Mortality Study of Workers in 1,3-Butadiene Production Units Identified from a Chemical Workers Cohort

Ward, Elizabeth; Fajen, J.M.; Ruder, Avima M.; Rinsky, Robert A.; Halperin, William; Fessler-Flesch, Cindy A.

doi:10.2307/3432437

Cited by 10 publications

(5 citation statements)

References 9 publications

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“…6,7 It is one of the constituents in gasoline and is released into the atmosphere due to incomplete combustion of gasoline and diesel fuels. It is identified as a carcinogenic compound for humans 8 as well as rodents. 9,10 It is widely used in manufacturing of synthetic rubber, including neoprene, nitrile rubber, polybutadiene, acrylonitrile−butadiene−styrene resin, styrene−butadiene copolymer, and nylon-6,6.…”

Section: Introductionmentioning

confidence: 99%

Experimental and Theoretical Investigations on the Reaction of 1,3-Butadiene with Cl Atom in the Gas Phase

Vijayakumar

Rajakumar

2017

J. Phys. Chem. A

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Temperature dependent rate coefficients for the reaction of Cl atom with 1,3-butadiene were measured over the temperature range 269-363 K relative to its reaction with isoprene and 1-pentene. Theoretical calculations were performed for the title reaction using CVT/SCT in combination with CCSD(T)/6-31+G (d,p)//MP2/6-311+G(2df,2p) level of theory, to complement our experimental measurements. The test molecule would survive for 1 h in the atmosphere, and therefore, it can be considered as a very short-lived compound. 1,3-Butadience cannot contribute to global warming as it is very short-lived. However, 4 ppm of ozone is estimated to be formed by the test molecule, which can be considered to be reasonably significant.

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Section: Introductionmentioning

confidence: 99%

Experimental and Theoretical Investigations on the Reaction of 1,3-Butadiene with Cl Atom in the Gas Phase

Vijayakumar

Rajakumar

2017

J. Phys. Chem. A

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“…Long-term inhalation exposure to BD (6.25−1000 ppm) has caused tumor formation at multiple organ sites in mice and rats , . Lymphocytic and myelogenous leukemias and non-Hodgkin’s lymphomas have been associated with human occupational exposure , . In addition, exposure to BD is associated with anemia accompanied by bone marrow toxicity and testicular and ovarian atrophy .…”

Section: Introductionmentioning

confidence: 99%

Formation of Mono- and Bis-Michael Adducts by the Reaction of Nucleophilic Amino Acids with Hydroxymethylvinyl Ketone, a Reactive Metabolite of 1,3-Butadiene

Barshteyn

Elfarra

2009

Chem. Res. Toxicol.

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Previously, our laboratory has shown that hydroxymethylvinyl ketone (HMVK), a Michael acceptor oxidation product of the 1,3-butadiene metabolite, 3-butene-1,2-diol, readily reacts with hemoglobin at physiological conditions and that mass spectrometry of trypsin digested peptides suggested adduct formation with various nucleophilic amino acids. In the present study, we characterized reactions of HMVK (3 mM) with three model nucleophilic amino acids (6 and/or 15 mM): N-acetyl-L-cysteine (NAC), L-valinamide, and N-acetyl-L-lysine (NAL). NAC was the most reactive toward HMVK followed by L-valinamide and NAL. HMVK incubations with each amino acid at pH 7.4, 37°C resulted in formation of a mono-Michael adduct. In addition, HMVK incubated with NAL gave rise to two additional bis-Michael adducts characterized by LC/MS, LC/MS/MS, 1H NMR, and 1H-detected heteronuclear single quantum correlation (HSQC). The relative ratios of areas of NAL monoadduct (adduct 1) and diadducts (adducts 2 and 3) at 6 h were 49, 21, and 30% of total product area, respectively. Formation of adduct 2 was dependent upon the presence of both adduct 1 and HMVK whereas formation of adduct 3 was dependent upon presence of adduct 2 only. Monoadducts were formed by a Michael addition reaction of one HMVK moiety with nucleophilic amino acid whereas NAL diadducts were products of two Michael addition reactions of 2 HMVK moieties followed by enolization and formation of an octameric cyclic product. NAL diadduct (adduct 3) was formed by loss of a water molecule from adduct 2 followed by autooxidation of one of the hydroxy groups yielding a diketone conjugated system. Collectively, our results provide strong evidence that HMVK can react with various nucleophilic residues and form different types of adducts suggesting that a variety of proteins may be subjected to these modifications which could result in loss of protein function.

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“…With growing concerns about the potential risks to humans from exposure to BD, numerous epidemiologic studies of occupational workers exposed to BD have been performed. However, findings regarding BD carcinogenicity in humans have been equivocal, perhaps partly because reliable exposure assessment is lacking (6)(7)(8)(9).…”

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confidence: 99%

Human Physiologic Factors in Respiratory Uptake of 1,3-Butadiene

Lin¹,

Smith²,

Kelsey³

et al. 2001

Environmental Health Perspectives

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Articles 1,3-Butadiene (BD), a suspected human carcinogen, is used as the raw material in industries to make synthetic butyl rubber and plastics. Simulation models using experimental animal data have shown that physiologic factors play an important role in the kinetic behavior of BD. However, human data are limited. The aim of this inhalation study was to identify influential human physiologic factors in the respiratory uptake of BD. We recruited 133 healthy volunteers in Boston, Massachusetts, into this study and tested them under an approved human subjects protocol. Each subject was exposed to 2 ppm (4.42 mg/m 3) BD for 20 min, followed by purified air for another 40 min. Five exhaled breath samples collected during exposure were used to determine the respiratory uptake of BD, which was defined as absorbed BD (micrograms) per kilogram of body weight during exposure. Although subjects were given identical administered doses (40 ppm/min), there was a wide range of uptake, 0.6-4.9 µg/kg. Of the studied physiologic factors, the blood:air partition coefficient and alveolar ventilation were most significant in determining the respiratory uptake (p < 0.001 for each). In addition, in the multiple regression analysis, females had significantly higher respiratory uptake of BD than males on a weight basis. For all subjects, increasing age and cigarette smoking led to significantly decreased respiratory uptake of BD. The results of this human study are consistent with previous kinetic simulations and animal studies. The findings also suggest that interindividual variation in human physiologic factors that affect the exposure-internal dose relationship should be considered while also exploring exposure-disease associations in future epidemiologic research.

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Mortality Study of Workers in 1,3-Butadiene Production Units Identified from a Chemical Workers Cohort

Abstract: We thank David A. Dankovic for assistance in interpreting the toxicologic data and Bernice Vehr and the support group of the Industrywide Studies Branch at NIOSH for meticulously coding study information.

Cited by 10 publications

References 9 publications

Experimental and Theoretical Investigations on the Reaction of 1,3-Butadiene with Cl Atom in the Gas Phase

Experimental and Theoretical Investigations on the Reaction of 1,3-Butadiene with Cl Atom in the Gas Phase

Formation of Mono- and Bis-Michael Adducts by the Reaction of Nucleophilic Amino Acids with Hydroxymethylvinyl Ketone, a Reactive Metabolite of 1,3-Butadiene

Human Physiologic Factors in Respiratory Uptake of 1,3-Butadiene

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