API

Event: 868

Key Event Title

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Increase, Tissue Degeneration, Necrosis & Atrophy

Short name

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Increase, Tissue Degeneration, Necrosis & Atrophy

Key Event Component

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Process Object Action
atrophy olfactory epithelium increased
necrotic cell death increased

Key Event Overview


AOPs Including This Key Event

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Stressors

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Level of Biological Organization

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Biological Organization
Tissue


Organ term

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Organ term
olfactory organ


Taxonomic Applicability

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Term Scientific Term Evidence Link
rat Rattus norvegicus Strong NCBI
mouse Mus musculus Strong NCBI
human Homo sapiens Moderate NCBI

Life Stages

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Sex Applicability

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How This Key Event Works

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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

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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[1]. 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[2].


Evidence Supporting Taxonomic Applicability

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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.


References

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  1. 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
  2. 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