Research Topic

Advances and Refinements in the Development and Application of Threshold of Toxicological Concern (TTC)

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


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

06 July 2020 Abstract
06 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

06 July 2020 Abstract
06 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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