Comparison of creatinine and specific gravity for hydration corrections on measurement of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine.

Background: Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was measured in all participants aged 6 years and older from the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey 2007-2008. The suitability of using creatinine or specific gravity for urinary NNAL correction in exposure assessment is examined in this study.

Methods: Effects of both specific gravity and creatinine correction on urinary NNAL among smokers were investigated with multiple linear regression models using either normalization or the fitting of creatinine and specific gravity in the model as covariates.

Results: When log-scaled NNAL was normalized by either creatinine or specific gravity, R(2) was slightly higher for creatinine than for specific gravity (R(2) = 0.1694 and 0.1439, for creatinine and specific gravity, respectively). When log-scaled NNAL was normalized by both factors, the R(2) was improved (R(2) = 0.2068). When specific gravity or creatinine was included as a covariate separately in the models, they were highly significant factors (P < 0.001, R(2) = 0.2226 and 0.1681 for creatinine and specific gravity, respectively). However, when both were included in the model as covariates, creatinine remained highly significant (P < 0.001), whereas the significance of specific gravity was eliminated (P = 0.4294).

Conclusion: This study confirms significant relationships between NNAL concentrations and both urine creatinine and specific gravity. We conclude that creatinine is the more influential and preferred variable to account for urine dilution in tobacco-specific nitrosamine exposure assessment.