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

Background

Based on the Threshold of Regulation (ToR) that was introduced by the US Food and Drug Administration, the Threshold of Toxicological Concern (TTC) concept is a science-based tool to help regulators and industry to assess potential health risk from substances when specific toxicological data are not yet available.

Objectives

The Task Force aims to strengthen the scientific fundamentals for TTC and to expand its applicability as a risk assessment tool for substances to which humans are exposed at low levels.

Impact

The Task Force organised the EUROTOX Continuing Education Course (CEC) to expand the TTC concept awareness and provide an overview of current non-animal methods to deal with data gaps in hazard and exposure assessment.
The Task Force frequently collaborates with the CEFICLong-Range Research Initiative. One of their successfully completed projects involved the creation of a carcinogen database.

For more detailed information, please contact Angeliki Stavropoulou at AStavropoulou@ilsieurope.be  or Belinda Antonio at bantonio@ilsieurope.be

Task Force Members


* Scientific Advisor

Expert Groups

Cefic-LRI/ILSI Europe Joint Workshop on “Carcinogen Dose-Response Database for Threshold of Toxicological Concern (TTC)

Background – Carcinogen Dose-Response Database for Threshold of Toxicological Concern
Building on the evaluation of the Cancer Potency Database (CPDB) developed by the ILSI Europe CPDB Expert Group the joint research project ‘Carcinogen Dose-Response Database for TTC’ (B18) supported by ILSI Europe, Liverpool John Moores University (UK), Molecular Networks GmbH (DE), Fraunhofer Institute for Toxicology and Experimental Medicine (DE) and the European Chemical Industry Council Long-Range Research Initiative (CEFIC LRI) aims to generate a fully-curated, quality-controlled and publically-available database on cancer potency data for genotoxic and non-genotoxic carcinogens. The add-on project B18.2, run by Fraunhofer ITEM, collected non-cancer endpoint data for the non-DNA-reactive subset of carcinogens of B18.

Workshop Objectives
A broad range of stakeholders including US FDA, EFSA, WHO, JRC etc. had voiced in previous evaluations of the TTC cancer thresholds that it would be advisable to update and reanalyse the cancer database forming the basis of the current TTC threshold. Consequently, the organisation of a workshop is envisaged in order to discuss the results of the joint project with relevant experts familiar with cancer data interpretation and TTC. In particular, the workshop aims:

  • To introduce the final database and the methods applied
  • To achieve consensus on
    • appropriate study and data selection
    • the preferred statistical approach to biologically relevant cancer potency descriptors
    • should the expert group agree that an update of the existing TTC threshold of 0.15 µg/person/day were warranted, on appropriate extrapolation for practical TTC cancer thresholds
  • To develop recommendations for optimal use of the cancer potency database

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

Background & 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 as 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

Cefic-LRI/ILSI Europe Joint Workshop on “Carcinogen Dose-Response Database for Threshold of Toxicological Concern (TTC)

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

Publications

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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.

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