About this Research Topic
The Threshold of Toxicological Concern (TTC) is an exposure threshold below which there is no appreciable risk to human health. There are two main approaches: TTC values based on cancer potency data from which a one in a million risk is estimated; and TTC values based on non-cancer effects. For the latter approach, a distribution is fitted to the No Observed Adverse Effect Levels (NOAELs) from repeat-dose toxicity studies from which a 5% percentile value is taken and adjusted using a safety factor. The current established TTC values are based on oral chronic studies. The genesis of TTC was to facilitate food contact, food flavoring, and additive assessments. The World Health Organization (WHO) and the European Food Safety Authority (EFSA) have determined that the TTC approach is sound but it is typically applied on a chemical-by-chemical basis. The use of TTC to prioritize large numbers of chemicals has not yet been thoroughly applied in practice. In the case of cancer TTC, the CPDB database along with the methodologies (TD10, BMDL10, etc.) have been updated by CEFIC. And the thresholds are being revisited.
A similar approach, called ecoTTC, has been proposed for the establishment of environmental thresholds of concern. These can be derived for different species and modes of action. The underlying toxicity distributions can also be used to inform cross-species extrapolation. To date, the ecoTTC approach has not been used for regulatory purposes.
There are several important considerations that need to be investigated such as:
1) Applicability of established TTC values to different chemistries or are new TTC values warranted;
2) Evaluating the performance of assignment of chemicals to specific TTC categories based on different tools;
3) Addressing other routes of entry or exposure durations e.g. TTCs for inhalation, internal vs external TTCs.
4) Regulatory acceptance of TTC in different countries.
5) Definition of modes of action for aquatic organisms covering different chemistries and assignment of appropriate threshold values
6) Regulatory acceptance of the ecoTTC approach in environmental risk assessment
Please submit articles that describe the application of TTCs, ecoTTCs, or their refinement.
Topic editor, Dr. Yang has declared potential conflicts of interest with Molecular Networks GmbH. All other topic editors declare no competing interests with regards to the Research Topic subject.
Keywords: TTC, Threshold of toxicological concern, EcoTTC
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