PUBLICATION
Pharmacokinetics and effects of tetrabromobisphenol a (TBBPA) to early life stages of zebrafish (Danio rerio)
- Authors
- Liu, H., Ma, Z., Zhang, T., Yu, N., Su, G., Giesy, J.P., Yu, H.
- ID
- ZDB-PUB-171011-15
- Date
- 2018
- Source
- Chemosphere 190: 243-252 (Journal)
- Registered Authors
- Keywords
- HPLC-MS, Internal dose, Kinetics model, Receptor-mediated network, Transcriptional co-regulators
- MeSH Terms
-
- Animals
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/drug effects
- Flame Retardants/metabolism
- Flame Retardants/pharmacokinetics
- Flame Retardants/pharmacology
- Flame Retardants/toxicity
- Gene Expression Regulation/drug effects
- Polybrominated Biphenyls/metabolism
- Polybrominated Biphenyls/pharmacokinetics
- Polybrominated Biphenyls/pharmacology*
- Polybrominated Biphenyls/toxicity
- Signal Transduction/drug effects
- Water Pollutants/pharmacology
- Water Pollutants/toxicity
- Zebrafish/embryology
- Zebrafish/metabolism*
- Zebrafish/physiology
- PubMed
- 28992476 Full text @ Chemosphere
Citation
Liu, H., Ma, Z., Zhang, T., Yu, N., Su, G., Giesy, J.P., Yu, H. (2018) Pharmacokinetics and effects of tetrabromobisphenol a (TBBPA) to early life stages of zebrafish (Danio rerio). Chemosphere. 190:243-252.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping