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Threshold of Toxicological Concern

Supporting science in the advancement of the TTC concept as a non-animal
safety assessment tool for low level exposures


Background

In 1995, the US Food and Drug Administration (FDA) introduced the Threshold of Regulation (ToR) programme, according to which, at sufficiently low enough exposure, the associated risk related to the consumption of substances used in food contact articles (food packaging and food processing equipment) may be deemed negligible. Based on the principles of the ToR, the Threshold of Toxicological Concern (TTC) concept is a pragmatic but conservative science-based tool to help regulators and industry assess potential health risk from substances when specific toxicological data are not yet available (R. Kroes, et al. 2000). The use of the TTC principle enables to:

  • Recognise that exposures lower than the TTC levels do not pose safety concerns;
  • Decrease the use of laboratory animals;
  • Make better use of financial and human resources in both industry and governments
  • Apply a practical risk assessment tool that is needed to address low level exposures as more and more sensitive analytical techniques become available.

Objectives

The objectives of the task force are to strengthen the scientific underpinnings for the TTC, expanding its applicability as an important risk assessment tool for exposures to substances to which humans are exposed to at low levels. It allows for better use of resources for compounds with high exposures and/or high toxicity and for decreasing the use of animals in laboratory experiments.


Impact 

  • The task force was one of the first groups in Europe to further develop the underlying science of the TTC concept.

  • Since 1996, ILSI Europe has played a major role in advancing and promoting a broad application of the TTC concept in Europe. The scientific approach of the TTC concept is now recognised by scientific committees of international authorities that have issued favourable opinions on the use of TTC as a risk assessment tool.

  • In 2011, the task force organised a workshop on ‘Evaluation of the Threshold of Toxicological Concern (TTC) – Challenges and Approaches’ with support of the European Chemical Industry Council (Cefic-LRI), the European Partnership for Alternatives Approaches to Animal Testing (EPAA) and the International Society of Regulatory
    Toxicology (ISRTP). Participants reached the general consensus that the TTC approach is a valid first tier approach to risk characterisation (I. Dewhurst and A.G. Renwick, 2013).

  • The task force presented its current and completed scientific activities on TTC at the EFSA/WHO Stakeholder Meeting on Threshold of Toxicological Concern, held on 2 December 2014.


What's New

• The task force developed a new activity proposal on ‘Uncertainty within the TTC Concept in Comparison to Traditional Risk
  Assessment’. This activity plans to provide a differentiated review and comparison of quantitative and qualitative uncertainties
  associated with different steps of:

  • Data generation in toxicological studies and No Observed Adverse Effect Level (NOAEL)/ Benchmark Dose, Lower Confidence Limit (BMDL) derivation;
  • Assumptions made in risk assessment based on specific data;
  • Derivation of thresholds from large groups of substances, i.e. TTC;
  • Derivation of thresholds from small groups of substances.


For more detailed information, please contact Mr Cyril Marsaux at cmarsaux@ilsieurope.be



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COLLABORATION 

  • EU-project COSMOS: Integrated In Silico Models for the Prediction of Human Repeated Dose Toxicity of Cosmetics to Optimise Safety