title: Subchronic inhalation by rats of mainstream smoke from a cigarette that primarily heats tobacco compared to a cigarette that burns tobacco.
abstract: A subchronic, nose-only inhalation study comparing the potential biological activity of mainstream smoke from a cigarette that primarily heats tobacco (Eclipse) to mainstream smoke from a 1R4F reference cigarette was conducted using Sprague-Dawley rats of each gender. Smoke exposures were for 1 h/day, 5 days/wk for 13 wk, at concentrations of 0, 0.16, 0.32, or 0.64 mg wet total particulate matter (WTPM)/L air. Smoke was generated at the Federal Trade Commission standard of a 2-s puff of 35 ml, taken once per minute. Clinical signs, body and organ weights, clinical chemistry, hematology, carboxyhemoglobin, serum nicotine, plethysmography, gross pathology, and histopathology were determined. Plethysmography indicated that respiratory rate was decreased at all concentrations of 1R4F smoke, but only at the high concentration of Eclipse smoke. Tidal volume was depressed and minute volume was lower for all smoke-exposed rats. Rats exposed to Eclipse smoke inhaled more smoke at the low and mid-concentration exposures than rats exposed to equivalent concentrations 1R4F smoke. Carboxyhemoglobin and serum nicotine were directly related to the exposure concentrations of carbon monoxide (CO) and nicotine in an exposure-dependent manner. Body weights were slightly lower in smoke-exposed rats, while no treatment-related effects were seen in clinical signs, clinical chemistry, hematology, or gross changes at necropsy. The only treatment-related effect seen in organ weights was an increase in heart weight in females in the Eclipse high-concentration exposure group, attributed to higher CO in the Eclipse exposure atmosphere. Higher CO resulted from the lower dilution of Eclipse smoke required to maintain WTPM concentrations equal to those of the 1R4F smoke, and not from a higher CO yield from Eclipse cigarettes. Nasal epithelial hyperplasia and ventral laryngeal squamous metaplasia were noted after exposure to either the 1R4F or Eclipse smoke. The degree of change was less in Eclipse smoke-exposed rats. Lung macrophages were increased to a similar extent in the Eclipse and 1R4F smoke-exposed groups. Brown/gold pigmented macrophages were detected in the lungs of rats exposed to 1R4F smoke, but not those exposed to Eclipse smoke. Subsets of rats from each group were maintained for an additional 13 wk without smoke exposures. Most of the changes noted at the end of the smoke exposures had disappeared, while those that remained were regressing toward normal. Evaluation of these findings indicated the overall biological activity of Eclipse smoke was less than 1R4F smoke at comparable exposure concentrations.
authors.affiliation: R. J. Reynolds Tobacco Co., Research and Development, Division of Toxicology, PO Box 1236, Winston-Salem, NC 27102, USA. ayresp@rjrt.com
authors.forename: P H
authors.initials: PH
authors.lastname: Ayres
authors.forename: J R
authors.initials: JR
authors.lastname: Hayes
authors.forename: M A
authors.initials: MA
authors.lastname: Higuchi
authors.forename: A T
authors.initials: AT
authors.lastname: Mosberg
authors.forename: J W
authors.initials: JW
authors.lastname: Sagartz
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000032:analysis; D002263:Carboxyhemoglobin / Q000378:metabolism; D005260:Female; D006358:Hot Temperature; D006813:Humidity; D008297:Male; D009538:Nicotine / Q000032:analysis / Q000097:blood; D009666:Nose / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D010991:Plethysmography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000032:analysis; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology
chemical_list: D012906:Smoke; D009538:Nicotine; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin