TBBPA exposure during a sensitive developmental window produces neurobehavioral changes in larval zebrafish

Chen, Jiangfei; Tanguay, Robert L.; Xiao, Yanyan; Haggard, Derik E.; Ge, Xiaoqing; Jia, Yinhang; Zheng, Yi; Dong, Qian; Huang, Changjiang; Lin, Kuangfei

doi:10.1016/j.envpol.2016.05.059

Cited by 82 publications

(28 citation statements)

References 49 publications

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“…Similarly, an absence of behavioral changes in zebrafish embryos or larvae exposed to TBBPA was reported by several other investigators (Noyes et al 2015;Dach et al 2019;Jarema et al 2015;Truong et al 2014). In contrast, Chen et al (2016) found that zebrafish embryos exposure to 5 µM TBBPA altered larval behavior as evidenced by diminished activity bursts, lower speed of movement, motor deficits, delayed cranial motor neuron development, and inhibited primary motor neuron development. However, Fraser et al (2017) demonstrated that larval zebrafish behavioral responses to TBBPA were dependent on the photo-regime, larval age and arena size.…”

Section: Zebrafishsupporting

confidence: 68%

Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish

Kacew

Hayes

2019

Arch Toxicol

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Tetrabromobisphenol A (2,2′,6,6′-tetrabromo-4,4′-isopropylidenediphenol, CAS no. 79-94-7) (TBBPA) is an effective brominated flame retardant present in many consumer products whose effectiveness is attributable to its ability to retard flames and consequently save human lives. Toxicokinetic studies revealed that TBBPA when absorbed via the gastrointestinal tract is rapidly metabolized to glucuronide or sulfate metabolites which are rapidly eliminated by the kidney. TBBPA does not accumulate in the body and there is no evidence that the parent compound is present in the brain. Although this brominated flame retardant was detected in human breast milk and serum, there was no evidence that TBBPA reached the brain in in vivo animal studies as reflected by the absence of neuropathological, neurotoxic, or behavioral alterations indicating that the central nervous system is not a target tissue. These animal investigations were further supported by use of the larval/embryo observations that TBBPA did not produce behavioral changes in a larval/embryo zebrafish a model of chemical-induced neurotoxicity. Although some protein expressions were increased, deceased or not affected in the blood-brain barrier indicating no evidence that TBBPA entered the brain, the changes were contradictory, or gender related, and behavior was not affected supporting that this compound was not neurotoxic. Taken together, TBBPA does not appear to target the brain and is not considered as a neurotoxicant.

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Section: Zebrafishsupporting

confidence: 68%

Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish

Kacew

Hayes

2019

Arch Toxicol

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“…TBBPA-DBPE was chosen as a derivative and transformative product of TBBPA and both of these are used as FRCs in polymers (Knudsen et al, 2007;Qu et al, 2013). While TBBPA can induce oxidative stress and neurobehavioral deficits (Chen et al, 2016;Wu et al, 2016), our data showed that the predominant effect was likely disruption of protein localization and disruption of translation resulting in large-scale morphological effects. For TBBPA-DBPE, neurodevelopment was an important targeted gene process (Figure 9), consistent with its behavioral phenotype.…”

Section: Tbbpa Vs Tbbpa-dbpe-role Of Transformationmentioning

confidence: 71%

Phenotypically Anchored mRNA and miRNA Expression Profiling in Zebrafish Reveals Flame Retardant Chemical Toxicity Networks

Dasgupta

Dunham

Truong

et al. 2021

Front. Cell Dev. Biol.

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The ubiquitous use of flame retardant chemicals (FRCs) in the manufacture of many consumer products leads to inevitable environmental releases and human exposures. Studying toxic effects of FRCs as a group is challenging since they widely differ in physicochemical properties. We previously used zebrafish as a model to screen 61 representative FRCs and showed that many induced behavioral and teratogenic effects, with aryl phosphates identified as the most active. In this study, we selected 10 FRCs belonging to diverse physicochemical classes and zebrafish toxicity profiles to identify the gene expression responses following exposures. For each FRC, we executed paired mRNA-micro-RNA (miR) sequencing, which enabled us to study mRNA expression patterns and investigate the role of miRs as posttranscriptional regulators of gene expression. We found widespread disruption of mRNA and miR expression across several FRCs. Neurodevelopment was a key disrupted biological process across multiple FRCs and was corroborated by behavioral deficits. Several mRNAs (e.g., osbpl2a) and miRs (e.g., mir-125b-5p), showed differential expression common to multiple FRCs (10 and 7 respectively). These common miRs were also predicted to regulate a network of differentially expressed genes with diverse functions, including apoptosis, neurodevelopment, lipid regulation and inflammation. Commonly disrupted transcription factors (TFs) such as retinoic acid receptor, retinoid X receptor, and vitamin D regulator were predicted to regulate a wide network of differentially expressed mRNAs across a majority of the FRCs. Many of the differential mRNA-TF and mRNA-miR pairs were predicted to play important roles in development as well as cancer signaling. Specific comparisons between TBBPA and its derivative TBBPA-DBPE showed contrasting gene expression patterns that corroborated with their phenotypic profiles. The newer generation FRCs such as IPP and TCEP produced distinct gene expression changes compared to the legacy FRC BDE-47. Our study is the first to establish a mRNA-miR-TF regulatory network across a large group of structurally diverse FRCs and diverse phenotypic responses. The purpose was to discover common and unique biological targets that will help us understand mechanisms of action for these important chemicals and establish this approach as an important tool for better understanding toxic effects of environmental contaminants.

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“…The identification of all PBDEs were confirmed, and concentrations were measured using an external quantification standard containing known amounts of all the target PBDE congeners. The detailed method for TBBPA analysis was described previously (Chen et al, 2016b) with 13 C-polychlorinated biphenyls (PCB) 208 as the internal standard. HMs (PbAc and CdCl 2 ) were measured using an inductively coupled plasma-mass spectrometer as described previously (Chen et al, 2016c; Wu et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

“…In the e-waste sites, PBDEs and TBBPA were widely detected in different environmental media including water, air, dust, and food (Tang et al, 2015; Wang et al, 2015; Wu et al, 2016). As endocrine disruptors, both PBDEs and TBBPA had effects on reproduction, neurobehavior, and development (Chen et al, 2016a; Chen et al, 2016b; Chen et al, 2012; He et al, 2011). HMs, such as lead (Pb) and cadmium (Cd), were also important hazardous substances that were released from e-waste recycling.…”

Section: Introductionmentioning

confidence: 99%

Chronic co-exposure to low levels of brominated flame retardants and heavy metals induces reproductive toxicity in zebrafish

Chen

Tian

et al. 2018

Toxicol Ind Health

Self Cite

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Brominated flame retardants (BFRs) and heavy metals (HMs) are two main types of pollutants in electronic waste recycling sites, which are also ubiquitously detectable in environmental media and human tissues. However, the adverse health effects of exposure to the mixture of these types of pollutants are unknown. In this study, we investigated the reproductive toxicity of a mixture of decabromodiphenyl ether (BDE-209), tetrabromobisphenol A, cadmium chloride, and lead acetate (PbAc) at the environmental relevant levels. Zebrafish were waterborne and exposed to chemical mixtures for one generation. The reproductive effects were evaluated for F0 adults and F1 offspring. Chemical residues were also analyzed in the exposed adults and their eggs at the end of exposure. Our findings demonstrated that exposure to the chemical mixture for 150 days had no effect on the survival rate of zebrafish, but it decreased body length and weight in females and increased body weight and condition factor in males. The mixture exposure resulted in a female-biased sex ratio in adults and decreased sperm density and motility in males and egg production in females. For the F1 offspring, decreased fertilization, delayed hatching, and increased malformation were found in all exposure groups. In conclusion, chronic co-exposure to BFRs and HMs at the environmental relevant levels not only affected growth, sex ratio, and sperm quantity/quality and egg production in adults but also reduced the reproductive success in the offspring, implying that multi-pollutants in the environmental media may pose a public health risk to other exposed organisms or human beings.

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TBBPA exposure during a sensitive developmental window produces neurobehavioral changes in larval zebrafish

Cited by 82 publications

References 49 publications

Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish

Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish

Phenotypically Anchored mRNA and miRNA Expression Profiling in Zebrafish Reveals Flame Retardant Chemical Toxicity Networks

Chronic co-exposure to low levels of brominated flame retardants and heavy metals induces reproductive toxicity in zebrafish

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