This is a legacy representation of this AOP. Please see the current version here:
Dries Knapen , [dries.knapen (at)uantwerpen.be]
Lucia Vergauwen , [lucia.vergauwen(at)uantwerpen.be]
Evelyn Stinckens , [evelyn.stinckens(at)uantwerpen.be]
Dan Villeneuve , [villeneuve.dan*(at)epa.gov]
-  Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium
- United States Environmental Protection Agency, Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN, USA.
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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 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|
|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|
|Population trajectory, Decrease|
Relationships Among Key Events and the Adverse Outcome
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Life Stage Applicability
|fathead minnow||Pimephales promelas||NCBI|
Overall Assessment of the AOP
Domain of Applicability
Life Stage 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
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