Reference range concentrations of N-acetyl-S-(2-hydroxyethyl)-L -cysteine, a common metabolite of several volatile organic compounds, in the urine of adults in the United States

Abstract

N-acetyl-S-(2-hydroxyethyl)-L-cysteine (2-hydroxyethyl mercapturic acid, HEMA) is a urinary metabolite of several hazardous chemicals, including vinyl chloride (VC), ethylene oxide (EO), and ethylene dibromide (EDB). Information about the levels of HEMA in the general population is useful for assessing human exposures to HEMA parent compounds, including VC, EO, and EDB. To establish reference range concentrations for HEMA, we analyzed urine samples from 412 adult participants in the Third National Health and Nutrition Examination Survey (NHANES III) by using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). HEMA was detected in 71% of the samples examined. Creatinine-corrected concentrations ranged from less than 0.68 g/g creatinine to 58.7 g/g creatinine; the 95th percentile concentration was 11.2 g/g creatinine; and the geometric mean and median creatinine-corrected concentrations were both 1.6 g/g creatinine. We observed a statistically significant difference (P=0.0001) in the creatinine-corrected geometric mean concentration values of HEMA between smokers (2.8 g/g creatinine) and nonsmokers (1.1 g/g creatinine). The high levels of HEMA seen among smokers likely originated from HEMA-producing chemicals known to be present in tobacco smoke.

Exposure to Ethylene Oxide in Hospitals: Biological Monitoring and Influence of Glutathione S-Transferase and Epoxide Hydrolase Polymorphisms

“…This agrees well with the median concentrations of 1.1 and 2.9 Ag/g creatinine, respectively, found by Calafat et al (19) in the frame of the National Health and Nutrition Examination Survey by isotope dilution high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.…”

“…Furthermore, HEMA in frozen urine samples seems to be stable, as suggested by Barr and Ashley (28). Finally, the median concentrations found in this study were very comparable with those reported by Calafat et al (19), which does not suggest that conservation over a 2-year period could have been a source of bias.…”

“…Owing to the scarcity of published results (17)(18)(19), power calculations were impossible. An expert opinion based on similar studies suggested that a true difference in metabolite concentrations could be detected by comparing 20 exposed and 20 control subjects.…”

Mercapturic acids revisited as biomarkers of exposure to reactive chemicals in occupational toxicology: a minireview

“…The potential interest of such biomarkers remains to be assessed, as for 1,3-butadiene, allyl chloride and 1,3-dichloropropene, in field or controlled studies to propose biological exposure indices. This is the case for the metabolite of ethylene oxide, 2-hydroxyethylmercapturic acid (HEMA), which is also a metabolite of vinyl chloride and ethylene dibromide (Calafat et al 1999;Popp et al 1994). As for acrylamide exposure, two different MAs have been measured in human urine and should be further investigated; AA-MA which results from the direct conjugation of GSH on acrylamide and GA-MA, the MA of glycidamide which is formed by epoxidation of acrylamide (Boettcher et al 2005).…”

“…As an illustration, a rapid LC-MS/MS method has been developed for the determination of MHBMA and DHBMA (metabolites of 1,3-butadiene) with LOD of 0.9 and 23 lg/l, respectively, in order to assess the smoking-related exposure to 1,3-butadiene (Urban et al 2003). A similar approach has been taken to determine the reference range of and the effect of smoking habits on HEMA (ethylene oxide metabolite) concentration in the urine of adults in the United States, using a LC-MS/MS method with a LOD of 0.68 lg/l (Calafat et al 1999). Similarly, LC-MS/MS methods have been validated for the measurement of PMA (benzene metabolite) with LODs of 0.1 lg/l (Melikian et al 1999) or 0.35 lg/l (Liao et al 2002).…”