title: Updated recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests.
abstract: In 2008 we published recommendations on chemicals that would be appropriate to evaluate the sensitivity and specificity of new/modified mammalian cell genotoxicity tests, in particular to avoid misleading positive results. In light of new data it is appropriate to update these lists of chemicals. An expert panel was convened and has revised the recommended chemicals to fit the following different sets of characteristics: • Group 1: chemicals that should be detected as positive in in vitro mammalian cell genotoxicity tests. Chemicals in this group are all in vivo genotoxins at one or more endpoints, either due to DNA-reactive or non DNA-reactive mechanisms. Many are known carcinogens with a mutagenic mode of action, but a sub-class of probable aneugens has been introduced. • Group 2: chemicals that should give negative results in in vitro mammalian cell genotoxicity tests. Chemicals in this group are usually negative in vivo and non-DNA-reactive. They are either non-carcinogenic or rodent carcinogens with a non-mutagenic mode of action. • Group 3: chemicals that should give negative results in in vitro mammalian cell genotoxicity tests, but have been reported to induce gene mutations in mouse lymphoma cells, chromosomal aberrations or micronuclei, often at high concentrations or at high levels of cytotoxicity. Chemicals in this group are generally negative in vivo and negative in the Ames test. They are either non-carcinogenic or rodent carcinogens with an accepted non-mutagenic mode of action. This group contains comments as to any conditions that can be identified under which misleading positive results are likely to occur. This paper, therefore, updates these three recommended lists of chemicals and describes how these should be used for any test evaluation program.
authors.affiliation: Kirkland Consulting, PO Box 79, Tadcaster LS24 0AS, England, UK.
authors.forename: David
authors.initials: D
authors.lastname: Kirkland
authors.affiliation: Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger Allee 3, D-53175 Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kasper
authors.affiliation: Novartis Institutes for Biomedical Research, Preclinical Safety, CH-4002 Basel, Switzerland.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Martus
authors.affiliation: F. Hoffmann-La Roche Ltd., Pharmaceutical Science and Roche Innovation Center Basel, CH-4070 Basel, Switzerland.
authors.forename: Lutz
authors.initials: L
authors.lastname: Müller
authors.affiliation: RIVM-National Institute for Public Health and the Environment, Bilthoven, Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: van Benthem
authors.affiliation: European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Systems Toxicology Unit, Institute for Health and Consumer Protection (IHCP), European Commission-Joint Research Centre, TP 126, Via E. Fermi 2749, I-21027 Ispra, Varese, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Madia
authors.affiliation: European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Systems Toxicology Unit, Institute for Health and Consumer Protection (IHCP), European Commission-Joint Research Centre, TP 126, Via E. Fermi 2749, I-21027 Ispra, Varese, Italy. Electronic address: raffaella.corvi@ec.europa.eu.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Corvi
mesh_terms: D024422:Aneugens / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000139:chemically induced; D004249:DNA Damage / Q000187:drug effects*; D016208:Databases, Factual; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods*; D012377:Rodentia; D012680:Sensitivity and Specificity
chemical_list: D024422:Aneugens; D002273:Carcinogens
keywords: EURL ECVAM; Genotoxicity; Improved tests; In vitro test; Reference chemicals; Reliability