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