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1.
Environ Int ; 150: 106409, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33556913

RESUMO

BACKGROUND: Findings from epidemiological studies of prenatal phthalate exposure and child cognitive development are inconsistent. Methods for evaluating mixtures of phthalates, such as weighted quantile sum (WQS) regression, have rarely been applied. We developed a new extension of the WQS method to improve specificity of full-sample analyses and applied it to estimate associations between prenatal phthalate mixtures and cognitive and language outcomes in a diverse pregnancy cohort. METHODS: We measured 22 phthalate metabolites in third trimester urine from mother-child dyads who completed early childhood visits in the Conditions Affecting Neurodevelopment and Learning in Early childhood (CANDLE) study. Language and cognitive ability were assessed using the Bayley Scales of Infant Development (age 3) and the Stanford Binet-5 (age 4-6), respectively. We used multivariable WQS regression to identify phthalate mixtures that were negatively and positively associated with language score and full-scale IQ, in separate models, adjusted for maternal IQ, race, marital status, smoking, BMI, socioeconomic status (SES), child age, sex, and breastfeeding. We evaluated effect modification by sex and SES. If full sample 95% WQS confidence intervals (which are known to be anti-conservative) excluded the null, we calculated a p-value using a permutation test (ppermutation). The performance of this new approach to WQS regression was evaluated in simulated data. We compared the power and type I error rate of WQS regression conducted within datasets split into training and validation samples (WQSSplit) and in the full sample (WQSNosplit) to WQS regression with a permutation test (WQSpermutation). Individual metabolite associations were explored in secondary analyses. RESULTS: The analytic sample (N = 1015) was 62.1% Black/31.5% White, and the majority of mothers had a high school education or less (56.7%) at enrollment. Associations between phthalate mixtures and primary outcomes (language score and full-scale IQ) in the full sample were null. Individual metabolites were not associated with IQ, and only one metabolite (mono-benzyl phthalate, MBzP) was associated with Bayley language score (ß = -0.68, 95% CI: -1.37, 0.00). In analyses stratified by sex or SES, mixtures were positively and negatively associated with outcomes, but the precision of full-sample WQS regression results were not supported by permutation tests, with one exception. In the lowest SES category, a phthalate mixture dominated by mono-methyl phthalate (MMP) and mono-carboxy-isooctyl phthalate (MCOP) was associated with higher language scores (ßlow SES = 2.41, full-sample 95%CI: 0.58, 4.24; ppermutation = 0.04). Performance testing in simulated data showed that WQSpermutation had improved power over WQSSplit (90% versus 56%) and a lower type I error rate than WQSNosplit (7% versus 47%). CONCLUSIONS: In the largest study of these relationships to date, we observed predominantly null associations between mixtures of prenatal phthalates and both language and IQ. Our novel extension of WQS regression improved sensitivity to detect true associations by obviating the need to split the data into training and test sets and should be considered for future analyses of exposure mixtures.

2.
Environ Int ; 151: 106443, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33610054

RESUMO

IMPORTANCE: Exposure to phthalates may affect fetal growth, but previous studies are inconsistent and have not explored the trimester-specific effects of phthalates on repeated measures of fetal growth. OBJECTIVE: To assess the associations of maternal phthalate metabolites urine concentrations with fetal growth measures and birth outcomes and identify potential windows of vulnerability to exposure. DESIGN: Population-based prospective cohort study, the Generation R Study (2002-2006). Data analysis was performed from November 2019 to June 2020. SETTING: Rotterdam, the Netherlands. PARTICIPANTS: 1379 pregnant women. EXPOSURES: Maternal phthalate metabolites urine concentrations in first, second and third trimester. MAIN OUTCOMES AND MEASURES: Fetal head circumference, length and weight measured in the second and third trimester by ultrasound and at birth and preterm birth and small size for gestational age at birth. RESULTS: Higher pregnancy-averaged phthalic acid, low molecular weight phthalate (LMWP), high molecular weight phthalate (HMWP) and di-2-ethylhexylphthalate (DEHP) concentrations tended to be associated with lower fetal weight SDS across gestation. The associations of phthalic acid and LMWP with fetal weight became stronger as pregnancy progressed (differences -0.08 (95% CI -0.14 to -0.02) SDS and -0.09 (95% CI -0.16 to -0.02) SDS at 40 weeks per interquartile range increase in phthalic acid and LMWP, respectively). Higher concentrations of specific LMWP, HMWP and DEHP metabolites were also associated with smaller head circumference and lower length SDS at birth and an increased risk of preterm birth and small size for gestational age at birth (p-values < 0.05). We observed differences by timing of exposure in these associations. CONCLUSIONS AND RELEVANCE: Higher maternal phthalate metabolites urine concentrations seem to be related with fetal growth restriction and preterm birth. Phthalates may have trimester specific effects on fetal growth and birth outcomes. Further studies are needed to explore the underlying mechanisms and long-term consequences.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33603093

RESUMO

BACKGROUND: The Children's Health Exposure Analysis Resource (CHEAR) program allows researchers to expand their research goals by offering the assessment of environmental exposures in their previously collected biospecimens. Samples are analyzed in one of CHEAR's network of six laboratory hubs with the ability to assess a wide array of environmental chemicals. The ability to assess inter-study variability is important for researchers who want to combine datasets across studies and laboratories. OBJECTIVE: Herein we establish a process of evaluating inter-study variability for a given analytic method. METHODS: Common quality control (QC) pools at two concentration levels (A and B) in urine were created within CHEAR for insertion into each batch of samples tested at a rate of three samples of each pool per 100 study samples. We assessed these QC pool results for seven phthalates analyzed for five CHEAR studies by three different lab hubs utilizing multivariate control charts to identify out-of-control runs or sets of samples associated with a given QC sample. We then tested the conditions that would lead to an out-of-control run by simulating outliers in an otherwise "in-control" set of 12 trace elements in blood QC samples (NIST SRM 955c). RESULTS: When phthalates were assessed within study, we identified a single out-of-control run for two of the five studies. Combining QC results across lab hubs, all of the runs from these two studies were now in-control, while multiple runs from two other studies were pushed out-of-control. In our simulation study we found that 3-6 analytes with outlier values (5xSD) within a run would push that run out of control in 65-83% of simulations, respectively. SIGNIFICANCE: We show how acceptable bounds of variability can be established for a given analytic method by evaluating QC materials across studies using multivariate control charts.

4.
Environ Res ; 195: 110732, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33484721

RESUMO

BACKGROUND: Endometriosis is an estrogen-dependent disease. Endocrine disrupting chemicals (EDCs) and their mixtures may play an etiologic role. OBJECTIVES: We evaluated an adipose-to-serum ratio (ASR) of lipophilic EDCs and their mixtures associated with incident endometriosis. METHODS: We quantified 13 polychlorinated biphenyl (PCB) congeners, 6 polybrominated diphenyl ether (PBDE) congeners, and 11 organochlorine pesticides (OCPs) in serum and omental fat among women from the ENDO Study (2007-2009) aged 18-44 years diagnosed with (n=190) or without (n=283) surgically-visualized incident endometriosis. Odds ratios (OR) and 95% confidence intervals (CI) between ASR and endometriosis were estimated using logistic regression models adjusted for age (years), body mass index (kg/m2), serum cotinine (ng/ml), and breastfeeding conditional on parity. Bayesian hierarchical models (BHM) compared estimated associations for adipose and ASR to serum. Bayesian kernel machine regression (BKMR) estimated change in latent health and 95% posterior intervals (PI) between chemical mixtures and endometriosis. RESULTS: Select ASR for estrogenic PCBs and OCPs were associated with an increased odds of an endometriosis diagnosis, but not for anti-estrogenic PCBs or PBDEs. Across all chemicals, BHMs generated ORs that were on average 14% (95% PI: 6%, 22%) higher for adipose and 20% (95% PI: 12%, 29%) higher for ASR in comparison to serum. ORs from BHMs were greater for estrogenic PCBs and OCPs, with no differences for PBDEs. BKMR models comparing the 75th to 25th percentile were moderately associated with endometriosis for estrogenic PCBs [adipose 0.27 (95% PI: 0.18, 0.72) and ASR 0.37 (95% PI: 0.06, 0.80)] and OCPs [adipose 0.17 (95% PI: 0.21, 0.56) and ASR 0.26 (95% PI: 0.05, 0.57)], but not for antiestrogenic PCBs and PBDEs. DISCUSSION: ASR added little insight beyond adipose for lipophilic chemicals. BKMR results supported associations between ASR and adipose estrogenic PCB and OCP mixtures and incident endometriosis. These findings underscore the importance of choice of biospecimen and considering mixtures when assessing exposure-disease relationships.

5.
Environ Res ; 195: 110796, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33508256

RESUMO

Biomonitoring is a commonly used tool for exposure assessment of organic environmental chemicals with urine and blood samples being the most commonly used matrices. However, for children's studies, blood samples are often difficult to obtain. Dried blood spots (DBS) represent a potential matrix for blood collection in children that may be used for biomonitoring. DBS are typically collected at birth to screen for several congenital disorders and diseases; many of the states that are required to collect DBS archive these spots for years. If the archived DBS can be accessed by environmental health researchers, they potentially could be analyzed to retrospectively assess exposure in these children. Furthermore, DBS can be collected prospectively in the field from children ranging in age from newborn to school-aged with little concern from parents and minimal risk to the child. Here, we review studies that have evaluated the measurement of organic environmental toxicants in both archived and prospectively collected DBS, and where available, the validation procedures that have been performed to ensure these measurements are comparable to traditional biomonitoring measurements. Among studies thus far, the amount of validation has varied considerably with no studies systematically evaluating all parameters from field collection, shipping and storage contamination and stability to laboratory analysis feasibility. These validation studies are requisite to ensure reliability of the measurement and comparability to more traditional matrices. Thus, we offer some recommendations for validation studies and other considerations before DBS should be adopted as a routine matrix for biomonitoring.

6.
Obesity (Silver Spring) ; 29(2): 409-417, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33491307

RESUMO

OBJECTIVE: The purpose of this study was to investigate the associations of urinary phthalates and bisphenols at age 6 years old with body fat and cardiovascular risk factors at 6 and 10 years and with the change from 6 to 10 years. METHODS: Among 471 Dutch children, the phthalates and bisphenols urinary concentrations at 6 years and BMI, fat mass index, android fat mass, blood pressure, glucose, insulin, and lipids blood concentrations at 6 and 10 years were measured. RESULTS: An interquartile range increase in di-n-octyl phthalate (DNOP) metabolites concentrations at 6 years was associated with an increased risk of overweight at 6 and 10 years (odds ratio: 1.44; 95% CI: 1.11-1.87, and 1.43; 95% CI: 1.09-1.86, respectively). Also, higher DNOP metabolites concentrations were associated with higher fat mass index at 6 years, higher systolic blood pressure at 10 years, a decrease in high-density lipoprotein cholesterol, and an increase in triglycerides concentrations from 6 to 10 years (P < 0.05). Higher total bisphenols and bisphenol A concentrations were associated with a decrease in BMI from 6 to 10 years (P < 0.01). CONCLUSIONS: DNOP metabolites are associated with overweight and an adverse cardiovascular profile in childhood. Total bisphenols and bisphenol A are associated with a decrease in BMI from 6 to 10 years.

7.
Neurotoxicol Teratol ; 83: 106947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33412243

RESUMO

BACKGROUND: Prenatal exposure to environmental chemicals has been associated with Autism Spectrum Disorder (ASD) symptoms in some, but not all, studies, but most research has not accounted for other childhood behavior problems. OBJECTIVES: To evaluate the specific associations of prenatal phthalate exposures with ASD symptoms in children (ages 3-6) accounting for other behavior problems, and to assess sex differences in these associations. METHODS: We measured phthalate metabolites in prenatal urine samples. Mothers completed the Social Responsiveness Scale-2nd edition (SRS-2) to assess child ASD symptoms and the Child Behavior Checklist (CBCL) to assess general behavior problems. We assessed associations of the sum of di-(2-ethylhexyl) phthalate metabolites, monobutyl phthalate, mono-isobutyl phthalate, and monoethyl phthalate (mEP) with ASD symptoms, adjusting for other behavior problems, using linear regression models (n=77). RESULTS: Most associations were null, and the sample size limited power to detect associations, particularly in the stratified analyses. After adjusting for internalizing and externalizing problems from the CBCL, ASD symptoms increased for each doubling of prenatal mEP concentration among boys only. CONCLUSIONS: Further investigation of maternal prenatal urinary phthalate metabolite concentrations and ASD symptoms while adjusting for other behavioral problems is warranted.

9.
Sci Total Environ ; 769: 144577, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33482550

RESUMO

Widespread environmental contamination of per- and polyfluoroalkyl substances (PFAS) is well established. Nevertheless, few studies have reported on the aquatic toxicity of PFAS, especially in indicator species such as Daphnia. In this study, the toxicity of two major PFAS, namely perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS), was investigated on water flea (Daphnia carinata) using a battery of comprehensive toxicity tests, including a 48 h acute and a 21-day chronic assays. The survival, growth, and reproduction of D. carinata were monitored over a 21-day life cycle. PFOS exhibited higher toxicity than PFOA. The 48 h LC50 values (confidence interval) based on acute toxicity for PFOA and PFOS were 78.2 (54.9-105) mg L-1 and 8.8 (6.4-11.6) mg L-1, respectively. Chronic exposure to PFOS for 21 days displayed mortality and reproductive defects in D. carinata at a concentration as low as 0.001 mg L-1. Genotoxicity assessment using comet assay revealed that exposure for 96 h to PFOS at 1 and 10.0 mg L-1 significantly damaged the organism's genetic makeup. The results of this study have great implications for risk assessment of PFOS and PFOA in aquatic ecosystems, given the potential of PFOS to pose a risk to Daphnia even at lower concentrations (1 µg L-1).

10.
Artigo em Inglês | MEDLINE | ID: mdl-33473152

RESUMO

BACKGROUND: Women who work in agriculture may have greater risk of pesticide exposure than men who share this occupation. Despite an increase in the fraction of the agricultural workforce comprised by women, few studies have characterized pesticide exposure in the USA with a focus on among these workers. OBJECTIVE: This pilot study aimed to describe pesticide exposure in a cohort of Latina farmworkers in farming communities in southwestern Idaho. METHODS: We collected urine samples from 29 Latina farmworkers, which were analyzed for 11 pesticide biomarkers. We evaluated the effect of pesticide spray season on urinary biomarker levels, and explored the effect of self-reported status as a pesticide handler on measured exposures. RESULTS: No significant differences were found between biomarker levels in samples collected during the nonspray and spray seasons. We observed 11 extreme outlying values in samples collected during the pesticide spray season. The most extreme outlying values (MDA: 51.7 ng/mL; 3-PBA: 11.8 ng/mL; trans-DCCA: 23.4 ng/mL; and 2,4-D: 31.1 ng/mL) were all provided during the spray season by women who reported loading, mixing or applying pesticides. CONCLUSIONS: These results provide suggestive evidence that Latina farmworkers who handle pesticides during the spray season may be at an increased risk of exposure to organophosphate and pyrethroid insecticides, as well as the herbicide 2,4-D. We recommend that future research into pesticide exposures among farmworkers should include particular focus on this group.

11.
J Hazard Mater ; 401: 123892, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33113753

RESUMO

Poly- and perfluoroalkyl substances (PFASs) are synthetic chemicals, which are introduced to the environment through anthropogenic activities. Aqueous film forming foam used in firefighting, wastewater effluent, landfill leachate, and biosolids are major sources of PFAS input to soil and groundwater. Remediation of PFAS contaminated solid and aqueous media is challenging, which is attributed to the chemical and thermal stability of PFAS and the complexity of PFAS mixtures. In this review, remediation of PFAS contaminated soils through manipulation of their bioavailability and destruction is presented. While the mobilizing amendments (e.g., surfactants) enhance the mobility and bioavailability of PFAS, the immobilizing amendments (e.g., activated carbon) decrease their bioavailability and mobility. Mobilizing amendments can be applied to facilitate the removal of PFAS though soil washing, phytoremediation, and complete destruction through thermal and chemical redox reactions. Immobilizing amendments are likely to reduce the transfer of PFAS to food chain through plant and biota (e.g., earthworm) uptake, and leaching to potable water sources. Future studies should focus on quantifying the potential leaching of the mobilized PFAS in the absence of removal by plant and biota uptake or soil washing, and regular monitoring of the long-term stability of the immobilized PFAS.

12.
Sci Total Environ ; 750: 141507, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32841807

RESUMO

Studies on the occurrence of emerging pesticides in surface and drinking water in Vietnam are limited. In this study, lake water (n = 7), river water (n = 1), tap water (n = 46), and bottled water (n = 3) collected from Hanoi and other four provinces in northern Vietnam were analyzed for selected pesticides (including insecticides such as neonicotinoids, fipronil, and chlorpyrifos; fungicide carbendazim; herbicides such as atrazine, terbuthylazine, simazine, 2,4-dichlorophenoxyacetic acid, 2-methyl-4-chlorophenoxyacetic acid, and bentazon) and some of their degradates by liquid chromatography-tandem mass spectrometry. Carbendazim (median: 86.7 ng/L) and triazines (49.3 ng/L) were the major pesticides found in lake water samples, followed by neonicotinoids and their degradation products (15.1 ng/L), chlorpyrifos and its degradate (13.4 ng/L), fipronil and its degradates (3.76 ng/L), chlorophenoxy acid herbicides (2.10 ng/L), and bentazon (0.62 ng/L). Triazines (164 ng/L) were the major pesticides in river water. Higher concentrations (median: 39.3 ng/L; range: 1.20-127) of selected pesticides were found in tap water from Hanoi than those from four other provinces studied (5.49 ng/L; 4.73-66.8 ng/L). Bottled water samples collected from Hanoi contained lower concentrations of pesticide residues (median: 3.54 ng/L, range: 2.18-8.09) than those of tap water samples. The calculated risks from pesticide exposure through ingestion of tap water by the general populations were low. However, fipronil concentrations in lake water exceeded the benchmark value recommended for freshwater in the United States or the Netherlands. Degradation of acetamiprid into desmethyl-acetamiprid was found in lake water.


Assuntos
Clorpirifos , Água Potável , Herbicidas , Praguicidas , Poluentes Químicos da Água , Benzimidazóis , Benzotiadiazinas , Carbamatos , Água Potável/análise , Herbicidas/análise , Neonicotinoides , Países Baixos , Praguicidas/análise , Pirazóis , Vietnã , Poluentes Químicos da Água/análise
13.
Environ Pollut ; 267: 115427, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254620

RESUMO

Persistent organic pollutants (POPs) are believed to alter metabolic homeostasis during fetal development, leading to childhood obesity. However, limited studies have explored how fetal chemical exposures relate to birth and infant weight outcomes in low-income Hispanic families at the highest risk of obesity. Therefore, we sought to determine associations between neonatal POPs exposure measured in newborn dried blood spots (DBS) and prenatal diet quality, birth weight, and overweight status at 18 months old. We conducted a case-control study nested within the Starting Early Program randomized controlled trial comparing POPs concentrations in infants with healthy weight (n = 46) and overweight status (n = 52) at age 18 months. Three categories of POPs, organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) were measured in archived newborn DBS. We assessed correlations between prenatal diet quality and neonatal POPs concentrations. Multivariable regression analyses examined associations between POPs (dichotomized at the mean) and birth weight z-score and weight status at 18 months, controlling for confounders. Seven of eight chemicals had detectable levels in greater than 94% of the sample. Higher protein, sodium and refined grain intake during pregnancy were correlated with lower POPs in newborn DBS. We found that high concentrations of perfluorooctanesulfonate (unstandardized coefficient [B]: -0.62, 95% confidence interval [CI]: -0.96 to -0.29) and perfluorohexanesulfate (B: -0.65, 95% CI: -0.99 to -0.31) were related to lower birth weight z-scores compared to those with low concentrations. We did not find associations between PBDEs, OCPs, and the other PFASs with birth weight z-scores, or between any POPs and weight status at 18 months. In conclusion, two PFASs were associated with lower birth weight, an important indicator of child health and growth, although direct associations with infant overweight status were not found. Whether neonatal POPs exposures contribute to economic and ethnic disparities in early obesity remains unclear.

14.
Environ Res ; : 110445, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33186575

RESUMO

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with adverse health outcomes, especially when exposure occurs within sensitive time windows such as the pre- and post-natal periods and early childhood. However, few studies have focused on PFAS exposure distribution and predictors in pregnant women, especially among African American women. We quantified serum concentrations of the four most common PFAS collected in all 453 participants and an additional 10 PFAS in 356 participants who were pregnant African American women enrolled from 2014 to 2018 in Atlanta, Georgia, and investigated the sociodemographic predictors of exposure. Additional home environment and behavior predictors were also examined in 130 participants. Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in >95% of the samples with PFOS having the highest concentrations (geometric mean (GM) 2.03 ng/mL). N-Methyl perfluorooctane sulfonamido acetic acid (NMeFOSAA), perfluoropentanoic acid (PFPeA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were found in 40-50% of the samples, whereas the detection frequencies for the other six PFAS were below 15%. When compared to National Health and Nutrition Examination Survey (NHANES) participants matching sex, race, and age with this study, our results showed similar concentrations of most PFAS, but higher concentrations of PFHxS (GM 0.99 ng/mL in this study; 0.63 and 0.4 ng/mL in NHANES, 2014-2015 and 2016-2017 cycles). A decline in concentrations over the study period was found for most PFAS but not PFPeA. In adjusted models, education, sampling year, parity, BMI, tobacco and marijuana use, age of house, drinking water source, and cosmetic use were significantly associated with serum PFAS concentrations. Our study reports the first PFAS exposure data among pregnant African American women in the Atlanta area, Georgia. The identified predictors will facilitate the setting of research priorities and enable development of exposure mitigation strategies.

15.
Sci Total Environ ; : 143466, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33243495

RESUMO

Bisphenol A (BPA) is a well-known endocrine disruptor that has obesogenic properties. We have previously reported sex- and age-dependent changes in hepatic transcriptome and proteome of several lipid homeostasis-related genes in rat offspring prenatally exposed to BPA. To further understand the impacts of prenatal BPA exposure, we analyzed lipidomic profiles in the postnatal day (PND) 21 and 60 rats using a high-resolution QTOF mass spectrometer coupled with a HPLC system. We found that the total lipid content was significantly decreased in PND21 females prenatally exposed to 5000 µg/kg bw/day of BPA. Levels of total fatty acids, acylcarnitines, and monoacylglycerols significantly increased in both female and male BPA-exposed rats at PND21. An elevation in total cholesterol esters and reductions in triacylglycerols and monogalactosyl diacylglycerols were found only in PND21 females prenatally exposed to BPA. Interestingly, opposite responses were observed for phospholipids and sphingolipids between PND21 females and males following BPA exposure. The effects on the body weight and total lipid content were mitigated in the latter stage, although the alterations of lipid profiles continued until PND60. A Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) revealed a high correlation of the lipidome with our previously published transcriptome data. DIABLO also identified potential biomarkers of prenatal exposure to BPA; glycerol-3-phosphate dehydrogenase 1 (Gpd1) and glyceronephosphate O-acyltransferase (Gnpat), which are involved in the glycerophospholipid metabolism, in females and males, respectively. Collectively, we highlighted the sex- and age-dependent effects of prenatal BPA exposure on hepatic lipid homeostasis in rat offspring.

16.
PLoS Med ; 17(10): e1003384, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33052911

RESUMO

BACKGROUND: Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD. METHODS AND FINDINGS: Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) and white (58.3%), and participants had a median age of 11.0 years (interquartile range 7.6 to 14.6) at the baseline visit. In urine samples collected serially over an average of 3.0 years (standard deviation [SD] 1.6), concentrations of BPA, phthalic acid (PA), and phthalate metabolites were measured as well as biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and F2-isoprostane). Clinical renal function measures included estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Linear mixed models were fit to estimate the associations between urinary concentrations of 6 chemical exposure measures (i.e., BPA, PA, and 4 phthalate metabolite groups) and clinical renal outcomes and urinary concentrations of KIM-1, NGAL, 8-OHdG, and F2-isoprostane controlling for sex, age, race/ethnicity, glomerular status, birth weight, premature birth, angiotensin-converting enzyme inhibitor use, angiotensin receptor blocker use, BMI z-score for age and sex, and urinary creatinine. Urinary concentrations of BPA, PA, and phthalate metabolites were positively associated with urinary KIM-1, NGAL, 8-OHdG, and F2-isoprostane levels over time. For example, a 1-SD increase in ∑di-n-octyl phthalate metabolites was associated with increases in NGAL (ß = 0.13 [95% CI: 0.05, 0.21], p = 0.001), KIM-1 (ß = 0.30 [95% CI: 0.21, 0.40], p < 0.001), 8-OHdG (ß = 0.10 [95% CI: 0.06, 0.13], p < 0.001), and F2-isoprostane (ß = 0.13 [95% CI: 0.01, 0.25], p = 0.04) over time. BPA and phthalate metabolites were not associated with eGFR, proteinuria, or blood pressure, but PA was associated with lower eGFR over time. For a 1-SD increase in ln-transformed PA, there was an average decrease in eGFR of 0.38 ml/min/1.73 m2 (95% CI: -0.75, -0.01; p = 0.04). Limitations of this study included utilization of spot urine samples for exposure assessment of non-persistent compounds and lack of specific information on potential sources of exposure. CONCLUSIONS: Although BPA and phthalate metabolites were not associated with clinical renal endpoints such as eGFR or proteinuria, there was a consistent pattern of increased tubular injury and oxidative stress over time, which have been shown to affect renal function in the long term. This raises concerns about the potential for clinically significant changes in renal function in relation to exposure to common environmental toxicants at current levels.

17.
Environ Toxicol Chem ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074584

RESUMO

Per- and polyfluoroalkyl substances (PFAS) have emerged as contaminants of global concern. Among several PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent and bioaccumulative compounds. We investigated the cyto-genotoxic potential of PFOS to Allium cepa root meristem cells. The A. cepa root tips were exposed to 6 different concentrations (1-100 mg L-1 ) of PFOS for 48 h. Reduction in mitotic index and chromosomal aberrations was measured as genotoxic endpoints in meristematic root cells. Exposure to PFOS significantly affected cell division by reducing the miotic index at higher concentrations (>10 mg L-1 ). The median effect concentration of PFOS to elicit cytotoxicity based on the mitotic index was 43.2 mg L-1 . Exposure to PFOS significantly increased chromosomal aberrations at concentrations >25 mg L-1 . The common aberrations were micronuclei, vagrant cells, and multipolar anaphase. The alkaline comet assay revealed a genotoxic potential of PFOS with increased tail DNA percentage at concentrations >25 mg L-1 . To our knowledge, this is the first study to report the cyto-genotoxic potential of PFOS in higher plants. Environ Toxicol Chem 2020;00:1-7. © 2020 SETAC.

18.
Environ Int ; 146: 106160, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068853

RESUMO

BACKGROUND: Most pregnant women are exposed to bisphenols, a group of chemicals that can interfere with various components of the thyroid system. OBJECTIVES: To investigate the association of maternal urinary bisphenol concentrations during pregnancy with maternal, newborn and early childhood thyroid function. METHODS: This study was embedded in Generation R, a prospective, population-based birth cohort (Rotterdam, the Netherlands). Maternal urine samples were analyzed for eight bisphenols at early (<18), mid (18-25) and late (>25 weeks) pregnancy. Maternal serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and total thyroxine (TT4) were measured in early pregnancy and child TSH and FT4 were measured in cord blood and childhood. RESULTS: The final study population comprised 1,267 mothers, 853 newborns and 882 children. Of the eight bisphenols measured, only bisphenol A (BPA) was detected in >50% of samples at all three time-points and bisphenol S (BPS) at the first time-point. There was no association of BPA or the bisphenol molar sum with maternal thyroid function. Higher BPS concentrations were associated with a higher maternal TT4 (ß [95% CI] per 1 (natural-log) unit increase: 0.97 [0.03 to 1.91]) but there was no association with TSH or FT4. Furthermore, higher BPS was associated with an attenuation of the association between maternal FT4 and TSH (Pinteraction = 0.001). There was no association of early or mid-pregnancy BPA or early pregnancy BPS with cord blood or childhood TSH and FT4. A higher late pregnancy maternal BPA exposure was associated with a higher TSH in female newborns (Pinteraction = 0.06) and a higher FT4 during childhood in males (Pinteraction = 0.08). DISCUSSION: Our findings show that exposure to bisphenols may interfere with the thyroid system during pregnancy. Furthermore, the potential developmental toxicity of exposure to bisphenols during pregnancy could affect the thyroid system in the offspring in a sex-specific manner.

19.
Environ Int ; : 106151, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33092866

RESUMO

Per- and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), and organophosphate esters (OPEs) are found in building materials and associated with thyroid disease, infertility, and impaired development. This study's objectives were to (1) compare levels of PFAS, PBDEs, and OPEs in dust from spaces with conventional versus "healthier" furniture and carpet, and (2) identify other product sources of flame retardants in situ. We measured 15 PFAS, 8 PBDEs, and 19 OPEs in dust from offices, common areas, and classrooms having undergone either no intervention (conventional rooms in older buildings meeting strict fire codes; n = 12), full "healthier" materials interventions (rooms with "healthier" materials in buildings constructed more recently or gut-renovated; n = 7), or partial interventions (other rooms with at least "healthier" foam furniture but more potential building contamination; n = 28). We also scanned all materials for bromine and phosphorus as surrogates of PBDEs and OPEs respectively, using x-ray fluorescence. In multilevel regression models, rooms with full "healthier" materials interventions had 78% lower dust levels of PFAS than rooms with no intervention (p < 0.01). Rooms with full "healthier" interventions also had 65% lower OPE levels in dust than rooms with no intervention (p < 0.01) and 45% lower PBDEs than rooms with only partial interventions (p < 0.10), adjusted for covariates related to insulation, electronics, and furniture. Bromine loadings from electronics in rooms were associated with PBDE concentrations in dust (p < 0.05), and the presence of exposed insulation was associated with OPE dust concentrations (p < 0.001). Full "healthier" materials renovations successfully reduced chemical classes in dust. Future interventions should address electronics, insulation, and building cross-contamination.

20.
Environ Int ; 144: 106063, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889482

RESUMO

BACKGROUND AND AIMS: Fetal exposure to endocrine disruptors such as phthalates and bisphenols may lead to developmental metabolic adaptations. We examined associations of maternal phthalate and bisphenol urine concentrations during pregnancy with lipids, insulin, and glucose concentrations at school age. METHODS: In a population-based, prospective cohort study among 757 mother-child pairs, we measured maternal phthalate and bisphenol urine concentrations in first, second and third trimester of pregnancy. We measured non-fasting lipids, glucose and insulin blood concentrations of their children at a mean age of 9.7 (standard deviation 0.2) years. Analyses were performed for boys and girls separately. RESULTS: An interquartile range (IQR) higher natural log transformed third trimester maternal urine phthalic acid concentration was associated with a 0.20 (95% confidence interval (CI) 0.07-0.34) standard deviation score (SDS) higher triglycerides concentration among boys. Maternal bisphenol urine concentrations were not associated with non-fasting lipid concentrations during childhood. An IQR higher natural log transformed second trimester maternal high molecular weight phthalates (HMWP) and di-2-ethylhexylphthalate (DEHP) urine concentration were associated with a 0.19 (95% CI 0.31-0.07) respectively 0.18 (95% CI 0.31-0.06) SDS lower glucose concentration among boys. An IQR higher natural log transformed third trimester maternal bisphenol F urine concentration was associated with a 0.22 (95% CI 0.35-0.09) SDS lower non-fasting insulin concentration among boys. CONCLUSIONS: Our results suggest potential persisting sex specific effects of fetal exposure to phthalates and bisphenols on childhood lipid concentrations and glucose metabolism. Future studies are needed for replication and exploring underlying mechanisms.

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