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1.
Ecotoxicology ; 28(9): 1038-1045, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31489593

RESUMO

Endocrine-disrupting chemicals have been known to alter important animal behaviors by modulating serotonin (5-hydroxytryptamine, 5-HT) and dopamine. F. heteroclitus (mummichog) brain serotonin and dopamine levels were quantified by enzyme-linked immunosorbent assay (ELISA) following a 28-day exposure regimen involving daily doses of either 0.1 mg l-1 benzyl butyl phthalate (BBP) dissolved in acetone or acetone alone (0.1 mg l-1). No differences in mean brain mass or total protein homogenate were induced by exposure to the acetone vehicle or BBP in acetone. The acetone vehicle had no effect on dopamine, serotonin, or tyrosine hydroxylase levels, but acetone did decrease tryptophan hydroxylase levels (p = 0.011). Exposure to BBP in acetone decreased dopamine (p = 0.024), increased serotonin (p < 0.001), reduced tryptophan hydroxylase as compared to the acetone vehicle alone (p < 0.001), and had no significant effect on tyrosine hydroxylase levels. This study is the first to report modulation of F. heteroclitus brain serotonin and its enzyme tryptophan hydroxylase following sub-lethal exposure to BBP in an acetone vehicle. In addition, modulation of brain dopamine in F. heteroclitus, sans simultaneous modulation of tyrosine hydroxylase, was also observed. These findings support the use of F. heteroclitus for assessing sub-lethal BBP exposure.


Assuntos
Encéfalo/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Plastificantes/efeitos adversos , Serotonina/metabolismo , Poluentes Químicos da Água/efeitos adversos , Animais , Feminino , Fundulidae , Distribuição Aleatória
2.
Environ Sci Pollut Res Int ; 26(27): 28256-28269, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31368075

RESUMO

Environmental exposure to phthalates may contribute to an increased risk of asthma in children and adults. We aimed to assess the direction and strength of the association between urinary phthalates metabolites and current asthma in children and adults that participated in the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Data on ten urinary phthalate metabolites, self-reported questionnaires, spirometry measures, and covariates were obtained from 7765 participants (28.1% were children aged 6-17 years) taking part in the NHANES 2007-2012. Asthma was assessed using self-reported questionnaires for children and adults, and via spirometry measures for adults alone. We used crude and adjusted logistic regression models to estimate the odds ratios (ORs) and 95% confidence interval (CI) per one log10 unit change in the concentration of phthalate metabolites. We further modeled the effect modification by sex. Out of 10 metabolites, only mono-benzyl phthalate (MBzP) was positively associated with the prevalence of self-reported asthma in children, after adjusting for a range of potential confounders (odds ratio 1.54; 95% confidence interval 1.05-2.27). No significant relationship was observed for adults. The association of mono-ethyl phthalate (MEP) was modified by sex, with significantly increased odds of asthma among males [boys (2.00; 1.14-3.51); adult males (1.32; 1.04-1.69)]. While no other phthalates showed a positive relationship with current asthma in males, mono-(carboxynonyl) phthalate (MCNP) and mono-(3-carboxylpropyl) phthalate (MCPP) were inversely associated with spirometrically defined asthma in adult females. A sex-specific relationship in adults was evident when spirometry, but not self-reported measures were used to define asthma. We found no clear association between exposure to phthalates and current asthma, except for a significant relationship between MBzP metabolites and self-reported asthma in children. As a result, exposure to phthalates and asthma development and/or exacerbations remains controversial, suggesting a need for a well-designed longitudinal study.


Assuntos
Asma/induzido quimicamente , Exposição Ambiental/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Ácidos Ftálicos/química , Adolescente , Adulto , Criança , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Inquéritos Nutricionais , Razão de Chances , Ácidos Ftálicos/metabolismo , Autorrelato , Inquéritos e Questionários , Adulto Jovem
3.
Eur J Obstet Gynecol Reprod Biol ; 240: 293-299, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400564

RESUMO

BACKGROUND: Phthalates are chemical compounds present in a wide range of consumer products and are thought to be endocrine disruptors. Though not commonly known, phthalates are present in some medication with previous studies finding up to 50-fold higher urinary metabolite concentrations among exposed compared to the general population. Previous studies on environmental phthalate exposure and pregnancy outcomes have been contradictory and inconclusive and all previous studies have assessed phthalate exposure using biomarkers despite a known rapid metabolism of phthalates. OBJECTIVE: To determine whether phthalate exposure from pharmaceutical drugs have effects on preterm birth (PTB) and small for gestational age (SGA). STUDY DESIGN: We conducted a nested case-control study among women in Denmark with a recorded singleton birth and included women who conceived between January 1st, 2004 and December 31st, 2015. To mitigate drug effect and confounding by underlying disease we included pregnancies exposed to selected study drugs, and compared pregnancies exposed to phthalate containing drugs to pregnancies exposed to phthalate free generic drugs. Using Danish health registries, we identified 30,899 singleton pregnancies exposed to study drugs available in both phthalate-containing and phthalate free versions. Using conditional logistic regression, we estimated associations between phthalate exposure and the risk of PTB and SGA. Birth weight according to gestational age was defined by INTERGROWTH-21st (SGA-I) and by Marsal's equation (SGA-M) for expected birthweight. RESULTS: We included 1965 PTBs, 1315 SGA-Is, and 891 SGA-M cases, matched to 19,537, 12,008, and 7573 controls, respectively. Orthophthalate exposure during the third trimester was positively associated with PTB with a crude OR of 1.36 (95% CI: 1.06-1.76). The association was mainly due to diethyl phthalate. Exposure to phthalate polymers in third trimester was associated with a risk of PTB with crude ORs of 2.08 (CI: 1.16-3.71. No associations were found between orthophthalate or phthalate polymer exposure and SGA. CONCLUSION: Exposure to some phthalate-containing pharmaceutical drugs during third trimester is associated with preterm birth.


Assuntos
Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Exposição Materna/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Adulto , Estudos de Casos e Controles , Dinamarca , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Nascimento Prematuro/etiologia , Sistema de Registros , Risco
4.
Artigo em Inglês | MEDLINE | ID: mdl-31296107

RESUMO

The study determined concentrations of and estimated human exposure to house dust-ingested phthalates from 99 homes in Bangkok, Thailand. Phthalates in dust collected using a handheld vacuum cleaner was analyzed by gas chromatography/mass spectrometry revealing a median content of 3,477 µg g-1, range 753-13,810 µg g-1, with di-2-ethylhexylphthalate (DEHP) having the highest level (median = 1,739 µg g-1, range 467-8,172 µg g-1) followed by di-iso-nonyl phthalate (DiNP) (median = 611 µg g-1, range 15.2-11,052 µg g-1). DEHP in house dust from multi-family apartments with polyvinyl (PVC) floor material (n = 34), multi-family apartments without PVC floor material (n = 55) and single family houses without PVC floor material (n = 10) was median and range 3,009 and 568-6,898; 1,479 and range 467-8,172 and 1,207 µg g-1 and 611-3518 µg g-1, respectively. At high-end house dust DEHP level, preschool children in all three types of homes were exposed above US Environment Protection Agency reference dose (20 µg g-1). The results suggest phthalate-containing house products constitute a likely major source of phthalates in indoor home environment and pose a potential health risk to residents, particularly preschool children, in Bangkok.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Exposição Ambiental/análise , Ácidos Ftálicos/análise , Plastificantes/análise , Criança , Pré-Escolar , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Habitação , Humanos , Lactente , Masculino , Ácidos Ftálicos/efeitos adversos , Plastificantes/efeitos adversos , Tailândia , Estados Unidos , United States Environmental Protection Agency
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(5): 585-589, 2019 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-31177743

RESUMO

Objective: The urine concentrations of phthalate metabolites were used to estimate the cumulative risk assessment in preschool children in Ma'anshan of Anhui province. Methods: Based on the China-Anhui Birth Cohort, the demographic information and urine samples of 3 743 children were collected in Ma'anshan from April 2014 to April 2015. The concentrations of 7 metabolites' [monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl- 5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)] of 5 phthalates [dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP)] in the urine samples of the children were measured by solid-phase extration-triple quadrupole high performance liquid chromatography-tandem mass spectrometry-isotope method. In addition, the estimated daily intakes (EDIs) of 5 phthalates were calculated according to the metabolites' concentrations. Cumulative risk assessment was performed using hazard quotient (HQ) and hazard index (HI) methods. Results: The M (Q(R)) of seven metabolite concentrations were 29.58 (18.69-48.26), 26.65 (13.44-56.09), 256.86 (150.99-438.51), 0.12 (0.04-0.32), 6.27 (3.71-11.13), 17.94 (11.94-28.42) and 24.80 (16.05-40.32) µg/g creatinine, respectively. For the EDIs of 5 phthalates, DBP ranked first, followed by DEHP, DMP, DEP and BBzP with the M (Q(R)) of 7.54 (4.41-12.85), 3.35 (2.20-5.42), 0.75 (0.47-1.24), 0.71 (0.36-1.52) and 0.003 (0.001-0.009) µg/(kg·d), respectively. The HQ and HI varied with age, gender and sampling season, the differences were significant (P<0.05). Conclusions: These results indicated that risk of cumulative exposure to phthalates was high in preschool children aged 3-6 years in Ma'anshan. Age, gender and sampling season were influencing factors.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/urina , Medição de Risco/métodos , Biomarcadores/urina , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Ácidos Ftálicos/efeitos adversos , Estações do Ano
6.
J Pharm Biomed Anal ; 172: 238-242, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31063881

RESUMO

Endocrine disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) are substances that may interfere with the actions of endogenous hormones and may be associated with estrogen-related diseases such as endometriosis. This paper describes a case-control study to evaluate the relationship between endometriosis and phthalates and BPA exposure, through biomarkers analysis in urine. The biomarkers of exposure analyzed were metabolites mono-methyl phthalate, mono-isobutyl phthalate (MiBP), mono-butyl phthalate, mono-cyclohexyl phthalate, mono-(ethylhexyl) phthalate, mono-isononyl phthalate, mono-octyl phthalate (MOP), mono-benzyl phthalate and BPA. Urine samples were collected from women aged 18-45 years old. The Study group (n = 30) and Control group (n = 22) were composed of women using as criteria confirmation of endometriosis by videolaparoscopy surgery with histological diagnosis and the absence of the disease, respectively. The analytical method used liquid phase microextraction with determination by gas chromatography coupled to mass spectrometry. The concentrations of biomarkers were adjusted by the creatinine concentration in urine samples of the two groups. The values obtained for the Study Group were compared with the values obtained for the Control Group. The chi-square test and Odds Ratio were used to compare dichotomized phthalate metabolites and BPA metabolite by endometriosis. All nine metabolites were found in different concentrations in the urine samples in both groups The phthalate metabolites that had the highest concentrations, were MOP and MiBP, in which the values of 670 µg g-1 and 560 µg g-1, respectively. The relationship between endometriosis and the all grouped metabolites was evaluated, but was not statistically significant with a 95% CI [X2 (df = 1) = 1.471; p = 0.225]. However, odds ratio (95% confidence interval - CI) for MiBP, which was found at relatively high concentrations in the samples, by endometriosis was 1.929 (0.507-7.332). The food habits and gynecologic history were evaluated and no difference was found between groups. Although no evidences of causal link was found, this study contributes to show that other analysis must be done for evaluating the association between endometriosis and compounds suspected of being EDC.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Endometriose/induzido quimicamente , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Adolescente , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Disruptores Endócrinos/efeitos adversos , Endometriose/metabolismo , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Estrogênios/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Pessoa de Meia-Idade , Adulto Jovem
7.
Sci Total Environ ; 683: 109-115, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31129321

RESUMO

Clothing easily adsorbed the chemicals in the environment, and became a source of human exposure to chemicals. However, large contacted surface area and long exposure duration have elevated human exposure to chemicals from clothing, such as phthalates. Among them, cotton clothing, which infants prefer to wear, has been proven to adsorb phthalates more easily than other fabrics. While infants are developing, they are easily affected by phthalates. In this study, in order to study accumulation of phthalates in infant cotton clothing during the whole process from production to the first wearing, 24 infant cotton clothing samples were collected from shopping malls in Harbin, China. High detection rates and concentrations suggest that phthalates in the environment are widely adsorbed to infant cotton clothing, and traditional laundering for infant clothing cannot remove phthalates completely. The median concentration of the total phthalates was 4.15 µg/g. Di-(2-ethylhexyl) phthalate (DEHP) has become the dominant phthalate. For the estimated daily intakes (EDIs) for infants, dibutyl phthalate (DBP) had the highest contribution, followed by di-iso-butyl phthalate (DiBP) and DEHP. Dermal absorption has become the main route of infant exposure to phthalates, and ingestion contributed very little. The result of comparing with the EDIs via dermal absorption from house air and dust suggests that clothing plays an important role of dermal absorption exposure to phthalates. For risk assessment, the carcinogenic risk of BBP and DEHP indicates that the level of DEHP in infant cotton clothing might pose potential adverse effects to infant health.


Assuntos
Vestuário , Fibra de Algodão/análise , Exposição Ambiental , Poluentes Ambientais/análise , Ácidos Ftálicos/análise , China , Monitoramento Ambiental , Poluentes Ambientais/efeitos adversos , Humanos , Lactente , Recém-Nascido , Ácidos Ftálicos/efeitos adversos , Medição de Risco
9.
Acta Oncol ; 58(6): 852-858, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30882263

RESUMO

Background: Phthalates are used as excipients in some drug products, and up to a 50-fold increased urinary excretion of phthalate metabolites compared to non-users has been demonstrated in users of such products. In vitro studies have demonstrated that phthalates stimulate mechanisms involved in gastric cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and the risk of gastric adenocarcinomas. Methods: Using the Danish Cancer Registry, we identified all patients with incident gastric adenocarcinoma from 2008 to 2015 (n = 1525). Cancer cases were matched to 10 controls. Linking information retrieved from nationwide Danish registries, we determined individual cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP) and enteric phthalate polymers from prescription drugs. The association between cumulative phthalate exposure and gastric adenocarcinoma was estimated using conditional logistic regression, adjusting for socioeconomical status and drugs or comorbidities known or suspected to modify the risk of gastric adenocarcinoma. Results: No association was seen for the risk of gastric adenocarcinomas among individuals with high cumulative exposure to ortho-phthalates (exceeding 500 mg) (ORadj 1.22, 95% CI: 0.84-1.77). Likewise, no associations were observed individually for DEP (ORadj 1.06 95% CI: 0.63-1.76) or DBP (ORadj 1.32 95% CI: 0.78-2.23). Cumulative exposure to enteric phthalate polymers exceeding 10,000 mg, did not reveal an association with gastric adenocarcinoma (ORadj 0.79, 95% CI: 0.54-1.16) and no association was seen for individual compounds. Additionally, no dose-response pattern was observed across exposure strata (p = .39, test for trend). Conclusion: We did not find an increased risk of gastric adenocarcinoma among Danish users of phthalate-containing drug products. Our study is limited by a low number of cases exposed to high cumulative doses of phthalates.


Assuntos
Contaminação de Medicamentos/estatística & dados numéricos , Excipientes/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Medicamentos sob Prescrição/farmacologia , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/epidemiologia , Idoso , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/tratamento farmacológico
10.
Environ Res ; 172: 437-443, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826666

RESUMO

BACKGROUND: Research suggests that dietary supplements may be a source of exposure to phthalates, given that diethyl phthalate (DEP) or di-n-butyl phthalate (DBP) can be components of coatings that facilitate extended release or encapsulate dietary supplements. METHODS: Using nationally representative data on a population of 12,281 adults ages 20 y + surveyed between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES), we evaluated the association between dietary supplement use in relation to urinary phthalate metabolites of DEP (monoethyl phthalate, MEP) and DBP (mono-n-butyl phthalate, MBP). We examined associations pertaining to regular use of multivitamin/multimineral (MVMM) supplements, as well as regular use of any other non-MVMM supplement products, the number of non-MVMM supplement products used, as well as individual supplements potentially containing phthalates (exclusive of MVMM). For each urinary phthalate metabolite, results are presented as the minimally-adjusted and multivariable-adjusted ratio, comparing the geometric mean among users to non-users. RESULTS: In multivariable models, we observed a significant positive association between regular use of MVMM use and MEP, with persons using MVMM supplements having 11% higher geometric mean MEP than non-users (Ratio: 1.11; 95% CI: 1.04-1.20); no association was observed for MVMM in relation to MBP. No other significant multivariable-adjusted associations were observed, although power was limited in analyses of individual supplements. Associations did not markedly vary by gender; however, the associations of garlic supplement use with MEP and MBP varied by calendar time, with statistically significant positive associations observed in later years. CONCLUSIONS: A modest significant association was observed between MVMM use and MEP. No other significant associations were observed in our overall multivariable models. Follow-up on the positive association observed between garlic and urinary phthalate metabolite concentrations observed in later years in a well-powered, prospective study would further clarify study findings.


Assuntos
Suplementos Nutricionais , Poluentes Ambientais , Inquéritos Nutricionais , Ácidos Ftálicos , Adulto , Suplementos Nutricionais/análise , Suplementos Nutricionais/estatística & dados numéricos , Exposição Ambiental , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/análise , Poluentes Ambientais/urina , Feminino , Humanos , Masculino , Inquéritos Nutricionais/estatística & dados numéricos , Ácidos Ftálicos/efeitos adversos , Ácidos Ftálicos/análise , Ácidos Ftálicos/urina , Estudos Prospectivos , Adulto Jovem
11.
Fertil Steril ; 111(5): 953-961, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30879714

RESUMO

OBJECTIVE: To explore whether follicular fluid (FF) concentrations of phthalate metabolites are associated with levels of intrafollicular reproductive hormones in women undergoing in vitro fertilization. DESIGN: Cross-sectional study. SETTING: University-affiliated reproductive medicine center. PATIENT(S): A total of 194 women each contributed one FF sample at oocyte retrieval. INTERVENTION(S): FF aspirates from individual follicles (≥18 mm in diameter) were collected. We measured eight phthalate metabolites and four ovarian hormones in the FF samples. MAIN OUTCOME MEASURE(S): Per-follicle E2, P, total T, and antimüllerian hormone (AMH) concentrations. RESULT(S): Most phthalate metabolites were highly detected in FF samples. We observed a dose-response relationship between increasing monomethyl phthalate (MMP) tertiles and lower E2, P, and T levels. Women in the third tertile of MMP had decreases of 34.23%, 9.44 ng/L, and 23.28% in E2, P, and T, respectively, compared with women in the first tertile. Tertiles of monoethyl phthalate and the percentage of di(2-ethylhexyl) phthalate) metabolites excreted as mono(2-ethylhexyl) phthalate were inversely associated with P. We also identified a negative relationship between monobenzyl phthalate tertiles and AMH. In addition, positive correlations between some of the phthalate metabolites and ovarian hormones were detected. CONCLUSION(S): FF concentrations of certain phthalate metabolites were associated with altered levels of intrafollicular reproductive hormones, which raises concern over a potential deleterious effect of environmental phthalate exposure on the endocrine capacity and viability of theca and granulosa cells.


Assuntos
Exposição Ambiental/efeitos adversos , Fertilização In Vitro/métodos , Líquido Folicular/metabolismo , Recuperação de Oócitos/métodos , Ácidos Ftálicos/metabolismo , Adulto , Estudos Transversais , Feminino , Líquido Folicular/química , Humanos , Pessoa de Meia-Idade , Ácidos Ftálicos/efeitos adversos , Ácidos Ftálicos/análise , Adulto Jovem
12.
Chemosphere ; 223: 504-513, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30784757

RESUMO

Testicular dysgenesis syndrome includes the hypospadias, cryptorchidism and abnormal fetal testis in male neonate. This is possibly caused by the environmental phthalates, which down-regulate the expression of androgen synthetic genes and Insl3 or directly inhibits steroidogenic enzymes. There are distinct structure-activity relationships (SARs) for phthalate-mediated developmental and reproductive toxicity. Here, we review the SAR for phthalate-mediated testicular dysgenesis syndrome. Of phthalates of straight side chains, C5-C6 ones are the most potent, C4 or C7 are moderate, C3 is weakest, and C1-2 or C8-13 are ineffective. The branching and unsaturation of side chains increases the toxicity. The cycling of side chains does not increase the toxicity.


Assuntos
Ácidos Ftálicos/efeitos adversos , Reprodução/efeitos dos fármacos , Doenças Testiculares/induzido quimicamente , Testosterona/metabolismo , Animais , Feminino , Humanos , Masculino , Relação Estrutura-Atividade , Testículo/patologia
13.
Sci Total Environ ; 662: 714-721, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30703729

RESUMO

We performed repeated measurements of phthalate metabolite concentrations during childhood and investigated the association of phthalate exposure with lipid levels and insulin resistance. This study included 164 subjects from the Korean Ewha Birth and Growth Cohort Study who underwent follow-up examinations at 3-5 and 7-9 years of age. We measured nine urinary phthalate metabolites, as well as fasting blood glucose, triglyceride (TG), and high-density lipoprotein-cholesterol (HDL-c) levels and the homeostatic model assessment for insulin resistance (HOMA-IR) value. We found that phthalate levels were higher in children at 3-5 years than at 7-9 years of age. Some phthalate metabolites were associated with increased TG and HOMA-IR levels at both age ranges. Repeated measurements of phthalate metabolites were performed to identify long-term exposure patterns. An increased level of mono(2­ethylhexyl) phthalate (MEHP) was significantly associated with an increased TG level, and increased levels of MEHP, mono(2­ethyl­5­oxohexyl) phthalate (MEOHP), and monoisononyl phthalate (MiNP) were significantly associated with an increased HOMA-IR value, at both age ranges. An increased level of mono-benzyl phthalate was associated with a decreased level of HDL-c at both ages. Our findings suggest that phthalate exposure during childhood is association with effects in terms of insulin-sensitivity index.


Assuntos
Exposição Ambiental , Poluentes Ambientais/efeitos adversos , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Ácidos Ftálicos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , República da Coreia
14.
Sci Total Environ ; 662: 615-621, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30699382

RESUMO

While it has been acknowledged that exposure to endocrine-disrupting chemicals (EDCs) is associated with human diseases, the overall disease burden attributable to the exposure to a specific EDC has rarely been evaluated. Based on existing models for assessing probabilities of causation and a comprehensive review of available data, we analyzed the burden of three diseases, i.e., male infertility, adult obesity, and diabetes, among the general Chinese population resulting from exposure to phthalates. Our estimation indicates that exposure to phthalates is associated with ~2.50 million cases of the three diseases across China in 2010, causing ~57.2 billion Chinese Yuan (equivalent to ~9 billion US dollars) of health care costs in a year. Male infertility has the largest number of cases, followed by adult obesity and diabetes. Based on these phthalate-specific estimates, we further estimated that the total disease cost due to exposure to the overall EDCs amounted to ~429.43 billion Chinese Yuan in China in 2010, accounting for 1.07% of nationwide gross domestic product (GDP). When comparing our results with an earlier estimate for the European Union (EU) member countries, we find that exposure to phthalates leads to quite a similar disease burden per unit of GDP in both regions. Our study illustrates the considerable socio-economic impact of EDC exposure on human society, implying the imperative need for global risk reduction actions on EDCs, especially in view of the 2030 Sustainable Development Goals.


Assuntos
Diabetes Mellitus/economia , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Infertilidade Masculina/economia , Obesidade/economia , Ácidos Ftálicos/efeitos adversos , China , Efeitos Psicossociais da Doença , Diabetes Mellitus/induzido quimicamente , Poluentes Ambientais/efeitos adversos , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Obesidade/induzido quimicamente
15.
Prenat Diagn ; 39(3): 209-218, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30476355

RESUMO

BACKGROUND: Phthalates are used extensively in commercial and personal care products and maternal exposure is ubiquitous. Phthalates are anti-androgenic, but the potential effects of phthalates on male penile development have not been assessed in utero. OBJECTIVE: The study aims to investigate the association between early pregnancy phthalate exposure and fetal penile development, overall and by race. METHODS: Prospective cohort study of women with singleton pregnancies presenting for prenatal ultrasound between 18 and 22 weeks' gestation. Maternal urine samples were assayed for eight phthalate monoester metabolites. We used maternal phthalate levels at 18 to 22 weeks' gestation as predictors of fetal size using multiple linear regression models, adjusted for fetal gestational age, maternal age, race, smoking, and education. We incorporated a phthalate by race interaction into a second set of regression models. RESULTS: We detected statistically significant race interactions for continuous phthalates with penile width. Race interactions were also suggested for penile length and volume using tertiles of phthalates with point estimates generally positive for whites and negative for African Americans. CONCLUSION: Penile development is significantly influenced by race, and the impact of maternal phthalates on penile measurements also varies by race. Maternal phthalate exposure can adversely affect in utero penile growth and development, especially among African Americans.


Assuntos
Exposição Materna/efeitos adversos , Pênis/embriologia , Ácidos Ftálicos/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pênis/efeitos dos fármacos , Gravidez , Estudos Prospectivos , Adulto Jovem
16.
Hum Reprod ; 34(1): 109-117, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30517665

RESUMO

STUDY QUESTION: Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls? SUMMARY ANSWER: We found some associations of altered pubertal timing in girls, but little evidence in boys. WHAT IS KNOWN ALREADY: Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies. STUDY DESIGN, SIZE, DURATION: Data were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women were enrolled in 1999-2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers. MAIN RESULTS AND THE ROLE OF CHANCE: In girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben. LIMITATIONS, REASONS FOR CAUTION: These chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Cosméticos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Maturidade Sexual/efeitos dos fármacos , Adulto , Criança , Estudos de Coortes , Cosméticos/química , Disruptores Endócrinos/urina , Feminino , Humanos , Estudos Longitudinais , Masculino , Exposição Materna/efeitos adversos , Troca Materno-Fetal/fisiologia , Parabenos/efeitos adversos , Parabenos/análise , Fenóis/efeitos adversos , Fenóis/urina , Ácidos Ftálicos/efeitos adversos , Ácidos Ftálicos/urina , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fatores Sexuais , Maturidade Sexual/fisiologia , Fatores de Tempo , Adulto Jovem
17.
Sci Total Environ ; 653: 212-222, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30408669

RESUMO

Phthalic acid esters (PAEs), such as dimethyl phthalate (DMP) and dibutyl phthalate (DBP), are widely distributed as environmental pollutants. In this study, the effects of these chemicals were investigated in black soils using a metagenomics approach. The results clearly showed that DMP or DBP increased the abundance of genes involved in transcription, replication and repair in black soils. In addition, the abundances of genes associated with metabolic functions was improved following treatment with DMP or DBP, including those involved in lipid transport and metabolism, carbohydrate transport and metabolism, and energy production and conversion. There could be many reasons for these observed changes. First, the DMP or DBP treatments increased the abundances of genes associated with the LuxR family, the UvrABC repair system, DNA replication pathways, the RNA polymerase complex and base excision repair. Second, the abundances of genes associated with isocitrate lyase regulator (IclR) family transcriptional regulators, lipid metabolism and carbohydrate active enzymes (CAZys) were altered by the DMP or DBP treatments. Finally, the DMP or DBP treatments also increased the emission load of CO2 and altered the fluorescence intensity of humic acid. Therefore, the results of this study suggested that DMP and DBP contamination altered the abundances of genes associated with genetic information processing and improved the carbon metabolism in black soils.


Assuntos
Bactérias/efeitos dos fármacos , Carbono/metabolismo , Genes Bacterianos/efeitos dos fármacos , Ácidos Ftálicos/efeitos adversos , Microbiologia do Solo , Poluentes do Solo/efeitos adversos , Bactérias/genética , Bactérias/metabolismo , Ésteres/efeitos adversos , Genes Bacterianos/genética , Solo/química
18.
Chemosphere ; 214: 812-820, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30300839

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant with endocrine disrupting properties. As a plasticizer, DEHP can be leach from the plastic to transfer the external environment and thus enters the animal food chain, causing serious damage to the animal organs. The heat-shock response (HSR) comprising heat-shock protein (HSPs) and heat-shock transcription factor (HSFs) plays a pivotal role in various toxic stress conditions. For the sake of investigating the effects of DEHP exposure on cardiac toxicity and the regulation of HSR, male quail were fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45 days. Histopathological changes including cardiomyocyte swelling and muscle fiber dilatation were observed in the hearts exposed to DEHP. During the DEHP treatment, the mRNA expression of HSP60 and HSP70 were universally reduced, while the expression of other HSPs (HSP10, HSP25, HSP27, HSP40, HSP47, HSP90, HSP110) had different degrees of growth. In addition, the levels of HSF1, HSF2, and HSF3 were significantly increased. Given the facts above, DEHP exposure induced the toxic effects of quail heart. DEHP exposure did great harm to HSR via affecting the synthesis of HSFs to mediate the transcription of the HSPs. Ultimately, this study provided new evidence that DEHP-induced cardiotoxicity in quail was related to activation of HSR and playing a protective role.


Assuntos
Cardiotoxicidade/etiologia , Dietilexilftalato/efeitos adversos , Resposta ao Choque Térmico/genética , Ácidos Ftálicos/efeitos adversos , Animais , Cardiotoxicidade/patologia , Codorniz
19.
Pediatr Allergy Immunol ; 30(1): 36-46, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30338578

RESUMO

BACKGROUND: The prevalence of asthma and allergy is increasing in US children. In utero exposure to chemicals used in personal care products and plastics may contribute to increase in these diseases. METHODS: We quantified urinary concentrations of eight phthalate metabolites and bisphenol A in mothers twice during pregnancy in 1999-2000 in Salinas, California. We assessed probable asthma, aeroallergies, eczema, and spirometry in their children at age 7, and measured T helper 1 and T helper 2 cells in blood at ages 2, 5, and 7 (N = 392). We employed Bayesian model averaging to select confounders from additional biomarkers measured in this population and controlled for them in logistic and linear regressions. RESULTS: Monocarboxyisooctyl phthalate was associated with increased odds for probable asthma (odds ratio: 1.54, 95% CI: 1.12, 2.12), and with lower forced expiratory volume in one second (ß: -0.09 L, 95% CI: -0.15, -0.03) and forced expiratory flow from 25% to 75% of forced vital capacity (ß: -7.06 L/s, 95% CI: -11.04, -2.90). Several other associations were attenuated in final models that controlled for additional biomarkers. CONCLUSION: Monocarboxyisooctyl phthalate was associated with lower respiratory health after controlling for related chemical exposure, which suggests that confounding by multiple chemical exposures should be considered in future research.


Assuntos
Asma/epidemiologia , Compostos Benzidrílicos/urina , Eczema/epidemiologia , Fenóis/urina , Ácidos Ftálicos/urina , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adolescente , Adulto , Asma/etiologia , Teorema de Bayes , Compostos Benzidrílicos/efeitos adversos , Biomarcadores/urina , California , Criança , Pré-Escolar , Eczema/etiologia , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Feminino , Humanos , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Gravidez , Prevalência , Espirometria/métodos , Linfócitos T Auxiliares-Indutores , Adulto Jovem
20.
J Clin Endocrinol Metab ; 104(5): 1491-1499, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462244

RESUMO

CONTEXT: Recent epidemiological observations have reported an association among phthalates exposure and insulin resistance, obesity, and diabetes but have not related exposure to these environmental pollutants with microvascular complications of diabetes. OBJECTIVE: To explore the relationship between phthalates and renal function in subjects with diabetes. DESIGN: Cross-sectional, case-only study. Concentrations of three urinary metabolites of di-2-ethylhexylphthalate were quantified in a spot morning urine sample, normalized for creatinine urinary excretion, and related to clinical parameters and phenotype, adjusting for confounders. PATIENTS: Two hundred and nine patients with diabetes consecutively referred to our clinic. MAIN OUTCOME MEASURES: Relationship between phthalates and renal function [evaluated with estimated glomerular filtration rate (eGFR) and albuminuria]. RESULTS: Creatinine-adjusted urinary concentrations of mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-2-ethyl-5-hydroxyhexyl phthalate were 7.53 µg/g (range, 4.84 to 12.60), 3.04 µg/g (range, 1.03 to 5.14), and 10.70 µg/g (7.02 to 17.40), respectively. Age, sex, body mass index, diabetes duration, smoking, blood pressure, glycated Hb, and eGFR did not influence their levels. Exposure to MEHP and MEOHP was greater in individuals with microalbuminuria/macroalbuminuria (MEHP, P = 0.0173; MEOHP, P = 0.0306). The fourth vs first quartile showed a greater risk of albuminuria (MEHP: OR, 4.83; 95% CI, 1.45 to 16.06; P = 0.0297; MEOHP: OR, 3.29; 95% CI, 1.08 to 10.04); P = 0.0352). MEOHP was greater (P = 0.034) in subjects with cardiovascular events; MEHP showed a positive trend (P = 0.061). CONCLUSION: Our findings have revealed an association between exposure to di-2-ethylhexylphthalate metabolites and the degree of albuminuria in subjects with diabetes; the lack of a relationship with eGFR suggests their urinary levels are independent of renal function.


Assuntos
Albuminúria/patologia , Diabetes Mellitus Tipo 2/complicações , Exposição Ambiental/efeitos adversos , Rim/fisiopatologia , Ácidos Ftálicos/efeitos adversos , Idoso , Albuminúria/induzido quimicamente , Biomarcadores/análise , Estudos Transversais , Feminino , Seguimentos , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico
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