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Increase, Premature molting leads to Increase, Mortality
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|S-adenosylmethionine depletion leading to population decline (2)||adjacent||You Song (send email)||Under development: Not open for comment. Do not cite|
|S-adenosylmethionine depletion leading to population decline (1)||adjacent||You Song (send email)||Under development: Not open for comment. Do not cite|
|Chitinase inhibition leading to mortality||adjacent||Moderate||Low||Simon Schmid (send email)||Under development: Not open for comment. Do not cite|
|Chitobiase inhibition leading to mortality||adjacent||Moderate||Low||Simon Schmid (send email)||Under development: Not open for comment. Do not cite|
|Chitin synthase 1 inhibition leading to mortality||adjacent||Moderate||Low||Simon Schmid (send email)||Open for comment. Do not cite|
|Sulfonylureareceptor binding leading to mortality||adjacent||High||High||Simon Schmid (send email)||Under development: Not open for comment. Do not cite|
Life Stage Applicability
Key Event Relationship Description
During molting, arthropods pause food uptake and in certain cases also respiration (Camp et al. 2014; Song et al. 2017a). If molting is disrupted and the organism is not able to shed the old exoskeleton, the organism may eventually die of starvation, suffocation or the rupture of the exoskeleton.
Evidence Supporting this KER
In order to grow and develop, arthropods need to molt periodically (Heming 2018). Since molting is a determining point in arthropod development, the disruption of molting leads to increased mortality (Arakawa et al. 2008; Merzendorfer et al. 2012; Song et al. 2017a; Song et al. 2017b). During ecdysis, arthropods pause food intake and respiration (Camp et al. 2014; Song et al. 2017a). Therefore, if the molt cannot be completed, the organism may die of starvation or suffocation. Additionally, if the cuticle is immature, it may not withstand the stresses associated with ecdysis (Clarke 1957; Lee 1961; Dall et al. 1978; deFur et al. 1985), and the organism may die of desiccation or increased susceptibility to pathogens. Given the well understood biological processes, the biological plausibility of this KER was rated as high.
Uncertainties and Inconsistencies
The absence of studies (quantitatively) assessing premature molting constitutes a major data gap. A further data gap is the absence of studies which assess both, increase in premature molting and the increase in mortality are lacking.
Due to the lack of studies linking the increase in premature molting with the increase in mortality, it is not possible to describe the nature of the response-response relationship.
Death occurs after premature molting. However, an exact time frame in which death occurs cannot be defined yet.
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Taxonomic: Likely, this KER is applicable to the whole phylum of arthropods as they all depend on molting in order to develop.
Life stage: This KER is applicable for organisms molting in order to grow and develop, namely larval stages of insects and all life stages of crustaceans and arachnids.
Sex: This KER is applicable to all sexes.
Chemical: Occurrence of premature molting and an increase in mortality observed after treatment with the pyrimidine nucleosides ( e.g. polyoxin D, polyoxin B and nikkomycin Z) (Gijswijt et al. 1979; Tellam et al. 2000; Tellam and Eisemann 2000; Arakawa et al. 2008; New Zealand Environmental Protection Authority 2015). However, studies causally linking both endpoints are lacking.
Arakawa T, Yukuhiro F, Noda H. 2008. 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). Appl Entomol Zool. 43(2):173–181. doi:10.1303/aez.2008.173.
Camp AA, Funk DH, Buchwalter DB. 2014. A stressful shortness of breath: Molting disrupts breathing in the mayfly Cloeon dipterum. Freshw Sci. 33(3):695–699. doi:10.1086/677899.
Clarke KU. 1957. On the Increase in Linear Size During Growth in Locusta Migratoria L. Proc R Entomol Soc London Ser A, Gen Entomol. 32(1–3):35–39. doi:10.1111/j.1365-3032.1957.tb00361.x.
Dall W, Smith DM, Press B. 1978. Water uptake at ecdysis in the western rock lobster. J Exp Mar Bio Ecol. 35(1960). doi:10.1016/0022-0981(78)90074-6.
deFur PL, Mangum CP, McMahon BR. 1985. Cardiovascular and Ventilatory Changes During Ecdysis in the Blue Crab Callinectes Sapidus Rathbun. J Crustac Biol. 5(2):207–215. doi:10.2307/1547867.
Gijswijt MJ, Deul DH, de Jong BJ. 1979. Inhibition of chitin synthesis by benzoyl-phenylurea insecticides, III. Similarity in action in Pieris brassicae (L.) with Polyoxin D. Pestic Biochem Physiol. 12(1):87–94. doi:10.1016/0048-3575(79)90098-1.
Heming BS. 2018. Insect development and evolution. Ithaca: Cornell University Press.
Lee RM. 1961. The variation of blood volume with age in the desert locust (Schistocerca gregaria Forsk.). J Insect Physiol. 6(1):36–51. doi:10.1016/0022-1910(61)90090-7.
Merzendorfer H, Kim HS, Chaudhari SS, Kumari M, Specht CA, Butcher S, Brown SJ, Robert Manak J, Beeman RW, Kramer KJ, et al. 2012. Genomic and proteomic studies on the effects of the insect growth regulator diflubenzuron in the model beetle species Tribolium castaneum. Insect Biochem Mol Biol. 42(4):264–276. doi:10.1016/j.ibmb.2011.12.008. http://dx.doi.org/10.1016/j.ibmb.2011.12.008.
New Zealand Environmental Protection Authority. 2015. Application for approval to import ESTEEM for release. https://www.epa.govt.nz/assets/FileAPI/hsno-ar/APP202334/fbce9a39e6/APP202334-APP202334-Staff-Report-Final-updated.pdf.
Song Y, Evenseth LM, Iguchi T, Tollefsen KE. 2017b. Release of chitobiase as an indicator of potential molting disruption in juvenile Daphnia magna exposed to the ecdysone receptor agonist 20-hydroxyecdysone. J Toxicol Environ Heal - Part A Curr Issues. 80(16–18):954–962. doi:10.1080/15287394.2017.1352215. https://doi.org/10.1080/15287394.2017.1352215.
Song Y, Villeneuve DL, Toyota K, Iguchi T, Tollefsen KE. 2017a. Ecdysone Receptor Agonism Leading to Lethal Molting Disruption in Arthropods: Review and Adverse Outcome Pathway Development. Environ Sci Technol. 51(8):4142–4157. doi:10.1021/acs.est.7b00480.
Tellam RL, Eisemann C. 2000. Chitin is only a minor component of the peritrophic matrix from larvae of Lucilia cuprina. Insect Biochem Mol Biol. 30(12):1189–1201. doi:10.1016/S0965-1748(00)00097-7.
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):6025–6043. doi:10.1046/j.1432-1327.2000.01679.x.