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Table 7 Adverse Outcome Pathway of ecdysone receptor agonism leading to incomplete ecdysis-associated mortality [130]

From: Commentary: Assessing the endocrine disrupting effects of chemicals on invertebrates in the European Union

KE Event description Level of organisation Upstream to downstream KE relationship Support for essentiality Biological plausibility Empirical support Overall WoE Quantitative understanding Detection method Target for detection
MIE EcR, activation Macromolecular D S S S S W In vitro ECR binding assay; transcriptional analysis EcR transfected mammalian cells; mRNA from cell, tissue, and whole organism
KE-1 E75b gene, induction Molecular/cellular D S S S S W Transcriptional analysis mRNA from cell, tissue, and whole organism
KE-2 Ftz-f1 gene, suppression Molecular/cellular D M S M M W Transcriptional analysis mRNA from cell, tissue, and whole organism
KE-3 Release of circulating Eth, reduction Tissue/organ I S S M M W Enzyme immunoassay; immunohistochemical staining Haemolymph; isolated endocrine tissue
KE-4 Release of circulating Ccap, reduction Tissue/organ D S S M M W Enzyme immunoassay; immunohistochemical staining Haemolymph; isolated endocrine tissue
KE-5 Ecdysis motoneuron bursts, reduction Tissue/organ D S S M M W Electrophysiological recording Isolated CNS, abdominal ganglion
KE-6 Excitatory postsynaptic potential, reduction Tissue/organ D M S M M W Electrophysiological recording; FM1-43 fluorescent labelling Skeletal muscles
KE-7 Abdominal muscle contraction, reduction Tissue/organ D M S M M W Electrophysiological recording; behavioural (air/water swallowing) assays Skeletal muscles; whole organism
KE-8 Incomplete ecdysis, induction Individual D S S S S S Light microscope, histopathology Cuticle; whole organism
AO Mortality, increased Individual D S S S S St Survival test Whole organism
  1. MIE Molecular Initiating Event, KE key event, AO Adverse Outcome, EcR ecdysone receptor, E75b nuclear receptor E75B, Ftz-f1 Fushi tarazu factor-1, Eth ecdysis triggering hormone, Ccap crustacean cardioactive peptide D direct, I indirect, S strong, M moderate, W weak