SNAPSHOT

AOP ID and Title:

AOP 4: Ecdysone receptor agonism leading to mortality
Short Title: EcR agonism leading to mortality

Authors

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


Status

Open for citation & comment

Abstract

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

Stressors


We will add things to here soon

Molecular Initiating Event

Title Short name Essentiality
Activation, Ecdysone receptor Activation, EcR Strong

Key Events

Title Short name Essentiality
Reduction, Release of circulating ecdysis triggering hormone Reduction, Release of circulating ETH Moderate
Reduction, Abdominal muscle contraction Reduction, Abdominal muscle contraction Moderate
Induction, Incomplete ecdysis Induction, Incomplete ecdysis Strong

Adverse Outcomes

Title Short name Essentiality
Increased, Mortality Increased, Mortality

Relationships between Key Events

Upstream Event Relationship Type Downstream Event
Activation, Ecdysone receptor directly leads to Reduction, Release of circulating ecdysis triggering hormone
Reduction, Release of circulating ecdysis triggering hormone directly leads to Reduction, Abdominal muscle contraction
Reduction, Abdominal muscle contraction directly leads to Induction, Incomplete ecdysis
Induction, Incomplete ecdysis directly leads to Increased, Mortality

Life Stage Applicability

Life Stage Evidence
Juvenile Strong
Adult Moderate

Taxon Applicability

Term Scientific Term Evidence
insects insects Strong
crustaceans Daphnia magna Moderate

Sex Applicability

Sex Evidence
Unspecific Moderate

Graphical Representation

Molecular Initating Event

Event ID and Title

103: Activation, Ecdysone receptor
Short Name: Activation, EcR

Key Event Overview

AOPs Including This Key Event

AOP ID and Name Event Type Essentiality
4: Ecdysone receptor agonism leading to mortality MolecularInitiatingEvent Strong

Stressors

The following are stressors that operate directly through this Event.
Will need to add a loop here once we have chemicals figured out
  1. chemical one
  2. chemical two

Taxonomic Applicability

There are no Taxonomic Terms associated with this Event

Level of Biological Organization
Molecular

Life Stage Applicability

There are no Life Stages associated with this Event

Sex Applicability

There are no Sexes associated with this Event

Key Events

Event ID and Title

988: Reduction, Release of circulating ecdysis triggering hormone
Short Name: Reduction, Release of circulating ETH

Key Event Overview

AOPs Including This Key Event

AOP ID and Name Event Type Essentiality
4: Ecdysone receptor agonism leading to mortality KeyEvent Moderate

Stressors

The following are stressors that operate directly through this Event.
Will need to add a loop here once we have chemicals figured out
  1. chemical one
  2. chemical two

Taxonomic Applicability

There are no Taxonomic Terms associated with this Event

Level of Biological Organization
Tissue

Life Stage Applicability

There are no Life Stages associated with this Event

Sex Applicability

There are no Sexes associated with this Event

Event ID and Title

993: Reduction, Abdominal muscle contraction
Short Name: Reduction, Abdominal muscle contraction

Key Event Overview

AOPs Including This Key Event

AOP ID and Name Event Type Essentiality
4: Ecdysone receptor agonism leading to mortality KeyEvent Moderate

Stressors

The following are stressors that operate directly through this Event.
Will need to add a loop here once we have chemicals figured out
  1. chemical one
  2. chemical two

Taxonomic Applicability

There are no Taxonomic Terms associated with this Event

Level of Biological Organization
Tissue

Life Stage Applicability

There are no Life Stages associated with this Event

Sex Applicability

There are no Sexes associated with this Event

Event ID and Title

990: Induction, Incomplete ecdysis
Short Name: Induction, Incomplete ecdysis

Key Event Overview

AOPs Including This Key Event

AOP ID and Name Event Type Essentiality
4: Ecdysone receptor agonism leading to mortality KeyEvent Strong

Stressors

The following are stressors that operate directly through this Event.
Will need to add a loop here once we have chemicals figured out
  1. chemical one
  2. chemical two

Taxonomic Applicability

There are no Taxonomic Terms associated with this Event

Level of Biological Organization
Individual

Life Stage Applicability

There are no Life Stages associated with this Event

Sex Applicability

There are no Sexes associated with this Event

Adverse Outcome

Event ID and Title

351: Increased, Mortality
Short Name: Increased, Mortality

Key Event Overview

AOPs Including This Key Event

AOP ID and Name Event Type
16: Acetylcholinesterase inhibition leading to acute mortality AdverseOutcome
96: Axonal sodium channel modulation leading to acute mortality AdverseOutcome
104: Altered ion channel activity leading impaired heart function AdverseOutcome
113: Glutamate-gated chloride channel activation leading to acute mortality AdverseOutcome
160: Ionotropic gamma-aminobutyric acid receptor activation mediated neurotransmission inhibition leading to mortality AdverseOutcome
161: Glutamate-gated chloride channel activation leading to neurotransmission inhibition associated mortality AdverseOutcome
138: Organic anion transporter (OAT1) inhibition leading to renal failure and mortality AdverseOutcome
177: Cyclooxygenase 1 (COX1) inhibition leading to renal failure and mortality AdverseOutcome
186: unknown MIE leading to renal failure and mortality AdverseOutcome
4: Ecdysone receptor agonism leading to mortality AdverseOutcome

Stressors

The following are stressors that operate directly through this Event.
Will need to add a loop here once we have chemicals figured out
  1. chemical one
  2. chemical two

Taxonomic Applicability

There are no Taxonomic Terms associated with this Event

Level of Biological Organization
Population

Life Stage Applicability

There are no Life Stages associated with this Event

Sex Applicability

There are no Sexes associated with this Event

Overall Assessment of the AOP

Applicability of the AOP

Life Stage Applicability

Life Stage Evidence
Juvenile Strong
Adult Moderate

Taxon Applicability

Term Scientific Term Evidence
insects insects Strong
crustaceans Daphnia magna Moderate

Sex Applicability

Sex Evidence
Unspecific Moderate

References