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AOP: 368
Title
Cytochrome oxidase inhibition leading to olfactory nasal lesions
Short name
Graphical Representation
Point of Contact
Contributors
- Katy Goyak
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on April 29, 2023 16:03
Revision dates for related pages
Page | Revision Date/Time |
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Inhibition, cytochrome oxidase | February 19, 2021 13:59 |
Increase, Cell death | August 23, 2024 10:42 |
Increase, Site of Contact Nasal Tumors | September 16, 2017 10:16 |
Abstract
The AOP is initiated by inhibition of cytochrome oxidase, one of the complexes that carry out oxidative phosphorylation, the main process through which cellular energy is created in the form of ATP (Kühlbrandt 2015; Cogliati et al. 2018). With sufficient inhibition, cell death can occur, particularly for cells with high energy demand like neurons (Kann and Kovács 2007; Rugarli and Langer 2012). Under continued chemical insult, neuronal cell death in the olfactory epithelium may exceed the capacity of olfactory neurons to generate, resulting in adaptive tissue remodeling and basal cell hyperplasia (here defined as olfactory nasal lesions) (Monticello et al. 1990; Hardisty et al. 1999; Teeguarden 2017).
AOP Development Strategy
Context
This AOP was developed for the purpose of bringing mechanistic information as one input into the selection of a point of departure in chemical-specific exposure limit. Based on that purpose, key events were defined and organized into hypothesized AOPs based on previously published systematic reviews on a single chemical (hydrogen sulfide); follow-up literature searches were conducted to inform the WOE assessment to include additional chemical stressors that activate the MIE (potassium cyanide, sodium azide, beta amyloid peptides).
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
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MIE | 1840 | Inhibition, cytochrome oxidase | Inhibition, cytochrome oxidase |
KE | 1825 | Increase, Cell death | Increase, Cell death |
AO | 872 | Increase, Site of Contact Nasal Tumors | Increase, Site of Contact Nasal Tumors |
Relationships Between Two Key Events (Including MIEs and AOs)
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Quantitative Understanding
Considerations for Potential Applications of the AOP (optional)
References
Cogliati S, Lorenzi I, Rigoni G, Caicci F, Soriano ME. 2018. Regulation of Mitochondrial Electron Transport Chain Assembly. Journal of Molecular Biology. 430(24):4849-4873.
Hardisty JF, Garman RH, Harkema JR, Lomax LG, Morgan KT. 1999. Histopathology of Nasal Olfactory Mucosa from Selected Inhalation Toxicity Studies Conducted with Volatile Chemicals. Toxicologic Pathology. 27(6):618-627.
Kann O, Kovács R. 2007. Mitochondria and neuronal activity. American Journal of Physiology-Cell Physiology. 292(2):C641-C657.
Kühlbrandt W. 2015. Structure and function of mitochondrial membrane protein complexes. BMC Biology. 13(1):89.
Monticello TM, Morgan KT, Uraih L. 1990. Nonneoplastic nasal lesions in rats and mice. Environmental health perspectives. 85:249-274.
Rugarli EI, Langer T. 2012. Mitochondrial quality control: a matter of life and death for neurons. The EMBO Journal. 31(6):1336-1349.
Teeguarden JG. 2017. AOP136: Intracellular acidification induced olfactory epithelial injury leading to site of contact nasal tumors (status as of 5 July 2019: "Open for citation & Comment"). Last modified 20 March 2017. https://aopwiki.org/aops/136.