title: In vivo metabolism of organophosphate flame retardants and distribution of their main metabolites in adult zebrafish.
abstract: Understanding the metabolism of chemicals as well as the distribution and depuration of their main metabolites in tissues are essential for evaluating their fate and potential toxicity in vivo. Herein, we investigated the metabolism of six typical organophosphate (OP) flame retardants (tripropyl phosphate (TPRP), tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tri-p-cresyl phosphate (p-TCP)) in adult zebrafish in laboratory at three levels (0, 1/150 LC50(environmentally relevant level), and 1/30 LC50per OP analog). Twenty main metabolites were detected in the liver of OPs-exposed zebrafish using high resolution mass spectrometry (Q-TOF). The reaction pathways involving scission of the ester bond (hydrolysis), cleavage of the ether bond, oxidative hydroxylation, dechlorination, and coupling with glucuronic acid were proposed, and were further confirmed by the frontier electron density and point charge calculations. Tissue distribution of the twenty metabolites revealed that liver and intestine with the highest levels of metabolites were the most active organs for OPs biotransformation among the studied tissues of intestine, liver, roe, brain, muscle, and gill, which showed the importance of hepatobiliary system (liver-bile-intestine) in the metabolism and excretion of OPs in zebrafish. Fast depuration of metabolites from tissues indicated that the formed metabolites might be not persistent in fish, and easily released into water. This study provides comprehensive information on the metabolism of OPs in the tissue of zebrafish, which might give some hints for the exploration of their toxic mechanism in aquatic life.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China.
authors.forename: Hanyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China.
authors.forename: Zhongkun
authors.initials: Z
authors.lastname: Du
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China.
authors.forename: Zunyao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China. Electronic address: ecsxg@nju.edu.cn.
authors.forename: Shixiang
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D001711:Biotransformation; D004952:Esters; D005411:Flame Retardants / Q000378:metabolism*; D010755:Organophosphates / Q000378:metabolism*; D014018:Tissue Distribution; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D004952:Esters; D005411:Flame Retardants; D010755:Organophosphates
keywords: Frontier electron density; Metabolism; Metabolites distribution; Organophosphorus esters; Zebrafish