API

Relationship: 888

Title

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Increase, Tissue Degeneration, Necrosis & Atrophy leads to Increase, Respiratory or Squamous Metaplasia

Upstream event

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Increase, Tissue Degeneration, Necrosis & Atrophy

Downstream event

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Increase, Respiratory or Squamous Metaplasia

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors adjacent Moderate Moderate

Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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Key Event Relationship Description

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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.

Evidence Supporting this KER

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Biological Plausibility

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The biological plausibility of the linkage between these key events is well established. Metaplastic change is a commonly observed adaptive response to chronic toxicant induced injury to olfactory epithelium and tissues in general.

Empirical Evidence

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Tissue degeneration, necrosis and atrophy have been observed consistently after inhalation exposure to the chemical initiator vinyl acetate[1].

Uncertainties and Inconsistencies

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We are unaware of any uncertainties or inconsistencies.

Quantitative Understanding of the Linkage

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Refer to exposure-response tables.

Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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Necrosis, tissue degeneration and atrophy of the olfactory epithelium preceding metaplasia have been observed in rats and mice[2].

References

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  1. Bogdanffy, Dreef-van der Meulen, Beems, Feron, Cascieri, Tyler, Vinegar and Rickard (1994). Chronic toxicity and oncogenicity inhalation study with vinyl acetate in the rat and mouse. Fundam Appl Toxicol. 23: 215-229, Bogdanffy, Gladnick, Kegelman and Frame (1997). FOUR-WEEK INHALATION CELL PROLIFERATION STUDY OF THE EFFECTS OF VINYL ACETATE ON RAT NASAL EPITHELIUM. Inhalation Toxicology, Taylor & Francis. 9: 331-350, Hotchkiss, Krieger, Harkema and Mahoney (2013). Draft Report: VINYL ACETATE: EVALUATION OF VINYL ACETATE-SPECIFIC DNA ADDUCTS, HISTOPATHOLOGY AND EPITHELIAL CELL PROLIFERATION IN NASAL AIRWAYS OF Crl:CD(SD) RATS REPEATEDLY EXPOSED TO VINYL ACETATE VAPORS. Washington, DC, The Vinyl Acetate Council
  2. Bogdanffy, Dreef-van der Meulen, Beems, Feron, Cascieri, Tyler, Vinegar and Rickard (1994). Chronic toxicity and oncogenicity inhalation study with vinyl acetate in the rat and mouse. Fundam Appl Toxicol. 23: 215-229, Bogdanffy, Gladnick, Kegelman and Frame (1997). FOUR-WEEK INHALATION CELL PROLIFERATION STUDY OF THE EFFECTS OF VINYL ACETATE ON RAT NASAL EPITHELIUM. Inhalation Toxicology, Taylor & Francis. 9: 331-350, Hotchkiss, Krieger, Harkema and Mahoney (2013). Draft Report: VINYL ACETATE: EVALUATION OF VINYL ACETATE-SPECIFIC DNA ADDUCTS, HISTOPATHOLOGY AND EPITHELIAL CELL PROLIFERATION IN NASAL AIRWAYS OF Crl:CD(SD) RATS REPEATEDLY EXPOSED TO VINYL ACETATE VAPORS. Washington, DC, The Vinyl Acetate Council