| 1. |
- England-Mason, Gillian, et al.
(författare)
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Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants : An epigenome-wide association study
- 2022
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood.Objective: Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs).Methods: Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders.Results: One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs.Discussion: Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.
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| 2. |
- England-Mason, Gillian, et al.
(författare)
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Similar names, different results : Consistency of the associations between prenatal exposure to phthalates and parent-ratings of behavior problems in preschool children
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental health research has reported mixed findings on the associations between prenatal exposure to phthalates and parent-ratings of child behavioral problems.Objective: We examined the consistency of the associations between prenatal urinary phthalate concentrations and child behavior scores across two standardized instruments - the Behavior Assessment System for Children-Second Edition (BASC-2) and the Child Behavior Checklist (CBCL) - using two analytical approaches used to correct for urine dilution.Method: A sample of 351 mother-child pairs were selected from a prospective birth cohort of pregnant women enrolled between 2009 and 2012. Women provided spot urine samples during the second trimester of pregnancy, which were analyzed for levels of nine urinary phthalate metabolites. When their typically developing children were 3-4 years of age, mothers completed the BASC-2 and CBCL on the same day. Adjusted regression analyses examined the associations between maternal prenatal phthalate concentrations and child behavior scores on the BASC-2 and CBCL. To correct for urine dilution, primary regression analyses included urinary creatinine concentration as a separate independent variable (i.e., covariate). In the secondary regression analyses, creatinine-adjusted phthalate concentrations were used.Results: Primary logistic regression analyses that included urinary creatinine as a covariate showed that higher prenatal phthalate concentrations were related to increased odds of scores falling into the borderline or clinical range on the Hyperactivity, Aggression, Anxiety, Depression, Withdrawal, Externalizing Problems, Internalizing Problems, and Behavioral Symptoms Index scales on the BASC-2 (ORs from 1.39 to 2.07), but only the Anxious/ Depressed and Externalizing Problems scales on the CBCL (ORs from 1.80 to 3.28). Primary linear regression analyses showed that higher prenatal phthalate concentrations were related to higher scores on the Externalizing Problems (beta's = 0.16), Internalizing Problems (beta's from 0.16 to 0.20), and Behavioral Symptoms Index (beta's from 0.18 to 0.21) scales on the BASC-2, but not related to any CBCL scales. Sex-stratified analyses found that many associations were only significant for male children. Secondary analyses using creatinine-adjusted phthalate concentrations revealed that some of the associations from the primary analyses remained significant; however, a number of unique associations were observed.Conclusion: Prenatal phthalate exposure was associated with preschool behavioral development; however, findings were not consistent for the BASC-2 and CBCL, especially related to the clinical/syndrome scales and Internalizing Problems scale. Further, many findings differed based on the analytical approach used to correct for urine dilution. Future work is needed to delineate the similarities and differences between similarly named child behavior constructs assessed by different neurodevelopmental assessments. Also, research is needed to better understand why and how different analytical approaches influence the reported associations between maternal prenatal phthalate concentrations and children's behavior problems.
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| 3. |
- Liu, Jiaying, et al.
(författare)
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Exposure and dietary sources of bisphenol A (BPA) and BPA-alternatives among mothers in the APrON cohort study
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 119, s. 319-326
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Tidskriftsartikel (refereegranskat)abstract
- Diet is regarded as the main source of bisphenol A (BPA) exposure, but comparatively little is known about dietary sources of BPA-alternatives. Here we measured exposure of BPA and BPA-alternatives among pregnant women in Canada, estimated their 24-h intakes and examined the importance of various dietary sources. Free and total BPA, bisphenol S (BPS) and bisphenol F (BPF) were measured in 467 second trimester maternal urine samples, and in 455 paired samples collected M three months postpartum. Linear regression was used to evaluate associations between urinary concentrations of bisphenols and 24-h dietary recall data. The geometric means of total BPA in second trimester and postpartum urine (1.2 and 0.95 ng/mL, respectively) were 5-7 times higher than corresponding total BPS (0.16 and 0.17 ng/mL). The detection frequency of BPF was only 9% (i.e. > 1.0 ng/mL). However, M both time points 95th percentiles of total BPF (7.3 and 4.2 ng/mL, respectively) were similar to total BPA (8.2 and 5.0 ng/mL). Free BPS and BPF were detected in < 2% of samples, but were detectable when total BPS or BPF concentrations were highest, always M < 1% of the total concentration. The tolerable daily intake for total BPA (i.e. 18 nmol/kg BW/d) was not exceeded, but for BPS the estimated 24-h intake was as high as 14 nmol/kg BW/d (95th percentile: 0.12 nmol/kg BW/d), and for BPF was even higher among the highest centile of exposure (maximum and 95th percentile: 30, 0.81 nmol/kg BW/d). Canned food consumption was associated with higher total BPA, but was not associated with BPS. For BPF, mustard consumption may be an important exposure source, particularly among the highest exposed. Relatively high exposure to BPS and BPF in a minority of pregnant women highlights the need to better understand the associated health risks and exposure sources of BPA-alternatives.
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| 4. |
- Liu, Jiaying, et al.
(författare)
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Interaction of prenatal bisphenols, maternal nutrients, and toxic metal exposures on neurodevelopment of 2-year-olds in the APrON cohort
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies suggest that Bisphenol-A (BPA) is a developmental neurotoxicant, but the modifying effects of maternal nutrient status or neurotoxicant metal co-exposures have not been reported. Bisphenol-S (BPS) is being used as a BPA-alternative, but few epidemiological studies have evaluated its effects.Objectives: To examine if prenatal maternal BPA or BPS exposure are associated with children's neurodevelopment at two years of age while adjusting for effect-measure modification by sex, maternal nutrients, and co-exposure to neurotoxic metals.Methods: Total BPA and BPS concentrations were analyzed in spot maternal urine from the second trimester; metals and maternal nutrient status were analyzed in blood. Child neurodevelopment was evaluated with the Bayley Scales of Infant Development-III (Bayley-III) at age 2 (394 maternal-child pairs) and linear regression was used to investigate associations.Results: Among nutrients and neurotoxic metals, selenium (Se) and cadmium (Cd) were the most significant predictors of Bayley-III scale scores. Higher maternal Cd was significantly correlated with poorer motor performance (p < 0.01), and higher levels of maternal Se were significantly associated with poorer performance on the cognitive, motor, and adaptive behavior scales (p < 0.05). While maternal Cd did not modify relationships between bisphenol exposures and Bayley-III scores, both maternal Se and child sex were significant effectmeasure modifiers. Associations between BPA exposure and social emotional scores were negative for boys (p = 0.056) but positive for girls (p = 0.046). Higher exposure to bisphenols was associated with lower motor scores among children with lower levels of maternal Se.Conclusion: Higher maternal Cd was associated with poorer motor development, but it was not an effect-measure modifier of bisphenols' effects on motor development. Maternal Se may be protective against adverse effects of bisphenols, and additional nutrient-bisphenol interaction studies examining sex-specific effects of BPA and BPS on child development are warranted.
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| 5. |
- Liu, Yanna, et al.
(författare)
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Temporal trends of perfluorooctanesulfonate isomer and enantiomer patterns in archived Swedish and American serum samples
- 2015
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 75, s. 215-222
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Tidskriftsartikel (refereegranskat)abstract
- Human perfluorooctanesulfonate (PFOS) body burdens are attributable to both direct PFOS and indirect PFOS precursor (PreFOS) exposure. The relative importance of these two pathways has been estimated, but the relative temporal trajectory of exposure to PFOS and PreFOS has not been examined. Here, two hypothesized biomarkers of PreFOS exposure, PFOS isomer profiles (quantified as percent branched PFOS, %br-PFOS) and chiral 1m-PFOS enantiomer fractions (1m-PFOS EF) were analyzed in archived human serum samples of individual American adults (1974-2010) and pooled samples of Swedish primiparous women (1996-2010). After correcting for potential confounders, significant correlations between %br-PFOS and 1m-PFOS EFs were observed in American samples and in Swedish samples for the 1996-2000 period, supporting the hypothesis that both %br-PFOS and 1m-PFOS EF are biomarkers of PreFOS exposure. Significant trends of increasing %br-PFOS, from 2000 to 2010, and increasingly non-racemic 1m-PFOS EFs, from 1996 to 2000, were detected in Swedish samples. No statistically significant trend for %br-PFOS or 1m-PFOS EF was observed in American samples, but American males had significantly higher %br-PFOS and significantly lower 1m-PFOS EF (i.e. more non-racemic) than females, and a similar significant difference was shown in the older age group, relative to the younger age group. These temporal trends in %br-PFOS and 1m-PFOS EF are not easily explained and the results highlight uncertainties about how humans are exposed to PFOS.
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| 6. |
- Nyanza, Elias C., et al.
(författare)
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Effects of prenatal exposure and co-exposure to metallic or metalloid elements on early infant neurodevelopmental outcomes in areas with small-scale gold mining activities in Northern Tanzania
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 149
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artisanal and small-scale gold mining (ASGM) is associated with release of neurotoxic metallic or metalloid chemical elements including lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As).Objective: To examine associations between prenatal exposure and co-exposure to total lead (T-Pb), total mercury (T-Hg), total cadmium (T-Cd) and total arsenic (T-As) and infant neurodevelopment at 6 to 12 months of age in areas with ASGM activities in Tanzania.Methods: Women in their second trimester of pregnancy who resided in ASGM areas were enrolled from 2015 to 2017 (n = 883). At 6 to 12 months of age, children were assessed with the Malawi Developmental Assessment Tool (MDAT) (n = 439). We measured T-Pb, T-Hg, and T-Cd in maternal dried blood spots and T-As in maternal urines. Poisson regression was used to examine associations between prenatal concentrations of these elements and neurodevelopmental outcomes.Results: Prenatal T-Hg concentration was associated with global neurodevelopment status (aPR 1.03, CI:1.01-1.04; p < 0.001) and language impairment (aPR 1.05, CI:1.03-1.07; p < 0.001) on the MDAT. When prenatal T-Hg and T-As values were at or above the human biomonitoring reference values (>= 95%) of the German Environmental Survey for Human Biomonitoring, that is 0.80 mu g/L and 15 mu g/L, respectively, the prevalence ratio of global neurodevelopmental impairment was two times higher (aPR 2.1, CI:1.0-4.3; p = 0.034). There was a 40% increase in the prevalence ratio of global neurodevelopmental impairment (aPR 1.4, CI:0.90-2.10, p = 0.027), when prenatal T-Hg was at or above the reference value of 0.80 mu g/L and T-Pb was at or above the reference value of 35 mu g/L. When prenatal T-Hg was at or above the reference value of 0.80 mu g/L and T-As was at or above the reference value of 15 mu g/L, the prevalence ratio of global neurodevelopmental impairment was two times higher (aPR 2.1, CI:1.0-4.3; p < 0.034).Discussion: Infants born to women in areas with ASGM activities are at significant risk for neurodevelopmental impairment and this is associated with exposure to higher concentrations of Hg prenatally. Co-exposure to high concentrations of Hg and Pb, or Hg and As appeared to have negative potentiated effects on infants' neurodevelopment.
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| 7. |
- Nyanza, Elias C., et al.
(författare)
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Maternal exposure to arsenic and mercury and associated risk of adverse birth outcomes in small-scale gold mining communities in Northern Tanzania
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to arsenic and mercury in artisanal and small-scale gold mining (ASGM) communities is an issue that predominantly affects low and middle-income countries. Large epidemiology studies in these communities are rare, and the impact of such exposures on reproductive outcomes are not well understood.Objective: To examine associations between prenatal maternal arsenic and mercury exposure and birth outcomes in both ASGM and non-ASGM communities in Northern Tanzania.Methods: This longitudinal prospective study included 961 women (ASGM = 788, non-ASGM = 173) of the original cohort of 1056 who were followed until a pregnancy outcome was registered. Maternal spot urine samples and dried blood spots were used to measure total arsenic (T-As) and total mercury (T-Hg) in the second trimester of pregnancy. Data on adverse birth outcomes were collected in 5 categories: spontaneous abortion, stillbirth, preterm birth, low birth weight, and visible congenital anomalies. Mann-Whitney U-tests were used to test for differences between median T-As and T-Hg by area of residence. Logistic regression models were used to estimate the odds of stillbirth and visible congenital anomalies given maternal T-As and T-Hg levels. Modified Poisson regressions were used to estimate relative risk ratios between maternal T-As and T-Hg levels and composite adverse birth outcome, spontaneous abortion, low birth weight, and preterm birth.Results: Statistically significant differences were found in median T-As (9.6 vs. 6.3 mu g/L, Mann-Whitney U-tests, Z = -3.50, p < 0.001) and median T-Hg blood concentrations (1.2 vs. 0.70 mu g/L, Z = -9.88, p-value < 0.001) between women living in ASGM and non-ASGM areas respectively. In ASGM areas, the adjusted relative risk (aRR) of a composite adverse birth outcome increased with increasing T-As (aRR 1.23, 95%CI: 1.14-1.33, p < 0.0001) and T-Hg (aRR 1.17, 95%CI: 1.1-1.25, p < 0.0001) exposure. Spontaneous abortion (aRR 1.53, 95%CI: 1.28-1.83), stillbirth (adjusted odds ratio (aOR) 1.97, 95%CI: 1.45-2.66) and preterm birth (1.17, 95%CI: 1.01-1.36) were significantly associated with elevated T-As, whereas elevated T-Hg was significantly associated with stillbirth (aOR 2.49, 95%CI: 1.88-3.29) and visible congenital anomalies (aOR 2.24, 95%CI: 1.3-3.87).Conclusion: Over half (54.7%) of women in ASGM areas of Northern Tanzania had adverse birth outcomes and the risk of adverse birth outcomes was significantly associated with increased prenatal exposure to arsenic and mercury.
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| 8. |
- Reardon, Anthony J. F., et al.
(författare)
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Longitudinal analysis reveals early-pregnancy associations between perfluoroalkyl sulfonates and thyroid hormone status in a Canadian prospective birth cohort
- 2019
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 129, s. 389-399
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Tidskriftsartikel (refereegranskat)abstract
- Serum perfluoroalkyl acids (PFAAs) have been linked to disruption of maternal thyroid hormone homeostasis, but results have varied between studies which we hypothesized was due to timing of the thyroid hormone measurements, variability in PFAA isomer patterns, or presence of other stressors. In a longitudinal study design, we investigated the time-dependency of associations between PFAA isomers and thyroid hormones during pregnancy and post-partum while considering thyroid peroxidase antibody (TPOAb) status and mercury (Hg) co-exposure. In participants of a prospective Canadian birth cohort (n = 494), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH) and TPOAb were quantified in maternal plasma collected in each trimester and 3-months postpartum, and 25 PFAAs (15 linear and 10 branched) and Hg were quantified in samples collected during the second trimester. Perfluorohexane sulfonate (PFHxS) and total branched isomers of perfluorooctane sulfonate (PFOS) were positively associated with TSH in mixed-effect models, with strongest associations early in gestation. Throughout pregnancy and post-partum, PFHxS was inversely associated with FT4, consistent with elevated TSH, while Hg was inversely associated with FT3. In TPOAb-positive women, negative associations were found between PFUnA and FT4, and 1m-PFOS and TSH, supporting previous studies that thyroid disorder could increase susceptibility to PFAA-mediated hormone dysregulation. Hg did not confound associations but was a significant interaction term, revealing further positive associations between PFOS isomers (Sigma 3m + 4m-PFOS) and TSH. Higher perfluoroalkyl sulfonate exposures were associated with higher TSH and/or lower FT4, strongly suggestive that PFHxS and branched PFOS isomers are risk factors for subclinical maternal hypothyroidism. Isomer-specific analysis is important in future studies, as crude measures of 'totalPFOS' masked the associations of branched isomers. A concerning result was for PFHxS which had consistent negative associations with FT4 at all time points and a positive association with TSH in early pregnancy when fetal development is most sensitive to disruption.
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| 9. |
- Reardon, Anthony J. F., et al.
(författare)
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Maternal co-exposure to mercury and perfluoroalkyl acid isomers and their associations with child neurodevelopment in a Canadian birth cohort
- 2023
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Ingår i: Environment International. - 0160-4120 .- 1873-6750. ; 178
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Tidskriftsartikel (refereegranskat)abstract
- Background: Perfluoroalkyl acids (PFAAs) within the broader class of per- and polyfluoroalkyl substances (PFAS) are present in human serum as isomer mixtures, but epidemiological studies have yet to address isomer-specific associations with child development and behavior. Objectives: To examine associations between prenatal exposure to 25 PFAAs, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) isomers, and child neurodevelopment among 490 mother-child pairs in a prospective Canadian birth cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. To consider the influence of a classic neurotoxicant, total mercury (THg), based on its likelihood of co-exposure with PFAAs from common dietary sources. Methods: Maternal blood samples were collected in the second trimester and child neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III). Linear or curvilinear multiple regression models were used to examine associations between exposures and neurodevelopment outcomes. Results: Select PFAAs were associated with lower Cognitive composite scores, including perfluoroheptanoate (PFHpA) (& beta; = -0.88, 95% confidence interval (CI): -1.7, -0.06) and perfluorododecanoate (PFDoA) (& beta; = -2.0, 95% CI: -3.9, -0.01). Non-linear relationships revealed associations of total PFOS (& beta; = -4.4, 95% CI: -8.3, -0.43), and linear-PFOS (& beta; = -4.0, 95% CI: -7.5, -0.57) and 1m-PFOS (& beta; = -1.8, 95% CI: -3.3, -0.24) isomers with lower Language composite scores. Although there was no effect modification, including THg interaction terms in PFAA models revealed negative associations between perfluorononanoate (PFNA) and Motor (& beta; = -3.3, 95% CI: -6.2, -0.33) and Social-Emotional (& beta; = -3.0, 95% CI: -5.6, -0.40) composite scores. Discussion: These findings reinforce previous reports of adverse effects of maternal PFAA exposure during pregnancy on child neurodevelopment. The unique hazards posed from isomers of PFOS justify isomer-specific analysis in future studies. To control for possible confounding, mercury co-exposure may be considered in studies of PFAAs.
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| 10. |
- Sun, Chenxing, et al.
(författare)
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Nontarget profiling of organic compounds in a temporal series of hydraulic fracturing flowback and produced waters
- 2019
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- Hydraulic fracturing (HF) flowback and produced water (FPW) can be toxic to aquatic life but its chemical content is largely unknown, variable and complex. Seven FPW samples were collected from a HF operation in the Duvernay Formation (Alberta, Canada) over 30 days of flowback and characterized by a nontarget workflow based on high performance liquid chromatography - high resolution mass spectrometry (HRMS). A modified Kendrick mass defect plot and MS/MS spectral interpretation revealed seven series of homologues composed of ethylene oxide (i.e. -CH2CH2O-), among which a series of aldehydes was proposed as degradation products of polyethylene glycols, and two series of alkyl ethoxylate carboxylates could be proprietary HF additives. Many other ions were confidently assigned a formula by accurate mass measurement and were subsequently prioritized for identification by matching to records in ChemSpider and the US EPA's CompTox Chemistry Dashboard. Quaternary ammonium compounds, amine oxides, organophosphorous compounds, phthalate diesters and hydroxyquinoline were identified with high confidence by MS/MS spectra (Level 3), matching to reference spectra in MassBank (Level 2) or to authentic standards (Level 1). Temporal trends showed that most of the compounds declined in abundance over the first nine days of flowback, except for phthalate diesters and hydroxyquinoline that were still observed on Day 30 and had disappearance half-lives of 61 and 91 days, respectively. All the compounds followed first-order disappearance kinetics in flowback, except for polyoxygenated acids which followed second-order kinetics. This analysis and the workflow, based largely on public on-line databases, enabled profiling of complex organic compounds in HF-FPW, and will likely be useful for further understanding the toxicity and chemical fate of HF-FPW.
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