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Background In recent years, due to the global shortage of helium gas, the development of gas chromatography (GC) analytical methods using alternatives to helium carrier gases is necessary. Objective The objective of this study was to examine the applicability of hydrogen and nitrogen as alternative carrier gases using the test method for azo compounds in the Act on Control of Household Products Containing Harmful Substances of Japan. Method The gas chromatograph mass spectrometer (GC-MS) analytical method using hydrogen and nitrogen as alternative carrier gases was compared with a method using helium for 26 primary aromatic amines (PAAs) originated from azo dyes. Results When hydrogen and nitrogen were used as carrier gases under the same conditions used during analysis using helium (same column, gas flow rate, oven temperature conditions, etc.), sufficient peak separation of 26 PAAs was obtained. The sensitivities of the methods using helium and hydrogen were comparable, whereas the sensitivity was lower when nitrogen was used, with the detection limits ranging from 1/220 to 1/25. However, all carrier gases achieved quantification at concentrations below the standard value (30 μg/g) of the Act on Control of Household Products Containing Harmful Substances, and the results were in agreement with the standard value for the target product. Conclusions Our results indicated that hydrogen or nitrogen can be used as alternative carrier gases to helium for GC-MS analysis of azo compounds producing specific aromatic amines. Highlights Using hydrogen or nitrogen as an alternative carrier gas to helium, azo compounds could be quantified with excellent accuracy. [ABSTRACT FROM AUTHOR]

The reduction of nitroarenes to arylamines is a synthetically important transformation both in the laboratory and in industry. Herein, Palladium (Pd) nanoparticles were synthesized via incorporation with mesoporous fumed silica material by doping technique. Water was used as a solvent and the as-synthetized material was reduced by using NaBH4 to ensure the total transformation of PdO into Pd nanoparticles. The synthesized sample was characterized by using inductively coupled plasma (ICP) elemental analysis, X-ray powder diffraction (XRD), N2 sorption measurement, scanning electron microscope (SEM), energy-dispersive spectroscopy (EDX), and transmission electron microscopy (TEM). Data showed that the Pd nanoparticles were successfully synthesized and supported on the mesoporous silica with an average size in the ranges of 10–20 nm, with an irregular shape. The purity of the synthesized sample was confirmed by EDX analysis which exhibits the presence of Si, O, and Pd. The catalytic activity of the prepared sample was evaluated in the heterogeneous reduction of nitroarenes to aromatic amines. Reduction reaction was monitored by Shimadzu GC-17A gas chromatography (GC, Japan) equipped with flam ionization detector and RTX-5 column, 30 m × 0.25 mm, 1-μm film thickness. Helium was used as carrier gas at flow rate 0.6 mL/min. Interestingly, the green hydrogenation of nitroarenes to primary amine compounds was achieved in an aqueous solution with high efficiency and in a short time; moreover, the reusability of heterogeneous Pd-SiO2 was performed for four repeated cycles with more than 88% of efficiency at the fourth run. Finally, the heterogeneity of catalysis with high reliability and eco-friendly processes is a super new trend of nitroarenes reduction in the industry and economic scales. [ABSTRACT FROM AUTHOR]

Purpose: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). Methods: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. Results: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7–104.3) and apparent dose–response relationships were revealed between the SIR and the surrogate exposure level in the 0–10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose–response relationships were observed. Conclusions: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa. [ABSTRACT FROM AUTHOR]

Heterocyclic aromatic amines (HAAs), which are formed from the reaction of creatine or creatinine, amino acids, and sugars in meat and fish cooked at high temperatures, have been shown to be mutagenic in bacterial assays and carcinogenic in animal models. Following advances in the dietary assessment of HAA intake in epidemiological studies - including development of a validated meat-cooking module and a specialized food composition database - a number of epidemiological studies have specifically examined the association of HAA intake and cancer risk, most of which were conducted in Western countries. Given that dietary habits and cooking methods differ across countries, however, epidemiological investigation of dietary HAA intake requires a population-specific assessment method. Here, we developed a practical method for assessing dietary HAA intake among Japanese using a food frequency questionnaire (FFQ) and evaluated its validity for use in epidemiological studies by comparison with 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) levels in human hair. The Japan Public Health Center-based Prospective Study reported that daily intake of HAAs among Japanese was relatively low, and that more than 50% of total intake in mainland Japan was derived from fish. Only four case-control studies in Japan have been reported so far, for colorectal, stomach and prostate cancer, and colorectal adenoma. A statistically significant positive association was found between 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ) and the risk of colorectal adenoma and between individual and total HAAs and the risk of prostate cancer. In contrast, no association was observed for colorectal or stomach cancer, or for colorectal adenoma among men. We also found that the limited and inconsistent findings among epidemiological studies are due to the difficulty in assessing exposure levels of HAAs. In addition to further evidence from prospective cohort studies in Japanese based on dietary HAA intake estimated by FFQs, studies using other methods to assess HAA exposure, such as biomarkers, are highly anticipated. [ABSTRACT FROM AUTHOR]

Recent epidemiological studies have indicated that occupational exposure to the aromatic amine acetoaceto-o-toluidide (AAOT) was associated with a marked increase in urinary bladder cancers in Japan. However, little is known about the carcinogenicity of AAOT. To evaluate the urinary bladder carcinogenicity of AAOT, male and female F344 rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks followed by dietary administration of 0, 0.167, 0.5, or 1.5% AAOT for 31 weeks. The incidences and multiplicities of bladder tumors were significantly increased in the 0.5 and 1.5% groups of male and female rats in a dose-response manner. AAOT and seven downstream metabolites were detected in the urine of the male and female rats administered AAOT with levels increasing in a dose-dependent manner. The most abundant urinary metabolite of AAOT was the human bladder carcinogen o-toluidine (OTD), which was at least one order of magnitude higher than AAOT and the other AAOT metabolites. In a second experiment, male F344 rats were administered 0, 0.167, or 1.5% AAOT for 4 weeks. Gene expression analyses revealed that the expression of JUN and its downstream target genes was increased in the urothelium of male rats treated with 1.5% AAOT. These results demonstrate that AAOT promotes BBN-induced urinary bladder carcinogenesis in rats and suggest that overexpressed of JUN and its downstream target genes may be involved the bladder carcinogenicity of AAOT. In conclusion, AAOT, like other carcinogenic aromatic amines, is likely to be a carcinogen to the urinary bladder, and OTD metabolized from AAOT is the ultimate carcinogen. [ABSTRACT FROM AUTHOR]

The Japanese Ministry of Health, Labour, and Welfare recently reported an outbreak of bladder cancer among workers who handled aromatic amines in Japan. 2,4-dimethylaniline (2,4-DMA) is one of the chemicals that workers are considered to have the most opportunities to be exposed. Genotoxic events are known to be crucial steps in the initiation of cancer. However, studies on the genotoxicity of 2,4-DMA are limited, particularly studies investigating the mechanism behind the genotoxicity by 2,4-DMA are completely lacking. We examined genotoxic properties of 2,4-DMA using phosphorylated histone H2AX (γ-H2AX), a sensitive and reliable marker of DNA damage, in cultured human urothelial and hepatic cells. Our results clearly showed that 2,4-DMA at a concentration range of 1-10 mM generates γ-H2AX in both cell lines, indicating that 2,4-DMA is genotoxic. During mechanistic investigation, we found that 2,4-DMA boosts intracellular reactive oxygen species, an effect clearly attenuated by disulfiram, a strong inhibitor of cytochrome P450 2E1 (CYP2E1). In addition, CYP2E1 inhibitors and the antioxidant, N-acetylcysteine, also attenuated γ-H2AX generation following exposure to 2,4-DMA. Collectively, these results suggest that γ-H2AX is formed following exposure to 2,4-DMA via reactive oxygen species produced by CYP2E1-mediated metabolism. Continuous exposure to genotoxic aromatic amines such as 2,4-DMA over a long period of time may have contributed to the development of bladder cancer. Our results provide important insights into the carcinogenicity risk of 2,4-DMA in occupational bladder cancer outbreaks at chemical plants in Japan. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify the actual condition of 26 types of carcinogenic primary aromatic amines (PAAs) originated from azo dyes in commercial textile products in Japan. In the case of textiles made of various fibers of various colors, the fibers were separated by color and analyzed. A total of 86 textile products (117 samples) were analyzed. Twenty-one kinds of PAAs were detected in the samples and almost all the PAAs were detected at low concentrations. However, the concentrations of benzidine, 3,3'-dimethoxybenzidine, and 2,4-diaminotoluene (56-440 μg g-1) in placemats made of cotton were found to exceed EU regulation limits of 30 μg g-1. Although such placemats do not always come into contact with the user's skin, it is thought that they should be handled more carefully. Finally, 7 products (8 samples) contained PAAs at concentrations that exceeded the regulation limits. Two sample preparation methods (with and without solvent extraction) were performed on the same sample in order to compare the PAAs in samples in which it is difficult to separate the component materials, such as a cotton fabric that contained polyester fibers. In a comparison of the results obtained from the two methods, it was observed that the concentrations and/or kinds of PAAs detected in the samples were different. It was therefore thought that textile products that present this particular challenge should be analyzed by both methods. [ABSTRACT FROM AUTHOR]

Photochemical reactions of dissolved organic compounds, fluorescent dissolved organic matter (FDOM) in particular, are implicated as an important source of peroxides, but their contribution to overall peroxide formation is not well understood. We studied the photochemical formation of peroxides (hydrogen peroxide and organic peroxides), together with changes in fluorescent properties of water-soluble fraction (WSF) solutions of bulk aerosols (n=28) collected in Okinawa, Japan. Monochromatic wavelengths of 313, 334, 366, and 405nm were used to examine the samples, and the changes in peroxide concentrations and fluorescence intensities (FIs) during these illuminations were measured. For many samples, two peaks of fluorescence were found in the WSF solutions at excitation/emission wavelengths (Ex/Em) of 250–275/375–455 and 300–320/400–440nm, which can be signatures for fulvic acid-like compounds. Several samples collected between November and April (winter samples) showed another fluorescence peak at 260–290/305–345nm, which could be due to the presence of aromatic amines. As illumination time increased, the peroxide concentrations increased and the FI changed, but not uniformly. The FI and peroxide photo-production rates were only weakly correlated (R<0.36), and the correlation between FI and dissolved organic carbon (DOC) concentrations was also weak (R<0.75). These results suggest that the photochemistry of FDOM may not comprise a dominant pathway to form peroxides in the WSF solutions, but that peroxides are formed as a result of complex processes in the WSF solutions of aerosols collected in Okinawa. [Copyright &y& Elsevier]

• The Ames test as a bio-detector for drug-metabolizing studies. • Gene cloning of bacterial enzymes to improve the sensitivity of Ames tester strains. • DNA polymerases in E. coli and Salmonella typhimurium. • Transgenic rodent gene mutation assays to examine the Ames test results in vivo. I first became acquainted with the Ames test at the very beginning of my career in 1978, when my task at the National Institute of Health Sciences (Tokyo) was to screen for mutagenicity of food additives used in Japan, using the Ames test. I also used this test to research the metabolic activation mechanisms of chemical carcinogens, in particular, the analgesic drug, phenacetin. This chemical was not mutagenic in Salmonella typhimurium TA100 with standard 9000 × g supernatant of liver homogenates (S9) from rat but was mutagenic with hamster S9. It was revealed that hamster S9 had much higher deacetylation activities than rat S9, which accounts for the species difference. Then, my work was focused on molecular biology. We cloned the genes encoding nitroreductase and acetyltransferase in Salmonella typhimurium TA1538. Plasmids carrying these genes made strain TA98 more sensitive to mutagenic nitroarenes and aromatic amines. Because of their high sensitivity, the resulting strains such as YG1021 and YG1024 are widely used to monitor mutagenic nitroarenes and aromatic amines in complex mixtures. Later, we disrupted the genes encoding DNA polymerases in TA1538 and classified chemical mutagens into four classes depending on their use of different DNA polymerases. I was also involved in the generation of gpt delta transgenic rodent gene mutation assays, which examine the results of the Ames test in vivo. I have unintentionally developed my career under the influence of Dr. Ames and I would like to acknowledge his remarkable achievements in the field of environmental mutagenesis and carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Red meat and processed meat consumption are established risk factors for colorectal cancer. One hypothesized mechanism for this association is through exposure to heterocyclic aromatic amines (HAAs), which are formed when meat is cooked at high temperature for a long duration. Although they are mutagenic and carcinogenic in nonhuman primates, the findings of epidemiologic studies that have specifically examined the association between HAA intake and colorectal cancer risk have been inconsistent. Moreover, since N -acetyltransferase 2 (NAT2) has been shown to play a critical role in the bioactivation of HAAs, an interaction between HAA intake and NAT2 on colorectal cancer has been hypothesized and the findings in the previous studies have been inconsistent. Aim: To investigate the association of meat- and fish-derived HAA intake, which were estimated by our validated food frequency questionnaire and population-specific data on HAA contents in meat and fish items with the risk of colorectal adenoma, precursor of colorectal cancer, among middle-aged and elderly Japanese in Japan and Japanese Brazilians in Sao Paulo. In addition, to test the modifying effect of NAT2 on the association of HAA intake on colorectal adenoma risk. Methods: Tokyo adenoma study includes 738 patients with adenoma and 697 controls who underwent total colonoscopy in National Cancer Center, Japan. Brazil adenoma study includes 316 patients with adenoma and 403 controls who underwent total colonoscopy in 2 hospitals in Sao Paulo. HAA intake was estimated from meat and fish intake based on an HAA database that was validated against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) values measured in human hair. NAT2 acetylation genotype was inferred using 2 SNPs in the NAT2 gene. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence interval (CI) for the association between HAA intake and colorectal adenoma risk after adjusting for potential confounders. Results: Tokyo adenoma study showed that high intake of 2-amino-3,4-dimethylimidazo[4, 5-f]quinoline (MeIQ) and total HAA was significantly associated with an increased risk of colorectal adenoma in women but not in men. No clear association with PhIP or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intakes and no effect modification by NAT2 genotype was observed. Brazil adenoma study found no association for HAAs and no effect modification by NAT2 genotype. Conclusion: Tokyo Adenoma Study suggests that high MeIQ and total HAA intakes are positively associated with colorectal adenoma risk among Japanese women in Japan. However, Brazil adenoma study failed to observe positive associations. The possible explanations of inconsistent findings and the difficulty of the studies will be discussed. [ABSTRACT FROM AUTHOR]