Review of the Threshold of Toxicological Concern (TTC) approach and development of new TTC decision tree

In light of improving analytical methods, it can be expected that many more unintended chemicals will be detected in our environment, including food and drinking water, and in our bodies. The TTC approach is a screening and prioritization tool for the safety assessment of chemicals when hazard data are incomplete and human exposure can be estimated. TTC is not applicable when compound-specific assessment and toxicity data are available or are required under existing regulations. EFSA and WHO embarked in this project to review the current TTC approach and propose some modifications, building on previous activities and recommendations. An expert workshop was implemented, informed through a public call for data and an open stakeholder meeting. The experts concluded that the TTC approach is based on scientific risk assessment principles and fit for purpose as a screening tool, to assess low dose chemical exposures and to identify those for which further data are necessary to assess the human health risk. The expert group made recommendations to improve and expand the TTC concept, and proposed a tiered approach (revised decision tree), considering the current state-of-the-science and available toxicological databases. The proposed TTC for genotoxic compounds of 0.0025 µg/kg bw/day, based on linear extrapolation for known genotoxic carcinogens, is sufficiently protective. Exceptions are high potency carcinogens, i.e. aflatoxin-like, azoxy- or N-nitroso-compounds and benzidines, which are excluded from the current TTC approach. Carcinogens that are not DNA reactive are adequately covered by the other TTC tiers. For some categories of substances, as inorganic chemicals, metals, organometallics, proteins, steroids, organo-silicon compounds, TTC is not applicable.  A number of recommendations were given to further strengthen the TTC approach, including the need for a permanent repository for data supporting TTC and the Cramer scheme, based on merging of existing databases and establishment of clear inclusion criteria for studies.
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First published in EFSA Supporting Publications:
10 March 2016