title: 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.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Despite increased cigarette consumption, reductions in BoE and BoED were detectable.
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Shepperd
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Nik
authors.initials: N
authors.lastname: Newland
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK. Electronic address: alison_eldridge@bat.com.
authors.forename: Alison
authors.initials: A
authors.lastname: Eldridge
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Linsey
authors.initials: L
authors.lastname: Haswell
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Frazer
authors.initials: F
authors.lastname: Lowe
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Ermioni
authors.initials: E
authors.lastname: Papadopoulou
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Oscar
authors.initials: O
authors.lastname: Camacho
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Proctor
authors.affiliation: Celerion, 621 Rose Street, Lincoln, NE 68502, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Graff
authors.affiliation: MPS Hamburg GmbH, Kieler Strasse 99-105, Hamburg 22769, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Meyer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004781:Environmental Exposure / Q000032:analysis; D005260:Female; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000097:blood* / Q000652:urine*; D011795:Surveys and Questionnaires; D062789:Tobacco Products / Q000633:toxicity*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015386:Hazardous Substances
keywords: Biomarker of biological effect; Biomarker of effective dose; Biomarker of exposure; MRTP; Modified risk tobacco product; PREP; Potential reduced-exposure product; Reduced toxicant prototype cigarettes; Smoking; Tobacco smoke toxicants