TTC dataset on non-genotoxic carcinogens

Cefic-LRI B18_2: Subset of the curated CPDB database from the Cefic-LRI B18 project, comprising 137 organic, non DNA-reactive, carcinogenic compounds with their NOEL, BMDL10, and ETD10 values

Project description

TTC project dataset
© Fraunhofer ITEM
TTC project dataset.

Human carcinogens may act by different modes of action, but generally can be classified as genotoxic or non-genotoxic carcinogens. The TTC concept comprises a threshold for genotoxic compounds that is based on the evaluation of tumor incidences (TD50 values) from the CPDB database (Kroes et al. 2004; Cheeseman et al. 1999; Boobis et al. 2017). Recently, the CPDB database was updated by inclusion of more carcinogenic compounds and recent cancer and chronic studies (Cefic-LRI B18 project – link). A total of 232 compounds were classified as non-genotoxic carcinogens, using a straight-forward decision tree. Following a detailed review of all available peer-reviewed literature, experimental and predicted data, the dataset was reduced to 137 organic compounds.

For these 137 non-genotoxic carcinogens, we aimed to identify most sensitive endpoints and/or points of departure after chronic oral exposure (link to LRI-B18_2 webpage Cefic-LRI). NOEL values were derived from chronic and (if required) subchronic studies after oral exposure using well-established high-quality databases, e.g. RepDose, ToxRefDB, and COSMOS, or peer-reviewed publications. As far as possible, NOEL values were derived from the same study as used in the CPDB database for the calculation of carcinogenic potency (TD50 values).

The dataset includes NOELs for the most sensitive apical effect in the entire study as well as a description of the data quality and reference to the study. Furthermore, the lower benchmark dose level (BMDL) per compound is given. BMDLs were calculated based on tumor incidences with model averaging, as implemented in the Proast software. The minimal BMDL per compound is provided at a benchmark dose risk of 10 percent.

Publications

  • Boobis A, Brown P, Cronin MTD, Edwards J, Galli CL, Goodman J, Jacobs A, Kirkland D, Luijten M, Marsaux C, Martin M, Yang C, Hollnagel HM et al. (2017). Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation. Critical Reviews in Toxicology, Vol. 47, pp. 705-727, ISSN: 1040-8444.
  • Cheeseman MA, Machuga EJ and Bailey AB (1999). A tiered approach to threshold of regulation. Fd Chem Toxicol, Vol. 37, pp. 387-412.
  • Kroes, R., Renwick, A. G., Cheeseman, M., Kleiner, J., Mangelsdorf, I., Piersma, A., Schilter, B., Schlatter, J., van Schothorst, F., Vos, J. G., et al. (2004). Structure-based thresholds of toxicological concern (TTC): Guidance for application to substances present at low levels in the diet. Food Chem. Toxicol, Vol. 42, pp. 65-83.

Contact

Sylvia Escher

Contact Press / Media

Dr. Sylvia Escher

Head of Department of In-silico Toxicology

Phone +49 511 5350-330