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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 and Flari, Villie and Gosling, John Paul and Hart, Andy and Craig, Peter and Rushton, Lesley and Idahosa-Taylor, Ehi (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 . pp. 106-118.

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.

Item Type:Article
Full text:(AM) Accepted Manuscript
Available under License - Creative Commons Attribution Non-commercial No Derivatives.
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1016/j.fct.2013.03.003
Publisher statement:© 2013 This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Date accepted:02 March 2013
Date deposited:04 July 2017
Date of first online publication:15 March 2013
Date first made open access:No date available

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