The Relationship Between Cigarette Smoking and Biomarkers of Exposure Across Two Study Centers in Europe

Frazer J. Lowe*, a, Evan O. Greggb, Antonella Bassia, Riccardo Puntonib
a British American Tobacco, GR&D Regents Park Road, Southampton, SO15 8TL, UK
b Consultant to British American Tobacco GR&D, Southampton, UK

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© 2010 Lowe et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the British American Tobacco, GR&D Regents Park Road, Southampton, SO15 8TL, UK; Tel: +44 (0)2380 793647; Fax: +44 (0)2380 793076; E-mail:


The relationship between biomarkers of exposure to cigarette smoke in 24h urine samples collected from groups of 80 smokers (44 males, 36 females) and 40 never smokers (17 males, 23 females) at two centers in Europe was studied. Eight biomarkers (nicotine, cotinine, hydroxycotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and all of the respective glucuronide conjugates) were measured. Subjects from the two centers were pooled and biomarker data analyzed according to the machine smoked tar yield of the brand each subject smoked and the recorded number of cigarettes smoked per day (CPD). A statistically significant relationship between CPD and all of the biomarkers analyzed was found. Smokers of less than 11 CPD had the lowest mean 24h urinary concentrations for all biomarkers measured. However, if the amount of constituent obtained from each cigarette smoked was calculated, then the amount of nicotine obtained per cigarette was highest in this group although the variation was also greatest for this group. The amount of NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone, the parent molecule of NNAL) obtained per cigarette was not statistically significantly different across all groups. In conclusion, these results confirm the reliability of 24h urinary total nicotine and NNAL concentrations as biomarkers of exposure to specific cigarette smoke constituents across two centers in Europe. These measurements may provide an objective alternative to CPD when grouping smokers for are studies of other endpoints.

Keywords: Biomarker, smoking, NNAL, nicotine, NNK, cotinine.