Monitoring occupational exposure to styrene from hemoglobin adducts and metabolites in blood.

Christakopoulos, Alexandros; Bergmark, Emma; Zorcec,; Norppa, Hannu; Mäki‐Paakkanen, Jorma; Osterman-Golkar, Siv

doi:10.5271/sjweh.1476

Cited by 51 publications

(34 citation statements)

References 22 publications

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“…Farm er et al (16) have studie d occ upa tio nal ex pos ure to styre ne with a limi ted number of sa mples , but no addu cts have so far been detected. Recently Christ ak opoulos et al (7) found styrene-7,8-oxide addu cts on hem oglobin (mean 28 pm ol · g'") in styrene-exposed wor kers (mean = ± 300 mg . m').…”

Section: Discussionmentioning

confidence: 99%

“…Styrene exposure and urinary mandelic acid levels of the exposed workers in the different units. resulting in the formation of two diastereoisomers of the valine adduct (7 ). After derivatization of the adduct, both isomers were separated by means of gas chromatography on a DB-5-ms capillary column.…”

Section: Optimization Of the Gas Chromatography-mass Spec Trometry Prmentioning

confidence: 99%

“…Brenn er et al (6) fou nd high er adduc t levels in styrene-ex posed wo rkers than in un exposed refere nts. C hris takopou los et al (7) fo und low bu t detectable 45 1…”

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confidence: 99%

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Urinary mandelic acid and hemoglobin adducts in fiberglass-reinforced plastics workers exposed to styrene.

Severi¹,

Pauwels²,

Hummelen³

et al. 1994

Scand J Work Environ Health

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Section: Discussionmentioning

confidence: 99%

Section: Optimization Of the Gas Chromatography-mass Spec Trometry Prmentioning

confidence: 99%

See 1 more Smart Citation

Urinary mandelic acid and hemoglobin adducts in fiberglass-reinforced plastics workers exposed to styrene.

Severi¹,

Pauwels²,

Hummelen³

et al. 1994

Scand J Work Environ Health

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“…kHB can be determined in in vitro experiments and, accordingly, the relationship between AUC and resulting adduct levels can be established. Table 1 presents data on hemoglobin adduct levels from exposure to butadiene and some related compounds (styrene, ethylene, ethylene oxide, and acrylonitrile) in nonsmokers, smokers, and subjects with occupational exposure (52,53,(78)(79)(80)(81)(82). The HBI of butadiene, on the order of 1 x 10-3 pmol/g globin per ppm x hr, is low when compared to the value calculated for rats (50x 10-3), indicating a lower overall efficiency of butadiene in humans than in rats.…”

Section: In Vivo Staility Ofadductsmentioning

confidence: 99%

Biomonitoring of 1,3-butadiene and related compounds.

Osterman-Golkar

Bond²

1996

Environ Health Perspect

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The 1990 Clean Air Act Amendments list several volatile organic chemicals as hazardous air pollutants, including ethylene oxide, butadiene, styrene, and acrylonitrile. The toxicology of many of these compounds shares several common elements such as carcinogenicity in laboratory animals, genotoxicity of the epoxide intermediates, involvement of cytochrome P450 for metabolic activation (except ethylene oxide), and involvement of at least two enzymes for detoxication of the epoxides (e.g., hydrolysis or conjugation with glutathione). These similarities facilitate research strategies for identifying and developing biomarkers of exposure. This article reviews the current knowledge about biomarkers of butadiene. Butadiene is carcinogenic in mice and rats, which raises concern for potential carcinogenicity in humans. Butadiene is metabolized to DNAreactive metabolites, including 1,2-epoxy-3-butene and diepoxybutane. These epoxides are thought to play a critical role in butadiene carcinogenicity. Butadiene and some of its metabolites (e.g., epoxybutene) are volatile. Exhalation of unchanged butadiene and excretion of butadiene metabolites in urine represent major routes of elimination. Therefore, biomonitoring of butadiene exposure could be based on chemical analysis of butadiene in exhaled breath, blood levels of butadiene epoxides, excretion of butadiene metabolites in urine, or adducts of butadiene epoxides with DNA or blood proteins. Mutation induction in specific genes (e.g., HPRT) following butadiene exposure can be potentially used as a biomarker. Excretion of 1,2-dihydroxy-4-(N-acetylcysteinyl-S)butane or the product of epoxybutene with N-7 in guanine in urine, epoxybutene-hemoglobin adducts, and HPRT mutation have been used as biomarkers in recent studies of occupational exposure to butadiene. Data in laboratory animals suggest that diepoxybutane may be a more important genotoxic metabolite than epoxybutene. Biomonitoring methods need to be developed for diepoxybutane and other putative reactive butadiene metabolites. With butadiene and related compounds, the ultimate challenge is to identify useful biomarkers of exposure in which quantitative linkages between exposure and internal dose of the important DNA-reactive metabolites are established. Environ Health Perspect 104(Suppl 5): 907-915 (1996)

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“…Among the proteins, albumin and hemoglobin are the only two proteins that have been studied intensively. GC/MS methods coupled with different techniques, such as Edman degradation (18)(19)(20), macromolecule hydrolysis (21), and Raney nickel reduction (22)(23)(24), have been used in these studies. Albumin and hemoglobin styrene oxide adducts have been identified both in vitro and invivo.…”

Section: Introductionmentioning

confidence: 99%

Development of Polyclonal Antibodies for the Detection of Styrene Oxide Modified Proteins

Wei

Chung

Gee

et al. 2007

Chem. Res. Toxicol.

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Styrene is widely used as one of the most important industrial materials for the production of synthetic rubbers, plastic, insulation, fiberglass, and automobile parts. Inhaled styrene has been reported to produce respiratory toxicity in humans and animals. Styrene oxide, a reactive metabolite of styrene formed via cytochrome P450 enzymes, has been reported to form covalent bonds with proteins, such as albumin and hemoglobin. Among all of the amino acids, cysteine is the most reactive amino acid to be modified by electrophilic species. The purpose of this study is to develop polyclonal antibodies for the detection of styrene oxide cysteinyl protein adducts. Two immunogens were designed, synthesized, and used to induce polyclonal antibodies in rabbits. Immune responses were observed from the raised antibodies by antiserum dilution tests. Competitive ELISA demonstrated that the resulting antibodies specifically recognized the styrene oxide-derived N-acetylcysteine adduct. Western blot results showed that the antibodies recognize styrene oxide-modified albumin. The binding was found to depend on the amount of protein adducts blotted and hapten loading in protein adducts. No cross reaction was observed from the native protein. Competitive Western blots further indicated that these antibodies specifically recognized styrene oxide cysteinyl-protein adducts. Immunoblots revealed the presence of several bands at a molecular weight ranging from 50 to 80 kDa in rat nasal mucosa treated with styrene. In conclusion, we successfully raised polyclonal antibodies to detect styrene oxide-derived protein/cysteine adducts.

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Monitoring occupational exposure to styrene from hemoglobin adducts and metabolites in blood.

Cited by 51 publications

References 22 publications

Urinary mandelic acid and hemoglobin adducts in fiberglass-reinforced plastics workers exposed to styrene.

Urinary mandelic acid and hemoglobin adducts in fiberglass-reinforced plastics workers exposed to styrene.

Biomonitoring of 1,3-butadiene and related compounds.

Development of Polyclonal Antibodies for the Detection of Styrene Oxide Modified Proteins

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