Aop:33

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Status

This is a legacy representation of this AOP. Please see the current version here:

https://aopwiki.org/aops/33


AOP Title

Kidney toxicity induced by activation of 5HT2C
Short name: Kidney toxicity induced by activation of 5HT2C

Authors

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

Status

Please follow the link to snapshots page to view and create Snapshots of this AOP.

Alert: This is a putative AOP based on statistical associations between in vitro data and in vivo outcome.

Under development: Do not distribute or cite.

(x) Under development

( ) Under review

( ) Final as will ever be....

OECD Project 1.29: A catalog of putative AOPs that will enhance the utility of US EPA Toxcast high throughput screening data for hazard identification

This AOP page was last modified on 12/11/2016.

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Abstract

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.

Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
5HT2c, Activation

Key Events

Event Support for Essentiality
Unknown, N/A Weak

Adverse Outcome

Adverse Outcome
Kidney Failure, Increased

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
5HT2c, Activation Indirectly Leads to Unknown, N/A Weak Weak
Unknown, N/A Indirectly Leads to Kidney Failure, Increased Weak Weak

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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.

Weight of Evidence Summary

Summary Table
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Quantitative Considerations

Summary Table
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Applicability of the AOP

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Considerations for Potential Applications of the AOP (optional)

References

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