IPCS framework for analyzing the relevance of a cancer mode of action for humans

Alan R. Boobis, Samuel M. Cohen, Vicki Dellarco, Douglas McGregor, M. E. Meek, Carolyn Vickers, Deborah Willcocks, William Farland

Research output: Contribution to journalReview article

318 Scopus citations

Abstract

The use of structured frameworks can be invaluable in promoting harmonization in the assessment of chemical risk. IPCS has therefore updated and extended its mode of action (MOA) framework for cancer to address the issue of human relevance of a carcinogenic response observed in an experimental study. The first stage is to determine whether it is possible to establish an MOA. This comprises a series of key events along the causal pathway to cancer, identified using a weight-of-evidence approach based on the Bradford Hill criteria. The key events are then compared first qualitatively and then quantitatively between the experimental animals and humans. Finally, a clear statement of confidence, analysis, and implications is produced. The IPCS human relevance framework for cancer provides an analytical tool to enable the transparent evaluation of the data, identification of key data gaps, and structured presentation of information that would be of value in the further risk assessment of the compound, even if relevancy cannot be excluded. This might include data on the shape of the dose-response curve, identification of any thresholds and recognition of potentially susceptible subgroups, for example, the basis of genetic or life-stage differences.

Original languageEnglish (US)
Pages (from-to)781-792
Number of pages12
JournalCritical reviews in toxicology
Volume36
Issue number10
DOIs
StatePublished - Dec 1 2006

Keywords

  • Animal-Human Concordance
  • Carcinogens
  • DNA-Reactive
  • Human Relevance Framework for Cancer
  • Key Events
  • Mode of Action
  • Risk Assessment

ASJC Scopus subject areas

  • Toxicology

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    Boobis, A. R., Cohen, S. M., Dellarco, V., McGregor, D., Meek, M. E., Vickers, C., Willcocks, D., & Farland, W. (2006). IPCS framework for analyzing the relevance of a cancer mode of action for humans. Critical reviews in toxicology, 36(10), 781-792. https://doi.org/10.1080/10408440600977677