API

Aop: 114

AOP Title

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HPPD inhibition leading to corneal papillomas and carcinomas (in rat)

Short name:

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HPPD- corneal papilloma/carcinoma

Authors

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Cancer AOP group. National Health and Environmental Effects Research Laboratory, Office of Research and Development, Integrated Systems Toxicology Division, US Environmental Protection Agency, Research Triangle Park, NC. Corresponding author for wiki entry (wood.charles@epa.gov)

Point of Contact

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Charles Wood

Contributors

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  • Charles Wood

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite Under Development 1.29 Included in OECD Work Plan


This AOP was last modified on December 03, 2016 16:37

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Revision dates for related pages

Page Revision Date/Time
Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme December 03, 2016 16:37
Increased, Plasma tyrosine September 16, 2017 10:16
Increase, Cytotoxicity (corneal cells) September 16, 2017 10:16
Increase, Inflammation (corneal cells) September 16, 2017 10:16
Increase, Regenerative cell proliferation (corneal cells) September 16, 2017 10:16
Increase, Papillomas/carcinomas (squamous cells) September 16, 2017 10:16
Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme leads to Increased, Plasma tyrosine December 03, 2016 16:38
Increased, Plasma tyrosine leads to Increase, Cytotoxicity (corneal cells) December 03, 2016 16:38
Increase, Cytotoxicity (corneal cells) leads to Increase, Inflammation (corneal cells) December 03, 2016 16:38
Increase, Inflammation (corneal cells) leads to Increase, Regenerative cell proliferation (corneal cells) December 03, 2016 16:38
Increase, Regenerative cell proliferation (corneal cells) leads to Increase, Papillomas/carcinomas (squamous cells) December 03, 2016 16:38

Abstract

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This putative adverse outcome pathway (AOP) outlines potential key events leading to a tumor outcome in standard carcinogenicity models. This information is based largely on modes of action described previously in cited literature sources and is intended as a resource template for AOP development and data organization. Presentation in this Wiki does not indicate EPA acceptance of a particular pathway for a given reference agent, only that the information has been proposed in some manner. In addition, this putative AOP relates to the model species indicated and does not directly address issues of human relevance.


Background (optional)

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Summary of the AOP

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Stressors

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Molecular Initiating Event

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Title Short name
Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme Inhibition, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) enzyme

Key Events

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Title Short name
Increased, Plasma tyrosine Increased, Plasma tyrosine
Increase, Cytotoxicity (corneal cells) Increase, Cytotoxicity (corneal cells)
Increase, Inflammation (corneal cells) Increase, Inflammation (corneal cells)
Increase, Regenerative cell proliferation (corneal cells) Increase, Regenerative cell proliferation (corneal cells)

Adverse Outcome

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Title Short name
Increase, Papillomas/carcinomas (squamous cells) Increase, Papillomas/carcinomas (squamous cells)

Relationships Between Two Key Events (Including MIEs and AOs)

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Network View

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Life Stage Applicability

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Rattus norvegicus Rattus norvegicus NCBI

Sex Applicability

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Sex Evidence
Male
Female

Graphical Representation

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Click to download graphical representation template

Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Weight of Evidence Summary

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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

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References

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Lewis, R. W., & Botham, J. W. (2013). A review of the mode of toxicity and relevance to humans of the triketone herbicide 2-(4-methylsulfonyl-2-nitrobenzoyl)-1,3-cyclohexanedione. Crit Rev Toxicol, 43(3), 185-199. doi: 10.3109/10408444.2013.764279

U.S. Environmental Protection Agency. (September 7, 2007). Tembotrione Human Health Risk Assessment.: Retrieved from http://www.regulations.gov/.