Characterization of US population levels of urinary methylcarbamoyl mercapturic acid, a metabolite of N,N-dimethylformamide and methyl isocyanate, in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 and 2011–2016

• Authors: Brandon M Kenwood, National Center for Environmental Health; Pritha Bagchi, Emory University; Luyu Zhang, National Center for Environmental Health; Wanzhe Zhu, National Center for Environmental Health; David M Chambers, National Center for Environmental Health; Benjamin C Blount, National Center for Environmental Health; Víctor R De Jesús, National Center for Environmental Health
• Journal Title: Environmental Science and Pollution Research
• Volume: Volume 28, Number 13
• Publisher: Springer Nature | 2021-04-01, Pages 16781-16791
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s11356-020-12135-7
• Subjects: Health Sciences, Public Health
• Keywords: Methyl isocyanate; Methylcarbamoyl mercapturic acid; N,N-Dimethylformamide; N-acetyl-S-(N-methylcarbamoyl)-L-cysteine; Tobacco smoke exposure; Volatile organic compounds; Acetylcysteine; Biomarkers; Child; Cotinine; Dimethylformamide; Humans; Isocyanates; Nutrition Surveys; Tobacco Smoke Pollution

Abstract

Methylcarbamoyl mercapturic acid (MCAMA, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine) is a urinary metabolite of N,N-dimethylformamide and methyl isocyanate, which are volatile organic compounds that are harmful to humans. N,N-dimethylformamide exposure causes liver damage, and methyl isocyanate inhalation damages the lining of the respiratory tract, which can increase risk of chronic obstructive pulmonary disease and asthma. This study characterizes urinary MCAMA levels in the US population and explores associations of MCAMA concentrations with select demographic and environmental factors. We used liquid chromatography tandem mass spectrometry to measure MCAMA in urine collected from study participants ≥ 12 years old (N = 8272) as part of the National Health and Nutrition Examination Survey 2005–2006 and 2011–2016. We produced multiple regression models with MCAMA concentrations as the dependent variable and sex, age, fasting time, race/ethnicity, diet, and cigarette smoking as independent variables. Cigarette smokers and nonsmokers had median urinary MCAMA concentrations of 517 μg/g creatinine and 127 μg/g creatinine, respectively. Sample-weighted multiple regression analysis showed that MCAMA was positively associated with serum cotinine (p < 0.0001). Compared to non-exposed participants (serum cotinine ≤ 0.015 ng/mL), presumptive exposure to second-hand tobacco smoke (serum cotinine > 0.015–≤ 10 ng/mL and 0 cigarettes smoked per day) was associated with 20% higher MCAMA (p < 0.0001). Additionally, smoking 1–10 cigarettes per day was associated with 261% higher MCAMA (p < 0.0001), smoking 11–20 cigarettes per day was associated with 357% higher MCAMA (p < 0.0001), and smoking > 20 cigarettes per day was associated with 416% higher MCAMA (p < 0.0001). These findings underscore the strong association of tobacco smoke exposure with urinary MCAMA biomarker levels.