Aop:33
Status
This is a legacy representation of this AOP. Please see the current version here:
AOP Title
Authors
Kevin M. Crofton, US EPA, crofton.kevin-at-epa.gov
Status
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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....
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 |
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5HT2c, Activation |
Key Events
Event | Support for Essentiality |
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Unknown, N/A | Weak |
Adverse Outcome
Adverse Outcome |
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Kidney Failure, Increased |
Relationships Among Key Events and the Adverse Outcome
Event | Description | Triggers | Weight of Evidence | Quantitative Understanding |
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5HT2c, Activation | Indirectly Leads to | Unknown, N/A | Weak | Weak |
Unknown, N/A | Indirectly Leads to | Kidney Failure, Increased | Weak | Weak |
Network View
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Life Stage Applicability
Life Stage | Evidence | Links |
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Taxonomic Applicability
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Sex Applicability
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Graphical Representation
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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
Provide an overall assessment of the essentiality for the key events in the AOP. Support calls for individual key events can be included in the molecular initiating event, key event, and adverse outcome tables above.
Quantitative Considerations
Summary Table
Provide an overall discussion of the quantitative information available for this AOP. Support calls for the individual relationships can be included in the Key Event Relationship table above.
Applicability of the AOP
Life Stage Applicability,
Taxonomic Applicability,
Sex Applicability
Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains.
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