Quantification of N-(3-chloro-2-hydroxypropyl)valine in human haemoglobin as a biomarker of epichlorohydrin exposure by gas chromatography–tandem mass spectrometry with stable-isotope dilution☆

Bader, Michael; Rosenberger, W.; Gutzki, Frank‐Mathias; Tsikas, Dimitrios

doi:10.1016/j.jchromb.2008.11.028

Cited by 17 publications

(11 citation statements)

References 26 publications

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“…As a full SCAN chromatogram of a processed standard of both Nmethyl-and N-ethylvaline showed, there is a very large, co-eluting peak in this part of the chromatogram, suppressing the ionisation of these analytes in NCI-mode and precluding reproducible tandem mass spectrometric determination. The use of modern, highly sensitive and specific tandem mass spectrometry with negative chemical ionisation led to a drastic reduction of LODs compared to previous methods, as recently shown for the haemoglobin adduct of epichlorohydrin [21].…”

Section: General Remarksmentioning

confidence: 99%

Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS

Schettgen

Müller

Fromme³

et al. 2010

Journal of Chromatography B

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Section: General Remarksmentioning

confidence: 99%

Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS

Schettgen

Müller

Fromme³

et al. 2010

Journal of Chromatography B

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“…This was confirmed by investigation of the reaction of GSH with DCP or ECH (unpublished observations). The formation of adducts from reaction of ECH with globin has been described, and several adducts were identified, including 2,3-dihydroxypropylvaline 46 (which is not specific for ECH but can be formed by reaction with glycidol) and chlorohydroxypropylvaline, 47 which, although formed by ECH, could also be formed by reaction of 3-chloro-1,2-propanediol. 46 Therefore, glutathione conjugates, mercapturic acids, or protein adducts could not be used to distinguish DCP and ECH.…”

Section: Discussionmentioning

confidence: 99%

Formation of Epichlorohydrin, a Known Rodent Carcinogen, Following Oral Administration of 1,3-Dichloro-2-propanol in Rats

Waidyanatha

Gaudette

Hong

et al. 2014

Chem. Res. Toxicol.

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The observed toxicity and carcinogenicity of 1,3-dichloro-2-propanol (DCP) in rodents is thought to be due to the formation of reactive metabolites, epichlorohydrin (ECH) and dichloroacetone (DCA). However, there is no direct evidence for the formation of these metabolites from exposure to DCP in rodents due to the challenges of measuring these reactive intermediates directly in vivo. The objective of this work was to investigate the metabolism of DCP to ECH and DCA in vivo by first developing a sensitive analytical method in a suitable biological matrix and analyzing samples from rats administered DCP. DCA reacted rapidly in vitro in rat blood, plasma, and liver homogenate, precluding its detection. Because ECH rapidly disappeared in liver homogenate, but was relatively long-lived in plasma and blood in vitro, blood was selected for analysis of this metabolite. Following a single oral dose of 50 mg/kg DCP in male or female Harlan Sprague–Dawley rats, ECH was detected in blood with a maximum concentration reached at ≤13.7 min. ECH was cleared rapidly with a half-life of ca. 33 and 48 min in males and females, respectively. Following a single oral dose of 25 mg/kg ECH in male and female rats, the elimination half-life of ECH was ca. 34 and 20 min, respectively; the oral bioavailability of ECH was low (males, 5.2%; females, 2.1%), suggesting extensive first pass metabolism of ECH following oral administration. The area under the concentration vs time curve for ECH following oral administration of DCP and intravenous administration of ECH was used to estimate the percent of the DCP dose converted to ECH in rats. On the basis of this analysis, we concluded that in male and female rats following oral administration of 50 mg/kg DCP, ≥1.26% or ≥1.78% of the administered dose was metabolized to ECH, respectively.

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“…Für die beiden Hämoglobinaddukte CHPV und DHPV existieren Verfahren auf Basis des modifizieren Edman-Abbaus mittels GC-MS/MS (Bader et al 2009) und GC-MS (Müller et al 2012). Die Bestimmungsgrenzen liegen jeweils bei 25 pmol/g Globin.…”

Section: Untersuchungsmethodenunclassified

“…Epichlorhydrin bildet die Hämoglobinaddukte N-(2,3-Dihydroxypropyl) -valin (DHPV) (Hindsø Landin et al 1996) sowie N-(3-Chlor-2-hydroxypropyl)-valin (CHPV) (Bader et al 2009). Das Kopplungsprodukt DHPV wird bei der Ratte nach intraperitonealer Gabe von 40 mmol/kg Körpergewicht nachgewiesen (Hindsø Landin et al 1999).…”

Section: Metabolismusunclassified

1‐Chlor‐2,3‐epoxypropan (Epichlorhydrin) [BAT Value Documentation in German language, 2017]

Göen

Bader

Drexler

et al. 2017

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated EKA (exposure equivalents for carcinogenic substances) for epichlorohydrin (CAS‐No 106‐89‐8) in 2017. Available publications are described in detail. In rodents, epichlorohydrin induces malignant lymphomas, hyperplasias, forestomach papillomas and carcinomas, subcutaneous fibromas and lung and pituitary tumours. Epichlorohydrin was classified in category 2 for carcinogenic substances. The substance can easily pass through the skin, so biological monitoring is indicated for a valid individual risk assessment. In several biomonitoring studies the mercapturic acids derivatives N‐acetyl‐S‐(3‐chloro‐2‐hydroxypropyl)‐L‐cysteine (CHPMA) and N‐acetyl‐S‐(2,3‐dihydroxypropyl)‐L‐cysteine (DHPMA) in urine as well as the hemoglobin adducts N‐(3‐chloro‐2‐hydroxypropyl)valine and N‐(2,3‐dihydroxypropyl)valine are suggested as biomarkers after epichlorohydrin exposure. Validated analytical procedures for their quantification are available. Data of a correlation of epichlorohydrin in the air and the CHPMA‐excretion in urine were considered for the evaluation of exposure equivalents for carcinogenic substances. Sampling time is at the end of exposure or end of shift and after long term exposure at the end of the shift after several shifts.

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Quantification of N-(3-chloro-2-hydroxypropyl)valine in human haemoglobin as a biomarker of epichlorohydrin exposure by gas chromatography–tandem mass spectrometry with stable-isotope dilution☆

Cited by 17 publications

References 26 publications

Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS

Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS

Formation of Epichlorohydrin, a Known Rodent Carcinogen, Following Oral Administration of 1,3-Dichloro-2-propanol in Rats

1‐Chlor‐2,3‐epoxypropan (Epichlorhydrin) [BAT Value Documentation in German language, 2017]

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