Evaluation of the Threshold of Toxicological Concern (TTC)--challenges and approaches.
Thresholds of Toxicological Concern (TTCs) have been used in the risk assessment of chemicals to which humans are exposed at very low levels. TTC values were developed using data from rodent cancer bioassays and from oral chronic and sub-chronic toxicity studies for non-cancer effects. The workshop assessed the adequacy and fitness for purpose of the TTC approach and the potential for future modifications of critical aspects. The current TTC value for cancer was considered adequate and fit for purpose because it is derived by linear extrapolation from the lowest TD(50) for each compound in the largest available rodent carcinogenicity database. The database on non-cancer endpoints was considered adequate and fit for purpose because the chemical domain, the distributions of NOAELs and the calculated TTC values are comparable across different databases. Application of the TTC approach gives conclusions compatible with the risk assessment approaches currently used by international advisory committees. The workshop recognised the desirability of developing better tools to assess the comparability of the chemical domain covered in different toxicological databases, and the need to develop an internationally acceptable framework and databases for updating the aspects critical to application of the TTC approach.
Mammalian Toxicology, Chemicals Regulation, Directorate Health and Safety Executive, Mallard House, York YO1 7PX, UK. publications@ilsieurope.be
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D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007391:International Cooperation; D009369:Neoplasms / Q000139:chemically induced; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment / Q000379:methods*; D012377:Rodentia; D014116:Toxicology / Q000379:methods*
D002273:Carcinogens