Aop:155

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AOP Title

Deiodinase 2 inhibition leading to reduced young of year survival via posterior swim bladder inflation
Short name: DIO2i posterior swim bladder

Authors

Dries Knapen [1], [dries.knapen (at)uantwerpen.be]

Lucia Vergauwen [1], [lucia.vergauwen(at)uantwerpen.be]

Evelyn Stinckens [1], [evelyn.stinckens(at)uantwerpen.be]

Dan Villeneuve [2], [villeneuve.dan*(at)epa.gov]

[1] Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium
[2]United States Environmental Protection Agency, Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN, USA.

Status

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Under development: Do not distribute or cite.

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

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OECD EAGMST AOP Development Programme Project 1.35: The adverse outcome pathway on thyroperoxidase and/or deiodinase inhibition leading to impaired swim bladder inflation in fish during early life stages.

Abstract

The AOP describes the effects of inhibition of deiodinase 2 (DIO2) on posterior swim bladder inflation leading to reduced young of year survival and population trajectory decline. The inhibition of DIO2 is the molecular-initiating event (MIE), which results in decreased circulating concentrations of triiodothyronine (T3) in serum. Disruption of the thyroid hormone (TH) system is increasingly being recognized as an important MoA that can lead to adverse outcomes, especially during embryonic development. In fish, many different adverse effects during early development resulting from disruption of the TH endocrine system have been reported (e.g.,effects on body and eye size, head-to-trunk angle, heartbeat, otolith formation, pigmentation index, swim bladder inflation, hatching time, somite formation, escape response and photoreceptor development). As in amphibians, the transition in fish between the different developmental phases, including maturation and inflation of the swim bladder, have been shown to be mediated by THs. Chemicals interfering with the conversion of T4 to T3 have the potential to inhibit posterior chamber inflation which may result in reduced swimming capacity of the fish, a relevant adverse outcome that can affect feeding behaviour and predator avoidance, resulting in lower survival probability and ultimately population trajectory decline (Czesny et al., 2005; Woolley and Qin, 2010).

Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Deiodinase 2, Inhibition

Key Events

Event Support for Essentiality
Triiodothyronine (T3) in serum, Decreased
Posterior swim bladder inflation, Reduced
Swimming performance, Reduced
Young of year survival, Reduced
Anterior swim bladder inflation, Reduced
Hearing, Reduced

Adverse Outcome

Adverse Outcome
Population trajectory, Decrease

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Deiodinase 2, Inhibition Directly Leads to Triiodothyronine (T3) in serum, Decreased
Triiodothyronine (T3) in serum, Decreased Directly Leads to Posterior swim bladder inflation, Reduced
Posterior swim bladder inflation, Reduced Directly Leads to Swimming performance, Reduced
Swimming performance, Reduced Directly Leads to Young of year survival, Reduced
Young of year survival, Reduced Directly Leads to Population trajectory, Decrease
Posterior swim bladder inflation, Reduced Directly Leads to Anterior swim bladder inflation, Reduced
Anterior swim bladder inflation, Reduced Directly Leads to Hearing, Reduced
Hearing, Reduced Directly Leads to Young of year survival, Reduced
Anterior swim bladder inflation, Reduced Directly Leads to Swimming performance, Reduced
Posterior swim bladder inflation, Reduced Indirectly Leads to Young of year survival, Reduced Strong Weak
Deiodinase 2, Inhibition Indirectly Leads to Posterior swim bladder inflation, Reduced

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Life Stage Applicability

Life Stage Evidence Links
development

Taxonomic Applicability

Name Scientific Name Evidence Links
fathead minnow Pimephales promelas NCBI
zebrafish Danio rerio NCBI

Sex Applicability

Sex Evidence Links
Unspecific

Graphical Representation

Dio2-post.jpg

Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Weight of Evidence Summary

Summary Table
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Quantitative Considerations

Summary Table
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Considerations for Potential Applications of the AOP (optional)

References