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Key Event Title
Increase, Tissue Degeneration, Necrosis & Atrophy
Key Event Components
|necrotic cell death||increased|
Key Event Overview
AOPs Including This Key Event
Key Event Description
Sustained cytotoxicity of cell types comprising the olfactory epithelium, (e.g. olfactory sensory neurons, sustentacular cells, Bowmans glands) causes cell death and a reduction in cell numbers/volume of cells. Normal replacement of the cells may not occur in the presence of the cytotoxic agent. Tissue necrosis, degeneration (deterioration and loss of function) and atrophy (reduction in tissue mass), are observed.
How It Is Measured or Detected
Tissue atrophy/degeneration/necrosis is measured histologically is cross-sections of the nose. The absence of cell types specific to the olfactory epithelium, including Bowmans Glands, Sustanticular cells and sensory cells is commonly reported as evidence of atrophy/degeneration of olfactory epithelium after exposure, for example for vinyl acetate, and a family of related esters. The presence or absence of specific cell types can be determined histologically (e.g. by structure and location) or through immunohistochemical staining. Olfactory sensory neurons can be identified with great specificity by staining for olfactory marker protein.
Domain of Applicability
This event has been observed in the olfactory epithelium of rats and mice exposed by inhalation to one or more of the listed chemical initiators. Degeneration, necrosis and atrophy are expected in humans based conserved properties of the olfactory epithelium across species.
- Hardisty, Garman, Harkema, Lomax and Morgan (1999). Histopathology of nasal olfactory mucosa from selected inhalation toxicity studies conducted with volatile chemicals. Toxicol Pathol. 27: 618-627
- Islam, Amuzie, Harkema and Pestka (2007). Neurotoxicity and inflammation in the nasal airways of mice exposed to the macrocyclic trichothecene mycotoxin roridin a: kinetics and potentiation by bacterial lipopolysaccharide coexposure. Toxicol Sci. 98: 526-541