This Article Free Full Text Free Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Sells, D. M. Articles by Walker, N. J. Search for Related Content PubMed PubMed Citation Articles by Sells, D. M. Articles by Walker, N. J. Social Bookmarking                   What's this?

Respiratory Tract Lesions in Noninhalation Studies

¹ Battelle Columbus Laboratories, Columbus, OH 43201, USA
² Experimental Pathology Laboratories, Research Triangle Park, NC 27709, USA
³ Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA
⁴ Pathology Associates—Charles River Laboratories, Durham, NC 27703, USA

Correspondence: Address correspondence to: Nigel Walker, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, 111 Alexander Drive, P.O. Box 12233, MD EC-34, Research Triangle Park, NC 27709, USA; e-mail: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

Toxicologic Pathology, Vol. 35, No. 1, 170-177 (2007)
DOI: 10.1080/01926230601059969


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. J. Walker, K. Yoshizawa, R. A. Miller, A. E. Brix, D. M. Sells, M. P. Jokinen, M. E. Wyde, M. Easterling, and A. Nyska Pulmonary Lesions in Female Harlan Sprague-Dawley Rats Following Two-Year Oral Treatment with Dioxin-Like Compounds Toxicol Pathol, December 1, 2007; 35(7): 880 - 889. [Abstract] [Full Text] [PDF]