Structure-mutagenicity relationships of four amino-imidazonaphthyridines and imidazoquinolines

We tested four isomeric imidazonaphthyridines and one imidazoquinoline compound for mutagenic activity in the Ames/Salmonella mutagenicity assay, using strain TA98 and strain YG1024, an analogue of strain TA98 with elevated O-acetyl-transferase levels. Their potency was related to calculated electronic parameters. Five compounds with a linear arrangement of 3 rings showed a positive response in strain YG1024. Compound 2 (1-methyl-imidazo[4,5-b][1,7]naphthyridin-2-amine) is the most mutagenic in both strains, giving specific activities of about 200 and 30 revertants per microgram in strains YG1024 and TA98, respectively. Three of the compounds were weak mutagens, giving a positive dose-response only in strain YG1024, with 3–5 revertants per microgram. A higher response of all five compounds in strain YG1024 as opposed to TA98 indicates that they require O-acetyltransferase activity for their metabolism. Mutagenic potencies in strain YG1024 were positively correlated to the energy of the LUMO (lowest unoccupied molecular orbital) of the nitrenium ion. © 1995 Wiley-Liss, Inc.     

Characterization of mutagenic activity in instant hot beverage powders

Extracts of several grain-based coffee-substitute blends and instant coffees were mutagenic in the Ames/Salmonella test using TA98, YG1024, and YG1029 with metabolic activation. The beverage powders induced 150 to 500 TA98 and 1,150 to 4,050 YG1024 revertant colonies/g, respectively. Increased sensitivity was achieved using strain YG1024. No mutagenic activity was found in instant hot cocoa products. The mutagenic activity in the beverage powders was shown to be stable to heat and the products varied in resistance to acid nitrite treatment. Differential bacterial strain specificity, and a requirement for metabolic activation suggest that aromatic amines are present. Characterization of the mutagenic activity, using HPLC and the Ames test of the collected fractions, showed the coffee-substitute blends and instant coffees contain several mutagenic compounds. Known heterocyclic amines are not responsible for the major part of the mutagenic activity. The main mutagenic activity in grain-based coffee-substitute blends and instant coffees is due to several unidentified compounds, which are most likely aromatic amines. © 1995 Wiley-Liss, Inc.     

Mutagenic activities and physicochemical properties of selected nitrobenzanthrones

Mutagenic activity of nine nitro derivatives of benzanthrone, namely 1-nitro-, 2-nitro-, 3-nitro-, 9-nitro-, 11-nitro-, 1,9-dinitro-, 3,9-dinitro-, 3,11-dinitro- and 3,9,11-trinitrobenzanthrone were tested with Salmonella strains TA98, TA100, YG1021 and YG1024 in both the presence and absence of an S9 mix. Each compound exhibited mutagenic activity with all the strains. Among these nine isomers, 3-nitrobenzantrone exhibited the most mutagenic activity with all the strains without the S9 mix. The mutagenic activities of the dinitro and trinitro derivatives of benzanthrone were lower than that of the 3-nitro derivative; this is evident from the mutagenic activity of nitrated polyaromatic hydrocarbons (PAH), which is generally enhanced with an increase in nitration. The physicochemical properties of nitrated benzanthrone (reduction potential, hydrophobicity and orientation of nitro groups to the aromatic ring) demonstrated that mononitrated benzanthrone exhibits a lower reduction potential than mononitroPAHs such as 1-nitropyrene and 3-nitrofluoranthene, but was almost equivalent to that of dinitroPAH. Moreover, the mutagenic activity of mononitrobenzanthrones clearly depend on the reduction potential of each compound; however, this tendency was not observed in polynitrobenzanthrones, probably because the reduction of the nitro groups to amino groups of polynitrated benzanthrone might be predominant without a sufficient formation of corresponding hydroxyamines. These results suggest that aromatic compounds that contain keto groups, when nitrated, may act as potentially powerful direct-acting mutagens.     

Prostaglandin H synthase-dependent genotoxicity of 2,4-diaminotoluene.

2,4-Diaminotoluene (2,4-DAT), a high volume synthetic compound, is moderately carcinogenic to rodents. We report here that 2,4-DAT is a substrate for the peroxidase activity of prostaglandin H synthase (PHS). In contrast to many aromatic amines which are activated as mutagens by PHS, we find that 2,4-DAT is not mutagenic to six S. typhimurium strains with this activation system. The strains tested include YG1006, YG1024, and YG1029, which are far more sensitive to the mutagenicity of aromatic amines and nitroarenes than are the standard tester strains. Although not mutagenic itself, 2,4-DAT does enhance the mutagenicity of 2-aminofluorene (2-AF) in the PHS-catalyzed system in strains TA98, YG1006, and YG1024, with maximal enhancement of 140%, 1831%, and 1216%, respectively. Half-maximal enhancement of 2-AF mutagenicity is observed at 15-20 microM 2,4-DAT for strains YG1006 and YG1024, and about 80 microM for TA98. Studies with compounds structurally related to 2,4-DAT revealed enhancement of 2-AF mutagenicity with 2,5-DAT and o-phenylenediamine (o-PD) but not for other DAT isomers, toluidines, and phenylenediamines. Maximal enhancement of 2-AF mutagenicity observed in TA98 with PHS-catalyzed activation was 110% for o-PD and 60% for 2,5-DAT. This comutagenic effect of 2,4-DAT appears quite specific for 2-AF, as it fails to enhance either the PHS-dependent mutagenicity of the aromatic amines benzidine and 2-naphtylamine, or the direct mutagenicity of N-acetoxy-acetylaminofluorene,2-nitrofluorene,4- nitroquinoline-N-oxide and 1,1,1-trichloropropene-2,3-oxide. Enhancement of 2-AF mutagenicity by 2,4-DAT is also observed with cytochrome P-450-dependent activation, however the half-maximal 2,4-DAT concentration was 400 microM, and the maximal enhancement was only 50%. The ability of 2,4-DAT, under conditions where it is not itself mutagenic, to enhance the genotoxicity of the potent carcinogen 2-AF comprises an intriguing toxicological interaction, and underscores the inherent difficulties in assessing the genotoxic risks posed by mixtures of compounds.     

Urinary mutagenicity on TA98 and YG1024 Salmonella typhimurium strains after a hamburger meal: influence of GSTM1 and NAT2 genotypes

Mutagenicity on TA98 and YG1024 Salmonella typhimurium strainsof pan–fried hamburger extracts and of 24 h post–mealurine from 32 non–smoking volunteers was evaluated. Eachparticipant in the study was GSTM1 and NAT2 genotyped. Aftercooking the meat showed mutagenic activity (mean ± SD)on strains TA98 and YG1024 of 114 ± 129 and 1437 ±1536 net revertants/g respectively. Twenty three of 32 urinesamples showed clear mutagenic activity (i.e. caused at leasta doubling of the number of spontaneous revertants) on the 0-acetyltransferaseoverproducing strain YG1024, while none of the post-meal 24h urine samples was clearly mutagenic on strain TA98. Total24 h post–meal YG1024–active urinary mutagens werewell correlated with the levels of mutagen intake with the meal(r² = 0.5977, F = 44.58, P < 0.01). In the group under studyGSTM1 genotypes did not influence urinary mutagenicity. Highlyexposed subjects (n = 15) with the NAT2–ss genotype showedsignificantly increased levels of urinary mutagenicity on strainYG1024 in comparison with NAT2-R subjects (mutagen intake-adjustedtotal 24 h mutagen excretion = 1.00 ± 0.29 versus 0.66± 0.32, Mann-Whitney U test, U = 12.5, P < 0.05).Our results suggest that the levels of urinary mutagens derivedfrom diets rich in heterocyclic aromatic amines, which are specificallydetected by the YG1024 Salmonella strain, are modulated by NAT2-dependentenzyme activity, slow acetylators having higher levels of mutagensin their urine. Subjects with the rapid acetylator genotype,who are known to be at risk for colon cancer, seem to be partiallyprotected with respect to the risk of bladder cancer. ⁴To whom correspondence should be addressed. Tel: 498216637; Fax: 498216621; Email: clonfero{at}uxl.unipd.it     

Reduction in the mutagenicity of synthetic dyes by successive treatment with activated sludge and the ligninolytic fungus, Irpex lacteus

Synthetic dyes are released in wastewater from textile manufacturing plants, and many of these dyes are genotoxic. In the present study, the mutagenicity of azo, anthraquinone, and triphenyl methane dyes was investigated before and after successive biodegradation with activated sludge and the ligninolytic fungus, Irpex lacteus. Two biodegradation systems were used to reduce the genotoxicity of dyes that were not efficiently inactivated by activated sludge alone. Mutagenicity was monitored with the Salmonella reversion assay conducted with the base-pair substitution detector strains, TA100 and YG1042, and the frame-shift detector strains, TA98 and YG1041, with and without rat liver S9. All dyes except for Congo Red (CR) were mutagenic with S9 activation. Assays conducted with the dyes indicated that only the azo dye Reactive Orange 16 (RO16) was mutagenic in both TA98 and TA100. Methyl Red and Disperse Blue 3 (DB3) were mutagenic in TA98, YG1041 and YG1042, while Reactive Black 5 was mutagenic in YG1041 and YG1042. Remazol Brilliant Blue R (RBBR), Crystal violet (CV) and Bromophenol Blue (BPB) were mutagenic only in TA98, but the toxicity of the latter two dyes complicated the evaluation of their mutagenicity. CR was not mutagenic in any of the tester strains. Biodegradation studies conducted with RO16 and DB3 indicated that the two-step biodegradation process reduced the mutagenic potential of RO16 and DB3 to a greater extent than activated sludge alone; the mutagenicity of the two dyes was reduced by 95.2% and 77.8%, respectively, by the two-step process. These data indicate that the combined biodegradation process may be useful for reducing the mutagenicity associated with wastewater from textile factories that contain recalcitrant dyes.     

1-nitropyrene as a marker for the mutagenicity of diesel exhaust-derived particulate matter in workplace atmospheres

The use of 1-nitropyrene (1-NP) as a marker for the occupational exposure to diesel exhaust (DE) mutagens was investigated in workplace atmospheres contaminated with DE from a variety of emission sources, such as power supplies, forklifts, trucks, caterpillar vehicles, trains, ships' engines, and vehicles in city traffic. Total suspended particulate matter was collected by area sampling. The 1-NP content of acetone extracts of these samples as determined by gas chromatography-high resolution mass spectrometry varied from 0.080 to 17 μg/g acetone extractable matter, corresponding to air concentrations of 0.012 to 1.2 ng/m³. A sample collected in a rural area contained 0.0017 ng/m³ 1-NP. The mutagenicity of the extracts was tested in the Salmonella typhimurium strains TA98 and TA1538, using the microsuspension assay with and without metabolic activation by an exogeneous metabolizing system (rat liver S9-fraction). In addition, the S. typhimurium strains YG1021 and YG1024 were used because of their high sensitivity towards the mutagenicity of nitro polycyclic aromatic hydrocarbons. When plotting the mutagenic potency of the air sample extracts as determined in the absence of liver S9 versus the particle-associated 1-NP level, a relatively high correlation (r = 0.80–0.91) was observed in all of the S. typhimurium strains. High correlations (r = 0.80–0.93) were also observed when plotting the results of mutagenicity testing after activation by S9 versus the outcome of chemical analysis. These results show that the 1-NP content of workplace air samples is associated with their mutagenic potency, suggesting that 1-NP may be used as a marker for occupational exposure to DE-de-rived particle-associated mutagens © 1995 Wiley-Liss, Inc.     

Mutagenicity of blue rayon extracts of fish bile as a biomarker in a field study

Blue rayon (BR) in combination with the Salmonella/microsome assay was used to evaluate the mutagenicity of fish bile samples. Specimens of Mugil curema from two sites were collected over a 1‐year period. Piaçaguera channel contains high concentrations of total polycyclic aromatic hydrocarbons (PAHs) and other contaminants, while Bertioga channel was considered the reference sites in this study. Bile was extracted with BR and tested with TA98, TA100, and YG1041 strains with and without S9 in dose response experiments. PAH metabolite equivalents were analyzed using reverse‐phase high performance liquid chromatography /fluorescence. Higher mutagenic responses were observed for the contaminated site; YG1041 with S9 was the most sensitive strain/condition. Mutagenicity ranged from 3,900 to 14,000 rev./mg at the contaminated site and from 1,200 to 2,500 rev./mg of BR at the reference site. The responses of YG1041 were much higher in comparison with the TA98 indicating the presence of polycyclic compounds from the aromatic amine class that cause frameshift mutation. TA100 showed a positive mutagenic response that was enhanced following S9 treatment at both sites suggesting the presence of polycyclic compounds that require metabolic activation. benzo(a)pyrene, naphthalene, and phenanthrene metabolite equivalents were also higher in the bile of fish collected at the contaminated site. It was not possible to correlate the PAH metabolite quantities with the mutagenic potency. Thus, a combination of the Salmonella/microsome assay with YG1041 with S9 from BR bile extract seems to be an acceptable biomarker for monitoring the exposure of fish to mutagenic polycyclic compounds. Environ. Mol. Mutagen., 2010. © 2009 Wiley‐Liss, Inc.     

A promising Ames battery for mutagenicity characterization of new dyes

When testing new products, potential new products, or their impurities for genotoxicity in the Ames test, the quantity available for testing can be a limiting factor. This is the case for a dye repository of around 98,000 substances the Max Weaver Dye Library (MWDL). Mutagenicity data on dyes in the literature, although vast, in several cases is not reliable, compromising the performance of the in silico models. In this report, we propose a strategy for the generation of high‐quality mutagenicity data for dyes using a minimum amount of sample. We evaluated 15 dyes from different chemical classes selected from 150 representative dyes of the MWDL. The purity and molecular confirmation of each dye were determined, and the microplate agar protocol (MPA) was used. Dyes were tested at the limit of solubility in single and concentration‐response experiments using seven strains without and with metabolic activation except for anthraquinone dyes which were tested with eight strains. Six dyes were mutagenic. The most sensitive was YG1041, followed by TA97a > TA98 > TA100 = TA1538 > TA102. YG7108 as well as TA1537 did not detect any mutagenic response. We concluded that the MPA was successful in identifying the mutagenicity of dyes using less than 12.5 mg of sample. We propose that dyes should be tested in a tiered approach using YG1041 followed by TA97a, TA98, and TA100 in concentration‐response experiments. This work provides additional information on the dye mutagenicity database available in the literature.     

Detection of direct-acting mutagens in ambient air: a comparison of two highly sensitive mutagenicity assays.

Ambient air has been shown to contain numerous hazardous pollutants, many of which are known or suspected carcinogens and mutagens. Bioassays play a prominent role in the characterization of these genotoxic pollutants, and as new test methods are developed, it is incumbent upon researchers to evaluate assay performance and report relative merits. In this study, two Salmonella test methods (the spiral and preincubation assays) were assessed to determine their usefulness as screening methods for monitoring direct-acting mutagens in ambient air. The spiral assay automates the conventional plate-incorporation assay and has been shown to reduce the labor, materials, and sample mass required to perform mutagenicity testing. The preincubation assay has been shown to enhance test sensitivity for certain classes of compound, thereby reducing the amount of sample required for dose-response analysis. Both assays were used to test organic extracts of airborne particulate matter collected in Tokyo during the winters of 1988 and 1990. In addition to the conventional tester strains TA98 and TA100, two newly developed YG strains were evaluated. Strains YG1024 and YG1029-derived from TA98 and TA100, respectively-contain an acetyltransferase plasmid that confers upon the strains greater sensitivity towards nitroarenes. Results from this study indicated that both assays were able to detect direct-acting mutagens in the Tokyo air samples. The mutagenic activity associated with the samples was directly related to the particle mass present in a given volume of air. Mutagenic response was greater in the spiral assay relative to the preincubation assay, especially when YG tester strains were used. The YG strains were significantly more sensitive to mutation than the TA strains in both assays, which suggests that nitroaromatics are an important class of genotoxic contaminant present in Tokyo air.     

LUMO energies and hydrophobicity as determinants of mutagenicity by nitroaromatic compounds in Salmonella typhimurium

Quantitative structure-activity relationships have been derived for the mutagenic activity of 47 nitroaromatic compounds acting on Salmonella typhimurium (TA100) and 66 acting on TA98. The mutagenicity is linearly dependent on the energy of the lowest occupied molecular orbital and bilinearly dependent on the hydrophobicity (octanol/water log P) of the mutagens. The mechanism of action is considered in the light of these findings.     

9-Methoxytariacuripyrone, a naturally occurring nitro-aromatic compound with strong mutagenicity in Salmonella typhimurium

9-Methoxytariacuripyrone, a nitro-aromatic compound isolatedfrom Aristolochia brevipesshowed strong mutagenic activity instrain TA98, TA100 and some YG strains of Salmonella typhimuriumwithand without S9 mix. Incubation with cytosol resulted in a heavyincrease in mutagenicity. When incubated with microsomes theactivity was dramatically decreased. The results are discussedin view of the enzymes possibly involved in activation and detoxificationof the compound. The role of the basic structure on the mutagenicitymediated through the nitro group was also considered.     

Increased mutagenicity of chromium compounds by nitrilotriacetic acid

Nitrilotriacetic acid trisodium salt (NTA), which is a substitute for polyphosphates in household laundry detergents, and N-nitrosoiminodiacetic acid (NIDA), a derivative of NTA produced by metabolism of soil microorganisms, were tested for in vitro mutagenicity in bacteria and yeasts. No gene reversions in five strains of Salmonella typhimurium (TA 1535, TA1537, TA1538, TA98, and TA100), no forward gene mutations in Schizosaccharomyces pombe P1, and no mitotic gene conversions at two loci in Saccharomyces cerevisiae D4 were induced by NTA (up to 870 micrograms/plate or 40 micrograms/ml) and NIDA (up to 2,000 micrograms/plate or 1,000 micrograms/ml), independently of the presence of rat liver metabolic activation. The influence of NTA on the mutagenic and clastogenic activity of several chromium compounds was examined in the Salmonella/microsome assay and in the sister chromatid exchange (SCE) assay in mammalian cell cultures (Chinese hamster ovary [CHO] line). NTA does not affect the genetic inactivity of water-soluble Cr(III) (Cr2[SO4]3) and the direct mutagenicity of soluble Cr(VI) (Na2CrO4,K2Cr2O7) compounds. The very insoluble Cr(VI) compounds PbCrO4 and PbCrO4 X PbO are instead clearly mutagenic in the Salmonella/microsome assay (TA100 strain) only in the presence of NTA or NaOH. The mutagenicity of lead chromates is correlated with the amounts of Cr(VI) solubilized by NTA or alkali, as detected by the colorimetric reaction with diphenylcarbazide and atomic absorption spectrophotometry. In the SCE assay, the insoluble lead chromates are directly clastogenic owing to prolonged treatment conditions and cellular endocytosis. The chromosome-damaging activity of PbCrO4 is significantly increased by NTA but not by NaOH.     

Mutagenicity of resin acids identified in pulp and paper mill effluents using the salmonella/mammalian-microsome assay

Ten resin acids which have been identified as constituents of pulp and paper mill effluents have been examined for potential mutagenicity in the Salmonella/mammalian-microsome assay. Only neoabietic acid has been found to be mutagenic. Neoabietic acid showed dose-related increases in mutagenicity in strains TA1535, TA100, TA1538, and TA98, but not in strain TA1537. Metabolic activation with a preparation of Aroclor 1254-induced liver homogenate (S9) slightly reduced the mutagenic responses. Negative responses were found for abietic acid, dehydroabietic acid, levopimaric acid, 7-oxodehydroabietic acid, monochlorodehydroabietic acid, dichlorodehydroabietic acid, pimaric acid, isopimaric acid, and sandaracopimaric acid.     

Mutagenicity of carbon tetrachloride and chloroform in Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and Escherichia coli WP2uvrA/pKM101 and WP2/pKM101, using a gas exposure method

The volatile solvents carbon tetrachloride and chloroform are carcinogens that are often reported as nonmutagenic in bacterial mutagenicity assays. In this study, we evaluated the mutagenicity of these compounds in Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and Escherichia coli WP2uvrA/pKM101 and WP2/pKM101, with and without S9 mix, using a gas exposure method. Tests were also conducted with a glutathione-supplemented S9 mix. Carbon tetrachloride was mutagenic in TA98 without S9 mix, and in WP2/pKM101 and WP2uvrA/pKM101 with and without S9 mix; carbon tetrachloride was not mutagenic in TA100, TA1535 or TA1537. Chloroform was mutagenic in WP2/pKM101, but only in the presence of glutathione-supplemented S9 mix. Chloroform was not mutagenic in TA98, TA100, TA1535, TA1537, or WP2uvrA/pKM101 with or without S9 mix, and was not mutagenic in TA98, TA100, TA1535, TA1537, or WP2uvrA/pKM101 in the presence of glutathione-supplemented S9 mix. The data indicate that carbon tetrachloride and chloroform are bacterial mutagens when adequate exposure conditions are employed and suggest that a genotoxic mode of action could contribute to the carcinogenicity of these compounds.     

Effects of the nitro-group on the mutagenicity and toxicity of some benzamines

The Ames Salmonella/microsomal assay was employed to test the mutagenicity of some benzamines (aniline, and o- and p-phenylenediamine) and their nitro-derivatives (p-nitroaniline, 2-nitro-p-phenylenediamine 3- and 4-nitro-o-phenylenediamine), using strains TA98) and TA100 and their nitroreductase-deficient mutants, TA98NR and TA100NR, in the presence and absence of rat S9 mix. The addition of the nitro-group to benzamine molecules converted them into direct mutagens. Furthermore, the position of the nitro-group affected their mutagenic activities. Cytotoxicity testing with Chinese hamster ovary cells (CHO-K1) showed that the presence of the nitro-group in these compounds had no specific effect on toxicity. The test compounds all showed a dose-related increase in inducing chromosomal aberrations in CHO cells. However, the presence of the nitro-group did not affect potency in inducing chromosomal aberrations. Compounds containing the nitro-group had higher initial oxidation potentials and dipole moments (μ) than their nonnitro-containing counterparts. The mutagenicity and toxicity of these compounds were not related to physico-chemical properties, including oxidation potential, energy difference (ΔE) between the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO), ionization potential (I.P.), and μ. © 1996 Wiley-Liss, Inc.     

Studies on the induction of gene mutations in bacterial and mammalian cells by the ring-opened benzene metabolites trans,trans-muconaldehyde and trans,trans-muconic acid

t,t-Muconaldehyde and t,t-muconic acid have been investigated for the induction of gene mutations in Salmonella typhimurium (reversion of the his- strains TA97, TA98, TA100, TA102, TA104 and TA1535), Escherichia coli (reversion of the trp- strain WP2 uvrA) and Chinese hamster V79 cells (acquisition of resistance toward 6-thioguanine). t,t-Muconaldehyde proved weakly mutagenic in strain TA104 in the presence and absence of NADPH-fortified postmitochondrial fraction from rat liver homogenate (S9 mix). In strains TA97, TA100 and TA102, weak positive responses were observed only in the presence of S9 mix. In strains TA98, TA1535 and WP2 uvrA, the result was negative. In V79 cells, the mutation frequency was increased from approximately 7 X 10(-6) to 90 X 10(-6) in cultures exposed to t,t-muconaldehyde at optimal concentration (1.7-3 microM in separate experiments). The concentration-response curve showed pronounced hyperlinearity, with no mutagenic effect being observed at a third of the optimal concentration. t,t-Muconic acid was greater than 100 times less toxic than t,t-muconaldehyde in both bacteria and mammalian cells, and it did not show any mutagenic effect. These results complete a previous mutagenicity study, carried out on benzene and 13 metabolites. It is concluded that the newly investigated metabolites cannot account for the bacterial mutagenicity of bioactivated benzene and benzene-trans-1,2-dihydrodiol, since these compounds exhibited their strongest response in strain TA1535. t,t-Muconaldehyde showed similarities in its mutagenicity to p-benzoquinone and hydroquinone. All three compounds showed, at most, weak effects in bacteria, but were strongly mutagenic in V79 cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L.

Studies of the mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L. (Bignoniaceae), were performed using the liquid preincubation method of the Salmonella/microsome test. At the highest dose tested, 100 micrograms/plate, both compounds showed no mutagenicity and no cytotoxicity toward S. typhimurium strains TA98 and TA100 either in the presence or absence of S9 mix. However, these substances were antimutagens toward 2-aminoanthracene, aflatoxin B1 (in TA98), and dimethylnitrosamine (in TA100); but neither substance inhibited the direct mutagenic activity of 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide nor that of sodium azide in strains TA98 and TA100, respectively.     

Mutagenicity tests of fabric-finishing agents in salmonella typhimurium: Fiber-reactive wool dyes and cotton flame retardants

Thirty-nine fabric-finishing agents were tested for mutagenic activity in Salmonella typhimurium. Twenty-four fiber-reactive wool dyes and three acid dyes (not fiber-reactive) were screened by spot tests in strains TA100, TA98, TA1535, and TA1537. Among these dyes, seven bromoacrylamide dyes and one vinyl sulfone dye were mutagenic. Additionally, one of the three acid dyes was mutagenic in spot tests. The mutagenicity of the acid dye was due to an impurity or breakdown product rather than to the dye itself; the origin of the activities of the other dyes is unknown. No mutagenicity was observed among five chlorotriazine or four sulfonyl-ethane sulfonic acid dyes. Eight phosphorus-containing flame retardants (phosphonium, phosphine, phosphine oxide, and phosphonic acid derivatives) and methyl-N-methylolcarbamate, which is employed to obtain a flame-retardant finish on cotton, were tested for mutagenicity in strains TA100, TA98, TA1535, and TA1537, using quantitative incorporation assays. All were nonmutagenic. Two of three bromoalkyl-substituted triazine flame retardants were mutagenic in strains TA100 and TA1535. It is unknown whether this activity is due to impurities or to the parent compound. The flame retardants tested were either in actual commercial use or in experimental development for potential commercial processes. These results indicate the need for early testing of potential fabric-finishing agents and processes.     

Mutagenicity of resin acids identified in pulp and paper mill effluents using the Salmonella/mammalian-microsome assay.

Ten resin acids which have been identified as constituents of pulp and paper mill effluents have been examined for potential mutagenicity in the Salmonella/mammalian-microsome assay. Only neoabietic acid has been found to be mutagenic. Neoabietic acid showed dose-related increases in mutagenicity in strains TA1535, TA100, TA1538, and TA98, but not in strain TA1537. Metabolic activation with a preparation of Aroclor 1254-induced liver homogenate (S9) slightly reduced the mutagenic responses. Negative responses were found for abietic acid, dehydroabietic acid, levopimaric acid, 7-oxodehydroabietic acid, monochlorodehydroabietic acid, dichlorodehydroabietic acid, pimaric acid, isopimaric acid, and sandaracopimaric acid.