The use of reporter genes for mutagenicity testing in animals

Chemical substances capable of modifying the body’s genetic material (DNA) possess genotoxic properties. Mutations are irreversible changes to DNA. Such changes can affect any of the various types of cells in the body, and can lead to cancer. In addition, mutations in germ cells can also be transmitted to future generations. Assays for genotoxic properties in chemical substances form the basis for measures aimed at reducing these risks. Genotoxicity can be established using a variety of assays. Mutagenicity assays are particularly important, as they can identify changes in DNA. Using in vivo assays, experimental animals are exposed to the substance under investigation. In vitro assays involve the use of cells or microorganisms. If in vitro and in vivo assays produce contradictory results, then more weight is usually given to the experimental animal results, since these organisms more closely resemble human beings. Indirect evidence is also taken into account when reaching a verdict with regard to genotoxicity. This can relate to (in vitro or in vivo) assays of the formation of DNA adducts (covalent bonding to DNA). In this advisory report, the in vivo data is similarly conclusive, therefore ‘genotoxic’ (or ‘non-genotoxic’) really means ‘genotoxic in vivo’ (or ‘non-genotoxic in vivo’).

Committee

• Dr GMH Swaen, epidemiologist; University Medical Centre, Maastricht (until 1 September 2004), Dow Benelux, BV, Terneuzen (from 1 September 2004), chairman until 1 September 2004
• Dr PJ Boogaard, toxicologist; Shell International BV, The Hague
• HC Dreef - van der Meulen, toxicological pathologist; NV Organon, Oss
• Prof. VJ Feron (until 19 February 2004), Emeritus Professor of Biological Toxicology; Zeist
• Prof. H van Loveren (from 14 November 2003), Professor of Immunotoxicology, University of Maastricht; also National Institute of Public Health and the Environment, Bilthoven
• Prof. GR Mohn (until 1 January 2004), Professor of Cellular Mutation Genetics, Leiden University Medical Center
• Prof. GJ Mulder, Professor of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden
• Dr MJM Nivard, molecular biologist and genetic toxicologist, Leiden University Medical Center
• Dr PC Noordam, Ministry of Social Affairs and Employment, The Hague, consultant (until 19 February 2004)
• Dr H te Riele, molecular biologist; The Netherlands Cancer Institute, Amsterdam
• Dr H Roelfzema,Ministry of Health, Welfare and Sport, The Hague, consultant
• Prof. W Slob, Professor of Quantitative Risk Assessment, University of Utrecht; also National Institute of Public Health and the Environment, Bilthoven
• Prof. ALM Verbeek, Professor of Clinical Epidemiology, Radboud University Nijmegen
• Prof. AA van Zeeland, Professor of Molecular Radiation Dosimetry and Radiation Mutagenesis, Leiden University Medical Center, (from 1 February 2004, chairman from 1 September 2004)
• Prof. EJJ van Zoelen, Professor of Cell Biology, Radboud University Nijmegen
• Dr JA van Zorge, Ministry of Housing, Spatial Planning and the Environment, The Hague, consultant
• Dr PW van Vliet, Health Council, The Hague, secretary