Assessing exposure to tobacco-specific carcinogen NNK using its urinary metabolite NNAL measured in US population: 2011–2012

Abstract

Carcinogenic tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are found only in tobacco and derived products. Food and Drug Administration of the United States (US FDA) lists NNK as one of the 93 harmful and potentially harmful constituents (HPHCs) found in tobacco products and tobacco smoke. The aim of this study was to use the urinary concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite of NNK, to quantitatively estimate exposure to NNK in the US general population. In 2011–2012, the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey (NHANES) collected urine and serum samples from a representative sample of US residents. We used a serum cotinine cutoff of 10 ng/ml with combination of questionnaire data to select non-users from cigarette users and used self-reported data to determine different tobacco product user groups. We estimated the absorbed total daily dose of NNK using a probabilistic method based on a two-compartment model. The geometric mean (GM) for the daily dose of NNK among smokers aged 12–16 years was significantly higher than that for non-users at the same age stage exposed to second-hand smoke (SHS) (P < 0.001). Among those exposed to SHS, the GM for daily dose of NNK in young children (6–11 years) was nearly three times of those for adults in the age range 21–59 years. Among cigarette users, non-Hispanic Whites had the highest NNK daily dose and Mexican Americans had the lowest levels. Exclusive snuff or chewing product users had significantly higher daily dose of NNK than did cigarette smokers. Our study found that the maximum daily dose of NNK for children aged from 6 to 11 years and that for a significant percentage of cigarette users, chewing product and snuff users were higher than an estimated provisional “reference” risk level.

Stereospecific Metabolism of the Tobacco-Specific Nitrosamine, NNAL

“…20, 27 The NNAL enantiomers and their glucuronides can also be detected in the urine of past and current smokers. 3, 22–25, 28–32 It has been found that while ( S )-NNAL is stereoselectively retained in rat lung and has a higher tumorigenicity than ( R )-NNAL, ( R )-NNAL exhibits a higher rate of glucuronidation in rats 33–36 and the A/J mouse. 26, 36 However, studies indicate that ( S )-NNAL may be stereo-selectively retained in smokeless tobacco users 37 but exhibits a higher rate of glucuronidation in the patas monkey.…”

Urinary NNAL in hookah smokers and non-smokers after attending a hookah social event in a hookah lounge or a private home

“…33 Similarly, previous biomonitoring studies found that hookah tobacco smokers are exposed to NNK, though at levels lower than found in cigarette smokers. 12 …”

“…33 In non-daily hookah smokers, the GM urinary NNAL levels were 1.3 times and 2.9 times higher than U.S. non-tobacco users (GM, pre event:1.45 pg/mg and post event: 3.13 pg/mg vs. NHANES: 1.09 pg/mg). 33 …”

“…33 Because of the California clean indoor air laws, non-smokers in California are generally exposed to less tobacco smoke than is the representative U.S. non-smoker person. 35 …”

Passive Smoking

“…Sigara içmeyenlerde de tütün dumanındaki karsinojenlerin albümine bağlandıkları ve hücresel DNA'yı etkiledikleri bildirilmiştir. İESD'ye maruz kalanların tütün dumanında bulunan karsinojenik bir nitrozamin olan NNAL'yi idrarla attıkları gösterilmiştir (100) . Kanserin histolojik tipleri bakımından, küçük hücre-li akciğer kanseri ile daha güçlü bir ilişki görülmüş-tür (97) .…”