Tice RR, Bassan A, Amberg A, Anger LT, Beal MA, Bellion P, Benigni R, Birmingham J, Brigo A, Bringezu F, Ceriani L, Crooks I, Cross K, Elespuru R, Faulkner DM, Fortin MC, Fowler P, Frericks M, Greets HHJ, Jahnke GD, Jones DR, Krulak NL, Piparo EL, Lopez-Belmonte J, Luniwal A, Luu A, Madia F, Manganelli S, Manickam B, Mestres J, Mihalchik-Burhans AL, Neilson L, Pandiri A, Pavan M, Rider CV, Rooney JP, Trejo-Martin A, Wantanabe-Sailor KH, White AT, Wooley D, Myatt GJ. 2021. In silico approaches in carcinogenicity hazard assessment: Current status and future needs. Comp Toxicol 20:100191 (Special issue: The in silico toxicology protocols initiative).
Abstract
Historically, identifying carcinogens has relied primarily on tumor studies in rodents, which require enormous resources in both money and time. In silico models have been developed for predicting rodent carcinogens but have not yet found general regulatory acceptance, in part due to the lack of a generally accepted protocol for performing such an assessment as well as limitations in predictive performance and scope. There remains a need for additional, improved in silico carcinogenicity models, especially ones that are more human-relevant, for use in research and regulatory decision-making. As part of an international effort to develop in silico toxicological protocols, a consortium of toxicologists, computational scientists, and regulatory scientists across several industries and governmental agencies evaluated the extent to which in silico models exist for each of the recently defined 10 key characteristics (KCs) of carcinogens. This position paper summarizes the current status of in silico tools for the assessment of each KC and identifies the data gaps that need to be addressed before a comprehensive in silico carcinogenicity protocol can be developed for regulatory use.