title: Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic.
abstract: This paper presents the work of an expert group established by the International Life Sciences Institute - European branch (ILSI Europe) to follow up the recommendations of an international conference on "Risk Assessment of Compounds that are both Genotoxic and Carcinogenic: New Approaches". Twelve genotoxic and carcinogenic chemicals that can be present in food were selected for calculation of a Margin of Exposure (MOE) between a point of departure on the dose-response for oral carcinogenicity in animal studies and estimates of human dietary exposure. The MOE can be used to support prioritisation of risk management action and, if the MOE is very large, on communication of a low level of human health concern. Depending on the approaches taken in determining the point of departure and the estimation of exposure, it is possible to derive very different values for the MOE. It is therefore essential that the selection of the cancer endpoint and mathematical treatment of the data are clearly described and justified if the results of the MOE approach are to be trusted and of value to risk managers. An outline framework for calculating an MOE is proposed in order to help to ensure transparency in the results.
authors.affiliation: Food Standards Agency, UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Benford
authors.forename: P Michael
authors.initials: PM
authors.lastname: Bolger
authors.forename: Philip
authors.initials: P
authors.lastname: Carthew
authors.forename: Myriam
authors.initials: M
authors.lastname: Coulet
authors.forename: Michael
authors.initials: M
authors.lastname: DiNovi
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Leblanc
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Renwick
authors.forename: Woodrow
authors.initials: W
authors.lastname: Setzer
authors.forename: Josef
authors.initials: J
authors.lastname: Schlatter
authors.forename: Benjamin
authors.initials: B
authors.lastname: Smith
authors.forename: Wout
authors.initials: W
authors.lastname: Slob
authors.forename: Gary
authors.initials: G
authors.lastname: Williams
authors.forename: Tanja
authors.initials: T
authors.lastname: Wildemann
mesh_terms: D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005060:Europe; D005506:Food Contamination / Q000032:analysis* / Q000706:statistics & numerical data; D006801:Humans; D015233:Models, Statistical; D009153:Mutagens / Q000633:toxicity*; D012015:Reference Standards; D018570:Risk Assessment; D035501:Uncertainty; D014944:World Health Organization
chemical_list: D002273:Carcinogens; D009153:Mutagens