Browsing by Subject "Flame Retardants"

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    Developmental exposure to an organophosphate flame retardant alters later behavioral responses to dopamine antagonism in zebrafish larvae.
    (Neurotoxicology and teratology, 2018-05) Oliveri, Anthony N; Ortiz, Erica; Levin, Edward D
    Human exposure to organophosphate flame retardants (OPFRs) is widespread, including pregnant women and young children with whom developmental neurotoxic risk is a concern. Given similarities of OPFRs to organophosphate (OP) pesticides, research into the possible neurotoxic impacts of developmental OPFR exposure has been growing. Building upon research implicating exposure to OP pesticides in dopaminergic (DA) dysfunction, we exposed developing zebrafish to the OPFR tris(1,3-dichloroisopropyl) phosphate (TDCIPP), during the first 5 days following fertilization. On day 6, larvae were challenged with acute administration of dopamine D1 and D2 receptor antagonists and then tested in a light-dark locomotor assay. We found that both developmental TDCIPP exposure and acute dopamine D1 and D2 antagonism decreased locomotor activity separately. The OPFR and DA effects were not additive; rather, TDCIPP blunted further D1 and D2 antagonist-induced decreases in activity. Our results suggest that TDCIPP exposure may be disrupting dopamine signaling. These findings support further research on the effects of OPFR exposure on the normal neurodevelopment of DA systems, whether these results might persist into adulthood, and whether they interact with OPFR effects on other neurotransmitter systems in producing the developmental neurobehavioral toxicity.
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    Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish.
    (Toxicological sciences : an official journal of the Society of Toxicology, 2018-10) Glazer, Lilah; Hawkey, Andrew B; Wells, Corinne N; Drastal, Meghan; Odamah, Kathryn-Ann; Behl, Mamta; Levin, Edward D
    As the older class of brominated flame retardants (BFRs) are phased out of commercial use because of findings of neurotoxicity with developmental exposure, a newer class of flame retardants have been introduced, the organophosphate flame retardants (OPFRs). Presently, little is known about the potential for developmental neurotoxicity or the behavioral consequences of OPFR exposure. Our aim was to characterize the life-long neurobehavioral effects of 4 widely used OPFRs using the zebrafish model. Zebrafish embryos were exposed to 0.1% DMSO (vehicle control); or one of the following treatments; isopropylated phenyl phosphate (IPP) (0.01, 0.03, 0.1, 0.3 µM); butylphenyl diphenyl phosphate (BPDP) (0.003, 0.03, 0.3, 3 µM); 2-ethylhexyl diphenyl phosphate (EHDP) (0.03, 0.3, 1 µM); isodecyl diphenyl phosphate (IDDP) (0.1, 0.3, 1, 10 µM) from 0- to 5-days postfertilization. On Day 6, the larvae were tested for motility under alternating dark and light conditions. Finally, at 5-7 months of age the exposed fish and controls were tested on a battery of behavioral tests to assess emotional function, sensorimotor response, social interaction and predator evasion. These tests showed chemical-specific short-term effects of altered motility in larvae in all of the tested compounds, and long-term impairment of anxiety-related behavior in adults following IPP, BPDP, or EHDP exposures. Our results show that OPFRs may not be a safe alternative to the phased-out BFRs and may cause behavioral impacts throughout the lifespan. Further research should evaluate the risk to mammalian experimental models and humans.
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    Developmental exposure to the flame retardant, triphenyl phosphate, causes long-lasting neurobehavioral and neurochemical dysfunction.
    (Birth defects research, 2023-02) Hawkey, Andrew B; Evans, Janequia; Holloway, Zade R; Pippen, Erica; Jarrett, Olivia; Kenou, Bruny; Slotkin, Theodore A; Seidler, Frederic J; Levin, Edward D

    Background

    Human exposures to organophosphate flame retardants result from their use as additives in numerous consumer products. These agents are replacements for brominated flame retardants but have not yet faced similar scrutiny for developmental neurotoxicity. We examined a representative organophosphate flame retardant, triphenyl phosphate (TPP) and its potential effects on behavioral development and dopaminergic function.

    Methods

    Female Sprague-Dawley rats were given low doses of TPP (16 or 32 mg kg-1  day-1 ) via subcutaneous osmotic minipumps, begun preconception and continued into the early postnatal period. Offspring were administered a battery of behavioral tests from adolescence into adulthood, and littermates were used to evaluate dopaminergic synaptic function.

    Results

    Offspring with TPP exposures showed increased latency to begin eating in the novelty-suppressed feeding test, impaired object recognition memory, impaired choice accuracy in the visual signal detection test, and sex-selective effects on locomotor activity in adolescence (males) but not adulthood. Male, but not female, offspring showed marked increases in dopamine utilization in the striatum, evidenced by an increase in the ratio of the primary dopamine metabolite (3,4-dihydroxyphenylacetic acid) relative to dopamine levels.

    Conclusions

    These results indicate that TPP has adverse effects that are similar in some respects to those of organophosphate pesticides, which were restricted because of their developmental neurotoxicity.
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    Increased coiling frequency linked to apoptosis in the brain and altered thyroid signaling in zebrafish embryos (Danio rerio) exposed to the PBDE metabolite 6-OH-BDE-47.
    (Chemosphere, 2018-05) Wang, Feng; Fang, Mingliang; Hinton, David E; Chernick, Melissa; Jia, Shenglan; Zhang, Yingdan; Xie, Lingtian; Dong, Wenjing; Dong, Wu
    Polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants that are ubiquitously detected in the environment and associated with adverse health outcomes. 6-OH-BDE-47 is a metabolite of the flame retardant, 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), and there is increasing concern regarding its developmental neurotoxicity and endocrine disrupting properties. In this study, we report that early life exposure in zebrafish (Danio rerio) embryos to 6-OH-BDE-47 (50 and 100 nM) resulted in higher coiling frequency and significantly increased apoptotic cells in the brain. These effects were partially rescued by overexpression of thyroid hormone receptor β (THRβ) mRNA. Moreover, exposure to 100 nM 6-OH-BDE-47 significantly reduced the number of hypothalamic 5-hydroxytryptamine (5-HT, serotonin)-immunoreactive (5-HT-ir) neurons and the mRNA expression of tryptophan hydroxylase 2 (TPH2). These results indicate that 6-OH-BDE-47 affected thyroid hormone regulation through THRβ and negatively impacted the nervous system, in turn, affecting coiling behavior. Correlations of these endpoints suggest that coiling frequency could be used as an indicator of neurotoxicity in embryos.
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    Levels of Urinary Metabolites of Organophosphate Flame Retardants, TDCIPP, and TPHP, in Pregnant Women in Shanghai.
    (J Environ Public Health, 2016) Feng, Liping; Ouyang, Fengxiu; Liu, Liangpo; Wang, Xu; Wang, Xia; Li, Yi-Ju; Murtha, Amy; Shen, Heqing; Zhang, Junfeng; Zhang, Jun Jim
    Flame retardants are widely used in consumer products to reduce their flammability. Previously used flame retardants have been sequentially banned due to their environmental and human toxicity. Currently, tris(1,3-dichloropropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) are among the most commonly used flame retardants. TDCIPP and TPHP are reproductive toxins and have carcinogenic, neurotoxic, and endocrine-disrupting properties. Although high levels of TDCIPP and TPHP have been found in drinking water, seawater, and office air in China, data regarding human exposure are lacking. In this study, we assessed the level of urinary TPHP and TDCIPP metabolites (DPHP and BDCIPP, resp.) in a cohort of pregnant women (N = 23) from Shanghai, China, using liquid chromatography-tandem mass spectrometry. DPHP were detected in 100% urine samples, while only four urine samples had detectable level of BDCIPP in this cohort (17% detected). Geometric means of DPHP and BDCIPP concentrations were 1.1 ng/mL (interquartile range [IQR]: 0.6, 1.5 ng/mL) and 1.2 ng/mL (IQR: 0.6, 2.2 ng/mL), respectively. In this small cohort, urinary DPHP and BDCIPP levels were not significantly correlated with miscarriages, neonatal birthweight, gestational diabetes, or maternal age. These data suggest that exposure to TPHP is widespread, and they demonstrate the feasibility of using urinary biomarkers to measure exposures to modern flame-retardant chemicals.
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    Results from Screening Polyurethane Foam Based Consumer Products for Flame Retardant Chemicals: Assessing Impacts on the Change in the Furniture Flammability Standards.
    (Environmental science & technology, 2016-10) Cooper, Ellen M; Kroeger, Gretchen; Davis, Katherine; Clark, Charlotte R; Ferguson, P Lee; Stapleton, Heather M
    Flame retardant (FR) chemicals have often been added to polyurethane foam to meet required state and federal flammability standards. However, some FRs (e.g., PBDEs and TDCIPP) are associated with health hazards and are now restricted from use in some regions. In addition, California's residential furniture flammability standard (TB-117) has undergone significant amendments over the past few years, and TDCIPP has been added to California's Proposition 65 list. These events have likely led to shifts in the types of FRs used, and the products to which they are applied. To provide more information on the use of FRs in products containing polyurethane foam (PUF), we established a screening service for the general public. Participants residing in the US were allowed to submit up to 5 samples from their household for analysis, free of charge, and supplied information on the product category, labeling, and year and state of purchase. Between February 2014 and June 2016, we received 1141 PUF samples for analysis from various products including sofas, chairs, mattresses, car seats and pillows. Of these samples tested, 52% contained a FR at levels greater than 1% by weight. Tris(1,3-dichloroisopropyl)phosphate (TDCIPP) was the most common FR detected in PUF samples, and was the most common FR detected in all product categories. Analysis of the data by purchasing date suggests that the use of TDCIPP decreased in recent years, paralleled with an increase in the use of TCIPP and a nonhalogenated aryl phosphate mixture we call "TBPP." In addition, we observed significant decreases in FR applications in furniture products and child car seats, suggesting the use of additive FRs in PUF may be declining, perhaps as a reflection of recent changes to TB-117 and Proposition 65. More studies are needed to determine how these changes in FR use relate to changes in exposure among the general population.