Nonneoplastic changes in the olfactory epithelium--experimental studies.

Abstract

Interest in the olfactory mucosa has increased in recent years, since it has been shown to possess a considerable amount of cytochrome P-450-dependent monooxygenase activity and a wide variety of chemicals have been identified as olfactory toxins. Many chemicals induce lesions of a general nature in the olfactory mucosa, i.e., inflammation, degeneration, regeneration, and proliferation, whereas others cause more specific effects. Changes in the olfactory mucosa with reference to chemicals that initiate them are reviewed in this paper. Studies with 3-trifluoromethyl pyridine (3FMP) illustrate some of these general changes and show the importance of examining the olfactory mucosa at early time periods. The earliest damage seen by light microscopy was 6 hr after a single inhalation exposure to 3FMP, and by day 3, early regenerative changes were observed. Changes were seen by electron microscopy 30 min after an oral dose, and the primary site of toxicity appeared to be the Bowman's glands. Although atrophy of nerve bundles in the lamina propria would be the expected consequence of severe necrosis of the sensory cells, this is not always the case. Exposure to irritants such as acetaldehyde, formaldehyde, and dimethylamine results in nerve bundle atrophy, but with chemicals such as 3FMP, 3-methylindole, and 3-methylfuran--which are activated by mixed-function oxidases--the nerve bundles remain intact. Future work, including metabolism studies, will provide information on the mode of action of these chemicals.

INHALATION TOXICITY STUDIES OF THE α,β-UNSATURATED KETONES: Ethyl Vinyl Ketone

“…Histological changes within the olfactory epithelium consisted of necrosis (degeneration) and regeneration in the rat, and primarily atrophy in the mouse. These changes commonly affected the anterior dorsal meatus, adjacent nasoturbinates, and nasal septum, and were typical of changes seen in the olfactory epithelium following exposure to gaseous irritants or volatile chemicals (Gaskell, 1990;Monticello et al, 1990;Hardisty et al, 2000). Respiratory epithelial changes consisted of hyperplasia and squamous metaplasia primarily along the nasal septum, lateral wall, and turbinates.…”

Proliferative and Nonproliferative Lesions of the Rat and Mouse Respiratory Tract

“…If the injury is not repeated, the affected area will be repaired with epithelium of the same type as the original. Epithelial degeneration, necrosis, and regeneration are often present together in nasal tissues repeatedly exposed to injurious chemicals, resulting in a disorganized morphologic picture (Gaskell 1990;Hardisty et al 1999).…”

“…The area of olfactory epithelium most frequently affected by inhalation of direct-acting gaseous irritants is the most rostral olfactory epithelium lining the dorsal medial meatus (Buckley et al 1984;Hardisty et al 1999). Chemicals requiring metabolism to a toxic intermediate to damage olfactory epithelium usually induce lesions throughout the olfactory epithelium (Gaskell 1990) and may also induce necrosis in adjacent Bowman's glands. A frequent sequela to loss of sensory cells (either through aging or toxic injury) is atrophy of nerve bundles within the lamina propria.…”

Differential effects of olfactory toxicants on olfactory regeneration

“…An increasing number of chemicals are now known to induce extensive morphological changes in the rodent olfactory mucosa, preferentially following inhalation but also following non-inhalatory routes of exposure (Gaskell 1990;Bahrami et al 2000). Olfactory toxicity is often related to a tissue-specific and cytochrome P450 (CYP) -dependent metabolic activation of the chemicals into reactive intermediates (Eriksson and Brittebo 1991;Brittebo et al 1992;Brittebo 1995;Ding et al 1996;Eriksson et al 1996;Bergman and Brittebo 1999).…”