Development of an updated carcinogenicity potency database and analysis of thresholds of toxicological concern

The existing Carcinogenicity Potency Database (CPDB) has been curated and extended with new data to facilitate a re-evaluation ofthe Threshold of Toxicological Concern (TTC) for carcinogenicity. New data have been added from the National Toxicology Program (NTP) and other open sources. All data were subject to a thorough review to ensure accuracy of the chemical structure as well as toxicological information. The new CPDB now comprises data for more than 650 chemicals with acceptable studies, according to defined criteria, of which >570 were carcinogens with >450 associated with reliable genotoxicity data. The CPDB was subjected to various analyses to determine points of departure, notably TD25 and TD50 as well as Benchmark Dose Levels. These analyses were compared and demonstrated the need for appropriate dose response data. A strategy was also implemented to identify mode of action with regard to genotoxicity. In vivo, in vitro and in silico data were applied through a defined strategy to identify genotoxic and non-genotoxic carcinogens. Specifically, where available, experimental genotoxicity (mutagenicity or clastogenicity) data or information from computational models (QSARs and structural alerts) for DNA reactivity, in vivo micronucleus effects and chromosomal aberration were utilised. Analysis of the new CPDB confirmed the conservative nature of the current TTC values for carcinogens. The new CPDB is publicly available as an Access file and searchable via COSMOS DB (cosmosdb.eu) and is intended to support further TTC evaluations for carcinogenicity. The funding of the CEFIC LRI-B18 Project is gratefully acknowledged.