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AOP Title

Deiodinase 1 inhibition leading to reduced young of year survival via anterior swim bladder inflation
Short name: DIO1i anterior swim bladder


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

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

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

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

[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.


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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.

The AOP describes the effects of inhibition of deiodinase 1 (DIO1) on anterior swim bladder inflation leading to reduced young of year survival and population trajectory decline. The inhibition of DIO1 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. Fish larvae exposed to PTU, a known DIO1 inhibitor, has been known to result in impairment of swim bladder inflation. Chemicals interfering with the conversion of T4 to T3 have the potential to inhibit anterior chamber inflation which may result in reduced auditory capacity and 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 1, Inhibition

Key Events

Event Support for Essentiality
Triiodothyronine (T3) in serum, Decreased
Anterior swim bladder inflation, Reduced
Hearing, Reduced
Swimming performance, Reduced
Young of year survival, 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 1, Inhibition Directly Leads to Triiodothyronine (T3) in serum, Decreased
Triiodothyronine (T3) in serum, Decreased Directly Leads to Anterior swim bladder inflation, Reduced
Anterior swim bladder inflation, Reduced Directly Leads to Hearing, Reduced
Anterior swim bladder inflation, Reduced Directly Leads to Swimming performance, Reduced
Swimming performance, Reduced Directly Leads to Young of year survival, Reduced
Hearing, Reduced Directly Leads to Young of year survival, Reduced
Young of year survival, Reduced Directly Leads to Population trajectory, Decrease
Deiodinase 1, Inhibition Indirectly Leads to Anterior swim bladder inflation, Reduced

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Life Stage Applicability

Life Stage Evidence Links

Taxonomic Applicability

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

Sex Applicability

Sex Evidence Links

Graphical Representation


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)