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Threshold of Toxicological Concern

Background and Objectives

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;
  • Better use 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.


  • 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).

For more detailed information, please contact Dr Tobias Recker at



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