title: Ecdysone Receptor Agonism Leading to Lethal Molting Disruption in Arthropods: Review and Adverse Outcome Pathway Development.
abstract: Molting is critical for growth, development, reproduction, and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting chemicals (EDCs). Based on several known ED mechanisms, a wide range of pesticides has been developed to combat unwanted organisms in food production activities such as agriculture and aquaculture. Meanwhile, these chemicals may also pose hazards to nontarget species by causing molting defects, and thus potentially affecting the health of the ecosystems. The present review summarizes the available knowledge on molting-related endocrine regulation and chemically mediated disruption in arthropods (with special focus on insects and crustaceans), to identify research gaps and develop a mechanistic model for assessing environmental hazards of these compounds. Based on the review, multiple targets of EDCs in the molting processes were identified and the link between mode of action (MoA) and adverse effects characterized to inform future studies. An adverse outcome pathway (AOP) describing ecdysone receptor agonism leading to incomplete ecdysis associated mortality was developed according to the OECD guideline and subjected to weight of evidence considerations by evolved Bradford Hill Criteria. This review proposes the first invertebrate ED AOP and may serve as a knowledge foundation for future environmental studies and AOP development.
authors.affiliation: Norwegian Institute for Water Research (NIVA), Section of Ecotoxicology and Risk Assessment, Gaustadalléen 21, N-0349 Oslo, Norway.
authors.forename: You
authors.identifier: 0000-0001-8523-3513
authors.initials: Y
authors.lastname: Song
authors.affiliation: US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, Minnesota 55804, United States.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
authors.affiliation: Environmental Genomics Group, School of Biosciences, University of Birmingham , Edgbaston, Birmingham B15 2TT, United Kingdom.
authors.forename: Kenji
authors.initials: K
authors.lastname: Toyota
authors.affiliation: Department of Basic Biology, Faculty of Life Science, SOKENDAI (Graduate University for Advanced Studies), Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences , Okazaki, Aichi 444-8787, Japan.|Graduate School of Nanobioscience, Yokohama City University , Yokohama 236-0027, Japan.
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
authors.affiliation: Norwegian Institute for Water Research (NIVA), Section of Ecotoxicology and Risk Assessment, Gaustadalléen 21, N-0349 Oslo, Norway.|Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Norwegian University of Life Sciences (NMBU) , P.O. Box 5003, N-1432, Ås, Norway.
authors.forename: Knut Erik
authors.initials: KE
authors.lastname: Tollefsen
mesh_terms: D000818:Animals; D001181:Arthropods; D003445:Crustacea; D052244:Endocrine Disruptors / Q000378:metabolism / Q000494:pharmacology*; D018978:Molting / Q000187:drug effects*; D012098:Reproduction / Q000187:drug effects
chemical_list: D052244:Endocrine Disruptors