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Respiratory Tract Lesions in Noninhalation Studies

Battelle Columbus Laboratories, Columbus, OH 43201, USA

Amy E. Brix

Experimental Pathology Laboratories, Research Triangle Park, NC 27709, USA

Abraham Nyska

Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA

Micheal P. Jokinen

Pathology Associates-Charles River Laboratories, Durham, NC 27703, USA

Denise P. Orzech

Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA

Nigel J. Walker

Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA, walker3{at}niehs.nih.gov

This paper reviews respiratory tract lesions observed in rodents administered various chemicals by noninhalation routes. Chemicals administered by inhalation caused lesions in the respiratory tract and were well described; however, when chemicals were administered by noninhalation routes the effort to evaluate tissues for lesions may have been less or not considered, especially in the upper respiratory tract, and some lesions may have gone undetected. Lesions described in this review mostly occurred in rodent chronic noninhalation studies conducted by the National Toxicology Program; however, some were noted in studies of shorter duration. The nasal cavity was vulnerable to damage when chemicals were administered by noninhalation routes. Changes included respiratory epithelial hyperplasia, degeneration and necrosis of olfactory epithelium, olfactory epithelial metaplasia, adenoma, adenocarcinoma, squamous cell carcinoma, and neuroblastoma. In the lung, compound-related lesions included alveolar histiocytosis, alveolar epithelial hyperplasia, bronchiolar metaplasia of the alveolar epithelium, squamous metaplasia, alveolar/bronchial adenoma and carcinoma, and squamous tumors. Pathogenesis of these lesions included regurgitation of volatiles, metabolites arriving from the blood stream, and additional metabolism by olfactory epithelium or Clara cells. The presence of respiratory tract lesions in noninhalation studies emphasizes the need for a thorough examination of the respiratory tract including nasal passages, regardless of the route of administration.

Key Words: Toxicology • pathology • respiratory tract • rats • mice • lung • nasal epithelium.

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