Urinary biomarkers of smokers’ exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach

Abstract

There are established guidelines for bioanalytical assay validation and qualification of biomarkers. In this review, they were applied to a panel of urinary biomarkers of tobacco smoke exposure as part of a “fit for purpose” approach to the assessment of smoke constituents exposure in groups of tobacco product smokers. Clinical studies have allowed the identification of a group of tobacco exposure biomarkers demonstrating a good doseresponse relationship whilst others such as dihydroxybutyl mercapturic acid and 2-carboxy-1-methylethylmercapturic acid – did not reproducibly discriminate smokers and non-smokers. Furthermore, there are currently no agreed common reference standards to measure absolute concentrations and few inter-laboratory trials have been performed to establish consensus values for interim standards. Thus, we also discuss in this review additional requirements for the generation of robust data on urinary biomarkers, including toxicant metabolism and disposition, method validation and qualification for use in tobacco products comparison studies.

Changes in levels of biomarkers of exposure and biological effect in a controlled study of smokers switched from conventional cigarettes to reduced-toxicant-prototype cigarettes

“…(1,3-butadiene) no significant changes were seen from baseline to the end of the study and the BoE for one smoke constituent (pyrene) significantly decreased in the control group. The levels of BoEs in non-smokers were in keeping with published data (Shepperd et al, 2013a;Gregg et al, 2013). In the test group smoke yields for all of these toxicants were reduced compared with the control product, and significant reductions were also seen in the levels of all BoE, except o-toluidine, which again showed no significant change.…”

Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users

“…However, given the lack of long-term data, we chose this pragmatic design to evaluate quickly potentially important associations of EC use with carcinogen and toxicant intake to inform further longitudinal work. Moreover, the relatively slow pharmacokinetics of the assessed metabolites (71) provides stable estimates of recent exposure and should militate against variations associated with different usage patterns of different products. Future work should attempt to sample a larger range of biomarkers over a longer period of time, including biomarkers of actual harm such as lung function measures, and evaluate the impact of potential interactions of user with device characteristics on delivery of toxicants to users and bystanders.…”

Magnitudes of biomarker reductions in response to controlled reductions in cigarettes smoked per day: A one-week clinical confinement study

“…Many of the selected biomarkers were similar to those reported elsewhere (Gregg et al, 2013;Institute of Medicine, 2011;Krautter and Borgerding, 2014). Analytical methods are essentially as recently reported elsewhere (Krautter and Borgerding, 2014).…”