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Aop: 4

AOP Title

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Ecdysone receptor agonism leading to mortality

Short name:

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EcR agonism leading to mortality

Authors

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You Song1 and Knut Erik Tollefsen1,2
1 Norwegian Institute for Water Research (NIVA), Section of Ecotoxicology and Risk Assessment, Gaustadalléen 21, N-0349 Oslo, Norway
2 Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV). P.O. Box 5003, N-1432 Ås, Norway
Contact: knut.erik.tollefsen@niva.no

Point of Contact

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Knut Erik Tollefsen

Contributors

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  • Knut Erik Tollefsen
  • You Song

Status

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Author status OECD status OECD project SAAOP status
Open for citation & comment Under Development


This AOP was last modified on February 15, 2017 13:49

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Revision dates for related pages

Page Revision Date/Time
Activation, Ecdysone receptor September 16, 2017 10:14
Reduction, Release of circulating ecdysis triggering hormone September 16, 2017 10:14
Induction, Incomplete ecdysis September 16, 2017 10:14
Reduction, Abdominal muscle contraction September 16, 2017 10:14
Increased, Mortality May 15, 2017 11:34
Induction, Nuclear receptor E75b gene September 16, 2017 10:14
Suppression, Fushi tarazu factor-1 gene September 16, 2017 10:14
Reduction, Release of circulating crustacean cardioactive peptide September 16, 2017 10:14
Reduction, Ecdysis motoneuron bursts September 16, 2017 10:14
Reduction, Excitatory postsynaptic potential September 16, 2017 10:14
Activation, EcR leads to Induction, E75b gene February 09, 2017 03:33
Induction, E75b gene leads to Suppression, Ftz-f1 gene February 09, 2017 03:33
Suppression, Ftz-f1 gene leads to Reduction, Release of circulating ETH February 09, 2017 03:34
Reduction, Release of circulating ETH leads to Reduction, Release of circulating CCAP February 09, 2017 03:34
Reduction, Release of circulating CCAP leads to Reduction, Ecdysis motoneuron bursts February 09, 2017 03:35
Reduction, Ecdysis motoneuron bursts leads to Reduction, Excitatory postsynaptic potential February 09, 2017 03:35
Reduction, Excitatory postsynaptic potential leads to Reduction, Abdominal muscle contraction February 09, 2017 03:36
Reduction, Abdominal muscle contraction leads to Induction, Incomplete ecdysis December 03, 2016 16:38
Induction, Incomplete ecdysis leads to Increased, Mortality December 03, 2016 16:38
Tebufenozide February 09, 2017 03:06
20-hydroxyecdysone February 09, 2017 03:06
Ponasterone A February 09, 2017 03:06
Methoxyfenozide February 09, 2017 03:42
Halofenozide February 06, 2017 12:28
Chromafenozide February 09, 2017 03:41
Cyasterone February 09, 2017 03:42
Makisterone A February 09, 2017 03:43
Inokosterone February 09, 2017 03:43
Ecdysone February 09, 2017 03:43
RH-5849 February 09, 2017 03:43

Abstract

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Molting is a natural biological process in arthropods. During a molt cycle, the animals generate new exoskeletons by the epidermis and shed the old ones in order to grow. Successful molting is key to survival, development and reproduction. Over half a century research on arthropod endocrinology reveals that molting is precisely controlled by complex multi-hormone systems, with 20-hydroxyecdysone (20E) being the key effective hormone to mediate different biological processes that are necessary for molting. The hormonal actions of 20E are exerted through binding and modulation of the ecdysone receptors (EcR), which are nuclear transcriptional factors that regulate a wide range of physiological and behavioral changes. Based on this knowledge, endocrine disrupting chemicals (EDCs) targeting at the EcRs are developed as pesticides and anti-parasite pharmaceuticals in order to disrupt the molting cycles of “harmful” arthropods and protect the agriculture and aquaculture. However, environmental residues of these EDCs may also affect non-target species, such as a number of crustaceans (e.g. crabs and lobsters) with great ecological and economical values, due to highly conserved endocrine systems in arthropods. Substantial efforts are therefore needed to assess the environmental hazards and risks of EDCs on non-target species. Due to the high number (over a million described) of species in the phylum of Arthopoda, it is not feasible to perform toxicity testing for each species as well as EDC. Construction of universal models on basis of systems (eco)toxicology and phylogenetic similarities for understanding the environmental endocrine disruption (ED) effects may serve as a potential solution. The current AOP is therefore developed based on available information in the databases to identify knowledge gaps in this research field. The conceptual AOP will be further expanded using a combination of laboratory studies and advance in sillico predictions of potential EcR ligands and taxonomic appllicablity to inform environmental risk assessment as an ultimate goal.


Background (optional)

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Summary of the AOP

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Stressors

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Name Evidence Term
Tebufenozide Strong
20-hydroxyecdysone Strong
Ponasterone A Strong
Methoxyfenozide Strong
Halofenozide Strong
Chromafenozide Strong
Cyasterone Strong
Makisterone A Strong
Inokosterone Strong
Ecdysone Strong
RH-5849 Strong

Molecular Initiating Event

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Title Short name
Activation, Ecdysone receptor Activation, EcR

Key Events

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Title Short name
Induction, Nuclear receptor E75b gene Induction, E75b gene
Suppression, Fushi tarazu factor-1 gene Suppression, Ftz-f1 gene
Reduction, Release of circulating ecdysis triggering hormone Reduction, Release of circulating ETH
Reduction, Release of circulating crustacean cardioactive peptide Reduction, Release of circulating CCAP
Reduction, Ecdysis motoneuron bursts Reduction, Ecdysis motoneuron bursts
Reduction, Excitatory postsynaptic potential Reduction, Excitatory postsynaptic potential
Reduction, Abdominal muscle contraction Reduction, Abdominal muscle contraction
Induction, Incomplete ecdysis Induction, Incomplete ecdysis

Adverse Outcome

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Title Short name
Increased, Mortality Increased, Mortality

Relationships Between Two Key Events (Including MIEs and AOs)

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Network View

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Life Stage Applicability

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Life stage Evidence
Juvenile Strong
Adult Moderate

Taxonomic Applicability

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Term Scientific Term Evidence Link
insects insects Strong NCBI
crustaceans Daphnia magna Moderate NCBI

Sex Applicability

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Sex Evidence
Unspecific Moderate

Graphical Representation

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Click to download graphical representation template

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Weight of Evidence Summary

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Quantitative Considerations

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Considerations for Potential Applications of the AOP (optional)

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References

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