title: Mercapturic acids as metabolites of alkylating substances in urine samples of German inhabitants.
abstract: Hydroxyalkyl mercapturic acids (HAMA) are the main urinary metabolites of several alkylating substances that possess a carcinogenic potential, like acrolein, 1,3-butadiene, ethylene oxide, propylene oxide and glycidol. These alkylating substances are used extensively in industrial processes, but they do also occur environmentally, e.g. in tobacco smoke. The aim of this study was the determination of six HAMA, as biomarkers of exposure, in human urine of smokers and non-smokers. We applied a sensitive analytical method, using hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS) for the determination of 2-hydroxyethyl mercapturic acid (HEMA, biomarker for ethylene oxide), 2-hydroxypropyl mercapturic acid (2-HPMA, biomarker for propylene oxide), 3-hydroxypropyl mercapturic acid (3-HPMA, biomarker for acrolein), 2,3-dihydroxypropyl mercapturic acid (DHPMA, biomarker for glycidol) as well as 3,4-dihydroxybutyl mercapturic acid and 3-monohydroxybutenyl mercapturic acids (DHBMA and MHBMA, biomarkers for 1,3-butadiene). Background concentrations of four HAMA were detected in each urine sample we analyzed. The mercapturic acids HEMA and MHBMA were detected in 55% and 10% of the samples, respectively. In the urine of non-smokers (n = 54) we observed median levels of 206, 1.6, 12.1, 146, 159, and <5.0 μg/g creatinine for DHPMA, HEMA, 2-HPMA, 3-HPMA, DHBMA and MHBMA, respectively. Among smokers (n = 40) median levels of DHPMA, HEMA, 2-HPMA, 3-HPMA, DHBMA and MHBMA were determined to be 217, 4.9, 46.2, 884, 211 and <5.0 μg/g creatinine, respectively. The excretion rate of the biomarkers HEMA, 2-HPMA and 3-HPMA was distinctly higher in smokers than in non-smokers. Furthermore, our study revealed a comparatively high background level of DHPMA in urine of smokers and non-smokers whose origin is still unknown. The presented data may contribute to the evaluation of reference values for urinary HAMA levels in the general population.
authors: Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-University of Erlangen-Nuremberg, Schillerstrasse 25/29, D-91054 Erlangen, Germany.
authors: Elisabeth
authors: E
authors: Eckert
authors: Klaus
authors: K
authors: Schmid
authors: Barbara
authors: B
authors: Schaller
authors: Kerstin
authors: K
authors: Hiddemann-Koca
authors: Hans
authors: H
authors: Drexler
authors: Thomas
authors: T
authors: Göen
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism / Q000652:urine*; D000293:Adolescent; D000328:Adult; D000477:Alkylating Agents / Q000378:metabolism / Q000652:urine*; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D003404:Creatinine / Q000652:urine; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000378:metabolism / Q000652:urine*; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012907:Smoking / Q000378:metabolism; D055815:Young Adult
chemical_list: D000477:Alkylating Agents; D015415:Biomarkers; D004785:Environmental Pollutants; D003404:Creatinine; D000111:Acetylcysteine