Abstract

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

Highlights

  • The U.S National Toxicology Program 14th Report on Carcinogens classifies acrylonitrile as “reasonably anticipated to be a human carcinogen” based on sufficient evidence of carcinogenicity from studies in experimental animals [1]

  • Our data demonstrate that the longitudinal consistency of cyanoethyl mercapturic acid (CEMA) (ICC, 0.67) is similar to that of total nicotine equivalents (TNE) (ICC, 0.68) and superior to that of 3-hydroxypropyl mercapturic acid (3-HPMA) (ICC, 0.46)

  • Quantitation of CEMA and 3-HPMA as urinary biomarkers of exposure to acrylonitrile and acrolein, respectively, has been reported extensively, but to our knowledge this is the first study to investigate the longitudinal consistency of these biomarkers in humans

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Summary

Introduction

The U.S National Toxicology Program 14th Report on Carcinogens classifies acrylonitrile as “reasonably anticipated to be a human carcinogen” based on sufficient evidence of carcinogenicity from studies in experimental animals [1]. Data from epidemiological studies are considered inadequate to evaluate specific exposures to acrylonitrile as causes of human cancer. Jakubowski et al were the first to measure CEMA in humans exposed to acrylonitrile They used gas chromatography with flame ionization detection [5]. Schettgen et al developed a column-switching liquid chromatography tandem mass spectrometry (LC-MS/MS) method for CEMA in human urine and found a relationship to cigarette smoking as well as passive smoke exposure [6]. Scherer et al reported a method for CEMA in human urine using derivatization with pentafluorobenzyl bromide followed by LC-MS/MS analysis. They observed a significant decrease in CEMA levels upon smoking cessation [7]. Multiple other investigators have confirmed and extended these results, including application to studies of marijuana smokers, waterpipe users, and e-cigarette users [9,10,11,12,13,14,15,16,17,18,19,20,21]

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