{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:10:18Z","timestamp":1792267818800,"version":"4.4.0"},"reference-count":97,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":1344,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":86,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"H2020 Marie Sklodowska-Curie Actions","award":["859891"],"award-info":[{"award-number":["859891"]}]}],"content-domain":{"domain":["setac.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,5]]},"abstract":"<jats:title>INTRODUCTION AND BACKGROUND<\/jats:title>\n               <jats:p>Arthropods (including insects, crustaceans, and arachnids) rely on the synthesis of chitin to complete their life cycles (Merzendorfer 2011). The highly conserved chitin synthetic process and the absence of this process in vertebrates make it an exploitable target for pest management and veterinary medicines (Merzendorfer 2013; Junquera et al. 2019). Susceptible, nontarget organisms, such as insects and aquatic invertebrates, exposed to chitin synthesis inhibitors may suffer population declines, which may have a negative impact on ecosystems and associated services. Hence, it is important to properly identify, prioritize, and regulate relevant chemicals posing potential hazards to nontarget arthropods.<\/jats:p>\n               <jats:p>The need for a more cost-efficient and mechanistic approach in risk assessment has been clearly evident and triggered the development of the adverse outcome pathway (AOP) framework (Ankley et al. 2010). An AOP links a molecular initiating event (MIE) through key events (KEs) to an adverse outcome. The mechanistic understanding of the underlying toxicological processes leading to a regulation-relevant adverse outcome is necessary for the utilization of new approach methodologies (NAMs) and efficient coverage of wider chemical and taxonomic domains. In the last decade, the AOP framework has gained traction and expanded within the (eco)toxicological research community. However, there exists a lack of mature invertebrate AOPs describing molting defect\u2013associated mortality triggered by direct inhibition of relevant enzymes in the chitin biosynthetic pathway (chitin synthesis inhibitors) or interference with associated endocrine systems by environmental chemicals (endocrine disruptors).<\/jats:p>\n               <jats:p>Arthropods undergo molting to grow and reproduce (Heming 2018). This process is comprised of the synthesis of a new exoskeleton, followed by the exuviation of the old exoskeleton (Reynolds 1987). The arthropod exoskeleton (cuticle) can be divided into 2 layers, the thin and nonchitinous epicuticle, which is the outermost layer of the cuticle, and the underlying chitinous procuticle. A single layer of epithelial cells is responsible for the synthesis and secretion of both cuticular layers (Neville 1975). The cuticle protects arthropods from predators and desiccation, acts as a physical barrier against pathogens, and allows for locomotion by providing support for muscular function (Vincent and Wegst 2004). Because the procuticle mainly consists of chitin microfibrils embedded in a matrix of cuticular proteins supplemented by lipids and minerals in insects (Muthukrishnan et al. 2012) and crustaceans (Cribb et al. 2009; Nagasawa 2012), chitin is a determinant factor for the appropriate composition of the cuticle and successful molting (Cohen 2001). A detailed overview of the endocrine mechanisms regulating chitin synthesis is given in Supplemental Data, Figure S1. The shedding of the old exoskeleton in insects is mediated by a sequence of distinct muscular contractions, the ecdysis motor program (EMP; Ayali 2009; Song et al. 2017a). Like the expression of chitin synthase isoform 1 (CHS-1), the expression of peptide hormones regulating the EMP is also controlled by ecdysteroids (Antoniewski et al. 1993; Gagou et al. 2002; Ayali 2009).<\/jats:p>\n               <jats:p>Cuticular chitin is polymerized from uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) by the transmembrane enzyme CHS-1, which is localized in the epithelial plasma membrane in insects (Locke and Huie 1979; Binnington 1985; Merzendorfer and Zimoch 2003; Merzendorfer 2006). Because crustaceans are also dependent on the synthesis of chitin, the underlying mechanisms are believed to be similar, although less is known about different CHS isoforms and their localization (Rocha et al. 2012; Qian et al. 2014; Uddowla et al. 2014; Har\u00f0ard\u00f3ttir et al. 2019).<\/jats:p>\n               <jats:p>Disruption of either chitin synthesis or the upstream endocrine pathways can lead to lethal molting disruption (Arakawa et al. 2008; Merzendorfer et al. 2012; Song et al. 2017a, 2017b). In the case of chitin synthesis inhibition, molting disruption can be referred to as \u201cpremature molting.\u201d If ecdysis cannot be completed because of decreased chitin synthesis, the organism may not successfully molt. Even if ecdysis can be completed on inhibition of chitin synthesis, the organism may not survive because of the poor integrity of the new cuticle. These effects are observed in arthropods following molting, which fail to survive subsequent molts (Arakawa et al. 2008; Chen et al. 2008) or animals being stuck in their exuviae (Wang et al. 2019) and ultimately dying as a result of insufficient food or oxygen intake (Camp et al. 2014; Song et al. 2017a). The term \u201cpremature molting\u201d is used to differentiate from the term \u201cincomplete ecdysis,\u201d which describes inhibition of ecdysis on a behavioral level, namely through reduction of the EMP (Song et al. 2017a).<\/jats:p>\n               <jats:p>The present AOP describes molting-associated mortality through direct inhibition of the enzyme CHS-1. It expands the small but increasing number of invertebrate AOPs that have relevance to arthropods, the largest phylum within the animal kingdom (Bar-On et al. 2018). The development of this AOP will be useful in further research and regulatory initiatives related to assessment of CHS inhibitors and identification of critical knowledge gaps and may suggest new strategies for ecotoxicity testing efforts. Environ Toxicol Chem 2021;40:2112\u20132120. \u00a9 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.<\/jats:p>","DOI":"10.1002\/etc.5058","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T12:51:47Z","timestamp":1617627107000},"page":"2112-2120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["AOP Report: Inhibition of Chitin Synthase 1 Leading to Increased Mortality in Arthropods"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-1325","authenticated-orcid":false,"given":"Simon","family":"Schmid","sequence":"first","affiliation":[{"name":"Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life Sciences \u00c5s Norway"},{"name":"Section of Ecotoxicology and Risk Assessment, Norwegian Institute for Water Research Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Song","sequence":"additional","affiliation":[{"name":"Section of Ecotoxicology and Risk Assessment, Norwegian Institute for Water Research Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7534-0937","authenticated-orcid":false,"given":"Knut Erik","family":"Tollefsen","sequence":"additional","affiliation":[{"name":"Centre for Environmental Radioactivity Norwegian University of Life Sciences \u00c5s Norway"},{"name":"Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life Sciences \u00c5s Norway"},{"name":"Section of Ecotoxicology and Risk Assessment, Norwegian Institute for Water Research Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,5]]},"reference":[{"key":"2025010313395152900_etc5058-bib-0001","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/etc.34","article-title":"Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment","volume":"29","author":"Ankley","year":"2010","journal-title":"Environ Toxicol Chem"},{"key":"2025010313395152900_etc5058-bib-0002","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0965-1748(93)90088-A","article-title":"Structural features critical to the activity of an ecdysone receptor binding site","volume":"23","author":"Antoniewski","year":"1993","journal-title":"Insect Biochem Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0003","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ibmb.2010.09.011","article-title":"Both UDP N-acetylglucosamine pyrophosphorylases of Tribolium castaneum are critical for molting, survival and fecundity","volume":"41","author":"Arakane","year":"2011","journal-title":"Insect Biochem Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0004","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1365-2583.2005.00576.x","article-title":"The Tribolium chitin synthase genes TcCHS1 and TcCHS2 are specialized for synthesis of epidermal cuticle and midgut peritrophic matrix","volume":"14","author":"Arakane","year":"2005","journal-title":"Insect Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0005","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1303\/aez.2008.173","article-title":"Insecticidal effect of a fungicide containing polyoxin B on the larvae of Bombyx mori (Lepidoptera: Bombycidae), Mamestra brassicae, Mythimna separata, and Spodoptera litura (Lepidoptera: Noctuidae)","volume":"43","author":"Arakawa","year":"2008","journal-title":"Appl Entomol Zool"},{"key":"2025010313395152900_etc5058-bib-0006","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1042\/bj1640653","article-title":"Chitin biosynthesis in protoplasts and subcellular fractions of Aspergillus fumigatus","volume":"164","author":"Archer","year":"1977","journal-title":"Biochem J"},{"key":"2025010313395152900_etc5058-bib-0007","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1242\/jeb.023879","article-title":"The role of the arthropod stomatogastric nervous system in moulting behaviour and ecdysis","volume":"212","author":"Ayali","year":"2009","journal-title":"J Exp Biol"},{"key":"2025010313395152900_etc5058-bib-0008","doi-asserted-by":"crossref","first-page":"6506","DOI":"10.1073\/pnas.1711842115","article-title":"The biomass distribution on Earth","volume":"115","author":"Bar-On","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025010313395152900_etc5058-bib-0009","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.yrtph.2015.04.004","article-title":"Increasing scientific sonfidence in adverse outcome pathways: Application of tailored Bradford-Hill considerations for evaluating weight of evidence","volume":"72","author":"Becker","year":"2015","journal-title":"Regul Toxicol Pharmacol"},{"key":"2025010313395152900_etc5058-bib-0010","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0040-8166(85)90021-7","article-title":"Ultrastructural changes in the cuticle of the sheep blowfly, Lucilia, induced by certain insecticides and biological inhibitors","volume":"17","author":"Binnington","year":"1985","journal-title":"Tissue Cell"},{"key":"2025010313395152900_etc5058-bib-0011","doi-asserted-by":"crossref","first-page":"253","DOI":"10.7164\/antibiotics.37.253","article-title":"Inhibition of chitin metabolism by avermectin in susceptible organisms","volume":"37","author":"Calcott","year":"1984","journal-title":"J Antibiot (Tokyo)"},{"key":"2025010313395152900_etc5058-bib-0012","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1086\/677899","article-title":"A stressful shortness of breath: Molting disrupts breathing in the mayfly Cloeon dipterum","volume":"33","author":"Camp","year":"2014","journal-title":"Freshw Sci"},{"key":"2025010313395152900_etc5058-bib-0013","doi-asserted-by":"crossref","first-page":"124551","DOI":"10.1016\/j.chemosphere.2019.124551","article-title":"Ecdysteroid-mimicking compounds act as both agonists and antagonists to the crustacean ecdysone receptor","volume":"237","author":"Chan","year":"2019","journal-title":"Chemosphere"},{"key":"2025010313395152900_etc5058-bib-0014","first-page":"e0010133","article-title":"Different functions of the insect soluble and membrane-bound trehalase genes in chitin biosynthesis revealed by RNA interference","volume":"5","author":"Chen","year":"2010","journal-title":"PLoS One"},{"key":"2025010313395152900_etc5058-bib-0015","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1017\/S0007485308005932","article-title":"Disruption of Spodoptera exigua larval development by silencing chitin synthase gene A with RNA interference","volume":"98","author":"Chen","year":"2008","journal-title":"Bull Entomol Res"},{"key":"2025010313395152900_etc5058-bib-0016","author":"Clarke","year":"1957"},{"key":"2025010313395152900_etc5058-bib-0017","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/ps.363","article-title":"Chitin synthesis and inhibition: A revisit","volume":"57","author":"Cohen","year":"2001","journal-title":"Pest Manag Sci"},{"key":"2025010313395152900_etc5058-bib-0018","first-page":"289","article-title":"In vitro chitin synthesis in an insect: Formation and structure of microfibrils","volume":"26","author":"Cohen","year":"1982","journal-title":"Eur J Cell Biol"},{"key":"2025010313395152900_etc5058-bib-0019","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0048-3575(90)90131-K","article-title":"Insect and fungal chitin synthetase activity: Specificity of lectins as enhancers and nucleoside peptides as inhibitors","volume":"37","author":"Cohen","year":"1990","journal-title":"Pestic Biochem Physiol"},{"key":"2025010313395152900_etc5058-bib-0020","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0048-3575(82)90141-9","article-title":"Properties and inhibition of insect integumental chitin synthetase","volume":"17","author":"Cohen","year":"1982","journal-title":"Pestic Biochem Physiol"},{"key":"2025010313395152900_etc5058-bib-0021","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/ps.1378","article-title":"Natural products that have been used commercially as crop protection agents","volume":"63","author":"Copping","year":"2007","journal-title":"Pest Manag Sci"},{"key":"2025010313395152900_etc5058-bib-0022","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.asd.2008.11.002","article-title":"Structure, composition and properties of naturally occurring non-calcified crustacean cuticle","volume":"38","author":"Cribb","year":"2009","journal-title":"Arthropod Struct Dev"},{"key":"2025010313395152900_etc5058-bib-0023","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/BF00446834","article-title":"Stoffwechselprodukte von Mikroorganismen\u2014154. Mitteilung. Nikkomycin, ein neuer Hemmstoff der Chitinsynthese bei Pilzen","volume":"160","author":"D\u00e4hn","year":"1976","journal-title":"Arch Microbiol"},{"key":"2025010313395152900_etc5058-bib-0024","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0022-0981(78)90074-6","article-title":"Water uptake at ecdysis in the western rock lobster","volume":"35","author":"Dall","year":"1978","journal-title":"J Exp Mar Biol Ecol"},{"key":"2025010313395152900_etc5058-bib-0025","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2307\/1547867","article-title":"Cardiovascular and ventilatory changes during ecdysis in the blue crab Callinectes sapidus Rathbun","volume":"5","author":"deFur","year":"1985","journal-title":"J Crustac Biol"},{"key":"2025010313395152900_etc5058-bib-0026","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1128\/jb.104.1.189-196.1970","article-title":"Mechanism of action of the antifungal agent polyoxin D","volume":"104","author":"Endo","year":"1970","journal-title":"J Bacteriol"},{"key":"2025010313395152900_etc5058-bib-0027","author":"European Chemicals Agency","year":"2017"},{"key":"2025010313395152900_etc5058-bib-0028","author":"European Chemicals Agency","year":"2008"},{"key":"2025010313395152900_etc5058-bib-0029","author":"European Commission","year":"2020"},{"key":"2025010313395152900_etc5058-bib-0030","doi-asserted-by":"crossref","first-page":"100091","DOI":"10.1016\/j.comtox.2019.100091","article-title":"In silico site-directed mutagenesis of the Daphnia magna ecdysone receptor identifies critical amino acids for species-specific and inter-species differences in agonist binding","volume":"12","author":"Evenseth","year":"2019","journal-title":"Comput Toxicol"},{"key":"2025010313395152900_etc5058-bib-0031","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1371\/journal.pbio.0030349","article-title":"How the ecdysozoan changed its coat","volume":"3","author":"Ewer","year":"2005","journal-title":"PLoS Biol"},{"key":"2025010313395152900_etc5058-bib-0032","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0965-1748(01)00101-1","article-title":"Stage-specific expression of the chitin synthase DmeChSA and DMeChSB genes during the onset of Drosophila metamorphosis","volume":"32","author":"Gagou","year":"2002","journal-title":"Insect Biochem Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0033","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0742-8413(86)90073-3","article-title":"The pharate adult clasper as a tool for measuring chitin synthesis and for identifying new chitin synthesis inhibitors","volume":"85","author":"Gelman","year":"1986","journal-title":"Comp Biochem Physiol C Comp Pharmacol"},{"key":"2025010313395152900_etc5058-bib-0034","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0048-3575(79)90098-1","article-title":"Inhibition of chitin synthesis by benzoyl-phenylurea insecticides, III. Similarity in action in Pieris brassicae (L.) with polyoxin D","volume":"12","author":"Gijswijt","year":"1979","journal-title":"Pestic Biochem Physiol"},{"key":"2025010313395152900_etc5058-bib-0035","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cbpa.2018.10.008","article-title":"Chitin synthesis and degradation in Lepeophtheirus salmonis: Molecular characterization and gene expression profile during synthesis of a new exoskeleton","volume":"227","author":"Har\u00f0ard\u00f3ttir","year":"2019","journal-title":"Comp Biochem Physiol A Mol Integr Physiol"},{"key":"2025010313395152900_etc5058-bib-0036","volume-title":"Insect Development and Evolution","author":"Heming","year":"2018"},{"key":"2025010313395152900_etc5058-bib-0037","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphys.2020.00117","article-title":"Determination of chitin content in insects: An alternate method based on calcofluor staining","volume":"11","author":"Henriques","year":"2020","journal-title":"Front Physiol"},{"key":"2025010313395152900_etc5058-bib-0038","doi-asserted-by":"crossref","first-page":"7490","DOI":"10.1021\/ja01054a045","article-title":"Studies on polyoxins, antifungal antibiotics. XIII. The structure of polyoxins","volume":"91","author":"Isono","year":"1969","journal-title":"J Am Chem Soc"},{"key":"2025010313395152900_etc5058-bib-0039","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1051\/parasite\/2019026","article-title":"Benzoylphenyl ureas as veterinary antiparasitics. An overview and outlook with emphasis on efficacy, usage and resistance","volume":"26","author":"Junquera","year":"2019","journal-title":"Parasite"},{"key":"2025010313395152900_etc5058-bib-0040","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4052\/tigg.11.187","article-title":"Functional domains in the chitin oligosaccharide synthase NodC and related \u03b2-polysaccharide synthases","volume":"11","author":"Kamst","year":"1999","journal-title":"Trends Glycosci Glycotechnol"},{"key":"2025010313395152900_etc5058-bib-0041","first-page":"1709","article-title":"Neopolyoxins A, B, and C, new chitin synthetase inhibitors","volume":"44","author":"Kobinata","year":"1980","journal-title":"Agric Biol Chem"},{"key":"2025010313395152900_etc5058-bib-0042","first-page":"1617","article-title":"The use of a Tribolium chitin synthetase assay in studying the effects of benzimidazoles with a terpene moiety and related compounds","volume":"48","author":"Kuwano","year":"1984","journal-title":"Agric Biol Chem"},{"key":"2025010313395152900_etc5058-bib-0043","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/toxsci\/kfw119","article-title":"Sequence alignment to predict across species susceptibility (SeqAPASS): A web-based tool for addressing the challenges of cross-species extrapolation of chemical toxicity","volume":"153","author":"LaLone","year":"2016","journal-title":"Toxicol Sci"},{"key":"2025010313395152900_etc5058-bib-0044","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10646-006-0115-z","article-title":"Crustacean endocrine toxicology: A review","volume":"16","author":"LeBlanc","year":"2007","journal-title":"Ecotoxicology"},{"key":"2025010313395152900_etc5058-bib-0045","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/0022-1910(61)90090-7","article-title":"The variation of blood volume with age in the desert locust (Schistocerca gregaria Forsk.)","volume":"6","author":"Lee","year":"1961","journal-title":"J Insect Physiol"},{"key":"2025010313395152900_etc5058-bib-0046","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1128\/iai.12.5.987-992.1975","article-title":"Chitin assay used to demonstrate renal localization and cortisone-enhanced growth of Aspergillus fumigatus mycelium in mice","volume":"12","author":"Lehmann","year":"1975","journal-title":"Infect Immun"},{"key":"2025010313395152900_etc5058-bib-0047","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1002\/ps.4492","article-title":"MicroRNA and dsRNA targeting chitin synthase A reveal a great potential for pest management of the hemipteran insect Nilaparvata lugens","volume":"73","author":"Li","year":"2017","journal-title":"Pest Manag Sci"},{"key":"2025010313395152900_etc5058-bib-0048","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0040-8166(79)90042-9","article-title":"Apolysis and the turnover of plasmamembrane plaques during cuticle formation in an insect","volume":"11","author":"Locke","year":"1979","journal-title":"Tissue Cell"},{"key":"2025010313395152900_etc5058-bib-0049","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1641\/0006-3568(2006)56[311:TEVOES]2.0.CO;2","article-title":"The economic value of ecological services provided by insects","volume":"56","author":"Losey","year":"2006","journal-title":"Bioscience"},{"key":"2025010313395152900_etc5058-bib-0050","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1006\/abio.2002.5594","article-title":"A nonradioactive, high throughput assay for chitin synthase activity","volume":"305","author":"Lucero","year":"2002","journal-title":"Anal Biochem"},{"key":"2025010313395152900_etc5058-bib-0051","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1126\/science.127.3299.650","article-title":"2-Thiazolidinethione-4-carboxylic acid from the reaction of captan with cysteine","volume":"127","author":"Lukens","year":"1958","journal-title":"Science"},{"key":"2025010313395152900_etc5058-bib-0052","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1095-8312.1979.tb00037.x","article-title":"Why do adult insects not moult?","volume":"11","author":"Maiorana","year":"1979","journal-title":"Biol J Linn Soc"},{"key":"2025010313395152900_etc5058-bib-0053","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1002\/etc.4733","article-title":"In silico identification of chemicals capable of binding to the ecdysone receptor","volume":"39","author":"Mellor","year":"2020","journal-title":"Environ Toxicol Chem"},{"key":"2025010313395152900_etc5058-bib-0054","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1744-7917.2012.01535.x","article-title":"Chitin synthesis inhibitors: Old molecules and new developments","volume":"20","author":"Merzendorfer","year":"2013","journal-title":"Insect Sci"},{"key":"2025010313395152900_etc5058-bib-0055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00360-005-0005-3","article-title":"Insect chitin synthases: A review","volume":"176","author":"Merzendorfer","year":"2006","journal-title":"J Comp Physiol B"},{"key":"2025010313395152900_etc5058-bib-0056","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.ejcb.2011.04.014","article-title":"The cellular basis of chitin synthesis in fungi and insects: Common principles and differences","volume":"90","author":"Merzendorfer","year":"2011","journal-title":"Eur J Cell Biol"},{"key":"2025010313395152900_etc5058-bib-0057","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ibmb.2011.12.008","article-title":"Genomic and proteomic studies on the effects of the insect growth regulator diflubenzuron in the model beetle species Tribolium castaneum","volume":"42","author":"Merzendorfer","year":"2012","journal-title":"Insect Biochem Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0058","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1242\/jeb.00709","article-title":"Chitin metabolism in insects: Structure, function and regulation of chitin synthases and chitinases","volume":"206","author":"Merzendorfer","year":"2003","journal-title":"J Exp Biol"},{"key":"2025010313395152900_etc5058-bib-0059","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-09858-y","article-title":"Characterization and RNAi-mediated knockdown of chitin synthase A in the potato tuber moth, Phthorimaea operculella","volume":"7","author":"Mohammed","year":"2017","journal-title":"Sci Rep"},{"key":"2025010313395152900_etc5058-bib-0060","first-page":"193","author":"Muthukrishnan","year":"2012"},{"key":"2025010313395152900_etc5058-bib-0061","doi-asserted-by":"crossref","first-page":"711","DOI":"10.2741\/e412","article-title":"The crustacean cuticle: Structure, composition and mineralization","volume":"4","author":"Nagasawa","year":"2012","journal-title":"Front Biosci (Elite Ed)"},{"key":"2025010313395152900_etc5058-bib-0062","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-80910-1","volume-title":"Biology of the Arthropod Cuticle","author":"Neville","year":"1975"},{"key":"2025010313395152900_etc5058-bib-0063","author":"New Zealand Environmental Protection Authority","year":"2015"},{"key":"2025010313395152900_etc5058-bib-0064","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1584\/jpestics.4.367","article-title":"Effect of chitin synthesis inhibitors on cuticle formation of the cultured integument of Chilo suppressalis","volume":"4","author":"Nishioka","year":"1979","journal-title":"J Pestic Sci"},{"key":"2025010313395152900_etc5058-bib-0065","author":"NORMAN","year":"2021"},{"key":"2025010313395152900_etc5058-bib-0066","author":"Organisation for Economic Co-operation and Development","year":"2011"},{"key":"2025010313395152900_etc5058-bib-0067","author":"Organisation for Economic Co-operation and Development","year":"2004"},{"key":"2025010313395152900_etc5058-bib-0068","author":"Organisation for Economic Co-operation and Development","year":"2003"},{"key":"2025010313395152900_etc5058-bib-0069","author":"Organisation for Economic Co-operation and Development","year":"2018"},{"key":"2025010313395152900_etc5058-bib-0070","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/s41429-019-0237-1","article-title":"Discovery and applications of nucleoside antibiotics beyond polyoxin","volume":"72","author":"Osada","year":"2019","journal-title":"J Antibiot (Tokyo)"},{"key":"2025010313395152900_etc5058-bib-0071","first-page":"89","article-title":"The regulation of crustacean metamorphosis","volume":"1","author":"Passano","year":"1961","journal-title":"Integr Comp Biol"},{"key":"2025010313395152900_etc5058-bib-0072","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbpa.2014.02.011","article-title":"Identification of ecdysteroid signaling late-response genes from different tissues of the Pacific white shrimp, Litopenaeus vannamei","volume":"172","author":"Qian","year":"2014","journal-title":"Comp Biochem Physiol A Mol Integr Physiol"},{"key":"2025010313395152900_etc5058-bib-0073","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0021-9258(18)65959-9","article-title":"A modified colorimetric method for the estimation of N-acetylamino sugars","volume":"217","author":"Reissig","year":"1955","journal-title":"J Biol Chem"},{"key":"2025010313395152900_etc5058-bib-0074","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ps.2780200207","article-title":"The cuticle, growth and moulting in insects: The essential background to the action of acylurea insecticides","volume":"20","author":"Reynolds","year":"1987","journal-title":"Pestic Sci"},{"key":"2025010313395152900_etc5058-bib-0075","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.aquaculture.2011.12.024","article-title":"Cuticular chitin synthase and chitinase mRNA of whiteleg shrimp Litopenaeus vannamei during the molting cycle","volume":"330\u2013333","author":"Rocha","year":"2012","journal-title":"Aquaculture"},{"key":"2025010313395152900_etc5058-bib-0076","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2307\/1309750","article-title":"Influence of on arthropods ecosystems","volume":"34","author":"Seastedt","year":"1984","journal-title":"Bioscience"},{"key":"2025010313395152900_etc5058-bib-0077","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ibmb.2016.07.012","article-title":"Physiological roles of trehalose in Leptinotarsa larvae revealed by RNA interference of trehalose-6-phosphate synthase and trehalase genes","volume":"77","author":"Shi","year":"2016","journal-title":"Insect Biochem Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0078","author":"Society for the Advancement of Adverse Outcome Pathways","year":"2016"},{"key":"2025010313395152900_etc5058-bib-0079","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1080\/15287394.2017.1352215","article-title":"Release of chitobiase as an indicator of potential molting disruption in juvenile Daphnia magna exposed to the ecdysone receptor agonist 20-hydroxyecdysone","volume":"80","author":"Song","year":"2017","journal-title":"J Toxicol Environ Health A"},{"key":"2025010313395152900_etc5058-bib-0080","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1021\/acs.est.7b00480","article-title":"Ecdysone receptor agonism leading to lethal molting disruption in arthropods: Review and adverse outcome pathway development","volume":"51","author":"Song","year":"2017","journal-title":"Environ Sci Technol"},{"key":"2025010313395152900_etc5058-bib-0081","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-56354-1","volume-title":"Baltic Crustaceans","author":"Szaniawska","year":"2018"},{"key":"2025010313395152900_etc5058-bib-0082","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/S0965-1748(00)00097-7","article-title":"Chitin is only a minor component of the peritrophic matrix from larvae of Lucilia cuprina","volume":"30","author":"Tellam","year":"2000","journal-title":"Insect Biochem Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0083","doi-asserted-by":"crossref","first-page":"6025","DOI":"10.1046\/j.1432-1327.2000.01679.x","article-title":"Insect chitin synthase. cDNA sequence, gene organization and expression","volume":"267","author":"Tellam","year":"2000","journal-title":"Eur J Biochem"},{"key":"2025010313395152900_etc5058-bib-0084","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1071\/BI9820491","article-title":"Effects of several larvicidal compounds on chitin biosynthesis by isolated larval integuments of the sheep blowfly Lucilia cuprina","volume":"35","author":"Turnbull","year":"1982","journal-title":"Aust J Biol Sci"},{"key":"2025010313395152900_etc5058-bib-0085","first-page":"1000298","article-title":"cDNAs encoding chitin synthase from shrimp (Pandalopsis japonica): Molecular characterization and expression analysis","volume":"6","author":"Uddowla","year":"2014","journal-title":"J Aquac Res Dev"},{"key":"2025010313395152900_etc5058-bib-0086","doi-asserted-by":"crossref","first-page":"16928","DOI":"10.1038\/srep16928","article-title":"Exploiting a moment of weakness: Male spiders escape sexual cannibalism by copulating with moulting females","volume":"5","author":"Uhl","year":"2015","journal-title":"Sci Rep"},{"key":"2025010313395152900_etc5058-bib-0087","author":"US Environmental Protection Agency","year":"2020"},{"key":"2025010313395152900_etc5058-bib-0088","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.asd.2004.05.006","article-title":"Design and mechanical properties of insect cuticle","volume":"33","author":"Vincent","year":"2004","journal-title":"Arthropod Struct Dev"},{"key":"2025010313395152900_etc5058-bib-0089","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1038\/s41598-018-37488-5","article-title":"Molecular cloning, expression, and functional analysis of the chitin synthase 1 gene and its two alternative splicing variants in the white-backed planthopper, Sogatella furcifera (Hemiptera: Delphacidae)","volume":"9","author":"Wang","year":"2019","journal-title":"Sci Rep"},{"key":"2025010313395152900_etc5058-bib-0090","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/BF00394837","article-title":"Size regulation in larvae of the crustacean Balanus eburneus (Cirripedia: Thoracica)","volume":"96","author":"West","year":"1987","journal-title":"Mar Biol"},{"key":"2025010313395152900_etc5058-bib-0091","doi-asserted-by":"crossref","first-page":"1700165","DOI":"10.1002\/pmic.201700165","article-title":"Identification and functional analysis of chitin synthase A in oriental armyworm, Mythimna separata","volume":"17","author":"Zhai","year":"2017","journal-title":"Proteomics"},{"key":"2025010313395152900_etc5058-bib-0092","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.ibmb.2006.06.002","article-title":"Characterization of a chitin synthase cDNA and its increased mRNA level associated with decreased chitin synthesis in Anopheles quadrimaculatus exposed to diflubenzuron","volume":"36","author":"Zhang","year":"2006","journal-title":"Insect Biochem Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0093","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.1744-7917.2012.01568.x","article-title":"Biochemical characterization of chitin synthase activity and inhibition in the African malaria mosquito, Anopheles gambiae","volume":"20","author":"Zhang","year":"2013","journal-title":"Insect Sci"},{"key":"2025010313395152900_etc5058-bib-0094","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1365-2583.2010.01029.x","article-title":"Chitosan\/double-stranded RNA nanoparticle-mediated RNA interference to silence chitin synthase genes through larval feeding in the African malaria mosquito (Anopheles gambiae)","volume":"19","author":"Zhang","year":"2010","journal-title":"Insect Mol Biol"},{"key":"2025010313395152900_etc5058-bib-0095","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1093\/jmedent\/44.6.1047","article-title":"Comparative studies on effects of three chitin synthesis inhibitors on common malaria mosquito (Diptera: Culicidae)","volume":"44","author":"Zhu","year":"2007","journal-title":"J Med Entomol"},{"key":"2025010313395152900_etc5058-bib-0096","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1007\/s11033-014-3288-1","article-title":"Chitin synthase A: A novel epidermal development regulation gene in the larvae of Bombyx mori","volume":"41","author":"Zhuo","year":"2014","journal-title":"Mol Biol Rep"},{"key":"2025010313395152900_etc5058-bib-0097","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ibmb.2005.01.008","article-title":"Regulation of chitin synthesis in the larval midgut of Manduca sexta","volume":"35","author":"Zimoch","year":"2005","journal-title":"Insect Biochem Mol Biol"}],"container-title":["Environmental Toxicology and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/etc.5058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/etc.5058","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/40\/8\/2112\/59785283\/etc5058.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/40\/8\/2112\/59785283\/etc5058.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T14:21:54Z","timestamp":1735914114000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/etc\/article\/40\/8\/2112\/7734306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,5]]},"references-count":97,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4,5]]},"published-print":{"date-parts":[[2021,4,5]]}},"URL":"https:\/\/doi.org\/10.1002\/etc.5058","relation":{},"ISSN":["0730-7268","1552-8618"],"issn-type":[{"value":"0730-7268","type":"print"},{"value":"1552-8618","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,8,1]]},"published":{"date-parts":[[2021,4,5]]},"assertion":[{"value":"2021-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}