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

TitleA proposed framework for assessing risk from less-than-lifetime exposures to carcinogens.
Publication TypeJournal Article
Year of Publication2011
AuthorsFelter SP, Conolly RB, Bercu JP, Bolger MP, Boobis AR, Bos PMJ, Carthew P, Doerrer NG, Goodman JI, Harrouk WA, Kirkland DJ, Lau SS, Llewellyn CG, Preston JR, Schoeny R, Schnatter RA, Tritscher A, van Velsen F, Williams GM
JournalCrit Rev Toxicol
Date Published2011 Jul
KeywordsBiological Assay, Carcinogens, Databases, Factual, Decision Trees, Dose-Response Relationship, Drug, Endpoint Determination, Environmental Exposure, Food Contamination, Guidelines as Topic, Household Products, Humans, Mutagens, National Institute of Environmental Health Sciences (U.S.), Neoplasms, Pesticides, Risk Assessment, Time Factors, United States, United States Environmental Protection Agency, United States Food and Drug Administration

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.

Alternate JournalCrit. Rev. Toxicol.
PubMed ID21591905