The Threshold of Toxicological Concern (TTC) approach as currently applied is a "valid, science-based screening tool useful for the prioriti[z]ation of chemicals and for more general applications in chemical risk assessment," according to a recently published European Food Safety Authority (EFSA)/World Health Organization (WHO) draft report. The draft report, Threshold of Toxicological Concern Approach: Conclusions and Recommendations of the EFSA/WHO Expert Workshop, is the result of a project by EFSA and WHO to provide recommendations on how the existing TTC framework can be improved and expanded.
The TTC approach is used to assess potential human health concerns for a chemical when hazard data are incomplete, although it may not be used for certain classes of chemicals. This approach integrates data on exposure, chemical structure, metabolism, and toxicity, with the structural scheme most often used being the Cramer decision tree. The report noted that the TTC approach is not applicable when compound-specific assessment and toxicity data are required under existing regulations. Additionally, it should not be used to supersede evaluation of available toxicological data but, in certain circumstances such as the prioritization of a large number of chemicals, it can be used as a preliminary screening assessment tool.
The expert group concluded that major restructuring of the Cramer decision tree, which is used to classify structures into hazard classes of oral toxicity based on questions about a chemical's structure as they relate to known toxicity, is not necessary since it is reproducible and has been validated by applying it to numerous newer databases. However, the group suggested that future modifications to the Cramer scheme should include the toxicological rationale for each question to provide increased transparency. Another recommendation was that a permanent repository for data supporting TTC and the Cramer decision tree should be created and a group should be identified to be responsible for the database. Also, with respect to databases, the expert group also recommended that the different non-cancer databases should be merged and made public.
The draft report identified categories of chemicals for which the TTC approach should not be used. These included high potency carcinogens, compounds not adequately covered in the database, and nanomaterials. The expert group did suggest that the TTC approach can be used to evaluate the safety of exposures in infants but cautioned that there is a need to ensure that exposure data are suitable for an infant assessment. Moreover, for infants under three months of age, the group stated that case-by-case considerations are needed if the estimated exposure approaches the TTC value.
EFSA has requested comments by March 29, 2015, on the draft report. For information on how to comment, see EFSA's website.