated as low. Importantly, the TTC approach is not applicable where substance-specific data exist or where they are required under EU legislation.
1. How does it work?
2. What are the current and proposed uses of TTC at EFSA?
3. Could the TTC approach become a short-cut to the approval of pesticides, food additives and other regulated substances?
4. Does TTC have widespread scientific support?
5. Is EFSA the only organisation using the TTC approach?
6. There are some that argue that the TTC approach is not effective when assessing endocrine-active substances, including those that could have so-called low-dose effects. What is EFSA’s view on this?
EFSA’s Scientific Committee has carefully considered the applicability of the TTC approach to endocrine-active substances, including those that could have “low-dose effects”. It concluded that:
- If there are data showing that an endocrine-active substance has adverse effects, then the TTC approach should not be applied and a full risk assessment should be carried out based on these data.
- If there are data showing that a substance has endocrine activity but the relevance to human health is unclear, then a decision should be made by risk assessors on a case-by-case basis whether or not to apply the TTC approach.
- There is currently extensive work going on at an EU-level about how scientists should define and assess endocrine-active substances; once finalised, the impact of this work will need to be considered in relation to the use of the TTC approach.
7. Is the TTC approach adequately protective of infants and children?
EFSA has found that the TTC approach adequately protects infants and children. Broadly speaking, this is because the TTC values are expressed according to body weight and therefore take into account the lower body weights of infants and children.
EFSA also noted that in the first weeks of life young infants are capable of metabolising and eliminating substances, particularly when exposures are low, and that the differences between young infants and children or adults in this respect are small enough not to invalidate the use of the TTC approach.
However, EFSA does recommend that if the estimated exposure is in the range of the TTC value for young infants, additional considerations, such as predicted metabolism, frequency and duration of exposure, need to be made, on a case-by-case basis, to determine whether the TTC approach can be relied on.
8. What happens next?
Since its original development and application to food, further scientific developments have taken place which mean there may be a need to update the TTC approach. EFSA and the World Health Organization (WHO) have therefore embarked on a review of the TTC approach. As part of this project EFSA and the WHO are holding a workshop in December 2014 involving stakeholders and scientific experts.