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Aop: 4

AOP Title

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Ecdysone receptor agonism leading to incomplete ecdysis associated mortality

Short name:

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EcR agonism leading to incomplete ecdysis associated mortality

Graphical Representation

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Click to download graphical representation template

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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: you.song@niva.no; knut.erik.tollefsen@niva.no

Point of Contact

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Knut Erik Tollefsen   (email point of contact)

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 May 24, 2018 16:51

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Revision dates for related pages

Page Revision Date/Time
Increase, Ecdysone receptor agonism May 24, 2018 16:30
Decrease, Circulating ecdysis triggering hormone May 24, 2018 16:34
Increase, Incomplete ecdysis May 24, 2018 16:41
Decrease, Abdominal muscle contraction May 24, 2018 16:41
Increase, Nuclear receptor E75b gene expression May 24, 2018 16:32
Increase, Fushi tarazu factor-1 gene expression May 24, 2018 16:33
Decrease, Circulating crustacean cardioactive peptide May 24, 2018 16:37
Decrease, Ecdysis motoneuron bursts May 24, 2018 16:38
Decrease, Excitatory postsynaptic potential May 24, 2018 16:39
Increase, Mortality December 03, 2016 16:33
Increase, EcR agonism leads to Increase, E75b expression February 09, 2017 03:33
Increase, E75b expression leads to Increase, Ftz-f1 expression February 09, 2017 03:33
Increase, Ftz-f1 expression leads to Decrease, Circulating ETH February 09, 2017 03:34
Decrease, Circulating ETH leads to Decrease, Circulating CCAP February 09, 2017 03:34
Decrease, Circulating CCAP leads to Decrease, Ecdysis motoneuron bursts February 09, 2017 03:35
Decrease, Ecdysis motoneuron bursts leads to Decrease, Excitatory postsynaptic potential February 09, 2017 03:35
Decrease, Excitatory postsynaptic potential leads to Decrease, Abdominal muscle contraction February 09, 2017 03:36
Decrease, Abdominal muscle contraction leads to Increase, Incomplete ecdysis December 03, 2016 16:38
Increase, Incomplete ecdysis leads to Increase, 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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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 103 Increase, Ecdysone receptor agonism Increase, EcR agonism
2 KE 1264 Increase, Nuclear receptor E75b gene expression Increase, E75b expression
3 KE 1265 Increase, Fushi tarazu factor-1 gene expression Increase, Ftz-f1 expression
4 KE 988 Decrease, Circulating ecdysis triggering hormone Decrease, Circulating ETH
5 KE 1266 Decrease, Circulating crustacean cardioactive peptide Decrease, Circulating CCAP
6 KE 1267 Decrease, Ecdysis motoneuron bursts Decrease, Ecdysis motoneuron bursts
7 KE 1268 Decrease, Excitatory postsynaptic potential Decrease, Excitatory postsynaptic potential
8 KE 993 Decrease, Abdominal muscle contraction Decrease, Abdominal muscle contraction
9 KE 990 Increase, Incomplete ecdysis Increase, Incomplete ecdysis
KE 350 Increase, Mortality Increase, Mortality

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Increase, EcR agonism leads to Increase, E75b expression adjacent High Low
Increase, E75b expression leads to Increase, Ftz-f1 expression adjacent High Low
Increase, Ftz-f1 expression leads to Decrease, Circulating ETH adjacent Moderate Low
Decrease, Circulating ETH leads to Decrease, Circulating CCAP adjacent Moderate Low
Decrease, Circulating CCAP leads to Decrease, Ecdysis motoneuron bursts adjacent Moderate Low
Decrease, Ecdysis motoneuron bursts leads to Decrease, Excitatory postsynaptic potential adjacent Moderate Low
Decrease, Excitatory postsynaptic potential leads to Decrease, Abdominal muscle contraction adjacent Moderate Low
Decrease, Abdominal muscle contraction leads to Increase, Incomplete ecdysis adjacent Moderate Low
Increase, Incomplete ecdysis leads to Increase, Mortality adjacent High High

Network View

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Stressors

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Life Stage Applicability

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Life stage Evidence
Juvenile High
Adult High

Taxonomic Applicability

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

Sex Applicability

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Sex Evidence
Unspecific Moderate

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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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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Song, Y.; Villeneuve, D. L.; Toyota, K.; Iguchi, T.; Tollefsen, K. E., 2017. Ecdysone receptor agonism leading to lethal molting disruption in arthropods: review and adverse outcome pathway development. Environ Sci Technol, 51, (8), 4142-4157.

Song, Y., Evenseth, L.M., Iguchi, T., Tollefsen, K.E., 2017. Release of chitobiase as an indicator of potential molting disruption in juvenile Daphnia magna exposed to the ecdysone receptor agonist 20-hydroxyecdysone. J Toxicol Environ Health A, 1-9

Fay, K. A., Villeneuve, D. L., LaLone, C. A., Song, Y., Tollefsen, K. E. and Ankley, G. T., 2017. Practical approaches to adverse outcome pathway (AOP) development and weight of evidence evaluation as illustrated by ecotoxicological case studies. Environ. Toxicol. Chem. 36(6):1429-1449.

Miyakawa, H., Sato, T., Song, Y., Tollefsen, K.E., Iguchi, T., 2017. Ecdysteroid and juvenile hormone biosynthesis, receptors and their signaling in the freshwater microcrustacean Daphnia. J Steroid Biochem Mol Biol. pii: S0960-0760(17), 30370-30379.