Mutations bacterial tests

In the bacterial mutation test, the mutagenic potential of a pharmaceutical and its metabolites is evaluated by measuring and quantifying its ability to induce reverse mutations at selected loci of Salmonella typhimurium or Escherichia coli in the presence and absence of metabolic activation. This test system has been shown to detect a diverse group of chemical mutagens.3,4 The technical details of this test have been reported in the literature.5-7... 

Chamberlain, M., and C. M. Tarmy (1977). Asbestos and glass fibers in bacterial mutation tests. Mutagen. Res. 43 159-164. 

Anderson D, Styles JA. 1978. Appendix 2 The bacterial mutation test. Br J Cancer 37 924-930. 

Venitt, S., Crofton-Sleigh, C. Bosworth, D. A. (1982) UKEMS trial bacterial mutation tests of 4-chlororncthylbiphcnyl. 4-hydroxymethylbiphenyl, and benzyl chloride, using E. coli WP2 uvrA(pKM101) and 5. typhimurium TA98 and TAIOO. Mutat. Res., 100, 39-43... 

Chamberlain M, Tarmy EM. 1977. Asbestos and glass fibres in bacterial mutation tests. Mutat Res 43 159-164. 

Mutagenicity Before human exposure, a bacterial mutation test (or in vitro mammalian cell mutation test), and a chromosomal damage test. A full battery of mutagenicity tests before Phase 111 clinical trials. 

The Ames test is recommended by the International Conference on Harmonisation Guidelines as part of a standard genetic toxicology battery. The other assays include the mouse lymphoma and micronucleus tests. This bacterial mutation test may not be appropriate for the evaluation of certain classes of chemicals, for example highly bactericidal compounds (e.g., certain antibiotics), any compounds that may interfere with cell division or replication, and possibly some peptides. In such cases, mammalian mutation tests may be more appropriate. 

While the USEPA report cited some evidence of T-cell-independent and -dependent immunity in mice injected with a mixture of PAHs that included 2-methylnaphthalene, is was not clear if the effects were due to 2-methylnaph-thalene or other PAHs in the mixture. The USEPA report noted there was no evidence of 2-methylnaphthalene s mutagenicity in Salmonella typhimurium bacterial mutation tests. The USEPA report also stated that there was a lack of information on many toxicological endpoints for 2-methylnaphthalene, including little information on its developmental, reproductive, or neurological toxicity, as well as no available toxicology data on humans exposed to this chemical via an oral route (USEPA 2003). Overall, the USEPA reported concluded that the primary effect of 2-methylnaphthalene exposure is pulmonary toxicity (from studies in mice), though it is not known if the parent compound or metabolites are responsible for the observed pulmonary alveolar proteinosis. 

Genotoxicity studies were conducted across all product classes and the test batteries used by companies were variable. Twelve of the 15 respondents who completed questionnaires with regard to their strategy for hormones, GFs and CSFs, indicated that that they usually conduct such studies when assessing the safety of these products. In seven of these 12 cases, the studies conducted were those recommended as the ICH test battery, i.e. an in vitro bacterial mutation test, an in vivo mouse bone marrow micronucleus test, and an in vitro chromosome aberration test, either in human peripheral lymphocytes or mammalian cell lines. For four out of these seven cases, these tests were conducted because of regulatory requests. 

Figure 4.7 An explanation of the bacterial reverse-mutation test (the Ames test).

Genotoxicity Bacterial reverse mutation test (Ames test) OECD, US Approved... 

Houk VS, Schaikowsky S, Claxton LD. 1989. Development and validation of the spiral Salmonella assay An automated approach to bacterial mutagenicity testing. Mutat Res 223 49-64. 

Gatehouse, D.G., Wilcox, P., Forster, R., Rowland, I.R., and Callander, R.D. (1990). Bacterial mutation assays. In Basic Mutagenicity Tests UKEMS Recommended Procedures (Kirkland, D.J., Ed.). Cambridge University Press, pp. 13-61. 

Bacterial Reverse Mutation Test (Updated Guideline, adopted 21 July 1997)... 

The 3R concept lies behind efforts to improve ethical standards for the use of experimental animals throughout the scientific community, including toxicity testing. A number of in vitro methods for genetic toxicology testing have been established as guideline methods for many years, e.g., the bacterial reverse mutation test, more popularly known as the Ames test. 

The bacterial reverse mutation test OECD TG 471 US-EPA OPPTS 870.5100 EU Annex VB. 13/14... 

Positive results from the bacterial reverse mutation test (often referred to as the Ames test) indicate that a substance induces point mutations by base pair substimtion or frameshift in the... 

When testing antibacterial compounds where bacterially based mutation tests will be of limited value. 

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