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Event Title

Respiratory or Squamous Metaplasia, Increase
Respiratory or Squamous Metaplasia, Increase

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors KE Strong

Taxonomic Applicability

Name Scientific Name Evidence Links
rat Rattus norvegicus Strong NCBI
mouse Mus musculus Strong NCBI
human Homo sapiens Weak NCBI

Level of Biological Organization

Biological Organization

How this Key Event works

Sustained atrophy/degeneration olfactory epithelium under the influence of a cytotoxic agent leads to adaptive tissue remodeling. Cell types unique to olfactory epithelium, e.g. olfactory neurons, sustentacular cells and Bowmans glands, are replaced by cell types comprising respiratory epithelium or squamous epithelium.

How it is Measured or Detected

Respiratory or squamous metaplasia is measured histologically is cross-sections of the nose after H&E staining and/or use of immunohistochemical markers to show the absence of olfactory epithelial cell types and the presence of cell types of the respiratory or squamous epithelium. Olfactory epithelium is normally composed of X cell types. Respiratory epithelium is composed of Y cell types: The squamous epithelium is composed of Z cell types. The absence of structures such as Bowmans glands and olfactory bundles are also markers of the initial step of respiratory metaplasia. Immunohistochemical staining for olfactory marker protein[1] is used to determine the absence of olfactory sensory neurons. Staining for AB/PAS-positive mucosubstances[2] is used to determine the presence mucous cells, which are normally present in respiratory epithelium. The key features of transitional epiethelium metaplasia are the presence of tall columnar cells with cilia on the luminal surface, basal cells, and nonciliated cuboidal to columnar cells[3].

Evidence Supporting Taxonomic 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.


  1. 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
  2. Wagner, Van Dyken, Hotchkiss and Harkema (2001). Endotoxin enhancement of ozone-induced mucous cell metaplasia is neutrophil-dependent in rat nasal epithelium. Toxicol Sci. 60: 338-347
  3. 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