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Event: 868

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increase, Tissue Degeneration, Necrosis & Atrophy

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Tissue

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term
olfactory organ

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
atrophy	olfactory epithelium	increased
necrotic cell death		increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
pH Induced Nasal Tumors	KeyEvent	Undefined (send email)	Open for citation & comment	Under Review

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

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

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

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

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

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].

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

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

List of the literature that was cited for this KE description. More help

↑ 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