Revisiting the bacterial mutagenicity assays: Report by a workgroup of the International Workshops on Genotoxicity Testing (IWGT)

• Published in: Mutation research Vol. 849; p. 503137
• Main Authors: Schoeny, Rita, Cross, Kevin P., DeMarini, David M., Elespuru, Rosalie, Hakura, Atsushi, Levy, Dan D., Williams, Richard V., Zeiger, Errol, Escobar, Patricia A., Howe, Jonathan R., Kato, Masayuki, Lott, Jasmin, Moore, Martha M., Simon, Stephanie, Stankowski, Leon F., Sugiyama, Kei-ichi, van der Leede, Bas-jan M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2020
• Subjects: Animals; Bacterial mutagenicity testing; Biological Specimen Banks - organization & administration; Databases, Chemical - supply & distribution; Escherichia coli - drug effects; Escherichia coli - genetics; Guidelines as Topic; Humans; International Cooperation; IWGT; Mutagenesis; Mutagenicity Tests - standards; Mutagens - classification; Mutagens - toxicity; OECD TG471; Salmonella mutagenicity testing; Salmonella typhimurium - drug effects; Salmonella typhimurium - genetics; Tokyo; Tokyo; Bacterial mutagenicity testing; Salmonella mutagenicity testing; IWGT; OECD TG471
• ISSN: 1383-5718; 1879-3592; 1873-135X
• DOI: 10.1016/j.mrgentox.2020.503137

•International Workshop on Genotoxicity Testing met in 2017 to address OECD TG471.•Strains sub-group concluded that most mutagens would be detected with fewer strains.•Laboratory proficiency sub-group identified many criteria for laboratory proficiency.•Criteria sub-group noted several criteria to assure quality data.•The in silico sub-group made no specific recommendations. The International Workshop on Genotoxicity Testing (IWGT) meets every four years to obtain consensus on unresolved issues associated with genotoxicity testing. At the 2017 IWGT meeting in Tokyo, four sub-groups addressed issues associated with the Organization for Economic Cooperation and Development (OECD) Test Guideline TG471, which describes the use of bacterial reverse-mutation tests. The strains sub-group analyzed test data from >10,000 chemicals, tested additional chemicals, and concluded that some strains listed in TG471 are unnecessary because they detected fewer mutagens than other strains that the guideline describes as equivalent. Thus, they concluded that a smaller panel of strains would suffice to detect most mutagens. The laboratory proficiency sub-group recommended (a) establishing strain cell banks, (b) developing bacterial growth protocols that optimize assay sensitivity, and (c) testing “proficiency compounds” to gain assay experience and establish historical positive and control databases. The sub-group on criteria for assay evaluation recommended that laboratories (a) track positive and negative control data; (b) develop acceptability criteria for positive and negative controls; (c) optimize dose-spacing and the number of analyzable doses when there is evidence of toxicity; (d) use a combination of three criteria to evaluate results: a dose-related increase in revertants, a clear increase in revertants in at least one dose relative to the concurrent negative control, and at least one dose that produced an increase in revertants above control limits established by the laboratory from historical negative controls; and (e) establish experimental designs to resolve unclear results. The in silico sub-group summarized in silico utility as a tool in genotoxicity assessment but made no specific recommendations for TG471. Thus, the workgroup identified issues that could be addressed if TG471 is revised. The companion papers (a) provide evidence-based approaches, (b) recommend priorities, and (c) give examples of clearly defined terms to support revision of TG471.