Title: Can in vitro mammalian cell genotoxicity test results be used to complement positive results in the Ames test and help predict carcinogenic or in vivo genotoxic activity? II. Construction and analysis of a consolidated database
Publication Year: 2014
JRC N°: JRC91332
ISSN: 1383-5718
URI: http://www.sciencedirect.com/science/article/pii/S1383571814002848
DOI: 10.1016/j.mrgentox.2014.10.006
Type: Articles in periodicals and books
Abstract: A Workshop sponsored by EURL ECVAM was held in Ispra, Italy in 2013 to address the question of whether the in vitro mammalian cell genotoxicity test results could complement and mitigate the implications of a positive Ames test response for the prediction of in vivo genotoxicity and carcinogenicity, and if patterns of results could be identified. Databases of Ames-positive chemicals that were tested for in vivo genotoxicity and/or carcinogenicity were collected from different sources and analysed individually (Kirkland et al., xxxx, this issue). Because there were overlaps and inconsistent test results among chemicals in the different databases, a combined database which eliminated the overlaps and evaluated the inconsistencies would be preferable for addressing the above question. A database of >700 Ames-positive chemicals also tested in vivo was compiled, and the results in in vitro mammalian cell tests were analysed. Because the database was limited to Ames-positive chemicals, the majority (>85%) of carcinogens and in vivo genotoxins were positive when tested in both in vitro gene mutation and genotoxicity/clastogenicity tests. However, about half (>45%) of chemicals that were not carcinogenic or genotoxic in vivo also gave the same patterns of mammalian cell results. Although the different frequencies were statistically significant, positive results in 2 in vitro mammalian cell tests did not, per se, add to the predictivity of the positive Ames test. By contrast, negative results in both in vitro mammalian cell tests were rare for Ames-positive carcinogens and in vivo genotoxins but, were significantly more frequent for Ames-positive chemicals that are not carcinogenic or genotoxic in vivo. Thus, in the case of an Ames-positive chemical, negative results in 2 in vitro mammalian cell tests covering both mutation and clastogenicity/aneugenicity endpoints should be considered as indicative of absence of in vivo genotoxic or carcinogenic potential.
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