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Updated: May 29, 2026

Impact Assessment of Repeated Exposure of Organotypic 3D Bronchial and Nasal Tissue Culture Models to Whole Cigarette Smoke
Published on: February 12, 2015
Urinary biomarkers for secondhand smoke
Toshihiro Ino1, Tetsuya Ohtani, Itsuro Yoshimi
1Faculty of Health Science, Gunma Paz College, Takasaki, Gunma, Japan. ino-t@sk9.so-net.ne.jp
NNAL and its glucuronides are the most reliable biomarkers for secondhand smoke (SHS) exposure, even in children. Cotinine is also useful but affected by CYP2A6 gene variations.
Area of Science:
- Environmental Health
- Biomarkers
- Toxicology
Background:
- Quantitative analysis of secondhand smoke (SHS) exposure necessitates reliable biomarkers.
- Urinary biomarkers offer a non-invasive method for assessing SHS exposure.
Purpose of the Study:
- To review and summarize quantifiable urinary biomarkers for SHS exposure.
- To highlight the utility and limitations of NNAL and cotinine as SHS biomarkers.
Main Methods:
- Review of existing literature on urinary biomarkers for SHS exposure.
- Analysis of NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) and its glucuronides as metabolites of tobacco-specific nitrosamines.
- Evaluation of urinary cotinine levels and the influence of CYP2A6 genetic polymorphism.
Main Results:
- NNAL and NNAL-Glucuronides are highly reliable SHS exposure biomarkers, detected in 50% of children with undetectable cotinine.
- Urinary cotinine is a useful biomarker, but its levels can be underestimated due to CYP2A6*4 allele variations affecting nicotine metabolism.
- Approximately 20% of Japanese subjects possess CYP2A6*4 alleles, impacting cotinine-based SHS exposure assessment.
Conclusions:
- NNAL and its glucuronides are superior biomarkers for SHS exposure, unaffected by CYP2A6 polymorphism.
- CYP2A6 gene polymorphism must be considered when using cotinine for SHS exposure assessment.
- Combining cotinine measurement with parental smoking self-reports may improve SHS exposure assessment in mass screenings.
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