RESUMO
Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T1-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (ß per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (ß for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.
Assuntos
Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Feminino , Humanos , Criança , Gravidez , Adolescente , Estudos Longitudinais , Plastificantes , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/urina , Substância Cinzenta , Exposição MaternaRESUMO
Environmental chemical exposures have been associated with cancer, diabetes, hormonal and immunological disorders, and cardiovascular diseases. Some direct effects of chemical exposure that are precursors to adverse health outcomes, including oxidative stress, nitrative stress, hormonal imbalance, neutrophilia, and eosinophilia, can be assessed through the analysis of biomarkers in urine. In this study, we describe a novel methodology for the determination of 19 biomarkers of health effects: malondialdehyde (MDA), 8-isoprostaglandin-F2α (8-PGF2α), 11-ß-prostaglandin-F2α (11-PGF2α), 15-prostaglandin-F2α (15-PGF2α), 8-iso-15-prostaglandin-F2α (8,15-PGF2α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-HdG), 8-hydroxyguanine (8-HG), dityrosine (diY), allantoin (Alla), and two metabolic products of 4-hydroxynonenal (HNE), namely 4-hydroxy-2-nonenal glutathione (HNE-GSH) and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) (in total, 12 oxidative stress biomarkers, OSBs); 8-nitroguanosine (8-NdG), 8-nitroguanine (8-NG), and 3-nitrotyrosine (NY) (3 nitrative stress biomarkers, NSBs); chlorotyrosine (CY) and bromotyrosine (BY) (2 inflammatory biomarkers); and the advanced glycation end-products (AGEs) Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL) (2 metabolic disorder biomarkers). Since these biomarkers are trigged by a variety of environmental insults and produced by different biomolecular pathways, their selective and sensitive determination in urine would help broadly elucidate the pathogenesis of diseases mediated by environmental factors.
Assuntos
Doenças Metabólicas , Espectrometria de Massas em Tandem , Biomarcadores/urina , Cromatografia Líquida , Humanos , Inflamação , Estresse OxidativoRESUMO
BACKGROUND: Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods. METHODS: In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth. RESULTS: An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth. CONCLUSIONS: Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.
Assuntos
Compostos Benzidrílicos/urina , Disruptores Endócrinos/urina , Fenóis/urina , Sulfonas/urina , Adulto , Peso ao Nascer , Feminino , Fêmur/anatomia & histologia , Fêmur/crescimento & desenvolvimento , Desenvolvimento Fetal , Cabeça/anatomia & histologia , Cabeça/crescimento & desenvolvimento , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVES: Fetal exposure to phthalates and bisphenols might have long-lasting effects on growth and fat development. Not much is known about the effects on general and organ fat development in childhood. We assessed the associations of fetal exposure to phthalates and bisphenols with general and organ fat measures in school-aged children. METHODS: In a population-based, prospective cohort study among 1128 mother-child pairs, we measured maternal urinary phthalate metabolites and bisphenol concentrations in first, second, and third trimester. Offspring body mass index, fat mass index by dual-energy X-ray absorptiometry, and visceral and pericardial fat indices and liver fat fraction were measured by magnetic resonance imaging at 10 years. RESULTS: After adjustment for confounders and correction for multiple testing, an interquartile range increase in first trimester phthalic acid concentrations remained associated with a 0.14 (95% confidence interval: 0.05, 0.22) standard deviation score increase in pericardial fat index. We also observed tendencies for associations of higher maternal low molecular weight phthalate urinary concentrations in second trimester with childhood pericardial fat index, but these were not significant after adjustment for multiple testing. High molecular weight phthalate, di-2-ethylhexyl phthalate, and di-n-octyl phthalate concentrations were not associated with childhood outcomes. Maternal urinary bisphenol concentrations were not associated with childhood adiposity. CONCLUSIONS: Maternal first trimester phthalic acid concentrations are associated with increased childhood pericardial fat index at 10 years of age, whereas maternal bisphenol concentrations are not associated with childhood adiposity. We did not find significant sex-specific effects. These findings should be considered as hypothesis generating and need further replication and identification of underlying mechanisms.
Assuntos
Adiposidade , Compostos Benzidrílicos/urina , Índice de Massa Corporal , Exposição Materna/efeitos adversos , Fenóis/urina , Ácidos Ftálicos/urina , Adulto , Criança , Feminino , Humanos , Masculino , Países Baixos , Obesidade Infantil/epidemiologia , Pericárdio , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Exposure to bisphenols and phthalates might influence bone health. We hypothesized that exposure to bisphenols and phthalates during fetal life has persistent effects on bone development. OBJECTIVES: To analyze the associations of fetal exposure to bisphenols and phthalates with bone health in school-aged children. METHODS: Among 1,362 mother-child pairs participating in a population-based cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at first, second and third trimester with high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Total body bone mineral density (BMD) and bone area (BA) were measured using dual-energy X-ray absorptiometry (DXA) at 6 and 10 years, and were both used to calculate bone mineral content (BMC) and area-adjusted BMC (aBMC, a measure of volumetric BMD). RESULTS: Maternal bisphenol concentrations were not associated with childhood bone measures at 6 years. After adjustment for covariates and multiple testing correction, an interquartile range increase in maternal first trimester bisphenol S (BPS) concentrations was associated with lower BMD and aBMC at 10 years (-6.08 (95% confidence interval (CI), -9.97 to -2.19) mg/cm2 and -0.12 (95% CI, -0.20 to -0.04) g). Maternal third trimester low molecular weight (LMW) phthalate concentrations were associated with higher aBMC at 6 years whereas, maternal third trimester di-n-octylphthalate (DNOP) concentrations were associated with lower aBMC at 10 years. However, these associations did not remain statistically significant after multiple testing correction. DISCUSSION: Maternal first trimester BPS concentrations are associated with lower BMD and aBMC in school-aged children. These findings should be considered as hypothesis generating and need further replication and exploration of potential underlying mechanisms.
Assuntos
Densidade Óssea , Ácidos Ftálicos , Criança , Estudos de Coortes , Feminino , Humanos , Ácidos Ftálicos/toxicidade , Gravidez , Estudos ProspectivosRESUMO
The discovery of new diagnostic tools for the early detection of diseases with poor prognosis such as pancreatic adenocarcinoma (PAC) is of high importance. The results from a control-case study (20 PAC patients, 19 healthy controls) for the search of new biomarkers of pancreatic cancer based in differences in the serum volatolome are presented in this work. Volatolomics were performed following a non-targeted HS-SPME-GC/MS approach, and a total of 433 volatile organic compounds (VOCs) was detected in the human serum samples. Of these, 125 VOC indexes showed a significant variation when controls and patients were compared (p-value < 0.05). Bonferroni corrected p-values < 0.05 were found for 40 features. PCA analysis showed the control-PAC discrimination capability of VOCs in serum, and PLS-DA was performed to select the best candidate biomarkers for the diagnosis of PAC. For the 40 selected VOCs, calculated areas under the curve (AUC) ranged from 0.98 to 0.85, and 11 of them were successfully validated using an independent set of samples (5 PAC patients, 5 healthy controls). Four of the proposed PAC biomarkers were identified as toluene, 2-ethyl-1-hexanol, pentylbenzene, and butoxymethylbenzene. Combinations of the identified PAC biomarkers were tested and showed AUC > 0.90, with the more promising candidate being butoxymethylbenzene (AUC = 0.98).
Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Compostos Orgânicos Voláteis , Humanos , Adenocarcinoma/diagnóstico , Biomarcadores , Neoplasias Pancreáticas/diagnóstico , Estudos de Caso Único como Assunto , Compostos Orgânicos Voláteis/análise , Estudos de Casos e ControlesRESUMO
This study presents a focused ultrasound solid-liquid extraction (FUSLE) and gas chromatography tandem mass spectrometry method for the determination of brominated diphenyl ethers (BDEs), from mono- to hexa-congeners, in indoor dust. This approach provided a simple, fast, and economical method. After the solvent extraction selection, the FUSLE conditions were studied using a central composite design. Finally, the number of extraction cycles was studied. The selected conditions were 8 mL of 3:1 n-hexane-acetone mixture as extraction solvent, at a power of 65% for 20 s. The proposed method allowed accurate determination of BDEs, with recovery values around 100% and detection limits between 0.05 and 0.8 ng g(-1). It also has advantages over other existing methods in terms of simplicity, analysis time, and solvent consumption. The analysis of several indoor dust samples showed high concentration values of BDEs 47, 99, 100, 153, and 154 in some of the samples, moreover, BDEs 47 and 99 were found in all samples.
RESUMO
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants. Urinary concentrations of mono-hydroxylated metabolites of PAHs (OH-PAHs) have been used as biomarkers of these chemicals' exposure in humans. Little is known, however, with regard to intra- and inter-individual variability in OH-PAH concentrations and their association with oxidative stress. We conducted a longitudinal study of measurement of urinary concentrations of 15 OH-PAHs and 7 oxidative stress biomarkers (OSBs) of DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)], lipid [malondialdehyde (MDA) and F2-isoprostanes (PGF2α)] and protein [o,o'-dityrosine (diY)] peroxidation in 19 individuals for 44 consecutive days. Metabolites of naphthalene (OHNap), fluorene (OHFlu), phenanthrene (OHPhe), and pyrene (OHPyr) were found in >70% of 515 urine samples analyzed, at sum concentrations (∑OH-PAH) measured in the range of 0.46-60 ng/mL. After adjusting for creatinine, OHNap and ∑OH-PAH concentrations exhibited moderate predictability, with intra-class correlation coefficients (ICCs) ranging from 0.359 to 0.760. However, ICC values were low (0.001-0.494) for OHFlu, OHPhe, and OHPyr, which suggested poor predictability for these PAH metabolites. Linear mixed-effects analysis revealed that an unit increase in ∑OH-PAH concentration corresponded to 4.5%, 5.3%, 20%, and 21% increase in respective urinary 8-OHdG, MDA, PGF2α, and diY concentrations, suggesting an association with oxidative damage to DNA, lipids, and proteins. The daily intakes of PAHs, calculated from urinary concentrations of OH-PAHs, were 10- to 100-fold below the current reference doses. This study provides valuable information to design sampling strategies in biomonitoring studies and in assigning exposure classifications of PAHs in epidemiologic studies.
Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Biomarcadores , Exposição Ambiental/análise , F2-Isoprostanos , Humanos , Estudos Longitudinais , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidadeRESUMO
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.
Assuntos
Tecido Adiposo/química , Compostos Benzidrílicos/urina , Índice de Massa Corporal , Fenóis/urina , Ácidos Ftálicos/urina , Glicemia/análise , Pressão Sanguínea/fisiologia , Criança , Fatores de Risco de Doenças Cardíacas , Humanos , Países Baixos , Sobrepeso/epidemiologiaRESUMO
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.
Assuntos
Ácidos Ftálicos , Nascimento Prematuro , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Humanos , Recém-Nascido , Exposição Materna , Países Baixos , Gravidez , Estudos ProspectivosRESUMO
Human exposure to neonicotinoid insecticides (hereafter "neonics") is a concern. Spot urine samples have been widely used in the assessment of exposure to neonics. Urinary concentrations, however, can vary greatly over time due to variable exposure, potentially leading to exposure misclassification. In this study, within- and between-individual variability of urinary concentrations of 13 neonics and their metabolites collected consecutively for up to 44 days from 19 individuals were examined. We also measured seven oxidative stress biomarkers (OSBs) in repeated urine samples to elucidate their relationship with neonic exposure by mixed regression models. Intraclass correlation coefficients (ICCs, a ratio of between-individual variance to total variance) were used to assess the reproducibility of neonic/metabolite concentrations. Sensitivity and specificity were used to evaluate how well spot urine samples determined an individual's average exposure over 44 days. A fair to good reproducibility was observed for N-desmethyl-acetamiprid (ICC = 0.42), whereas thiamethoxam, imidacloprid, clothianidin, imidaclothiz, 6-chloronicotinic acid, and sulfoxaflor showed poor reproducibility (ICC = 0.02-0.37). Use of single-spot urine samples to classify high (top 33%) exposure showed higher specificities (0.68-0.92) than sensitivities (0.32-0.88). The minimum number of specimens (k) required to estimate participant-specific mean for neonic exposures within 20% of the "true" values ranged from 16 to 172. Significant positive correlations were found between some of neonic and OSB concentrations. The high variability found in the urinary concentrations of most neonics/metabolites suggests that a single measurement can result in exposure misclassification.
Assuntos
Estresse Oxidativo , Biomarcadores , Exposição Ambiental , Humanos , Inseticidas , Neonicotinoides , Reprodutibilidade dos TestesRESUMO
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.
Assuntos
Ácidos Ftálicos , Criança , Estudos de Coortes , Feminino , Glucose , Humanos , Lactente , Lipídeos , Masculino , Exposição Materna , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVES: Fetal exposure to phthalates and bisphenols may lead to vascular developmental adaptations, which program later cardiovascular disease. We examined the associations of fetal exposure to phthalates and bisphenols with childhood blood pressure. METHODS: In a population-based, prospective cohort study among 1,064 mother-child pairs, we measured maternal urine phthalate and bisphenol concentrations in first, second and third trimester of pregnancy. We measured childhood blood pressure at the mean age of 9.7 years (standard deviation 0.2 years) old. Analyses were performed for the total group, and for boys and girls separately. RESULTS: Maternal urine phthalate concentrations were not associated with childhood blood pressure among boys. Higher third trimester maternal urine concentrations of high molecular weight phthalates (HMWP), di-2-ehtylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) were associated with lower systolic and diastolic blood pressure among girls (p-values < 0.01). Also, higher second trimester maternal urine total bisphenol and bisphenol A concentrations were associated with higher systolic blood pressure among boys (p values < 0.01), but tended to be associated with a lower diastolic blood pressure among girls. CONCLUSIONS: Our results suggest sex-dependent associations of maternal urine phthalate and bisphenol concentrations during pregnancy with childhood blood pressure. Further studies are needed to explore the underlying mechanisms and long term consequences.
Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Compostos Benzidrílicos , Pressão Sanguínea , Criança , Feminino , Humanos , Masculino , Exposição Materna , Fenóis , Gravidez , Estudos ProspectivosRESUMO
Oxidative stress in humans is affected by the health and nutritional status as well as exposure to external environmental factors. To evaluate the effects of external factors, an assessment of baseline levels as well as diurnal variations in oxidative stress status of healthy individuals is needed. In this study, we examined intra- and inter-individual variability of oxidative stress biomarkers (OSBs) of lipids (malondialdehyde [MDA] and four F2-isoprostane isomers, namely, 8-isoprostaglandinF2α [8-PGF2α], 11ß-prostaglandinF2α [11-PGF2α], 15(R)-prostaglandinF2α [15-PGF2α], and 8-iso,15(R)-prostaglandinF2α [8,15-PGF2α]); proteins (o,o'-dityrosine [diY]); and DNA (8-hydroxy-2'-deoxyguanosine [8-OHdG]) in urine from healthy individuals. The significance of creatinine correction, which is typically used to account for urinary dilution, on OSB concentrations was evaluated. Analysis of 515 urine samples, collected longitudinally from 19 healthy individuals daily for over a month, showed inter-individual coefficient of variation (CV) in concentrations from 112% for MDA to 272% for 15-PGF2α. Intra-individual CV in concentrations ranged from 29% for 8-OHdG to 149% for 15-PGF2α. MDA was the most abundant OSB found in urine. The intra- and inter-individual variability in F2-isoprostane concentrations were higher than the values calculated for diY, 8-OHdG, and MDA. All seven OSB concentrations were significantly correlated with each other and with creatinine. Creatinine normalization of OSB concentrations improved predictability in OSB concentrations over time. Our results suggest that 8-OHdG, showing the highest ICC (0.96), yielded more reproducible measurements with a low CV, and is the most suitable biomarker of OSB in spot urine samples. The measured concentrations and diurnal variability in urinary OSB levels in healthy individuals reported in this study are useful as a benchmark for future toxicological and epidemiological studies.
Assuntos
Biomarcadores/urina , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Creatinina/urina , DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Voluntários Saudáveis , Humanos , Lipídeos , Masculino , Malondialdeído/urina , Estado Nutricional , Oxirredução , Valores de Referência , Tirosina/análogos & derivados , Tirosina/urinaRESUMO
Exposure of humans to pesticides is widespread. Measurement of urinary levels of pesticides and their metabolites is often used in the assessment of body burdens and exposure doses to these chemicals. An understanding of temporal variability in urinary levels of pesticides within individuals is critical for accurate exposure assessment. We examined within- and between-individual variability in concentrations of nine organophosphate and pyrethroid insecticides as well as two phenoxy herbicides in urine collected consecutively for up to 44â¯days from 19 individuals. Seven oxidative stress biomarkers also were measured in urine samples to elucidate their relationship with pesticide exposure. Intraclass correlation coefficients (ICCs) were calculated to assess reproducibility in urinary pesticide concentrations from repeated measures. Sensitivity and specificity analyses were performed to evaluate the suitability of spot urine to characterize average exposures. Data analysis was further limited to seven pesticides and their metabolites, which had a detection frequency of >60%. Poor reproducibility was found for the seven pesticides and their metabolites in both spot (ICCs ≤0.24) and first-morning-void (FMV) samples (ICCs <0.38) collected during the 44-day study period. Use of single-spot or FMV sample to classify high (top 33%) concentrations showed high specificities (0.73-0.85) but low sensitivities (0.45-0.70). The minimum number of samples (k) required per individual to estimate participant-specific mean value for pesticides (within 20% of the "true" values) were 28-140 and 18-119 for spot and FMV samples, respectively. Repeated longitudinal measurements of these pesticides and their metabolites in urine showed considerable within-individual variability in both spot and FMV samples. Urinary concentrations of seven pesticides and their metabolites were significantly correlated with oxidative damage to lipids, proteins, and DNA.
Assuntos
Biomarcadores/urina , Exposição Ambiental , Estresse Oxidativo , Praguicidas/urina , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Humanos , Organofosfatos/urina , Piretrinas/urina , Reprodutibilidade dos TestesRESUMO
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer products, which contributes to widespread exposure of humans. OPE diester metabolites in urine have been used as biomarkers of human exposure to these chemicals. Little is known, however, about occurrence and temporal variability in urinary concentrations of OPE metabolites in humans. In this study, 11 OPE metabolites were measured in 213 urine samples collected from 19 volunteers from Albany, New York, United States, at 3-day intervals for five weeks to investigate temporal variability in urinary concentrations. Diphenyl phosphate (DPHP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the major OPE metabolites, detected in all urine samples at specific gravity (SG)-adjusted concentrations (geometric mean, GM) of 1060 and 414â¯pg/mL and creatinine (Cr)-adjusted concentration (GM) of 404 and 156â¯ng/g, respectively. Inter-day variability in urinary OPE metabolite concentrations in 19 individuals was evaluated by intraclass correlation coefficients (ICCs). The inter-day variability in Cr-adjusted OPE metabolite concentrations (ICC: 0.31-0.67) was lower than those of SG-adjusted (ICC: 0.19-0.71) and unadjusted urinary concentrations (ICC: 0.24-0.74). BDCIPP (ICC: 0.68) and bis(2-chloroethyl) phosphate (BCEP) (ICC: 0.67) concentrations showed a moderate-to-high reliability over the sampling period, whereas the other nine OPE metabolites exhibited a moderate reliability (ICC: 0.31-0.55). Urine samples were further stratified by gender, age, ethnicity, and body mass index (BMI). The concentrations of BDCIPP and DPHP were significantly lower in males with normal BMI (BMI: 18.5-25â¯kg/m2) than in females and other BMI categories (pâ¯<â¯0.01). Relatively high ICCs, indicating low inter-day variability, were observed for males (ICC: 0.35-0.71) of 30-40â¯years of age (ICC: 0.34-0.87) with normal BMI (ICC: 0.28-0.64). The daily exposure doses to OPEs were estimated from urinary concentrations of corresponding OPE metabolites. The estimated doses of triphenyl phosphate (TPHP) and triethyl phosphate (TEP), based on median urinary concentrations of their metabolites, were 19.4 and 24.0â¯ng/kgâ¯bw/day, and the exposure dose to ∑OPEs was estimated at 65.3â¯ng/kgâ¯bw/day. Overall, our results indicate a high ICC for Cr-adjusted urinary concentrations of 11 OPE metabolites in urine.
Assuntos
Exposição Ambiental , Ésteres/urina , Organofosfatos/urina , Adulto , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Masculino , New York/epidemiologiaRESUMO
Human exposure to phthalates is ubiquitous and has received considerable attention due to their association with adverse health outcomes, including type 2 diabetes mellitus (T2DM). Nevertheless, earlier studies that link phthalate exposure to T2DM yielded ambiguous results. Furthermore, studies that associate phthalate exposure with oxidative stress and then with T2DM are scant. In this diabetic case-control study, urine samples collected from 101 individuals aged 28-68â¯years from Jeddah, Saudi Arabia, were analyzed to determine 20 phthalate metabolites (PhMs) and seven oxidative stress biomarkers (OSBs). Unconditional logistic regression was used to estimate odds ratios for the association between diabetes and urinary PhMs and OSBs in participants, stratified by age, gender, nationality, smoking status, occupation, and urinary creatinine. Twelve PhMs and five OSBs were found at detection rates above 50%, with geometric mean concentrations of 0.61-100 and 0.35-10.7â¯ng/mL (1.04-171 and 0.61-18.6⯵g/g creatinine), respectively. Almost all exposures were significantly higher in diabetic cases than in controls. The 12 PhMs were positively associated with higher urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-PGF2α). Individuals in the 3rd and/or 4th quartile(s) for urinary concentrations of PhMs and OSBs showed 3.7- and 7.3-fold increase, respectively, in the odds of having diabetes compared with those in the 1st quartile. The rank order of association of PhMs/OSBs with diabetes followed the order of: mEPâ¯≈â¯mBPâ¯>â¯mEHPâ¯>â¯mCPPâ¯>â¯mECPPâ¯≈â¯mEOHPâ¯≈â¯mEHHPâ¯≈â¯mIBPâ¯≈â¯mMPâ¯>â¯mCMHPâ¯≈â¯mBzP and 8-OHdGâ¯>â¯8-PGF2αâ¯≈â¯15-PGF2α. The relationship between phthalate exposure and risk of developing T2DM was mediated in part by phthalate-induced oxidative stress, especially 8-OHdG. Our study suggests that human exposure to phthalates is associated with increased oxidative stress which mediates the development of T2DM.
Assuntos
Diabetes Mellitus Tipo 2/urina , Poluentes Ambientais/urina , Estresse Oxidativo , Ácidos Ftálicos/urina , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Biomarcadores/urina , Estudos de Casos e Controles , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Dinoprosta/análogos & derivados , Dinoprosta/urina , Monitoramento Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Arábia Saudita/epidemiologiaRESUMO
In this work, a method based on selective pressurised liquid extraction followed by microextraction by packed sorbents (MEPS) for the determination of brominated diphenyl ethers (BDEs) in sewage sludge is presented. The factors affecting the MEPS procedure were optimised. Acetone:water (25:75) sPLE extracts were drawn-ejected 10 times through C18 cartridges at 5 µL s(-1). The cartridge was dried five times with 250 µL of air and the BDEs were eluted at 25 µL s(-1) with 100 µL of n-hexane that were directly injected at 13 µL s(-1) in the GC-MSMS system. Under these conditions, there were no carry-over effects. The method was characterised in terms of limits of detection, repeatability, intermediate precision and accuracy. The use of MEPS for the determination of BDEs in sewage sludge means an improvement of the limits of detection due to the preconcentration and clean-up performed before the injection of the whole elute in the PTV injector. The GC-MSMS LODs (25 pg mL(-1)) were improved with MEPS to less than 3 pg mL(-1). RSD less than 7% and recovery values from 92% to 102% were shown. Finally, the method was applied to the sPLE extract analyses of sewage sludge from several wastewater treatment plants in La Rioja. To our knowledge, this is the first time that the MEPS technique has been applied to the analysis of BDEs, and the first time that it has been used for the analysis of extracts from a solid sample.