To the extent possible under law, AOP-Wiki has waived all copyright and related or neighboring rights to KE:768

Event: 768

Key Event Title

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

Increase, Cytotoxicity

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
Increase, Cytotoxicity
Explore in a Third Party Tool

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
Cellular

Cell 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
Cell term
eukaryotic cell

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

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
cell death increased
leukocyte mediated cytotoxicity 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
PDK inhibition- HCC KeyEvent Charles Wood (send email) Under Development: Contributions and Comments Welcome
pH Induced Nasal Tumors KeyEvent Justin Teeguarden (send email) Open for citation & comment EAGMST Under Review
Oxidative stress in chronic kidney disease KeyEvent Frederic Y. Bois (send email) Under development: Not open for comment. Do not cite

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
Rattus sp. ABTC 42503 Rattus sp. ABTC 42503 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

Reductions in cellular pH that exceed homeostatic controls leads to denatured/dysfunctional cellular apparatus (enzymes)[1] and cell death[2].

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

Cytotoxicity is measured in vitro using one of many available standardized methods, including the release of the intracellular enzyme lactate dehydrogenase[3], alkaline phosphatase[4] cell counts [5], mitochondrial function[6] and dye exclusion assays[7]. Cytotoxicity is measured in vivo by histopathological evaluation of tissue. The presence of dead cells and/or cellular debris is direct evidence of cytotoxicity at the time of tissue sampling. Histological evidence of previous cytotoxicity is reported as tissue degeneration and/or atrophy.

Domain of Applicability

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

Cell death is the inevitable outcome of sufficient cellular disruption in any living cell. Cytotoxicity has been observed in the olfactory epithelium of rats and mice exposed by inhalation to one or more of the listed chemical initiators. Cytotoxicity is expected in humans based conserved properties of the of the olfactory epithelium across species.

References

List of the literature that was cited for this KE description. More help
  1. Bogdanffy (2002). Vinyl acetate-induced intracellular acidification: implications for risk assessment. Toxicol Sci. 66: 320-326
  2. Bogdanffy (2002). Vinyl acetate-induced intracellular acidification: implications for risk assessment. Toxicol Sci. 66: 320-326, Izumi, Torigoe, Ishiguchi, Uramoto, Yoshida, Tanabe, Ise, Murakami, Yoshida, Nomoto and Kohno (2003). Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer Treat Rev. 29: 541-549, Fais (2010). Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism. J Intern Med. 267: 515-525
  3. (2008). Principles and Methods of Toxicology. Boca Raton, FL, Taylor and Francis: 2193
  4. Kuykendall, Taylor and Bogdanffy (1993). Cytotoxicity and DNA-protein crosslink formation in rat nasal tissues exposed to vinyl acetate are carboxylesterase-mediated. Toxicol Appl Pharmacol. 123: 283-292
  5. Theiszova, Jantova, Dragunova, Grznarova and Palou (2005). Comparison the cytotoxicity of hydroxyapatite measured by direct cell counting and MTT test in murine fibroblast NIH-3T3 cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 149: 393-396, (2008). Principles and Methods of Toxicology. Boca Raton, FL, Taylor and Francis: 2193
  6. Theiszova, Jantova, Dragunova, Grznarova and Palou (2005). Comparison the cytotoxicity of hydroxyapatite measured by direct cell counting and MTT test in murine fibroblast NIH-3T3 cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 149: 393-396, (2008). Principles and Methods of Toxicology. Boca Raton, FL, Taylor and Francis: 2193
  7. Weisenthal, Dill, Kurnick and Lippman (1983). Comparison of dye exclusion assays with a clonogenic assay in the determination of drug-induced cytotoxicity. Cancer Res. 43: 258-264, Elia, Storer, Harmon, Kraynak, McKelvey, Hertzog, Keenan, DeLuca and Nichols (1993). Cytotoxicity as measured by trypan blue as a potentially confounding variable in the in vitro alkaline elution/rat hepatocyte assay. Mutat Res. 291: 193-205