Aryl organophosphate flame retardants induced cardiotoxicity during zebrafish embryogenesis: By disturbing expression of the transcriptional regulators

Du, Zhongkun; Wang, Guowei; Gao, Shixiang; Wang, Zunyao

doi:10.1016/j.aquatox.2015.01.027

Cited by 181 publications

(86 citation statements)

References 35 publications

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“…Previous studies involving short‐term exposure to 1000 μg/L to 2000 µg/L TPP have shown that such exposures impede normal development of organs such as the heart, which could lead to hindrance of normal growth and development in zebrafish . In the present study, we observed that exposure to relatively lower levels of TPP (5–500 µg/L) for relatively shorter terms (14 dpf and 40 dpf) did not affect overall fish growth.…”

Section: Resultssupporting

confidence: 42%

Long‐term exposure to triphenylphosphate alters hormone balance and HPG, HPI, and HPT gene expression in zebrafish (Danio rerio)

Liu

Jung

et al. 2016

Enviro Toxic and Chemistry

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With the global decline in the use of polybrominated diphenyl ethers, the demand for alternative flame retardants, such as triphenylphosphate (TPP), has increased substantially. Triphenylphosphate is now detected in various environments including aquatic ecosystems worldwide. However, studies on the toxicological consequences of chronic TPP exposure on aquatic organisms are scarce. The zebrafish model was used to investigate the effects of long-term TPP exposure on the endocrine system. Zebrafish embryos were exposed to 5 µg/L, 50 µg/L, or 500 µg/L TPP for 120 d, and hormonal and transcriptional responses were measured along the hypothalamic-pituitary-gonad (HPG) axis, the hypothalamic-pituitary-interrenal (HPI) axis, and the hypothalamic-pituitary-thyroid (HPT) axis. Exposure to TPP significantly increased plasma 17β-estradiol, but decreased 11-ketotestosterone in both sexes. Gene expression data support these changes. In the HPI axis, plasma cortisol and proopiomelanocortin (pomc) and mineralocorticoid receptor transcripts increased in females, but in males cortisol decreased whereas pomc increased (p < 0.05). Thyroxine and triiodothyronine increased, and thyrotrophin-releasing hormone receptor 2 (trhr2) and trh expression were affected only in females (p < 0.05). In summary, long-term exposure to TPP enhanced estrogenicity in both males and females, potentially through influencing the HPG axis, but modulated the HPI, and HPT axes differently by sex, suggesting that both genomic and nongenomic responses might be involved. Environ Toxicol Chem 2016;35:2288-2296. © 2016 SETAC.

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Section: Resultssupporting

confidence: 42%

Long‐term exposure to triphenylphosphate alters hormone balance and HPG, HPI, and HPT gene expression in zebrafish (Danio rerio)

Liu

Jung

et al. 2016

Enviro Toxic and Chemistry

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“…We also found that exposure to the tested organophosphate flame retardants (except TCEP) resulted in heart rate reduction in the medaka embryos (Table ). Similarly, it has been reported that TPHP exposure could induce cardiac developmental defects (including decreased heart rate) in zebrafish embryos at concentrations above 0.5 mg/L, which might be related to the disturbed expression of key transcriptional regulators in cardiogenesis . Volz and colleagues suggested that these TPHP‐induced cardiac impairments, accompanied by reduced survival rate and body length, were aryl hydrocarbon receptor–independent but might have been mediated instead through the retinoic acid receptor .…”

Section: Discussionmentioning

confidence: 94%

“…Although organophosphate flame retardants consist of the same organophosphate frame, there is great variation in their physical and chemical properties, as well as toxicity, depending on the specific moieties of each organophosphate flame retardant . In fact, the correlation between the hydrophobicity and toxicity of organophosphate flame retardants has been well documented.…”

Section: Discussionmentioning

confidence: 99%

Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes)

Sun

Tan

Peng

et al. 2016

Enviro Toxic and Chemistry

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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.

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“…Toxicological studies have shown that OPFRs have the potential to cause adverse reproductive, endocrine and systemic effects in animals as a result of long term exposure to animals (Dishaw et al, 2011;Liu et al, 2012;Porter et al, 2014;Van der Veen and de Boer, 2012). Aryl-OPFRs have been shown to contribute to heart toxicity by disturbing the expression of transcriptional regulators in zebrafish (Du et al, 2015). Chlorinated OPFRs, such as TCEP, TCIPP and TDCIPP, have been proven to be neurotoxic and carcinogenic (Ni et al, 2007;WHO, 1998WHO, , 2000.…”

Section: Introductionmentioning

confidence: 99%

Review of OPFRs in animals and humans: Absorption, bioaccumulation, metabolism, and internal exposure research

2016

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h i g h l i g h t sThe absorption, bioaccumulation, metabolism and internal exposure of OPFRs are reviewed. Inhalation, ingestion and dermal contact are the main OPFRs absorptionpathways for humans. General in vivo and in vitro metabolic pathways of three different types of OPFRs are proposed. DAPs and MAPs are considered as putative biomarkers for the assessment of internal exposure of OPFRs in humans. a r t i c l e i n f o t r a c tDue to their widespread use, organophosphate flame retardants (OPFRs) are commonly detected in various environmental matrices and have been identified as emerging contaminants. Considering the adverse effects of OPFRs, many researchers have paid their attention on the absorption, bioaccumulation, metabolism and internal exposure processes of OPFRs in animals and humans. In this article, we first review the diverse absorption routes of OPFRs by animals and humans (e.g., inhalation, ingestion, dermal absorption and gill absorption). Bioaccumulation and biomagnification potentials of OPFRs in different types of organisms and food webs are also summarized, based on quite limited available data and results. For metabolism, we review the Phase-I and Phase-II metabolic processes for each type of OPFRs (chlorinated OPFRs, alkyl-OPFRs and aryl-OPFRs) in the animals and humans, as well as toxicokinetic information and putative exposure biomarkers on OPFRs. Finally, we highlight gaps in our knowledge and critical directions for future internal exposure studies of OPFRs in animals and humans.

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Aryl organophosphate flame retardants induced cardiotoxicity during zebrafish embryogenesis: By disturbing expression of the transcriptional regulators

Cited by 181 publications

References 35 publications

Long‐term exposure to triphenylphosphate alters hormone balance and HPG, HPI, and HPT gene expression in zebrafish (Danio rerio)

Long‐term exposure to triphenylphosphate alters hormone balance and HPG, HPI, and HPT gene expression in zebrafish (Danio rerio)

Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes)

Review of OPFRs in animals and humans: Absorption, bioaccumulation, metabolism, and internal exposure research

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