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Risk Assessment of Genotoxic Carcinogens Task Force

Assessment of Benefits and Risks

Background

Carcinogens are chemicals that can increase the occurrence of tumours; those carcinogens that can damage DNA are referred to as genotoxic. There is no international consensus on how to evaluate the risk of genotoxic carcinogens that can be contained in food at low levels.

Objective

The Risk Assessment of Genotoxic Carcinogens Task Force aims to improve risk assessment of cancer caused by genotoxic carcinogens and collaborates closely with the World Health Organization (WHO) and the European Food Safety Authority (EFSA). Although the task force generally focuses on low levels in food and the risk to the consumer from dietary intake, the approaches developed and results obtained by the task force are relevant to risk assessments following other routes of exposure.

Impact

The task force is contributing to the harmonisation of risk assessment procedures by scientifically evaluating available data.

Activities

Data Selection for Benchmark Dose (BMD) Modelling of Substances that are Genotoxic and Carcinogenic

A key conclusion of Benford et al. (2010) was that “Depending on the tumour endpoint that is selected to be used in this approach and the ways in which the data are analysed, it is possible to generate very different Point of Departures (PoDs) to be used in calculating the Margin of Exposure (MoE), and hence in the value of the MoE itself. 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.” The successive expert group, which started in 2010, is investigating further issues related to tumour data selection and analysis.

Key to the discussions of the expert group will be considerations on:

The biological relevance of an observed tumour type in experimental animals for humans;
The mode of action (MoA);
Key steps of the BMD approach and associated questions regarding uncertainties;
Experimental study designs, study quality and associated uncertainties.

The draft guidance document on how to select the most appropriate data set to be used in BMD modelling will be submitted to a scientific journal early 2012 for publication.

Eurotox 2013

The task force has submitted a proposal to co-sponsor a session on ‘Advances in the application of the Threshold of Toxicological Concern (TTC) as a pragmatic risk assessment tool for cosmetics’ together with the TTC Task Force at Eurotox 2013, 1-4 September 2013, in Interlaken, Switzerland.

In addition, the task force will support a presentation on `Use of TTC for contaminants with potential genotoxic hazard´ in Eurotox 2013.

Potential Future Activities

Recently, the task force members discussed potential new projects which could start in the future:

Conference on the margin of exposure (MoE), most likely not before 2013, to review how the use of the approach has progressed in regulatory circles and discuss advances.
DNA-adducts: Analytical tools have advanced so that it might be possible to prepare dose-response curves for specific DNA-adducts and use adduct data in risk assessments of genotoxic carcinogens. The task force is considering the feasibililty of using such data.
Application of the MoE approach to mixtures of genotoxic carcinogens.

The discussion on these topics will be continued in future meetings of the task force.

Task Force Collaborators

Members - 2012

Dr. Benjamin Smith - Chair -	Firmenich	CH
Dr. Myriam Coulet - Co-chair -	Nestlé	CH

Dr. Philip Carthew	Unilever	UK
Dr. Hervé Lafforgue	Danone	FR
Dr. Josef Schlatter	Swiss Federal Office of Public Health	CH
Dr. Angelika Tritscher*	World Health Organization (WHO)	CH

Mr. Massimo Ambrosio	ILSI Europe	BE
Dr. Stéphane Vidry	ILSI Europe	BE
Ms. Belinda Antonio	ILSI Europe	BE

*Observer

Expert Group on the Data Selection for BMD Modelling of Substances that are Genotoxic and Carcinogenic

Dr. Lutz Edler - Chair -	German Cancer Research Centre (DKFZ)	DE

Dr. Diane Benford	Food Standards Agency	UK
Dr. Paolo Boffetta	International Prevention Research Institute	FR
Prof. Alan Boobis	Imperial College London	UK
Dr. Philip Carthew	Unilever	UK
Dr. Myriam Coulet	Nestlé	CH
Dr. Peter Greaves	Leicester Royal Infirmary	UK
Dr. Andy Hart	Food and Environment Research Agency (FERA)	UK
Dr. Josef Schlatter	Swiss Federal Office of Public Health	CH
Dr. Benjamin Smith	Firmenich	CH

Mr. Massimo Ambrosio	ILSI Europe	BE
Dr. Stéphane Vidry	ILSI Europe	BE

Corresponding member
Prof. Gary Williams	New York Medical College	US

Publications

A. Boobis, Editor. Application of the Margin of Exposure (MoE) Approach to Substances in Food that are Genotoxic and Carcinogenic. Food and Chemical Toxicology 2010;48(Suppl.1):S1-111.

A. Constable and S. Barlow. Application of the Margin of Exposure Approach to Compounds in Food which are both Genotoxic and Carcinogenic. ILSI Europe Report Series 2009:1-35.

S. Barlow et al. Risk Assessment of Substances that are both Genotoxic and Carcinogenic. Food and Chemical Toxicology 2006;44(10):1636-1650

J. O'Brien et al. Approaches to the Risk Assessment of Genotoxic Carcinogens in Food: A Critical Appraisal. Food and Chemical Toxicology 2006;44(10):1613-1635.

Softwares used by the Expert Group on Margin of Exposure

Source code for the version of mabmd
Source code for the R package used to run mabmd (includes a GUI interface to facilitate using mabmd)
Executable or binary of the R package (which includes the executable for mabmd)
Instructions for setting up the compilation environment for turning the source codes into executables

To download the poster of the task force, click here.

To download the poster on Margin of Exposure (MoE) that was presented at the XII International Congress of Toxicology (IUTOX), 19 - 23 July 2010 in Barcelona, click here.

For more information, please contact info@ilsieurope.be.