Cardiovascular mortality among munitions workers exposed to nitroglycerin and dinitrotoluene.

Stayner, Leslie T.; Dannenberg, Andrew L.; Thun, Michael J.; Reeve, Gordon R.; Bloom, Thomas F.; Boeniger, Mark F.; Halperin, William

doi:10.5271/sjweh.1610

Cited by 23 publications

(21 citation statements)

References 14 publications

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“…The U.S. Environmental Protection Agency established a cancer slope factor (equal to the upper limit of the lifetime probability that a cancer-causing chemical will cause cancer at a dose of 1.0 mg/kg/d) of 0.23, 0.68, 0.68, and 0.03 (mg/kg/d) À1 , for 2NT, 24DNT, 26DNT, and TNT, respectively (www.epa.gov/iris). An excess of hepatobiliary cancer was found among munitions workers exposed to DNT (2). The incidence of urothelial and renal cancer cases found in miners exposed to explosives containing DNT was increased by a factor of 4.5 and 14.3, respectively (3).…”

Section: Introductionmentioning

confidence: 84%

Biomarkers of Exposure, Effect, and Susceptibility in Workers Exposed to Nitrotoluenes

Sabbioni

Jones

Sepai

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Nitrotoluenes, such as 2-nitrotoluene, 2,4-dinitrotoluene (24DNT), and 26DNT, are carcinogenic in animal experiments. Humans are exposed to such chemicals in the workplace and in the environment. It is therefore important to develop methods to biomonitor people exposed to nitrotoluenes to prevent the potential harmful effects. For the present study, workers exposed to high levels of these chemicals were investigated. The external dose (air levels), the internal dose (urine metabolites), the biologically effective dose [hemoglobin (Hb) adducts and urine mutagenicity], and biological effects (chromosomal aberrations and health effects) were determined. Individual susceptibility was assessed by determining genetic polymorphisms of enzymes assumed to function in nitrotoluene metabolism, namely glutathione S-transferases (GSTM1, GSTT1, GSTP1), N-acetyltransferases (NAT1, NAT2), and sulfotransferases (SULT1A1, SULT1A2). The levels of urinary metabolites did not correlate with the air levels. The urinary mutagenicity levels determined in a subset of workers correlated with the levels of a benzylalcohol metabolite of DNT. The Hbadducts correlated with the urine metabolites but not with the air levels. The frequency of chromosomal aberrations (gaps included) was increased (P < 0.05) in the exposed workers in comparison with a group of factory controls and correlated with the level of 24DNT Hb-adducts in young subjects (<31 years). The GSTM1-null genotype was significantly more prevalent in the controls than in the exposed group, which probably reflected an elevated susceptibility of the GSTM1-null genotype to adverse health effects of DNT exposure, such as nausea (odds ratio, 8.8; 95% confidence interval, 2.4-32.2). A statistically significant effect was seen for SULT1A2 genotype on a 24DNT Hb-adduct; GSTP1 genotype on a 2,4,6-trinitrotoluene Hb-adduct; and SULT1A1, SULT1A2, NAT1, GSTT1, and GSTP1 genotypes on chromosomal aberrations in the exposed workers.

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Section: Introductionmentioning

confidence: 84%

Biomarkers of Exposure, Effect, and Susceptibility in Workers Exposed to Nitrotoluenes

Sabbioni

Jones

Sepai

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…2,4-DNT induced cancers and has toxic effects on reproductive organs in rats (3,4). Hepatobiliary cancer and urethal tumor possibly caused by DNT exposure were found in workers at munition facilities and miners who have used dinitrotoluenes as the explosive in underground copper mining (5,6). 2,4-DNT was cytotoxic, but less so than TNT, in H4IIE rat hepatoma cell cultures (7).…”

Section: Introductionmentioning

confidence: 97%

Phytotransformation of 2,4‐Dinitrotoluene in Arabidopsis thaliana: Toxicity, Fate, and Gene Expression Studies in Vitro

Yoon¹,

Oliver²,

Shanks³

2006

Biotechnology Progress

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Basic knowledge of the plant transformation pathways and toxicity of 2,4-dinitrotoluene (2,4-DNT) will assist in the design and assessment of a phytoremediation strategy. This study presents the toxicity and fate of 2,4-DNT and gene expression in response to 2,4-DNT exposure using the model plant Arabidopsis thaliana, an increasingly popular system for genetic and biochemical studies of phytotransformation of explosives. From the results of biomass and root growth assays for toxicity, 2,4-DNT was toxic to the plants at concentrations as low as 1 mg/L. In the uptake study, 95% of the initial 2,4-DNT was removed by 15-day-old seedlings from liquid media regardless of the initial 2,4-DNT concentrations while 30% accounted for the adsorption to the autoclaved plant materials. The mass balance was over 86% using [U-14C]2,4-DNT, and the mineralization by the plants was less than 1% under sterile conditions during 14 days of exposure. The percentage of the bound radioactivity increased from 49% to 72% of the radioactivity in the plants, suggesting transformed products of 2,4-DNT may be incorporated into plant tissues such as lignin and cellulose. Monoaminonitrotoluene isomers and unknown metabolites with short retention times were detected as transformed products of 2,4-DNT by the plants. Most (68%) of the radioactivity taken up by the plants was in the root tissues in nonsterile hydroponic cultures. Glutathione and expression of related genes (GSH1 and GSH2) in plants exposed to 2,4-DNT were 1.7-fold increased compared to untreated plants. Genes of a glutathione S-transferase and a cytochrome P450, which were induced by 2,4,6-trinitrotoluene exposure in previous studies, were upregulated by 10- and 8-fold, respectively. The application of phytoremediation and the development of transgenic plants for 2,4-DNT may be based on TNT phytotransformation pathway characteristics because of the similar fate and gene expression in plants.

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“…The toxic effects of nitrate esters on a variety of animal species (cats, rabbits, rats, and aquatic organisms) have been reviewed (Johansson et al 1987;Ellis et al 1984;Imoto et al 1986;Lowry et al 2001;Zalta et al 1985;Tai and Tsuruta 1997). In humans the most prominent manifestations of nitrate esters toxicity are severe headaches and adverse cardiovascular effects, including organic nitrate dependence in the case of chronic exposure (Kanerva et al 1991;Lamm et al 1993;Fukuchi 1981;Santoro et al 2001;Stayner et al 1992).…”

Section: Introductionmentioning

confidence: 98%

Toxic effect of nitroesters on plant tissue cultures

Podlipná

Fialová

Vaněk

2008

Plant Cell Tiss Organ Cult

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Nitroglycerine (NG) is used in manufacture of dynamite, gunpowder, and rocket propellants, and as a therapeutic agent primarily to angina pectoris. Ethylene glycol dinitrate (EGDN) is an explosive ingredient (60-80%) in dynamite along with nitroglycerine (40-20%). Both compounds are pollutants, and due to recalcitrance to biodegradation they persist in the environment. In our study we concentrated on the phytotoxicity of these compounds, looking in particular at their effects on germination, growth and development. We used mustard (Sinapis alba) seedlings, in vitro cultivated regenerants of Juncus inflexus and Phragmites australis and suspension cultures of flax (Linum usitatissimum). The flax cells absorbed NG and transformed it to both dinitroglycerine isomers. By measuring their effect on the length of primary root of white mustard seedlings we demonstrated that the toxicity of these degradation products was lower than the original compound. The phytotoxic effect of EGDN on wetland plant species is described for the first time. High concentrations of EGDN (500 mg l -1 and higher) in the medium induced wilting and browning and subsequent death of reed and rush plants.

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Cardiovascular mortality among munitions workers exposed to nitroglycerin and dinitrotoluene.

Cited by 23 publications

References 14 publications

Biomarkers of Exposure, Effect, and Susceptibility in Workers Exposed to Nitrotoluenes

Biomarkers of Exposure, Effect, and Susceptibility in Workers Exposed to Nitrotoluenes

Phytotransformation of 2,4‐Dinitrotoluene in Arabidopsis thaliana: Toxicity, Fate, and Gene Expression Studies in Vitro

Toxic effect of nitroesters on plant tissue cultures

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