Dataset Information

Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish.

ABSTRACT: 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.

SUBMITTER: Glazer L

PROVIDER: S-EPMC6154272 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish.

Glazer Lilah L Hawkey Andrew B AB Wells Corinne N CN Drastal Meghan M Odamah Kathryn-Ann KA Behl Mamta M Levin Edward D ED

Toxicological sciences : an official journal of the Society of Toxicology 20181001 2

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 ...[more]

PMID: 29982741

Similar Datasets

Project description:BackgroundPolybrominated diphenyl ethers (PBDEs) were widely used as flame retardants until the early 2000s, mainly in home furnishings and electronics. The persistence of PBDEs in the environment leads to continued ubiquitous exposure to low levels, with infants and children experiencing higher exposures than adults. Accumulating evidence suggest that low-level exposures during early life stages can affect brain development and lead to long-term behavioral impairments. We investigated the effects of zebrafish exposure to low doses of the two prominent PBDEs; 2,2',4,4',5,-Pentabromodiphenyl ether (BDE-99) and 2,2',4,4',-Tetrabromodiphenyl ether (BDE-47), during embryo-development on short- and long-term behavioral endpoints. We included the organophosphate pesticide chlorpyrifos (CPF) due to its well documented neurotoxicity across species from zebrafish to humans.MethodsZebrafish embryos were exposed to the following individual treatments; 0.1% DMSO (vehicle control); 0.3μM CPF; 0.01, 0.03, 0.1, 0.3μM BDE-47; 0.003, 0.03, 0.3, 1, 3, 10, 20μM BDE-99 from 5 until 120h post fertilization (hpf). Low exposure levels were determined as those not causing immediate overt toxicity, and behavior assays were conducted in the low-level range. At 144 hpf the larvae were tested for locomotor activity. At approximately 6 months of age adult zebrafish were tested in a behavioral battery including assays for anxiety-related behavior, sensorimotor response and habituation, social interaction, and predator avoidance.ResultsIn the short-term, larval locomotor activity was reduced in larvae treated with 0.3μM CPF and 0.1μM BDE-47. BDE-99 treatment caused non-monotonic dose effects, with 0.3μM causing hyperactivity and 1μM or higher causing hypoactivity. In the long-term, adult anxiety-related behavior was reduced in all treatments as measured in both the novel tank dive test and tap test.DiscussionWe show that exposure of zebrafish embryos to low concentrations of the brominated flame retardants BDE-47 and BDE-99, and the organophosphate pesticide CPF, caused both short- and long-term behavioral impairments. Interestingly, we also found that at very low exposure concentrations, where there were no visible effects on larval activity, adult behavior was still strongly affected.

Project description:The increased use of flammable plastics and electronic devices along with stricter fire safety standards has led to the heavy use of flame retardant chemicals in many consumer, commercial, and industrial products. Although flame retardant use has increased, a great deal of uncertainty surrounds their safety with some evidence showing toxicity and risk to human and environmental health. Recent efforts have focused on designing high-throughput biological platforms with nonmammalian models to evaluate and prioritize chemicals with limited hazard information. To complement these efforts, this study used a new morphological and behavioral testing platform with embryonic zebrafish to characterize the developmental toxicity of 44 halogenated and organophosphate flame retardants, including several of their known metabolites. Zebrafish were exposed to flame retardants from 6 to 120 h post fertilization (hpf) across concentrations spanning 4 orders of magnitude (eg, 6.4 nM to 64 µM). Flame retardant effects on survival and development were evaluated at 24 and 120 hpf, and neurobehavioral changes were measured using 2 photomotor response (PMR) assays. Compared to controls, 93% (41/44) of flame retardants studied elicited adverse effects among one or more of the bioassays and concentrations tested with the aryl phosphate ester (APE)-based mono-isopropylated triaryl phosphate and the brominated-bisphenol-A analog tetrabromobisphenol-A producing the greatest array of malformations. Hierarchical clustering showed that APE flame retardants with isopropyl, butyl, and cresyl substituents on phenyl rings clustered tightly and were particularly potent. Both PMR assays were highly predictive of morphological defects supporting their use as nonlethal means of evaluating teratogenicity that could allow for additional evaluations of long-term or delayed effects in older animals. Taken together, evidence presented here indicates that zebrafish neurodevelopment is highly sensitive to many flame retardants currently in use and can be used to understand potential vulnerabilities to human health.

Project description:BackgroundOrganophosphate esters (OPEs), used as flame retardants and plasticizers, are chemicals of concern for maternal and infant health. Prior studies examining temporal trends and predictors of OPE exposure are primarily limited by small sample sizes.ObjectivesCharacterize temporal trends and predictors of OPE exposure biomarkers.MethodsWe determined urinary concentrations of eight biomarkers of OPE exposure at three timepoints during pregnancy for participants in the LIFECODES Fetal Growth Study (n = 900), a nested case-cohort recruited between 2007 and 2018. We examined biomarker concentrations, their variability during pregnancy, and temporal trends over the study period. In addition, we identified sociodemographic and pregnancy characteristics associated with biomarker concentrations. Analyses were conducted using both the within-subject pregnancy geometric means and biomarker concentrations measured at individual study visits.ResultsFive OPE biomarkers were detected in at least 60% of the study participants. Biomarkers were not strongly correlated with one another and intraclass correlation coefficients, measuring within-subject variability during pregnancy, ranged from 0.27 to 0.51. Biomarkers exhibited varying temporal trends across study years. For example, bis(1-chloro-2-propyl) phosphate (BCIPP) increased monotonically, whereas bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), displayed non-monotonic trends with concentrations that peaked between 2011 and 2014. We observed associations between sociodemographic characteristics and OPE biomarkers. In general, concentrations of most OPE biomarkers were higher among participants from racial and ethnic minority populations, participants who were younger, had higher pre-pregnancy body mass index (BMI), and less than a college degree. We observed consistent results using either averaged or visit-specific biomarker concentrations.SignificanceWe observed widespread exposure to several OPEs and OPE biomarkers displayed varying temporal trends in pregnant people from 2007 to 2018. Concentrations of most OPE biomarkers varied according to sociodemographic factors, suggesting higher burdens of exposure among participants with higher pre-pregnancy BMI, those belonging to racial and ethnic minority populations, and lower educational attainment.

Project description:BACKGROUND:Following the phase-out of polybrominated diphenyl ethers (PBDEs), organophosphate esters (OPEs) have been increasingly used in consumer products and building materials for their flame retardant and plasticizing properties. As a result, human exposure to these chemicals is widespread as evidenced by common detection of their metabolites in urine. However, little is known about the major exposure pathways, or factors that influence children's exposure to OPEs. Furthermore, little data is available on exposure to the novel aryl OPEs. OBJECTIVES:To examine predictors of children's internal exposure, we assessed relationships between OPEs in house dust and on hand wipes and levels of their corresponding metabolites in paired urine samples (n?=?181). We also examined associations between urinary metabolites and potential covariates, including child's age and sex, mother's educational attainment and race, and average outdoor air temperature. METHODS:Children aged 3 to 6?years provided urine and hand wipe samples. Mothers or legal guardians completed questionnaires, and a house dust sample was taken from the main living area during home visits. Alkyl chlorinated and aryl OPEs were measured in dust and hand wipes, and composite urine samples were analyzed for several metabolites. RESULTS:Tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), 2-ethylhexyl diphenyl phosphate (EHDPHP), triphenyl phosphate (TPHP), and 2-isopropylphenyl diphenyl phosphate (2IPPDPP) were detected frequently in hand wipes and dust (>80%), indicating that these compounds were near-ubiquitous in indoor environments. Additionally, bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), mono-isopropyl phenyl phenyl phosphate (ip-PPP), and mono-tert-butyl phenyl phenyl phosphate (tb-PPP) were detected in >94% of tested urine samples, signifying that TESIE participants were widely exposed to OPEs. Contrary to PBDEs, house dust OPE concentrations were generally not correlated with urinary OPE metabolite levels; however, hand wipe levels of OPEs were associated with internal dose. For example, children with the highest mass of TDCIPP on hand wipes had BDCIPP levels that were 2.73 times those of participants with the lowest levels (95% CI: 1.67, 4.48, p?<?0.0001). Of the variables examined, hand wipe level was the most consistent and strongest predictor of OPE urinary metabolite concentrations. Outdoor air temperature was also a significant predictor of urinary BDCIPP concentrations, with a 1?°C increase in temperature corresponding to a 4% increase in urinary BDCIPP (p?<?0.0001). CONCLUSIONS:OPE exposures are highly prevalent, and data provided herein further substantiate hand-to-mouth contact and dermal absorption as important pathways of OPE exposure, especially for young children.

Dataset Information

Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish.

Publications

Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets