Mutagenicity typhimurium

Physicochemical properties requked include melting/boiling point, vapor pressure, solubiUty, and flammabiUty/explosion characteristics. The toxicological studies include acute toxicity tests, oral, inhalation, and dermal skin and eye kritation skin sensiti2ation subacute toxicity, oral, inhalation, and dermal and mutagenicity tests. In vitro reverse mutation assay (Ames test) on Salmonella typhimurium and/or E.scherichia coli and mammalian cytogenic test. In vivo mouse micronucleus test. 

Acute oral toxicity (rat)3 Ames mutagenicity screening test (Salmonella typhimurium)... 

Three examples concerning toxicity of heterogeneous data sets are given below. The first [50] relates to mutagenicity to Salmonella typhimurium of aromatic and heteroaromatic nitro-compounds ... 

Current evidence favors a-hydroxylation as a major activation pathway for NPYR. The model compounds, 2-acetoxyNPYR and 4-(N-carbethoxy-N-nitrosamino)butanal are both highly mutagenic towards typhimurium without enzymatic activation (21, 22). 

The mutagenic activity of the extracts was assayed using Salmonella typhimurium strain TA 1535, as described by McCann et al. (58). Ten ul of fish extract were spot-tested without addition of an S9-enzyme preparation (57). MNNG (20 ug/plate) was used as a positive control. 

Sayama M, M Inoue, M-A Mori, Y Maruyama, H Kozuka (1992) Bacterial metabolism of 2,6-dinitrotoluene with Salmonella typhimurium and mutagenicity of the metabolites of 2,6- dinitrotoluene and related compounds. Xenobiotica 22 633-640. 

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. 

Table 1 Antimutagenic Effects of Flavones on Mutagenicity Induced by IQ IN Salmonella typhimurium TA98...

MacGregor, J. T. Jurd, L. Mutagenicity of plant flavonoids structural requirements for mutagenic activity in Salmonella typhimurium. Mutat. Res. 1978, 54, 297-309. 

The mutagenic potential of diisopropyl methylphosphonate was investigated using the Ames assay. The compound was obtained from two different sources and tested on Salmonella typhimurium strains TA-1535, TA-1537, TA-1538, TA-98, and TA-100, both with and without S-9 activation. The compound did not demonstrate mutagenic activity in any of the assays (Hart 1980). Diisopropyl methylphosphonate was also negative for gene mutation in Saccharomyces cerevisiae (Hart 1980). 

Genotoxic Effects. The Ames test with Salmonella typhimurium with and without s9 liver fractions from male Syrian golden hamsters or Sprague-Dawley rats indicates that hydrogen sulfide is not a mutagen (EPA 1984). A summary of genotoxicity studies is presented in Table 2-3. 

Berglin EH, Carlsson J. 1986. Effect of hydrogen sulfide on the mutagenicity of hydrogen peroxide in Salmonella typhimurium strain TA102. Mutat Res 175 5-9. 

Connor TH, Forti GC, Sitra P, et al. 1979. Bile as a source of mutagenic metabolites produced in vivo and detected by Salmonella typhimurium. Environ Mutagen 1 269-276. 

Khudoley W, Mizgireuv I, Pliss GB. 1987. The study of mutagenic activity of carcinogens and other chemical agents with Salmonella typhimurium assays Testing of 126 compounds. Arch Geschwulstforsch 57 453-462. 

Lijinsky W, Andrews AW. 1980. Mutagenicity of vinyl compounds in Salmonella typhimurium. Teratogenesis Carcinog Mutagen 1 259-267. 

Mutagenicity of tetrahydroepoxides. The mutagenic activity, without metabolic activation, of fourteen PAH tetrahydroepoxides has been measured in S. typhimurium strain TA 100. The logarithms of the relative mutagenic activities are plotted in Figure 3 vs. the value of AEj / calculated for conversion of each tetrahydro-... 

Figure 3. Plot of the logarithms of the relative mutagenicity of PAH tetrahydroepoxides toward typhimurium TA 100 versus AEdeloc/ (Adapted from Ref. 33.)...

Mutagenicity of diol epoxides. The intrinsic mutagenicities of ten diol epoxides-1 and twelve diol epoxides-2 toward S. typhimurium strain TA 100 and Chinese hamster V79 cells have been determined (14,28,29). For diol epoxides-1, the logarithms of the relative mutagenicities vs. the calculated values of AE(je oc/8 are given in... 

Figure 5. Plots of log rel. mutagenicity toward Sj typhimurium TA 100 and Chinese hamster V79 cells versus AE eioc/3 for PAH diol epoxides-1. Numbers refer to the position of the epoxide the epoxide is at a bay region if the number is not given. (Adapted from Refs. 14, 28, and 29.)...

The mutagenicities of the bay region diol epoxides derived from BA, BaAcr and BcAcr toward S. typhimurium strain TA 100 (similar results are obtained in strain TA 98) and Chinese hamster V79 cells... 

Figure 7. Mutagenicities of BA, BaAcr, and BcAcr bay region diol epoxides in S. typhimurium TA 100 and Chinese hamster V79 cells. (Adapted from Ref. 29).

McCann et al. (67) had shown that benzo[a]pyrene was mutagenic for j>. typhimurium only if the bacteria carried the mutation enhancing plasmid pKMIOl whose activity was later shown by Walker (23) to be entirely dependent on bacterial recA and lexA controlled functions. 

Mutagenicity. The mutagenicity of nitro PAHs has been studied most extensively in the Ames Salmonella typhimurium reversion assay ( 5). The mutagenicities of representative nitro PAHs in this assay are shown in Table I. Some of the more important features regarding their mutagenicity can be summarized as follows ... 

Table I. Mutagenicity of Representative Nitro PAHs in Salmonella typhimurium strains TA98 and TA100 (revertants per nmole)...

Salmonella typhimurium. Although most nitro PAHs are direct-acting mutagens in Salmonella typhimurium, these compounds must be metabolized to bind covalently to DNA (71,92,112). S. typhimurium contains a family of nitroreductases which are capable of reducing nitro PAHs, and strains which are deficient in these enzymes generally show decreased sensitivity toward nitro PAH-induced mutations (27,92,113-114). These observations suggest that reduced metabolic intermediates may be the critical reactive electrophiles. 

Compared to the extensive data that have been obtained on the mutagenicity of nitro PAHs in S. typhimurium, relatively little is known about the metabolism of these compounds in this organism. Messier et al. (67) reported that incubation of 1-nitropyrene with S. typhimurium TA98 yielded 1-aminopyrene and 1-acetylaminopyrene as major and minor metabolites, respectively. The reduction of 1-nitropyrene was slow and was accompanied by a slow formation of DNA adducts. When incubations were conducted with the nitroreductase-deficient strain, TA100 F50, both the extent of 1-amino-pyrene formation and DNA binding decreased. Howard ej al. (71,115) also found reduction of 1-nitropyrene to 1-aminopyrene in strains TA98, TA1538 and ATCC 14028. 

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