Beyond key characteristics of carcinogens: an archetypal MOA-based evidence system for hypothesis testing to advance carcinogen risk assessment
by:
Becker RA, Dourson M, Onyema C, Ryman J
Becker RA, Dourson M, Onyema C, Ryman J
Summary:
The International Agency for Research on Cancer's (IARC) key characteristics of carcinogens (KCCs) have sparked debate, offering a framework to organize data for simplifying cancer hazard identification and risk assessment. However, guidance for integrating KCC evidence into decisions is limited and inconsistent; examples of KCC use show failure to predict classifications and can lead to mislabeling compared to IARC and U.S. EPA outcomes. Modern understanding of chemical carcinogenesis—encompassing multifaceted molecular, cellular, and dose-dependent processes—far surpasses knowledge from decades ago, demanding application in risk assessments to safeguard public health while enabling chemical benefits. Scientific progress in cancer and risk evaluation trends toward greater complexity, emphasizing hypothesis testing and causal analysis; simplistic approaches like the Delaney Clause or standalone KCCs hinder this. Becker et al. advocate returning to hypothesis generation and testing via four archetypal chemical carcinogenesis modes of action (MOA), exemplified by an advanced causal evidence scoring system that compares support for each MOA, identifies the probable operative one, and advances it with toxicity values for risk assessment.
The International Agency for Research on Cancer's (IARC) key characteristics of carcinogens (KCCs) have sparked debate, offering a framework to organize data for simplifying cancer hazard identification and risk assessment. However, guidance for integrating KCC evidence into decisions is limited and inconsistent; examples of KCC use show failure to predict classifications and can lead to mislabeling compared to IARC and U.S. EPA outcomes. Modern understanding of chemical carcinogenesis—encompassing multifaceted molecular, cellular, and dose-dependent processes—far surpasses knowledge from decades ago, demanding application in risk assessments to safeguard public health while enabling chemical benefits. Scientific progress in cancer and risk evaluation trends toward greater complexity, emphasizing hypothesis testing and causal analysis; simplistic approaches like the Delaney Clause or standalone KCCs hinder this. Becker et al. advocate returning to hypothesis generation and testing via four archetypal chemical carcinogenesis modes of action (MOA), exemplified by an advanced causal evidence scoring system that compares support for each MOA, identifies the probable operative one, and advances it with toxicity values for risk assessment.