Approaches to the risk assessment of genotoxic carcinogens in food: A critical appraisal

O’Brien, John; Renwick, A.G.; Constable, Anne; Dybing, Erik; Müller, D.J.G.; Schlatter, Josef Rudolf; Slob, Wout; Tueting, W.; Benthem, Jan van; Williams, Gary M.; Wolfreys, Alison

doi:10.1016/j.fct.2006.07.004

Cited by 114 publications

(83 citation statements)

References 47 publications

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“…Notably, this testing is applied very differently in different sectors, allowing for example, TTC approaches for food contaminants (Barlow and Schlatter, 2010;Kroes et al, 2004Kroes et al, , 2005Munro et al, 2008;O'Brien et al, 2006;Pratt et al, 2009), or margin of exposure (MOE) approaches (Benford et al, 2010), in which differences between actual human exposure and the point of departure of toxicity in animal experiments are used. Some authors have an alternative way of stating this discrepancy: "Analysis also indicates that many ordinary foods would not pass the regulatory criteria used for synthetic chemicals" (Ames and Gold, 2000;Silva Lima and Van der Laan, 2000).…”

Section: In Silico Approachesmentioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

203

165

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Section: In Silico Approachesmentioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

203

165

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“…Only relatively few MOE assessment can be found in the literature (e.g. for acrylamide, aflatoxin B 1 , benzo(a) pyrene, dimethylnitrosamine and some other compounds in a summary by O'Brien et al [45], as well as some separate evaluation for acetaldehyde [48], ethyl carbamate [49,50], or furan [51]). Hopefully, new forms of internet publication such as the "Open Toxicology Journal" will facilitate the dissemination of MOE studies, which are often difficulty to place at traditional journals.…”

Section: Discussionmentioning

confidence: 99%

“…The preferred quantitative approach for risk assessment appears to be the so-called margin of exposure (MOE), which can be used to compare animal dose-response data with human exposure scenarios [45][46][47]. The MOE can be used for prioritization of risk management actions, but is was described being difficult to interpret in terms of health risk [46].…”

Section: Discussionmentioning

confidence: 99%

Carcinogens in Food: Opportunities and Challenges for Regulatory Toxicology

Lachenmeier¹

2009

TOTOXIJ

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Abstract:The risk of developing cancer from carcinogens occurring in food is of widespread interest to scientific researchers, food policymakers and food surveillance institutions, as well as to the general public. When evaluating the risk of carcinogenic food contaminants or carcinogenic foodstuff per se (e.g., alcoholic beverages), the level of scientific evidence should be reflected more clearly. In the past, interest often focused on 'fashionable' agents with only moderate levels of evidence of their carcinogenicity (e.g., acrylamide or furan); whereas agents with the highest level of evidence (e.g., substances classified by the International Agency for Research on Cancer (IARC) as group 1, being 'carcinogenic to humans') were sometimes disregarded. For example, important carcinogens such as arsenic (a contaminant in drinking water), cadmium and other heavy metals, but also benzene, were not even mentioned in a recent review article about carcinogenic food contaminants. Research, control and prevention strategies for carcinogenic agents in food should comprise a risk-oriented approach and should not lose sight of agents that pose an immediate and scientifically quantifiable threat. Suitable strategies include the use of quantitative risk assessments, for example the use of the Margin of Exposure (MOE) approach.

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“…In the former, the information is often translated into a risk management strategy of reducing exposure to levels that are "as low as reasonably achievable/practicable" (ALARA/P). However, the output of the risk assessment does not provide a clear basis for deciding on the urgency or extent of risk management action nor does it enable any prioritisation of competing hazards (EFSA, 2005;O'Brien et al, 2006;Benford et al, 2010). In the latter approach, a decision needs to be taken as to the form of the dose-response relationship below that tested experimentally.…”

Section: Introductionmentioning

confidence: 99%

“…A rather large (theoretically infinite) number of dose-response models for genotoxic carcinogens exist; these include both linear and non-linear models (Bolt et al, 2004;Neumann, 2009;O'Brien et al, 2006;Swenberg et al, 2008;Williams et al, 2005). Most of the models used in dose-response analysis software (e.g.…”

Section: Introductionmentioning

confidence: 99%

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

Flari

Gosling

et al. 2013

Food and Chemical Toxicology

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Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. ABSTRACTThe 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 low levels of exposure; 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 and most importantly, query the rigour of the assumption of a linear relationship.Highlights  Experts are reluctant to express views on the dose-response curve for genotoxic carcinogens *Manuscript for revision (track changes hidden) Click here to view linked ReferencesPage 2 of 48  The POD can be extrapolated first from high to low dose in animals and then to humans, or vice versa  Expert judgement was that the dose-response curve is highly non-linear at human relevant exposures  Stochastic events and the distribution of susceptibilities will contribute, to an unknown extent  Interpretation of the MOE requires consideration of MOA, species differences and human variability Keywords Dose-response function; expert judgment; genotoxic carcinogens; low dose extrapolation; margins of exposure; risk assessment

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Approaches to the risk assessment of genotoxic carcinogens in food: A critical appraisal

Cited by 114 publications

References 47 publications

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Carcinogens in Food: Opportunities and Challenges for Regulatory Toxicology

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

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