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1.
J Pediatr Endocrinol Metab ; 35(7): 931-937, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35667704

RESUMO

OBJECTIVES: Phthalate is one of the endocrine-disrupting chemicals found in many daily consumer products. Chronic exposure to phthalate may associate with obesity and metabolic abnormalities. However, there is limited information showing a direct relationship between phthalate and body compositions. The aim of the study was to determine the association between urinary phthalate concentration and body composition measure among Thai children. METHODS: A cross-sectional analytic study on urinary phthalate concentrations and body composition in elementary school children, aged 6-13 years in Bangkok, was conducted during October 2019 to 2020. Urinary phthalate metabolites; (mono-methyl phthalate-MMP, mono-ethyl phthalate- MEP, mono-buthyl phthalate-MBP, and mono-ethylhexyl phthalate-MEHP), in early morning spot urine samples were measured by liquid chromatography tandem mass spectrometry (LC-MSMS) with a quantitation limit of 1 ng/mL. Phthalate exposures were identified through questionnaires. Body composition was measured by Tanita BC-418®. Multivariate logistic regression analysis was performed to determine significant associations. RESULTS: A total of 364 children were enrolled in the study (boy 51.4%). After adjusting for confounders (sex, caregiver educations, family income, BMI-SDS: Body mass index-standard deviation score, TV watching, and exercise frequency), total urinary phthalate concentrations were associated with fat mass 8.24 (0.94, 15.53), trunk percent fat 7.69 (3.26, 12.12), arm percent fat 3.69 (0.47, 6.91), arm fat mass 72.88 (1.08, 144.67), and leg fat mass 17.79 (2.37, 33.22). CONCLUSIONS: Higher urinary phthalate concentrations were significantly associated with elevated total fat mass among Thai school-aged children. These findings were not mediated through the degree of obesity defined by BMI. These finding emphasized to be careful when being use phthalate-containing products.


Assuntos
Poluentes Ambientais , Criança , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluentes Ambientais/urina , Humanos , Masculino , Obesidade/urina , Ácidos Ftálicos , Tailândia/epidemiologia
2.
Environ Res ; 212(Pt C): 113393, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35504341

RESUMO

Phthalate acid esters (PAEs) are environmental endocrine disruptors that can interfere with endocrine processes and cause adverse reproductive outcomes. The link between PAE exposure and unexplained recurrent spontaneous abortion (URSA) remains unknown. In this study, nine urinary metabolites of PAEs (mPAEs) were measured in 594 URSA cases and 569 healthy controls. The measured mPAEs were ubiquitously detected and present at higher levels (median: 203 ng/mL) in the URSA cases than in the controls (median: 161 ng/mL). Multiple logistic regression analysis showed that URSA was associated with higher concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mono (2-ethylhexyl) phthalate (mEHP), and mono-ethyl phthalate (mEP) and lower concentrations of mono-isobutyl phthalate (miBP). Moreover, a quantile-based g-computation (QGC) model revealed a positive association between mPAEs mixture and URSA. The URSA cases showed significantly higher concentrations of di-(2-ethylhexyl) phthalate (DEHP) than the controls. This was consistent with the health risk assessment, which suggested that DEHP is the main contributors to potential non-carcinogenic risk. DEHP accounted for over 80% of total risk. The large case-control study results suggest that PAE exposure may increase the risk of URSA, and that policy-makers and public health experts should pay more attention to DEHP exposure.


Assuntos
Aborto Espontâneo , Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia , Estudos de Casos e Controles , Dietilexilftalato/urina , Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urina , Ésteres , Feminino , Humanos , Ácidos Ftálicos/urina , Gravidez
3.
Int J Hyg Environ Health ; 243: 113954, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35588565

RESUMO

Phthalates are a class of widely used synthetic chemicals found in commonly used materials and products. Epidemiological studies suggest phthalate exposure is associated with asthma outcomes, though most studies have not investigated phthalates as triggers of exacerbations in children diagnosed with asthma. This study used data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine relationships between phthalate exposure and outcomes related to childhood asthma exacerbation. We used measures of phthalate metabolites and respiratory health measures including fractional exhaled nitric oxide (FENO), the Asthma Control Test (ACT), caregiver report of symptoms, and urinary leukotriene E4 (uLTE4) to estimate longitudinal associations using mixed effects models, adjusted for covariates. For 100% (i.e., doubling) increases in mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and mono-ethyl phthalate (MEP), concentrations of FENO increased by 8.7% (95% CI: 0.7-17.3), 7.2% (95% CI: 0.0-14.9), and 6.4% (95% CI: 0.0-13.3), respectively. All phthalate metabolites demonstrated associations with uLTE4, effect sizes ranging from an 8.7% increase in uLTE4 (95% CI: 4.3-12.5) for a 100% increase in MEHP to an 18.1% increase in uLTE4 (95% CI: 13.3-23.1) for a 100% increase in MNBP. In models of caregiver report of symptoms, no phthalate metabolites were significantly associated in primary models. No phthalate metabolites were associated with standardized ACT score. Our results suggest urinary phthalate metabolites are significant predictors of inflammatory biomarkers related to asthma exacerbation in children but not child and caregiver report of airway symptomatology.


Assuntos
Asma , Poluentes Ambientais , Ácidos Ftálicos , Agricultura , Asma/epidemiologia , Criança , Exposição Ambiental , Poluentes Ambientais/urina , Humanos , Ácidos Ftálicos/urina , Washington
4.
Int J Hyg Environ Health ; 243: 113977, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35533529

RESUMO

AIM: To prospectively investigate the associations of urinary phthalate metabolite concentrations measured at four time points spanning pubertal development with semen parameters in Russian men. DESIGN: 516 boys were enrolled at ages 8-9 years (2003-2005) and followed annually. METHODS: Urine samples were collected annually and pooled into four exposure windows [prepuberty, early puberty, late puberty and sexual maturity] based on physician assessed Tanner genitalia stages and testicular volume. Fifteen phthalate metabolites were quantified using isotope dilution HPLC-MS/MS at Moscow State University. We calculated molar sums (∑) of di-2-ethylhexyl phthalate (DEHP), di-isononyl phthalate (DiNP), di-isodecyl phthalate (DiDP) and anti-androgenic phthalate (AAP) metabolites. At sexual maturity (ages 18-19 years), the men provided 1-2 semen samples for analysis. We estimated the associations of quintiles of urinary ∑phthalate metabolites as well as mono-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and mono-benzyl phthalate (MBzP) at each pubertal window, with semen parameters by fitting generalized linear mixed models with random intercepts and adjusting for confounders. RESULTS: A total of 223 men who provided semen samples had phthalates measured at one or more pubertal windows. Higher urinary concentrations of ∑DiNP metabolites during late puberty were related to poorer semen quality (men with the highest quintile of urinary ∑DiNP had 30% lower sperm concentration, 32% lower count and 30% lower progressive motile count, compared to men in the lowest quintile). Also, young men with higher urinary concentrations of MiBP metabolites in early puberty tended to have poorer semen quality. No associations were observed for ∑DEHP metabolites, ∑DiDP metabolites, ∑AAP, MBzP or MnBP metabolites with semen quality parameters. CONCLUSIONS: ∑DiNP metabolites measured during late puberty and MiBP metabolites at early puberty were related to poorer semen quality, highlighting the importance of considering specific windows of exposure when investigating chemical exposures in relation to measures of reproductive health in men.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Adolescente , Antagonistas de Androgênios , Criança , Dibutilftalato , Exposição Ambiental/análise , Poluentes Ambientais/urina , Humanos , Masculino , Ácidos Ftálicos/urina , Puberdade , Análise do Sêmen , Espectrometria de Massas em Tandem , Adulto Jovem
5.
Neurotoxicol Teratol ; 92: 107102, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35588931

RESUMO

Phthalates are ubiquitous endocrine-disrupting chemicals, and research indicates that prenatal exposure to some phthalates may affect neurodevelopment. In a prospective birth cohort study, five first-morning urine samples collected across pregnancy were pooled and the following phthalate biomarkers assessed: sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of diisononyl phthalate metabolites (ΣDINP), sum of dibutyl phthalate metabolites (ΣDBP), sum of anti-androgenic metabolites (ΣAA), monoethyl phthalate (MEP), and sum of all phthalate metabolites (ΣAll). The Ages & Stages Questionnaires® (ASQ), a standardized parent-reported, age-adapted screening tool, measured communication, personal-social, problem solving, and motor domains in infants at 4.5 and 7.5 months (n = 123). Adjusting for maternal age, annual household income, gestational age at birth, infant age at assessment, and sex, repeated-measures generalized linear regression models were used to examine associations between prenatal phthalate urine biomarker concentrations and domain scores (assuming a Poisson distribution). Beta estimates were exponentiated back to the domain scale for ease of interpretation. Mothers were mostly white and college-educated, and most reported an annual household income of ≥$60,000. Associations of phthalate concentrations with ASQ outcomes are presented as follows: (1) anti-androgenic phthalate metabolites (ΣDEHP, ΣDINP, ΣDBP, and ΣAA), (2) MEP, which is not anti-androgenic, and (3) ΣAll. Overall, anti-androgenic phthalates were associated with higher (i.e., better) scores. However, there were exceptions, including the finding that a one-unit increase in ΣDBP was associated with a 12% increase in problem solving scores in 4.5-month-old females (ß = 1.12; 95% CI: 0.99, 1.28; p = 0.067) but a 85% decrease for 7.5-month-old females (ß = 0.54; 95% CI: 0.3, 0.99; p = 0.047). In contrast, MEP was associated with poorer scores on several outcomes. Sex- and timepoint-specific estimates demonstrated a one-unit increase in MEP was associated with: a 52% decrease in personal-social scores in 7.5-month-old males (ß = 0.66; 95% CI: 0.46, 0.95; p = 0.02), a 39% decrease in fine motor scores in 7.5-month-old males (ß = 0.72; 95% CI: 0.52, 0.98; p = 0.035), and a 6% decrease in fine motor scores in 4.5-month-old females (ß = 0.94; 95% CI: 0.88, 0.99; p = 0.03). A one-unit increase in ΣAll was associated with a 4% increase in personal-social scores in 4.5-month-old males (ß = 1.04; 95% CI: 0.99, 1.1; p = 0.08) but a 17% decrease in 7.5-month-old males (ß = 0.85; 95% CI: 0.73, 0.99; p = 0.03). These data suggest age- and sex-specific associations of prenatal phthalates with infant neurobehavior. The current findings should be confirmed by longitudinal studies with larger sample sizes.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Biomarcadores , Estudos de Coortes , Exposição Ambiental , Poluentes Ambientais/urina , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/urina , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos Prospectivos
6.
Environ Int ; 165: 107288, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35588674

RESUMO

Phthalates are used as plasticizers in many products used in daily life worldwide. Due to industrial and economic developments, exposure among general population to phthalates may vary geographically and temporally. However, studies are lacking for investigating temporal changes in phthalate exposure in the Japanese population. In the present study, the temporal trends in exposure to various phthalates were assessed among a group of Japanese adult female population over 1993-2016 and derived associated risks. For this purpose, urine samples of healthy Japanese females in Kyoto, Japan (N = 132) collected in 1993, 2000, 2003, 2009, 2011, and 2016, were employed and measured for the concentrations of 18 phthalate metabolites. Over this period, the detection rates of mono(3-carboxypropyl) phthalate (MCPP) and monoisobutyl phthalate (MiBP) decreased, and the geometric means of the urinary concentrations of mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) showed a significant decreasing trend. Cumulative risk due to exposure to dibutyl phthalate (DBP), diisobutyl phthalate (DiBP), butyl benzyl phthalate (BBP), and di-2-ethylhexyl phthalate (DEHP) showed a dramatic decrease only between 1993 and 2000. The maximum hazard quotient (HQM) was attributed to DEHP in most subjects regardless of sampling year. This study showed the temporal trend of the exposure of Japanese females to several phthalate esters over two decades. As of the late 2010's, DEHP was still the predominant component of phthalate ester exposure in the population. The HI value, however, indicates that direct risk due to phthalate exposure was unlikely among the studied population.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Adulto , Dietilexilftalato/urina , Exposição Ambiental/análise , Poluentes Ambientais/urina , Ésteres , Feminino , Humanos , Japão , Ácidos Ftálicos
7.
Environ Res ; 212(Pt A): 113218, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35390299

RESUMO

BACKGROUND: Although phthalate exposures have been associated with adverse effects on male reproductive health, few studies have explored longitudinal associations with male pubertal development. OBJECTIVES: We examined the association of prepubertal urinary concentrations of phthalate metabolites with age at pubertal onset in a prospective cohort of Russian boys. METHODS: At enrollment at ages 8-9 years, medical history, dietary, and demographic information was collected. At entry and annually, physical examinations and pubertal staging [Genitalia (G), Pubarche (P), and testicular volume (TV, in ml)] were conducted and spot urines were collected. Prepubertal urine samples (defined as either TV = 1, 2 and G = 1, 2 or TV = 3 and G = 1) were pooled for each boy and phthalate metabolite concentrations were quantified using isotope dilution LC-MS/MS at Moscow State University. We measured 15 metabolites including those from anti-androgenic parent phthalates (AAPs) such as di (2-ethylhexyl) (DEHP) and di-isononyl (DiNP) phthalates as well as monobenzyl (MBzP), mono-n-butyl (MnBP), and mono-isobutyl (MiBP) metabolites. We calculated the molar sums of DEHP (∑DEHP), DiNP (∑DiNP), and AAP (∑AAP) metabolites. Separate interval-censored models were used to assess associations of quartiles of prepubertal phthalate metabolites with each pubertal onset indicator, G2+, P2+ and TV > 3 mL, adjusted for covariates and urine specific gravity. RESULTS: 304 boys had 752 prepubertal urine samples (median 2, range: 1-6) for pooling. In adjusted models, higher urinary AAPs were consistently associated with later pubertal onset (P2) with mean shifts ranging from 8.4 to 14.2 months for the highest versus lowest quartiles. Significantly later onset for G2 and TV > 3 mL was observed for higher versus lower quartiles of MiBP, MBzP, ∑DEHP and ∑DiNP. CONCLUSIONS: On average, boys with higher concentrations of prepubertal urinary AAPs had later pubertal onset by six months to over a year. The impact of AAPs on timing of male puberty may be attributable to disruption of androgen-dependent biological pathways.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Antagonistas de Androgênios , Criança , Cromatografia Líquida , Exposição Ambiental/análise , Poluentes Ambientais/urina , Humanos , Masculino , Ácidos Ftálicos/urina , Estudos Prospectivos , Espectrometria de Massas em Tandem
8.
Environ Res ; 212(Pt B): 113320, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35461845

RESUMO

BACKGROUND: Early life phthalate exposures may disrupt metabolism but results from human studies are inconsistent and few have examined body composition during adolescence. We investigated associations of gestational and childhood urinary phthalate biomarker concentrations with body composition at age 12 years. METHODS: We used data from 206 mother-child pairs in a prospective pregnancy and birth cohort enrolled in Cincinnati, OH from 2003 to 2006. We measured nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children at 1, 2, 3, 4, 5, 8, and 12 years. At age 12 years, we assessed fat and lean mass of the whole body and android and gynoid subregions, and visceral fat area with dual x-ray absorptiometry, and calculated android to gynoid %fat ratio and age- and sex-standardized fat and lean mass index z-scores. Using a multiple informant model, we estimated covariate-adjusted associations between urinary phthalate biomarker concentrations at each time period and outcomes at age 12 years. We assessed effect measure modification by child sex using stratified models. RESULTS: Generally, urinary mono-benzyl phthalate (MBzP) concentrations were modestly associated with lower fat and lean mass. Each 10-fold increase in urinary MBzP concentrations during gestation and at ages 5 and 8 years was associated with a -0.34 (95%CI: -0.72, 0.05), -0.44 (95% CI: -0.83, -0.05), and -0.35 (95% CI: -0.71, 0.00) z-score difference in lean body mass index, respectively. Urinary monoethyl phthalate, mono-(3-carboxypropyl) phthalate, and summed di(2-ethylhexyl) phthalate metabolites were associated with greater lean mass at some exposure periods. Slightly weaker but similar patterns of association were found with other body composition measures; associations did not differ by child sex. CONCLUSION: While most associations were weak, exposure to certain phthalates during gestation and childhood may be associated with adolescent body composition, particularly lean mass.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Adolescente , Composição Corporal , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental , Poluentes Ambientais/urina , Feminino , Humanos , Ácidos Ftálicos/urina , Gravidez , Estudos Prospectivos
9.
Environ Res ; 212(Pt B): 113342, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35461852

RESUMO

Phthalate exposure has been associated with adverse reproductive outcomes and oxidative stress is a potential mechanism by which they act. However, few human studies have explored co-exposure confounding or joint effects. Furthermore, most studies examine associations between biomarkers of exposure and oxidative stress from the same urine sample. We investigated single-exposure, co-exposure-adjusted, and joint associations between phthalate metabolites and oxidative stress in the Environment and Reproductive Health (EARTH) study among couples undergoing fertility treatment. We examined cross-sectional associations in both women and men, and longitudinal associations in women. Urine was collected in the follicular phase (women only) and at the time of fertility procedure (women and men), and analyzed for 11 phthalate metabolites. Urine from the time of fertility procedure was analyzed for oxidative stress biomarkers, including free 8-iso-prostaglandin F2α (8-iso-PGF2α), its primary metabolite (2,3-dinor-5,6-dihydro-15-F2t-isoprostane [F2-IsoP-M]), and prostaglandin F2α (PGF2α). Linear mixed effects models were used to estimate single-exposure associations. Bayesian Kernel Machine Regression (BKMR) was used to adjust for co-exposures and to estimate joint effects. Among women, we observed positive associations between all phthalate metabolites and oxidative stress biomarkers in single-exposure models, but there was clear co-exposure confounding. For instance, in a single-exposure model, we estimated a 63% (95% confidence interval: 51, 77) increase in the 8-iso-PGF2α metabolite per interquartile range (IQR) difference in mono-n-butyl phthalate (MBP) versus a 34% (95% credible interval: 12, 60) increase in co-adjusted models. However, several phthalate metabolites remained associated with oxidative stress in co-exposure models, and the joint effects of all exposures were high (e.g., an 114% increase in the 8-iso-PGF2α metabolite per IQR difference in all exposures). Longitudinal results were also attenuated compared to cross-sectional results in women; however, the joint effect of all exposures and the 8-iso-PGF2α metabolite remained positive and statistically significant (11% increase per IQR difference in all exposures, 95% credible interval: 0.2, 23). In men, associations were generally less pronounced, although the joint effect of the mixture on 8-iso-PGF2α was above the null. Because oxidative stress is related to reproductive success among couples seeking fertility treatment, mitigating phthalate exposure should be considered as a potentially beneficial measure.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Teorema de Bayes , Biomarcadores/urina , Estudos Transversais , Poluentes Ambientais/urina , Feminino , Humanos , Masculino , Estresse Oxidativo , Ácidos Ftálicos/urina , Prostaglandinas
10.
Environ Health ; 21(1): 32, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264146

RESUMO

BACKGROUND: Plasticizers, also called phthalates, are a group of chemicals widely used in daily life. A previous report showed no significant association between phthalate metabolite concentrations and mortality. We investigated the association of urinary phthalate levels and individual phthalate metabolite levels with all-cause and cardiovascular disease (CVD) mortality after standardizing the phthalate concentration. METHODS: A total of 6,625 participants were recruited from a nationally representative sample of adults aged 40 years or older who were enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2014 and were followed up through December 31, 2015. Data were analyzed from January 2021 to June 2021. NHANES-linked updated National Death Index public access files were used to acquire information on mortality status and cause of death. The present study conducted extended follow-up of an earlier analysis. Cox proportional hazard models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of covariate-adjusted creatinine standardization urinary phthalate concentrations with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables. RESULTS: The mean ± standard deviation age of all participants in the final study was 59.9±12.6 years old, and 49.6% of the participants were male. The median follow-up time was 73 months (range 1-157 months). At the censoring date of December 31, 2015, 3,023 participants were identified as deceased (13.4%). A fully adjusted Cox model showed that a urinary di(2-ethylhexyl) phthalate (DEHP) concentration >= 83.4 ng/mL was associated with a slight increase in all-cause mortality (HR 1.27, 95% CI 1.03, 1.57, P for trend= 0.014) and CVD mortality (HR 2.19, 95% CI 1.35, 3.54, P for trend= 0.002). Similarly, urinary mono-2-ethyl-5-carboxypentyl phthalate (MECPP) levels >= 39.2 ng/mL were associated with increased CVD mortality (HR 2.33, 95% CI 1.45, 3.73, P for trend < 0.001). Restricted cubic spline analyses suggested linear associations of DEHP and MECPP levels with all-cause and CVD mortality. CONCLUSION: In this large nationally representative sample of American adults, high urinary DEHP and MECPP were significantly associated with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables.


Assuntos
Doenças Cardiovasculares , Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Adulto , Idoso , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Exposição Ambiental/análise , Poluentes Ambientais/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Ácidos Ftálicos/urina , Plastificantes
11.
Front Public Health ; 10: 843971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35317511

RESUMO

Background: Phthalates are non-persistent chemicals with endocrine-disrupting abilities widely used in a variety of consumer products. Evidence for the effects of phthalate exposure on liver function in adolescents is lacking. Methods: Data were analyzed from the combined 2007-2016 National Health and Nutrition Examination Survey (NHANES). Ultimately, a total of 1,650 adolescents aged 12-19 years were selected as the samples. Weighted linear regression was used to investigate the effects of urinary phthalate metabolites on liver function indexes. Results: Weighted Linear regression models showed that MCOP was negatively associated with TBIL (ß = -0.0435, P FDR = 0.007), ΣDEHP (ß = -0.0453, P FDR = 0.003) and MCOP (ß = -0.0379, P FDR = 0.006) were negatively correlated with ALB, while MCPP was positively correlated with ALB (ß = 0.0339, P FDR = 0.024), and MCOP was negatively correlated with TP (ß = -0.0551; P FDR = 0.004). Conclusions: Phthalate metabolites were significantly but weakly associated with changes in liver function indicators among US adolescents. Future work should further examine these relationships.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Adolescente , Poluentes Ambientais/urina , Humanos , Fígado , Inquéritos Nutricionais , Ácidos Ftálicos/urina
12.
Environ Health Perspect ; 130(3): 37009, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35333099

RESUMO

BACKGROUND: Humans are exposed to complex mixtures of phthalate chemicals from a range of consumer products. Previous studies have reported significant associations between individual phthalate metabolites and pregnancy outcomes, but mixtures research is limited. OBJECTIVES: We used the Puerto Rico Testsite for Exploring Contamination Threats longitudinal pregnancy cohort to investigate associations between phthalate metabolite mixtures and pregnancy outcomes. METHODS: Women (n=462 carrying females, n=540 carrying males) provided up to three urine samples throughout gestation (median 18, 22, and 26 wk), which were analyzed for 13 phthalate metabolites. Pregnancy outcomes including preterm birth (PTB), spontaneous PTB, small and large for gestational age (SGA, LGA), birth weight z-score, and gestational age at delivery were abstracted from medical records. Environmental risk scores (ERS) were calculated as a weighted linear combination of the phthalates from ridge regression and adaptive elastic net, which are variable selection methods to handle correlated predictors. Birth outcomes were regressed on continuous ERS. We assessed gestational average and visit-specific ERS and stratified all analyses by fetal sex. Finally, we used Bayesian kernel machine regression (BKMR) to explore nonlinear associations and interactions between metabolites. RESULTS: Differences in metabolite weights from ridge and elastic net were apparent between birth outcomes and between fetal sexes. An interquartile range increase in gestational average phthalate ERS was associated with increased odds of PTB [male odds ratio (OR)=1.56; 95% confidence interval (CI): 1.08, 2.27; female OR=1.91; 95% CI: 1.23, 2.98], spontaneous PTB (male OR=2.32; 95% CI: 1.46, 3.68; female OR=2.00; 95% CI: 1.04, 3.82), and reduced gestational age at birth (male ß=-0.39 wk, 95% CI: -0.62, -0.15; female ß=-0.29 wk, 95% CI: -0.52, -0.05). Analyses by study visit suggested that exposure at ∼22 wk (range 20-24 wk) was driving those associations. Bivariate plots from BKMR analysis revealed some nonlinear associations and metabolite interactions that were different between fetal sexes. DISCUSSION: These results suggest that exposure to phthalate mixtures was associated with increased risk of early delivery and highlight the need to study mixtures by fetal sex. We also identified various metabolites displaying nonlinear relationships with measures of birth weight. https://doi.org/10.1289/EHP8990.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Nascimento Prematuro , Teorema de Bayes , Biomarcadores , Peso ao Nascer , Poluentes Ambientais/urina , Feminino , Humanos , Recém-Nascido , Masculino , Ácidos Ftálicos/urina , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Porto Rico/epidemiologia
13.
Environ Res ; 212(Pt A): 113194, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35358548

RESUMO

Phthalates are a large group of chemicals used in many everyday consumer products such as food packaging, household cleaners, cosmetics, fragrances and personal care products (PCPs). A number of diseases such as obesity, hypertension, as well as reproductive system effects and endocrine disorders have been linked to phthalate exposure through the use of PCPs, due to their frequent use and high phthalate content. In this study we review available literature on phthalates and their metabolites in urine and report the various determinants of exposure through the use of PCPs in infants, toddlers, children and adults. The range of creatinine-adjusted concentrations for each phthalate was 1.5-14956.1 µg/g for MEP, 0.4-94.5 µg/g for MEHP, 0.39-425.9 µg/g for MEHHP, 0.5-481.3 µg/g for MEOHP, 0.1-755.1 µg/g for MBzP, and 0.3-401.4 µg/g for MiBP. Time of sampling, frequency of use, race and age are critical factors that influence phthalate concentrations. Using PCPs 48 h before urine collection, using a combination of PCPs (i.e., particularly leave-on versus rinse-off products), being younger (i.e., children compared to their mothers), and being a woman of colour (i.e., Mexican-American and black versus white) leads to higher phthalate levels in urine. The most striking association between any phthalate and PCPs was observed between MEP and perfumes or fragrance-containing products such as shampoos, body lotions and hair products. Future studies should focus on different types and brands of PCPs (i.e., branded versus generic), explore possible ethnic/racial differences and the applicability of non-invasive matrices such as nails and hair for phthalate biomonitoring, as well as intervention studies that explore behavioural changes.


Assuntos
Cosméticos , Poluentes Ambientais , Perfumes , Ácidos Ftálicos , Adulto , Cosméticos/química , Exposição Ambiental/análise , Poluentes Ambientais/urina , Feminino , Humanos , Lactente , Mães , Ácidos Ftálicos/urina
14.
Environ Res ; 212(Pt A): 113203, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35358547

RESUMO

Previous studies have provided data on determinants of phthalates in pregnant women, but results were disparate across regions. We aimed to identify the food groups and demographic factors that predict phthalate exposure in an urban contemporary pregnancy cohort in the US. The study included 450 pregnant women from the New York University Children's Health and Environment Study in New York City. Urinary concentrations of 22 phthalate metabolites, including metabolites of di-2-ethylhexylphthalate (DEHP), were determined at three time points across pregnancy by liquid chromatography coupled with tandem mass spectrometry. The Diet History Questionnaire II was completed by pregnant women at mid-pregnancy to assess dietary information. Linear mixed models were fitted to examine determinants of urinary phthalate metabolite concentrations. Using partial-linear single-index (PLSI) models, we assessed the major contributors, among ten food groups, to phthalate exposure. Metabolites of DEHP and its ortho-phthalate replacement, diisononyl phthalate (DiNP), were found in >90% of the samples. The sum of creatinine-adjusted DiNP metabolite concentrations was higher in older and single women and in samples collected in summer. Hispanic and non-Hispanic Black women had lower urinary concentrations of summed metabolites of di-n-octyl phthalate (DnOP), but higher concentrations of low molecular weight phthalates compared with non-Hispanic White women. Each doubling of grain products consumed was associated with a 20.9% increase in ∑DiNP concentrations (95%CI: 4.5, 39.9). PLSI models revealed that intake of dried beans and peas was the main dietary factor contributing to urinary ∑DEHP, ∑DiNP, and ∑DnOP levels, with contribution proportions of 76.3%, 35.8%, and 27.4%, respectively. Urinary metabolite levels of phthalates in pregnant women in NYC varied by age, marital status, seasonality, race/ethnicity, and diet. These results lend insight into the major determinants of phthalates levels, and may be used to identify exposure sources and guide interventions to reduce exposures in susceptible populations.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Idoso , Criança , Exposição Ambiental/análise , Poluentes Ambientais/urina , Feminino , Humanos , Cidade de Nova Iorque , Ácidos Ftálicos/urina , Gravidez , Gestantes
15.
J Expo Sci Environ Epidemiol ; 32(3): 400-407, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35347231

RESUMO

BACKGROUND: Persistent organic pollutant exposures are well-documented in the Arctic, but fewer studies examined non-persistent chemicals, despite increased market food and consumer product consumption. OBJECTIVE: To measure phenol, paraben, phthalate, and alternative plasticizer concentrations in Inuit adults. METHODS: The study included 30 pooled urine samples from Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017) participants. Creatinine-adjusted geometric mean concentrations (GM) and 95% confidence intervals (CI) were compared across sex, age, and regions, and compared to those in the Canadian Health Measures Survey (CHMS) and the First Nations Biomonitoring Initiative (FNBI). RESULTS: Q2017 bisphenol-A concentrations were double the CHMS 2018-2019 concentrations [GM (95% CI): 1.98 (1.69-2.31) versus 0.71 (0.60-0.84) µg/g creatinine], but in line with FNBI [1.74 (1.41-2.13) µg/g creatinine]. Several phthalate concentrations were higher in Q2017 versus CHMS, particularly monobenzyl phthalate, which was was 19-fold higher in Q2017 versus CHMS 2018-2019 [45.26 (39.35-52.06) versus 2.4 (2.0-2.9) µg/g creatinine] and four-fold higher than FNBI. There were also four-fold higher concentrations of the two alternate plasticizer 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TIXB) metabolites in Q2017 compared to CHMS 2018-2019. Women and people living in Ungava Bay had generally higher concentrations of non-persistent chemicals. SIGNIFICANCE: The results suggest higher concentrations of certain non-persistent chemicals in Inuit versus the general Canadian population. IMPACT: Few studies have explored non-persistent chemical distributions in Northern communities, despite the increasing consumer product and market food consumption. We analyzed 30 pooled samples from the Qanuilirpitaa? Nunavik Inuit Health Survey 2017 to assess exposures to common plasticizes and plastic constituents and compare their levels with the general Canadian population and First Nation groups. We observed particularly higher levels of bisphenol-A, of monobenzyl phthalate, and of two 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB) metabolites among Nunavimmiut compared to the general Canadian population, notably among women and Ungava Bay residents. Larger studies are required to confirm our findings and identify potential adverse health effects from these exposures.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Adulto , Canadá , Creatinina , Monitoramento Ambiental , Poluentes Ambientais/urina , Feminino , Humanos , Ácidos Ftálicos/urina , Plastificantes , Plásticos
16.
Artigo em Inglês | MEDLINE | ID: mdl-35270433

RESUMO

Fibroid etiology is poorly understood but is likely hormonally mediated. Therefore, we evaluated associations between midlife phthalates (hormone-altering chemicals) and prior fibroid diagnosis, and considered differences by weight gain status. Women (ages: 45-54; n = 754) self-reported past fibroid diagnosis. We pooled 1-4 urines collected after fibroid diagnosis over the consecutive weeks to analyze nine phthalate metabolites and calculate relevant molar sums (e.g., di(2-ethylhexyl) phthalate, ΣDEHP; anti-androgenic phthalates, ΣAA; all metabolites, ΣPhthalates). Using Poisson regression, we evaluated associations between phthalate biomarkers and the risk of having fibroid diagnosis. We explored if associations differed by weight gain from age 18 to 45-54 or in women diagnosed with fibroids within 5 years of phthalate assessment. Our major finding was that women had a 13% (RR: 1.13; 95%CI: 1.02, 1.26) and 16% (RR: 1.16; 95% CI: 1.03, 1.31) greater risk of prior fibroid diagnosis for each two-fold increase in ΣDEHP or ΣAA, respectively. These associations were strongest in women who became overweight/obese from age 18 to 45-54 and in those diagnosed <5 years before phthalate assessment. Based on these results, prospective studies should corroborate our findings related to associations between phthalates and fibroids, and may consider evaluating the role that weight gain may play in these associations.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Leiomioma , Ácidos Ftálicos , Exposição Ambiental , Poluentes Ambientais/urina , Feminino , Humanos , Leiomioma/epidemiologia , Pessoa de Meia-Idade , Ácidos Ftálicos/urina , Estudos Prospectivos , Aumento de Peso
17.
Environ Res ; 209: 112885, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35131323

RESUMO

Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Compostos Benzidrílicos , Monitoramento Biológico , Dietilexilftalato/urina , Exposição Ambiental/análise , Poluentes Ambientais/urina , Humanos , Fenóis , Ácidos Ftálicos/urina
18.
Ecotoxicol Environ Saf ; 233: 113313, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35182801

RESUMO

BACKGROUND: A few studies have reported phthalate exposure as a risk factor for depressive symptoms, but the results have been inconsistent. Whether chronic inflammation mediates the relationship between phthalates (PAEs) and depressive symptoms remains unclear. In this study, we establish mediating models of inflammatory factors and explore the mediating role of chronic inflammation in the association between PAEs exposure and depressive symptoms. METHODS: The sample included 989 participants from the Study on Health and Environment of the Elderly in Lu'an City, Anhui Province. Geriatric depression scale (GDS-30) was used to screen depressive symptoms of the elderly. The levels of seven kinds of PAEs in urine samples and four inflammatory factors in serum of the elderly were measured. To establish the mediating effect of inflammatory factors to explore the potential effect of PAEs exposure on the increased odds of depressive symptoms. RESULTS: Adjusted for multiple variables, the highest tertiles of Mono (2-ethylhexyl) phthalate (MEHP) (95%CI = 1.051-2.112), Mono benzyl phthalate (MBzP) (95%CI = 1.016-2.082) and Mono butyl phthalate (MBP) (95%CI = 1.102-2.262) were positively correlated with depressive symptoms. The mediating effect of IL-6 and generalized inflammation factor between MEHP exposure and depressive symptoms were 15.96% (95%CI=0.0288-0.1971) and 14.25% (95%CI = 0.0167-0.1899). CONCLUSIONS: High levels of MEHP, MBzP and MBP increased the odds of depressive symptoms in the elderly, and chronic inflammation had a partial mediating effect on the increased odds of depressive symptoms due to MEHP exposure.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Idoso , Depressão/induzido quimicamente , Dibutilftalato , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urina , Humanos , Inflamação/induzido quimicamente , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/urina
19.
Environ Int ; 160: 107083, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35051840

RESUMO

BACKGROUND: Exposure to individual phthalates and the mediation effect of oxidative stress in association with asthma and allergic symptoms have been studied previously. Little is known about the mixture effect of phthalates on health outcomes. Thus, we investigated the effect of a mixture of ten phthalate metabolites in association with wheeze, rhino-conjunctivitis, and eczema. The mediating effect of three oxidative stress biomarkers was also assessed. METHODS: Levels of 10 phthalate metabolites and 3 oxidative stress biomarkers were measured in 386 urine samples from 7-year-old children. Parents reported demographic and allergic symptoms using ISAAC questionnaires. Logistic regression for individual metabolites and mixture analysis weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were fitted to examine the association between phthalate metabolite exposure and health outcomes. Baron and Kenny's regression approach was used for mediation analysis. RESULTS: In logistic regression model showed mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) (OR = 1.41, 95% CI 1.02-1.97) and mono carboxy-isononyl phthalate (cx-MINP) (OR = 1.40, 95% CI 1.07-1.86) were associated with wheeze. The WQS index had a significant association (OR = 1.46, 95% CI 1.09-1.96) with wheeze and (OR = 1.40, 95% CI 1.07-1.82) with eczema. Mono-isononyl phthalate (MINP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were the most highly weighted metabolites. In the BKMR model, diisononyl phthalate (DINP) metabolites showed the highest group posterior inclusion probability (PIP). Among DINP metabolites, MINP in wheeze, cx-MINP in rhino-conjunctivitis and OH-MINP in eczema showed the highest conditional PIPs. The overall metabolites mixture effect was associated with eczema. We did not find any mediation of oxidative stress in the association between phthalates and symptoms. No significant association between phthalate metabolites and oxidative stress was observed in this study. CONCLUSION: Mixture of phthalate metabolites were associated with wheeze and eczema. The main contributors to the association were DEHP and DINP metabolites. No mediation of oxidative stress was observed.


Assuntos
Poluentes Ambientais , Hipersensibilidade , Ácidos Ftálicos , Teorema de Bayes , Biomarcadores/urina , Criança , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urina , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Estresse Oxidativo/fisiologia , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/toxicidade
20.
J Expo Sci Environ Epidemiol ; 32(3): 384-391, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35075242

RESUMO

BACKGROUND: Phthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes. OBJECTIVE: To explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort. METHODS: We measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalate metabolites and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, mono-unsaturated, polyunsaturated) which were then regressed on phthalate metabolites. Associations were adjusted for false discovery. RESULTS: After controlling for multiple comparisons, 33 phthalate-lipid associations were identified (False discovery rate adjusted p value < 0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and mono-unsaturated fatty acid chains. SIGNIFICANCE: Characterization of associations between lipidomic markers and phthalate metabolites during pregnancy will yield mechanistic insight for maternal and child health outcomes. IMPACT: This study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy. The greatest lipid signatures of phthalate exposure were observed for diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1. Polymerized glycerides are important for energy production and regulated through hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling. Characterization of these mechanisms are relevant for informing the etiology of maternal and children's health outcomes.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Biomarcadores/urina , Diglicerídeos , Poluentes Ambientais/urina , Feminino , Humanos , Lipidômica , Fosfatidilcolinas , Ácidos Ftálicos/urina , Gravidez , Gestantes , Porto Rico
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