IARC Workshop on the Key Characteristics of Carcinogens: Assessment of Endpoints for Evaluating Mechanistic Evidence of Carcinogenic Hazards

Background: The 10 key characteristics (KCs) of carcinogens form the basis of a framework to identify, organize, and evaluate mechanistic evidence relevant to carcinogenic hazard identification. The 10 KCs are related to mechanisms by which carcinogens cause cancer. The IARC Monographs Programme has successfully applied the KCs framework for the mechanistic evaluation of different types of exposures, including chemicals, metals, and complex exposures such as environmental, occupational, or dietary exposures. The use of this framework has significantly enhanced the identification and organization of relevant mechanistic data, minimized bias in evaluations and enriched the knowledge base about the mechanisms of known and suspected carcinogens. Objectives: IARC convened a Scientific Workshop with the goal of ensuring appropriate, transparent, and uniform application of the KCs in future IARC Monographs evaluations. Methods: A group of experts from different disciplines reviewed the Monographs experience with the KCs of carcinogens, discussing three main themes: the interpretation of endpoints forming the evidence base for the KCs; the incorporation of data from novel assays on the KCs; and the integration of the mechanistic evidence as part of cancer hazard identification. Discussion: The workshop participants assessed the relevance and the informativeness of multiple KCs-associated endpoints for the evaluation of the mechanistic evidence in studies of exposed humans and experimental systems. Consensus was reached on how to enhance the use of in silico, molecular, and cellular high-output and high-throughput data. In addition, approaches to integrate evidence across the KCs and opportunities to improve methodologies of mechanistic evaluation of cancer hazards were explored. The findings described herein and in a forthcoming IARC Technical Report will support future Working Groups of experts in the reporting and interpretation of results under the KCs framework within the IARC Monographs or in other contexts.

DEMARINI David M.;  GWINN William;  WATKINS Emily;  REISFELD Brad;  CHIU Weihsueh A.;  ZEISE Lauren;  BARUPAL Dinesh;  BHATTI Parveen;  CROSS Kevin;  DOGLIOTTI Eugenia;  FRITZ Jason M.;  GERMOLEC Dori;  GUERRA ANDERSEN Maria Helena;  GUYTON Kathryn Z.;  JINOT Jennifer;  PHILLIPS David H.;  REDDEL Roger Robert;  ROTHMAN Nathaniel;  VAN DEN BERG Martin;  VERMEULEN Rudolf C. H.;  VINEIS Paolo;  WANG Amy;  WHELAN Maurice;  GHANTOUS Akram;  KORENJAK Michael;  ZAVADIL Jiri;  HERCEG Zdenko;  PERDOMO Sandra;  DOSSUS Laure;  CHITTIBOYINA Shirisha;  CUOMO Danila;  KALDOR John;  PASQUAL Elisa;  RIGUTTO Gabrielle;  WEDEKIND Roland;  FACCHIN Caterina;  EL GHISSASSI Fatiha;  DE CONTI Aline;  SCHUBAUER-BERIGAN Mary K.;  MADIA Federica; 

2025-04-07

US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE

JRC140970

1552-9924 (online),   

https://ehp.niehs.nih.gov/doi/10.1289/EHP15389,    https://publications.jrc.ec.europa.eu/repository/handle/JRC140970,   

10.1289/EHP15389 (online),