The Nose Revisited: A Brief Review of the Comparative Structure, Function, and Toxicologic Pathology of the Nasal Epithelium

Abstract

The nose is a very complex organ with multiple functions that include not only olfaction, but also the conditioning (e.g., humidifying, warming, and filtering) of inhaled air. The nose is also a "scrubbing tower" that removes inhaled chemicals that may be harmful to the more sensitive tissues in the lower tracheobronchial airways and pulmonary parenchyma. Because the nasal airway may also be a prime target for many inhaled toxicants, it is important to understand the comparative aspects of nasal structure and function among laboratory animals commonly used in inhalation toxicology studies, and how nasal tissues and cells in these mammalian species may respond to inhaled toxicants. The surface epithelium lining the nasal passages is often the first tissue in the nose to be directly injured by inhaled toxicants. Five morphologically and functionally distinct epithelia line the mammalian nasal passages--olfactory, respiratory, squamous, transitional, and lymphoepithelial--and each nasal epithelium may be injured by an inhaled toxicant. Toxicant-induced epithelial lesions in the nasal passages of laboratory animals (and humans) are often site-specific and dependent on the intranasal regional dose of the inhaled chemical and the sensitivity of the nasal epithelial tissue to the specific chemical. In this brief review, we present examples of nonneoplastic epithelial lesions (e.g., cell death, hyperplasia, metaplasia) caused by single or repeated exposure to various inhaled chemical toxicants. In addition, we provide examples of how nasal maps may be used to record the character, magnitude and distribution of toxicant-induced epithelial injury in the nasal airways of laboratory animals. Intranasal mapping of nasal histopathology (or molecular and biochemical alterations to the nasal mucosa) may be used along with innovative dosimetric models to determine dose/response relationships and to understand if site-specific lesions are driven primarily by airflow, by tissue sensitivity, or by another mechanism of toxicity. The present review provides a brief overview of comparative nasal structure, function and toxicologic pathology of the mammalian nasal epithelium and a brief discussion on how data from animal toxicology studies have been used to estimate the risk of inhaled chemicals to human health.

Morphofunctional Adaptations of the Olfactory Mucosa in Postnatally Developing Rabbits

“…Reports on the basic structure of the adult rabbit olfactory system date as far back as 1940s (Allison and Warwick, 1949;Le Gros Clark, 1951, 1956Allison, 1953;Mulvaney and Heist, 1970;Yamamoto, 1976;Mori et al, 1985;Onoda and Fujita, 1988;Harkema et al, 2006). However, regarding postnatal development in this species, relatively little is known particularly regarding how the OM structurally adapts to the unusually high olfactory functional demands.…”

Inhaled aerosol particle dosimetry in mice: A review

“…The shape and complexity of the nasal turbinates is important factor in the filtration of inhaled aerosols by the ET region. Other factors influencing particle deposition in the nasal airways include the high volume of airflow through the ventral aspect of the nasal cavity over the nasal and maxillary turbinates and the pressure drop generated by the nasal region (Harkema et al, 2006). Gross et al (1982) determined the nasal cavity length, and the total surface area and volume for the B6C3F1 mouse (Table 2).…”

On the Olfactory Anatomy in an Archaic Whale (Protocetidae, Cetacea) and the Minke Whale Balaenoptera acutorostrata (Balaenopteridae, Cetacea)

“…The mammalian nose also traps inhaled particles (Kelly et al, 2000), metabolizes airborne xenobiotics (Brain, 1970), helps regulate water balance and heat exchange (Schmidt-Nielsen et al, 1970;Hillenius, 1992;Van Valkenburgh et al, 2004, 2011Rowe et al, 2005), and removes inhaled chemicals that may be harmful to the more sensitive tissues in the lower tracheobronchial airways and pulmonary parenchyma (Harkema et al, 2006). On the basis of the diversity of nasal-cavity architectures in mammals, it is well known that not all nasal/ olfactory functions are equally developed (Negus, 1958;Schreider and Raabe, 1981;Van Valkenburgh et al, 2004;Harkema et al, 2006;Craven et al, 2007). During the course of their evolutionary history from terrestrial artiodactyls to an obligate aquatic lifestyle, cetaceans have modified their olfactory/nasal respiratory apparatus more so than any other mammalian group (Edinger, 1955).…”