Threshold of Toxicological Concern

Threshold of Toxicological Concern

Expanding the use of a science-based tool for toxicological health risk assessment objectives

Task Force Information

Objectives and list of Task Force members

Contact Information

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Activity Overview

Overview of ongoing and
upcoming activities

Expert Groups

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Publications

List of publications of this
Task Force

Multimedia

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Completed Expert Groups

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each activity

Task Force Information

Objectives

  • Drive acceptance of  the Threshold of Toxicological Concern (TTC) concept by increasing confidence in its scientific basis.
  • Describe the sources of uncertainty within the TTC  concept in comparison to animal-data based hazard characterization.
  • Develop more specific approaches for assessment of data-poor mixtures with the TTC concept but also beyond.
  • Foster discussion of differences in regulatory implementations of TTC across regions to increase understanding and reduce divergence.

Task Force Members

WP DataTables

Contact Information

For more detailed information, please contact Geraldine Borja at gborja@ilsieurope.be

Activity Overview

Ongoing

- Uncertainty in Hazard Assessment: a Comparison of TTC versus Chemical-Specific Approaches

The review will aid to develop knowledge and understanding of different stakeholders about the sources of uncertainty and allow a conclusion if and if so, how much additional uncertainty may be associated with the application of the TTC approach as compared to substance-specific risk assessment. Such understanding will enable appropriate communication of uncertainty, and would also allow to design future activities to minimize potential additional uncertainties.

Start date: Jan 2017 | End date: July 2025

- Building Cumulative Assessments Groups for Combined Exposure Risk Assessment Based on TTC Thresholds or Read-Across

An Expert Group aims to strengthen the scientific foundation for combined toxicity screening assessment using TTC thresholds. There is a growing need for screening and prioritisation of risk assessment on combinations of compounds in regulatory contexts involving poorly characterised compounds at low exposure levels. These compounds might be metabolites/impurities of pesticides, chemicals, or biocides, as well as food contact material migrants, packaging materials, or process-related contaminants.

Start date: Jul 2021 | End date: Dec 2025

In the pipeline

- Different regulatory approaches of the TTC concept

This activity will include a workshop (tentative for 2027) aiming at gathering regulatory perspectives about how TTC is seen and applied across Europe, and will result in a peer-reviewed publication, to be submitted after the workshop.

Expected kick-off: Q4 2025

Expert Groups

Uncertainty in Hazard Assessment: a Comparison of TTC versus Chemical-Specific Approaches

Background and Objectives

The probabilistic approach using the genotoxicity and non-cancer (Cramer class) Thresholds of Toxicological Concern (TTC) is often perceived as accepting a higher risk than traditional risk assessments. However, robust scientific activities to describe the sources of uncertainty within the TTC approach have not yet been conducted or published.

Output
The Expert Group examines how much uncertainty may be associated with the application of the TTC approach, compared to a substance-specific risk assessment. The group expects to produce two reviews: an initial focus on qualitative description and ranking of the identified sources of uncertainty. A subsequent quantitative assessment of the remaining quantifiable uncertainties.

Expert Group Members

 

WP DataTables

Building cumulative assessment groups for combined exposure risk assessment based on TTC thresholds or read-across

Background and Objectives

Develop scientific approaches for refinement of TTC-based co-exposure risk assessments, using real-world case examples and focus on data-poor substances and poorly characterized compounds at low exposure levels (metabolites/impurities of pesticides, chemicals, or biocides, food contact material migrants, packaging materials, or process-related contaminants). Solidify the scientific basis for combined toxicity screening assessment using TTC threshold values
Output

Provide guidance on methods to predict specific toxicity or general toxicological similarity to enable grouping into cumulative assessment groups. Develop a workflow relevant for different regulations for coexposure risk assessment based on TTC thresholds, possibly combined with specific read-across groups. Evaluate if and in which cases it might be sufficient to compare the TTC thresholds to individual coexposure component levels and in which cases all or some coexposure components should be added.

Expert Group Members

 

WP DataTables

Publications

Filter

All Publications

Evaluating the consistency of judgments derived through both in silico and expert application of the Cramer classification scheme

Food and Chemical Toxicology, 2024

The Cramer classification scheme has emerged as one of the most extensively-adopted predictive toxicology tools, owing in part to its employment for chemical categorisation within threshold of toxicological concern evaluation. The characteristics of several of its rules have contributed to inconsistencies with respect to degree of hazard attributed to common (particularly food-relevant) substances. This investigation examines these discrepancies, and their origins, raising awareness of such issues amongst users seeking to apply and/or adapt the rule-set.

Read more

The Role of Hazard- and Risk-Based Approaches in Ensuring Food Safety

2015

  • ILSI Europe

Trends in Food Science & Technology. 2015;46(2) Part A:176-188. Supported by the following task forces: Emerging Microbiological Issues, Food Allergy, Food Intake Methodology, Novel Foods and Nanotechnology, Process Related Compounds and Natural Toxins, Risk Analysis in Food Microbiology, and Threshold of Toxicological Concern.

Read more

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		Abstract
	

	The Cramer classification scheme has emerged as one of the most extensively-adopted predictive toxicology tools, owing in part to its employment for chemical categorisation within threshold of toxicological concern evaluation. The characteristics of several of its rules have contributed to inconsistencies with respect to degree of hazard attributed to common (particularly food-relevant) substances. This investigation examines these discrepancies, and their origins, raising awareness of such issues amongst users seeking to apply and/or adapt the rule-set.
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Commissioned by the Threshold of Toxicological Concern Task Force

			
						Read the full article here
					


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		Abstract
	

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Commissioned by the Threshold of Toxicological Concern Task Force

			
						Read the full article here
					


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Multimedia

One-Pager

Completed Expert Groups

Overview of completed activities

 

- Is the 0.15 µG/Day Tier of the Threshold of Toxicological Concern (TTC) still Appropriate?