A proposed framework for assessing risk from less-than-lifetime exposures to carcinogens

Susan P. Felter, Rory B. Conolly, Joel P. Bercu, P. Michael Bolger, Alan R. Boobis, Peter M.J. Bos, Philip Carthew, Nancy G. Doerrer, Jay I. Goodman, Wafa A. Harrouk, David J. Kirkland, Serrine S. Lau, G. Craig Llewellyn, R. Julian Preston, Rita Schoeny, A. Robert Schnatter, Angelika Tritscher, Frans Van Velsen, Gary M. Williams

Research output: Contribution to journalReview article

29 Scopus citations

Abstract

Quantitative methods for estimation of cancer risk have been developed for daily, lifetime human exposures. There are a variety of studies or methodologies available to address less-than-lifetime exposures. However, a common framework for evaluating risk from less-than-lifetime exposures (including short-term and/or intermittent exposures) does not exist, which could result in inconsistencies in risk assessment practice. To address this risk assessment need, a committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute conducted a multisector workshop in late 2009 to discuss available literature, different methodologies, and a proposed framework. The proposed framework provides a decision tree and guidance for cancer risk assessments for less-than-lifetime exposures based on current knowledge of mode of action and dose-response. Available data from rodent studies and epidemiological studies involving less-than-lifetime exposures are considered, in addition to statistical approaches described in the literature for evaluating the impact of changing the dose rate and exposure duration for exposure to carcinogens. The decision tree also provides for scenarios in which an assumption of potential carcinogenicity is appropriate (e.g., based on structural alerts or genotoxicity data), but bioassay or other data are lacking from which a chemical-specific cancer potency can be determined. This paper presents an overview of the rationale for the workshop, reviews historical background, describes the proposed framework for assessing less-than-lifetime exposures to potential human carcinogens, and suggests next steps.

Original languageEnglish (US)
Pages (from-to)507-544
Number of pages38
JournalCritical Reviews in Toxicology
Volume41
Issue number6
DOIs
StatePublished - Jul 2011

Keywords

  • Cancer risk assessment
  • Haber's Rule
  • dose-rate correction factors (DRCFs)
  • intermittent exposure
  • lessthan-lifetime exposure (LTL)
  • short-term exposure
  • threshold of toxicological concern (TTC)

ASJC Scopus subject areas

  • Toxicology

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    Felter, S. P., Conolly, R. B., Bercu, J. P., Bolger, P. M., Boobis, A. R., Bos, P. M. J., Carthew, P., Doerrer, N. G., Goodman, J. I., Harrouk, W. A., Kirkland, D. J., Lau, S. S., Llewellyn, G. C., Preston, R. J., Schoeny, R., Schnatter, A. R., Tritscher, A., Van Velsen, F., & Williams, G. M. (2011). A proposed framework for assessing risk from less-than-lifetime exposures to carcinogens. Critical Reviews in Toxicology, 41(6), 507-544. https://doi.org/10.3109/10408444.2011.552063