Interpretation of the margin of exposure for genotoxic carcinogens – Elicitation of expert knowledge about the form of the dose response curve at human relevant exposures

Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

Abstract

The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to “as low as reasonably achievable/practicable” (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the “Margin of Exposure” (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose–response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose–response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose–response relationships at human relevant exposures; the generality of judgments about such dose–response relationships; uncertainties affecting judgments on the nature of such dose–response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts’ views on the form of the dose–response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship.

Citation

Boobis, A., Flari, V., Gosling, J. P., Hart, A., Craig, P., Rushton, L., & Idahosa-Taylor, E. (2013). Interpretation of the margin of exposure for genotoxic carcinogens – Elicitation of expert knowledge about the form of the dose response curve at human relevant exposures. Food and Chemical Toxicology, 57, 106-118. https://doi.org/10.1016/j.fct.2013.03.003

• Journal Article Type: Article
• Acceptance Date: Mar 2, 2013
• Online Publication Date: Mar 15, 2013
• Publication Date: Jul 1, 2013
• Deposit Date: Nov 8, 2013
• Publicly Available Date: Jul 4, 2017
• Journal: Food and Chemical Toxicology
• Print ISSN: 0278-6915
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 57
• Pages: 106-118
• DOI: https://doi.org/10.1016/j.fct.2013.03.003
• Public URL: https://durham-repository.worktribe.com/output/1467168