Fourteen-Day Inhalation Study in Rats, Using Aged and Diluted Sidestream Smoke from a Reference Cigarette: I. Inhalation Toxicology and Histopathology

Sprague-Dawley rats were exposed 6 hr per day for 14 consecutivedays to aged and diluted sidestream smoke (ADSS), used as asurrogate for Environmental Tobacco Smoke (ETS), at concentrationsof 0.1 (typical), 1 (extreme), or 10 (exaggerated) mg of particulatesper cubic meter. Animals were exposed nose-only, inside whole-bodychambers, to ADSS from the 1R4F reference cigarette. End-pointsincluded histopathology, CO-ox-imetry plasma nicotine and cotinine,clinical pathology, and organ and body weights. The only pathologicalresponse observed was slight to mild epithelial hyperplasiaand inflammation in the most rostral part of the nasal cavity,in the high-exposure group only. No effects were noted at mediumor low exposures. The minimal changes noted were reversible,using a subgroup of animals kept without further treatment foran additional 14 days. Overall, the end-points used in the studydemonstrated that there was no detectable biological activityof ADSS at typical or even 10-fold ETS concentrations and thatthe activity was only minimal at very exaggerated concentrations(particle concentrations 100 times higher than typical real-worldconcentrations).