Longitudinal stability in cigarette smokers of urinary biomarkers of exposure to the toxicants acrylonitrile and acrolein

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.

[1]  P. Lorkiewicz,et al.  Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco. , 2019, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[2]  Jason D. Robinson,et al.  Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial , 2018, JAMA.

[3]  F. Sung,et al.  Investigating the association between urinary levels of acrylonitrile metabolite N-acetyl-S-(2-cyanoethyl)-L-cysteine and the oxidative stress product 8-hydroxydeoxyguanosine in adolescents and young adults. , 2018, Environmental pollution.

[4]  D. Chatfield,et al.  Acrolein Exposure in Hookah Smokers and Non-Smokers Exposed to Hookah Tobacco Secondhand Smoke: Implications for Regulating Hookah Tobacco Products , 2018, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[5]  Nicole L. Nollen,et al.  Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes , 2016, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[6]  J. Bakdash,et al.  Repeated Measures Correlation , 2017, Front. Psychol..

[7]  N. Benowitz,et al.  Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study , 2017, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[8]  L. Valentín-Blasini,et al.  Chemical Characterization of Mainstream Smoke from SPECTRUM Variable Nicotine Research Cigarettes. , 2017, Tobacco regulatory science.

[9]  H. Rosenfeldt,et al.  Proposed Mode of Action for Acrolein Respiratory Toxicity Associated with Inhaled Tobacco Smoke. , 2016, Toxicological sciences : an official journal of the Society of Toxicology.

[10]  M. Dellarco,et al.  Assessment of Exposure to VOCs among Pregnant Women in the National Children’s Study , 2016, International journal of environmental research and public health.

[11]  B. Blount,et al.  Urinary concentrations of PAH and VOC metabolites in marijuana users. , 2016, Environment international.

[12]  C. Haiman,et al.  Mercapturic Acids Derived from the Toxicants Acrolein and Crotonaldehyde in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer , 2015, PloS one.

[13]  Delshanee Kotandeniya,et al.  Evaluation of toxicant and carcinogen metabolites in the urine of e-cigarette users versus cigarette smokers. , 2015, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[14]  B. Blount,et al.  Acrolein Exposure in U.S. Tobacco Smokers and Non-Tobacco Users: NHANES 2005–2006 , 2015, Environmental health perspectives.

[15]  Nikola Pluym,et al.  Analysis of 18 urinary mercapturic acids by two high-throughput multiplex-LC-MS/MS methods , 2015, Analytical and Bioanalytical Chemistry.

[16]  L. Le Marchand,et al.  Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups. , 2014, Carcinogenesis.

[17]  H. Hou,et al.  Simultaneous determination of five mercapturic acid derived from volatile organic compounds in human urine by LC-MS/MS and its application to relationship study. , 2014, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[18]  Hu Qingyuan,et al.  Simultaneous measurement of N-Acetyl-S-(2-cyanoethyl)-cysteine and N-acetyl-S-(2-hydroxyethyl)-cysteine in human urine by liquid chromatography-tandem mass spectrometry. , 2014, Journal of chromatographic science.

[19]  S. Hecht,et al.  High throughput liquid chromatography-tandem mass spectrometry assay for mercapturic acids of acrolein and crotonaldehyde in cigarette smokers' urine. , 2013, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[20]  S. Feng,et al.  Evaluation of spot urine as an alternative to 24h urine collection for determination of biomarkers of exposure to cigarette smoke in adult smokers. , 2013, Environmental toxicology and pharmacology.

[21]  N. Benowitz,et al.  Comparison of Nicotine and Carcinogen Exposure with Water Pipe and Cigarette Smoking , 2013, Cancer Epidemiology, Biomarkers & Prevention.

[22]  H. Hou,et al.  A column-switching liquid chromatography-tandem mass spectrometry method for quantitation of 2-cyanoethylmercapturic acid and 2-hydroxyethylmercapturic acid in Chinese smokers. , 2012, Analytical biochemistry.

[23]  W. Morgan,et al.  Mainstream smoke chemistry analysis of samples from the 2009 US cigarette market. , 2012, Regulatory toxicology and pharmacology : RTP.

[24]  T. Schettgen,et al.  Accurate quantification of the mercapturic acids of acrylonitrile and its genotoxic metabolite cyanoethylene-epoxide in human urine by isotope-dilution LC-ESI/MS/MS. , 2012, Talanta.

[25]  H. Haussmann.  Use of hazard indices for a theoretical evaluation of cigarette smoke composition. , 2012, Chemical research in toxicology.

[26]  S. Uang,et al.  Simultaneous quantitation of urinary cotinine and acrylonitrile-derived mercapturic acids with ultraperformance liquid chromatography–tandem mass spectrometry , 2012, Analytical and Bioanalytical Chemistry.

[27]  A. Morin,et al.  Estimation and correlation of cigarette smoke exposure in Canadian smokers as determined by filter analysis and biomarkers of exposure. , 2011, Regulatory toxicology and pharmacology : RTP.

[28]  E. Minet,et al.  Urinary excretion of the acrylonitrile metabolite 2-cyanoethylmercapturic acid is correlated with a variety of biomarkers of tobacco smoke exposure and consumption , 2010, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[29]  K. Newland,et al.  An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories , 2011, BMC Research Notes.

[30]  S. Feng,et al.  Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[31]  Jian-Min Yuan,et al.  Applying tobacco carcinogen and toxicant biomarkers in product regulation and cancer prevention. , 2010, Chemical research in toxicology.

[32]  T. Church,et al.  Temporal stability of urinary and plasma biomarkers of tobacco smoke exposure among cigarette smokers , 2010, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[33]  M. Borgerding,et al.  Development and validation of a direct LC-MS-MS method to determine the acrolein metabolite 3-HPMA in urine. , 2010, Journal of chromatographic science.

[34]  A. Zuckerman,et al.  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans , 1995, IARC monographs on the evaluation of carcinogenic risks to humans.

[35]  D. Mariner,et al.  A study to estimate and correlate cigarette smoke exposure in smokers in Germany as determined by filter analysis and biomarkers of exposure. , 2009, Regulatory toxicology and pharmacology : RTP.

[36]  D. Hatsukami,et al.  Effects of smoking cessation on eight urinary tobacco carcinogen and toxicant biomarkers. , 2009, Chemical research in toxicology.

[37]  T. Schettgen,et al.  A method for the quantification of biomarkers of exposure to acrylonitrile and 1,3-butadiene in human urine by column-switching liquid chromatography–tandem mass spectrometry , 2009, Analytical and bioanalytical chemistry.

[38]  Robert K. Boyd,et al.  Trace Quantitative Analysis by Mass Spectrometry: Boyd/Trace Quantitative Analysis by Mass Spectrometry , 2008 .

[39]  J. F. Stevens,et al.  Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. , 2008, Molecular nutrition & food research.

[40]  D. Hatsukami,et al.  Quantitation of acrolein-derived (3-hydroxypropyl)mercapturic acid in human urine by liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry: effects of cigarette smoking. , 2007, Chemical research in toxicology.

[41]  G. Scherer,et al.  Influence of Smoking Charcoal Filter Tipped Cigarettes on Various Biomarkers of Exposure , 2006, Inhalation toxicology.

[42]  E. Van Miert,et al.  Determination of the major mercapturic acids of 1,3-butadiene in human and rat urine using liquid chromatography with tandem mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[43]  E. Schmid,et al.  High-performance liquid chromatographic-tandem mass spectrometric determination of 3-hydroxypropylmercapturic acid in human urine. , 2001, Journal of Chromatography B: Biomedical Sciences and Applications.

[44]  T. Fennell,et al.  Urinary metabolites from F344 rats and B6C3F1 mice coadministered acrylamide and acrylonitrile for 1 or 5 days. , 1997, Chemical research in toxicology.

[45]  D. Cicchetti.  Guidelines, Criteria, and Rules of Thumb for Evaluating Normed and Standardized Assessment Instruments in Psychology. , 1994 .

[46]  J. Kopecký,et al.  2-Cyanoethylmercapturic acid (CEMA) in the urine as a possible indicator of exposure to acrylonitrile. , 1987, British journal of industrial medicine.

[47]  W. R. Johnson,et al.  Chemistry of the Conversion of Nitrate Nitrogen to Smoke Products , 1973, Nature.