IARC Cancer Evaluation

ToxStrategies professionals can assist clients in preparing for the review of their substance of interest within the IARC (International Agency for Research on Cancer) Monograph Program. This program evaluates the potential of a substance to be a human carcinogen. An IARC staff member initiates the evaluation process by identifying experts to participate in the working group. The working group then reviews pertinent information and drafts a summary. At the cancer evaluation meeting, these drafts are reviewed, discussed, integrated, and finalized, which includes voting on the classification of the agent. Meeting summaries are published in The Lancet within weeks of the meeting, followed by meeting monographs approximately a year later. Though not issued by a regulatory body, final IARC classification status has stark global impact, given the use of agent classifications by regulatory entities (e.g., Proposition 65).

ToxStrategies’ scientists have first-hand knowledge of the IARC process, having served as working-group members, and meeting observers, and providing support to clients in preparing for these evaluations and developing follow-up strategies subsequently. In our experience, we have found it integral to be engaged in this process, beginning prior to the meeting announcement, allowing for ample time to potentially fill data gaps. Moreover, because working-group members vary with each individual monograph meeting, actual evaluation and interpretation of data are unique to each meeting, thus highlighting the potential role of an observer to ensure that key data are reviewed by the working group. Selected examples of relevant staff experience include the following:

  • Education regarding the IARC process
  • Outlining the process and identifying specific client needs based on the agent being evaluated
  • Early recognition of data submission needs
  • Implementation of strategies to fulfill data needs
  • Identification and nomination of experts
  • Meeting observation and/or observer preparation
  • IARC-like evaluation of cancer studies in human and animals
    • Study quality and reliability
    • Evaluation of body of evidence for causality
  • Assessment of mechanistic data via the Ten Key Characteristics of Carcinogens (Smith et al., 2015)
    • Identification and evaluation of information via the peer-reviewed literature
    • Mining, mapping, and critical evaluation of high-throughput screening (HTS) data (e.g., ToxCast/Tox21)
  • Summarizing exposure data
    • Characterization of agent components/contaminants
    • Identification of possible contaminants/metabolites of agent that might contribute to evaluation
  • Evaluation of other relevant information
    • Evaluate relevant toxicokinetic information, noting key metabolites, as well as their cancer and toxicity profiles if available
    • Assess information pertaining to susceptibility
    • Determine cancer process mode of action and relevance to humans
  • Preliminary categorization of potential IARC classification to anticipate outcome
  • Collaboration on and support of public relations efforts
  • Follow-up strategies based on classification of agent