title: Development of an adverse outcome pathway for acetylcholinesterase inhibition leading to acute mortality.
abstract: Adverse outcome pathways (AOPs) are designed to describe linkages of key events within a biological pathway that result in an adverse outcome associated with chemical perturbation of a well-defined molecular initiating event. Risk assessors have traditionally relied on data from apical endpoints (e.g., mortality, growth, reproduction) to derive benchmark values for use in determining the potential adverse impacts of chemicals. One goal in building reliable and well-characterized AOPs is to identify relevant in vitro assays and/or in vivo biomarkers that could be used in screening the potential hazard of substances, thereby reducing costs and increasing the number of chemicals that can be evaluated in a timely fashion. The purpose of this review article is to build an AOP for substances with a molecular initiating event of acetylcholinesterase inhibition leading to acute mortality following guidance developed by the Organisation for Economic Cooperation and Development. In contrast to most other AOPs developed to date, in which coverage is for a relatively limited taxonomic group or life stage, this AOP is applicable to a wide range of species at multiple life stages. Furthermore, while development of most AOPs has relied on data for a few model chemicals, the AOP described in the present review captures information from a large number of studies with a diversity of organophosphate and carbamate insecticides.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, Mid-Continent Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Russom
authors.forename: Carlie A
authors.initials: CA
authors.lastname: LaLone
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000633:toxicity*; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002800:Cholinesterase Inhibitors; D004785:Environmental Pollutants; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase inhibition; Adverse outcome pathway; Ecotoxicology; Species sensitivity