Inhaled naphthalene causes dose dependent Clara cell cytotoxicity in mice but not in rats

West, JAA; Pakehham, G; Morin, D; Fleschner, CA; Buckpitt, AR; Plopper, CG

HERO ID

1469209

Reference Type

Journal Article

Year

2001

Language

English

PMID

11384213

HERO ID 1469209
In Press No
Year 2001
Title Inhaled naphthalene causes dose dependent Clara cell cytotoxicity in mice but not in rats
Authors West, JAA; Pakehham, G; Morin, D; Fleschner, CA; Buckpitt, AR; Plopper, CG
Journal Toxicology and Applied Pharmacology
Volume 173
Issue 2
Page Numbers 114-119
Abstract Current OSHA standards for naphthalene exposure are set at 10 ppm (time-weighted average) with a standard threshold exposure concentration of 15 ppm. While several studies have thoroughly delineated the time course and dose response of injury by naphthalene administered ip, the pattern and severity of injury by inhalation exposure are unknown. These studies compare the regiospecific and dose-dependent cytotoxicity of naphthalene after inhalation exposure. Mice and rats were exposed for 4 h to naphthalene vapor at concentrations of 0-110 ppm. In rats, no injury was observed in the lung epithelium at exposure concentrations up to 100 ppm. Exposures as low as 2 ppm produced proximal airway injury in mice, with increased severity in a concentration-dependent fashion up to 75 ppm. Terminal airways of exposed mice exhibited little or no injury at low concentrations (1-3 ppm). Exposures of 8.5 ppm or higher were required to produce injury to Clara cells in the terminal airways. In contrast, administration of naphthalene (</=200 mg/kg ip) caused Clara cell cytotoxicity, which was limited to distal airways in mice. Higher doses (>300 mg/kg) extended the injury pattern toward the lobar bronchus. We conclude (1) the pattern of injury to naphthalene is highly dependent on the route of exposure, (2) lung injury to inhaled naphthalene is species dependent, and (3) Clara cells of mouse airways are exquisitely sensitive to inhaled naphthalene at concentrations well below the current OSHA standard for human exposure.
Doi 10.1006/taap.2001.9151
Pmid 11384213
Wosid WOS:000169241400005
Url <Go to ISI>://WOS:000169241400005
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science WOS:000169241400005
Is Public Yes
Language Text English
Keyword respiratory; epithelium; toxicity; naphthalene; mice; Clara cell toxicity; dose dependence; morphometry