Toxicol Sci. 2023 Dec 23:kfad134. doi: 10.1093/toxsci/kfad134. Online ahead of print.
ABSTRACT
Systematic review and evaluation of mechanistic evidence using the Key Characteristics approach was proposed by the International Agency for Research on Cancer (IARC) in 2012 and used by the IARC Monographs Working Groups since 2015. Key Characteristics are ten features of agents known to cause cancer in humans. From 2015 to 2022 a total of 19 Monographs (73 agents combined) used Key Characteristics for cancer hazard classification. We hypothesized that a retrospective analysis of applications of the Key Characteristics approach to cancer hazard classification using heterogenous mechanistic data on diverse agents would be informative for systematic reviews in decision-making. We extracted information on the conclusions, data types, and the role mechanistic data played in the cancer hazard classification from each Monograph. Statistical analyses identified patterns in the use of Key Characteristics, as well as trends and correlations among Key Characteristics, data types, and ultimate decisions. Despite gaps in data for many agents and Key Characteristics, several significant results emerged. Mechanistic data from in vivo animal, in vitro animal and in vitro human studies was most impactful for concluding that an agent could cause cancer via a Key Characteristic. To exclude the involvement of a Key Characteristic, data from large-scale systematic in vitro testing programs such as ToxCast were most informative. Overall, increased availability of systemized data streams, such as human in vitro data, would provide the basis for confident conclusions about both positive and negative associations and constitute relative contributions of various sources of weight in expert judgments.
PMID:38141214 | DOI:10.1093/toxsci/kfad134