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Antonia M Calafat - One of the best experts on this subject based on the ideXlab platform.
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Phthalates exposure and uterine fibroid burden among women undergoing surgical treatment for fibroids a preliminary study
Fertility and Sterility, 2019Co-Authors: Ami R Zota, Ruth J Geller, Cherie Q Marfori, Andrea Baccarelli, Antonia M Calafat, Gaby N MoawadAbstract:Objectives To examine the association between Phthalate exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume. Design Pilot, cross-sectional study. Setting Academic medical center. Patient(s) Fifty-seven premenopausal women undergoing either hysterectomy or myomectomy for fibroids. Intervention(s) None. Main Outcome Measure(s) The diameter of the largest fibroid and uterine dimensions were abstracted from medical records. Spot urine samples were analyzed for 14 Phthalate biomarkers using mass spectrometry. We estimated associations between fibroid outcomes and individual Phthalate metabolites, sum of di(2-ethylhexyl) Phthalate metabolites (∑DEHP), and a weighted sum of anti-androgenic Phthalate metabolites (∑AA Phthalates) using linear regression, adjusting for age, race/ethnicity, and body mass index. Fibroid outcomes were also examined dichotomously (divided at the median) using logistic regression. Results Most women were of black ethnicity, overweight or obese, and college educated. In multivariable models, higher levels of mono-hydroxyisobutyl Phthalate, monocarboxyoctyl Phthalate, monocarboxynonyl Phthalate, mono(2-ethylhexyl) Phthalate, mono(2-ethyl-5-hydroxyhexyl Phthalate) (MEHHP), mono(2-ethyl-5-oxohexyl) Phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) Phthalate (MECPP), ∑DEHP, and ∑AA Phthalates were positively associated with uterine volume. Associations were most pronounced for individual DEHP metabolites (MEHHP, MEOHP, MECPP), ∑DEHP, and ∑AA Phthalates. For example, a doubling in ∑DEHP and ∑AA Phthalates was associated with 33.2% (95% confidence interval 6.6–66.5) and 26.8% (95% confidence interval 2.2–57.4) increase in uterine volume, respectively. There were few associations between Phthalate biomarkers and fibroid size. Conclusions Exposure to some Phthalate biomarkers was positively associated with uterine volume, which further supports the hypothesis that Phthalate exposures may be associated with fibroid outcomes. Additional studies are needed to confirm these relationships.
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Phthalates exposure and uterine fibroid burden among women undergoing surgical treatment for fibroids a preliminary study
Fertility and Sterility, 2019Co-Authors: Ami R Zota, Ruth J Geller, Cherie Q Marfori, Andrea Baccarelli, Antonia M Calafat, Gaby N MoawadAbstract:Objectives To examine the association between Phthalate exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume. Design Pilot, cross-sectional study. Setting Academic medical center. Patient(s) Fifty-seven premenopausal women undergoing either hysterectomy or myomectomy for fibroids. Intervention(s) None. Main Outcome Measure(s) The diameter of the largest fibroid and uterine dimensions were abstracted from medical records. Spot urine samples were analyzed for 14 Phthalate biomarkers using mass spectrometry. We estimated associations between fibroid outcomes and individual Phthalate metabolites, sum of di(2-ethylhexyl) Phthalate metabolites (∑DEHP), and a weighted sum of anti-androgenic Phthalate metabolites (∑AA Phthalates) using linear regression, adjusting for age, race/ethnicity, and body mass index. Fibroid outcomes were also examined dichotomously (divided at the median) using logistic regression. Results Most women were of black ethnicity, overweight or obese, and college educated. In multivariable models, higher levels of mono-hydroxyisobutyl Phthalate, monocarboxyoctyl Phthalate, monocarboxynonyl Phthalate, mono(2-ethylhexyl) Phthalate, mono(2-ethyl-5-hydroxyhexyl Phthalate) (MEHHP), mono(2-ethyl-5-oxohexyl) Phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) Phthalate (MECPP), ∑DEHP, and ∑AA Phthalates were positively associated with uterine volume. Associations were most pronounced for individual DEHP metabolites (MEHHP, MEOHP, MECPP), ∑DEHP, and ∑AA Phthalates. For example, a doubling in ∑DEHP and ∑AA Phthalates was associated with 33.2% (95% confidence interval 6.6–66.5) and 26.8% (95% confidence interval 2.2–57.4) increase in uterine volume, respectively. There were few associations between Phthalate biomarkers and fibroid size. Conclusions Exposure to some Phthalate biomarkers was positively associated with uterine volume, which further supports the hypothesis that Phthalate exposures may be associated with fibroid outcomes. Additional studies are needed to confirm these relationships.
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Phthalates and Phthalate Alternatives Have Diverse Associations with Oxidative Stress and Inflammation in Pregnant Women
2019Co-Authors: Thomas J. Van ′t Erve, Antonia M Calafat, Sheela Sathyanarayana, Shanna H Swan, Emma M. Rosen, Emily S. Barrett, Ruby H.n. Nguyen, Ginger L. Milne, Kelly K. FergusonAbstract:Exposure to environmental chemicals such as Phthalates has been linked to numerous adverse pregnancy outcomes, potentially through an oxidative stress mediated mechanism. Most research examined urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) as the oxidative stress biomarker. However, 8-iso-PGF2α also originates from enzymatic sources linked to inflammation. Therefore, associations between Phthalates and 8-iso-PGF2α could have been misinterpreted. To clarify this, the 8-iso-PGF2α/prostaglandin F2α ratio approach was used to quantitatively distinguish between inflammation or oxidative stress derived 8-iso-PGF2α and estimate their associations with Phthalate metabolites in a cohort of 758 pregnant women from The Infant Development and Environment Study (TIDES). Most urinary Phthalate metabolites were associated with a significant increase in 8-iso-PGF2α. For example, a 22.4% higher 8-iso-PGF2α concentration (95% confidence interval = 14.4, 30.9) was observed with an interquartile range increase in mono-n-butyl Phthalate. For most metabolites, associations were observed solely with oxidative stress derived 8-iso-PGF2α. In contrast, monocarboxy-isononyl Phthalate and monoisononyl Phthalate (MNP) were associated with both sources of 8-iso-PGF2α. Metabolites of the Phthalate alternative 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH), were only associated with inflammation-derived 8-iso-PGF2α, which is interesting because DINCH metabolites and MNP have structural similarities.In conclusion, Phthalates metabolites are not exclusively associated with oxidative stress derived 8-iso-PGF2α. Depending on the metabolite structure, some are also associated with inflammation derived sources, which provides interesting insights in the toxicology of Phthalates
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urinary concentrations of biomarkers of Phthalates and Phthalate alternatives and ivf outcomes
Environment International, 2018Co-Authors: Antonia M Calafat, Ronit Machtinger, Audrey J Gaskins, Catherine Racowsky, Abdallah Mansur, Michal Adir, Andrea A Baccarelli, R. HauserAbstract:Phthalates are a class of chemicals found in a large variety of consumer products. Available experimental and limited human data show adverse effects of some Phthalates on ovarian function, which has raised concerns regarding potential effects on fertility. The aim of the current study was to determine whether urinary concentrations of metabolites of Phthalates and Phthalate alternatives are associated with intermediate and clinical in vitro fertilization (IVF) outcomes. We enrolled 136 women undergoing IVF in a Tertiary University Affiliated Hospital. Participants provided one to two urine samples per cycle during ovarian stimulation and before oocyte retrieval. IVF outcomes were abstracted from medical records. Concentrations of 17 Phthalate metabolites and two metabolites of the Phthalate alternative di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) were measured. Multivariable Poisson regression models with log link were used to analyze associations between tertiles of specific gravity adjusted Phthalate or DINCH metabolites and number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Multivariable logistic regression models were applied to evaluate the association between tertiles of specific gravity adjusted Phthalate or DINCH metabolites and probability of live birth. Urinary concentrations of the sum of di-2-ethylhexyl Phthalate metabolites (∑DEHP) and the individual metabolites mono-2-ethyl-5-hydroxyhexyl Phthalate, mono-2-ethyl-5-oxohexyl Phthalate, and mono-2-ethyl-5-carboxypentyl Phthalate were negatively associated with the number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Of the low molecular weight Phthalates, higher monoethyl Phthalate and mono-n-butyl Phthalate concentrations were associated with significantly fewer total, mature, and fertilized oocytes. None of the urinary Phthalate metabolite concentrations were associated with a reduced probability implantation, clinical pregnancy or live birth. Metabolites of DINCH were not associated with intermediate or clinical IVF outcomes. Our results suggest that DEHP may impair early IVF outcomes, specifically oocyte parameters. Additional research is needed to elucidate the potential effect of DEHP on female fertility in the general population.
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temporal trends in Phthalate exposures findings from the national health and nutrition examination survey 2001 2010
Environmental Health Perspectives, 2014Co-Authors: Ami R Zota, Antonia M Calafat, Tracey J WoodruffAbstract:Background: Phthalates are ubiquitous environmental contaminants. Because of potential adverse effects on human health, butylbenzyl Phthalate [BBzP; metabolite, monobenzyl Phthalate (MBzP)], di-n-b...
Pochin Huang - One of the best experts on this subject based on the ideXlab platform.
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increased risk of Phthalates exposure for recurrent pregnancy loss in reproductive aged women
Environmental Pollution, 2018Co-Authors: Kai Wei Liao, Han Bin Huang, Pochin Huang, Jung Wei Chang, Hung-che Chiang, Paolin KuoAbstract:Abstract 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.
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characterization of Phthalates exposure and risk for cosmetics and perfume sales clerks
Environmental Pollution, 2018Co-Authors: Pochin Huang, Jung Wei Chang, Kai Wei Liao, Shiou Hui Chan, Ching Chang LeeAbstract:Abstract High levels of Phthalates in name-brand cosmetics products have raised concerns about Phthalate exposure and the associated risk for cosmetics sales clerks. We assessed the exposure and risk of Phthalates in 23 cosmetics, 4 perfume, and 9 clothing department store sales clerks. We collected 108 urine samples pre- and post-shift and analyzed for Phthalate monoesters through liquid chromatography–electrospray ionization–tandem mass spectrometry. Phthalates in 32 air samples were collected and analyzed through gas chromatography–mass spectrometry. Demographic characteristics and information on the exposure scenarios were obtained through questionnaires. Principal component analysis, cluster and risk analysis were applied to identify the exposure profile and risk of Phthalate. Median post-shift levels of urinary mono-2-ethylhexyl Phthalate (MEHP) and monomethyl Phthalate (MMP) were significantly higher than the corresponding pre-shift levels in cosmetics group (53.3 vs. 30.9 μg/g-c for MEHP; 34.4 vs. 22.5 μg/g-c for MMP; both P
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Estimated Daily Intake and Cumulative Risk Assessment of Phthalates in the General Taiwanese after the 2011 DEHP Food Scandal
Scientific Reports, 2017Co-Authors: Jung Wei Chang, Han Bin Huang, Wei-chun Chou, Hung-che Chiang, Pochin HuangAbstract:A food scandal occurred in Taiwan in 2011 because the DEHP (di-2-ethylhexyl Phthalate) had been intentionally used in food products. We assessed the daily intakes (DIs) and cumulative risk of Phthalates in Taiwan’s general population after the scandal. The DIs of 6 Phthalates, including di-n-butyl Phthalate (DnBP), di-iso-butyl Phthalate (DiBP), and DEHP, were evaluated using urinary Phthalate metabolites. Hazard quotients of Phthalates classified as affecting the reproductive (HQ_rep) and hepatic (HQ_hep) systems were assessed using cumulative approach. The creatinine-based model showed that the highest DI values in children 7-to 12- years-old were for DEHP (males: median: 4.79 μg/kg bw/d; females: median: 2.62 μg/kg bw/d). The 95^th percentile (P95) of HQ_rep values were all >1 in the 7- to 12-year-old and 18- to 40-year-old male groups. The P95 of HQ_hep values were all >1 in the 7- to 18- year-old male groups. Most of the HQ_rep was attributable to the HQs of DnBP and DiBP (53.9–84.7%), and DEHP contributed most to HQ_hep (83.1–98.6%), which reveals that DnBP, DiBP and DEHP were the main risk of Phthalate exposure for Taiwanese. Taiwan’s general population is widely exposed to DnBP, DiBP and DEHP, especially for young children.
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early Phthalates exposure in pregnant women is associated with alteration of thyroid hormones
PLOS ONE, 2016Co-Authors: Chih Hsin Tsai, Wei Yen Liang, Sih Syuan Li, Pochin Huang, Han Bin HuangAbstract:Introduction Previous studies revealed that Phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of Phthalate exposure on thyroid hormones during early pregnancy. Method We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl Phthalate (MEP), mono-(2-ethyl-5-carboxypentyl) Phthalate (MECPP), mono-(2-ethylhexyl) Phthalate (MEHP), mono-butyl Phthalate (MnBP), of 9 Phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4), free T4, and thyroid-binding globulin (TBG). Results Three Phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%), MnBP (81%) and MECPP (86%). Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other Phthalates) of Phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other Phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = –5.41; p-value = 0.012; n = 97) in pregnant women using Bonferroni correction. Conclusion We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations.
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association between prenatal exposure to Phthalates and the health of newborns
Environment International, 2009Co-Authors: Pochin Huang, Paolin Kuo, Yen Yin Chou, Shio Jean Lin, Ching Chang LeeAbstract:Phthalates are developmental and reproductive toxicants for the fetus in pregnant rodents, and the ability of Phthalates to penetrate the placenta have been reported. The aims of this study were to evaluate the association between maternal urine excretion, the exposure of fetus to Phthalates in amniotic fluid, and the health of newborns. Amniotic fluid and urine samples from pregnant women were collected to measure five Phthalate monoesters using liquid chromatography/tandem mass spectrometry (LC/MS-MS) and the newborns' birth weight, gestational age, and anogenital distance (AGD) were collected. The median levels of three Phthalate monoesters in urine and amniotic fluid were 78.4 and 85.2 ng/mL monobutyl Phthalate (MBP); 24.9 and 22.8 ng/mL mono-(2-ethylhexyl) Phthalate (MEHP); 19.8 and Not Detected monoethyl Phthalate (MEP). We found a significant positive correlation only between creatinine adjusted urinary MBP and amniotic fluid MBP (R(2)=0.156, p<0.05) in all infants and, only in female infants, a significantly negative correlation between amniotic fluid MBP, AGD (R=-0.31, p<0.06), and the anogenital index adjusted by birth weight (AGI-W) (R=-0.32, p<0.05). Although the influence of prenatal di-n-butyl Phthalate (DBP) exposure on the endocrinology and physiology of the fetus is still a puzzle, our data clearly show that in utero exposure to Phthalates in general has anti-androgenic effects on the fetus.
Kurunthachalam Kannan - One of the best experts on this subject based on the ideXlab platform.
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A Review of Biomonitoring of Phthalate Exposures
MDPI AG, 2019Co-Authors: Yu Wang, Hongkai Zhu, Kurunthachalam KannanAbstract:Phthalates (diesters of phthalic acid) are widely used as plasticizers and additives in many consumer products. Laboratory animal studies have reported the endocrine-disrupting and reproductive effects of Phthalates, and human exposure to this class of chemicals is a concern. Several Phthalates have been recognized as substances of high concern. Human exposure to Phthalates occurs mainly via dietary sources, dermal absorption, and air inhalation. Phthalates are excreted as conjugated monoesters in urine, and some Phthalates, such as di-2-ethylhexyl Phthalate (DEHP), undergo secondary metabolism, including oxidative transformation, prior to urinary excretion. The occurrence of Phthalates and their metabolites in urine, serum, breast milk, and semen has been widely reported. Urine has been the preferred matrix in human biomonitoring studies, and concentrations on the order of several tens to hundreds of nanograms per milliliter have been reported for several Phthalate metabolites. Metabolites of diethyl Phthalate (DEP), dibutyl- (DBP) and diisobutyl- (DiBP) Phthalates, and DEHP were the most abundant compounds measured in urine. Temporal trends in Phthalate exposures varied among countries. In the United States (US), DEHP exposure has declined since 2005, whereas DiNP exposure has increased. In China, DEHP exposure has increased since 2000. For many Phthalates, exposures in children are higher than those in adults. Human epidemiological studies have shown a significant association between Phthalate exposures and adverse reproductive outcomes in women and men, type II diabetes and insulin resistance, overweight/obesity, allergy, and asthma. This review compiles biomonitoring studies of Phthalates and exposure doses to assess health risks from Phthalate exposures in populations across the globe
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urinary concentrations of Phthalates in couples planning pregnancy and its association with 8 hydroxy 2 deoxyguanosine a biomarker of oxidative stress longitudinal investigation of fertility and the environment study
Environmental Science & Technology, 2014Co-Authors: Ying Guo, Jennifer Weck, Rajeswari Sundaram, Alexandra E Goldstone, Germaine Buck M Louis, Kurunthachalam KannanAbstract:Oxidative stress has been recognized as one of the most important contributors to infertility in both males and females. Exposure to many environmental chemicals, such as Phthalates, has been shown to induce oxidative stress. In a longitudinal study designed to assess exposure to environmental chemicals and fecundity in couples who were planning pregnancy, 894 urine samples were collected from 469 couples from Michigan and Texas during 2005–2009. The concentrations of 14 Phthalate metabolites and a marker of oxidative stress, 8-hydroxy-2′-deoxyguanosine (8-OHdG), were determined in these samples. Concentrations, profiles, and estimated daily intakes (DIs) of Phthalates were positively associated with 8-OHdG. The median concentrations of monomethyl Phthalate (mMP), monoethyl Phthalate (mEP), mono(3-carboxypropyl) Phthalate (mCPP), mono-n-butyl Phthalate (mBP), mono(2-isobutyl) Phthalate (miBP), monobenzyl Phthalate (mBzP), Σ5mEHP (sum of five metabolites of di(2-ethylhexyl) Phthalate (DEHP)) and Σ14phthala...
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Phthalate concentrations and dietary exposure from food purchased in new york state
Environmental Health Perspectives, 2013Co-Authors: Arnold Schecter, Matthew Lorber, Ying Guo, Se Hun Yun, Kurunthachalam Kannan, Madeline Hommel, Nadia Imran, Linda S HynanAbstract:Background: Phthalates have been found in many personal care and industrial products, but have not previously been reported in food purchased in the United States. Phthalates are ubiquitous synthetic compounds and therefore difficult to measure in foods containing trace levels. Phthalates have been associated with endocrine disruption and developmental alteration. Objectives: Our goals were to report concentrations of Phthalates in U.S. food for the first time, specifically, nine Phthalates in 72 individual food samples purchased in Albany, New York, and to compare these findings with other countries and estimate dietary Phthalate intake. Methods: A convenience sample of commonly consumed foods was purchased from New York supermarkets. Methods were developed to analyze these foods using gas chromatography–mass spectroscopy. Dietary intakes of Phthalates were estimated as the product of the food consumption rate and concentration of Phthalates in that food. Results: The range of detection frequency of individual Phthalates varied from 6% for dicyclohexyl Phthalate (DCHP) to 74% for di-2-ethylhexyl Phthalate (DEHP). DEHP concentrations were the highest of the Phthalates measured in all foods except beef [where di-n-octyl Phthalate (DnOP) was the highest Phthalate found], with pork having the highest estimated mean concentration of any food group (mean 300 ng/g; maximum, 1,158 ng/g). Estimated mean adult intakes ranged from 0.004 μg/kg/day for dimethyl Phthalate (DMP) to 0.673 μg/kg/day for DEHP. Conclusions: Phthalates are widely present in U.S. foods. While estimated intakes for individual Phthalates in this study were more than an order of magnitude lower than U.S. Environmental Protection Agency reference doses, cumulative exposure to Phthalates is of concern and a more representative survey of U.S. foods is indicated.
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occurrence and profiles of Phthalates in foodstuffs from china and their implications for human exposure
Journal of Agricultural and Food Chemistry, 2012Co-Authors: Ying Guo, Zifeng Zhang, Liyan Liu, Nanqi Ren, Kurunthachalam KannanAbstract:Phthalate esters are used in a wide variety of consumer products, and human exposure to this class of compounds is widespread. Nevertheless, studies on dietary exposure of humans to Phthalates are limited. In this study, nine Phthalate esters were analyzed in eight categories of foodstuffs (n = 78) collected from Harbin and Shanghai, China, in 2011. Dimethyl Phthalate (DMP), diethyl Phthalate (DEP), dibutyl Phthalate (DBP), diisobutyl Phthalate (DIBP), benzyl butyl Phthalate (BzBP), and diethylhexyl Phthalate (DEHP) were frequently detected in food samples. DEHP was the major compound found in most of the food samples, with concentrations that ranged from below the limit of quantification (LOQ) to 762 ng/g wet weight (wt). The concentrations of Phthalates in food samples from China were comparable to concentrations reported for several other countries, but the profiles were different; DMP was found more frequently in Chinese foods than in foods from other countries. The estimated daily dietary intake of Phthalates (EDIdiet) was calculated based on the concentrations measured and the daily ingestion rates of food items. The EDIdiet values for DMP, DEP, DIBP, DBP, BzBP, and DEHP (based on mean concentrations) were 0.092, 0.051, 0.505, 0.703, 0.022, and 1.60 μg/kg-bw/d, respectively, for Chinese adults. The EDIdiet values calculated for Phthalates were below the reference doses suggested by the United States Environmental Protection Agency (EPA). Comparison of total daily intakes, reported previously based on a biomonitoring study, with the current dietary intake estimates suggests that diet is the main source of DEHP exposure in China. Nevertheless, diet accounted for only <10% of the total exposure to DMP, DEP, DBP, and DIBP, which suggested the existence of other sources of exposure to these Phthalates.
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Phthalate metabolites in urine from china and implications for human exposures
Environment International, 2011Co-Authors: Ying Guo, Kurunthachalam KannanAbstract:Abstract Phthalates are esters of phthalic acid and are mainly used as plasticizers (added to plastics to increase their flexibility, transparency, durability, and longevity). Humans are exposed to Phthalates through several routes. Urinary Phthalate metabolites can be used as biomarkers of human exposures to Phthalates. In this study, 14 Phthalate metabolites were analyzed in 183 urine samples collected in 2010 from Shanghai, Guangzhou, and Qiqihaer, China. Phthalate metabolites were found in all urine samples and their total concentrations ranged from 18.6 to 3160 ng/mL (median: 331 ng/mL). Mono-n-butyl Phthalate (mBP) and mono-2-isobutyl Phthalate (miBP) were the major metabolites found in urine, and their respective median concentrations were 61.2 and 51.7 ng/mL; concentrations of miBP were higher than the concentrations reported for other countries, to date. Based on the urinary concentrations of Phthalate metabolites, we estimated the daily intake rates in the Chinese population. The estimated daily intakes of dibutyl Phthalate (DBP), diethyl Phthalate (DEP), and di-(2-ethylhexyl) Phthalate (DEHP) in China were 12.2, 3.8, and ~ 5 μg/kg bw/day, respectively. Thirty nine percent of the samples exceeded the tolerable daily intake of 10 μg/kg bw/day, proposed for DBP, by the European Food Safety Authority, but none of the estimated daily intake values exceeded the reference dose recommended by the U.S. Environmental Protection Agency.
Annamaria Andersson - One of the best experts on this subject based on the ideXlab platform.
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urinary excretion of Phthalate metabolites in 129 healthy danish children and adolescents estimation of daily Phthalate intake
Environmental Research, 2011Co-Authors: Hanne Frederiksen, Niels E Skakkebaek, Lise Aksglaede, Kaspar Sorensen, Anders Juul, Annamaria AnderssonAbstract:Abstract Background Phthalates are a group of chemicals with widespread use in the industrial production of numerous consumer products. They are suspected to be involved in male reproductive health problems and have also been associated with several other health problems in children including obesity and asthma. Objectives To study the urinary excretion of Phthalate metabolites in Danish children recruited from the general population, and to estimate the daily intake of Phthalates in this segment of the population. Method One 24 h urine sample and to consecutive first morning urine samples were collected from 129 healthy Danish children and adolescents (range 6–21 yrs). The concentrations of 11 Phthalate metabolites of 5 different Phthalate diesters were analyzed by liquid chromatography–tandem mass spectrometry. Results The analyzed metabolites were detectable in almost all 24 h urine samples. The median concentrations of monoethyl Phthalate (MEP), monobenzyl Phthalate (MBzP) and the sums of the two monobutyl Phthalate isoforms (∑MBP(i+n)), metabolites of di-(2-ethylhexyl) Phthalate (∑DEHPm) and of di-iso-nonyl Phthalate (∑DiNPm) were 29, 17, 111, 107 and 31 ng/mL, respectively. The youngest children were generally more exposed to Phthalates than older children and adolescents (except diethyl Phthalate (DEP)). Boys were more exposed than girls. The median estimated daily intake of Phthalate diesters was: 4.29 (dibutyl Phthalate isoforms (DBP(i+n))), 4.04 (DEHP), 1.70 (DiNP), 1.09 (DEP) and 0.62 (butylbenzyl Phthalate (BBzP)), all calculated as μg/kg body weight/24 h. Between 40% and 48% of the absolute amount of Phthalate metabolites excreted over 24 h were excreted in first morning urine voids. Conclusion Danish children are exposed simultaneously to multiple Phthalates. The highest exposure levels were found for DBP(i+n) and DEHP, which in animal models are the known most potent anti-androgenic Phthalates. The combined exposure to the two isoforms of DBP, which have similar endocrine-disrupting potencies in animal models, exceeded the TDI for di-n-butyl Phthalate (DnBP) in several of the younger children.
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correlations between Phthalate metabolites in urine serum and seminal plasma from young danish men determined by isotope dilution liquid chromatography tandem mass spectrometry
Journal of Analytical Toxicology, 2010Co-Authors: Hanne Frederiksen, Niels Jorgensen, Annamaria AnderssonAbstract:Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several Phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen metabolites were determined in samples from 60 young Danish men. Metabolites of common di-ester Phthalates were detected in most urine samples. Summed di-(2-ethylhexyl) Phthalate (DEHP) metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL), followed by monoethyl Phthalate (MEP), mono-iso-butyl Phthalate (MiBP), mono-n-butyl Phthalate (MnBP), mono-benzyl Phthalate (MBzP), and finally summed di-isononyl Phthalate (DiNP) metabolites. All these metabolite levels correlated significantly, indicating that when a participant was highly exposed to one Phthalate he was also highly exposed to other Phthalates. Several metabolites were also detectable in serum and in seminal plasma, although in much lower levels. Significant correlations between MEP and MiBP levels in serum and urine were observed, showing that serum levels could be used as biomarkers of human exposure. For DEHP and DiNP metabolites, correlations between urine and serum levels were only observed for mono(2-ethyl-5-carboxypentyl) Phthalate (MECPP) and mono-(4-methyl-7-carboxyheptyl) Phthalate (MCiOP), indicating that these secondary carboxylated metabolites were better serum markers than primary metabolites [mono(2-ethylhexyl) Phthalate (MEHP) and mono-iso-nonyl Phthalate (MiNP)]. In seminal plasma, only MEP levels correlated significantly to levels in urine and in serum.
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metabolism of Phthalates in humans
Molecular Nutrition & Food Research, 2007Co-Authors: Hanne Frederiksen, Niels E Skakkebaek, Annamaria AnderssonAbstract:Phthalates are synthetic compounds widely used as plasticisers, solvents and additives in many consumer products. Several animal studies have shown that some Phthalates possess endocrine disrupting effects. Some of the effects of Phthalates seen in rats are due to testosterone lowering effects on the foetal testis and they are similar to those seen in humans with testicular dysgenesis syndrome. Therefore, exposure of the human foetus and infants to Phthalates via maternal exposure is a matter of concern. The metabolic pathways of Phthalate metabolites excreted in human urine are partly known for some Phthalates, but our knowledge about metabolic distribution in the body and other biological fluids, including breast milk, is limited. Compared to urine, human breast milk contains relatively more of the hydrophobic Phthalates, such as di-n-butyl Phthalate and the longer-branched, di(2-ethylhexyl) Phthalate (DEHP) and di-iso-nonyl Phthalate (DiNP); and their monoester metabolites. Urine, however, contains relatively more of the secondary metabolites of DEHP and DiNP, as well as the monoester Phthalates of the more short-branched Phthalates. This differential distribution is of special concern as, in particular, the hydrophobic Phthalates and their metabolites are shown to have adverse effects following in utero and lactational exposures in animal studies.
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possible impact of Phthalates on infant reproductive health
International Journal of Andrology, 2006Co-Authors: Grete Lottrup, Niels E Skakkebaek, Annamaria Andersson, Henrik Leffers, Gerda Krog Mortensen, Jorma Toppari, Katharina M MainAbstract:Phthalates adversely affect the male reproductive system in animals, inducing hypospadias, cryptorchidism, reduced testosterone production and decreased sperm counts. Phthalate effects are much more severe after in utero than adult exposure. Little is known about human health effects. This study discusses two recent studies on perinatal Phthalate exposure, which indicated that human testicular development might be susceptible to Phthalates. One study analysed Phthalate monoesters in breast milk and reproductive hormone levels in infants. Five of six Phthalates [monoethyl-(MEP), monobutyl- (MBP), monomethyl- (MMP), mono-2-ethylhexyl- (MEHP) and mono-isononyl Phthalate (MiNP)] showed correlation with hormone levels in healthy boys, which were indicative of lower androgen activity and reduced Leydig cell function. MEP and MBP were positively correlated with serum sex hormone-binding globulin (SHBG) levels. MMP, MEP, MBP, MEHP and MiNP were positively correlated with the LH/testosterone ratio. Another study found a reduction of the anogenital index (AGI) in infant boys with increasing levels of MBP, MEP, monobenzyl- and mono-isobutyl Phthalate in maternal urine samples during late-pregnancy. Boys with small AGI showed a high prevalence of cryptorchidism and small genital size. Taken together these studies suggest an antivirilizing effect of Phthalates in infants. Most of these findings are in line with animal observations. However, the possible effects of MEP appear to be limited to humans. This may be due to differences in exposure routes (inhalation and dermal absorption which circumvents liver detoxification in addition to oral) and metabolism, or this association could be spurious. As Phthalates are produced as bulk chemicals worldwide, these new findings raise concern about the safety of Phthalate exposure for pregnant women and infants.
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urinary concentrations of biomarkers of Phthalates and Phthalate alternatives and ivf outcomes
Environment International, 2018Co-Authors: Antonia M Calafat, Ronit Machtinger, Audrey J Gaskins, Catherine Racowsky, Abdallah Mansur, Michal Adir, Andrea A Baccarelli, R. HauserAbstract:Phthalates are a class of chemicals found in a large variety of consumer products. Available experimental and limited human data show adverse effects of some Phthalates on ovarian function, which has raised concerns regarding potential effects on fertility. The aim of the current study was to determine whether urinary concentrations of metabolites of Phthalates and Phthalate alternatives are associated with intermediate and clinical in vitro fertilization (IVF) outcomes. We enrolled 136 women undergoing IVF in a Tertiary University Affiliated Hospital. Participants provided one to two urine samples per cycle during ovarian stimulation and before oocyte retrieval. IVF outcomes were abstracted from medical records. Concentrations of 17 Phthalate metabolites and two metabolites of the Phthalate alternative di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) were measured. Multivariable Poisson regression models with log link were used to analyze associations between tertiles of specific gravity adjusted Phthalate or DINCH metabolites and number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Multivariable logistic regression models were applied to evaluate the association between tertiles of specific gravity adjusted Phthalate or DINCH metabolites and probability of live birth. Urinary concentrations of the sum of di-2-ethylhexyl Phthalate metabolites (∑DEHP) and the individual metabolites mono-2-ethyl-5-hydroxyhexyl Phthalate, mono-2-ethyl-5-oxohexyl Phthalate, and mono-2-ethyl-5-carboxypentyl Phthalate were negatively associated with the number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Of the low molecular weight Phthalates, higher monoethyl Phthalate and mono-n-butyl Phthalate concentrations were associated with significantly fewer total, mature, and fertilized oocytes. None of the urinary Phthalate metabolite concentrations were associated with a reduced probability implantation, clinical pregnancy or live birth. Metabolites of DINCH were not associated with intermediate or clinical IVF outcomes. Our results suggest that DEHP may impair early IVF outcomes, specifically oocyte parameters. Additional research is needed to elucidate the potential effect of DEHP on female fertility in the general population.
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maternal and early life exposure to Phthalates the plastics and personal care products use in pregnancy p4 study
Science of The Total Environment, 2016Co-Authors: Tye E Arbuckle, R. Hauser, Mandy Fisher, Susan Macpherson, Carly Lang, Gilles Provencher, Alain Leblanc, Mark Feeley, Pierre Ayotte, Angelica NeisaAbstract:Phthalates are a group of chemicals found in a number of consumer products; some of these Phthalates have been shown to possess estrogenic activity and display anti-androgenic effects. While a number of biomonitoring studies of Phthalates in pregnant women and infants have been published, there is a paucity of data based on both multiple sampling periods and in different matrices. Phthalate metabolites were measured in 80 pregnant women and their infants in Ottawa Canada (2009-2010) in urine, meconium and breast milk collected at various time periods pre- and post-parturition. At least 50% of the women had at least one urine sample greater than the limit of detection (LOD) for the various Phthalate metabolites, with the exception of mono-n-octyl Phthalate (MnOP), mono-isononyl Phthalate (MiNP) and mono(carboxy-isooctyl) Phthalate (MCiOP). Four major clusters of maternal urinary metabolites were identified. Among infants (n=61), the following metabolites were rarely (< 10%) detected: mono-cyclohexyl Phthalate (MCHP), mono-isononyl Phthalate (MiNP), mono-methyl Phthalate (MMP), and mono-n-octyl Phthalate (MnOP). While mono-benzyl Phthalate (MBzP), mono-3-carboxypropyl Phthalate (MCPP), MEHHP, and MEOHP were frequently detected in maternal urines at any time point, these metabolites were rarely detected in breast milk. Maternal urinary concentrations of MEP and the DEHP metabolites were higher in samples collected during pregnancy than postnatally. No statistically significant differences were observed in infant's urinary Phthalate concentrations between breast-fed and bottle-fed infants. Significant correlations were observed between maternal urinary MEHHP (r=0.35), MEOHP (r=0.35) and MEP (r=0.37) collected at <20weeks gestation with levels in meconium and between MBzP (r=0.78) and MEP (r=0.56) in maternal and infant urine collected 2-3months after birth. These results suggest at least some maternal-fetal-infant transfer of Phthalates and that meconium may be a useful matrix for measuring in utero exposure to Phthalates.
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identification of Phthalates in medications and dietary supplement formulations in the united states and canada
Environmental Health Perspectives, 2011Co-Authors: Katherine E Kelley, R. Hauser, Sonia Hernandezdiaz, Erica L Chaplin, Allen A MitchellAbstract:Background: In animal studies, some ortho-Phthalates, including di(2-ethylhexyl) Phthalate (DEHP) and di-n-butyl Phthalate (DBP), have been shown to be reproductive and developmental toxicants. Human studies show widespread population exposure to background levels of Phthalates. Limited evidence suggests that particularly high exposure levels may result from orally ingested medicinal products containing Phthalates as excipients (inactive ingredients). Objective: In this study we aimed to identify and describe the scope of prescription (RX) and nonprescription (over-the-counter; OTC) medicinal products and dietary supplements marketed in the United States and Canada since 1995 that include Phthalates as excipients. Methods: We used lists of modified-release drug products to identify potential drug products. Inclusion of Phthalates was verified using available electronic databases, print references, published package inserts, product packages, and direct communication from manufacturers. Additional products were identified using Internet searches utilizing keywords for Phthalates. Results: Based on labeling information, 6 RX drug products included DBP as an excipient, and 45 specified the use of diethyl Phthalate (DEP). Phthalate polymers with no known toxicity—hypromellose Phthalate (HMP), cellulose acetate Phthalate (CAP), and polyvinyl acetate Phthalate (PVAP)—were included in 75 RX products. Three OTC drug and dietary supplement products listed DBP, 64 listed DEP, and > 90 indicated inclusion of polymers. Conclusions: Numerous RX and OTC drug products and supplements from a wide range of therapeutic categories may use DBP or DEP as excipients in oral dosage forms. The potential effects of human exposure to these Phthalates through medications are unknown and warrant further investigation.
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di 2 ethylhexyl Phthalate metabolites may alter thyroid hormone levels in men
Environmental Health Perspectives, 2007Co-Authors: John D Meeker, Antonia M Calafat, R. HauserAbstract:Human exposure to some industrial compounds may result in adverse health outcomes mediated through the neuroendocrine axis. These chemicals may affect the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the human body that are responsible for maintaining homeostasis, reproduction, development, and/or behavior [U.S. Environmental Protection Agency (EPA) 1997]. In addition to being essential for normal brain development, thyroid hormones play an important role in many physiologic systems, and alterations in thyroid hormone levels can lead to a myriad of adverse clinical conditions (Nussey and Whitehead 2001). Although much is still unknown about mechanisms and consequences involved with the relationship between environmental exposures and changes in thyroid hormone levels, Phthalates and other environmental chemicals may bind to thyroid receptors and influence thyroid hormone signaling (Zoeller 2005). Phthalates are used extensively in many personal-care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media (Hauser and Calafat 2005). High-molecular-weight Phthalates [e.g., di(2-ethylhexyl) Phthalate (DEHP)], are primarily used as plasticizers in the manufacture of flexible vinyl, which is then used in consumer products, flooring and wall coverings, food contact applications, and medical devices [Agency for Toxic Substances and Disease Registry (ATSDR) 2002; Hauser and Calafat 2005]. Low-molecular-weight Phthalates [e.g., diethyl Phthalate (DEP), dibutyl Phthalate (DBP)] are used in personal-care products (e.g., perfumes, lotions, cosmetics), as solvents and plasticizers for cellulose acetate, and in formulating lacquers, varnishes, and coatings, including those used to provide timed releases in some pharmaceuticals (ATSDR 2001; Hauser and Calafat 2005). The Centers for Disease Control and Prevention’s (CDC) Third National Report on Human Exposure to Environmental Chemicals (CDC 2005) showed that the majority of males in the United States have detectable concentrations of several Phthalate monoesters in urine [monoethyl Phthalate (MEP), mono(2-ethyl-hexyl) Phthalate (MEHP), monobutyl Phthalate (MBP), and monobenzyl Phthalate (MBzP)], reflecting widespread exposure to the parent diester compounds among the general population. Two oxidative metabolites of DEHP, mono-(2-ethyl-5-hydroxylhexyl) Phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) Phthalate (MEOHP), were present in most subjects at urinary concentrations higher than those of MEHP, the hydrolytic metabolite of DEHP (CDC 2005). Animal studies have shown that some Phthalates, namely DBP, butylbenzyl Phthalate (BBzP), and DEHP, cause testicular toxicity and other adverse male reproductive health outcomes (ATSDR 2001, 2002; Hauser and Calafat 2005), whereas human studies on Phthalate exposure and male reproductive health have been inconsistent (Duty et al. 2003a, 2003b; Hauser et al. 2006; Hauser and Calafat 2005; Jonsson et al. 2005; Murature et al. 1987; Rozatti et al. 2002). Studies investigating the association between exposure to Phthalates and thyroid function are limited. In animal studies, rats with diets contaminated with DEHP were found to have thyroid alterations and lower plasma thyroxine (T4) concentrations compared with controls (Hinton et al. 1986; Howarth et al. 2001; Poon et al. 1997; Price et al. 1988). In addition, a recent in vitro study reported that DEHP and other Phthalates caused changes in the iodide uptake of thyroid follicular cells (Wenzel et al. 2005). A dose-dependent inverse association between DBP and both triiodothyronine (T3) and T4 has also been reported in male rats (O’Connor et al. 2002). We are unaware of human studies on Phthalates and thyroid function; therefore, we designed the present study to investigate potential relations between biological markers of Phthalate exposure and levels of T4, T3, and thyroid-stimulating hormone (thyrotrophin, TSH) in adult men.
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Phthalates and human health
Occupational and Environmental Medicine, 2005Co-Authors: R. Hauser, Antonia M CalafatAbstract:The diesters of 1,2-benzenedicarboxylic acid (phthalic acid), commonly known as Phthalates, are a group of man-made chemicals with a wide spectrum of industrial applications (fig 1, table 1). High molecular weight Phthalates (for example, di(2-ethylhexyl) Phthalate [DEHP], di-isononyl Phthalate [DiNP], di-n-octyl Phthalate [DnOP]), are primarily used as plasticizers in the manufacture of flexible vinyl which, in turn, is used in consumer products, flooring and wall coverings, food contact applications, and medical devices.1–3 Manufacturers use low molecular weight Phthalates (for example, diethyl Phthalate [DEP] and dibutyl Phthalate [DBP]) in personal-care products (for example, perfumes, lotions, cosmetics), as solvents and plasticizers for cellulose acetate, and in making lacquers, varnishes, and coatings, including those used to provide timed releases in some pharmaceuticals.3–5 View this table: Table 1 Potential sources of exposure and health effects of selected Phthalates Figure 1 Generic chemical structure of Phthalates diesters and Phthalate monoester metabolites. R is an alkyl and/or aryl group: CH3 (dimethyl Phthalate), CH2CH3 (diethyl Phthalate), CH2CH2CH2CH3 (dibutyl Phthalate), CH2CH(CH2CH3)CH2CH2CH2CH3 (di[2-ethylhexyl) Phthalate), CH2CH2CH2CH3 and CH2C6H5 (butylbenzyl Phthalate). In this paper, we review the uses and metabolism of Phthalates, and the studies on health effects of Phthalates in human populations published between 1973 and June 2005. The references included in this review were searched using the Web of Science database which provides interactive citation and literature searching of the Institute for Scientific Information’s Science Citation Index Expanded. The database contains data from more than 5000 scientific journals and covers the period from 1980 to present. We also searched the bibliography cited in the selected references for additional relevant citations. Because Phthalates are widely used in …
