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1.
Med Sci Sports Exerc ; 53(1): 236-243, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32694367

RESUMO

PURPOSE: Autologous blood transfusion is performance enhancing and prohibited in sport but remains difficult to detect. This study explored the hypothesis that an untargeted urine metabolomics analysis can reveal one or more novel metabolites with high sensitivity and specificity for detection of autologous blood transfusion. METHODS: In a randomized, double-blinded, placebo-controlled, crossover design, exercise-trained men (n = 12) donated 900 mL blood or were sham phlebotomized. After 4 wk, red blood cells or saline were reinfused. Urine samples were collected before phlebotomy and 2 h and 1, 2, 3, 5, and 10 d after reinfusion and analyzed by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. Models of unique metabolites reflecting autologous blood transfusion were attained by partial least-squares discriminant analysis. RESULTS: The strongest model was obtained 2 h after reinfusion with a misclassification error of 6.3% and 98.8% specificity. However, combining only a few of the strongest metabolites selected by this model provided a sensitivity of 100% at days 1 and 2 and 66% at day 3 with 100% specificity. Metabolite identification revealed the presence of secondary di-2-ethylhexyl phtalate metabolites and putatively identified the presence of (iso)caproic acid glucuronide as the strongest candidate biomarker. CONCLUSIONS: Untargeted urine metabolomics revealed several plasticizers as the strongest metabolic pattern for detection of autologous blood transfusion for up to 3 d. Importantly, no other metabolites in urine seem of value for antidoping purposes.


Assuntos
Transfusão de Sangue Autóloga , Doping nos Esportes/métodos , Transfusão de Eritrócitos , Urinálise , Adulto , Biomarcadores/urina , Caproatos/urina , Estudos Cross-Over , Dietilexilftalato/urina , Método Duplo-Cego , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Metabolômica , Adulto Jovem
2.
Food Chem Toxicol ; 143: 111510, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32615240

RESUMO

Phthalates are widely used as plasticisers in flexible plastics and containers for food and personal care products (PCPs) and contaminates foods and PCPs. A human biomonitoring (BM) study was performed to study exposure of chemicals from foods and PCPs. For two 24-h periods, adult volunteers (n = 144) in Norway kept diaries on food eaten and usage of PCPs, and collected 24-h urine. Aggregated exposure to di(2-ethylhexyl) phthalate (DEHP) from dietary and PCPs was estimated by Monte-Carlo simulation using Oracle Crystal Ball©. Simulated urinary concentrations using physiologically based pharmacokinetic (PBPK) models were compared with measured urinary metabolites of DEHP, mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono-2-ethyl 5-carboxypentyl phthalate (MECCP). DEHP exposure from food are approximately 10 times higher than exposure than from PCPs. The main contributors to dietary exposure are dairy, grain, fruits and vegetables, meat and fish. Body lotion contribute most to the exposure of DEHP from PCPs. Forward-dosimetry gives good convergence with 24-h urinary concentrations of simulated and measured BM data. The measured concentration of the MECCP metabolite correlated well with simulated high exposure, while the measured concentrations of MEHP, MEHHP and MEOHP partly overlapped with both simulated low, medium and high metabolite exposure.


Assuntos
Monitoramento Biológico , Cosméticos/química , Dietilexilftalato/administração & dosagem , Dietilexilftalato/urina , Modelos Biológicos , Adulto , Idoso , Dieta , Dietilexilftalato/metabolismo , Dietilexilftalato/farmacocinética , Feminino , Contaminação de Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Noruega , Adulto Jovem
3.
Environ Health Perspect ; 128(6): 67007, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32515996

RESUMO

BACKGROUND: Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women. OBJECTIVE: We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity. METHODS: This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005-2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4) and triiodothyronine (fT3, TT3), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores. RESULTS: We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of fT4, TT4, fT3, and TT3 [absolute difference: -0.62; 95% confidence interval (CI): -0.12, -0.01; p=0.04; absolute difference: -8.31; 95% CI: -13.8, -2.85; p=0.003; absolute difference: -0.37; 95% CI: 0.54, -0.19; p<0.0001; and absolute difference: -0.21; 95% CI: -0.32, -0.10; p=0.003, respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb. CONCLUSIONS: Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740.


Assuntos
Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Glândula Tireoide/fisiologia , Adulto , Autoimunidade/fisiologia , Teorema de Bayes , Biomarcadores/sangue , Estudos Transversais , Dietilexilftalato/urina , Feminino , Humanos , Iodeto Peroxidase/sangue , Hormônios Tireóideos/sangue , Tireotropina/sangue , Mulheres
4.
Rapid Commun Mass Spectrom ; 34(13): e8796, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32246863

RESUMO

RATIONALE: Several phthalates and bisphenol A are endocrine-disrupting chemicals (EDCs). Recently, their use has been partially restricted and less toxic compounds, such as di-2-ethylhexyl terephthalate (DEHTP), have been placed on the market. The aim of this work was to develop and validate a method for the simultaneous quantitation of bisphenol A and urinary metabolites of phthalates, including DEHTP. METHODS: An isotopic dilution high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) method for the determination of bisphenol A (BPA), monobenzyl phthalate (MBzP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP), mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP), monoethyl phthalate (MEP), and mono-n/i-butyl phthalates (MnBP/MiBP) in human urine was developed. A complete validation was carried out and the method was applied to 36 non-occupationally exposed adults. RESULTS: Limits of quantitation ranged from 0.02 (MECPP) to 1 µg/L (MnBP and MiBP). Relative standard deviations below 10% indicated a suitable precision; accuracy, evaluated using a standard reference material, ranged from 74.3% to 117.5%; isotopically labelled internal standards were suitable for correcting the matrix effect. The accuracy was confirmed by the successful participation in an external verification exercise. However, for terephthalates, the validation was incomplete due to the lack of reference materials and external verification. Levels of the investigated chemicals in subjects were in line with those previously reported. CONCLUSIONS: An LC/MS/MS assay for the simultaneous measurement of BPA and phthalate metabolites in human urine was developed and validated; it is useful to investigate exposure in epidemiological studies involving the general population.


Assuntos
Compostos Benzidrílicos/urina , Cromatografia Líquida/métodos , Dietilexilftalato/urina , Fenóis/urina , Espectrometria de Massas em Tandem/métodos , Adulto , Idoso , Compostos Benzidrílicos/química , Dietilexilftalato/química , Estabilidade de Medicamentos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenóis/química , Ácidos Ftálicos/química , Ácidos Ftálicos/urina , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Int J Hyg Environ Health ; 223(1): 93-105, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669154

RESUMO

During the past two decades human exposure to bisphenol A (BPA) and phthalates such as di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP) and di-(2-ethyl-hexyl) phthalate (DEHP) has received substantial interest due to widespread population exposures and potential endocrine disrupting effects. Therefore, these chemicals have gradually been restricted and phased out through legislation. However, humans are still exposed to a wide range of other less studied phthalates, phthalate substitutes and BPA analogues as well as other polychlorinated and phenolic substances. In this study, we investigated human exposure to these chemicals over the past decade. Three hundred urine samples collected in 2009, 2013 and 2017 (100 samples each year) from young Danish men of the general population, participating in a large on-going cross-sectional study, were selected for the present time trend study. The urinary concentration of metabolites of 15 phthalates, di-2-ethylhexyl terephthalate (DEHTP) and di-iso-nonyl-cyclohexane-1,2-dicarboxylate (DINCH), seven bisphenols including BPA, bisphenol S (BPS) and bisphenol F (BPF), as well as triclosan, triclocarban, benzophenone-3, three chlorophenols and two phenylphenols were analyzed by two new sensitive LC-MS/MS methods developed and validated for the present study. A significant decrease in urinary concentrations over time was observed for the majority of the chemicals. Median concentrations of BPA and the metabolites of DiBP, DnBP, BBzP and DEHP were more than halved from 2009 to 2017. Similar decreases were observed for triclosan and the chloro- and phenylphenols. In contrast, metabolites of the two phthalate substitutes DEHTP and DINCH increased more than 20 and 2 times, respectively. The potential BPA substitutes; BPS and BPF also increased, but only slightly. Despite these new exposure patterns, the exposure to the old well-known chemicals, such as DiBP, DnBP, BBzP, DEHP and BPA was still higher in 2017 compared to the exposure level of the new substitutes such as DEHTP, DINCH, BPS and BPF. A significant decrease in internal exposure to most of the common phthalates and BPA over the past decade was observed, reflecting market changes and regulatory measures implemented in EU. Despite increasing exposures to some of the known phthalate substitutes and BPA analogues, the total amount of each measured chemical group (original and substitute analytes combined) was lower in the more recently collected samples. This indicates only partial direct substitution or substitution by chemicals not covered in this approach, or a general decline in the exposure to these chemical/product groups over the last decade.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Adulto , Compostos Benzidrílicos/urina , Dinamarca , Dibutilftalato/análogos & derivados , Dibutilftalato/urina , Dietilexilftalato/urina , Disruptores Endócrinos/urina , Monitoramento Ambiental , Humanos , Masculino , Fenóis/urina , Plastificantes/metabolismo , Sulfonas/urina
6.
Chemosphere ; 241: 125093, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629241

RESUMO

Some studies have revealed thyrotoxicity of phthalates; however, associations of phthalate exposure with papillary thyroid cancer (PTC) remain unclear. We conducted a pair-matching case-control study of 111 PTC cases and 111 age- and sex-matched non-PTC controls to examine associations between urinary concentrations of phthalate metabolites and PTC. Phthalate metabolites were determined in fasting urine specimens by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS). After adjusting for potential confounders and other phthalate metabolites, the concentrations of the sum of di (2-ethylhexly) phthalate (DEHP) metabolites in urine were positively associated with PTC [odds ratio (OR) = 5.35; 95% confidence interval (CI): 1.61-17.83], suggesting the effect of phthalates exposure on PTC development. The findings require confirmation.


Assuntos
Ácidos Ftálicos/urina , Câncer Papilífero da Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/induzido quimicamente , Adulto , Estudos de Casos e Controles , Cromatografia Líquida , Dietilexilftalato/urina , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Espectrometria de Massas em Tandem , Câncer Papilífero da Tireoide/urina , Neoplasias da Glândula Tireoide/urina
7.
Sci Total Environ ; 707: 135671, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31780177

RESUMO

Epidemiological evidence on the associations between urinary di-(2-ethylhexyl) phthalate (DEHP) metabolites and residential characteristics is limited. Therefore, we investigated the associations of urinary DEHP metabolites with the residential characteristics of pregnant women. We collected completed questionnaires and maternal spot urine samples from 616 random pregnant women in Shengjing Hospital of China Medical University in Shenyang. Urinary DEHP metabolites concentrations, including mono-(2-ethylhexyl) phthalate (MEHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), were measured and analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). Multivariable linear regression models were performed to obtain regression estimates (ß) and 95% confidence intervals (CIs) after adjustment for sociodemographic characteristics. In all participants, the geometric mean of MEHP and MEHHP concentrations were 4.25 ± 4.34 and 5.72 ± 2.65 µg/L, respectively. In multivariable analyses after adjusting for sociodemographic characteristics, distance from residence to motor vehicle traffic (≥150 m versus <20 m) was negatively associated with MEHP (ß = -0.241, 95% CI: -0.448, -0.033) and MEHHP (ß = -0.279, 95% CI: -0.418, -0.140) concentrations. Compared with the one that had not recently been renovated, a renovated home was associated with higher MEHP (ß = 0.194, 95% CI: 0.064, 0.324) and MEHHP (ß = 0.111, 95% CI: 0.024, 0.197) concentrations. Air freshener use was associated with higher MEHP (ß = 0.322, 95% CI: 0.007, 0.636) concentrations. Moldy walls were positively associated with MEHP (ß = 0.299, 95% CI: 0.115, 0.482) and MEHHP (ß = 0.172, 95% CI: 0.050, 0.294) concentrations. In contrast, humidifier use was associated with a lower MEHP concentration (ß = -0.167, 95% CI: -0.302, -0.032). Residential characteristics were probably associated with the DEHP exposure of pregnant women in Shenyang. Living near the motor vehicle traffic, residential renovation, air freshener use, and moldy walls are likely risk factors for increased DEHP exposure, whereas using household humidifier could be considered a protective measure to reduce DEHP exposure.


Assuntos
Dietilexilftalato/urina , China , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Gravidez
8.
Food Chem Toxicol ; 132: 110700, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31356917

RESUMO

Postnatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, is associated with allergy development in childhood, suggesting that DEHP exposure may dysregulate immune response in infants. We investigated whether DEHP exposure in newborns through medical treatment affected the gut microbiota pattern and vaccine response, which are both related to immune development. In this prospective cohort study from May 1, 2016 through July 31, 2017, newborns with respiratory distress who were given intravenous infusions (IVs) were enrolled as the DEHP group, and newborns who did not receive IVs were enrolled as the control group. We excluded patients with perinatal maternal probiotics, vaginal delivery, antibiotic treatment, and exclusive human milk or formula feeding. Of 118 infants, urinary phthalate metabolite analysis revealed that the calculated DEHP concentrations of the newborns treated with IVs (n = 15) were higher than those in the control group (n = 10) (p = 0.0001). DEHP exposure altered bacterial communities both in composition and diversity, particularly decreases in Rothia sp. and Bifidobacterium longum in the DEHP group. Furthermore, DEHP exposure significantly enhanced anti-HBsAg-IgM responses in the DEHP group (p = 0.013). Early-life DEHP exposure alter gut microbiota of newborns and may change their immune responses in later life.


Assuntos
Dietilexilftalato/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Vacinas contra Hepatite B/administração & dosagem , Imunoglobulina M/sangue , Plastificantes/farmacologia , Dietilexilftalato/urina , Feminino , Hidratação , Humanos , Imunoglobulina M/imunologia , Recém-Nascido , Infusões Intravenosas , Masculino , Plastificantes/análise
9.
Arch Environ Contam Toxicol ; 77(4): 471-479, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31214748

RESUMO

Knowledge of population exposure to phthalates based on the urinary metabolite levels is of the highest importance for health risk assessment. Such data are scarce in the Czech population. In the study conducted in 2016, six urinary phthalate metabolites were analysed in a total of 370 first morning urine samples of healthy children aged 5 and 9 years, namely mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-benzyl phthalate (MBzP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP). The two latter mono-butyl phthalate isoforms dominated among all samples with geometric means of 63.0 µg/L (MnBP) and 44.1 µg/L (MiBP), followed by 5OH-MEHP (20.6 µg/L), 5oxo-MEHP (12.9 µg/L), MBzP (3.65 µg/L), and MEHP (2.31 µg/L). Daily intake (DI) of the parent phthalates was estimated using the creatinine-based model. The highest DI values were found for di-n-butyl phthalate (DnBP) (median 2.5 µg/kg bw/day; 95th percentile 7.8 µg/kg bw/day) and di-2-ethylhexyl phthalate (DEHP) (median 2.3 µg/kg bw/day; 95th percentile 8.9 µg/kg bw/day) in 5-year-old children. The tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA) was exceeded in case of DnBP (in 1% of 9-year-olds and in 3% of 5-year-olds). Exposure risk was assessed based on hazard quotients calculation and cumulative approach for similar health effect. The combined exposure to four phthalates expressed by hazard index (HI) for reprotoxicity revealed exceeding of HI threshold in 14% of 5-year-olds and in 9% of 9-year-olds. These findings strongly support the need to reduce the burden of children by phthalates.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Criança , Pré-Escolar , Creatinina/urina , República Tcheca , Dietilexilftalato/administração & dosagem , Dietilexilftalato/análogos & derivados , Dietilexilftalato/urina , Poluentes Ambientais/administração & dosagem , Feminino , Humanos , Masculino , Nível de Efeito Adverso não Observado , Ácidos Ftálicos/administração & dosagem , Medição de Risco , Instituições Acadêmicas
10.
Environ Pollut ; 251: 137-145, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31078085

RESUMO

Maternal exposure to phthalates may cause some adverse health effects on both mother and fetus, but variations of phthalate exposure and metabolism during pregnancy have not been thoroughly characterized. A total of 946 participants were selected from a cohort study conducted in Wuhan between 2014 and 2015 through which they had provided a complete set of urine samples at three trimesters. Eight phthalate metabolites were analyzed in 2838 urine samples. Based on urinary concentrations, various parameters (i.e. phthalate metabolite concentrations, ratios of metabolites of bis(2-ethylhexyl) phthalate (DEHP) in DEHP, and percentages of individual metabolites in total phthalates) were compared over three visits. We observed that levels of phthalate metabolites showed a U-shaped trend across three trimesters. The significant variations in the ratios of DEHP metabolites indicated that the efficiency in metabolizing DEHP declined during pregnancy and less recent exposure occurred in mid-pregnancy. The changes of percentages of individual compound in total phthalates suggested the inconsistent pattern over trimesters. This longitudinal study found that the exposure pattern, exposure timing and metabolic susceptibility varied by trimesters, which suggests that urine samples should be collected at multiple time points and mothers should be especially careful in the early pregnancy.


Assuntos
Poluentes Ambientais/metabolismo , Exposição Materna/estatística & dados numéricos , Ácidos Ftálicos/metabolismo , Adulto , Estudos de Coortes , Dietilexilftalato/urina , Exposição Ambiental , Feminino , Humanos , Estudos Longitudinais , Mães , Gravidez , Adulto Jovem
11.
Talanta ; 198: 377-389, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30876575

RESUMO

DiEthylHexylPhthalate (DEHP) can leach out of plasticized PVC medical devices (MD) and may enter into contact with patients. This phthalate is known for its reprotoxic and endocrine disrupting effects. Its use in medical devices (MD) has been restricted and alternative plasticizers have been developed. Nevertheless, no published clinical studies exist concerning patient exposure to these alternative plasticizers during medical care. This is particularly worrisome when high-risk populations, such as newborns, are exposed to these new plasticizers in intensive care units. Our study aimed to develop a novel sensitive and selective method to simultaneously identify and quantify DEHP and 17 other plasticizer metabolites (free or glucuronide conjugates), which are specific biomarkers of DEHTP, TOTM, DINP, DINCH and DEHA exposure in human urine. This robust method uses turbulent-flow online extraction technology coupled to high performance liquid chromatography - tandem mass spectrometry. Special care was taken to address two major problems in plasticizer analysis: contamination and chromatographic separation of interfering analogue structures. The validation was assessed in synthetic urine and the linearity of response was demonstrated for all compounds (R2 > 0.99), with limits of quantification from 0.01 to 0.1 ng/ml. Accuracies ranged from 86% to 117% and inter- and intra-day precisions were <20%. The clinical applicability and suitability of our new method was assessed in patients in a neonatal intensive care unit to measure urinary concentrations of DEHP and alternative plasticizer metabolites. These metabolites were found in the majority of urine samples, with a median detection frequency of 95.2% (ranging from 12.5% to 100%). The high sensitivity, selectivity and ruggedness make the method suitable for large-scale biomonitoring studies of high-risk and general populations.


Assuntos
Dietilexilftalato/urina , Plastificantes/análise , Cloreto de Polivinila/química , Extração em Fase Sólida , Cromatografia Líquida , Dietilexilftalato/metabolismo , Humanos , Espectrometria de Massas em Tandem
12.
Artigo em Inglês | MEDLINE | ID: mdl-30901880

RESUMO

In the current paper, we compare the inter-day variability of the metabolite concentration of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) in 247 morning urine samples obtained from 19 probands of different age and sex with the metabolite concentration in morning urine obtained from 215 probands of the "Tübingen Survey" cross-sectional study. In the first longitudinal study the morning urine of seven volunteers was collected four times a year for seven consecutive days (course of the year study). In a second study the morning urine of 12 students of a boarding school was collected on five consecutive days (course of a week study). For participants of the two different longitudinal studies we obtained mean concentrations in first void morning urine for mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) in the range from 21.3 to 110 µg/L, 10.5 to 35.6 µg/L for mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 45.5 to 143 µg/L for mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The corresponding relative standard deviations (rel. Std.D in %) for these DEHP-metabolites vary between 45.2% and 262%. The 50th percentiles vary for 5OH-MEHP between 17.5 and 65.6 µg/L, for 5oxo-MEHP between 9.0 and 20.3 µg/L and for 5cx-MEPP between 42.5 and 82.0 µg/L. For participants of the "Tübingen Survey" cross-sectional study the means vary for 5OH-MEHP between 58.2 and 85.0 µg/L, between 33.6 and 38.7 µg/L for 5oxo-MEHP and between 110 and 158 µg/L for 5cx-MEPP with rel. standard deviations in a range between 86.5 to 175%. The corresponding 50th percentiles vary for 5OH-MEHP between 26.5 and 42.3 µg/L, for 5oxo-MEHP between 18.0 and 26.3 µg/L, and for 5cx-MEPP between 57.2 and 77.6 µg/L. In order to compare the data from the longitudinal studies with the data from the cross-sectional study, the frequency distribution of the results of both types of studies was compared first. In a second step, the results of a t-test (p-values) was used to check whether the results of the long-term studies differ statistically significantly from the results of the cross-sectional study (p < 0.05). The present data show that the frequency distributions of DEHP-metabolites are comparable. For most of the participants respectively subject groups t-test results prove that no statistical significant difference between results obtained from longitudinal studies compared to the results of the cross-sectional study are apparent. The available data on the exposure of individual subjects mirror the data obtained from cross-sectional studies of the general population and give hints to the risk of individual increased DEHP exposure. Results also highlight the importance of living conditions on the risk of increased DEHP exposure.


Assuntos
Dibutilftalato/urina , Dietilexilftalato/urina , Adolescente , Fatores Etários , Estudos Transversais , Dietilexilftalato/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores Sexuais , Adulto Jovem
13.
Ann Thorac Surg ; 107(2): 567-572, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30071236

RESUMO

BACKGROUND: Industrial chemicals are increasingly recognized as potential developmental neurotoxicants. Di(2-ethylhexyl) phthalate (DEHP), used to impart flexibility and temperature tolerance to polyvinylchloride, and bisphenol A (BPA), used to manufacture polycarbonate, are commonly present in medical devices. The magnitude of exposure in neonates during hospitalization for cardiac operations is unknown. METHODS: We quantified urinary concentrations of DEHP metabolites and BPA preoperatively and postoperatively in neonates undergoing cardiac operations and their mothers. Urinary concentrations of these biomarkers reflect recent exposures (half-lives are approximately 6 to 24 hours). Biomarker concentrations in mothers' and infants' preoperative and postoperative samples were compared. RESULTS: Operations were performed in 18 infants (mean age, 5 ± 4 [SD] days). The maternal sample was obtained on postpartum day 4 ± 4. The preoperative urine sample was obtained on day-of-life 4 ± 2 and the postoperative sample on day-of-life 6 ± 4. Mean maternal concentrations for DEHP metabolites and BPA were at the 50th percentile for females in the United States general population. Infant preoperative concentrations of 1 DEHP metabolite and BPA were significantly higher than maternal concentrations. Postoperative concentrations for all DEHP metabolites were significantly greater than preoperative concentrations. CONCLUSIONS: There is considerable perioperative exposure to DEHP and BPA for neonates undergoing cardiac operations. Infant concentrations for both BPA and DEHP metabolites were significantly higher than maternal concentrations, consistent with the infant's exposure to medical devices. Further study is needed to determine the potential role of these suspect neurotoxicants in the etiology of neurodevelopmental disability after cardiac operations.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Dietilexilftalato/efeitos adversos , Exposição Ambiental/efeitos adversos , Equipamentos e Provisões/efeitos adversos , Cardiopatias Congênitas/cirurgia , Neurotoxinas/efeitos adversos , Fenóis/efeitos adversos , Compostos Benzidrílicos/urina , Biomarcadores/urina , Dietilexilftalato/urina , Feminino , Seguimentos , Cardiopatias Congênitas/urina , Humanos , Recém-Nascido , Masculino , Neurotoxinas/urina , Fenóis/urina , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Fatores de Risco
14.
Thyroid ; 29(2): 183-192, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30588877

RESUMO

BACKGROUND: Diethylhexyl phthalate (DEHP) is widely used in industrial products, particularly as plasticizers and softeners. Because it is used extensively, DEHP has been detected in humans worldwide. Although epidemiological studies suggest that DEHP can disrupt the function of the hypothalamic-pituitary-thyroid (HPT) axis, evidence on the association between DEHP exposure and thyroid function remains inconclusive. Therefore, a comprehensive meta-analysis was performed to investigate the association between DEHP exposure and the HPT axis in humans. METHODS: A literature search of the MEDLINE, EMBASE, and Web of Science databases was conducted to search for studies in which the correlation coefficient values or regression coefficient values between three major DEHP metabolites (i.e., monoethylhexyl phthalate [MEHP], mono [2-ethyl-5-hydroxyhexyl] phthalate [MEHHP], and mono [2-ethyl-5-oxohexyl] phthalate) and thyrotropin, free thyroxine (T4), or total T4 were determined. The association between DEHPs and thyroid hormone levels were evaluated using Pearson's correlation coefficients. RESULTS: Thirteen eligible articles were included. Urinary MEHP and MEHHP concentration was negatively correlated with total T4. Pooled correlation coefficients between MEHP/MEHHP and total T4 were -0.02 [confidence interval (CI) -0.05 to 0.00] and -0.03 [CI -0.05 to -0.01], respectively. Urinary mono (2-ethyl-5-oxohexyl) phthalate concentration was positively correlated with thyrotropin, and the pooled correlation coefficient was 0.02 [CI 0.00-0.04]. CONCLUSIONS: The findings of this meta-analysis suggest a significant association between the exposure of DEHP metabolites and the function of the HPT axis.


Assuntos
Dietilexilftalato/efeitos adversos , Dietilexilftalato/metabolismo , Glândula Tireoide/efeitos dos fármacos , Dietilexilftalato/análogos & derivados , Dietilexilftalato/urina , Exposição Ambiental , Humanos , Ácidos Ftálicos/urina , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue
15.
Artigo em Inglês | MEDLINE | ID: mdl-30423997

RESUMO

Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100⁻300 µg/m³ of deuterium-labelled diethyl phthalate (D4-DEP) and bis(2-ethylhexyl) phthalate (D4-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D4-DEP and D4-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D4-DEP excretion peaked 3.3 h (T½ of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m³ (nmol of urinary metabolites per phthalates air concentration in (nmol/m³)). After dermal exposure to D4-DEP, metabolite excretion peaked 4.6 h (T½ of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m³. After combined inhalation and dermal exposure to D4-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T½ of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m³ between participants. No dermal uptake of particle phase D4-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D4-DEP was three times higher than after combined exposure to D4-DEHP; and nine times higher than after dermal exposure of D4-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.


Assuntos
Dietilexilftalato/urina , Disruptores Endócrinos/urina , Exposição Ambiental/análise , Ácidos Ftálicos/urina , Adulto , Feminino , Humanos , Exposição por Inalação/análise , Masculino , Pessoa de Meia-Idade , Suécia , Voluntários , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-30200671

RESUMO

Phthalates are widely used in the industrial manufacture of many products. Some phthalates have shown reproductive toxicity in humans, acting as endocrine disruptors, so they were included in the authorization process defined in Reg. CE 1907/2006 (REACH). Two groups of population were recruited, before and after the inclusion of some phthalates in the authorization list in REACH: the first group of 157 volunteers was studied in 2011 and the second, 171 volunteers, in 2016. Each subject completed a questionnaire about personal lifestyle, working activities and use of chemical products. The main urinary metabolites of five phthalates were analyzed by HPLC/MS/MS: mono(2-ethylhexyl)phthalate (MEHP) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) for di(2-ethylhexyl)phthalate (DEHP) exposure; monoethylphthalate (MEP) for diethylphtahate (DEP); monobenzylphthalate (MBzP) for butylbenzylphtahalate (BBP) and dibenzylphthalate (DBzP), mono-n-butylphthalate (MnBP) for butylbenzylphtahalate (BBP) and di-n-butylphthalate (DnBP). The results show a significant difference for all metabolites between the two periods, with the exception of MEP in women. The comparison of the two sets of results shows a decrease in urinary metabolites excretion from 2011 to 2016, statistically significant for the three phthalates included in Annex XIV of REACH. DEP, not currently included in the list for authorization, maintains a constant presence in the daily life of the population, particularly for women.


Assuntos
Disruptores Endócrinos/urina , Exposição Ambiental/análise , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Adulto , Dibutilftalato , Dietilexilftalato/urina , Exposição Ambiental/legislação & jurisprudência , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem
17.
Environ Pollut ; 241: 969-977, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30029331

RESUMO

Recurrent pregnancy loss (RPL) is the termination of pregnancies, usually before 20 weeks of gestation, and is defined as the loss of two or more pregnancies. In Taiwan, after 2011 di-2-ethylhexyl phthalate (DEHP) exposure episode, more reproductive-aged women still expose to high levels of DEHP and di-butyl phthalate (DBP) than have women of other age groups. Phthalates might be involved in the RPL pathogenesis. This study assessed the association of phthalate exposure with RPL risk in reproductive-aged Taiwanese women. This study recruited 103 patients diagnosed by a physician with RPL of unknown etiology and 76 controls from the Department of Obstetrics and Gynecology at a medical center in southern Taiwan between August 2013 and August 2017. Urine samples were analyzed for 11 phthalate metabolites through liquid chromatography-tandem mass spectrometry; subsequently, principal component analysis (PCA) and hierarchical clustering analysis were performed to determine the main sources of phthalate exposure. Finally, multivariate logistic regression was used to determine the RPL risk. The creatinine-unadjusted median levels of mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) in RPL/control were 9.8/5.3, 27.2/13.1, 11.4/8.1, and 12.9/9.5 ng/mL, respectively; furthermore, ΣDBPm and ΣDEHPm in RPL/control were 0.18/0.10 and 0.15/0.12 nmol/mL, respectively. PCA revealed three primary components of phthalate exposure: diethyl phthalates (DEP), DEHP, and DBP. Plastic food container use and medication were identified as the main phthalate exposure sources. After adjustment for potential confounding factors (urinary creatinine, age, age at menarche, education, and plastic food container use), we found that the urinary level of ΣDBPm was significantly associated with elevated risk for RPL (OR = 2.85, p = 0.045). Our findings supported the hypothesis that exposure to phthalates increases RPL risk. The development of a strategy to reduce phthalate exposure among reproductive-aged women should be emphasized.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Ácidos Ftálicos/toxicidade , Resultado da Gravidez/epidemiologia , Adulto , Dibutilftalato , Dietilexilftalato/urina , Exposição Ambiental/análise , Poluentes Ambientais/análise , Poluentes Ambientais/metabolismo , Feminino , Humanos , Ácidos Ftálicos/análise , Ácidos Ftálicos/metabolismo , Gravidez , Reprodução , Risco , Taiwan
18.
Sci Total Environ ; 625: 1191-1197, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29996415

RESUMO

BACKGROUND: Animal studies have reported an association between phthalates and depression, although there is limited evidence from epidemiological studies. We investigated the association between phthalate exposure and symptoms of depression in an elderly population. METHODS: Repeated measures surveys up to three times were conducted during the study period (2012-2014) in the 535 elderly subjects. We measured the following urinary phthalate metabolite levels: mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-n-butyl phthalate (MnBP), and mono-benzyl phthalate (MBzP). MEHHP, MEOHP, and MECPP are metabolites of diethylhexyl phthalates (DEHP). MnBP and MBzP are metabolites of dibutyl phthalate and butyl benzyl phthalate, respectively. The phthalate metabolite concentrations were evaluated to identify associations with the symptoms of depression using the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K). After factor analysis of the components of SGDS-K, we evaluated the association between phthalate exposure and SGDS-K subgroups to determine which symptoms of depression were affected by phthalate exposure. RESULTS: Concentrations of DEHP metabolites were positively associated with the risk of depressive symptoms in the elderly population (Odds ratio (95% confidence interval); 1.92 (1.17-3.13) for sum of three DEHP metabolites), while we found no significant association between depressive symptoms and either MnBP or MBzP. When we evaluated the associations between phthalate metabolite concentrations and the SDGS-K subgroup, we found that affective and spiritual symptoms were significantly associated with DEHP metabolite concentrations. CONCLUSIONS: Our study suggests that DEHP exposure is associated with depressive symptoms, particularly, the affective and spiritual symptoms, among the elderly population.


Assuntos
Depressão/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Idoso , Depressão/urina , Dibutilftalato/urina , Dietilexilftalato/urina , Feminino , Humanos , Masculino
19.
Environ Int ; 116: 319-325, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29754027

RESUMO

Mounting evidence suggests possible adverse effects of intrauterine exposure to certain phenols and phthalates, two classes of endocrine disruptor chemicals, on the developing fetus, with consequences into later life. These findings have contributed to the replacement of some chemicals, such as di­2­ethylhexyl phthalate (DEHP) and bisphenol A (BPA), in consumer products. For the current study we quantified urinary concentrations of biomarkers of exposure among 50 pregnant women in Israel to several phthalates, bisphenols and personal care product chemicals, as well as DEHP and BPA alternatives. We detected 14 of the 31 biomarkers in more than 90% of the women. We detected biomarkers of 1,2­cyclohexane dicarboxylic acid, diisononyl ester (DINCH), bisphenol S, and bisphenol F not as frequently (27-56%). This study is the first to evaluate exposure to triclosan, bisphenols, parabens, and phthalates and BPA alternatives among Israeli pregnant women.


Assuntos
Compostos Benzidrílicos/urina , Dietilexilftalato/urina , Exposição Materna/estatística & dados numéricos , Fenóis/urina , Biomarcadores/urina , Cosméticos/química , Feminino , Humanos , Israel , Gravidez
20.
Int J Hyg Environ Health ; 221(3): 519-530, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29454883

RESUMO

In this study we analyzed one of the most comprehensive sets of 21 urinary phthalate metabolites representing exposure to 11 parent phthalates (DEP, DMP, DiBP, DnBP, BBzP, DEHP, DiNP, DiDP, DCHP, DnPeP, DnOP) in first morning urine samples of 112 Portuguese children (4-18 years) sampled in 2014/15. The study population consisted of two groups: group 1 with normal weight/underweight children (N = 43) following their regular diet and group 2 with obese/overweight children (N = 69) following a healthy diet (with nutritional counselling). Most of the metabolites were above the limits quantification (81-100%) except for MCHP, MnPEP and MnOP. Metabolite levels were generally comparable to other recent child and general populations sampled worldwide, confirming the steady decline in exposures to most phthalates. Compared to Portuguese children sampled in 2011/2012, median urinary metabolite levels decreased by approximately 50% for DEHP, DnBP, DiBP and BBzP. Risk assessments for individual phthalates and the sum of the anti-androgenic phthalates did not indicate to attributable health risks, also at the upper percentiles of exposure. In the healthy diet group the median concentration of the DEHP metabolites was significant lower, while all phthalate metabolites except MEP tended to be lower compared to the regular diet group. Multiple log-linear regression analyses revealed significantly lower daily intakes (DIs) for all phthalates in the healthy diet group compared to the regular diet group (geometric mean ratios (gMR) between 0.510-0.618; p ≤ 0.05), except for DEP (gMR: 0.811; p = 0.273). The same analyses with the continuous variable body mass index instead of the diet groups also showed effects on the DIs (gMRs between 0.926-0.951; p ≤ 0.05), however much smaller than the effects of the diet. The results indicate that obese children following a healthy diet composed of fresh and less packaged/processed food can considerably reduce their intake for most phthalates and can have lower phthalate intakes than regular weight/regular diet children.


Assuntos
Índice de Massa Corporal , Dieta/efeitos adversos , Exposição Ambiental/análise , Poluentes Ambientais/urina , Obesidade/complicações , Ácidos Ftálicos/urina , Plastificantes , Adolescente , Carga Corporal (Radioterapia) , Peso Corporal , Criança , Pré-Escolar , Dibutilftalato/análogos & derivados , Dibutilftalato/urina , Dietilexilftalato/urina , Comportamento Alimentar , Feminino , Humanos , Masculino , Plastificantes/análise , Portugal , Fatores de Risco
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