API

Aop: 33

AOP Title

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Kidney toxicity induced by activation of 5HT2C

Short name:

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Kidney toxicity induced by activation of 5HT2C

Authors

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Kevin M. Crofton, US EPA, crofton.kevin-at-epa.gov

Point of Contact

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Kevin Crofton

Contributors

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  • Kevin Crofton

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite Under Development


This AOP was last modified on June 06, 2017 21:53

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Revision dates for related pages

Page Revision Date/Time
Activation, 5HT2c September 16, 2017 10:14
Increased, Kidney Failure December 03, 2016 16:37
N/A, Unknown September 16, 2017 10:14
Activation, 5HT2c leads to N/A, Unknown December 03, 2016 16:38
N/A, Unknown leads to Increased, Kidney Failure December 03, 2016 16:38

Abstract

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This is a proposed AOP that is based on simple correlational analyses between ToxCast high-throughput screening data and significant increased odds rations for adverse outcomes. This specific proposed AOP is based on results presented in Thomas RS, Black MB, Li L, Healy E, Chu TM, Bao W, Andersen ME, Wolfinger RD.A comprehensive statistical analysis of predicting in vivo hazard using high-throughput in vitro screening. Toxicol Sci. 2012 Aug;128(2):398-417. doi: 10.1093/toxsci/kfs159. Epub 2012 Apr 26. PMID: 22543276

The main purpose of posting this proposed AOP that provides nothing more than a MIE and an adverse outcome is to generate input on whether there are any known biological key events that would link the MIE to the AO.


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
Activation, 5HT2c Activation, 5HT2c

Key Events

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Title Short name
N/A, Unknown N/A, Unknown

Adverse Outcome

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Title Short name
Increased, Kidney Failure Increased, Kidney Failure

Relationships Between Two Key Events (Including MIEs and AOs)

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Title Directness Evidence Quantitative Understanding
Activation, 5HT2c leads to N/A, Unknown Indirectly leads to Weak Weak
N/A, Unknown leads to Increased, Kidney Failure Indirectly leads to Weak Weak

Network View

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Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Graphical Representation

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Click to download graphical representation template

Overall Assessment of the AOP

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Consider the following criteria (may include references to KE Relationship pages): 1. concordance of dose-response relationships; 2. temporal concordance among the key events and adverse effect; 3. strength, consistency, and specificity of association of adverse effect and initiating event; 4. biological plausibility, coherence, and consistency of the experimental evidence; 5. alternative mechanisms that logically present themselves and the extent to which they may distract from the postulated AOP. It should be noted that alternative mechanisms of action, if supported, require a separate AOP; 6. uncertainties, inconsistencies and data gaps.

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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Thomas RS, Black MB, Li L, Healy E, Chu TM, Bao W, Andersen ME, Wolfinger RD.A comprehensive statistical analysis of predicting in vivo hazard using high-throughput in vitro screening. Toxicol Sci. 2012 Aug;128(2):398-417. doi: 10.1093/toxsci/kfs159. Epub 2012 Apr 26. PMID: 22543276