Effects of lowering the proposed top-concentration limit in an in vitro chromosomal aberration test on assay sensitivity and on the reduction of the number of false positives

Organization for Economic Co-operation and Development (OECD), Guideline for the testing of chemicals, No. 473, In vitro mammalian cell chromosome aberration test, adopted July 21, 1997 (updated). Available at http://www.oecd-ilibrary.org/environment/test-no-473-in-vitro-mammalian-chromosome-aberration-test_9789264071261-en (accessed August 26, 2013). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), S2A guideline, Guidance on genotoxicity testing and data interpretation for pharmaceuticals intended for human use, Step 4 in July 1995. Galloway, 1994, Report from working group on in vitro tests for chromosomal aberrations, Mutat. Res., 312, 241, 10.1016/0165-1161(94)00012-3 Scott, 1991, Genotoxicity under extreme culture conditions, a report from ICPEMC task group 9, Mutat. Res., 257, 147, 10.1016/0165-1110(91)90024-P Kirkland, 2007, How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: report of an ECVAM workshop, Mutat. Res., 628, 31, 10.1016/j.mrgentox.2006.11.008 Parry, 2010, Analysis of published data for top concentration considerations in mammalian cell genotoxicity testing, Mutagenesis, 25, 531, 10.1093/mutage/geq046 Kirkland, 2010, Further analysis of Ames-negative rodent carcinogens that are only genotoxic in mammalian cells in vitro at concentrations exceeding 1mM, including retesting of compounds of concern, Mutagenesis, 25, 539, 10.1093/mutage/geq041 Galloway, 2011, Workshop summary: top concentration for in vitro mammalian cell genotoxicity assays; and report from working group on toxicity measures and top concentration for in vitro cytogenetics assays (chromosome aberrations and micronucleus), Mutat. Res., 723, 77, 10.1016/j.mrgentox.2011.01.003 Morita, 2012, Effect of reducing the top concentration used in the in vitro chromosomal aberration test in CHL cells on the evaluation of industrial chemical genotoxicity, Mutat. Res., 741, 32, 10.1016/j.mrgentox.2011.10.005 Brookmire, 2013, Evaluation of the highest concentrations used in the in vitro chromosome aberrations assay, Environ. Mol. Mutagen., 54, 36, 10.1002/em.21738 ICH, S2(R1) guideline, Guidance on genotoxicity testing and data interpretation for pharmaceuticals intended for human use, Step 4 version, dated 9 November 2011. Available at http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S2_R1/Step4/S2R1_Step4.pdf (accessed August 26, 2013). OECD, OECD guideline for the testing of chemicals, Proposal for updating test guideline 473, In vitro mammalian chromosome aberration test, December 2013. Available at http://www.oecd.org/env/ehs/testing/TG473_Dec2013_WNT4thCR.pdf.(accessed June 3, 2014). Serafimova, 2010, Review of QSAR models and software tools for predicting genotoxicity and carcinogenicity JRC scientific and technical reports, EUR 24427 EN Williams, 2006, Derek for windows assessment of chromosomal aberration effects, Toxicol. Lett., 164, 292, 10.1016/j.toxlet.2006.07.265 Mekenyan, 2007, Identifying the structural requirements for chromosomal aberration by incorporating molecular flexibility and metabolic activation of chemicals, Chem. Res. Toxicol., 20, 1927, 10.1021/tx700249q Kirkland, 2005, Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. Sensitivity, specificity and relative predictivity, Mutat. Res., 584, 1, 10.1016/j.mrgentox.2005.02.004 Ishidate, 1988, A comparative analysis of data on the clastogenicity of 951 chemical substances tested in mammalian cell cultures, Mutat. Res., 195, 151, 10.1016/0165-1110(88)90023-1 Galloway, 1987, Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals, Environ. Mol. Mutagen., 10, 1, 10.1002/em.2850100502 Loveday, 1989, Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro: II. Results with 20 chemicals, Environ. Mol. Mutagen., 13, 60, 10.1002/em.2850130108 Loveday, 1990, Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. V: Results with 46 chemicals, Environ. Mol. Mutagen., 16, 272, 10.1002/em.2850160409 Anderson, 1990, Chromosome aberration and sister chromatid exchange test results with 42 chemicals, Environ. Mol. Mutagen., 16, 55, 10.1002/em.2850160505 National Toxicology Program (NTP), NTP website at http://ntp-server.niehs.nih.gov and NTP database search home page at http://tools.niehs.nih.gov/ntp_tox/ (accessed August 26, 2013). Sasaki, 1980, Cytogenetic effects of 60 chemicals on cultured human and Chinese hamster cells, Senshokuta (Kromosoma), 20, 574 1987, 19 Lioi, 1998, Cytogenetic damage and induction of pro-oxidant state in human lymphocytes exposed in vitro to gliphosphate, vinclozolin, atrazine, and DPX-E9636, Environ. Mol. Mutagen., 32, 39, 10.1002/(SICI)1098-2280(1998)32:1<39::AID-EM5>3.0.CO;2-6 Matsuoka, 1990, Mutagenicity of 3-tert-butyl-4-hydroxyanisole (BHA) and its metabolites in short-term tests in vitro, Mutat. Res., 241, 125, 10.1016/0165-1218(90)90115-I Harrington-Brock, 1998, Mutagenicity of three disinfection by-products: di- and trichloroacetic acid and chloral hydrate in L5178Y/TK+/− −3.7.2C mouse lymphoma cells, Mutat. Res., 413, 265, 10.1016/S1383-5718(98)00026-6 Matsuoka, 1996, Re-evaluation of chromosomal aberration induction on nine mouse lymphoma assay “unique positive” NTP carcinogens, Mutat. Res., 369, 243, 10.1016/S0165-1218(96)90029-4 Reisenbichler, 1993, Genotoxic effects of selected peroxisome proliferators, Mutat. Res., 286, 135, 10.1016/0027-5107(93)90177-H Knasmüller, 1997, Genotoxic effects of three Fusarium mycotoxins, fumonisin B1, moniliformin and vomitoxin in bacteria and in primary cultures of rat hepatocytes, Mutat. Res., 13, 39, 10.1016/S0165-1218(97)00030-X van den Berghe, 1974, Clastogenic effects of haloperidol in vivo and of haloperidol, droperidol and pipamperone in vitro, Arzneim. Forsch., 24, 2055 Kaul, 1979, Cytogenetic activity of some common antioxidants and their interaction with X-rays, Mutat. Res., 67, 239, 10.1016/0165-1218(79)90018-1 Mudry, 1994, Mutagenic bioassay of certain pharmacological drugs: III Metronidazole (MTZ), Mutat. Res., 305, 127, 10.1016/0027-5107(94)90230-5 Huang, 1996, Relationships between molecular structure and chromosomal aberrations in in vitro human lymphocytes induced by substituted nitrobenzenes, Bull. Environ. Contam. Toxicol., 57, 349, 10.1007/s001289900197 Matsuoka, 1991, Clastogenicity of 1-nitropyrene, dinitropyrenes, fluorene and mononitrofluorenes in cultured Chinese hamster cells, Mutat. Res., 259, 103, 10.1016/0165-1218(91)90114-2 Egeli, 1991, The clastogenic effect of pyrimethamine (Daraprim) on human chromosomes in lymphocyte cultures, Cell Biol. Toxicol., 7, 347, 10.1007/BF00124070 Sirianni, 1978, Further studies on cytogenetic effects of folpet, Mutat. Res., 53, 64, 10.1016/0165-1161(78)90341-2 Hilliard, 1998, Chromosome aberrations in vitro related to cytotoxicity of nonmutagenic chemicals and metabolic poisons, Environ. Mol. Mutagen., 31, 316, 10.1002/(SICI)1098-2280(1998)31:4<316::AID-EM3>3.0.CO;2-G Galloway, 1997, Multilaboratory comparison of in vitro tests for chromosome aberrations in CHO and CHL cells tested under the same protocols, Environ. Mol. Mutagen., 29, 189, 10.1002/(SICI)1098-2280(1997)29:2<189::AID-EM10>3.0.CO;2-A Rani, 1991, In vitro effect of fenthion on human lymphocytes, Bull. Environ. Contam. Toxicol., 47, 316, 10.1007/BF01688658 Caballo, 1992, Analysis of cytogenetic damage induced in CHO cells by the pyrethroid insecticide fenvalerate, Terato. Carcinogen. Mutagen., 12, 243, 10.1002/tcm.1770120602 Armstrong, 1992, A quantitative assessment of the cytotoxicity associated with chromosomal aberration detection in Chinese hamster ovary cells, Mutat. Res., 265, 45, 10.1016/0027-5107(92)90038-4 Galloway, 1998, DNA synthesis inhibition as an indirect mechanism of chromosome aberrations: comparison of DNA-reactive and non-DNA-reactive clastogens, Mutat. Res., 400, 169, 10.1016/S0027-5107(98)00044-X Anderson, 1990, Chromosome aberration and sister chromatid exchange test results with 42 chemicals, Environ. Mol. Mutagen., 16, 55, 10.1002/em.2850160505 Shelby, 1984, Chemicals showing no evidence of carcinogenicity in long-term, two-species rodent studies: the need for short-term test data, Environ. Mutagen., 6, 871, 10.1002/em.2860060613 Stemp, 1989, In vitro and in vivo cytogenetic studies of three ß-lactam antibiotics (penicillin VK, ampicillin and carbenicillin), Mutagenesis, 4, 439, 10.1093/mutage/4.6.439 Japan Existing Chemical (JEC) database, based on the Chemical Substances Control Low (CSCL), as website at http://dra4.nihs.go.jp/mhlw_data/jsp/SearchPageENG.jsp (accessed August 26, 2013). Chromosomal aberration test in cultured mammalian cells, 49 Kikyoku no. 392, Law concerning examination and regulation of manufacture, etc. of chemical substances, 1974. OECD, OECD Existing chemicals database, Website at http://webnet.oecd.org/HPV/UI/Search.aspx (accessed August 26, 2013). International Agency for Research on Cancer (IARC), IARC monographs on the evaluation of carcinogenic risks to humans, Website at http://monographs.iarc.fr/ (accessed August 26, 2013). Japan Chemical Industry Ecology Toxicology & Information Center (JETOC), Mutagenicity Test Data of Existing Chemical Substances. Based on the Toxicity Investigation System of the Industrial Safety and Health Law, JETOC, Tokyo, 1996, pp. 86.