title: Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes).
abstract: Because brominated flame retardants are being banned or phased out worldwide, organophosphate flame retardants have been used as alternatives on a large scale and have thus become ubiquitous environmental contaminants; this raises great concerns about their environmental health risk and toxicity. Considering that previous research has identified the nervous system as a sensitive target, Japanese medaka were used as an aquatic organism model to evaluate the developmental neurotoxicity of 4 organophosphate flame retardants: triphenyl phosphate, tri-n-butyl phosphate, tris(2-butoxyethyl) phosphate, and tris(2-chloroethyl) phosphate (TCEP). The embryo toxicity test showed that organophosphate flame retardant exposure could decrease hatchability, delay time to hatching, increase the occurrence of malformations, reduce body length, and slow heart rate. Regarding locomotor behavior, exposure to the tested organophosphate flame retardants (except TCEP) for 96 h resulted in hypoactivity for medaka larvae in both the free-swimming and the dark-to-light photoperiod stimulation test. Changes of acetylcholinesterase activity and transcriptional responses of genes related to the nervous system likely provide a reasonable explanation for the neurobehavioral disruption. Overall, the present study clearly demonstrates the developmental neurotoxicity of various organophosphate flame retardants with very different potency and contribute to the determination of which organophosphate flame retardants are appropriate substitutes, as well as the consideration of whether regulations are reasonable and required. Environ Toxicol Chem 2016;35:2931-2940. © 2016 SETAC.
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou, China.|Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Sun
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Hana
authors.initials: H
authors.lastname: Tan
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Food Science and Technology, Ocean College, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Xu
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Qian
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049628:Body Size / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D005411:Flame Retardants / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D010755:Organophosphates / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000633:toxicity; D009990:Oryzias / Q000254:growth & development* / Q000502:physiology; D018675:Toxicity Tests; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D029941:Fish Proteins; D005411:Flame Retardants; D010755:Organophosphates; D009943:Organophosphorus Compounds; C031324:tris(chloroethyl)phosphate; C009524:tributyl phosphate; D000110:Acetylcholinesterase; C013320:tris(2-butoxyethyl) phosphate
keywords: Behavioral toxicology; Embryo toxicity test; Gene transcriptional analysis; Neurotoxicity; Organophosphate