Mechanisms of 1,3-butadiene oxidations to butadiene monoxide and crotonaldehyde by mouse liver microsomes and chloroperoxidase

Elfarra, Adnan A.; Duescher, R J; Pasch, Christoph M.

doi:10.1016/0003-9861(91)90036-i

Cited by 61 publications

(42 citation statements)

References 22 publications

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“…The metabolic rate in rat nasal mucosa appeared similar to that observed in liver and lung (54). Recent studies have indicated that myeloperoxidase-mediated metabolism of butadiene may occur in the bone marrow (58).…”

Section: Pharmacokineticssupporting

confidence: 69%

A brief survey of butadiene health effects: a role for metabolic differences.

Birnbaum

1993

Environ Health Perspect

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1,3-Butadiene is a major monomer in the rubber and plastics industry and is one of the highest-production industrial chemicals in the United States. Although not highly acutely toxic to rodents, inhalation of concentrations as low as 6.25 ppm causes tumors in mice. Butadiene is oncogenic in rats, but much higher exposure concentrations are required than in mice. Chronic toxicity targets the gonads and hematopoetic system. Butadiene is also a potent mutagen and clastogen. Differences in the absorption, distribution, and elimination of butadiene appear to be relatively minor between rats and mice, although mice do retain more butadiene and its metabolites after exposure to the same concentration and have a higher rate of metabolic elimination. Recent studies have demonstrated that major species differences appear to occur in the rate of detoxication of the primary metabolite, 3-epoxybutene (butadiene monoepoxide [BDMO]). Mice have the greatest rate of production of BDMO as compared to other species, but the rate of removal of BDMO appears to be less than in other species. Mice have low levels of epoxide hydrolase; rats have intermediate levels; monkeys and humans appear to have high levels of this detoxifying enzyme. Thus, while only low levels of butadiene exposure may result in an accumulation of BDMO in the mouse, much higher levels would be required to result in an elevation of circulating BDMO in other species. The level of this reactive metabolite may be correlated with the species differences in butadiene sensitivity.

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Section: Pharmacokineticssupporting

confidence: 69%

A brief survey of butadiene health effects: a role for metabolic differences.

Birnbaum

1993

Environ Health Perspect

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“…1, production of crotonic acid as a result of BDD exposure suggests the formation of crotonaldehyde. Crotonaldehyde, a Michael acceptor, is a known rodent toxin (Chung et al, 1986;Eder and Eder, 2000), and our laboratory has detected crotonaldehyde in mouse liver microsomes incubated with BD (Elfarra et al, 1991;Sharer et al, 1992). Crotonic acid formation may be low because the oxidation of crotonaldehyde to crotonic acid is competing with other metabolic pathways, such as glutathione conjugation (Gray and Barnsley, 1971) or nonspecific addition of crotonaldehyde to cellular nucleophiles.…”

Section: Discussionmentioning

confidence: 99%

“…The proximity of the internal methylene moiety of 3-butenal to the vinyl and aldehyde moieties makes these internal hydrogens very acidic. As a result, 3-butenal could readily tautomerize to form crotonaldehyde (Elfarra et al, 1991;Duescher and Elfarra, 1993). Crotonaldehyde could then be oxidized to form crotonic acid via aldehyde dehydrogenase.…”

Section: Fig 1 Possible Pathways Of 3-butene-12-diol (Bdd) Metabolmentioning

confidence: 99%

Detection of Carboxylic Acids and Inhibition of Hippuric Acid Formation in Rats Treated With 3-Butene-1,2-Diol, a Major Metabolite of 1,3-Butadiene

Sprague

Elfarra²

2003

Drug Metab Dispos

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Epidemiological studies have indicated that 1,3-butadiene exposure is associated with an increased risk of leukemia. In human liver microsomes, 1,3-butadiene is rapidly oxidized to butadiene monoxide, which can then be hydrolyzed to 3-butene-1,2-diol (BDD). In this study, BDD and several potential metabolites were characterized in the urine of male B6C3F1 mice and SpragueDawley rats after BDD administration (i.p.

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“…It works as an initiator or end product of lipid peroxidation (Kawaguchi-Niida et al, 2006;Pan and Chung, 2002;Esterbauer et al, 1991;Chung et al, 1999Chung et al, , 1996. Furthermore, it can be produced during metabolism of the carcinogens N-nitrosopyrrolidine and 1, 3-butadiene (Sharer et al, 1992;Filser et al, 2001;Elfarra et al, 1991;Elfarra, 1992, 1993;Cheng and Ruth, 1993).…”

Section: Introductionmentioning

confidence: 99%

Acute exposure to crotonaldehyde induces dysfunction of immune system in male Wistar rats

Wang

Yang

et al. 2018

J. Toxicol. Sci.

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-Crotonaldehyde is a ubiquitous air pollutant in the environment. It is reported to be harmful to the biosystems in vivo and in vitro. The exposure to crotonaldehyde irritates the mucous membranes and induces edema, hyperemia, cell necrosis, inflammation, and acute respiratory distress syndrome in the lungs. However, the effects of crotonaldehyde on the immune system have not been reported. In the present study, 6-8 weeks old male Wistar rats were exposed to crotonaldehyde by intratracheal instillation at doses of 4, 8, and 16 μL/kg body weight (b.w.). The general damage in the animals was investigated; the cell counting and the biochemical analysis in the peripheral blood were tested. Furthermore, we investigated the functions of alveolar macrophages (AMs), the alterations of the T-lymphocyte subsets, and the cell composition in the bronchoalveolar lavage fluid (BALF). We found that the activities of the animals were changed after exposure to crotonaldehyde, the cellular ratios and the biochemical components in the peripheral blood were altered, the ratio of mononuclear phagocytes decreased, and the ratios of lymphocytes and granulocytes elevated significantly in BALF. Meanwhile, crotonaldehyde altered the ratio of the T-lymphocyte subsets, and the phagocytic rates and indices of AMs increased obviously. In conclusion, crotonaldehyde induces dysfunction of immune system in male Wistar rats.

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Mechanisms of 1,3-butadiene oxidations to butadiene monoxide and crotonaldehyde by mouse liver microsomes and chloroperoxidase

Cited by 61 publications

References 22 publications

A brief survey of butadiene health effects: a role for metabolic differences.

A brief survey of butadiene health effects: a role for metabolic differences.

Detection of Carboxylic Acids and Inhibition of Hippuric Acid Formation in Rats Treated With 3-Butene-1,2-Diol, a Major Metabolite of 1,3-Butadiene

Acute exposure to crotonaldehyde induces dysfunction of immune system in male Wistar rats

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