Respiratory tract lesions in noninhalation studies

Area of Science:

• Toxicology
• Pathology
• Rodent Studies

Background:

• Chemicals administered via inhalation are known to cause respiratory lesions.
• Noninhalation routes of chemical administration may lead to underappreciated or undetected respiratory tract lesions, especially in the upper respiratory tract.
• Lesions reviewed primarily originate from chronic rodent studies by the National Toxicology Program.

Purpose of the Study:

• To review and characterize respiratory tract lesions in rodents exposed to chemicals via noninhalation routes.
• To highlight the vulnerability of the nasal cavity to chemical damage through noninhalation exposure.
• To emphasize the importance of comprehensive respiratory tract examination in toxicology studies.

Main Methods:

• Review of rodent toxicology studies, focusing on noninhalation chemical administration.
• Analysis of histopathological findings in the respiratory tract, including nasal passages and lungs.
• Examination of lesions from both chronic and shorter-duration studies.

Main Results:

• Noninhalation routes can induce significant lesions in the nasal cavity, such as epithelial hyperplasia, olfactory epithelium degeneration/necrosis, metaplasia, and tumors (adenoma, adenocarcinoma, squamous cell carcinoma, neuroblastoma).
• Lung lesions observed include alveolar histiocytosis, epithelial hyperplasia, metaplasia, and tumors (adenoma, carcinoma, squamous tumors).
• Pathogenesis involves factors like regurgitation of volatiles, circulating metabolites, and local metabolism by olfactory epithelium or Clara cells.

Conclusions:

• Chemicals administered via noninhalation routes pose a risk for inducing lesions throughout the respiratory tract, including the nasal cavity.
• The findings underscore the necessity of detailed examination of the entire respiratory tract, including nasal passages, regardless of the chemical's route of administration.
• This comprehensive approach is vital for accurate toxicological assessment and understanding chemical-induced pathology.