<?xml version="1.0" encoding="UTF-8"?>
<data xmlns="http://www.aopkb.org/aop-xml">
  <chemical id="d0d8be17-db00-42e0-8b40-fb564c13ea29">
    <casrn>59456-70-1</casrn>
    <jchem-inchi-key>WWJFFVUVFNBJTN-UIBIZFFUSA-N</jchem-inchi-key>
    <indigo-inchi-key>WWJFFVUVFNBJTN-UIBIZFFUSA-N</indigo-inchi-key>
    <preferred-name>Nikkomycins</preferred-name>
    <synonyms>
      <synonym>β-D-Allofuranuronic acid, 5-[[(2S,3S,4S)-2-amino-4-hydroxy-4-(5-hydroxy-2-pyridinyl)-3-methyl-1-oxobutyl]amino]-1,5-dideoxy-1-(3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl)-</synonym>
    </synonyms>
    <dsstox-id>DTXSID5058436</dsstox-id>
  </chemical>
  <biological-object id="04426c67-4d85-4658-9360-e042a335b9d2">
    <source-id>CHEBI:17029</source-id>
    <source>CHEBI</source>
    <name>chitin</name>
  </biological-object>
  <biological-process id="5ab1abb0-7497-444e-8d76-c00c05b111cc">
    <source-id>GO:0006031</source-id>
    <source>GO</source>
    <name>chitin biosynthetic process</name>
  </biological-process>
  <biological-process id="efcf79dc-ab8e-4920-bb69-10a36230c5ff">
    <source-id>D009026</source-id>
    <source>MESH</source>
    <name>mortality</name>
  </biological-process>
  <biological-action id="919cb9fb-4039-429b-807a-7c50a607f62d">
    <source-id>1</source-id>
    <source>WIKI</source>
    <name>increased</name>
  </biological-action>
  <stressor id="b655060f-3863-450c-8e2c-35199974257e">
    <name>Polyoxin D</name>
    <description></description>
    <exposure-characterization></exposure-characterization>
    <creation-timestamp>2020-10-23T06:20:12</creation-timestamp>
    <last-modification-timestamp>2020-10-23T06:20:12</last-modification-timestamp>
  </stressor>
  <stressor id="68987880-11f4-4551-b937-6c669a01d08d">
    <name>Nikkomycins</name>
    <description></description>
    <chemicals>
      <chemical-initiator chemical-id="d0d8be17-db00-42e0-8b40-fb564c13ea29" user-term="Nikkomycins"/>
    </chemicals>
    <exposure-characterization></exposure-characterization>
    <creation-timestamp>2018-05-24T15:54:09</creation-timestamp>
    <last-modification-timestamp>2018-05-24T15:54:09</last-modification-timestamp>
  </stressor>
  <taxonomy id="ea814eb6-69f3-4e8c-ac5b-717a3a128152">
    <source-id>7375</source-id>
    <source>NCBI</source>
    <name>Lucilia cuprina</name>
  </taxonomy>
  <taxonomy id="ef4a2929-d427-4701-95e2-b111b1e3d7b2">
    <source-id>WCS_35525</source-id>
    <source>common ecological species</source>
    <name>Daphnia magna</name>
  </taxonomy>
  <key-event id="aaf15cda-f4e3-443b-847c-686d8b99981d">
    <title>Decrease, 20-hydroxyecdysone</title>
    <short-name>Decrease, 20-hydroxyecdysone</short-name>
    <biological-organization-level>Molecular</biological-organization-level>
    <description></description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2022-08-28T21:14:06</creation-timestamp>
    <last-modification-timestamp>2022-08-28T21:14:06</last-modification-timestamp>
  </key-event>
  <key-event id="a9410b05-6e49-4de7-9749-b76cfd73db3f">
    <title>Decrease, knickkopf gene</title>
    <short-name>Decrease, knickkopf gene</short-name>
    <biological-organization-level>Cellular</biological-organization-level>
    <description></description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2022-08-28T21:15:01</creation-timestamp>
    <last-modification-timestamp>2022-08-28T21:15:01</last-modification-timestamp>
  </key-event>
  <key-event id="24eb6e4c-ce8b-4375-9177-6500c616a656">
    <title>Decrease, Chitin laminar organization</title>
    <short-name>Decrease, Chitin laminar organization</short-name>
    <biological-organization-level>Tissue</biological-organization-level>
    <description></description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2022-08-28T21:16:27</creation-timestamp>
    <last-modification-timestamp>2022-08-28T21:16:27</last-modification-timestamp>
  </key-event>
  <key-event id="25b82b11-2954-4a0a-b069-f2a5edde14c3">
    <title>Decrease, Prevent chitin degradation by chitinases</title>
    <short-name>Decrease, Prevent chitin degradation by chitinases</short-name>
    <biological-organization-level>Tissue</biological-organization-level>
    <description></description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2022-08-28T21:17:28</creation-timestamp>
    <last-modification-timestamp>2022-08-28T21:17:28</last-modification-timestamp>
  </key-event>
  <key-event id="d4c5409e-bb8a-4fec-803b-afea1364c56a">
    <title>Weak, Procuticle protection</title>
    <short-name>Weak, Procuticle protection</short-name>
    <biological-organization-level>Organ</biological-organization-level>
    <description></description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2022-08-28T21:18:06</creation-timestamp>
    <last-modification-timestamp>2022-08-28T21:18:06</last-modification-timestamp>
  </key-event>
  <key-event id="c9c67735-e05d-41b3-a965-ae4bb135bdae">
    <title>Decrease, New cuticle secretion</title>
    <short-name>Decrease, New cuticle secretion</short-name>
    <biological-organization-level>Organ</biological-organization-level>
    <description></description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2022-08-28T21:18:54</creation-timestamp>
    <last-modification-timestamp>2022-08-28T21:18:54</last-modification-timestamp>
  </key-event>
  <key-event id="6e9963e7-4435-4374-8249-09cedb7f88b6">
    <title>Increase, Incomplete ecdysis</title>
    <short-name>Increase, Incomplete ecdysis</short-name>
    <biological-organization-level>Individual</biological-organization-level>
    <description></description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <biological-events>
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    </biological-events>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2016-11-29T18:41:28</creation-timestamp>
    <last-modification-timestamp>2018-05-24T16:41:34</last-modification-timestamp>
  </key-event>
  <key-event id="3d14fb6d-5ade-4235-97ce-d33b89b7ff3d">
    <title>Increase, developmental abnormalities</title>
    <short-name>Increase, developmental abnormalities</short-name>
    <biological-organization-level>Individual</biological-organization-level>
    <description></description>
    <measurement-methodology></measurement-methodology>
    <evidence-supporting-taxonomic-applicability></evidence-supporting-taxonomic-applicability>
    <applicability>
    </applicability>
    <references></references>
    <source>AOPWiki</source>
    <creation-timestamp>2022-08-28T20:41:02</creation-timestamp>
    <last-modification-timestamp>2022-08-28T20:41:02</last-modification-timestamp>
  </key-event>
  <key-event id="a793baeb-714c-4c16-8dcc-d2be7a048f16">
    <title>Increase, Mortality</title>
    <short-name>Increase, Mortality</short-name>
    <biological-organization-level>Individual</biological-organization-level>
    <description>&lt;p&gt;&lt;span style="font-size:14px"&gt;This key event is observed at the biological level of the individual and describes the increase of mortality of individuals upon exposure to a stressor.&lt;/span&gt;&lt;/p&gt;
</description>
    <measurement-methodology>&lt;p&gt;&lt;span style="font-size:14px"&gt;The AO can be detected by observation, for example by immobilization of the respective organisms. There exist guidelines for the characterization of this AO in arthropods. For example, the OECD 202 Daphnia sp. Acute immobilization test&amp;nbsp;&lt;/span&gt;&lt;!--[if supportFields]&gt;&lt;span lang=EN-US
style='font-size:11.0pt;line-height:107%;font-family:"Calibri",sans-serif;
mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:
minor-latin;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";
mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:
EN-US;mso-bidi-language:AR-SA'&gt;&lt;span style='mso-element:field-begin;mso-field-lock:
yes'&gt;&lt;/span&gt;ADDIN CSL_CITATION
{&amp;quot;citationItems&amp;quot;:[{&amp;quot;id&amp;quot;:&amp;quot;ITEM-1&amp;quot;,&amp;quot;itemData&amp;quot;:{&amp;quot;DOI&amp;quot;:&amp;quot;10.1787/9789264069947-en&amp;quot;,&amp;quot;ISBN&amp;quot;:&amp;quot;9789264069947&amp;quot;,&amp;quot;PMID&amp;quot;:&amp;quot;128&amp;quot;,&amp;quot;abstract&amp;quot;:&amp;quot;This
Test Guideline describes an acute toxicity test to assess effects of chemicals
towards daphnids (usually Daphnia magna Staus). Young daphnids, aged less than
24 hours at the start of the test, are exposed to the test substance at a range
of concentrations (at least five concentrations) for a period of 48 hours.
Immobilisation is recorded at 24 hours and 48 hours and compared with control
values. The results are analysed in order to calculate the EC50 at 48h. Determination
of the EC50 at 24h is optional. At least 20 animals, preferably divided into
four groups of five animals each, should be used at each test concentration and
for the controls. At least 2 ml of test solution should be provided for each
animal (i.e. a volume of 10 ml for five daphnids per test vessel). The limit
test corresponds to one dose level of 100 mg/L. The study report should include
the observation for immobilized daphnids at 24 and 48 hours after the beginning
of the test and the measures of dissolved oxygen, pH, concentration of the test
substance, at the beginning and end of the
test.&amp;quot;,&amp;quot;author&amp;quot;:[{&amp;quot;dropping-particle&amp;quot;:&amp;quot;&amp;quot;,&amp;quot;family&amp;quot;:&amp;quot;OECD&amp;quot;,&amp;quot;given&amp;quot;:&amp;quot;&amp;quot;,&amp;quot;non-dropping-particle&amp;quot;:&amp;quot;&amp;quot;,&amp;quot;parse-names&amp;quot;:false,&amp;quot;suffix&amp;quot;:&amp;quot;&amp;quot;}],&amp;quot;collection-title&amp;quot;:&amp;quot;OECD
Guidelines for the Testing of Chemicals, Section
2&amp;quot;,&amp;quot;container-title&amp;quot;:&amp;quot;OECD
Publishing&amp;quot;,&amp;quot;id&amp;quot;:&amp;quot;ITEM-1&amp;quot;,&amp;quot;issue&amp;quot;:&amp;quot;OECD
Guideline for the Testing of Chemicals, Section
2&amp;quot;,&amp;quot;issued&amp;quot;:{&amp;quot;date-parts&amp;quot;:[[&amp;quot;2004&amp;quot;,&amp;quot;11&amp;quot;,&amp;quot;23&amp;quot;]]},&amp;quot;number-of-pages&amp;quot;:&amp;quot;1-12&amp;quot;,&amp;quot;publisher&amp;quot;:&amp;quot;OECD&amp;quot;,&amp;quot;title&amp;quot;:&amp;quot;Test
No. 202: &amp;lt;i&amp;gt;Daphnia sp.&amp;lt;/i&amp;gt; Acute Immobilisation
Test&amp;quot;,&amp;quot;type&amp;quot;:&amp;quot;report&amp;quot;},&amp;quot;uris&amp;quot;:[&amp;quot;http://www.mendeley.com/documents/?uuid=53ebeac3-a1c9-3977-9697-df1efabeb4d3&amp;quot;]}],&amp;quot;mendeley&amp;quot;:{&amp;quot;formattedCitation&amp;quot;:&amp;quot;(OECD
2004)&amp;quot;,&amp;quot;plainTextFormattedCitation&amp;quot;:&amp;quot;(OECD
2004)&amp;quot;},&amp;quot;properties&amp;quot;:{&amp;quot;noteIndex&amp;quot;:0},&amp;quot;schema&amp;quot;:&amp;quot;https://github.com/citation-style-language/schema/raw/master/csl-citation.json&amp;quot;}&lt;span
style='mso-element:field-separator'&gt;&lt;/span&gt;&lt;/span&gt;&lt;![endif]--&gt;(OECD 2004)&lt;!--[if supportFields]&gt;&lt;span
lang=EN-US style='font-size:11.0pt;line-height:107%;font-family:"Calibri",sans-serif;
mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:
minor-latin;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";
mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:
EN-US;mso-bidi-language:AR-SA'&gt;&lt;span style='mso-element:field-end'&gt;&lt;/span&gt;&lt;/span&gt;&lt;![endif]--&gt;&lt;span style="font-size:14px"&gt; which can also be modified depending on the effect one expects.&lt;/span&gt;&lt;/p&gt;
</measurement-methodology>
    <evidence-supporting-taxonomic-applicability>&lt;p&gt;&lt;span style="font-size:14px"&gt;&lt;strong&gt;Taxonomic: &lt;/strong&gt;This AO is applicable to all living organisms.&lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style="font-size:14px"&gt;&lt;strong&gt;Life stage: &lt;/strong&gt;This AO&amp;nbsp;is applicable to all life stages.&lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style="font-size:14px"&gt;&lt;strong&gt;Sex: &lt;/strong&gt;This AO is applicable to all sexes.&lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style="font-size:14px"&gt;&lt;strong&gt;Chemical:&lt;/strong&gt; Substances known to increase mortality in arthropods are of the family of pyrimidine nucleosides (e.g. polyoxin D and nikkomycin Z) (Gijswijt et al. 1979; Tellam et al. 2000; Arakawa et al. 2008).&lt;/span&gt;&lt;/p&gt;
</evidence-supporting-taxonomic-applicability>
    <applicability>
      <sex>
        <evidence>High</evidence>
        <sex>Unspecific</sex>
      </sex>
      <life-stage>
        <evidence>High</evidence>
        <life-stage>All life stages</life-stage>
      </life-stage>
      <taxonomy taxonomy-id="ea814eb6-69f3-4e8c-ac5b-717a3a128152">
        <evidence>High</evidence>
      </taxonomy>
      <taxonomy taxonomy-id="ef4a2929-d427-4701-95e2-b111b1e3d7b2">
        <evidence>High</evidence>
      </taxonomy>
    </applicability>
    <biological-events>
      <biological-event process-id="efcf79dc-ab8e-4920-bb69-10a36230c5ff" action-id="919cb9fb-4039-429b-807a-7c50a607f62d"/>
    </biological-events>
    <references>&lt;p&gt;&lt;span style="font-size:14px"&gt;Arakawa T, Yukuhiro F, Noda H. 2008. Insecticidal effect of a fungicide containing polyoxin B on the larvae of &lt;em&gt;Bombyx mori&lt;/em&gt; (Lepidoptera: Bombycidae), &lt;em&gt;Mamestra brassicae&lt;/em&gt;, &lt;em&gt;Mythimna separata&lt;/em&gt;, and &lt;em&gt;Spodoptera litura&lt;/em&gt; (Lepidoptera: Noctuidae). Appl Entomol Zool. 43(2):173&amp;ndash;181. doi:10.1303/aez.2008.173.&lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style="font-size:14px"&gt;Gijswijt MJ, Deul DH, de Jong BJ. 1979. Inhibition of chitin synthesis by benzoyl-phenylurea insecticides, III. Similarity in action in &lt;em&gt;Pieris brassicae&lt;/em&gt; (L.) with Polyoxin D. Pestic Biochem Physiol. 12(1):87&amp;ndash;94. doi:10.1016/0048-3575(79)90098-1.&lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style="font-size:14px"&gt;OECD. 2004. Test No. 202: &lt;em&gt;Daphnia sp.&lt;/em&gt; Acute Immobilisation Test. OECD OECD Guidelines for the Testing of Chemicals, Section 2. [accessed 2020 Mar 3]. https://www.oecd-ilibrary.org/environment/test-no-202-daphnia-sp-acute-immobilisation-test_9789264069947-en.&lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style="font-size:14px"&gt;Tellam RL, Vuocolo T, Johnson SE, Jarmey J, Pearson RD. 2000. Insect chitin synthase. cDNA sequence, gene organization and expression. Eur J Biochem. 267(19):6025&amp;ndash;6043. doi:10.1046/j.1432-1327.2000.01679.x.&lt;/span&gt;&lt;/p&gt;
</references>
    <source>AOPWiki</source>
    <creation-timestamp>2016-11-29T18:41:24</creation-timestamp>
    <last-modification-timestamp>2020-10-26T05:18:16</last-modification-timestamp>
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    <source>AOPWiki</source>
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    <source>AOPWiki</source>
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  <aop id="c20f8718-c565-48e6-9a62-2ce4f42aa024">
    <title>Knickkopf leading to mortality</title>
    <short-name>Knickkopf leading to mortality</short-name>
    <point-of-contact>Agnes Aggy</point-of-contact>
    <authors>&lt;p&gt;Donggon Yoo&lt;sup&gt;1,2&lt;/sup&gt; , Ihn-Sil Kwak&lt;sup&gt;3,4&lt;/sup&gt;, Woo-Keun Kim&lt;sup&gt;1,2&lt;/sup&gt;*&lt;/p&gt;

&lt;p&gt;&amp;nbsp;&lt;/p&gt;

&lt;p&gt;&amp;nbsp;&lt;/p&gt;

&lt;p&gt;1.&amp;nbsp;Human and Environmental Toxicology, University of Science and Technology, Daejeon, 34113, Korea&lt;/p&gt;

&lt;p&gt;2.&amp;nbsp;Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, 34114, Korea&lt;/p&gt;

&lt;p&gt;3.&amp;nbsp;Fisheries Science Institute, Chonnam National University, Yeosu, 59626, Korea&lt;/p&gt;

&lt;p&gt;4. Faculty of Marine Technology, Chonnam National University, Yeosu, 59626, Korea&lt;/p&gt;
</authors>
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      <wiki-license>BY-SA</wiki-license>
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    <handbook-version>2.5</handbook-version>
    <abstract>&lt;p style="text-align:justify"&gt;&lt;span style="font-size:11pt"&gt;&lt;span style="font-family:&amp;quot;Times New Roman&amp;quot;,serif"&gt;&lt;span style="font-family:&amp;quot;Arial&amp;quot;,sans-serif"&gt;On the basis of the literature, we propose the AOP associated with the molting process. During growth, insects must undergo a process of molting along with the development of their cuticles, in which old cuticles are replaced with new ones. Chitinase present in the molting fluid breaks down chitin in old cuticles, providing a substrate for the synthesis of new cuticles. The presence of the chitin-binding protein Knickkopf (Knk) in a new procuticle under development has been shown to be important for protecting chitin from degradation by active chitinase. Knockout and repression of the KnK gene result in chitinase-dependent degradation of chitin in new cuticles, molt defects, developmental arrest, and mortality.&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style="font-size:11.0pt"&gt;&lt;span style="font-family:&amp;quot;Arial&amp;quot;,sans-serif"&gt;&lt;span style="color:black"&gt;This process affects chitin laminar organization and is prevented by chitinases. This results in the weakening of procuticle protection and a decrease in of new cuticle secretion. And it induces an incomplete moulting process, which causes malformations and increases the mortality rate of immature individuals&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
</abstract>
    <development-strategy>&lt;p&gt;&lt;span style="font-size:11.0pt"&gt;&lt;span style="font-family:&amp;quot;Arial&amp;quot;,sans-serif"&gt;&lt;span style="color:black"&gt;Based on a literature review, we proposed the conceptual AOP framework associated with Knickkopf, leading to mortality. Based on the paper, the molecular mechanism of Knickkopf&amp;#39;s molting is relatively clear. However, the supporting information on Knickkopf and related KEs is not sufficient yet. We believe our animal model experiment data and further gene analysis can validate the key regulators in the suggested AOP. Then, we can suggest essentiality and evidence for each KEs based on animal model studies. The process for this AOP validation needs at least one year. This AOP is related to the molting process and it is thought that it will be helpful for research use together with the existing AOP (4, 358~361).&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
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&lt;table class="table table-bordered table-fullwidth"&gt;
	&lt;thead&gt;
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			&lt;th&gt;KER(s) involved&lt;/th&gt;
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