Upper Respiratory Tract Lesions in Inhalation Toxicology

Abstract

This paper describes some important differences in normal histology of the upper respiratory tract of laboratory animals. It also provides examples of lesions observed or reported in the upper respiratory tract of laboratory animals, predominantly rodents, exposed via inhalation. The anatomy and physiology of upper respiratory tract tissues play a major role in the response to an insult, given that different epithelial types vary in susceptibility to injury and toxicant exposure concentrations throughout the airway vary due to airflow dynamics. Although dogs and nonhuman primates are utilized for inhalation toxicology studies, less information is available regarding sites of upper respiratory injury and types of responses in these species. Awareness of interspecies differences in normal histology and zones of transition from squamous to respiratory to olfactory epithelium in different areas of the upper respiratory tract is critical to detection and description of lesions. Repeated inhalation of chemicals, drugs, or environmental contaminants induces a wide range of responses, depending on the physical properties of the toxicant and concentration and duration of exposure. Accurate and consistent fixation, trimming, and microtomy of tissue sections using anatomic landmarks are critical steps in providing the pathologist the tools needed to compare the morphology of upper respiratory tract tissues from exposed and control animals and detect and interpret subtle differences.

Nasal Passages of Göttingen Minipigs from the Neonatal Period to Young Adult

“…Levels 3 and 4 were selected for the respiratory epithelium. Level 4 contained the most rostral part of the olfactory epithelium, which was found to be a sensitive site in the rat (Harkema, Carey, and Wagner 2006;Renne et al 2007). Levels with the soft palate tonsil were left out, because the soft palate tonsil is associated with the oral cavity, rather than with the nasal passages.…”

The respiratory system

“…If a complete evaluation of the nasal cavity is required then three or four standard sections of the mouse nasal turbinates may be cut with reference to the upper palate (Young 1981) and teeth (Renne et al 2007) (Figure 11.2a). The first section (level 1) is cut at the level of the upper incisor teeth (Figure 11.3).…”

“…The paired vomeronasal organs (Jacobson's organ) and nasolacrimal ducts are present in level 1. A high volume of air passes through the central region of the nasal cavity so it is vulnerable to inhaled compounds and pathogens and is a common site for lesions (Renne et al 2007).…”

“…The nasolacrimal duct has moved lateral to the incisor tooth. The olfactory epithelium in this level is especially susceptible to injury (Renne et al 2007). The third section is taken at the level of the second palatal ridge (Figure 11.5).…”

“…They are similar to serous salivary glands. The most frequent site of injury at level 3 in mice is the olfactory epithelium lining the dorsal medial meatus (Renne et al 2007).…”