PR:Q94900 PR glutamate-gated chloride channel (fruit fly) CHEBI:17996 CHEBI chloride PCO:0000003 PCO population quality GO:0005254 GO chloride channel activity GO:1902476 GO chloride transmembrane transport GO:0060081 GO membrane hyperpolarization MP:0001393 MP ataxia MP:0001399 MP hyperactivity MP:0000753 MP paralysis D009026 MESH mortality 1 WIKI increased 2 WIKI decreased WikiUser_22 all species 132113 NCBI Bombus impatiens WikiUser_10 ApacheUser chaetanaphothrips orchidii 46012 NCBI Radopholus similis WCS_35525 common ecological species Daphnia magna 83647 NCBI Orius insidiosus WikiUser_11 ApacheUser hymenoptera 7113 NCBI Helicoverpa zea WikiUser_12 ApacheUser lepidoptera 198433 NCBI Liriomyza trifolii WikiUser_13 ApacheUser orius isidiosus 34664 NCBI Acyrthosiphon kondoi Activation, Glutamate-gated chloride channel Activation, Glutamate-gated chloride channel Molecular AOPWiki 2016-11-29T18:41:26 2016-12-03T16:37:51 Increased, Chloride conductance Increased, Chloride conductance Cellular CL:0000540 CL neuron AOPWiki 2016-11-29T18:41:26 2017-09-16T10:16:11 hyperpolarisation, neuron hyperpolarisation, neuron Cellular CL:0000540 CL neuron AOPWiki 2016-11-29T18:41:26 2017-09-16T10:16:12 N/A, Ataxia, paralysis, or hyperactivity N/A, Ataxia, paralysis, or hyperactivity Organ UBERON:0001134 UBERON skeletal muscle tissue AOPWiki 2016-11-29T18:41:26 2017-09-16T10:16:11 Increased Mortality Increased Mortality Population <p><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Increased mortality refers to an increase in the number of individuals dying in an experimental replicate group or in a population over a specific period of time.</span></span></span></span></p> <p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="font-size:11pt"><span style="color:#212529"><span style="background-color:white">Mortality of animals is generally observed as cessation of the heart beat, breathing (gill or lung movement) and locomotory movements. Mortality is typically measured by observation. Depending on the size of the organism, instruments such as microscopes may be used. The reported metric is mostly the mortality rate: the number of deaths in a given area or period, or from a particular cause.</span></span></span></span></span></span></p> <p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="font-size:11pt"><span style="color:#212529"><span style="background-color:white">Depending on the species and the study setup, mortality can be measured:</span></span></span></span></span></span></p> <ul> <li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11pt"><span style="color:#212529"><span style="background-color:white">in the lab by recording mortality during exposure experiments</span></span></span></span></span></li> <li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11pt"><span style="color:#212529"><span style="background-color:white">in dedicated setups simulating a realistic situation such as mesocosms or drainable ponds for aquatic species</span></span></span></span></span></li> <li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11pt"><span style="color:#212529"><span style="background-color:white">in the field, for example by determining age structure after one capture, or by capture-mark-recapture efforts. The latter is a method commonly used in ecology to estimate an animal population&#39;s size where it is impractical to count every individual.</span></span></span></span></span></li> </ul> <p>All living things are susceptible to mortality.</p> Moderate Unspecific High All life stages High AOPWiki 2016-11-29T18:41:24 2022-07-08T07:32:26 Decreased, population 1 Decreased, population 1 Population AOPWiki 2016-11-29T18:41:26 2016-12-03T16:37:51 <upstream-id>b2dfe2d4-e2ed-47bd-9a70-9571f6a117b7</upstream-id> <downstream-id>2cfd7a3e-49e3-4360-a943-9c6742657ece</downstream-id> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 <upstream-id>cd7b4755-5312-4512-b968-77339ecbe947</upstream-id> <downstream-id>be29998a-41a7-4993-8547-176de7d195ba</downstream-id> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 <upstream-id>b6eb3100-d6b3-49af-a70d-3085b12374d9</upstream-id> <downstream-id>4f4f3006-3745-439c-bf96-7ba10ddff069</downstream-id> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 <upstream-id>be29998a-41a7-4993-8547-176de7d195ba</upstream-id> <downstream-id>b6eb3100-d6b3-49af-a70d-3085b12374d9</downstream-id> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 <upstream-id>2cfd7a3e-49e3-4360-a943-9c6742657ece</upstream-id> <downstream-id>cd7b4755-5312-4512-b968-77339ecbe947</downstream-id> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:00 Glutamate-gated chloride channel activation leading to acute mortality GluCl activation to mortality Helen Poynton <p>Helen Poynton, Lily Green, Alan Bartels</p> <p>Kellie Fay (putative AOP)</p> BY-SA 1.0 <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">This report describes a novel adverse outcome pathway (AOP) of activation of glutamate-gated chloride (GluCl) channels leading to acute mortality (AOPWiki, AOP113). Glutamate-gated chloride channels are a class of&nbsp; ligand-gated ion channels present in protostome invertebrate phyla. The macrocyclic lactone (ML) family of drugs (e.g. abermectin and ivermectin) target glutamate-gated chloride channels, activating them or potentiating their response to the endogenous agonist, glutamate. These drugs are widely used for the control of agricultural pests as well as medical and veterinary pathogens. Describing the mechanism of GluCl channel activation leading to acute mortality can facilitate understanding and environmental risk assessment of drugs that initiate this AOP. In this AOP, three proposed key events lead to two adverse outcomes of increased mortality and decreased population. The key events and key event relationships within the AOP are assessed for weight of evidence using evolved Bradford-Hill considerations. The overall confidence level of these events and relationships ranges from moderate to high, with few uncertainties and inconsistencies. The chemical applicability domain of the AOP mainly considers macrocyclic lactones as GluCl channel agonists. The biological domain of the AOP spans members of the protostome clade. The AOP described in this report is part of the larger AOP network connecting GluCl channel activation to death and is relevant and applicable to ecological risk assessments.</span></span></span></span></p> <p><span style="font-size:9pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Glutamate-gated chloride (GluCl) channels are pentameric transmembrane chloride ion channels unique to invertebrates. They are a member of the Cys-loop ligand-gated ion channel superfamily that are gated by invertebrate neurotransmitters such as histamine, serotonin, dopamine, acetylcholine, and GABA (Wolstenholme, 2012). GluCl channels are key components of the invertebrate nervous system, inhibiting neuronal signal transmission upon activation by the endogenous neurotransmitter glutamate. </span></span></span></span></p> <p><span style="font-size:9pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Glutamate-gated chloride channels are present in neurons and straited muscle tissue across protostome invertebrate phyla, including mollusks, flatworms, roundworms (nematodes), ticks, mites, insects, and crustaceans (Wolstenholme, 2012). Multiple protostome species are pathogenic or disease vectors in humans (e.g. river blindness and lymphatic filariasis), and are considered veterinary and agricultural pests (Degani-Katzav et al. 2016). The macrocyclic group of anthelmintics, insecticides, and acaricides (e.g. Ivermectin, Abamectin), target GluCls, activating them directly or potentiating their response to the endogenous agonist glutamate (Wolstenholme, 2012). The intensive usage of macrocyclic lactone drugs, ivermectin the most widely used, as well as the high acute toxicity of the drugs to invertebrates motivate the development of this AOP. This AOP describes the increase in individual mortality and population decline linked to the activation of the glutamate-gated chloride channel.</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The present AOP (Textbox 1 and Figure 2) links the activation of the glutamate-gated chloride channel (MIE, event 760), leading to increased mortality (adverse outcome, event 351) and decreased population (adverse outcome, event 765) via three key events, the increase in chloride conductance (KE1, event 761), hyperpolarization of the neuron (KE2, event 763), and ataxia, paralysis, or hyperactivity (KE3, event 764). The MIE constitutes the binding of an agonist to a receptor in the GluCl channel, leading to its activation. Upon binding and activation, the GluCl channel undergoes a conformational change, opening its internal pore to allow for increased flow of chloride ions into the cell, increasing chloride conductance, the first key event. The increase in chloride conductance depresses the membrane potential, causing hyperpolarization, the second key event, and preventing neuronal signal transmission. It is important to note that hyperpolarization is a standard though transient state of neurons. However, macrocyclic lactone compounds such as ivermectin trigger the MIE causing irreversible opening of the GluCl channels (Rohrer and Arena, 1995). This resultant permanent hyperpolarized neuronal state induces ataxia, the loss of controlled body movement, and paralysis, the loss of movement, which together comprises the third key event. Induced ataxia and paralysis in an individual indirectly lead to increased mortality, the first adverse outcome, through impairing its motility, ability to forage, and evade predators. Increased mortality directly leads to the second adverse outcome, population decline. </span></span></span></span></p> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><img 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" style="height:181px; width:362px" /></span></span></span></span></p> <p>Increased mortality is one of the most common regulatory assessment endpoints,&nbsp;along with reduced growth and reduced reproduction.</p> adjacent Not Specified Not Specified adjacent Not Specified Not Specified adjacent Not Specified Not Specified non-adjacent Not Specified Not Specified non-adjacent Not Specified Not Specified High Male High Female High Birth to < 1 month High Juvenile High Adult, reproductively mature Not Specified Not Specified Not Specified Not Specified Not Specified Not Specified Not Specified Not Specified Not Specified Not Specified Not Specified <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Strong evidence exists for population decline in pest species (e.g., worms, ticks and mites) resulting from targeted glutamate-gated chloride channels, as well for non-target species (bees, butterflies). These channels are found in members of the protostome clade, so it can be assumed that the present AOP is applicable to the whole clade. Effect data for ivermectin towards the mortality endpoint exists for mollusks, flatworms, roundworms, ticks, mites, insects, and crustaceans, further confirming the taxonomic applicability of the AOP (Wolstenholme, 2012).&nbsp;</span></span></span></span><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Glutamate-gated chloride channels are essential for neuronal and motor function and are present in all developmental stages. Experimental evidence also demonstrates that triggers of the MIE such as ivermectin have demonstrated toxicity on multiple species (Wolstenholme, 2012). Because GluCl channels are not sex specific, it is understood that this AOP would not be limited to a specific sex. </span></span></p> <p style="margin-left:8px; margin-right:9px; text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><img 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" style="height:170px; width:610px" /></span></span></p> <p style="margin-left:8px; margin-right:9px; text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><em><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Figure 2: Graphical representation of adverse outcome pathway 113: activation of glutamate-gated chloride channel leading to mortality and decreased population: green indicates molecular </span></span></em><em><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">initiating event (MIE), orange indicates key event (KE), and red indicates adverse outcome; stars indicate the weight of evidence, where 3 stars </span></span></em><em><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">indicate high, 2 stars indicate moderate, and 1 star indicates low; red stars indicate the overall weight of evidence of KE relationships (biological plausibility and empirical evidence), and black stars indicate the weight of evidence of the essentiality of KEs. Information on the level of biological </span></span></em><em><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">organization of the events is found in the dashed boxes above the MIE, KEs, and adverse outcome.</span></span></em></span></span></p> <table border="1" cellpadding="1" cellspacing="1" style="width:500px" summary="Summary of teh assessment of essentiality for key events"> <tbody> <tr> <td>Key Event</td> <td>Event Description</td> <td>Level of Evidence</td> <td>Support for essentiality</td> </tr> <tr> <td>MIE</td> <td>Activaiton, Glutamate-gated chloride channel</td> <td>High</td> <td>High</td> </tr> <tr> <td>KE1</td> <td>Increased, chloride conductance</td> <td>High</td> <td>High</td> </tr> <tr> <td>KE2</td> <td>Hyperpolarization, neuron</td> <td>High&nbsp;</td> <td>High</td> </tr> <tr> <td>KE3</td> <td>N/A, Ataxia, paralyisis, or hyperactivity</td> <td>High</td> <td>High</td> </tr> <tr> <td>AO1</td> <td>Increased Mortality</td> <td>High</td> <td>High</td> </tr> <tr> <td>AO2</td> <td>Decreased, population 1</td> <td>&nbsp;High</td> <td>High</td> </tr> </tbody> </table> <p>&nbsp;</p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Chemical applicability domain:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Multiple chemicals with the potential to bind and activate GluCl channels are known. The most widely used are macrocyclic lactones, which are products and chemical derivatives of Streptomyces soil microorganisms. Avermectins in commercial use include ivermectin, abamectin, doramectin, eprinomectin, and selamectin.</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Taxonomic applicability domain:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The groups of organisms for which this AOP might be relevant are those containing glutamate-gated chloride channels. These channels are found in members of the protostome clade, so it can be assumed that the present AOP is applicable to the whole clade. Effect data for ivermectin towards the mortality endpoint exists for mollusks, flatworms, roundworms, ticks, mites, insects, and crustaceans, further confirming the taxonomic applicability of the AOP (Wolstenholme, 2012)</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Life stage and sex applicability domain:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Glutamate-gated chloride channels are essential for neuronal and motor function and are present in all developmental stages. Experimental evidence also demonstrates that triggers of the MIE such as ivermectin have demonstrated toxicity on multiple species (Wolstenholme, 2012). Because GluCl channels are not sex specific, it is understood that this AOP would not be limited to a specific sex. </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Essentiality of KEs:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">To assess the essentiality of the different steps within this AOP, the essential nature of individual upstream key events to the occurrence of downstream events must be demonstrated experimentally. The essentiality of the MIE (Event 760, Activation, glutamate-gated chloride channel) has been demonstrated to be high in multiple experiments such as Pemberton et al., 2001, in which a mutant avr-15, which lacks a functional GluCl-a2 subunit showed no hyperpolarization response when dosed with ivermectin. The essentiality of KE1 (Event 761, Increased Chloride Conductance) and KE2 (Event 763, Hyperpolarization, Neuron) were both assessed to be high, as demonstrated in Cleland, 1996, who utilized the chloride channel blocker picrotoxin. In these experiments, the addition of picrotoxin inhibited the increase in chloride conductance and hyperpolarization effect of ivermectin on C. pagurus&nbsp; neurons. The essentiality of KE3 (Event 764, N/A, Ataxia, Paralysis, or Hyperactivity) was found to be moderate. GluCl channels have been found to be expressed in many different organ systems across a variety of species. Briefly, in the muscle cells of the pharynx in C. elegans, and in neurons that mediate light avoidance in D. melanogaster (Wolstenholme, 2012). The cell-specific mechanism by which ataxia or paralysis is achieved in an individual organism is likely to vary between species, and pathways other than paralysis may be more sensitive. However the compound ivermectin is lethal to both described species, indicating that KE3 is a step in the pathway. </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Essentiality of the different steps of AOP 113 has been assessed from the literature. In terms of the MIE, many experiments have been conducted showing that certain drugs like ivermectin, target the glutamate-gated chloride channels of invertebrates through means of dose-response tests. The increased chloride conductance and hyperpolarization events are essential as shown through the clamp tests done by Slimko, et al., 2002 that show the introduction of ivermectin to a virus with glutamate-channel subunits results in an increased conductance and lack of signal response to glutamate with action potentials. Tests looking at immunostaining to locate GluCl subunits (Portillo, et al., 2003) show them present in motor neuron commissures and the pharynx of H. contortus proving the essentiality of ataxia and paralysis in important locations that contribute to the movement of the species. Movement assays that show decreased thrashing (Castro, 2020) as well as increased foraging time (Verdu, et al., 2015) further show the essentiality of paralysis and increased mortality.</span></span></span></span></p> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Table 2: Summary of the overall weight</span></span><span style="font-size:10.0pt"><span style="font-family:&quot;Cambria Math&quot;,serif">‐</span></span><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">of</span></span><span style="font-size:10.0pt"><span style="font-family:&quot;Cambria Math&quot;,serif">‐</span></span><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">evidence considerations for all key event relationships</span></span></span></span></p> <table align="center" cellspacing="0" class="MsoTableGrid" style="border-collapse:collapse; border:none; width:618px"> <tbody> <tr> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:1px solid black; height:34px; vertical-align:top; width:42px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">KER no.</span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:1px solid black; height:34px; vertical-align:top; width:102px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Upstream event</span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:1px solid black; height:34px; vertical-align:top; width:78px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Relationship</span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:1px solid black; height:34px; vertical-align:top; width:108px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Downstream event</span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:1px solid black; height:34px; vertical-align:top; width:72px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Biological plausibility</span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:1px solid black; height:34px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Empirical evidence</span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:1px solid black; height:34px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Overall WoE</span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:1px solid black; height:34px; vertical-align:top; width:84px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Quantitative understanding</span></span></span></span></span></p> </td> </tr> <tr> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:42px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">1 </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:102px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Activation, Glutamate-gated chloride channels</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:78px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Directly leads to </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:108px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Increased, chloride conductance </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:72px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:84px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">High </span></span></span></span></span></p> </td> </tr> <tr> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:42px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">2 </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:102px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Increased, chloride conductance </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:78px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Directly leads to </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:108px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Hyperpolarization, neurons </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:72px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:84px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> </tr> <tr> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:42px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">3 </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:102px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Hyperpolarization, neurons </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:78px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Directly leads to </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:108px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">N/A, Ataxia, paralysis, or hyperactivity</span></span></span> </span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:72px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Moderate</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;Moderate</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:84px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;Moderate</span></span></span></span></span></p> </td> </tr> <tr> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:42px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">4 </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:102px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">N/A, Ataxia, paralysis, or hyperactivity</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:78px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Directly leads to </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:108px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Increased mortality </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:72px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;Moderate</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">High </span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:none; border-left:none; border-right:none; border-top:none; height:39px; vertical-align:top; width:84px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">High</span></span></span></span></span></p> </td> </tr> <tr> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:none; height:32px; vertical-align:top; width:42px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">5 </span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:none; height:32px; vertical-align:top; width:102px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Increased mortality </span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:none; height:32px; vertical-align:top; width:78px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Directly leads to </span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:none; height:32px; vertical-align:top; width:108px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Decreased, population </span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:none; height:32px; vertical-align:top; width:72px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">&nbsp;High</span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:none; height:32px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">High </span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:none; height:32px; vertical-align:top; width:66px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">High </span></span></span></span></span></p> </td> <td style="border-bottom:1px solid black; border-left:none; border-right:none; border-top:none; height:32px; vertical-align:top; width:84px"> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:8.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">High</span></span></span></span></span></p> </td> </tr> </tbody> </table> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Biological plausibility of KERs:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Biological plausibility relates the known structural or functional relationships between an upstream key event and a downstream key event under normal conditions or unperturbed biology (OECD, 2018). This biological understanding allows for the inference or ability to hypothesize the likely consequences of a biological perturbation elicited by a stressor. The biological plausibility of key event relationship (KER)1 (Relationship 752, Activation, Glutamate-gated chloride channel leads to Increased, Chloride conductance) is considered high. Glutamate-gated chloride channels are ligand-gated ion channels well characterized structurally and functionally, with published three-dimensional crystalline structures of GluCl channel binding to the exogenous ligand ivermectin (Hibbs et al., 2011). The binding and activation of the GluCl channel induces conformational changes and the opening of the central ion channel pore, allowing for chloride ions to diffuse down their electrochemical gradient across the membrane, increasing chloride conductance (Hibbs et al., 2011). It is important to note that so far, an agreement on the structure and conformation transition of the GluCl channel when bound to the conventional ligand glutamate has not been reached (Lynagh et al., 2012). </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">For KER2 (Relationship 758, Increased, Chloride conductance leads to hyperpolarization, neuron) the biological plausibility is considered high. Functionally, the flow of chloride ions from an increase in chloride conductance across a trans-membrane ion channel will move the membrane potential towards the chloride equilibrium potential. Because this potential is near the resting potential in adult neurons, chloride conductance induces a hyperpolarized state, and limits the ability of excitatory stimuli to depolarize the neuron (Lynagh et al., 2012). </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The biological plausibility of KER3 (Relationship 755, Hyperpolarization, neuron leads to N/A, Ataxia, paralysis, or hyperactivity) is found to be high. The inhibition of neuronal signal transmission between interneurons and excitatory motor neurons impairs coordination of voluntary muscle movement and causes loss of movement, increases of both ataxia and paralysis (Kass et al., 1980). </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The biological plausibility of KER4 (Relationship 757, N/A, Ataxia, paralysis, or hyperactivity leads to Increased Mortality) is considered moderate. Ataxia and paralysis impair an individual&#39;s foraging ability and increase risk of predation, which increases mortality (Verdu et al., 2015). </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The biological plausibility of KER5 (Relationship 756, Increased Mortality leads to Decreased, population) is considered high. Increased mortality of individuals reduces the number of individuals causing a decline in overall population. </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Empirical evidence of KERs:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The empirical support for the key event relationships in the AOP are overall high as there is direct evidence linking the events. There are many studies that focus on the effect that macrocyclic lactone anthelmintics such as avermectin and ivermectin have on glutamate-gated chloride channels in invertebrates. In C. elegans, Slimko, et al., 2002 and Pemberton, et al., 2001 measured conductance and electroclamp voltage potentials across C. elegans GluCl channels cloned into rat hippocampal neurons to show increased chloride concentrations (KER1) and resulting hyperpolarization (KER 2) upon the addition of ivermectin. Portillo, et al., 2003 showed moderate support that the location of the GluCl genes by motor neuron commissures can infer that hyperpolarization of those neuronal components plays an important role in the downstream event of ataxia or paralysis (KER3). There is direct evidence of ivermectin dosage to decreased movement through thrashing assays (Castro, 2020) as well as looking at increased foraging time (Verdu, et al., 2015). High empirical evidence is assessed for KER4 in studies such as Verdu, et al., which demonstrates that dung beetles exposed to increasing rates of ivermectin had increased rates of ataxia and death. High empirical evidence is assessed for KER5 in studies such as Iwasa et al., 2005, which showed that increased individual mortality due to non-target ivermectin exposure reduced the overall population of larval dung beetles.</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Uncertainties, Inconsistencies and Critical Gaps</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">There are a few uncertainties and critical gaps underlying this AOP. While the mechanism of GluCl channel activation, increased chloride conductance, and hyperpolarization have been thoroughly investigated, KE3, N/A, Ataxia, Paralysis, or Hyperactivity is less clear due to multiple reasons. First, we, the authors of this AOP report, believe N/A to be an error on the part of the initial AOP author. Second, we have not found evidence supporting hyperactivity as a result of GluCl activation, increased chloride conductance, or neuronal hyperpolarization. For these reasons we have written the report as if KE3 Event ID 764 reads as &ldquo;Ataxia and Paralysis.&rdquo;</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Further uncertainties exist for KE3. GluCl channels are found in many different protostome lineages, including arthropods, nematodes, mollusks and platyhelminths (Lynaugh et al., 2015). However, the location of the GluCl channels within the physiology organisms can differ between organisms. In C. elegans, GluCl channels are expressed highly in the pharynx, the pumping of which is required for feeding and maintaining hydrostatic pressure (Pemberton et al., 2001). In locusts, GluCl channels are expressed in dorsal unpaired median neurons, which innervate flight and leg muscles (Janssen et al., 2007). Many studies describe the location and role of GluCl channels in different species, as well as the mortal effect of Ivermectin on the species. However, the specific mechanism by which ataxia and paralysis of varying organ systems in different species lead to mortality e.g. lack of food, or predation, could vary. For these reasons, the quantitative understanding of KER3 was considered moderate.&nbsp;&nbsp; </span></span></span></span></p> <div> <table class="table table-bordered table-fullwidth"> <thead> <tr> <th>Modulating Factor (MF)</th> <th>Influence or Outcome</th> <th>KER(s) involved</th> </tr> </thead> <tbody> <tr> <td>&nbsp;</td> <td>&nbsp;</td> <td>&nbsp;</td> </tr> </tbody> </table> </div> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Quantitative Understanding:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Quantitative understanding describes whether the magnitude or probability of a downstream key event can be predicted by the magnitude or probability of an upstream key event with known uncertainties (OECD, 2018). The quantitative understanding of KER1 (Relationship 752, Activation, Glutamate-gated chloride channel leads to Increased, Chloride conductance) is considered high, as multiple mathematical models describing the relationship between glutamate binding and chloride conductance have been published (Degani-Katzav, et al., 2016). There are also experiment specific studies reporting the time constant relationship between GluCl channel activation and chloride conductance (Slimko et al.,&nbsp; 2002). </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The quantitative understanding of KER2 (Relationship 758, Increased, Chloride conductance leads to hyperpolarization, neuron) is considered high, given the well-established mechanism of neuronal signal transmission. Experimental studies report time constant relationships between the MIE and hyperpolarization (Slimko et al., 2002).</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The quantitative understanding of KER3 (Relationship 755, Hyperpolarization, neuron leads to N/A, Ataxia, paralysis, or hyperactivity) is considered moderate. Experimental studies such as Verdu et al., 2015, describe the dose dependent response of ivermectin on ataxia. </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The quantitative understanding of KER4 (Relationship 757, N/A, Ataxia, paralysis, or hyperactivity leads to Increased Mortality) is considered High. Ataxia and paralysis impair an individual&#39;s foraging ability and increase risk of predation, which increases mortality. Experimental studies such as Verdu et al., 2015, describe the dose dependent response of ivermectin on death. </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The quantitative understanding of KER5 (Relationship 756, Increased Mortality leads to Decreased, population) is considered high. Increased mortality of individuals reduces the number of individuals causing a decline in overall population.</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Environmental Relevance:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">This AOP is considered environmentally relevant because it addresses the lethal endpoints, mortality and population decline, in a large clade, protostomes. Additionally, drug compounds that are known to trigger this AOP, macrocyclic lactones, are used worldwide as anthelmintics, insecticides, and pesticides. The environmental fate and transport of these chemicals are also relevant due to the sensitivity of species to their effects. </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The main environmental exposure routes of these drugs are through direct crop spraying as an insecticide, directly through animal or human feces when given as an anti-parasitic, indirectly through feces spreading or washoff of topical products. The effects on nontarget dung insects and dung dispersal is a major concern with ML drugs. Ivermectin, the most extensively studied of the macrocyclic lactone drugs has an efficacy at low concentrations and a long soil half-life. Garric et al., 2007 found the EC5048hr, immobility of ivermectin to Daphnia magna to be 1.2-10.7ng/L in aquatic environments. In dry environments, Halley et al., 1989 found the the LC5028d to be 315mg/kg dry wt for the earthworm Eisenia fetida. Once in the sediment, the half-life of ivermectin was found to be &gt;265 days by Liebig, et al., 2010. Verdu et al., 2015 found that cattle feces contained between 62-98% of inoculated ivermectin. The variety of exposure methods, the amounts of drugs entering the environment, and the sensitivity to exposures of a wide variety of species increase the environmental relevance of this AOP. </span></span></span></span></p> <p>&nbsp;</p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Applications of the AOP:</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Glutamate-gated chloride channels are the molecular target of macrocyclic lactone anthelmintics, parasiticides, insecticides, and acaricides widely used in human and veterinary medicine (Wolstenholme, 2012). In therapeutic usage, these drugs eliminate unwanted insects and parasites. However, the large clade of protostomes that function in many ecosystem roles are all fatally susceptible to non-target exposure. This supports the need to develop AOPs that can increase knowledge of GluCl channels and protostome invertebrate nervous systems, to better design pragmatic approaches to protecting vulnerable species. </span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">The present AOP can be used to guide the development of in vitro screening of chemicals, and to identify GluCl activators for more in-depth testing. This AOP provides a basis for development of higher throughput assays and tests that can be used to quantify the KEs. For example, there are few if any high-throughput methods for assessing KE1 and KE2 due to their electrical nature at the cellular level. However, there are high throughput methods for assessing KE3 including motility assays, as well as the adverse outcomes. In the near term, this AOP is most applicable to hazard identification and tiered testing. With higher throughput assays, greater confidence in quantitative predictions can be given. The diversity of organ systems and organisms containing GluCls pose a challenge to the quantitative prediction ability of this AOP. Nonetheless, this AOP has the potential to link in vitro molecular events to regulatory endpoints, and improve the safety assessment of GluCl activators, protecting organisms of the diverse phyla protostoma.</span></span></span></span></p> <p style="text-align:center"><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"><img 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" style="height:312px; width:476px" /></span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">References</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Cleland, T. A. (1996). Inhibitory glutamate receptor channels. <em>Molecular Neurobiology</em>, <em>13</em>(2), 97&ndash;136.</span></span><a href="https://doi.org/10.1007/BF02740637" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1007/BF02740637</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Degani-Katzav, N., Gortler, R., Gorodetzki, L., &amp; Paas, Y. (2016). Subunit stoichiometry and arrangement in a heteromeric glutamate-gated chloride channel. <em>Proceedings of the National Academy of Sciences</em>, <em>113</em>(5), E644&ndash;E653.</span></span><a href="https://doi.org/10.1073/pnas.1423753113" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1073/pnas.1423753113</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Garric, J., Vollat, B., Duis, K., P&eacute;ry, A., Junker, T., Ramil, M., Fink, G., &amp; Ternes, T. A. (2007). Effects of the parasiticide ivermectin on the cladoceran Daphnia magna and the green alga Pseudokirchneriella subcapitata. <em>Chemosphere</em>, <em>69</em>(6), 903&ndash;910.</span></span><a href="https://doi.org/10.1016/j.chemosphere.2007.05.070" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1016/j.chemosphere.2007.05.070</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Halley, B. A., Jacob, T. A., &amp; Lu, A. Y. H. (1989). The environmental impact of the use of ivermectin: Environmental effects and fate. <em>Chemosphere</em>, <em>18</em>(7), 1543&ndash;1563.</span></span><a href="https://doi.org/10.1016/0045-6535(89)90045-3" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1016/0045-6535(89)90045-3</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Hibbs, R. E., &amp; Gouaux, E. (2011). Principles of activation and permeation in an anion-selective Cys-loop receptor. <em>Nature</em>, <em>474</em>(7349), 54&ndash;60.</span></span><a href="https://doi.org/10.1038/nature10139" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1038/nature10139</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Iwasa, M., Nakamura, T., Fukaki, K. &amp; Yamashita, N. Non-target effects of ivermectin on coprophagous insects in Japan. Environ. Entomol. 35, 1485&ndash;1492 (2005). </span></span><a href="https://doi.org/10.1603/0046-225X-34.6.1485" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">https://doi.org/10.1603/0046-225X-34.6.1485</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Janssen, D., Derst, C., Buckinx, R., Van den Eynden, J., Rigo, J.-M., &amp; Van Kerkhove, E. (2007). Dorsal Unpaired Median Neurons of Locusta migratoria Express Ivermectin- and Fipronil-Sensitive Glutamate-Gated Chloride Channels. <em>Journal of Neurophysiology</em>, <em>97</em>(4), 2642&ndash;2650.</span></span><a href="https://doi.org/10.1152/jn.01234.2006" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1152/jn.01234.2006</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Kass, I. S., Wang, C. C., Walrond, J. P., &amp; Stretton, A. O. (1980). Avermectin B1a, a paralyzing anthelmintic that affects interneurons and inhibitory motoneurons in Ascaris. <em>Proceedings of the National Academy of Sciences of the United States of America</em>, <em>77</em>(10), 6211&ndash;6215.</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Liebig, M., Fernandez, &Aacute;. A., Bl&uuml;baum-Gronau, E., Boxall, A., Brinke, M., Carbonell, G., Egeler, P., Fenner, K., Fernandez, C., Fink, G., Garric, J., Halling-S&oslash;rensen, B., Knacker, T., Krogh, K. A., K&uuml;ster, A., L&ouml;ffler, D., Cots, M. &Aacute;. P., Pope, L., Prasse, C., &hellip; Duis, K. (2010). Environmental risk assessment of ivermectin: A case study. <em>Integrated Environmental Assessment and Management</em>, <em>6</em>(S1), 567&ndash;587.</span></span><a href="https://doi.org/10.1002/ieam.96" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1002/ieam.96</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Lynagh, T., &amp; Lynch, J. (2012). Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin. <em>Frontiers in Molecular Neuroscience</em>, <em>5</em>, 60.</span></span><a href="https://doi.org/10.3389/fnmol.2012.00060" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.3389/fnmol.2012.00060</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Pemberton, D. J., Franks, C. J., Walker, R. J., &amp; Holden-Dye, L. (2001). Characterization of Glutamate-Gated Chloride Channels in the Pharynx of Wild-Type and Mutant Caenorhabditis elegansDelineates the Role of the Subunit GluCl-&alpha;2 in the Function of the Native Receptor. <em>Molecular Pharmacology</em>, <em>59</em>(5), 1037&ndash;1043.</span></span><a href="https://doi.org/10.1124/mol.59.5.1037" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1124/mol.59.5.1037</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Rohrer, S. P., &amp; Arena, J. P. (1995). Ivermectin Interactions with Invertebrate Ion Channels. In <em>Molecular Action of Insecticides on Ion Channels</em> (Vol. 591, pp. 264&ndash;283). American Chemical Society.</span></span><a href="https://doi.org/10.1021/bk-1995-0591.ch017" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1021/bk-1995-0591.ch017</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Sanderson, H., Laird, B., Pope, L., Brain, R., Wilson, C., Johnson, D., Bryning, G., Peregrine, A. S., Boxall, A., &amp; Solomon, K. (2007). Assessment of the environmental fate and effects of ivermectin in aquatic mesocosms. <em>Aquatic Toxicology</em>, <em>85</em>(4), 229&ndash;240.</span></span><a href="https://doi.org/10.1016/j.aquatox.2007.08.011" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1016/j.aquatox.2007.08.011</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Slimko, E. M., McKinney, S., Anderson, D. J., Davidson, N., &amp; Lester, H. A. (2002). Selective Electrical Silencing of Mammalian Neurons In Vitro by the Use of Invertebrate Ligand-Gated Chloride Channels. <em>The Journal of Neuroscience</em>, <em>22</em>(17), 7373.</span></span><a href="https://doi.org/10.1523/JNEUROSCI.22-17-07373.2002" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1523/JNEUROSCI.22-17-07373.2002</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Timothy, G. G., &amp; Yovany, M. (2012). Macrocyclic Lactone Anthelmintics: Spectrum of Activity and Mechanism of Action. <em>Current Pharmaceutical Biotechnology</em>, <em>13</em>(6), 866&ndash;872.</span></span></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Verd&uacute;, J. R., Cortez, V., Ortiz, A. J., Gonz&aacute;lez-Rodr&iacute;guez, E., Martinez-Pinna, J., Lumaret, J.-P., Lobo, J. M., Numa, C., &amp; S&aacute;nchez-Pi&ntilde;ero, F. (2015). Low doses of ivermectin cause sensory and locomotor disorders in dung beetles. <em>Scientific Reports</em>, <em>5</em>(1), 13912.</span></span><a href="https://doi.org/10.1038/srep13912" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1038/srep13912</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Wardhaugh, K. G., &amp; Rodriguez-Menendez, H. (1988). The effects of the antiparasitic drug, ivermectin, on the development and survival of the dung-breeding fly, Orthelia cornicina (F.) and the scarabaeine dung beetles, Copris hispanus L., Bubas bubalus (Oliver) and Onitis belial F. <em>Journal of Applied Entomology</em>, <em>106</em>(1&ndash;5), 381&ndash;389.</span></span><a href="https://doi.org/10.1111/j.1439-0418.1988.tb00607.x" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1111/j.1439-0418.1988.tb00607.x</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Wolstenholme, A. J. (2012). Glutamate-gated Chloride Channels *. <em>Journal of Biological Chemistry</em>, <em>287</em>(48), 40232&ndash;40238.</span></span><a href="https://doi.org/10.1074/jbc.R112.406280" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1074/jbc.R112.406280</span></span></a></span></span></p> <p><span style="font-size:11pt"><span style="font-family:&quot;Lucida Sans&quot;,sans-serif"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif">Wolstenholme, A. J., Maclean, M. J., Coates, R., McCoy, C. J., &amp; Reaves, B. J. (2016). How do the macrocyclic lactones kill filarial nematode larvae? <em>Invertebrate Neuroscience</em>, <em>16</em>(3), 7.</span></span><a href="https://doi.org/10.1007/s10158-016-0190-7" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.0pt"><span style="font-family:&quot;Arial&quot;,sans-serif"> https://doi.org/10.1007/s10158-016-0190-7</span></span></a></span></span></p> AOPWiki 2016-11-29T18:41:16 2026-01-11T16:56:07