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Chemosphere. 2018 Jan;190:243-252. doi: 10.1016/j.chemosphere.2017.09.137. Epub 2017 Sep 29.

Pharmacokinetics and effects of tetrabromobisphenol a (TBBPA) to early life stages of zebrafish (Danio rerio).

Author information

1
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China.
2
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China; Toxicology Centre and Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; School of Biological Sciences, University of Hong Kong, China.
3
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address: yuhx@nju.edu.cn.

Abstract

In silico and in vivo approaches were combined in an aggregate exposure pathway (AEP) to assess accumulation and effects of waterborne exposures of early life stages of zebrafish (Danio rerio) to tetrabromobisphenol A (TBBPA). Three metabolites, two of which were isomers, were detected in fish. Two additional metabolites were detected in the exposure solution. Based on kinetics modeling, proportions of TBBPA that were bioaccumulated and metabolized were 19.33% and 8.88%, respectively. Effects of TBBPA and its metabolites were predicted by use of in silico, surflex-Dock simulations that they were capable of interacting with ThRα and activating associated signaling pathways. TBBPA had a greater toxic contribution than its metabolites did when we evaluated the toxicity of these substances based on the toxicity unit method. The half of the internal lethal dose (ILD50) was 18.33 μg TBBPA/g at 74 hpf. This finding was further confirmed by changes in expressions of ThRα and other NRs as well as associated genes in their signal pathways. Specifically, exposure to 1.6 × 102, 3.3 × 102 or 6.5 × 102 μg TBBPA/L significantly down-regulated expression of ThRα and associated genes, ncor, c1d, ncoa2, ncoa3, and ncoa4, in the AR pathway and of er2a and er2b genes in the ER pathway.

KEYWORDS:

HPLC-MS; Internal dose; Kinetics model; Receptor-mediated network; Transcriptional co-regulators

[Indexed for MEDLINE]

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