Mutagens tests for

From the detailed studies performed either using individual alcohol sulfates and alcohol ether sulfates or formulated products by oral administration and skin contact, no evidence of carcinogen risk was found. Similar conclusions were obtained when these sulfates or formulated products were tested for mutagenic and teratogenic properties. 

Some toxicity studies were performed analyzing Bfx and Fx mutagenic effects [240-242], For example, Bfx and Bfz nitro-substituted were tested for mutagenicity in Salmonella typhimurium (S. typhimurium) TA 98 and TA 100 strains with and without metabolic activation (Ames test). All the Bfx (10/10) and some of the Bfz (9/15) are mutagenic without activation. Other study has demonstrated benzofuroxan (128, Fig. 20) is mutagenic in the Luria and Del-brueck s fluctuation test, with Klebsiella pneumoniae, and in the Ames test. In another study it has been found that compound 137 (Fig. 21) is not mutagenic to S. typhimurium. 

Crespi CL, Ryan CG, Seixas GM, et al. 1985. Tests for mutagenic activity using mutation assays at two loci in the human lymphoblast cell lines TK6 and AHH-1. In Ashby J, de serres FJ, et al., eds. 

In addition, tests for mutagenicity and carcinogenicity are not likely required for most biopharma-ceutical substances. The regulatory guidelines and industrial practices relating to biopharmaceuti-cal preclinical trials thus remain in an evolutionary mode, and each product is taken on a case-by-case basis. An overview of the main preclinical tests undertaken for a sample biopharmaceutical... 

In vivo testing for mutagenic potential has also not been conducted. The carcinogenic potential for hexachloroethane has only been evaluated for the oral route. 

Category A lists three types of studies for human health effects basic acute toxicity tests, a 28-day animal study (referred to in other discussions as a "sub-chronic" test), and a series of two (or more) screening tests for mutagenicity and carcinogenicity. 

This test will also demonstrate excess growth, which may indicate the presence of histidine or tryptophan or their precursors in the test material, which could make testing for mutagenicity impracticable by this method. 

Genotoxicity. 1,2-Dibromoethane has been tested for mutagenic activity in a battery of in vitro and in vivo assay systems. It is mutagenic in bacteria, fungi, fruit flies, and cultured mammalian cells (Ames andYanofasky 1971 Barber 1981 Brimeret al. 1982 Crespi etal. 1985 Moriya etal. 1983 ... 

Ames test a simple and widely used experimental test for mutagenicity. 

New developments in cell-culture in-vitro assay tests for mutagenicity and carcinogenicity are presented by William G. Thilly in Chapter 2. It is expected that the cell-culture methodology will represent another important technique for the rapid biological assay of carcinogenicity and toxicity. 

Toxicokinetic data can also be used to make informed decisions on testing of chemical substances. In specific circumstances, valid toxicokinetic data may be used to support a decision to omit testing for systemic effects, e.g., in cases where the toxicokinetic data provide sufficient evidence that a substance is not absorbed and therefore not systemically available, i.e., no plasma/blood concentrations were measurable and no parent compound or metabolites could be detected in urine, bile, or exhaled air. For example, in vivo testing for mutagenicity, reproductive toxicity, or carcinogenicity may be omitted if toxicokinetic data or other data indicate a lack of systemic availability. 

The term genotoxicity is a broader term and refers to potentially harmful effects on genetic material, which are not necessarily associated with mutagenicity. Thus, tests for genotoxicity include tests, which provide an indication of induced damage to DNA (but not direct evidence of mutation) via effects such as unscheduled DNA synthesis (UDS), sister chromatid exchange (SCE), DNA strand breaks, DNA adduct formation or mitotic recombination, as well as tests for mutagenicity. ... 

If the results of indicator tests, e.g., DNA binding and SCE, are not supported by results obtained in tests for mutagenicity, the results of mutagenicity tests are generally of higher signihcance. 

Mutagenicity - in vitro tests for mutagenicity and chromosome damage. Adapted from Scales ... 

In general, positive results were obtained when BCME was tested for mutagenicity in vitro. It has also been reported to increase unscheduled DNA synthesis and the level of transformed cells in in vitro assays. ... 

Dimethylphenol was tested for mutagenicity in the Salmonella microsome preincubation assay using the standard protocol of the National Toxicology Program and five strains of Salmonella-, results were negative. ... 

C. Tests for mutagenicity in Salmonella and covalent binding to DNA and protein in the rat of the riot control agent o-chlorobenzylldene malononitrlle (CS). Arch. Toxicol. 49 15-27, 1981. 

IARC (1989) statement that, with respect to results from any one specific short-term assay, The relative potency of agents in tests for mutagenicity and related effects is not a reliable indicator of carcinogenic potency. ... 

Fox, M. Delow, G.F. (1985) Tests for mutagenic activity at the HGPRT locus in Chinese hamster V79 cells in culture. In Ashby, J., de Serres, F.J., Draper, M., Ishidate, M., Jr, Margolin, B.H., Matter, B.E. Shelby, M.D., eds, Progress in Mutation Research, Volume 5, Evaluation of Short-Term Tests for Carcinogens. Report of the International Programme on Chemical Safety s Collaborative Study on in vitro assays, Amsterdam, Elsevier Science, pp. 517-523... 

Chloro-ort/20-toluidine gave variable results in the majority of bacterial tests for mutagenicity. While most of the mammalian tests were positive, chromosomal aberration assays gave conflicting results. These data overall indicate that 4-chloro-ort/2o-toluidine causes DNA damage in mammalian cells. 

Four hundred milliliters from each specimen were put through an XAD-2 column and the adsorbed material was eluted. Methylene chloride extracts of the post-column urine eluate were made and tested for mutagenicity with the Salmonella/... 

Fox, M. Delow. GF. (1985) Tests for mutagenic activity at the HGPRT locus in Chinese hamster V79 cells in culture. Prog. Mutat. Res., 5, 517-523... 

Moore, W.B. Chatfield, S.N. (1982) Evaluation of 4-hydroxymethylbiphenyl (4HMB), 4-chloromethylbiphenyl (4CMB) and benzyl chloride (BC) using the Ames Salmonella microsome incorporation test for mutagenicity. Mutat. Res., 100. 35-38... 

Sacks, L.E. MacGregor, J.T. (1982) The B. subtilis multigene spomlation test for mutagens detection of mutagens inactive in the Salmonella his reversion test. Mutat. Res.. 95, 191-202... 

Mitchell, I.D., Gilbert, P.J., Brice, A.J. White, D.J. (1981) Somatic eye mutation m Drosophila melanogaster as a short-term test for mutagens and carcinogens. Carcinogenesis, 2,783-786... 

Figure 9. Distribution of halogenated hydrocarbons and mutagenic activity in HPLC fractions of a drinking water concentrate (neutral fraction). HPLC fractions obtained by linear-gradient HPLC analysis (H2O-C2H3N) were tested for mutagenic activity in the Salmonella mutagenicity test (TA98) and assayed for halogenated hydrocarbon content as described in Materials...

The precursors of mutagenicity produced by chlorination seem to be widespread, naturally occurring substances. If the precursors can be identified, identification of their chlorination products may help to elucidate the nature of the mutagenic activity in treated water. Thus, a complementary approach to that just described involves laboratory chlorination of naturally occurring model compounds at concentrations and conditions that simulate treatment chlorination. The reaction products were first tested for mutagenic activity to identify possible precursors of mutagenicity produced during treatment chlorination. The products were then analyzed by GC-MS and HPLC to try to identify the compounds formed. 

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