Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines

Kim, Sujin; Jung, Joeun; Lee, Inae; Jung, Dawoon; Youn, Hyewon; Choi, Kyungho

doi:10.1016/j.aquatox.2015.01.016

Cited by 165 publications

(79 citation statements)

References 65 publications

(66 reference statements)

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“…A range of potencies for overt toxicity (i.e., lethality and malformations) has been reported by various groups: the highest was an LC 50 of 29.6 mg/L (90.7 µM) (Liu et al, 2013). Other estimates clustered with our POD for overt toxicity of 2 µM: TPHP-induced malformations and lethality were reported at 2 µM (McGee et al, 2013) or 0.5 µM (500 µg/L) (Kim et al, 2015). Whereas Noyes and coworkers (Noyes et al, 2015) reported decreased activity in both light and dark at the higher (64 and 6.4 µM) TPHP concentrations, the larvae that were treated develop-mentally with TPHP in our study showed behavioral changes at much lower concentrations.…”

Section: Discussionmentioning

confidence: 52%

“…Numerous groups have shown that TPHP affects thyroid development and function in zebrafish: Kim and coworkers (Kim et al, 2015) noted gene expression changes precipitated in the sub-micromolar range (0.6 to 1.5 µM) accompanied by increased T3 and T4 levels also at very low concentrations (40 µg/L = 0.123 µM), and Liu and coworkers (Liu et al, 2013) also found gene expression changes in larval zebrafish indicative of thyroid receptor perturbations at micromolar exposure concentrations. A range of potencies for overt toxicity (i.e., lethality and malformations) has been reported by various groups: the highest was an LC 50 of 29.6 mg/L (90.7 µM) (Liu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The developmentally neurotoxic PBDE flame retardants (Costa and Giordano, 2007; Costa et al, 2014) have been phased out and replaced with other halogenated (primarily chlorinated) and organophosphorus based chemicals (see Table 1 for chemicals, abbreviations and structures). There is some preliminary evidence that member(s) of both the halogenated and organophosphorus classes (BDE-47, TBBPA, TDCIPP, and TPHP) perturb the thyroid system in developing zebrafish (Chan and Chan, 2012; Kim et al, 2015; Liu et al, 2013). There is also evidence that developmental exposure to either TDCIPP or TCEP produces developmental neurotoxicity as assessed by changes in locomotor activity at 6 days post-fertilization (dpf) in larval zebrafish (Dishaw et al, 2014a, 2014b).…”

Section: Introductionmentioning

confidence: 99%

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Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

Jarema

Hunter

Shaffer

et al. 2015

Neurotoxicology and Teratology

145

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As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4′-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n ≈ 24 per dose per compound) were exposed to test compounds (0.4–120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

Jarema

Hunter

Shaffer

et al. 2015

Neurotoxicology and Teratology

145

View full text Add to dashboard Cite

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“…Preliminary toxicology studies suggest that TPHP may disrupt thyroid function (Kim et al 2015; Kojima et al 2013; Liu C et al 2013; Liu X et al 2016). Healthy thyroid function is critical for fetal and child growth and development and for maintaining important bodily systems in adults such as metabolism, mental health and cognition, and reproduction (Taylor et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Associations between urinary diphenyl phosphate and thyroid function

Preston

McClean

Henn

et al. 2017

Environment International

113

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Triphenyl phosphate (TPHP) is a commonly used organophosphate flame retardant and plasticizer with widespread human exposure. Data on health effects of TPHP are limited. Recent toxicological studies suggest TPHP may alter thyroid function. We used repeated measures to assess the temporal variability in urinary concentrations of the TPHP metabolite, diphenyl phosphate (DPHP), and to examine relationships between DPHP concentrations and thyroid hormones. We sampled 51 adults at months 1, 6, and 12 from 2010-2011. Urine samples were analyzed for DPHP. Serum samples were analyzed for free and total thyroxine (fT4, TT4), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH). We assessed variability in DPHP using intraclass correlation coefficients (ICCs) and kappa statistics. We used linear mixed-effects models to examine associations between DPHP and thyroid hormones. DPHP was detected in 95% of urine samples. Mean DPHP concentrations were 43% higher in women than men. DPHP showed high within-subject variability (ICC range, 0.13-0.39; Kappa range, 0.16-0.39). High versus low (≥2.65 vs. <2.65 ng/mL) DPHP in all participants was associated with a 0.43 μg/dL (95% confidence interval: 0.15, 0.72) increase in mean TT4 levels. In sex-stratified analyses, high versus low DPHP was associated with a 0.91 μg/dL (95% CI: 0.47, 1.36) increase in mean TT4 in women. The association was attenuated in men (βeta= 0.19; 95% CI: -0.15, 0.52). We found no significant associations between DPHP and fT4, TT3, or TSH. We found evidence that TPHP exposure may be associated with increased TT4 levels, especially in women.

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“…Exposure to FM 550 has been associated with weight gain, anxiety-like behavior, early-onset of puberty in females, and perturbed thyroid hormone levels in perinatally exposed rats (Patisaul et al, 2013). TPHP exposure has also been correlated with increases in both T3 and T4 concentrations in zebrafish larvae and an increase in the expression of genes involved in thyroid hormone synthesis in rat pituitary cell lines (Kim et al, 2015). In addition, a recent study on a range of brominated and organophosphate flame retardants flagged mono-ITP as a priority chemical warranting additional testing, as it was active in 10 out of 11 tested developmental and neurotoxicity assays at concentrations <30 lM (Behl et al, 2015).…”

mentioning

confidence: 99%

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Phillips¹,

Chen²,

Rock³

et al. 2016

Toxicol. Sci.

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FiremasterV R 550 (FM 550) is a commercial mixture of organophosphate and brominated flame retardants currently in use as a replacement for pentaBDE. Its organophosphate components include triphenyl phosphate (TPHP) and a suite of isopropylated triarylphosphate isomers (ITPs); its brominated components include 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP). Taken together, these chemicals have been shown to be endocrine disrupting and potentially toxic, and human exposure to them is widespread. In this study, maternal transfer of FM 550 components, and in some cases their metabolites, was investigated in dosed Wistar rats. Gestational and lactational transfer were examined separately, with dams orally exposed to 300 or 1000 mg of FM 550 for 10 consecutive days during gestation (gestational day [GD] 9-18) or lactation (postnatal day [PND] 3-12). Levels of parent compounds were measured in fetus and whole pup tissue homogenates, and in dam and pup serum, and several metabolites were measured in dam and pup urine. EH-TBB body burdens resulting from lactational transfer were approximately 200-to 300-fold higher than those resulting from placental transfer, whereas low levels of BEH-TEBP were transferred during both lactation and gestation. TPHP and ITPs were rapidly metabolized by the dams and were not detected in whole tissue homogenates. However, diphenyl phosphate (DPHP) and mono-isopropylphenyl phenyl phosphate (ip-PPP) were detected in urine from the dosed animals. This study is the first to confirm ip-PPP as a urinary metabolite of ITPs and establish a pharmacokinetic profile of FM 550 in a mammalian model.

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Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines

Cited by 165 publications

References 65 publications

Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish

Associations between urinary diphenyl phosphate and thyroid function

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

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