title: In situ naphthalene bioactivation and nasal airflow cause region-specific injury patterns in the nasal mucosa of rats exposed to naphthalene by inhalation.
abstract: Despite the fact that naphthalene (NA), a volatile, ubiquitous air pollutant, was recently identified as a probable human carcinogen, little is known about nasal cytotoxicity from inhaled NA. To define and compare acute nasal injury from inhalation and systemic NA exposures, male Sprague-Dawley rats were exposed to filtered air; 3.4 or 23.8 ppm NA by inhalation for 4 h; or to 0, 25, 50, 100, or 200 mg/kg NA via intraperitoneal injection. Severe cellular injury occurred exclusively in the olfactory mucosa 24 h postinhalation exposure to 3.4 ppm NA for 4 h. This level is significantly below both the current Occupational Safety and Health Administration standard (10 ppm; 8 h) for NA and the lowest observed adverse effect level (10 ppm; 2 years) for the incidence of rat olfactory neoplasms. Injury within the olfactory mucosa from inhaled NA was confined to the medial meatus, whereas systemic NA generated severe injury throughout the olfactory region. The pattern of nasal injury from inhaled NA in this study is consistent with previous studies of nasal airflow simulation within the olfactory region. The nonolfactory mucosa on the nasal septum, a high airflow region, metabolized naphthalene slowly, whereas the olfactory regions of the nasal septum and ethmoturbinates metabolized this substrate at high rates. This study concludes that 1) the incidence of acute nasal injury from systemic and inhaled NA correlates with the rates of regional microsomal NA metabolism and that 2) the nasal airflow pattern determines the pattern of olfactory mucosal injury from inhaled NA.
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. mglee@ucdavis.edu
authors.forename: Myong Gyong
authors.initials: MG
authors.lastname: Lee
authors.forename: Andrew
authors.initials: A
authors.lastname: Phimister
authors.forename: Dexter
authors.initials: D
authors.lastname: Morin
authors.forename: Alan
authors.initials: A
authors.lastname: Buckpitt
authors.forename: Charles
authors.initials: C
authors.lastname: Plopper
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D066298:In Vitro Techniques; D019570:Inhalation Exposure; D007274:Injections, Intraperitoneal; D008297:Male; D008861:Microsomes / Q000187:drug effects; D009281:Naphthalenes / Q000008:administration & dosage / Q000633:toxicity*; D009296:Nasal Cavity; D009297:Nasal Mucosa / Q000201:enzymology / Q000293:injuries* / Q000473:pathology; D012123:Pulmonary Ventilation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009281:Naphthalenes; C031721:naphthalene; D003577:Cytochrome P-450 Enzyme System