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

• Published in: Regulatory toxicology and pharmacology Vol. 72; no. 2; pp. 273 - 291
• Main Authors: Shepperd, Christopher J., Newland, Nik, Eldridge, Alison, Haswell, Linsey, Lowe, Frazer, Papadopoulou, Ermioni, Camacho, Oscar, Proctor, Christopher J., Graff, Don, Meyer, Ingo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2015
• Subjects: Adult; Biomarker of biological effect; Biomarker of effective dose; Biomarker of exposure; Biomarkers - blood; Biomarkers - urine; Environmental Exposure - analysis; Female; Hazardous Substances - toxicity; Humans; Male; Middle Aged; Modified risk tobacco product; MRTP; Potential reduced-exposure product; PREP; Reduced toxicant prototype cigarettes; Smoking; Smoking - blood; Smoking - urine; Surveys and Questionnaires; Tobacco Products - toxicity; Tobacco smoke toxicants; Young Adult; Germany; Germany, Hamburg; NAT; s-ICAM-1; MHBMA; MLE; PREP; NNK; Reduced toxicant prototype cigarettes; NNN; oxLDL; LTB4; Biomarker of effective dose; WHO; Potential reduced-exposure product; Biomarker of exposure; HMPMA; Biomarker of biological effect; GPx; hsCRP; Smoking; FDA; MCP-1; mmWG; MRTP; BLQ; BDL; AFR; RTP; HDL; BoED; 3-HPMA; LDL; ISRCTN; CA; 8-OHdG; ISO; NFDPM; IOM; EOS; MFCV; CEMA; SOD; HAC; Tobacco smoke toxicants; NAB; Modified risk tobacco product; BoBE; CU; LIP; CPD; PAH; BoE
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2015.04.016

•Volunteer smokers switched to prototype cigarettes with reduced smoke toxicants.•Clinical study monitored changes in biomarkers of exposure and biological effect.•Significant toxicant exposure reduction despite increase in cigarette consumption.•Minimal changes in biomarkers of biological effect due to low biomarker utility.•Lessons learned for biomarker choice and behavioural effects of study design. Development of cigarettes that reduce exposure to harmful smoke constituents is a suggested tobacco harm reduction strategy, but robust methods for measurement of change are required. We investigated whether changes in biomarkers of exposure (BoE), effective dose (BoED) and biological effect (BoBE) could be detected after switching from conventional cigarettes to a reduced-toxicant-prototype cigarette (RTP). Regular smokers of 6–8mg ISO tar yield cigarettes were recruited in Hamburg, Germany, and supplied with a conventional 7mg ISO tar yield cigarette for 2weeks then switched to the same cigarette with a different tipping paper (control) or the RTP for 6months. Subjects smoked mostly at home and attended five residential clinic visits where urine and blood samples were collected for analysis. Primary endpoints were changes in specific biomarker levels compared with non-smoker background levels. Changes in daily cigarette consumption were also investigated. BoE levels in controls generally increased over the study period, whereas most BoE and all BoED significantly declined in RTP smokers. Most BoBE data were similar across groups and/or too variable within individuals to detect changes. Increased daily cigarette consumption was affected by supply of free cigarettes, perceived shorter smoking time per cigarette than usual brands, and perceived reduced harm. Despite increased cigarette consumption, reductions in BoE and BoED were detectable.