Differential exposure to organophosphate flame retardants in mother-child pairs.
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ABSTRACT:
SUBMITTER: Gibson EA
PROVIDER: S-EPMC6460923 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
Publications
Differential exposure to organophosphate flame retardants in mother-child pairs.
Gibson Elizabeth A EA Stapleton Heather M HM Calero Lehyla L Holmes Darrell D Burke Kimberly K Martinez Rodney R Cortes Boris B Nematollahi Amy A Evans David D Anderson Kim A KA Herbstman Julie B JB
Chemosphere 20181204
<h4>Background</h4>Humans are ubiquitously exposed to flame retardants, including organophosphate esters (OPEs), through direct contact with consumer products or exposure through household dust. Children are at increased risk because of their proximity to dust, hand-to-mouth activity, and the importance of childhood as a critical period in neurodevelopment.<h4>Objectives</h4>To quantify differences in exposure levels between mothers and children (three to six years of age), we analyzed urinary m ...[more]
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Project description:The knowledge of the effects of organophosphate flame retardants on children's neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children's neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children's urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (β = -1.30; 95%CI = -2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (β = -0.98; 95%CI = -2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (β = -1.42; 95% CI = -2.70; -0.06; p-value = 0.04) and no clear association with DPHP (β = -1.09; 95% CI = -2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was -0.49 (95%CI = -1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was -0.35 (95%CI = -1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.
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Project description:Organophosphate flame retardants (PFRs) are becoming popular replacements for the phased-out polybrominated diphenyl ether (PBDE) mixtures, and they are now commonly detected in indoor environments. However, little is known about human exposure to PFRs because they cannot be easily measured in blood or serum.To investigate relationships between the home environment and internal exposure, we assessed associations between two PFRs, tris(1,3-dichloropropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP), in paired hand wipe and dust samples and concentrations of their metabolites in urine samples (n = 53). We also assessed short-term variation in urinary metabolite concentrations (n = 11 participants; n = 49 samples).Adult volunteers in North Carolina, USA, completed questionnaires and provided urine, hand wipe, and household dust samples. PFRs and PBDEs were measured in hand wipes and dust, and bis(1,3-dichloropropyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), metabolites of TDCIPP and TPHP, were measured in urine.TDCIPP and TPHP were detected frequently in hand wipes and dust (> 86.8%), with geometric mean concentrations exceeding those of PBDEs. Unlike PBDEs, dust TDCIPP and TPHP levels were not associated with hand wipes. However, hand wipe levels were associated with urinary metabolites. Participants with the highest hand wipe TPHP mass, for instance, had DPHP levels 2.42 times those of participants with the lowest levels (95% CI: 1.23, 4.77). Women had higher levels of DPHP, but not BDCIPP. BDCIPP and DPHP concentrations were moderately to strongly reliable over 5 consecutive days (intraclass correlation coefficients of 0.81 and 0.51, respectively).PFR exposures are widespread, and hand-to-mouth contact or dermal absorption may be important pathways of exposure.
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Project description:During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.
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Project description:Organophosphate flame retardants (PFRs) are widely used as replacements for polybrominated diphenyl ethers in consumer products. With high detection in indoor environments and increasing toxicological evidence suggesting a potential for adverse health effects, there is a growing need for reliable exposure metrics to examine individual exposures to PFRs. Silicone wristbands have been used as passive air samplers for quantifying exposure in the general population and occupational exposure to polycyclic aromatic hydrocarbons. Here we investigated the utility of silicone wristbands in measuring exposure and internal dose of PFRs through measurement of urinary metabolite concentrations. Wristbands were also compared to hand wipes as metrics of exposure. Participants wore wristbands for 5 consecutive days and collected first morning void urine samples on 3 alternating days. Urine samples were pooled across 3 days and analyzed for metabolites of the following PFRs: tris(1,3-dichloroisopropyl) phosphate (TDCIPP), tris(1-chloro-2-isopropyl) phosphate (TCIPP), triphenyl phosphate (TPHP), and monosubstituted isopropylated triaryl phosphate (mono-ITP). All four PFRs and their urinary metabolites were ubiquitously detected. Correlations between TDCIPP and TCIPP and their corresponding urinary metabolites were highly significant on the wristbands (rs = 0.5-0.65, p < 0.001), which suggest that wristbands can serve as strong predictors of cumulative, 5-day exposure and may be an improved metric compared to hand wipes.
| S-EPMC4872512 | biostudies-literature
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.
| S-EPMC10591987 | biostudies-literature
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.
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Project description:Organophosphorous flame retardants (PFRs) were first reported in the late 1970, and today they account for approximately 20 % of the total use of flame retardants in Europe. PFRs are found ubiquitously in the environment, including remote areas stretching from the Arctic to the Antarctic. Generally, similar levels of PFRs is observed between Arctic and more rural areas. The toxicity of PFRs varies depending on their chemical structure. The World Health Organization have reported LC50 values for mammals and aquatic organisms with high variation from 4.2 to 180 mg/L or 707 to 4700 mg/kg body weight, depending on substance and test species. However, little is known about the toxicity and physiological effects of PFRs to fish, particularly in the Arctic species. Hence, the objective of this study is to determine the effects of PFR exposure on hepatic gene expression patterns in Atlantic cod (Gadus morhua) using liver explants in vitro. Liver explants were exposed to 2-Ethylhexyl diphenyl phosphate (EHDPP), tris(2-chloroisopropyl)phosphate (TCPP), and a mixture of both EHDPP and TCPP for 0, 24 and 48 hours. Samples were analyzed for gene expresson profiling using RNAseq. RNAsequening results suggest that exposure to PFRs differentially expressed genes involved in xenobiotic metabolism. We did not observe any chemical-specific effects on gene expression patterns. However, temporal changes in gene expression were observed. Most of the differentially expressed genes (DE) in 24h exposed samples are related in xenobiotic metabolism, whereas in 48h samples DE genes belong to diverse physiological processes.
2017-12-31 | GSE103954 | GEO
Project description: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.
| S-EPMC6154272 | biostudies-literature
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| S-EPMC6960943 | biostudies-literature
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