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AOP Title

Ecdysone receptor agonism leading to mortality
Short name: EcR agonism leading to mortality


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


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This AOP was last modified on 12/5/2016.

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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.

Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Ecdysone receptor, Activation Strong

Key Events

Event Support for Essentiality
Secretion of ecdysis triggering hormone (ETH), Decreased Moderate
Incomplete ecdysis, Increased Strong
Body contraction, Decreased Moderate
Synthesis of molting fluid proteases, Decreased Moderate
Digestion of old cuticle, Decreased Moderate
Population, Decline
food-web structures, Altered

Adverse Outcome

Adverse Outcome
Food-web structures, Alterations
Mortality, Increased
Population size, Decreased

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Ecdysone receptor, Activation Indirectly Leads to Secretion of ecdysis triggering hormone (ETH), Decreased Moderate Weak
Secretion of ecdysis triggering hormone (ETH), Decreased Directly Leads to Body contraction, Decreased Moderate Weak
Body contraction, Decreased Directly Leads to Incomplete ecdysis, Increased Moderate Weak
Incomplete ecdysis, Increased Indirectly Leads to Mortality, Increased Moderate Weak
Mortality, Increased Indirectly Leads to Population size, Decreased Weak Weak
Ecdysone receptor, Activation Indirectly Leads to Synthesis of molting fluid proteases, Decreased Weak Weak
Synthesis of molting fluid proteases, Decreased Directly Leads to Digestion of old cuticle, Decreased Moderate Weak
Digestion of old cuticle, Decreased Directly Leads to Incomplete ecdysis, Increased Weak Weak

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Life Stage Applicability

Life Stage Evidence Links
Juvenile Strong
Adult Moderate

Taxonomic Applicability

Name Scientific Name Evidence Links
insects Strong
crustaceans Moderate

Sex Applicability

Sex Evidence Links
Unspecific Moderate

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Overall Assessment of the AOP

Weight of Evidence Summary

Summary Table
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Quantitative Considerations

Summary Table
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Applicability of the AOP

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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