Monitoring exposure to 4,4′-methylenedianiline by the gas chromatography-mass spectrometry determination of adducts to hemoglobin

Bailey, E.; Brooks, Alan G.; Bird, Ian N.; Farmer, Peter B.; Street, B. W.

doi:10.1016/0003-2697(90)90177-b

Cited by 48 publications

(35 citation statements)

References 20 publications

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“…We have recently developed methods for determining adducts to Hb of 4,4 '-methylenedianiline (MDA) (25) and 4,4'-methylene-bis(2-chloroaniline) (MOCA) (26). These both involve basic hydrolysis of Hb (which liberates 40% ofthe bound dose from its sulfinamide adduct), solvent extraction, conversion to the pentafluoropropionyl derivative, and EI GC-MS SIR, using a deuterated internal standard.…”

Section: Aromatic Aminesmentioning

confidence: 99%

Identification of endogenous electrophiles by means of mass spectrometric determination of protein and DNA adducts.

Farmer

Bailey

Naylor

et al. 1993

Environ Health Perspect

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Monitoring exposure to alkylating agents may be achieved by quantitatively determining the adduct levels formed with nucleic acids and/or proteins. One of the most significant results arising from the application of this approach has been the discovery in control populations of "background" levels of alkylated nudeic acid bases or alkylated proteins, in particular hemoglobin (Hb). In the case of Hb, a wide variety ofsuch adducts have been detected and quantitated by mass spectrometric techniques, with methylated, 2-carboxyethylated, and 2-hydroxyethylated modifications being most abundant. Although the source of these alkylation products is unknown, both endogenous and exogenous sources may be proposed. We have recently confirmed the presence of the N-terminal hydroxyethylvaline adduct in control human Hb using tandem mass spectrometry (MS-MS) and have now established background levels using GC-MS in more than 70 samples. Smoking raises the levels of the adduct up to 10-fold and occupational exposure to ethylene oxide up to 300-fold.Background levels of alkylated nucleic acids may be studied by analysis ofN7-alkylated guanine or N3-alkylated adenine, which are excised from nucleic acids after their formation and are excreted in urine. Although the presence of some of these urinary constituents may be accounted for by their natural occurrence in RNA or diet, the endogenous or exogenous source ofothers is unknown. Quantitative methods using MS-MS have now been developed for five ofthe observed urinary alkylguanines [N7-methyl-, N2-methyl-, N2-dimethyl-, N7-(2-hydroxyethyl)-, and N2-ethylguanine]. A GC-MS method has also been developed to measure urinary thymine glycol as a possible monitor of oxidative DNA damage.

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Section: Aromatic Aminesmentioning

confidence: 99%

Identification of endogenous electrophiles by means of mass spectrometric determination of protein and DNA adducts.

Farmer

Bailey

Naylor

et al. 1993

Environ Health Perspect

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“…Contrary to methods reported earlier (Bailey et al 1990;Schu¨tze et al 1995), no carrier was used during sample preparation in the present work. Nevertheless, the recovery in the overall procedure for all diarylamine derivatives used was between 65% and 88%.…”

Section: Methodological Aspectsmentioning

confidence: 74%

“…For precipitation of hemoglobin we used acetonitrile, instead of ethanol as reported by other authors (Bailey et al 1990;Schu¨tze et al 1995). With acetonitrile smaller amounts of organic solvent are necessary for quantitative precipitation of hemoglobin.…”

Section: Methodological Aspectsmentioning

confidence: 99%

“…However, the limit of detection using HPLC with electrochemically detection is determined mainly by the interference of other substances eluting with DCB or N-acetyl-3,3-dichlorobenzidine (acDCB). To increase the sensitivity and specificity, a method using gas chramatography/mass spectrometry-negative ion chemical ionization detection (GC/MS-NCI) after derivatization with fluorinated anhydrides was developed, based on procedures described for other diarylamines (Bailey et al 1990;Schu¨tze et al 1995). Particular attention was drawn to the following questions, which have been reported to be critical aspects:…”

Section: Introductionmentioning

confidence: 99%

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Determination of dichlorobenzidine-hemoglobin adducts by GC/MS-NCI

Joppich-Kuhn

Hänggi

Sagelsdorff

et al. 1997

International Archives of Occupational and Environmental Health

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A method based on gas chromatography/mass spectrometry-negative ion chemical ionization detection (GC/MS-NCI) was developed for the determination of 3,3'-dichlorobenzidine (DCB)-hemoglobin adducts. Adducts were released from hemoglobin by mild alkaline hydrolysis and determined by GC/MS-NCI after extraction and derivatization with heptafluorobutyric anhydride (HFBA). 2,2'-DCB was used as internal standard and the recovery of the diarylamine derivatives in the overall procedure was 65-88%. The limit of detection attained was below 0.1 ng/g hemoglobin for DCB as well as for the metabolite N-acetyl-3,3'-dichlorobenzidine (acDCB). The method was shown to be linear up to 150 ng/g hemoglobin. In the NCI mass spectra of the HFB derivatives the dominant ion is (M-HF)-. Due to the presence of two chlorines in the diarylamines, the characteristic ratio of 1.5 for m/z 624 to 626 (for diHFB-DCB and diHFB-2,2'-DCB) and m/z 470 to 472 (for HFB-acDCB) can be observed and used for identification. The method was applied to the determination of DCB-hemoglobin adducts formed in young female Wistar rats after treatment for 4 weeks with 0.006%, 0.0012% or 0.00024% DCB via the drinking water. Two adducts were detectable by GC/MS-NCI after alkaline hydrolysis of hemoglobin samples, extraction and derivatization. The structure of these adducts could be assigned to DCB and acDCB by co-chromatography with the synthetic standards and by the presence of the characteristic ion (M-HF)-. Assessment of the time dependence of hemoglobin adduct formation during subchronic treatment with DCB revealed an increase in adduct levels during weeks 1-3. After this time adduct levels essentially remained constant. In hemoglobin samples isolated from animals treated for 4 weeks with DCB a dose-proportional increase in the total amount DCB- and acDCB-hemoglobin adducts from 8.1 ng DCB/g hemoglobin at 0.3 mg/kg body weight per day (0.00024% in drinking water) to 159.9 ng DCB/g hemoglobin at 5.8 mg/kg body weight per day (0.006% in drinking water) was observed. The ratio of the DCB adduct to the acDCB adduct was strongly dose dependent. At low DCB doses the acDCB- and DCB adducts were formed at similar levels, whereas at high DCB doses the DCB adduct was predominant.

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“…Incidentally, it is known that TDI can be easily to be hydrolyzed, and changed to toluene diamine (TDA), although Sabbioni et al 11) also concluded that conjugation is the predominant reaction after TDI exposure in rats, and that TDA is not a primary in vivo reaction product under the conditions they tested. In rats, hemoglobin (Hb) adducts were found to correlate with the administered dose of either MDA (4,4'-methylenedianiline) or MDI [11][12][13] .…”

Section: Mechanisms Of Action After Exposurementioning

confidence: 99%

Review of the occupational exposure to isocyanates: Mechanisms of action

Nakashima

Takeshita

Morimoto

2002

Environ Health Prev Med

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Polyurethanes are useful polymers in a large variety of technical and consumer products that are generally made from diisocyanates and polyols or similar compounds. Toluene diisocyanate (TDI), 4,4'-methylenediphenyl diisocyanate (MDI) and 1,6'-hexamethylene diisocyanate (HDI) are useful for polyurethane products. Isocyanates are reactive chemicals that can be handled without problems in manufacturing or technical environments. In general, consumers may only have contact with these chemicals on rare occasions. The objective of this study was to review the mechanisms of action of inhalation of isocyanates. This paper describes, in summary, the potential occupational exposure to isocyanates, the chemistry and reactivity of isocyanates, the results from genotoxicity studies, investigative toxicity studies, metabolism and results from epidemiology studies on isocyanate-exposed workers. The overall conclusion is that because humans are not exposed to high levels of respiratory isocyanate particles, concerns over the possible development of lung tumors should not be relevant. There are many mechanisms of action induced by isocyanates, but those entities are unclear. This is because these mechanisms act simultaneously and are complex.

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Monitoring exposure to 4,4′-methylenedianiline by the gas chromatography-mass spectrometry determination of adducts to hemoglobin

Cited by 48 publications

References 20 publications

Identification of endogenous electrophiles by means of mass spectrometric determination of protein and DNA adducts.

Identification of endogenous electrophiles by means of mass spectrometric determination of protein and DNA adducts.

Determination of dichlorobenzidine-hemoglobin adducts by GC/MS-NCI

Review of the occupational exposure to isocyanates: Mechanisms of action

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