Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors.

PubMed

James-Todd, Tamarra M; Meeker, John D; Huang, Tianyi; Hauser, Russ; Ferguson, Kelly K; Rich-Edwards, Janet W; McElrath, Thomas F; Seely, Ellen W

2016-11-01

Epidemiologic studies suggest phthalate metabolite concentrations are associated with type 2 diabetes. GDM is a strong risk factor for type 2 diabetes. Little is known about phthalates and GDM risk factors (i.e. 1st trimester body mass index (BMI), gestational weight gain (GWG), and 2nd trimester glucose levels). A total of 350 women participating in Lifecodes pregnancy cohort (Boston, MA), delivered at term and had pregnancy urinary phthalate metabolite concentrations. Nine specific gravity-adjusted urinary phthalate metabolites were evaluated. General linear regression was used to assess associations between quartiles of phthalate metabolites and continuous 1st trimester BMI and late 2nd trimester blood glucose. Linear mixed models were used for total GWG. Multivariable logistic regression was used for phthalate concentrations and categorized GWG and impaired glucose tolerance defined as glucose≥140mg/dL based on a 50-gram glucose load test. Models were adjusted for potential confounders. There were no associations between 1st trimester urinary phthalate metabolite concentrations and 1st trimester BMI. Mono-ethyl phthalate concentrations averaged across pregnancy were associated with a 2.17 increased odds of excessive GWG (95% CI: 0.98, 4.79). Second trimester mono-ethyl phthalate was associated with increased odds of impaired glucose tolerance (adj. OR: 7.18; 95% CI: 1.97, 26.15). A summary measure of di-2-ethylhexyl phthalate metabolite concentrations were inversely associated with impaired glucose tolerance (adj. OR: 0.25; adj. 95% CI: 0.08, 0.85). Higher exposure to mono-ethyl phthalate, a metabolite of the parent compound of di-ethyl phthalate, may be associated with excessive GWG and impaired glucose tolerance; higher di-2-ethylhexyl phthalate was associated with reduced odds of impaired glucose tolerance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Associations of urinary 5-methyl-2'-deoxycytidine and 5-hydroxymethyl-2'-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men.

PubMed

Pan, Yitao; Jing, Jun; Yeung, Leo W Y; Sheng, Nan; Zhang, Hongxia; Yao, Bing; Dai, Jiayin

2016-09-01

5-methyl-2'-deoxycytidine (5mdC) and 5-hydroxymethyl-2'-deoxycytidine (5hmdC), products of DNA methylation and hydroxymethylation processes, have been detected previously in human urine, but their associations with environmental chemicals or healthy outcomes are unclear. The present investigation explored the associations between urinary 5mdC and 5hmdC with phthalate exposure and semen quality. We assessed semen parameters including sperm concentration, motility, and morphology, before measuring urinary 5mdC, 5hmdC and 13 phthalate metabolites among 562 subfertile men from Nanjing, China. Urinary 5mdC and 5hmdC were positively associated with the levels of low molecular weight phthalate metabolites (Low-MWP), high molecular weight phthalate metabolites (High-MWP), and the sum of all phthalate metabolites (ΣPAEs), respectively. Urinary 5mdC was associated with below-reference sperm concentration (odds ratios for increasing quartiles=1.0, 2.2, 3.0, 2.0; p for trend =0.02), sperm motility (1.0, 1.1, 1.9, 1.3; p for trend =0.05), and sperm morphology (1.0, 1.4, 2.3, 1.5; p for trend =0.05). Sperm concentration was associated with the highest quartile of urinary 5hmdC [odds ratio=1.9 (95% CI: 1.1, 3.6)]. Our findings showed significant associations between urinary 5mdC and 5hmdC with phthalate metabolites and semen parameters, which suggested urinary 5mdC and 5hmdC may be promising biomarkers in future epidemiological studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phthalate exposure and reproductive hormones and sex-hormone binding globulin before puberty - Phthalate contaminated-foodstuff episode in Taiwan.

PubMed

Wen, Hui-Ju; Chen, Chu-Chih; Wu, Ming-Tsang; Chen, Mei-Lien; Sun, Chien-Wen; Wu, Wen-Chiu; Huang, I-Wen; Huang, Po-Chin; Yu, Tzu-Yun; Hsiung, Chao A; Wang, Shu-Li

2017-01-01

In May 2011, a major incident involving phthalates-contaminated foodstuffs occurred in Taiwan. Di-(2-ethylhexyl) phthalate (DEHP) was added to foodstuffs, mainly juice, jelly, tea, sports drink, and dietary supplements. Concerns arose that normal pubertal development, especially reproductive hormone regulation in children, could be disrupted by DEHP exposure. To investigate the association between phthalate exposure and reproductive hormone levels among children following potential exposure to phthalate-tainted foodstuffs. A total of 239 children aged <12 years old were recruited from 3 hospitals in north, central, and south Taiwan after the episode. Structured questionnaires were used to collect the frequency and quantity of exposures to 5 categories of phthalate-contaminated foodstuffs to assess phthalate exposure in children. Urine samples were collected for the measurement of phthalate metabolites. The estimated daily intake of DEHP exposure at the time of the contamination incident occurred was calculated using both questionnaire data and urinary DEHP metabolite concentrations. Multiple regression analyses were applied to assess associations between phthalate exposure and reproductive hormone levels in children. After excluding children with missing data regarding exposure levels and hormone concentrations and girls with menstruation, 222 children were included in the statistical analyses. After adjustment for age and birth weight, girls with above median levels of urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and sum of mono-(2-ethylhexyl) phthalate concentrations had higher odds of above median follicle-stimulating hormone concentrations. Girls with above median estimated average daily DEHP exposures following the contamination episode also had higher odds of sex hormone-binding globulin above median levels. Phthalate exposure was associated with alterations of reproductive hormone levels in girls.

Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors

PubMed Central

James-Todd, TM; Meeker, JD; Huang, T; Hauser, R; Ferguson, KK; Rich-Edwards, JW; McElrath, TF; Seely, EW

2016-01-01

Background Epidemiologic studies suggest phthalate metabolite concentrations are associated with type 2 diabetes. GDM is a strong risk factor for type 2 diabetes. Little is known about phthalates and GDM risk factors (i.e. 1st trimester body mass index (BMI), gestational weight gain (GWG), and 2nd trimester glucose levels). Methods A total of 350 women participating in Lifecodes pregnancy cohort (Boston, MA), delivered at term and had pregnancy urinary phthalate metabolite concentrations. Nine specific gravity-adjusted urinary phthalate metabolites were evaluated. General linear regression was used to assess associations between quartiles of phthalate metabolites and continuous 1st trimester BMI and late 2nd trimester blood glucose. Linear mixed models were used for total GWG. Multivariable logistic regression was used for phthalate concentrations and categorized GWG and impaired glucose tolerance defined as glucose ≥ 140mg/dL based on a 50-gram glucose load test. Models were adjusted for potential confounders. Results There were no associations between 1st trimester urinary phthalate metabolite concentrations and 1st trimester BMI. Mono-ethyl phthalate (MEP) concentrations averaged across pregnancy were associated with a 2.17 increased odds of excessive GWG (95% CI: 0.98, 4.79). Second trimester MEP was associated with an increased odds of impaired glucose tolerance (adj. OR: 7.18; 95% CI: 1.97, 26.15). Di-2-ethylhexyl phthalate metabolite concentrations were inversely associated with impaired glucose tolerance (adj. OR: 0.25; adj. 95% CI: 0.08, 0.85). Conclusions Higher exposure to di-ethyl phthalate, the parent compound of MEP, may be associated with excessive GWG and impaired glucose tolerance; higher di-2-ethylhexyl phthalate was associated with reduced odds of impaired glucose tolerance. PMID:27649471

Urinary phthalate metabolites and male reproductive function parameters in Chongqing general population, China.

PubMed

Han, Xue; Cui, Zhihong; Zhou, Niya; Ma, Mingfu; Li, Lianbing; Li, Yafei; Lin, Hui; Ao, Lin; Shu, Weiqun; Liu, Jinyi; Cao, Jia

2014-03-01

This study was designed to investigate the phthalates exposure levels in general population in Chongqing City of China, and to determine the possible associations between phthalate exposure and male reproductive function parameters. We recruited 232 general men through Chongqing Family Planning Research Institute and Reproductive Center of Chongqing. In a single spot urine sample from each man, phthalate metabolites, including mono-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), mono-benzyl phthalate (MBzP), phthalic acid (PA), and total PA were analyzed using solid phase extraction and coupled with high-performance liquid chromatography and detection by tandem mass spectrometry. Semen parameters were dichotomized based on World Health Organization reference values. Sperm DNA damage were analyzed using the alkaline single-cell gel electrophoresis assay. Reproductive hormones were determined in serum by the radioimmunoassay kit. We observed a weak association between urinary MBP concentration and sperm concentration in Chongqing general population. MBP levels above the median were 1.97 times (95% confidence interval [CI] 0.97-4.04) more likely to have sperm concentration below the reference value. There were no other associations between phthalate metabolites and reproductive function parameters after adjusted for potential risk factors. Our study suggested that general population in Chongqing area of China exposure to the environmental level of phthalate have weak or without adverse effects on the reproduction. Copyright © 2013 Elsevier GmbH. All rights reserved.

PVC flooring is related to human uptake of phthalates in infants.

PubMed

Carlstedt, F; Jönsson, B A G; Bornehag, C-G

2013-02-01

Polyvinyl chloride (PVC) flooring material contains phthalates, and it has been shown that such materials are important sources for phthalates in indoor dust. Phthalates are suspected endocrine-disrupting chemicals (EDCs). Consecutive infants between 2 and 6 months old and their mothers were invited. A questionnaire about indoor environmental factors and family lifestyle was used. Urinary metabolites of the phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP), butylbenzyl phthalate (BBzP), and dietylhexyl phthalate (DEHP) were measured in the urine of the children. Of 209 invited children, 110 (52%) participated. Urine samples were obtained from 83 of these. Urine levels of the BBzP metabolite monobenzyl phthalate (MBzP) was significantly higher in infants with PVC flooring in their bedrooms (P < 0.007) and related to the body area of the infant. Levels of the DEHP metabolites MEHHP (P < 0.01) and MEOHP (P < 0.04) were higher in the 2-month-old infants who were not exclusively breast-fed when compared with breast-fed children. The findings indicate that the use of soft PVC as flooring material may increase the human uptake of phthalates in infants. Urinary levels of phthalate metabolites during early life are associated with the use of PVC flooring in the bedroom, body area, and the use of infant formula. This study shows that the uptake of phthalates is not only related to oral uptake from, for example, food but also to environmental factors such as building materials. This new information should be considered when designing indoor environment, especially for children. © 2012 John Wiley & Sons A/S.

Phthalate exposure and reproductive parameters in young men from the general Swedish population.

PubMed

Axelsson, Jonatan; Rylander, Lars; Rignell-Hydbom, Anna; Jönsson, Bo A G; Lindh, Christian H; Giwercman, Aleksander

2015-12-01

In animals, exposure to certain phthalates negatively affects the male reproductive function. Human results are conflicting and mostly based on subfertile males, in whom the association between exposure and reproductive function may differ from the general population. To study if levels of phthalate metabolites were associated with semen quality and reproductive hormones in general Swedish men. We recruited 314 young men delivering semen, urine and blood samples at the same visit. We analyzed reproductive hormones and several semen parameters including progressive motility and high DNA stainability (HDS)-a marker for sperm immaturity. In urine, we analyzed metabolites of phthalates, including diethylhexyl phthalate (DEHP). We studied associations between urinary levels of the metabolites and seminal as well as serum reproductive parameters, accounting for potential confounders. DEHP metabolite levels, particularly urinary mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), were negatively associated with progressive sperm motility, which was 11 (95% CI: 5.0-17) percentage points lower in the highest quartile of MECPP than in the lowest. Further, men in the highest quartile of the DEHP metabolite monoethylhexyl phthalate had 27% (95% CI: 5.5%-53%) higher HDS than men in the lowest quartile. DEHP metabolite levels seemed negatively associated with sperm motility and maturation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Measurement of Urinary Biomarkers of Parabens, Benzophenone-3, and Phthalates in a Belgian Population

PubMed Central

Dewalque, Lucas; Pirard, Catherine; Charlier, Corinne

2014-01-01

Parabens, benzophenone-3 (BP3), and phthalates are commonly used as antimicrobial conservator, UV-filter, and plasticizer, respectively, and are thought to exhibit endocrine disrupting properties. These endocrine disrupting activities have been recently assumed to lead to cutaneous malignant melanoma. Humans are exposed to these chemicals through different sources such as food, personal care products, or cosmetics. In this study, we measured urinary levels of 4 parabens, BP3, and 7 metabolites of phthalates in samples collected from 261 participants living in and around Liege (Belgium). The analyses were carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS) using isotopic dilution. To the best of our knowledge, this is the first time that the urinary levels of these 3 classes of chemicals are reported for the same general population in Belgium. Most of the parabens, the BP3, and all the phthalate metabolites were detected in 82.8 to 100.0% of the samples. For most of these chemicals, the exposure patterns significantly differ not only between children and adults, but also between males and females, especially with higher concentrations of parabens and phthalate metabolites in female and children subjects, respectively. PMID:24719881

Prenatal phthalate metabolite concentrations and infant fat mass across the first year of life: A pilot study

USDA-ARS?s Scientific Manuscript database

Phthalates are endocrine-disrupting chemicals associated with childhood obesity. While studies have found positive associations for certain prenatal and postnatal urinary phthalate metabolites and weight/length or BMI as indicators of adiposity levels, little is known about the direct associations b...

Associations between Repeated Measures of Maternal Urinary Phthalate Metabolites and Thyroid Hormone Parameters during Pregnancy

PubMed Central

Johns, Lauren E.; Ferguson, Kelly K.; McElrath, Thomas F.; Mukherjee, Bhramar; Meeker, John D.

2016-01-01

Background: Maintaining thyroid homeostasis during pregnancy is essential for normal fetal growth and development. Growing evidence suggests that phthalates interfere with normal thyroid function. Few human studies have investigated the degree to which phthalates may affect thyroid hormone levels in particularly susceptible populations such as pregnant women. Objectives: We examined the associations between repeated measures of urinary phthalate metabolites and plasma thyroid hormone levels in samples collected at up to four time points per subject in pregnancy. Additionally, we investigated the potential windows of susceptibility to thyroid hormone disturbances related to study visit of sample collection. Methods: Data were obtained from pregnant women (n = 439) participating in a nested case–control study of preterm birth with 116 cases and 323 controls. We measured 9 phthalate metabolite concentrations in urine samples collected at up to four study visits per subject during pregnancy (median = 10, 18, 26, and 35 weeks of gestation, respectively). We also measured a panel of thyroid function markers in plasma collected at the same four time points per subject during pregnancy. Results: Although our results were generally null, in repeated measures analyses we observed that phthalate metabolites were largely inversely associated with thyrotropin and positively associated with free and total thyroid hormones. Cross-sectional analyses by study visit revealed that the magnitude and/or direction of these relationships varied by timing of exposure during gestation. Conclusions: These results support previous reports showing the potential for environmental phthalate exposure to alter circulating levels of thyroid hormones in pregnant women. Citation: Johns LE, Ferguson KK, McElrath TF, Mukherjee B, Meeker JD. 2016. Associations between repeated measures of maternal urinary phthalate metabolites and thyroid hormone parameters during pregnancy. Environ Health Perspect 124:1808–1815; http://dx.doi.org/10.1289/EHP170 PMID:27152641

Associations between urinary phthalate concentrations and semen quality parameters in a general population

PubMed Central

Bloom, M.S.; Whitcomb, B.W.; Chen, Z.; Ye, A.; Kannan, K.; Buck Louis, G.M.

2015-01-01

STUDY QUESTION Are urinary phthalate concentrations associated with altered semen quality parameters among males recruited from the general population? SUMMARY ANSWER Urinary levels of metabolites of phthalate diesters are associated with lower total sperm counts, larger sperm head sizes, and higher percentages of morphologically abnormal sperm. WHAT IS KNOWN ALREADY High dose experiments in rats implicate phthalates as anti-androgens. Studies involving infertile men seeking care suggest that phthalates influence measures of semen quality raising concern about the implications for men in the general population. STUDY DESIGN, SIZE, DURATION This prospective cohort study comprised 501 male partners in couples discontinuing contraception to become pregnant, who were recruited from 16 US counties using population-based sampling frameworks from 2005 to 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS Urine and semen samples were obtained at baseline from 473 (94%) men, of whom 378 (80%) men provided a second sample the following month. Urine was analyzed for 14 monoester metabolites of phthalate diesters by high-performance liquid chromatography coupled to tandem mass spectrometry. Semen samples were analyzed for 34 quality parameters categorized as general, motility, morphology, sperm head and sperm chromatin structure. MAIN RESULTS AND THE ROLE OF CHANCE Urinary mono-[2-(carboxymethyl) hexyl] phthalate (MCMHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), and mono-isononyl phthalate (MNP) were significantly associated with lower total sperm counts and concentrations, larger sperm head sizes, higher proportions of megalo head sperm morphology, and/or other morphological changes. Urinary mono-methyl phthalate (MMP) and mono-cyclohexyl phthalate (MCPP) were significantly associated with lower sperm motility, and urine mono-2-ethylhexyl phthalate (MEHP) was significantly associated with higher sperm motility. LIMITATIONS, REASONS FOR CAUTION While adverse associations were observed, the implications of the findings for couple fecundity and fertility remain to be established. Cautious interpretation is needed in light of reliance on a single measurement of phthalate measure and no correction for multiple comparisons. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01-HD-3-3355, N01-HD-3-3356 and NOH-HD-3-3358). The authors declare they have no actual or potential competing financial interests. PMID:26350610

Characterization of phthalates exposure and risk for cosmetics and perfume sales clerks.

PubMed

Huang, Po-Chin; Liao, Kai-Wei; Chang, Jung-Wei; Chan, Shiou-Hui; Lee, Ching-Chang

2018-02-01

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 < 0.05) and the post-shift levels of urinary MMP was significantly higher than the corresponding pre-shift levels in perfume group (26.6 vs. 14.9 μg/g-c, P < 0.05). Median levels of air diethyl phthalate (DEP) in cosmetics (1.77 μg/m 3 ) and perfume (1.75 μg/m 3 ) groups and di-(2-ethylhexyl) phthalate (DEHP) in perfume group (6.98 μg/m 3 ) were higher than those in clothing group (DEP: 0.89; DEHP: 2.16 μg/m 3 ). Over half of cosmetic (70%) and perfume sale clerks had exceeded cumulative risk of phthalate exposure for anti-androgenic effect. We concluded that cosmetic and perfume workers had increased risks of reproductive or hepatic effects for DBP and DEHP exposure. We suggest that not only inhalation but dermal exposure is important route of phthalate exposure for cosmetics and perfume workers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association Between Urinary Phthalates and Pubertal Timing in Chinese Adolescents

PubMed Central

Shi, Huijing; Cao, Yang; Shen, Qing; Zhao, Yan; Zhang, Zhe; Zhang, Yunhui

2015-01-01

Background Phthalates are synthetic chemicals and ubiquitous environmental contaminants, with hormonal activity that may alter the course of pubertal development in children. Objectives To determine whether exposure to phthalate metabolites is associated with timing of pubertal development in a cross-sectional study of a school-based clustered sample of 503 children from a suburban district in Shanghai, China, who were 7–14 years of age at enrollment (2010 October to November). Methods We analyzed six phthalate metabolites in urine samples by isotope-dilution liquid chromatography tandem mass spectrometry. The associations of exposures to phthalates with pubertal timing of testes, breast, and pubic hair development (represented as Tanner stages) were evaluated using an ordered logistic regression model adjusted for chronological age, body fat proportion (BF%), and parental education. Results In boys, urinary mono-n-butyl phthalate (MBP) levels were negatively associated with testicular volume, and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) levels were negatively associated with pubic hair stages. The odds of being in an advanced stage were decreased by 43%–51%. In girls, mono (2-ethylhexyl) phthalate (MEHP), MEHHP, and MEOHP levels, as well as the sum of these levels, were positively associated with breast stages, and the association was much stronger in girls with high BF%; the odds of being in an advanced stage were increase by 29% to 50%. Conclusions Phthalate metabolites investigated in this study show significant associations with pubertal timing both in boys and in girls, especially among girls with high BF%. PMID:26212725

Urinary arsenic, pesticides, heavy metals, phthalates, polyaromatic hydrocarbons, and polyfluoroalkyl compounds are associated with sleep troubles in adults: USA NHANES, 2005-2006.

PubMed

Shiue, Ivy

2017-01-01

Links between environmental chemicals and human health have emerged, but the effects on sleep health were less studied. Therefore, the aim of the present study was to investigate the relationships of different sets of environmental chemicals and common sleep troubles in a national and population-based setting. Data were retrieved from the United States National Health and Nutrition Examination Surveys, 2005-2006 including demographics, serum measurements, lifestyle factors, self-reported sleep troubles, and urinary environmental chemical concentrations. Statistical analyses including descriptive statistics, t-test, chi-square test, and survey-weighted logistic regression models were performed. Of all 5563 Americans aged 18-85, 2331 (42.0%) had wake-up at night, 2914 (52.5%) felt unrested during the day, 740 (13.4%) had leg jerks while sleeping, and 1059 (19.1%) had leg cramps for 2+ times a month. Higher levels of urinary arsenic, phthalates, and polyfluoroalkyl compounds were associated with wake-up at night. Higher levels of urinary 4-tert-octylphenol and polyfluoroalkyl compounds were associated with being unrested during the day. Higher levels of urinary arsenic, polyaromatic hydrocarbons, and polyfluoroalkyl compounds were associated with leg jerks while sleeping. Higher levels of urinary pesticides, heavy metals, phthalates, and polyaromatic hydrocarbons were associated with leg cramps while sleeping. However, there were no significant associations with other environmental chemicals such as parabens, bisphenol A, benzophenone-3, triclosan, perchlorate, nitrate, or thiocyanate. Eliminating arsenic, heavy metals, phthalate, pesticides, polyaromatic hydrocarbons, and polyfluoroalkyl compounds to improve sleep health might be considered while understanding the biological pathway with a longitudinal or experimental approach in future research would be suggested.

Phthalates and risk of endometriosis

PubMed Central

Upson, Kristen; Sathyanarayana, Sheela; De Roos, Anneclaire J.; Thompson, Mary Lou; Scholes, Delia; Dills, Russell; Holt, Victoria L.

2013-01-01

Background Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood. Objective To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women. Methods We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year. Results The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1–0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ΣDEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant. Conclusions Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women. PMID:23890968

Third trimester phthalate exposure is associated with DNA methylation of growth-related genes in human placenta

NASA Astrophysics Data System (ADS)

Zhao, Yan; Chen, Jiao; Wang, Xiu; Song, Qi; Xu, Hui-Hui; Zhang, Yun-Hui

2016-09-01

Strong evidence implicates maternal phthalate exposure during pregnancy in contributing to adverse birth outcomes. Recent research suggests these effects might be mediated through the improper regulation of DNA methylation in offspring tissue. In this study, we examined associations between prenatal phthalate exposure and DNA methylation in human placenta. We recruited 181 mother-newborn pairs (80 fetal growth restriction newborns, 101 normal newborns) in Wenzhou, China and measured third trimester urinary phthalate metabolite concentrations and placental DNA methylation levels of IGF2 and AHRR. We found urinary concentrations of mono (2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were significantly inversely associated with placental IGF2 DNA methylation. The associations were much more evident in fetal growth restriction (FGR) newborns than those in normal newborns. These findings suggest that changes in placental DNA methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth.

Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study.

PubMed

Hauser, Russ; Gaskins, Audrey J; Souter, Irene; Smith, Kristen W; Dodge, Laura E; Ehrlich, Shelley; Meeker, John D; Calafat, Antonia M; Williams, Paige L

2016-06-01

Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831-839; http://dx.doi.org/10.1289/ehp.1509760.

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment.

PubMed

Wu, Haotian; Olmsted, Alexandra; Cantonwine, David E; Shahsavari, Shahin; Rahil, Tayyab; Sites, Cynthia; Pilsner, J Richard

2017-02-01

Epidemiological data suggest associations between phthalate exposures to a variety of adverse reproductive outcomes including reduced sperm quality and reproductive success. While mechanisms of these associations are not fully elucidated, oxidative stress has been implicated as a potential mediator. We examined associations of urinary metabolites of phthalates and phthalate alternative plasticizers with oxidative stress among couples seeking fertility treatment. Seventeen urinary plasticizer metabolites and 15-F2t isoprostane, a biomarker of oxidative stress, were quantified in spot samples from 50 couples seeking fertility treatment who enrolled in the Sperm Environmental Epigenetics and Development Study during 2014-2015. In multivariable analyses, percent change in isoprostane was positively associated with interquartile range increases for the oxidative metabolites of di-2-ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%, p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2-ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003), and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%, p=0.002). Stratification of participants by sex revealed that isoprostane was positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males. Our results suggest that exposure to phthalates and phthalate replacements are associated with higher levels of oxidative stress in a sex-specific manner. Additional studies are needed to replicate our findings and to examine the potential health implications of the use of phthalates and alternative phthalates in consumer end products. Copyright © 2016 Elsevier Inc. All rights reserved.

Life without plastic: A family experiment and biomonitoring study.

PubMed

Hutter, Hans-Peter; Kundi, Michael; Hohenblum, Philipp; Scharf, Sigrid; Shelton, Janie F; Piegler, Kathrin; Wallner, Peter

2016-10-01

Exposure to bisphenol-A (BPA) and phthalates has been associated with negative health outcomes in animal and human studies, and human bio-monitoring studies demonstrate widespread exposure in the US and Europe. Out of concern for the environment and health, individuals may attempt to modify their environment, diet, and consumer choices to avoid such exposures, but these natural experiments are rarely if ever quantitatively evaluated. The aim of the study was to evaluate the difference in urinary concentrations of BPA and phthalate metabolites following an exposure reduction intervention among an Austrian family of five. Urine samples were taken shortly after the family had removed all plastic kitchenware, toys, and bathroom products, and started a concerted effort to eat less food packaged in plastic. Two-months later, urine samples were collected at a follow-up visit, and concentrations of BPA and phthalate metabolites were compared. Shortly after removal of plastic urinary concentrations of BPA were below limit of quantification in all samples. Phthalate concentrations were low, however, 10 of 14 investigated metabolites could be found above limit of quantification. After the two-month intervention, phthalate urinary concentrations had declined in some but not all family members. In the mother most phthalate metabolites increased. The low levels might be partly due to the environmentally conscious lifestyle of the family and partly due to the fact that body levels had dropped already because of the delay of four days between finishing removal and first measurement. Further two months avoidance of dietary exposure and exposure to environmental plastics reduced urinary concentrations for all but one metabolite in the oldest son only, but decreased somewhat in all family members except the mother. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect modification by apoptosis-related gene polymorphisms on the associations of phthalate exposure with spermatozoa apoptosis and semen quality.

PubMed

Yang, Pan; Gong, Ya-Jie; Wang, Yi-Xin; Liang, Xin-Xiu; Liu, Qing; Liu, Chong; Chen, Ying-Jun; Sun, Li; Lu, Wen-Qing; Zeng, Qiang

2017-12-01

Human studies indicate that phthalate exposure is associated with adverse male reproductive health, and this association may be modified by genetic polymorphisms. We investigated whether apoptosis-related gene polymorphisms modified the associations of phthalate exposure with spermatozoa apoptosis and semen quality. In this Chinese population who sought for semen examination in an infertility clinic, we measured 8 phthalate metabolites in two urine samples to assess the individual's exposure levels. Apoptosis-related gene (Fas, FasL, and caspase3) polymorphisms were performed by real-time PCR. Spermatozoa apoptosis and semen quality parameters were evaluated by Annexin V/PI assay and computer-aided semen analysis, respectively. We found that Fas rs2234767, FasL rs763110, and caspase3 rs12108497 gene polymorphisms significantly modified the associations between urinary phthalate metabolites and spermatozoa apoptosis. For example, urinary monobutyl phthalate (MBP) associated with an increased percentage of Annexin V + /PI - spermatozoa of 25.11% (95% CI: 4.08%, 50.53%) were only observed among men with CT/TT genotype of FasL rs763110. In addition, we found that caspase3 rs12108497 gene polymorphisms significantly modified the associations of urinary mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with decreased sperm concentration and sperm count (both p-values for interactions = 0.02). Our results provided the first evidence that apoptosis-related gene polymorphisms might contribute to the effects of phthalate exposure on male reproductive health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study

PubMed Central

Hauser, Russ; Gaskins, Audrey J.; Souter, Irene; Smith, Kristen W.; Dodge, Laura E.; Ehrlich, Shelley; Meeker, John D.; Calafat, Antonia M.; Williams, Paige L.

2015-01-01

Background: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. Objective: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). Methods: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004–2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. Results: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were –0.19 (–0.29, –0.08) and –0.19 (–0.28, –0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. Conclusions: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. Citation: Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831–839; http://dx.doi.org/10.1289/ehp.1509760 PMID:26545148

Associations between paternal urinary phthalate metabolite concentrations and reproductive outcomes among couples seeking fertility treatment

PubMed Central

Dodge, LE; Williams, PL; Williams, MA; Missmer, SA; Souter, I; Calafat, AM; Hauser, R

2015-01-01

INTRODUCTION Limited evidence suggests that male exposure to ubiquitous environmental phthalates may result in poor reproductive outcomes among female partners. METHODS This analysis included male-female couples undergoing in vitro fertilization (IVF) and/or intrauterine insemination (IUI). We evaluated associations between the geometric mean of paternal specific gravity-adjusted urinary phthalate concentrations prior to the female partners’ cycle and fertilization, embryo quality, implantation, and live birth using generalized linear mixed models. RESULTS Two-hundred eighteen couples underwent 211 IVF and 195 IUI cycles. Trends were observed between paternal urinary mono-3-carboxypropyl phthalate (MCPP; P=0.01) and mono(carboxyoctyl) phthalate (MCOP; P=0.01) and decreased odds of implantation. MCPP and MCOP were also associated with decreased odds of live birth following IVF (P=0.01 and P=0.04, respectively), and monobutyl phthalate above the first quartile was significantly associated with decreased odds of live birth following IUI (P=0.04). However, most urinary phthalate metabolites were not associated with these reproductive outcomes. CONCLUSION Selected phthalates were associated with decreased odds of implantation and live birth. PMID:26456810

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment.

PubMed

Wu, Haotian; Ashcraft, Lisa; Whitcomb, Brian W; Rahil, Tayyab; Tougias, Ellen; Sites, Cynthia K; Pilsner, J Richard

2017-01-01

Are preconception urinary concentrations of phthalates and phthalate alternatives associated with diminished early stage embryo quality in couples undergoing IVF? Male, but not female, urinary concentrations of select metabolites of phthalates and phthalate alternatives are associated with diminished blastocyst quality. Although phthalates are endocrine disrupting compounds associated with adverse reproductive health, they are in widespread use across the world. Male and female preconception exposures to select phthalates have been previously associated with adverse reproductive outcomes in both the general population and in those undergoing IVF. This prospective cohort included 50 subfertile couples undergoing IVF in western Massachusetts. This study includes the first 50 couples recruited from the Baystate Medical Center's Fertility Center in Springfield, MA, as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Relevant data from both partners, including embryo quality at the cleavage (Day 3) and blastocyst (Day 5) stages, were collected by clinic personnel during the normal course of an IVF cycle. A spot urine sample was collected from both male and female partners on the same day as semen sample procurement and oocyte retrieval. Concentrations of 17 urinary metabolite were quantified by liquid chromatography mass spectrometry and normalized via specific gravity. Generalized estimating equations were used to estimate odds ratios (OR) and 95% CI, with urinary phthalates and phthalate alternatives fitted as continuous variables and embryo quality as a binary variable. The 50 couples contributed 761 oocytes, of which 423 progressed to the cleavage stage, 261 were high-quality cleavage stage embryos, 137 were transferrable quality blastocysts and 47 were high-quality blastocysts. At the cleavage stage, male urinary monoethyl phthalate concentrations were positively associated with high-quality cleavage stage embryos (OR = 1.20, 95% CI 1.01-1.43, P = 0.04); no other significant associations were observed at this stage. At the blastocyst stage, male urinary concentrations of monobenzyl phthalate (OR = 0.55, 95% CI 0.36-0.84, P = 0.01), mono-3-hydroxybutyl phthalate (OR = 0.37, 95% CI 0.18-0.76, P = 0.01), mono-n-butyl phthalate (OR = 0.55, 95% CI 0.42-0.73, P < 0.01) and monomethyl phthalate (OR = 0.39, 95% CI 0.26-0.60, P < 0.01) were inversely associated with high-quality blastocysts. A borderline statistically significant relationship was observed for male concentrations of mono(2-ethylhexyl) phthalate (OR = 0.52, 95% CI 0.27-1.00, P = 0.05) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (OR = 0.21, 95% CI 0.04-1.03, P = 0.05) at the blastocyst stage. Similar inverse associations were observed between male urinary phthalate metabolite concentrations and likelihood of transferrable quality blastocysts. For female partners, select metabolites were positively associated with odds of high or transferrable blastocyst quality, but the observed associations were not consistent across blastocyst quality measures or between sex-specific and couples-level models. All models were adjusted for age of both partners, urinary metabolite concentrations of female partners and male infertility status, while models of blastocysts were additionally adjusted for embryo quality at cleavage stage. Our modest sample included only 50 couples contributing one cycle each. In addition, non-differential misclassification of exposure remains a concern given the single-spot urine collection and the short half-life of phthalates. Our results suggest an inverse association between male preconception concentrations of select phthalate metabolites and blastocyst quality, likely occurring after genomic activation. If corroborated with other studies, such findings will have public health and clinical significance for both the general population and those undergoing IVF. This work was generously supported by grant K22-ES023085 from the National Institute of Environmental Health Sciences. The authors declare no competing interests. N/A. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones

PubMed Central

Tsai, Chih-Hsin; Liang, Wei-Yen; Li, Sih-Syuan; Huang, Han-Bin

2016-01-01

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. PMID:27455052

Characterization of Urinary Phthalate Metabolites Among Custodians

PubMed Central

Cavallari, Jennifer M.; Simcox, Nancy J.; Wakai, Sara; Lu, Chensheng; Garza, Jennifer L.; Cherniack, Martin

2015-01-01

Phthalates, a ubiquitous class of chemicals found in consumer, personal care, and cleaning products, have been linked to adverse health effects. Our goal was to characterize urinary phthalate metabolite concentrations and to identify work and nonwork sources among custodians using traditional cleaning chemicals and ‘green’ or environmentally preferable products (EPP). Sixty-eight custodians provided four urine samples on a workday (first void, before shift, end of shift, and before bedtime) and trained observers recorded cleaning tasks and types of products used (traditional, EPP, or disinfectant) hourly over the work shifts. Questionnaires were used to assess personal care product use. Four different phthalate metabolites [monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethylhexyl) phthalate (MEHP), and monobenzyl phthalate (MBzP)] were quantified using liquid chromatography mass spectrometry. Geometric means (GM) and 95% confidence intervals (95% CI) were calculated for creatinine-adjusted urinary phthalate concentrations. Mixed effects univariate and multivariate modeling, using a random intercept for each individual, was performed to identify predictors of phthalate metabolites including demographics, workplace factors, and personal care product use. Creatinine-adjusted urinary concentrations [GM (95% CI)] of MEP, MMP, MEHP, and MBzP were 107 (91.0–126), 2.69 (2.18–3.30), 6.93 (6.00–7.99), 8.79 (7.84–9.86) µg g−1, respectively. An increasing trend in phthalate concentrations from before to after shift was not observed. Creatinine-adjusted urinary MEP was significantly associated with frequency of traditional cleaning chemical intensity in the multivariate model after adjusting for potential confounding by demographics, workplace factors, and personal care product use. While numerous demographics, workplace factors, and personal care products were statistically significant univariate predictors of MMP, MEHP, and MBzP, few associations persisted in multivariate models. In summary, among this population of custodians, we identified both occupational and nonoccupational predictors of phthalate exposures. Identification of phthalates as ingredients in cleaning chemicals and consumer products would allow workers and consumers to avoid phthalate exposure. PMID:26240196

Mono-2-ethylhexyl phthalate associated with insulin resistance and lower testosterone levels in a young population.

PubMed

Chen, Szu-Ying; Hwang, Jing-Shiang; Sung, Fung-Chang; Lin, Chien-Yu; Hsieh, Chia-Jung; Chen, Pau-Chung; Su, Ta-Chen

2017-06-01

Phthalates are commonly used as plasticizers and are reported to associate with testicular dysfunction or insulin resistance in different studies, but the concurrent relationship between phthalate exposure, testosterone levels, and insulin resistance in the young population is not well understood. We recruited 786 subjects aged 12-30 years from a population-based sample of Taiwanese adolescents and young adults from 2006 to 2008. Generalized additive models were used to evaluate glucose homeostasis and testicular function in relation to seven urinary phthalate metabolites among adolescents (aged 12-20) and young adults (aged 20-30) in Taiwan. We observed a trend toward a decrease in male testosterone and an increase in urinary mono-2-ethylhexyl phthalate (MEHP) levels across four quartiles of homeostasis model assessment of insulin resistance (HOMA-IR). After adjusting for potential covariates, generalized additive models further showed that log-transformed insulin and HOMA-IR were raised by 0.055 [95% confidence interval (CI), 0.027-0.082] and 0.056 (95% CI, 0.027-0.084), respectively, with a one-unit increase in log-transformed MEHP in young adults. In male adults (aged 22-30), the log-testosterone levels were reduced by 0.018 (95% CI, 0.001-0.036), with a one-unit of increase in log-transformed MEHP. Such relationships were not observed in adolescents. In conclusion, this study demonstrated age-related associations of urinary MEHP metabolites with impaired metabolic homeostasis of glucose that were only observed in young adults. In addition, MEHP exposure was concurrently associated with lower testosterone levels in young, male adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Women’s exposure to phthalates in relation to use of personal care products

PubMed Central

Parlett, Lauren E.; Calafat, Antonia M.; Swan, Shanna H.

2014-01-01

Background Several phthalates, particularly diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP), can be used in personal care products (PCPs) to fix fragrance and hold color. We investigated associations between women’s reported use of personal care products within the 24 hours prior to urine collection and concentrations of several urinary phthalate metabolites. Methods Between 2002–2005, 337 women provided spot urine samples and answered questions regarding their use of thirteen PCPs at a follow-up visit 3–36 months after pregnancy. We examined associations between urinary concentrations of several phthalate metabolites and use of PCPs using linear regression. Results Use of individual PCPs ranged from 7% (nail polish) to 91% (deodorant). After adjusting for age, education, and urinary creatinine, women reporting use of perfume had 2.92 times higher (95% CI: 2.20–3.89) concentration of monoethyl phthalate (MEP, the primary metabolite of diethyl phthalate) than other women. Other PCPs that were significantly associated with MEP included: hair spray, nail polish, and deodorant. MEP concentrations increased with the number of PCPs used. Conclusion PCP use was widespread in this group of recently pregnant women. Women’s use of PCPs, particularly of perfumes and fragranced products, was positively associated with urinary concentration of multiple phthalate metabolites. PMID:23168567

Exposure sources and their relative contributions to urinary phthalate metabolites among children in Taiwan.

PubMed

Chen, Chu-Chih; Wang, Yin-Han; Wang, Shu-Li; Huang, Po-Chin; Chuang, Shu-Chun; Chen, Mei-Huei; Chen, Bai-Hsiun; Sun, Chien-Wen; Fu, Hsiao-Chun; Lee, Ching-Chang; Wu, Ming-Tsang; Chen, Mei-Lien; Hsiung, Chao A

2017-07-01

Phthalate exposure is omnipresent and known to have developmental and reproductive effects in children. The aim of this study was to determine the phthalate exposure sources and their relative contributions among children in Taiwan. During the first wave of the Risk Assessment of Phthalate Incident in Taiwan (RAPIT), in 2012, we measured 8 urinary phthalate metabolites in 226 children aged 1-11 years old and in 181 children from the same cohort for the wave 2 study in 2014. A two-stage statistical analysis approach was adopted. First, a stepwise regression model was used to screen 80 questions that explored the exposure frequency and lifestyle for potential associations. Second, the remaining questions with positive regression coefficients were grouped into the following 6 exposure categories: plastic container/packaging, food, indoor environment, personal care products, toys, and eating out. A mixed model was then applied to assess the relative contributions of these categories for each metabolite. The use of plastic container or food packaging were dominant exposure sources for mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). The indoor environment was a major exposure source of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), and mono-isobutyl phthalate (MiBP). The consumption of seafood showed a significant correlation with MEHP. The children's modified dietary behavior and improved living environment in the second study wave were associated with lower phthalate metabolite levels, showing that phthalate exposures can be effectively reduced. Copyright © 2017 Elsevier GmbH. All rights reserved.

Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study.

PubMed

Romano, Megan E; Eliot, Melissa N; Zoeller, R Thomas; Hoofnagle, Andrew N; Calafat, Antonia M; Karagas, Margaret R; Yolton, Kimberly; Chen, Aimin; Lanphear, Bruce P; Braun, Joseph M

2018-05-01

Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent. In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women and newborns. We measured nine phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at approximately 16 and 26 weeks' gestation among women in the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum at 16 weeks' gestation (n = 202) and cord serum at delivery (n = 276). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal or cord serum thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones. With each 10-fold increase in 16-week maternal urinary MEP, maternal serum total thyroxine (TT 4 ) decreased by 0.52 μg/dL (95% CI: -1.01, -0.03). For each 10-fold increase in average (16- and 26-week) maternal urinary MBzP, cord serum TSH decreased by 19% (95% CI: -33.1, -1.9). Among mothers, the phthalate index was inversely associated with maternal serum TT 4 (WQS beta = -0.60; 95% CI: -1.01, -0.18). Among newborns, the phthalate index was inversely associated with both cord serum TSH (WQS beta = -0.11; 95% CI: -0.20, -0.03) and TT 4 (WQS beta = -0.53; 95% CI: -0.90, -0.16). Our results suggest that co-exposure to multiple phthalates was inversely associated with certain thyroid hormones (TT 4 in pregnant women and newborns, and TSH in newborns) in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology. Copyright © 2018 Elsevier GmbH. All rights reserved.

Urinary phthalate metabolites and their biotransformation products: predictors and temporal variability among men and women

PubMed Central

Meeker, John D.; Calafat, Antonia M.; Hauser, Russ

2012-01-01

Most epidemiology studies investigating potential adverse health effects in relation to phthalates measure the urinary concentration of the free plus glucuronidated species of phthalate metabolites (i.e., total concentration) to estimate exposure. However, the free species may represent the biologically relevant dose. In this study, we collected 943 urine samples from 112 men and 157 women and assessed the between- and within-person variability and predictors of a) the free and total urinary concentrations of phthalate metabolites, and b) the percentage of free phthalate metabolites (a potential phenotypic indicator of individual susceptibility). We also explored the proportion of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolites contributed to by the bioactive mono-2-ethylhexyl phthalate (MEHP), considered a possible indicator of susceptibility to phthalate exposure. The percentage of phthalate metabolites present in the free form were less stable over time than the total metabolite concentration, and, therefore, it is not likely a useful indicator of metabolic susceptibility. Thus, the added costs and effort involved in the measurement of free in addition to total metabolite concentrations in large-scale studies may not be justified. Conversely, the proportion of DEHP metabolites contributed to by MEHP was more stable within individuals over time and may be a promising indicator of susceptibility if time of day of sample collection is carefully considered. PMID:22354176

Variability in urinary phthalate metabolite levels across pregnancy and sensitive windows of exposure for the risk of preterm birth

PubMed Central

Ferguson, Kelly K.; McElrath, Thomas F.; Ko, Yi-An; Mukherjee, Bhramar; Meeker, John D.

2014-01-01

Background Preterm birth is a significant public health problem, affecting over 1 in 10 live births and contributing largely to infant mortality and morbidity. Everyday exposure to environmental chemicals such as phthalates could contribute, and may be modifiable. In the present study we examine variability in phthalate exposure across gestation and identify windows of susceptibility for the relationship with preterm birth. Methods Women were recruited early in pregnancy as part of a prospective, longitudinal birth cohort at the Brigham and Women’s Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points during gestation for phthalate measurement, and birth outcomes were recorded at delivery. From this population we selected all 130 cases of preterm birth, defined as delivery before 37 weeks completed gestation, as well as 352 random controls. Results Urinary phthalate metabolite levels were moderately variable over pregnancy, but levels measured at multiple time points were associated with increased odds of preterm birth. Adjusted odds ratios (aOR) for spontaneous preterm birth were strongest in association with phthalate metabolite concentrations measured at the beginning of the third trimester (aOR for summed di-2-ethylhexyl phthalate metabolites [∑DEHP]=1.33, 95% confidence interval [CI]=1.02, 1.73). Odds ratios for placental preterm birth, defined as delivery with presentation of preeclampsia or intrauterine growth restriction, were slightly elevated in the first trimester for DEHP metabolites (aOR for ∑DEHP=1.33, 95% CI=0.99, 1.78). Conclusions Pregnant women with exposure to phthalates both early and late in pregnancy are at increased risk of delivering preterm, but mechanisms may differ based on etiology. PMID:24934852

Variability and Predictors of Urinary Concentrations of Phthalate Metabolites during Early Childhood

PubMed Central

2015-01-01

The variability and predictors of urinary concentrations of phthalate metabolites in preschool-aged children have not been thoroughly examined. Additionally, the impact of temporal changes in the use and restriction of phthalates in children’s products has not been assessed. Our objective was to identify demographic, behavioral, and temporal predictors of urinary phthalate metabolite concentrations in young children. Between 2004 and 2011, we collected up to five urine samples from each of 296 children participating in a prospective birth cohort during annual study visits at ages 1–5 years. We used linear mixed models to calculate intraclass correlation coefficients (ICCs), a measure of within-individual reproducibility, and identify demographic predictors of urinary phthalate metabolites. We used multivariable linear regression to examine cross-sectional relationships between food packaging or personal care product use and phthalate metabolites measured at age 5 years. Across annual measurements, monoethyl phthalate exhibited the least variation (ICC = 0.38), while di-2-ethylhexyl phthalate (ΣDEHP) metabolites exhibited the most variation (ICC = 0.09). Concentrations changed with age, suggesting age-related changes in phthalate exposure and perhaps metabolism. Our findings suggest that fast food consumption may be a source of butylbenzyl phthalate and di-isononyl phthalate (DiNP) exposure, and some personal care products may be sources of diethyl phthalate exposure. Concentrations of ΣDEHP metabolites decreased over the study period; however, concentrations of DiNP metabolites increased. This finding suggests that manufacturer practices and regulations, like the Consumer Product Safety Improvement Act of 2008, may decrease DEHP exposure, but additional work characterizing the nature and toxicity of replacements is critically needed. PMID:24977926

Occupational exposure to phthalates in relation to gender, consumer practices and body composition.

PubMed

Petrovičová, Ida; Kolena, Branislav; Šidlovská, Miroslava; Pilka, Tomáš; Wimmerová, Soňa; Trnovec, Tomáš

2016-12-01

The aim of our work was to find associations between urinary phthalate metabolite concentrations and occupation, consumer practices and body composition. We divided our cohort (n = 129) into occupationally exposed subjects, community service workers (group A; n = 45) and workers from plastic industry (group B; n = 35) and group of general population (control group C, n = 49). To estimate levels of five phthalate metabolites, we used high-performance liquid chromatography and tandem mass spectrometry analysis. We found in plastic industry workers compared to community service workers and subjects of the control group significantly higher urinary concentration mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-etylhexyl) phthalate (MEHP), sum di-(2-ethyl-5-oxohexyl) phthalate (DEHP), mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP). We identified by multivariate analysis of covariance inverse relationship between MEHP and body parameters as waist-to-height ratio, body mass index, waist-to-hip ratio, hip circumference and waist circumference among females, whereas in males, no significant association was found. Results of our study show, despite of variability in terms of occupational exposure to phthalates, that plastic manufactory represents a higher occupational risk in comparison with waste management. The differences in anthropometric parameters between the two occupationally exposed groups and the general population are suggesting a detrimental effect of occupational exposure on body weight homeostasis.

Elevated phthalates' exposure in children with constitutional delay of growth and puberty.

PubMed

Xie, Changming; Zhao, Yan; Gao, Lianlian; Chen, Jiao; Cai, Depei; Zhang, Yunhui

2015-05-15

Phthalates have been proven to be antiandrogenic, which may interfere with the timing of puberty. Children with Constitutional Delay of Growth and Puberty (CDGP) typically display short stature and pubertal delay. This study investigated whether phthalate's exposure was associated with CDGP, and evaluated the potential mediator role of testosterone. In this case-control study, a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were enrolled. We measured six major phthalate metabolites in urine samples using high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). The serum testosterone level was determined by radioimmunoassay. Children in the CDGP group were determined to have significantly elevated urinary phthalates concentration compared with control subjects (total phthalates median: case, 107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate (MEP) and total phthalate concentrations were significantly negatively associated with serum testosterone level (MBP: β = -45.7, p = 0.017; MEP: β = -31.6, p = 0.022; total phthalates: β = -24.6, p = 0.011); MBP, MEP, mono (2-ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a mediator of the association between phthalates' exposure and CDGP (p = 0.002) (proportion mediated: 34.4%). In this case-control study, elevated phthalates' level was detected in children with CDGP in Shanghai, China and phthalate level was associated with CDGP, which appeared to be mediated by circulating testosterone level. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In vitro effects of phthalate esters in human myometrial and leiomyoma cells and increased urinary level of phthalate metabolite in women with uterine leiomyoma.

PubMed

Kim, Jin Hee; Kim, Sung Hoon; Oh, Young Sang; Ihm, Hyo Jin; Chae, Hee Dong; Kim, Chung-Hoon; Kang, Byung Moon

2017-04-01

To investigate the possible role of phthalate, a ubiquitous chemical used in consumer products, in the pathogenesis of uterine leiomyoma. Experimental and prospective case-control study using human samples. University hospital. Fifty-three women with histologic evidence of uterine leiomyoma and 33 surgical controls without leiomyoma. Human myometrial and leiomyoma cells were treated with di-(2-thylhexyl)-phthalate (DEHP). Cell viability assay and Western blot analyses after in vitro DEHP treatment; high-performance liquid chromatography electrospray ionization tandem mass spectrometry in cases and controls. In vitro treatment with DEHP led to an increased viability and increased expressions of proliferating cell nuclear antigen, B-cell lymphoma 2 protein, and type I collagen in myometrial and leiomyoma cells. The urinary concentration of mono-(2-ethyl-5-carboxypentyl) phthalate was higher in women with leiomyoma compared with controls. These findings suggest that exposure to phthalate may play a role in the pathogenesis of uterine leiomyoma by enhancing proliferative activity, exerting an antiapoptotic effect, and increasing collagen contents in myometrial and leiomyoma cells. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Phthalate exposure associated with self-reported diabetes among Mexican women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Svensson, Katherine; National Institute of Public Health, Universidad No. 655, Col. Santa Maria Ahuacatitlan, Cerrada los Pinos y Caminera, CP. 62100 Cuernavaca, Morelos; Hernandez-Ramirez, Raul U.

Background: Phthalates are ubiquitous industrial chemicals used as plasticizers in plastics made of polyvinyl chloride (PVC) to confer flexibility and durability. They are also present in products used for personal-care, industry and in medical devices. Phthalates have been associated with several adverse health effects, and recently it has been proposed that exposure to phthalates, could have an effect on metabolic homeostasis. This exploratory cross-sectional study evaluated the possible association between phthalate exposure and self-reported diabetes among adult Mexican women. Methods: As part of an on-going case-control study for breast cancer, only controls were selected, which constituted 221 healthy women matchedmore » by age ({+-}5 years) and place of residence with the cases. Women with diabetes were identified by self-report. Urinary concentrations of nine phthalate metabolites were measured by online solid phase extraction coupled to high performance liquid chromatography-isotope-dilution tandem mass spectrometry. Results: Participants with diabetes had significantly higher concentrations of di(2-ethylhexyl) pththalate (DEHP) metabolites: mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) but lower levels of monobenzyl phthalate (MBzP) a metabolite of benzylbutyl phthalate, compared to participants without diabetes. A marginally significant positive associations with diabetes status were observed over tertiles with MEHHP (OR{sub T3vs.T1}=2.66; 95% CI: 0.97-7.33; p for trend=0.063) and MEOHP (OR{sub T3vs.T1}=2.27; 95% CI; 0.90-5.75; P for trend=0.079) even after adjusting for important confounders. Conclusions: The results suggest that levels of some phthalates may play a role in the genesis of diabetes. - Highlights: {yields} This study evaluated phthalate exposure and diabetes status among Mexican women. {yields} Urinary phthalates metabolite concentrations were used to determine association. {yields} Participants with diabetes had higher concentrations of three DEHP metabolites. {yields} A positive association with diabetes status was found with MEHHP and MEOHP metabolites. {yields} Results suggest phthalate exposure can have a role in diabetes.« less

Early-Life Phthalate Exposure and Adiposity at 8 Years of Age.

PubMed

Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Braun, Joseph M

2017-09-11

Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022.

Urinary levels of eight phthalate metabolites and bisphenol A in mother-child pairs from two Spanish locations.

PubMed

Cutanda, Francisco; Koch, Holger M; Esteban, Marta; Sánchez, Jinny; Angerer, Jürgen; Castaño, Argelia

2015-01-01

Exposure to some phthalate diesters and bisphenol A in the general population is a cause of increasing concern because of their potential adverse effects on the reproductive and endocrine systems and their broad presence in foodstuff and consumer products. The aims of this work are to assess patterns of exposure to phthalates and bisphenol A in a pilot sample of Spanish mothers and their children, and to provide basic information to address priorities in future Spanish surveys/research. Urinary levels of eight phthalate metabolites and bisphenol A have been measured in samples from 120 mother-child pairs in one rural and one urban location in central Spain, recruited as part of the European project DEMOCOPHES. More than 96% of the participants were exposed to all the compounds studied here with generally higher levels in children than their mothers. The sum of secondary DEHP metabolites gave a GM of 33.3μg/g creatinine (95% CI 30.2-36.6) for mothers and 63.0μg/g creatinine (95% CI 56.8-69.8) for children. Mono-ethyl phthalate (MEP) was the metabolite with the highest levels, with geometric means (GM) of 150.8μg/g creatinine (95% CI 124.0-183.5) for mothers and 198.9μg/g creatinine (95% CI 165.2-239.6) for children. Bisphenol A urinary levels were relatively low with geometric means of 2.0μg/g (95% CI 1.6-2.4) for mothers and 2.01μg/g (95% CI 1.7-2.4) for children. Personal care products like body lotions and fragrances showed associations with MEHP, MEP, MnBP and cx-MiNP and canteen food with MBzP and bisphenol A. Exposure of mothers and their children are correlated, except for MEP. As phthalates and bisphenol A are non-persistent chemicals, a daily, intermittent exposure of the population is taking place. Copyright © 2014 Elsevier GmbH. All rights reserved.

Urinary concentrations of phthalates and phenols in a population of Spanish pregnant women and children.

PubMed

Casas, Lidia; Fernández, Mariana F; Llop, Sabrina; Guxens, Mònica; Ballester, Ferran; Olea, Nicolás; Irurzun, Mikel Basterrechea; Rodríguez, Loreto Santa Marina; Riaño, Isolina; Tardón, Adonina; Vrijheid, Martine; Calafat, Antonia M; Sunyer, Jordi

2011-07-01

Phthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects. To evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women - according to their individual characteristics (age, social class, education, and body mass index) - and children who participated in the INMA - Infancia y Medio Ambiente (Environment and Childhood) project. One spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols. Three metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education. Phthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class. Copyright © 2011 Elsevier Ltd. All rights reserved.

Racial and ethnic variations in phthalate metabolite concentration changes across full-term pregnancies.

PubMed

James-Todd, Tamarra M; Meeker, John D; Huang, Tianyi; Hauser, Russ; Seely, Ellen W; Ferguson, Kelly K; Rich-Edwards, Janet W; McElrath, Thomas F

2017-03-01

Higher concentrations of certain phthalate metabolites are associated with adverse reproductive and pregnancy outcomes, as well as poor infant/child health outcomes. In non-pregnant populations, phthalate metabolite concentrations vary by race/ethnicity. Few studies have documented racial/ethnic differences between phthalate metabolite concentrations at multiple time points across the full-course of pregnancy. The objective of the study was to characterize the change in phthalate metabolite concentrations by race/ethnicity across multiple pregnancy time points. Women were participants in a prospectively collected pregnancy cohort who delivered at term (≥37 weeks) and had available urinary phthalate metabolite concentrations for ≥3 time points across full-term pregnancies (n=350 women). We assessed urinary concentrations of eight phthalate metabolites that were log-transformed and specific gravity-adjusted. We evaluated the potential racial/ethnic differences in phthalate metabolite concentrations at baseline (median 10 weeks gestation) using ANOVA and across pregnancy using linear mixed models to calculate the percent change and 95% confidence intervals adjusted for sociodemographic and lifestyle factors. Almost 30% of the population were non-Hispanic black or Hispanic. With the exception of mono-(3-carboxypropyl) (MCPP) and di-ethylhexyl phthalate (DEHP) metabolites, baseline levels of phthalate metabolites were significantly higher in non-whites (P<0.05). When evaluating patterns by race/ethnicity, mono-ethyl phthalate (MEP) and MCPP had significant percent changes across pregnancy. MEP was higher in Hispanics at baseline and decreased in mid-pregnancy but increased in late pregnancy for non-Hispanic blacks. MCPP was substantially higher in non-Hispanic blacks at baseline but decreased later in pregnancy. Across pregnancy, non-Hispanic black and Hispanic women had higher concentrations of certain phthalate metabolites. These differences may have implications for racial/ethnic differences in adverse pregnancy and child health outcomes.

Predictors of Urinary Bisphenol A and Phthalate Metabolite Concentrations in Mexican Children

PubMed Central

Lewis, Ryan C.; Meeker, John D.; Peterson, Karen E.; Lee, Joyce M.; Pace, Gerry G.; Cantoral, Alejandra; Téllez-Rojo, Martha Maria

2013-01-01

Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8–13 years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-hr. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-hr, there were statistically significant (p <0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-hr and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8–13 years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development, children may be susceptible to impacts from exposure to endocrine disrupting chemicals; thus, reduced or delayed use of certain personal care products among children may be warranted. PMID:24041567

Early-Life Phthalate Exposure and Adiposity at 8 Years of Age

PubMed Central

Papandonatos, George D.; Calafat, Antonia M.; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P.; Yolton, Kimberly; Braun, Joseph M.

2017-01-01

Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother–child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1–8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate–adiposity associations at each visit, test differences in phthalate–adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): −4.8, −0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 PMID:28935615

Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic

PubMed Central

Braun, Joe M.; Just, Allan C.; Williams, Paige L.; Smith, Kristen W.; Calafat, Antonia M.; Hauser, Russ

2014-01-01

Parabens and phthalates are potential endocrine disruptors frequently used in personal care/beauty products, and the developing fetus may be sensitive to these chemicals. We measured urinary butyl-paraben (BP), methyl-paraben (MP), propyl-paraben (PP), mono-n-butyl phthalate (MBP), and monoethyl phthalate (MEP) concentrations up to three times in 177 pregnant women from a fertility clinic in Boston MA. Using linear mixed models, we examined the relationship between self-reported personal care product use in the previous 24 hours and urinary paraben and phthalate metabolite concentrations. Lotion, cosmetic, and cologne/perfume use were associated with the greatest increases in the molar sum of phthalate metabolite and paraben concentrations, although the magnitude of individual biomarker increases varied by product used. For example, women who used lotion had BP concentrations 111% higher (95% confidence interval [CI]:41%, 216%) than non-users, while their MBP concentrations were only 28% higher (CI:2%, 62%). Women using/cologne/perfume had MEP concentrations 167% (CI:98%, 261%) higher than non-users, but BP concentrations were similar. We observed a monotonic dose-response relationship between the total number of products used and urinary paraben and phthalate metabolite concentrations. These results suggest that questionnaire data may be useful for assessing exposure to a mixture of chemicals from personal care products during pregnancy. PMID:24149971

Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester, a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), and markers of ovarian response among women attending a fertility center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mínguez-Alarcón, Lidia, E-mail: lminguez@hsph.harv

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), a non-phthalate plasticizer, was introduced commercially in 2002 as an alternative to ortho-phthalate esters because of its favorable toxicological profile. However, the potential health effects from DINCH exposure remain largely unknown. We explored the associations between urinary concentrations of metabolites of DINCH on markers of ovarian response among women undergoing in vitro fertilization (IVF) treatments. Between 2011 and 2015, 113 women enrolled a prospective cohort study at the Massachusetts General Hospital Fertility Center and provided up to two urine samples prior to oocyte retrieval. The urinary concentrations of two DINCH metabolites, cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH) andmore » cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), were quantified by isotope dilution tandem mass spectrometry. We used generalized linear mixed models to evaluate the association between urinary metabolite concentrations and markers of ovarian response, accounting for multiple IVF cycles per woman via random intercepts. On average, women with detectable urinary MHiNCH concentrations, as compared to those below LOD, had a lower estradiol levels (−325 pmol/l, p=0.09) and number of retrieved oocytes (−1.8, p=0.08), with a stronger association among older women. However, urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness. In conclusion, we found suggestive negative associations between urinary MHiNCH concentrations and peak estradiol levels and number of total oocyte yields. This is the first study evaluating the effect of DINCH exposure on human reproductive health and raises the need for further experimental and epidemiological studies to better understand the potential effects of this chemical on health. - Highlights: • Women with detectable urinary MHiNCH concentrations had a lower estradiol levels and number of retrieved oocytes. • The negative association between urinary MHiNCH concentrations and total oocyte yield was stronger in older women. • Urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness.« less

Dietary Phthalate Exposure in Pregnant Women and the Impact of Consumer Practices

PubMed Central

Serrano, Samantha E.; Karr, Catherine J.; Seixas, Noah S.; Nguyen, Ruby H. N.; Barrett, Emily S.; Janssen, Sarah; Redmon, Bruce; Swan, Shanna H.; Sathyanarayana, Sheela

2014-01-01

Phthalates are ubiquitous endocrine-disrupting chemicals that are contaminants in food and contribute to significant dietary exposures. We examined associations between reported consumption of specific foods and beverages and first trimester urinary phthalate metabolite concentrations in 656 pregnant women within a multicenter cohort study, The Infant Development and Environment Study (TIDES), using multivariate regression analysis. We also examined whether reported use of ecofriendly and chemical-free products was associated with lower phthalate biomarker levels in comparison to not following such practices. Consumption of one additional serving of dairy per week was associated with decreases of 1% in the sum of di-2-ethylhexyl phthalate (DEHP) metabolite levels (95% CI: −2.0, −0.2). Further, participants who reported sometimes eating homegrown food had monoisobutyl phthalate (MiBP) levels that were 16.6% lower (95% CI: −29.5, −1.3) in comparison to participants in the rarely/never category. In contrast to rarely/never eating frozen fruits and vegetables, participants who reported sometimes following this practice had monobenzyl phthalate (MBzP) levels that were 21% higher (95% CI: 3.3, 41.7) than rarely/ever respondents. Future study on prenatal dietary phthalate exposure and the role of consumer product choices in reducing such exposure is needed. PMID:24927036

Predictors and long-term reproducibility of urinary phthalate metabolites in middle-aged men and women living in urban Shanghai

PubMed Central

Starling, Anne P.; Engel, Lawrence S.; Calafat, Antonia M.; Koutros, Stella; Satagopan, Jaya M.; Yang, Gong; Matthews, Charles E.; Cai, Qiuyin; Buckley, Jessie P.; Ji, Bu-Tian; Cai, Hui; Chow, Wong-Ho; Zheng, Wei; Gao, Yu-Tang; Rothman, Nathaniel; Xiang, Yong-Bing; Shu, Xiao-Ou

2015-01-01

Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤ 0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl)phthalate, had a Spearman rank correlation coefficient ≥ 0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population. PMID:26255822

Vinyl flooring in the home is associated with children’s airborne butylbenzyl phthalate and urinary metabolite concentrations

PubMed Central

Just, Allan C.; Miller, Rachel L.; Perzanowski, Matthew S.; Rundle, Andrew G.; Chen, Qixuan; Jung, Kyung Hwa; Hoepner, Lori; Camann, David E.; Calafat, Antonia M.; Perera, Frederica P.; Whyatt, Robin M.

2015-01-01

Prior studies have shown that vinyl flooring, as well as the vinyl-softening plasticizers butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP), are associated with asthma and airway inflammation. While DEHP exposure is primarily dietary, whether home vinyl flooring contributes to indoor air and urinary metabolite concentrations for these two phthalates is unclear. Exposures to BBzP and DEHP were examined in a prospective birth cohort of New York City children (n=239) using: (1) visual observation of potential phthalate containing flooring, (2) a two-week home indoor air sample, and (3) concurrent urinary metabolites in a subset (n=193). The category “vinyl or linoleum” flooring was observed in 135 (56%) of monitored rooms; these rooms had statistically significantly higher indoor air geometric mean concentrations of BBzP (23.9 ng/m3) than rooms with wood or carpet flooring (10.6 ng/m3). Children from homes with “vinyl or linoleum” flooring also had significantly higher urinary BBzP metabolite concentrations than other children. Indoor air BBzP and urinary metabolite concentrations were correlated positively (Spearman’s rho 0.40). By contrast, indoor air DEHP was not associated with flooring type nor with its urinary metabolite concentrations. Vinyl flooring in the home may be an important source of children’s exposure to BBzP via indoor air. PMID:25690585

Vinyl flooring in the home is associated with children's airborne butylbenzyl phthalate and urinary metabolite concentrations.

PubMed

Just, Allan C; Miller, Rachel L; Perzanowski, Matthew S; Rundle, Andrew G; Chen, Qixuan; Jung, Kyung Hwa; Hoepner, Lori; Camann, David E; Calafat, Antonia M; Perera, Frederica P; Whyatt, Robin M

2015-01-01

Prior studies have shown that vinyl flooring as well as the vinyl-softening plasticizers butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) are associated with asthma and airway inflammation. Although DEHP exposure is primarily dietary, whether home vinyl flooring contributes to indoor air and urinary metabolite concentrations for these two phthalates is unclear. Exposures to BBzP and DEHP were examined in a prospective birth cohort of New York City children (n=239) using: (i) visual observation of potential phthalate containing flooring, (ii) a 2-week home indoor air sample, and (iii) concurrent urinary metabolites in a subset (n=193). The category "vinyl or linoleum" flooring was observed in 135 (56%) of monitored rooms; these rooms had statistically significantly higher indoor air geometric mean concentrations of BBzP (23.9 ng/m(3)) than rooms with wood or carpet flooring (10.6 ng/m(3)). Children from homes with "vinyl or linoleum" flooring also had significantly higher urinary BBzP metabolite concentrations than other children. Indoor air BBzP and urinary metabolite concentrations were correlated positively (Spearman's rho 0.40). By contrast, indoor air DEHP was not associated with flooring type nor with its urinary metabolite concentrations. Vinyl flooring in the home may be an important source of children's exposure to BBzP via indoor air.

The Association of Socio-Demographic Status, Lifestyle Factors and Dietary Patterns with Total Urinary Phthalates in Australian Men

PubMed Central

Bai, Peter Y.; Wittert, Gary A.; Taylor, Anne W.; Martin, Sean A.; Milne, Robert W.; Shi, Zumin

2015-01-01

Objective To investigate the associations between socio-demographic status, lifestyle factors, dietary patterns and urinary total phthalate concentration in a cohort of South Australian men. Method We randomly selected 1527 males aged 39 to 84 from wave two of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. Total phthalate concentration was examined in fasting morning urine samples. Socio-demographic and lifestyle factors were assessed by questionnaire. Food intake was assessed by food frequency questionnaire (FFQ). Dietary patterns were constructed using factor analysis. Results Total phthalates were detected in 99.6% of the urine samples. The overall geometric mean (95% CI) of total phthalate concentration was 112.4 (107.5–117.5) ng/mL. The least square geometric means (LSGMs) of total phthalate concentration were significantly higher among people who were obese (127.8 ng/mL), consuming less than two serves fruit per day (125.7 ng/mL) and drinking more than one can (375mL) of carbonated soft drink per day (131.9 ng/mL). Two dietary patterns were identified: a prudent dietary pattern and a western dietary pattern. Both the western dietary pattern (p = 0.002) and multiple lifestyle risk factors including smoking, obesity, insufficient physical activity and the highest quartile of the western dietary pattern (p<0.001), were positively associated with total phthalate levels. There was no significant relationship between total phthalate concentration and socio-demographic status. Conclusion Phthalate exposure is ubiquitous and positively associated with lifestyle risk factors in urban dwelling Australian men. PMID:25875472

Urinary phthalate metabolite concentrations among pregnant women in Northern Puerto Rico: distribution, temporal variability, and predictors.

PubMed

Cantonwine, David E; Cordero, José F; Rivera-González, Luis O; Anzalota Del Toro, Liza V; Ferguson, Kelly K; Mukherjee, Bhramar; Calafat, Antonia M; Crespo, Noe; Jiménez-Vélez, Braulio; Padilla, Ingrid Y; Alshawabkeh, Akram N; Meeker, John D

2014-01-01

Phthalate contamination exists in the North Coast karst aquifer system in Puerto Rico. In light of potential health impacts associated with phthalate exposure, targeted action for elimination of exposure sources may be warranted, especially for sensitive populations such as pregnant women. However, information on exposure to phthalates from a variety of sources in Puerto Rico is lacking. The objective of this study was to determine concentrations and predictors of urinary phthalate biomarkers measured at multiple times during pregnancy among women living in the Northern karst area of Puerto Rico. We recruited 139 pregnant women in Northern Puerto Rico and collected urine samples and questionnaire data at three separate visits (18 ± 2 weeks, 22 ± 2 weeks, and 26 ± 2 weeks of gestation). Urine samples were analyzed for eleven phthalate metabolites: mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5-oxohexyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-ethyl phthalate (MEP), mono-n-butyl phthalate, mono-benzyl phthalate, mono-isobutyl phthalate, mono-3-carboxypropyl phthalate (MCPP), mono carboxyisononyl phthalate (MCNP), and mono carboxyisooctyl phthalate (MCOP). Detectable concentrations of phthalate metabolites among pregnant women living in Puerto Rico was prevalent, and metabolite concentrations tended to be higher than or similar to those measured in women of reproductive age from the general US population. Intraclass correlation coefficients ranged from very weak (MCNP; 0.05) to moderate (MEP; 0.44) reproducibility among all phthalate metabolites. We observed significant or suggestive positive associations between urinary phthalate metabolite concentrations and water usage/storage habits (MEP, MCNP, MCOP), use of personal care products (MEP), and consumption of certain food items (MCPP, MCNP, and MCOP). To our knowledge this is the first study to report concentrations, temporal variability, and predictors of phthalate biomarkers among pregnant women in Puerto Rico. Preliminary results suggest several potentially important exposure sources to phthalates in this population and future analysis from this ongoing prospective cohort will help to inform targeted approaches to reduce exposure. © 2013.

Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children

PubMed Central

Huen, Karen; Calafat, Antonia M.; Bradman, Asa; Yousefi, Paul; Eskenazi, Brenda; Holland, Nina

2016-01-01

Phthalates are frequently used in personal care products and plasticizers and phthalate exposure is ubiquitous in the US population. Exposure to phthalates during critical periods in utero has been associated with a variety of adverse health outcomes but the biological mechanisms linking these exposures with disease are not well characterized. In this study, we examined the relationship of in utero phthalate exposure with repetitive element DNA methylation, an epigenetic marker of genome instability, in children from the longitudinal birth cohort CHAMACOS. Methylation of Alu and long interspersed nucleotide elements (LINE-1) was determined using pyrosequencing of bisulfite-treated DNA isolated from whole blood samples collected from newborns and 9 year old children (n=355). Concentrations of eleven phthalate metabolites were measured in urine collected from pregnant mothers at 13 and 26 weeks gestation. We found a consistent inverse association between prenatal concentrations of monoethyl phthalate, the most frequently detected urinary metabolite, with cord blood methylation of Alu repeats (β(95%CI):−0.14(−0.28,0.00) and −0.16(−0.31,−0.02)) for early and late pregnancy, respectively, and a similar but weaker association with LINE-1 methylation. Additionally, increases in urinary concentrations of di-(2-ethylhexyl) phthalate metabolites during late pregnancy were associated with lower levels of methylation of Alu repeats in 9 year old blood (significant p-values ranged from 0.003 to 0.03). Our findings suggest that prenatal exposure to some phthalates may influence differences in repetitive element methylation, highlighting epigenetics as a plausible biological mechanism through which phthalates may affect health. PMID:27019040

Variability of Urinary Phthalate Metabolite and Bisphenol A Concentrations before and during Pregnancy

PubMed Central

Braun, Joe M.; Smith, Kristen W.; Williams, Paige L.; Calafat, Antonia M.; Berry, Katharine; Ehrlich, Shelley

2012-01-01

Background: Gestational phthalate and bisphenol A (BPA) exposure may increase the risk of adverse maternal/child health outcomes, but there are few data on the variability of urinary biomarkers before and during pregnancy. Objective: We characterized the variability of urinary phthalate metabolite and BPA concentrations before and during pregnancy and the ability of a single spot urine sample to classify average gestational exposure. Methods: We collected 1,001 urine samples before and during pregnancy from 137 women who were partners in couples attending a Boston fertility clinic and who had a live birth. Women provided spot urine samples before (n ≥ 2) and during (n ≥ 2) pregnancy. We measured urinary concentrations of monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate, monobenzyl phthalate (MBzP), four metabolites of di-(2-ethylhexyl) phthalate (DEHP), and BPA. After adjusting for specific gravity, we characterized biomarker variability using intraclass correlation coefficients (ICCs) and conducted several surrogate category analyses to determine whether a single spot urine sample could adequately classify average gestational exposure. Results: Absolute concentrations of phthalate metabolites and BPA were similar before and during pregnancy. Variability was higher during pregnancy than before pregnancy for BPA and MBzP, but similar during and before pregnancy for MBP, MEP, and ΣDEHP. During pregnancy, MEP (ICC = 0.50) and MBP (ICC = 0.45) were less variable than BPA (ICC = 0.12), MBzP (ICC = 0.25), and ΣDEHP metabolites (ICC = 0.08). Surrogate analyses suggested that a single spot urine sample may reasonably classify MEP and MBP concentrations during pregnancy, but more than one sample may be necessary for MBzP, DEHP, and BPA. Conclusions: Urinary phthalate metabolites and BPA concentrations were variable before and during pregnancy, but the magnitude of variability was biomarker specific. A single spot urine sample adequately classified MBP and MEP concentrations during pregnancy. The present results may be related to unique features of the women studied, and replication in other pregnancy cohorts is recommended. PMID:22262702

Phthalate Metabolites, Consumer Habits and Health Effects

PubMed Central

Wallner, Peter; Kundi, Michael; Hohenblum, Philipp; Scharf, Sigrid; Hutter, Hans-Peter

2016-01-01

Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling) were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(5-carboxy-2-ethylpentyl) phthalate (5cx-MEPP), and 3-carboxy-mono-propyl phthalate (3cx-MPP) could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET) bottles and the diethyl phthalate (DEP) metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching. PMID:27428989

Phthalate Metabolites, Consumer Habits and Health Effects.

PubMed

Wallner, Peter; Kundi, Michael; Hohenblum, Philipp; Scharf, Sigrid; Hutter, Hans-Peter

2016-07-15

Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling) were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(5-carboxy-2-ethylpentyl) phthalate (5cx-MEPP), and 3-carboxy-mono-propyl phthalate (3cx-MPP) could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET) bottles and the diethyl phthalate (DEP) metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching.

Phthalate metabolite levels and menopausal hot flashes in midlife women.

PubMed

Ziv-Gal, Ayelet; Gallicchio, Lisa; Chiang, Catheryne; Ther, Sara N; Miller, Susan R; Zacur, Howard A; Dills, Russell L; Flaws, Jodi A

2016-04-01

During the menopausal transition, a woman's reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45-54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)=1.07-1.96), hot flashes in the past 30days (OR=1.43; 95%CI=1.04-1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06-2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women. Copyright © 2016 Elsevier Inc. All rights reserved.

Phthalate metabolite levels and menopausal hot flashes in midlife women

PubMed Central

Ziv-Gal, Ayelet; Gallicchio, Lisa; Chiang, Catheryne; Ther, Sara N.; Miller, Susan R.; Zacur, Howard A.; Dills, Russell L.; Flaws, Jodi A.

2016-01-01

During the menopausal transition, a woman’s reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal-care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45–54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal-care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)= 1.07–1.96), hot flashes in the past 30 days (OR=1.43; 95%CI=1.04–1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06–2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women. PMID:26867866

Phthalate exposure and childrens neurodevelopment: A systematic review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ejaredar, Maede, E-mail: mejareda@ucalgary.ca; Nyanza, Elias C.; Ten Eycke, Kayla

Background: Emerging evidence from observational studies suggests that prenatal exposure to phthalates affects neurodevelopment in children. Objective: To conduct a systematic review of the existing literature on the association between urinary phthalate concentrations and children's neurodevelopment. Methods: We searched electronic bibliographic databases (MEDLINE, PubMed, EMBASE, PsycINFO, CINAHL, Global Health, CAB abstracts, and ERIC) (1910 to February 21st, 2014); reference lists of included articles, and conference abstracts (American Psychiatric Association, American Academy of Neurology, and Pediatric Academic Societies). Two independent reviewers screened abstracts and extracted data. We included original studies reporting on the association between prenatal or childhood urinary phthalate metabolites,more » and cognitive and behavioral outcomes (e.g., IQ scores, BASC-2 scores or equivalent) in children 0–12 years of age. Results: Of 2804 abstracts screened, 11 original articles met our criteria for inclusion. Conclusions: A systematic review of the literature supports the contention that prenatal exposure phthalates is associated with adverse cognitive and behavioral outcomes in children, including lower IQ, and problems with attention, hyperactivity, and poorer social communication. Further research characterizing the associations between specific phthalate metabolites and children's neurodevelopmental outcomes is needed to support the development of mitigation strategies and enhance the development of appropriate health policy. - Highlights: • Prenatal maternal urinary concentrations of phthalate metabolites appear to be associated with adverse cognitive and behavioral outcomes in children. • Both low molecular weight (e.g., monobutyl phthalate, MBP) and high molecular weight (e.g., di(2-ethylhexyl) phthalate, DEHP) phthalate metabolites are associated with adverse cognitive and behavioral outcomes. • Sex-specific effects from phthalate exposure were noted between low (e.g., mono-n-butyl phthalate, MnBP) and high (e.g., DEHP) molecular weight phthalate metabolites, and cognitive and behavioral outcomes.« less

Maternal Phthalate and Personal Care Products Exposure Alters Extracellular Placental miRNA Profile in Twin Pregnancies.

PubMed

Zhong, Jia; Baccarelli, Andrea A; Mansur, Abdallah; Adir, Michal; Nahum, Ravit; Hauser, Russ; Bollati, Valentina; Racowsky, Catherine; Machtinger, Ronit

2018-01-01

Prenatal exposure to endocrine-disrupting chemicals (EDCs) exerts both short- and long-term adverse effects on the developing fetus. However, the mechanisms underlying these effects have yet to be uncovered. Maternal-fetal signaling is mediated in part by signaling molecules (eg, microRNAs [miRNAs]) contained in extracellular vesicles (EVs) that are released by the placenta into the maternal circulation. We investigated whether maternal exposure to the EDCs phthalates and personal care products alters the miRNA profile of placental-derived EVs circulating in maternal blood. Blood and urine samples from pregnant women with uncomplicated term dichorionic, diamniotic twin pregnancies were analyzed as part of a larger study investigating correlations between exposure of phthalate and personal care products and epigenetic alterations in twin pregnancies. We explored correlations between maternal urinary levels of 13 phthalate and 12 personal care products metabolites and the miRNA profile of placental EVs (EV-miRNAs) circulating in maternal blood. The expression of miR-518e was highest among women with high urinary levels of monobenzyl phthalate and methyl paraben. miR-373-3p was the least expressed in women exposed to high levels of methyl paraben, and miR-543 was significantly downregulated in women exposed to high levels of paraben metabolites, dichlorophenol metabolites, and triclosan. In conclusion, this pilot study reveals that prenatal exposure to EDCs is associated with altered profile of circulating placenta-derived EV-miRNAs. Further studies are needed to generalize these results to singleton pregnancies and to assess whether these alterations are associated with pregnancy complications.

Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses’ Health Studies: a prospective cohort study

PubMed Central

2013-01-01

Background Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies. Methods Women in the Nurses’ Health Study and Nurses’ Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid. Results Over 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results. Conclusions Single measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated. PMID:24034517

Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses' Health Studies: a prospective cohort study.

PubMed

Townsend, Mary K; Franke, Adrian A; Li, Xingnan; Hu, Frank B; Eliassen, A Heather

2013-09-13

Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies. Women in the Nurses' Health Study and Nurses' Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid. Over 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results. Single measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated.

Urinary phthalate metabolites and environmental phenols in university students in South China.

PubMed

Zhang, Xue-Mei; Lou, Xiang-Ying; Wu, Liu-Hong; Huang, Cong; Chen, Da; Guo, Ying

2018-04-14

In China, university students have unique lifestyles compared with the rest of the youth population, as they are almost entirely isolated in campuses. The number of university students is large, and since students represent the future of human reproduction, exposure to environmental endocrine disruptors (EEDs) may have a large impact on society. In this study, levels of several EEDs, including phthalate metabolites, parabens, bisphenol A (BPA) and its analogues, triclosan (TCS), and benzophenone-3, were determined in 169 urine samples collected from university students in Guangzhou, South China. In addition, to further understand the potential sources of EEDs in their daily lives, a survey of students' lifestyles was conducted. Based on the urinary concentrations of EEDs and the survey results, daily exposure doses of target EEDs and their potential sources were investigated. Our results indicated that nine phthalate metabolites, three parabens, and BPA were ubiquitous (detection frequency > 60%) in the urine of university students. The concentrations of total phthalates (median: 99.4 µg L -1 ) were orders of magnitude higher than those of total parabens (7.30 µg L -1 ) and of other environmental phenols (0.40 µg L -1 ). Significantly higher concentrations of phthalates, parabens, and TCS were found in female versus male students, partly due to the higher usage of personal care products (PCPs) by female students (p < 0.05). The estimated daily intakes (EDIs) of phthalates, parabens, BPA, and TCS were 0.46-1.35, 3.29-10.3, 0.007, and 0.67 µg/kg-bw/day, respectively. The EDIs of phthalates and BPA were much lower than those suggested by the European Food Safety guidelines (10, 50, and 50 µg/kg-bw/day for dibutyl phthalate, diethylhexyl phthalate, and BPA, respectively). Our results indicated that university students were widely exposed to EEDs, but at relatively low doses. PCP usage was the main reason for differences in levels of phthalates (especially diethyl phthalate) and parabens between male and female students in South Chinese universities. Copyright © 2018. Published by Elsevier Inc.

Hidden Toxicity in Neonatal Intensive Care Units: Phthalate Exposure in Very Low Birth Weight Infants

PubMed Central

Demirel, Atalay; Çoban, Asuman; Yıldırım, Şükran; Doğan, Canan; Sancı, Rukiye; İnce, Zeynep

2016-01-01

Objective: To determine exposure to endocrine-disrupting phthalates in preterm infants in neonatal intensive care units (NICU). Methods: Urine samples (n=151) from 36 preterm infants (<32 weeks of gestation and/or <1500 g of birth weight) were collected on the first 3 days of admission to the NICU and biweekly thereafter. Diethylhexyl phthalate contents of indwelling medical devices used in various procedures and the concentrations of phthalate metabolites in the urine samples were analyzed. The relationships between urinary excretion, exposure intensity, postnatal age and birth weight were examined. Results: The mean gestational age and mean birth weight of the study infants were 28.9±1.5 weeks and 1024±262 g, respectively. Diethylhexyl phthalate was detected in umbilical catheters, endotracheal tubes, nasogastric tubes, and nasal cannula. Monoethylhydroxyhexyl phthalate (MEHHP) was the most frequently detected metabolite (81.4%); its concentration increased during the first 4 weeks and then started to decrease but never disappeared. Patients who did not need indwelling catheters (except nasogastric tubes) after 2 weeks were classified as group 1 and those who continued to have indwelling catheters as group 2. Although not of statistical significance, MEHHP levels decreased in group 1 but continued to stay high in group 2 (in the 4th week, group 1: 65.9 ng/mL and group 2: 255.3 ng/mL). Levels of MEHHP in the first urinary samples were significantly higher in infants with a birth weight <1000 g (<1000 g: 63.2±93.8 ng/mL, ≥1000 g: 10.9±22.9 ng/mL, p=0.001). Conclusion: Phthalate metabolites were detected even in the first urine samples of very low birth weight newborns. Phthalate levels were higher in the first weeks of intensive invasive procedures and in preterm infants with a birth weight less than 1000 g. MEHHP was the most frequently detected metabolite and could be a suitable biomarker for the detection of phthalate exposure in preterm infants. PMID:27097850

Urinary concentrations of bisphenol A and phthalate metabolites and weight change: a prospective investigation in US women

PubMed Central

Song, Y; Hauser, R; Hu, FB; Franke, AA; Liu, S; Sun, Q

2015-01-01

OBJECTIVE Both bisphenol A (BPA) and phthalates are known endocrine-disrupting chemicals for which there is widespread general population exposure. Human exposure occurs through dietary and non-dietary routes. Although animal studies have suggested a potential role of these chemicals in obesity, evidence from human studies is sparse and inconsistent, and prospective evidence is lacking. This study evaluated urinary concentrations of BPA and major phthalate metabolites in relation to prospective weight change. METHODS The study population was from the controls in a prospective case-control study of type 2 diabetes in the Nurses’ Health Study (NHS) and NHSII. A total of 977 participants provided first-morning-void urine samples in 1996–2002. Urinary concentrations of BPA and nine phthalate metabolites were measured using liquid chromatography–mass spectrometry. Body weights were self-reported at baseline and updated biennially thereafter for 10 years. RESULTS On average, the women gained 2.09 kg (95% confidence interval (CI), − 2.27 to 6.80 kg) during the 10-year follow-up. In multivariate analysis with adjustment of lifestyle and dietary factors, in comparison with women in the lowest quartile of BPA concentration, those in the highest quartile had 0.23 kg per year (95% CI, 0.07–0.38 kg per year) greater weight gain during the 10-year follow-up (P-trend = 0.02). Several phthalate metabolites, including phthalic acid, MBzP and monobutyl phthalate, were also associated with faster prospective weight gain in a dose-response fashion (P-trend < 0.01), whereas other phthalates metabolites, including MEP and monoethylhexyl phthalate, were not monotonically associated with body weight change. CONCLUSIONS These data suggest urinary concentrations of BPA and certain individual phthalate metabolites that were associated with modestly greater weight gain in a dose-response fashion. These data are consistent with a potential role of BPA and phthalates in obesity, although more prospective data are needed to corroborate these observations. PMID:24722546

Urinary concentrations of bisphenol A and phthalate metabolites and weight change: a prospective investigation in US women.

PubMed

Song, Y; Hauser, R; Hu, F B; Franke, A A; Liu, S; Sun, Q

2014-12-01

Both bisphenol A (BPA) and phthalates are known endocrine-disrupting chemicals for which there is widespread general population exposure. Human exposure occurs through dietary and non-dietary routes. Although animal studies have suggested a potential role of these chemicals in obesity, evidence from human studies is sparse and inconsistent, and prospective evidence is lacking. This study evaluated urinary concentrations of BPA and major phthalate metabolites in relation to prospective weight change. The study population was from the controls in a prospective case-control study of type 2 diabetes in the Nurses' Health Study (NHS) and NHSII. A total of 977 participants provided first-morning-void urine samples in 1996-2002. Urinary concentrations of BPA and nine phthalate metabolites were measured using liquid chromatography-mass spectrometry. Body weights were self-reported at baseline and updated biennially thereafter for 10 years. On average, the women gained 2.09 kg (95% confidence interval (CI), -2.27 to 6.80 kg) during the 10-year follow-up. In multivariate analysis with adjustment of lifestyle and dietary factors, in comparison with women in the lowest quartile of BPA concentration, those in the highest quartile had 0.23 kg per year (95% CI, 0.07-0.38 kg per year) greater weight gain during the 10-year follow-up (P-trend=0.02). Several phthalate metabolites, including phthalic acid, MBzP and monobutyl phthalate, were also associated with faster prospective weight gain in a dose-response fashion (P-trend<0.01), whereas other phthalates metabolites, including MEP and monoethylhexyl phthalate, were not monotonically associated with body weight change. These data suggest urinary concentrations of BPA and certain individual phthalate metabolites that were associated with modestly greater weight gain in a dose-response fashion. These data are consistent with a potential role of BPA and phthalates in obesity, although more prospective data are needed to corroborate these observations.

Follicular fluid and urinary concentrations of phthalate metabolites among infertile women and associations with in vitro fertilization parameters.

PubMed

Du, Yao-Yao; Fang, Yue-Li; Wang, Yi-Xin; Zeng, Qiang; Guo, Na; Zhao, Hua; Li, Yu-Feng

2016-06-01

Evidence from toxicological studies has demonstrated that phthalates can lead to reduced fertility through effects on folliculogenesis, oocyte maturation and embryonic development, but human data are limited. Concentrations of eight phthalate metabolites in 110 follicular fluid (FF) and urine samples collected from 112 women attending an infertility clinic in Wuhan, China were quantified, and correlations between paired matrices were explored. Associations between metabolite concentrations and in vitro fertilization (IVF) parameters were evaluated with multivariable models. Six metabolites were detected in >72.73% of the FF samples. MEHP and MBP were the dominant metabolites with a median level of 2.80 and 2.05ng/mL, respectively. Significant correlations between the two matrices, urine and FF, were found for MEP (rs=0.44), and MBP (rs=0.22). FF and urinary metabolite concentrations were not associated with any IVF parameters. However, given the prevalence of phthalates exposure, further work is needed to elucidate the potential hazard on female reproduction. Copyright © 2016 Elsevier Inc. All rights reserved.

Prenatal phthalate exposures and child temperament at 12 and 24 months.

PubMed

Singer, Alison B; Wolff, Mary S; Silva, Manori J; Calafat, Antonia M; Engel, Stephanie M

2017-09-01

Gestational phthalate exposures have been adversely associated with attention, externalizing, and internalizing behaviors in childhood. Early childhood temperament may be a marker of later behavioral patterns. We therefore sought to determine whether gestational phthalate exposures were associated with infant and toddler temperament. The Mount Sinai Children's Environmental Health Study is a prospective cohort study of children born between May 1998 and July 2001 in New York City (N=404). Phthalate metabolites were measured in spot urine samples collected from pregnant women in their third trimester. Child temperament was assessed by parental report at 12-months using the Infant Behavior Questionnaire (IBQ) (N=204) and at 24-months using the Toddler Behavior Assessment Questionnaire (TBAQ) (N=279). We used multiple linear regression to evaluate associations between urinary phthalate metabolites and eleven temperament domains. Phthalate biomarker concentrations were weakly associated with lower gross motor activity levels as well as higher duration of orienting at the 12-month assessment. Mono(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP) and the sum of metabolites of di(2-ethylhexyl) phthalate (∑DEHP) were associated with lower levels of smiling and laughing at 12 months. At 24-months, social fear and lower pleasure was linked to higher concentrations of MCPP and MBzP, and higher ∑DEHP was weakly associated with increased anger levels at 24-months. Though we observed some weak associations between biomarkers of prenatal exposure to phthalates and temperament at 12- and 24-months, overall phthalates biomarkers were not strongly associated with alterations in temperament. Copyright © 2017. Published by Elsevier B.V.

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

PubMed Central

2015-01-01

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 Σ14phthalates (sum of 14 urinary phthalate metabolites) were 0.48, 85.2, 4.50, 7.66, 4.36, 3.80, 54.8, and 249 μg/g creatinine, respectively. The estimated DI values for DEHP in 39 individuals were above the U.S. Environmental Protection Agency’s (EPA) reference dose (RfD) of 20 μg/kg-bw/day. The mean and median concentrations of 8-OHdG were 6.02 and 3.13 μg/g creatinine, respectively, which were significantly higher in females than in males. Statistically significant associations were found between 8-OHdG and urinary concentrations of mEP, and Σ5mEHP for females. Similarly, a significant association was found between 8-OHdG and DIs estimated for select phthalates. Our results suggested that phthalate exposure increases oxidative stress, which can be a mechanism for the diminished fertility observed in couples who were highly exposed to select phthalates. PMID:25068827

Personal Care Product Use in Men and Urinary Concentrations of Select Phthalate Metabolites and Parabens: Results from the Environment And Reproductive Health (EARTH) Study.

PubMed

Nassan, Feiby L; Coull, Brent A; Gaskins, Audrey J; Williams, Michelle A; Skakkebaek, Niels E; Ford, Jennifer B; Ye, Xiaoyun; Calafat, Antonia M; Braun, Joseph M; Hauser, Russ

2017-08-18

Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men's exposure is understudied. We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men. In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004-2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for each PCP in a weighted binary score regression and modeled the resulting composite weighted PCP use. Four hundred men contributed 1,037 urine samples (mean of 3/man). The largest percent increase in monoethyl phthalate (MEP) was associated with use of cologne/perfume (83%, p -value<0.01) and deodorant (74%, p -value<0.01). In contrast, the largest percent increase for parabens was associated with the use of suntan/sunblock lotion (66-156%) and hand/body lotion (79-147%). Increases in MEP and parabens were generally greater with PCP use within 6 h of urine collection. A subset of 10 PCPs that were used within 6 h of urine collection contributed to at least 70% of the weighted score and predicted a 254-1,333% increase in MEP and parabens concentrations. Associations between PCP use and concentrations of the other phthalate metabolites were not statistically significant. We identified 10 PCPs of relevance and demonstrated that their use within 6 h of urine collection strongly predicted MEP and paraben urinary concentrations. https://doi.org/10.1289/EHP1374.

Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies.

PubMed

Jurewicz, Joanna; Hanke, Wojciech

2011-06-01

Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children's neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary levels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.

Fetal and Childhood Exposure to Phthalate Diesters and Cognitive Function in Children Up to 12 Years of Age: Taiwanese Maternal and Infant Cohort Study

PubMed Central

Huang, Han-Bin; Chen, Hsin-Yi; Su, Pen-Hua; Huang, Po-Chin; Sun, Chien-Wen; Wang, Chien-Jen; Chen, Hsiao-Yen

2015-01-01

Few studies have examined the association between environmental phthalate exposure and children’s neurocognitive development. This longitudinal study examined cognitive function in relation to pre-and postnatal phthalate exposure in children 2–12 years old. We recruited 430 pregnant women in their third trimester in Taichung, Taiwan from 2001–2002. A total of 110, 79, 76, and 73 children were followed up at ages 2, 5, 8, and 11, respectively. We evaluated the children’s cognitive function at four different time points using the Bayley and Wechsler tests for assessing neurocognitive functions and intelligence (IQ). Urine samples were collected from mothers during pregnancy and from children at each follow-up visit. They were analyzed for seven metabolite concentrations of widely used phthalate esters. These esters included monomethyl phthalate, monoethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, and three metabolites of di(2-ethylhexyl) phthalate, namely, mono-2-ethylhexyl phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. We constructed a linear mixed model to examine the relationships between the phthalate metabolite concentrations and the Bayley and IQ scores. We found significant inverse associations between the children’s levels of urinary mono(2-ethyl-5-oxohexyl) phthalate and the sum of the three metabolites of di(2-ethylhexyl) phthalate and their IQ scores (β = -1.818; 95% CI: -3.061, -0.574, p = 0.004 for mono(2-ethyl-5-oxohexyl) phthalate; β = -1.575; 95% CI: -3.037, -0.113, p = 0.035 for the sum of the three metabolites) after controlling for maternal phthalate levels and potential confounders. We did not observe significant associations between maternal phthalate exposure and the children’s IQ scores. Children’s but not prenatal phthalate exposure was associated with decreased cognitive development in the young children. Large-scale prospective cohort studies are needed to confirm these findings in the future. PMID:26121592

Prenatal Phthalate Exposures and Childhood Fat Mass in a New York City Cohort.

PubMed

Buckley, Jessie P; Engel, Stephanie M; Mendez, Michelle A; Richardson, David B; Daniels, Julie L; Calafat, Antonia M; Wolff, Mary S; Herring, Amy H

2016-04-01

Experimental animal studies and limited epidemiologic evidence suggest that prenatal exposure to phthalates may be obesogenic, with potential sex-specific effects of phthalates having anti-androgenic activity. We aimed to assess associations between prenatal phthalate exposures and childhood fat mass in a prospective cohort study. We measured phthalate metabolite concentrations in third-trimester maternal urine in a cohort of women enrolled in New York City between 1998 and 2002 (n = 404). Among 180 children (82 girls and 98 boys), we evaluated body composition using a Tanita scale at multiple follow-up visits between ages 4 and 9 years (363 total visits). We estimated associations of standard deviation differences or tertiles of natural log phthalate metabolite concentrations with percent fat mass using linear mixed-effects regression models with random intercepts for repeated outcome measurements. We assessed associations in multiple metabolite models and adjusted for covariates including prepregnancy body mass index, gestational weight gain, maternal smoking during pregnancy, and breastfeeding. We did not observe associations between maternal urinary phthalate concentrations and percent body fat in models examining continuous exposures. Fat mass was 3.06% (95% CI: -5.99, -0.09%) lower among children in the highest tertile of maternal urinary concentrations of summed di(2-ethylhexyl) phthalate (ΣDEHP) metabolites than in children in the lowest tertile. Though estimates were imprecise, there was little evidence that associations between maternal urinary phthalate concentrations and percent fat mass were modified by child's sex. Prenatal phthalate exposures were not associated with increased body fat among children 4-9 years of age, though high prenatal DEHP exposure may be associated with lower fat mass in childhood. Buckley JP, Engel SM, Mendez MA, Richardson DB, Daniels JL, Calafat AM, Wolff MS, Herring AH. 2016. Prenatal phthalate exposures and childhood fat mass in a New York City cohort. Environ Health Perspect 124:507-513; http://dx.doi.org/10.1289/ehp.1509788.

Exposure to select phthalates and phenols through use of personal care products among Californian adults and their children.

PubMed

Philippat, Claire; Bennett, Deborah; Calafat, Antonia M; Picciotto, Irva Hertz

2015-07-01

Certain phenols and phthalates are used in many consumer products including personal care products (PCPs). We aimed to study the associations between the use of PCPs and urinary concentrations of biomarkers of select phenols and phthalates among Californian adults and their children. As an additional aim we compared phenols and phthalate metabolites concentrations measured in adults and children urine samples collected the same day. Our study relied on a subsample of 90 adult-child pairs participating in the Study of Use of Products and Exposure Related Behavior (SUPERB). Each adult and child provided one to two urine samples in which we measured concentrations of selected phenols and phthalate metabolites. We computed Spearman correlation coefficients to compare concentrations measured in adults and children urine samples collected the same day. We used adjusted linear and Tobit regression models to study the associations between the use of PCPs in the past 24h and biomarker concentrations. Benzophenone-3 and parabens concentrations were higher in adults compared to their children. Conversely children had higher mono-n-butyl phthalate and mono-isobutyl phthalate concentrations. No significant difference was observed for the other compounds. The total number of different PCPs used was positively associated with urinary concentrations of methyl, propyl and butyl parabens and the main metabolite of diethyl phthalate in adults. Among children, the use of a few specific products including liquid soap, hair care products and sunscreen was positively associated with urinary concentrations of some phenols or phthalate metabolites. These results strengthen the body of evidence suggesting that use of PCPs is an important source of exposure to parabens and diethyl phthalate in adults and provide data on exposure to selected phenols and phthalates through use of PCPs in children. Copyright © 2015 Elsevier Inc. All rights reserved.

Exposure to select phthalates and phenols through use of personal care products among Californian adults and their children

PubMed Central

Philippat, Claire; Bennett, Deborah; Calafat, Antonia M.; Picciotto, Irva Hertz

2016-01-01

Introduction Certain phenols and phthalates are used in many consumer products including personal care products (PCPs). Aims We aimed to study the associations between the use of PCPs and urinary concentrations of bio-markers of select phenols and phthalates among Californian adults and their children. As an additional aim we compared phenols and phthalate metabolites concentrations measured in adults and children urine samples collected the same day. Methods Our study relied on a subsample of 90 adult–child pairs participating in the Study of Use of Products and Exposure Related Behavior (SUPERB). Each adult and child provided one to two urine samples in which we measured concentrations of selected phenols and phthalate metabolites. We computed Spearman correlation coefficients to compare concentrations measured in adults and children urine samples collected the same day. We used adjusted linear and Tobit regression models to study the associations between the use of PCPs in the past 24 h and biomarker concentrations. Results Benzophenone-3 and parabens concentrations were higher in adults compared to their children. Conversely children had higher mono-n-butyl phthalate and mono-isobutyl phthalate concentrations. No significant difference was observed for the other compounds. The total number of different PCPs used was positively associated with urinary concentrations of methyl, propyl and butyl parabens and the main metabolite of diethyl phthalate in adults. Among children, the use of a few specific products including liquid soap, hair care products and sunscreen was positively associated with urinary concentrations of some phenols or phthalate metabolites. Discussion These results strengthen the body of evidence suggesting that use of PCPs is an important source of exposure to parabens and diethyl phthalate in adults and provide data on exposure to selected phenols and phthalates through use of PCPs in children. PMID:25929801

URINARY BIOMARKERS OF DI-ISONONYL PHTHALATE IN RATS

EPA Science Inventory

Commercial di-isononyl phthalate (DiNP) is a mixture of various branched-chain dialkyl phthalates mainly containing ninecarbon alkyl isomers. At high doses in rodents, DiNP is a carcinogen, and a developmental toxicant. After exposure, the diester isomers are de-esterified to for...

Effects of maternal exposure to phthalates and bisphenol A during pregnancy on gestational age.

PubMed

Weinberger, Barry; Vetrano, Anna M; Archer, Faith E; Marcella, Stephen W; Buckley, Brian; Wartenberg, Daniel; Robson, Mark G; Klim, Jammie; Azhar, Sana; Cavin, Sarah; Wang, Lu; Rich, David Q

2014-03-01

Phthalates and bisphenol A (BPA) are ubiquitous environmental toxicants, present in high concentrations in numerous consumer products. We hypothesized that maternal exposure to phthalates and BPA in pregnancy is associated with shortened gestation. Urinary phthalate and BPA metabolites from 72 pregnant women were measured at the last obstetric clinic visit prior to delivery. Using linear regression models, we estimated the change in gestational age associated with each interquartile range (IQR) increase in phthalate and BPA metabolite concentration. IQR increases in urinary mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and BPA concentrations were associated with 4.2 and 1.1 d decreases in gestation, respectively. When stratified by gender, these alterations were found only in male infants. We conclude that MEHHP and BPA (free + glucuronide) are associated with reductions in gestation, with effects observed only in males. Our findings are consistent with the idea that these agents induce gender-specific alterations in signaling via PPAR-γ transcription factor, androgen precursors and/or inflammatory mediators during the initiation of labor.

Association between Phthalate Exposure and the Use of Plastic Containers in Shanghai Adults.

PubMed

Dong, Rui Hua; Zhang, Han; Zhang, Mei Ru; Chen, Jing Si; Wu, Min; Li, Shu Guang; Chen, Bo

2017-10-01

Consuming phthalates may be due to the presence of food contact materials, such as plastic containers. In this study, we investigated the association between plastic container use and phthalate exposure in 2,140 Shanghai adults. Participants completed a questionnaire on the frequency of using plastic containers in different scenarios in the previous year (e.g., daily, weekly) and on the consumption of plastic-packaged foods in the previous three days (yes or no). Urinary phthalate metabolites were used to assess the association between phthalate exposure and the use of plastic containers. The metabolites of di-(2-ethylhexyl) phthalate (DEHP) were the most frequently detected in urine. The results revealed that phthalate exposure was associated with consumption of plastic-packaged breakfast or processed food items in the previous three days. The consumption of these two food items had strong synergistic effects on increasing urinary concentrations of most phthalate metabolites. Our results of plastic-packaged breakfast and processed food may be explained by the use of flexible plastic containers, indicating the importance of risk assessment for the application of flexible plastic containers. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

First Trimester Phthalate Exposure and Infant Birth Weight in the Infant Development and Environment Study.

PubMed

Sathyanarayana, Sheela; Barrett, Emily; Nguyen, Ruby; Redmon, Bruce; Haaland, Wren; Swan, Shanna H

2016-09-23

Phthalate exposure is widespread among pregnant women but whether it is related to fetal growth and birth weight remains to be determined. We examined whether first trimester prenatal phthalate exposure was associated with birth weight in a pregnancy cohort study. We recruited first trimester pregnant women from 2010-2012 from four centers and analyzed mother/infant dyads who had complete urinary phthalate and birth record data (N = 753). We conducted multiple linear regression to examine if prenatal log specific gravity adjusted urinary phthalate exposure was related to birthweight in term and preterm (≤37 weeks) infants, stratified by sex. We observed a significant association between mono carboxy-isononyl phthalate (MCOP) exposure and increased birthweight in term males, 0.13 kg (95% CI 0.03, 0.23). In preterm infants, we observed a 0.49 kg (95% CI 0.09, 0.89) increase in birthweight in relation to a one log unit change in the sum of di-ethylhexyl phthalate (DEHP) metabolite concentrations in females (N = 33). In summary, we observed few associations between prenatal phthalate exposure and birthweight. Positive associations may be attributable to unresolved confounding in term infants and limited sample size in preterm infants.

Age and Gender Differences in Urinary Levels of Eleven Phthalate Metabolites in General Taiwanese Population after a DEHP Episode

PubMed Central

Huang, Po-Chin; Tsai, Chih-Hsin; Liang, Wei-Yen; Li, Sih-Syuan; Pan, Wen-Harn; Chiang, Hung-Che

2015-01-01

Introduction In 2011, the Taiwan FDA disclosed illegal di(2-ethylhexyl phthalate) (DEHP) and dibutyl phthalate (DBP) use in beverage and nutrition supplements. We aim to determine phthalate exposure and other relevant factors in a sample of the general Taiwanese population in order to evaluate actual phthalate exposure levels after this disclosure of DEHP use. Method We selected subjects aged 7 years old and older in 2013 from the general Taiwanese population. First morning urine samples from each participant were collected to analyze 11 phthalate metabolites representing 7 parent phthalates using on-line liquid chromatography/ tandem mass spectrometry. An interview questionnaire was applied to obtain participant demographic characteristics, lifestyle, and other relevant factors. Results The median levels of metabolites of DEHP, including mono-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), DBP (DnBP and DiBP), including mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP), and mono-ethyl phthalate (MEP) in urine samples of 290 adults/ 97 minors (<18 years) were 7.9/ 6.1, 12.6/ 17.8, 22.0/ 25.8, 25.4/ 30.8, 18.1/ 23.6, 9.4/ 13.6 and 14.5/ 12.4 μg/g creatinine, respectively. Women (≧18 years) were exposed to significantly higher levels of MEHHP (P=0.011), MECPP (P=0.01), MnBP (P=0.001) and MEP (P<0.001) than men (≧18 years), whereas no gender difference was observed in minors. We found significant higher level of MEP (creatinine-unadjusted) in subject aged between 18 to 40 years old (P<0.001), especially for women. Exposure levels of MEOHP (P<0.001), MECPP (P=0.002) and MnBP (P=0.044) in minors were significantly higher than those of adults. High frequency usage of food preservation film and bags, and personal care products are potential sources of phthalates exposure in general Taiwanese. Conclusion Our findings indicated that DEHP and DBP exposure in a sample of the general Taiwanese population varied by age and gender, possibly affected by different lifestyles, and continuing bio-monitoring surveillance is warranted. PMID:26207744

URINARY METABOLITES OF DI-N-OCTYL PHTHALATE IN RATS

EPA Science Inventory

Di-n-octyl phthalate (DnOP) is a plasticizer used in polyvinyl chloride plastics, cellulose esters, and polystyrene resins. The metabolism of DnOP results in the hydrolysis of one ester linkage to produce mono-n-octyl phthalate (MnOP), which subsequently metabolizes to form oxida...

Urinary phthalate metabolite concentrations in relation to history of infertility and use of assisted reproductive technology.

PubMed

Alur, Snigdha; Wang, Hongyue; Hoeger, Kathy; Swan, Shanna H; Sathyanarayana, Sheela; Redmon, Bruce J; Nguyen, Ruby; Barrett, Emily S

2015-11-01

To examine urinary phthalate metabolite concentrations in pregnant women with planned pregnancies in relation to history of infertility and use of assisted reproductive technology (ART). Phthalate metabolite concentrations were measured in first-trimester urine samples collected from women participating in a prospective pregnancy cohort study. Prenatal clinics. A total of 750 women, of whom 86 had a history of infertility. Forty-one women used ART to conceive. None. Primary outcomes were concentrations of four metabolites of diethylhexyl phthalate (DEHP) and their molar sum (∑DEHP). Multivariable analyses compared phthalate metabolite levels in [1] women reporting a history of infertility vs. those who did not (comparison group); and [2] those who used ART to conceive the index pregnancy vs. women with a history of infertility who did not use ART. Among women with a history of infertility, ∑DEHP was significantly lower in women who conceived after ART compared with those who did not (geometric mean ratio: 0.83; 95% confidence interval 0.71-0.98). Similar significant associations were observed for all of the individual DEHP metabolites. There were no differences in DEHP metabolite concentrations between women with a history of infertility and the comparison group. Women who used ART to conceive had lower first-trimester phthalate metabolite concentrations than women with a history of infertility who did not use ART. Further research is needed to explore whether those pursuing fertility treatments take precautions to avoid exposure to environmental toxins, to improve treatment outcomes. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Phthalate exposure associated with self-reported diabetes among Mexican women

PubMed Central

Svensson, Katherine; Hernández-Ramírez, Raúl U.; Burguete-García, Ana; Cebrián, Mariano E.; Calafat, Antonia M.; Needham, Larry L.; Claudio, Luz; López-Carrillo, Lizbeth

2016-01-01

Background Phthalates are ubiquitous industrial chemicals used as plasticizers in plastics made of polyvinyl chloride (PVC) to confer flexibility and durability. They are also present in products used for personal-care, industry and in medical devices. Phthalates have been associated with several adverse health effects, and recently it has been proposed that exposure to phthalates, could have an effect on metabolic homeostasis. This exploratory cross-sectional study evaluated the possible association between phthalate exposure and self-reported diabetes among adult Mexican women. Methods As part of an on-going case-control study for breast cancer, only controls were selected, which constituted 221 healthy women matched by age (±5 years) and place of residence with the cases. Women with diabetes were identified by self-report. Urinary concentrations of nine phthalate metabolites were measured by online solid phase extraction coupled to high performance liquid chromatography-isotope-dilution tandem mass spectrometry. Results Participants with diabetes had significantly higher concentrations of di(2-ethylhexyl) pththalate (DEHP) metabolites: mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) but lower levels of monobenzyl phthalate (MBzP) a metabolite of benzylbutyl phthalate, compared to participants without diabetes. A marginally significant positive associations with diabetes status were observed over tertiles with MEHHP (ORT3 vs. T1 = 2.66; 95% CI: 0.97–7.33; p for trend = 0.063) and MEOHP (ORT3 vs. T1 = 2.27; 95% CI; 0.90–5.75; P for trend = 0.079) even after adjusting for important confounders. Conclusions The results suggest that levels of some phthalates may play a role in the genesis of diabetes. PMID:21696718

Personal Care Product Use in Men and Urinary Concentrations of Select Phthalate Metabolites and Parabens: Results from the Environment And Reproductive Health (EARTH) Study

PubMed Central

Coull, Brent A.; Gaskins, Audrey J.; Williams, Michelle A.; Skakkebaek, Niels E.; Ford, Jennifer B.; Ye, Xiaoyun; Calafat, Antonia M.; Braun, Joseph M.; Hauser, Russ

2017-01-01

Background: Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men’s exposure is understudied. Objectives: We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men. Methods: In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004–2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for each PCP in a weighted binary score regression and modeled the resulting composite weighted PCP use. Results: Four hundred men contributed 1,037 urine samples (mean of 3/man). The largest percent increase in monoethyl phthalate (MEP) was associated with use of cologne/perfume (83%, p-value<0.01) and deodorant (74%, p-value<0.01). In contrast, the largest percent increase for parabens was associated with the use of suntan/sunblock lotion (66–156%) and hand/body lotion (79–147%). Increases in MEP and parabens were generally greater with PCP use within 6 h of urine collection. A subset of 10 PCPs that were used within 6 h of urine collection contributed to at least 70% of the weighted score and predicted a 254–1,333% increase in MEP and parabens concentrations. Associations between PCP use and concentrations of the other phthalate metabolites were not statistically significant. Conclusions: We identified 10 PCPs of relevance and demonstrated that their use within 6 h of urine collection strongly predicted MEP and paraben urinary concentrations. https://doi.org/10.1289/EHP1374 PMID:28886595

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example.

PubMed

Liu, Liangpo; Xia, Tongwei; Guo, Lihua; Cao, Lanyu; Zhao, Benhua; Zhang, Jie; Dong, Sijun; Shen, Heqing

2012-11-01

The urinary metabolites of phthalates are well-accepted exposure biomarkers for adults and children older than 6 years but are not commonly used for infants owing to non-convenient sampling. In the light of this situation, a novel sampling method based on monitoring the urine expressed from the gel diaper was developed. The urine was expressed from the gel absorbent after mixing the absorbent with CaCl(2) and then collected by a laboratory-made device; the urinary phthalate metabolites were extracted and cleaned using a solid-phase extraction (SPE) column and analyzed with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry / mass spectrometry. To evaluate the method's feasibility, the following factors were investigated: the proportion of CaCl(2) to gel absorbent, the urination volume variation and the target compounds' deposition bias in the diaper, the matrix blank of the different diaper brands, the storage stabilities and the recoveries of creatinine and phthalate metabolites in the expressed urine. Mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-2-ethylhexyl phthalate and mono-2-ethyl-5-oxohexyl phthalate were involved. 70-80% of the urine can be expressed from the diaper, and the expressed spiking recoveries and the limit of detection of mono-phthalates ranged from 88.5-115% and 0.21-0.50 ng/ml. The method was applied to measure phthalate metabolites in 65 gel diaper samples from 15 infants, and the pilot data suggests the infants are commonly exposed to phthalates. In summary, the method for monitoring of infant exposure to phthalates is sound and validated, and the potential health effects from the vulnerable infants' exposure to phthalates should be concerned.

Urinary Phthalate Metabolite Concentrations and Breast Cancer Incidence and Survival following Breast Cancer: The Long Island Breast Cancer Study Project.

PubMed

Parada, Humberto; Gammon, Marilie D; Chen, Jia; Calafat, Antonia M; Neugut, Alfred I; Santella, Regina M; Wolff, Mary S; Teitelbaum, Susan L

2018-04-26

Phthalates, known endocrine disruptors, may play a role in breast carcinogenesis. Few studies have examined phthalates in relation to breast cancer (BC), and, to our knowledge, none have considered survival following BC. We examined 11 urinary phthalate metabolites, individually and as molar sum groupings, in association with BC incidence and subsequent survival. Our study includes 710 women diagnosed with first primary BC in 1996-1997 and 598 women without BC from Long Island, New York. Within 3 mo of diagnosis, participants provided spot urine samples. Nine phthalate metabolites were measured in all women; two [monocarboxyoctyl phthalate (MCOP) and monocarboxy-isononyl phthalate (MCNP)] were measured in 320 women with and 205 without BC. Women with BC were followed since diagnosis using the National Death Index; during follow-up (median=17.6 y), we identified 271 deaths (98 BC related). We examined creatinine-corrected metabolite concentrations in association with: BC, using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and all-cause/BC-specific mortality, using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We also examined effect modification by body mass index (BMI) and estrogen receptor (ER) status. The highest (vs. lowest) quintiles of mono(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), MCNP, and MCOP were associated with BC ORs ranging from 0.71-0.73. The highest (vs. lowest) quintiles of mono(2-ethylhexyl) phthalate (MEHP) and MCOP were associated with BC-specific mortality HRs of 0.54 (95% CI: 0.28, 1.04) and 0.55 (95% CI: 0.23, 1.35), respectively. For BC-specific mortality, interactions were significant between BMI and mono(2-ethyl-5-oxyhexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), with positive associations among women with BMI<25 and inverse associations among women with BMI≥25.0 kg/m 2 . Consistent with laboratory evidence, we observed inverse associations between urinary concentrations of several phthalate metabolites and BC and subsequent survival; however, these results should be interpreted with caution given that biospecimen collection among women with BC occurred after diagnosis, which may be of particular concern for our case-control findings. https://doi.org/10.1289/EHP2083.

Urinary Biomarkers for Phthalates Associated with Asthma in Norwegian Children

PubMed Central

Carlsen, Karin C. Lødrup; Calafat, Antonia M.; Hoppin, Jane A.; Håland, Geir; Mowinckel, Petter; Carlsen, Kai-Håkon; Løvik, Martinus

2012-01-01

Background: High-molecular-weight phthalates in indoor dust have been associated with asthma in children, but few studies have evaluated phthalate biomarkers in association with respiratory outcomes. Objectives: We explored the association between urinary concentrations of phthalate metabolites and current asthma. Methods: In a cross-sectional analysis, 11 metabolites of 8 phthalates [including four metabolites of di(2-ethylhexyl) phthalate] were measured in one first morning void collected from 2001 through 2004 from 623 10-year-old Norwegian children. Logistic regression models controlling for urine specific gravity, sex, parental asthma, and income were used to estimate associations between current asthma and phthalate metabolite concentrations by quartiles or as log10-transformed variables. Results: Current asthma was associated with both mono(carboxyoctyl) phthalate (MCOP) and mono(carboxynonyl) phthalate (MCNP), although the association was limited to those in the highest quartile of these chemicals. The adjusted odds ratio (aOR) for current asthma was 1.9 (95% CI: 1.0, 3.3) for the highest MCOP quartile compared with the lowest quartile, and 1.3 (95% CI: 0.98, 1.7) for an interquartile-range increase. The aOR for current asthma was 2.2 (95% CI: 1.2, 4.0) for the highest MCNP quartile and 1.3 (95% CI: 1.0, 1.7) for an interquartile-range increase. The other phthalate metabolites were not associated with current asthma. Conclusions: Current asthma was associated with the highest quartiles of MCOP and MCNP, metabolites of two high molecular weight phthalates, diisononyl phthalate and diisodecyl phthalate, respectively. Given the short biological half-life of the phthalates and the cross-sectional design, our findings should be interpreted cautiously. PMID:23164678

Exposure to phthalates in house dust and associated allergies in children aged 6-12years.

PubMed

Ait Bamai, Yu; Araki, Atsuko; Kawai, Toshio; Tsuboi, Tazuru; Saito, Ikue; Yoshioka, Eiji; Cong, Shi; Kishi, Reiko

2016-11-01

Phthalates are widely used as plasticizers in household products. Several studies have reported an association between phthalate exposure and an increased risk of allergies. The present study estimated phthalate exposure in children aged 6-12years and assessed potential correlations with allergies. House dust samples were collected from floors and multi-surface objects >35cm above the floor. Urine samples were collected from the first morning void of the day. Daily phthalate intake (DI dust and DI) was estimated using both house dust and urinary metabolite concentrations. Exposure to di-2-ethylhexyl phthalate (DEHP) in floor dust was associated with parental-reported rhino-conjunctivitis. After stratification by gender, this trend was found to only occur in boys. Furthermore, urinary mono-isobutyl phthalate was inversely associated with parental-reported wheeze in boys. DI dust of benzyl butyl phthalate (BBzP) and DEHP were significantly correlated with DI_BBzP and DI_DEHP, respectively. These correlations were stronger with floor than with multi-surface dust. Our results suggest that, among Japanese children, house dust from low surfaces, such as living room floors, might play a meaningful role in the indoor environmental exposure pathway for BBzP and DEHP. Copyright © 2016 Elsevier Ltd. All rights reserved.

EFFECTS OF MATERNAL EXPOSURE TO PHTHALATES AND BISPHENOL A DURING PREGNANCY ON GESTATIONAL AGE

PubMed Central

Weinberger, Barry; Vetrano, Anna M.; Archer, Faith E.; Marcella, Stephen W.; Buckley, Brian; Wartenberg, Daniel; Robson, Mark G.; Klim, Jammie; Azhar, Sana; Cavin, Sarah; Wang, Lu; Rich, David Q.

2014-01-01

Objective Phthalates and bisphenol A (BPA) are ubiquitous environmental toxicants, present in high concentrations in numerous consumer products. We hypothesized that maternal exposure to phthalates and BPA in pregnancy is associated with shortened gestation. Methods Urinary phthalate and BPA metabolites from 72 pregnant women were measured at the last obstetric clinic visit prior to delivery. Using linear regression models, we estimated the change in gestational age associated with each interquartile range (IQR) increase in phthalate and BPA metabolite concentration. Results IQR increases in urinary mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and BPA concentrations were associated with 4.2 and 1.1 day decreases in gestation, respectively. When stratified by gender, these alterations were found only in male infants. Conclusions We conclude that MEHHP and BPA (free + glucuronide) are associated with reductions in gestation, with effects observed only in males. Our findings are consistent with the idea that these agents induce gender-specific alterations in signaling via PPAR-γ transcription factor, androgen precursors, and/or inflammatory mediators during the initiation of labor. PMID:23795657

Exposure to phthalates and bisphenol A are associated with atopic dermatitis symptoms in children: a time-series analysis.

PubMed

Kim, Eun-Hye; Jeon, Byoung-Hak; Kim, Jihyun; Kim, Young-Min; Han, Youngshin; Ahn, Kangmo; Cheong, Hae-Kwan

2017-03-09

Despite increasing evidence on the relationship between exposure to phthalates and bisphenol A with allergies and asthma, reports on atopic dermatitis (AD) with these chemicals are few. We assessed the association between AD symptoms and the exposure to phthalates and bisphenol A and in children. We surveyed 18 boys with AD (age 3-7 years) in a day care center in Seoul between May 2009 and April 2010. AD symptoms were recorded by using a daily symptom diary. We collected 460 series of pooled urine twice a day, in the morning and afternoon, over 230 working days and measured the concentrations of mono-2-ethyl-5-oxohexyl phthalate (5-oxo-MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (5-OH-MEHP), mono-isobutyl phthalate (MnBP) and bisphenol A glucuronide (BPAG) in the pooled urine. Logistic regression was used for statistical analysis. Most phthalate metabolite levels were higher in the morning than in the afternoon (p < 0.0001). There was seasonal variation in the levels of phthalates and bisphenol A metabolites. Levels of 5-OH-MEHP, MnBP, and BPAG were highest in summer (p < 0.0001). Manifestation of AD symptoms was associated with an increase in urinary levels of MnBP (adjusted odds ratio, aOR = 2.85, 95% CI: 1.12-7.26 per 1 μg/L of MnBP) and BPAG (aOR = 1.79, 95% CI: 0.91-3.52 per 1 μg/L BPAG) on the same day. The levels of MnBP and BPAG in the previous day increased AD symptoms (aOR = 2.74, 95% CI: 1.21-6.20, for 1 μg/L of MnBP and aOR = 2.01, 95% CI: 1.08-3.74 for 1 μg/L BPAG). Our results suggest that exposure to phthalates and bisphenol A is associated with aggravation of AD symptoms in children.

Exposure to Bisphenol A and phthalates metabolites in the third trimester of pregnancy and BMI trajectories.

PubMed

Yang, T C; Peterson, K E; Meeker, J D; Sánchez, B N; Zhang, Z; Cantoral, A; Solano, M; Tellez-Rojo, M M

2018-04-26

Bisphenol A (BPA) and phthalates metabolites are linked to a variety of adverse health consequences but studies have not explored their association with growth trajectories. Explore body mass index (BMI) trajectories for tertile exposures to BPA and phthalates metabolites in the third trimester of pregnancy. We constructed BMI (kg/m 2 ) trajectories from birth to 14 years in a birth cohort of 249 children from Mexico City using tertiles of third trimester maternal urinary concentrations of BPA and phthalates metabolites. Fractional age polynomials and mixed effects models were fit separately by sex. Predicted models were plotted for each metabolite tertile with the covariates mother's education and BMI centered at average values. Highest predicted BMI trajectories for female children were observed for third tertile exposure to the phthalate metabolite mono(2-ethyl-5-carboxypentyl) phthalate. In male children, first tertile exposure to mono-isobutyl phthalate and monobenzyl phthalate and second tertile exposure to mono(2-ethylhexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate predicted the highest BMI trajectory by adolescence. There was no relationshsip between BPA and child growth trajectory. These results suggest sex-specific differences in BMI trajectories by levels of metabolite exposure. Additional studies are needed to consider growth through adolescence in assessing the association of pregnancy exposures on child's BMI. © 2018 World Obesity Federation.

Associations of urinary phthalate metabolites with residential characteristics, lifestyles, and dietary habits among young children in Shanghai, China.

PubMed

Liao, Chenxi; Liu, Wei; Zhang, Jialing; Shi, Wenming; Wang, Xueying; Cai, Jiao; Zou, Zhijun; Lu, Rongchun; Sun, Chanjuan; Wang, Heng; Huang, Chen; Zhao, Zhuohui

2018-03-01

Exposure to household phthalates has been reported to have adverse effects on children's health. In this paper, we used phthalate metabolites in the first morning urine as indicators of household phthalate exposures and examined their associations with residential characteristics, lifestyles and dietary habits among young children. During 2013-2014, we collected morning urines from children aged 5-10years in Shanghai, China and obtained the related information about analyzed factors in this study by questionnaires. Urinary phthalate metabolites were analyzed by isotope dilution-high performance liquid chromatography (HPLC)-heated electrospray ionization source (HESI) coupled with a triple quadrupole mass spectrometry. ANOVA, the Mann-Whitney or Kruskai-Wallis rank tests, and multivariate linear regression analyses were used to examine the target associations. Ten metabolites of seven phthalates in 434 urine samples were analyzed. The detection rates of eight metabolites (MiBP, MnBP, MEHP, MECPP, MEHHP, MEOHP, MEP, and MMP) were >90%, except for MBzP (51.2%), and MCHP with <10.0% of detection rate was not included in analyses. By multivariate linear regression analyses, factors significantly associated with higher concentrations of metabolites included non-usage household air cleaners (MEP and MEHP), changing the child's pillowcase less than one time a week (DEHP metabolites), dusting furniture in the child's bedroom less than three times a week (MMP and MnBP), using more plastic toys (DEHP metabolites and MEP), often having soft drinks (DEHP metabolites) and candies (MiBP). Our results indicated that phthalate exposures were common among Shanghai children and residential characteristics had less significant associations with urinary phthalate metabolites compared with lifestyles and dietary habits. Using less plastic toys, having less candies and soft drinks, using household air cleaner, as well as frequently changing the child's pillowcase and dusting furniture in the child's bedroom could reduce phthalate exposures among children. Copyright © 2017 Elsevier B.V. All rights reserved.

Case study: Possible differences in phthalates exposure among the Czech, Hungarian, and Slovak populations identified based on the DEMOCOPHES pilot study results.

PubMed

Černá, Milena; Malý, Marek; Rudnai, Peter; Középesy, Szilvia; Náray, Miklós; Halzlová, Katarina; Jajcaj, Michal; Grafnetterová, Anna; Krsková, Andrea; Antošová, Danuše; Forysová, Kateřina; Den Hond, Elly; Schoeters, Greet; Joas, Reinhard; Casteleyn, Ludwine; Joas, Anke; Biot, Pierre; Aerts, Dominique; Angerer, Jürgen; Bloemen, Louis; Castaño, Argelia; Esteban, Marta; Koch, Holger M; Kolossa-Gehring, Marike; Gutleb, Arno C; Pavloušková, Jana; Vrbík, Karel

2015-08-01

Phthalates and their metabolites are classified as endocrine modulators. They affect the hormonal balance in both children and adults. The aim of this publication was to compare the urinary levels of phthalate metabolites in selected populations of the Czech Republic (CZ), Slovakia (SK), and Hungary (HU) in relation to the sources of phthalate exposure identified by means of questionnaire (personal care products, floor and wall coverings, plastic toys, and some kinds of foods). Data were obtained through the twin projects COPHES (COnsortium to Perform Human biomonitoring on a European Scale) and DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) from 2009 to 2012. The target groups were children aged 6-11 years old and their mothers up to 45 years of age. The metabolites of phthalates (monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), mono-cyclohexyl phthalate (MCHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), and mono-(2-ethyl-5-oxohexyl) phthalate (5OXO-MEHP)) were analysed in first morning urine samples. After enzymatic glucuronide cleavage, the urine sample analyses were performed using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) in one laboratory that qualified in the External Quality Assessment exercises organised by COPHES. Significant differences in phthalate exposure between countries were revealed for children only but not for mothers. The concentrations of 5-OH-MEHP (P<0.001), 5OXO-MEHP (P<0.001), and their sum (P<0.001) were the highest in SK compared to CZ and HU. The health based guidance values for the sum of DEHP metabolites 5-OH MEHP and 5OXO-MEHP established by the German Commission for biomonitoring of 300 µg/L and 500 µg/L for women adults and children, respectively, were only exceeded in one mother and three boys. A significant difference was also found for MEP (P=0.0149), with the highest concentrations detected in HU. In all countries, the increasing frequency of using personal care products significantly elevated the concentrations of MEP. Some differences were observed between countries in the concentrations of individual urinary phthalate metabolites in children. However, the questionnaire results give no direct explanation for the differences between the countries except the variation in using personal care products. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of phthalate exposure with anthropometric indices and blood pressure in first-grade children.

PubMed

Wu, Wei; Wu, Ping; Yang, Fang; Sun, Dan-Ling; Zhang, De-Xing; Zhou, Yi-Kai

2018-06-02

We aimed to assess the relationship of urine phthalate metabolite concentrations with anthropometric indices, and blood pressure in first-grade children. We detected 11 phthalate metabolites in urine and estimated anthropometric indices, including skinfold measurements, waist circumference (WC), and body mass index (BMI) in 276 children aged 6-8 years. Multivariate linear regression models were used to assess the associations between urinary phthalate metabolite levels, and anthropometric and blood pressure indices in a gender-specific manner. In boys, a 1-ng/mL increase in monobenzyl phthalate (MBzP) concentration was associated with a 0.027-cm decrease in the skinfold measurement (95% confidence interval [CI], - 0.053 to 0.001), whereas a 1-ng/mL increase in mono-ethyl-phthalate (MEP) concentration was associated with a 0.016-mm Hg decrease in systolic blood pressure (95% CI, - 0.031 to 0.001). MBzP, mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and MEOHP concentrations were also inversely associated with WC. However, in girls, MEP concentrations were positively associated with chest measurements, but were inversely associated with WC. A 1-ng/mL increase in monomethyl phthalate concentrations was associated with a 0.039-cm increase in skinfold measurements (95% CI, 0.002 to 0.076), whereas a 1-ng/mL increase in MECPP concentrations was associated with a 0.050 cm decrease in skinfold measurements (95% CI, - 0.095 to - 0.005). In this exploratory, cross-sectional analysis, we identified various interesting associations between different phthalate metabolite levels and anthropometric indices, which suggest that some of phthalate metabolite should be considered in addition to the prevalence rates of overweight and obesity.

Levels of metabolites of organophosphate pesticides, phthalates, and bisphenol A in pooled urine specimens from pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa)

PubMed Central

Ye, Xibiao; Pierik, Frank H.; Angerer, Jürgen; Meltzer, Helle Margrete; Jaddoe, Vincent W.V.; Tiemeier, Henning; Hoppin, Jane A.; Longnecker, Matthew P.

2013-01-01

Concerns about reproductive and developmental health risks of exposure to organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6-trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were measured in 10 pooled urine samples representing 110 pregnant women who participated in the Norwegian Mother and Child Birth Cohort (MoBa) study in 2004. Daily intakes were estimated from urinary data and compared with reference doses (RfDs) and daily tolerable intakes (TDIs). The MoBa women had a higher mean BPA concentration (4.50 μg/L) than the pregnant women in the Generation R Study (Generation R) in the Netherlands and the National Health and Nutrition Examination Survey (NHANES) in the United States. The mean concentration of total DAP metabolites (24.20 μg/L) in MoBa women was higher than that in NHANES women but lower than that in Generation R women. The diethyl phthalate metabolite mono-ethyl phthalate (MEP) was the dominant phthalate metabolite in all three studies, with the mean concentrations of greater than 300 μg/L. The MoBa and Generation R women had higher mean concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) than the NHANES women. The estimated average daily intakes of BPA, chlorpyrifos/chlorpyrfios-methyl and phthalates in MoBa (and the other two studies) were below the RfDs and TDIs. The higher levels of metabolites in the MoBa participants may have been from intake via pesticide residues in food (organophosphates), consumption of canned food, especially fish/seafood (BPA), and use of personal care products (selected phthalates). PMID:19394271

Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China.

PubMed

Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken

2006-11-01

Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.

Decreased Serum Free Testosterone in Workers Exposed to High Levels of Di-n-butyl Phthalate (DBP) and Di-2-ethylhexyl Phthalate (DEHP): A Cross-Sectional Study in China

PubMed Central

Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken

2006-01-01

Background Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Objective Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. Methods We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Results Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 μg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 μg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 μg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = −0.25, p = 0.03) and MEHP (r = −0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = −0.26, p = 0.002). Conclusion We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers. PMID:17107847

Exposure of Preschool-Age Greek Children (RHEA Cohort) to Bisphenol A, Parabens, Phthalates, and Organophosphates.

PubMed

Myridakis, Antonis; Chalkiadaki, Georgia; Fotou, Marianna; Kogevinas, Manolis; Chatzi, Leda; Stephanou, Euripides G

2016-01-19

Phthalate esters (PEs), bisphenol A (BPA), and parabens (PBs), which are used in numerous consumer products, are known for their endocrine disrupting properties. Organophosphate chemicals (OPs), which form the basis of the majority of pesticides, are known for their neurotoxic activity in humans. All of these chemicals are associated with health problems to which children are more susceptible. Once they enter the human body, PEs, BPA, PBs, and OPs are metabolized and/or conjugated and finally excreted via urine. Hence, human exposure to these substances is examined through a determination of the urinary concentrations of their metabolites. This study assessed the exposure of Greek preschool-age children to PEs, BPA, PBs, and OPs by investigating the urinary levels of seven PEs metabolites, six PBs, BPA, and six dialkyl phosphate metabolites in five-hundred samples collected from 4-year-old children, subjects of the "RHEA" mother-child cohort in Crete, Greece. Daily intake of endocrine disruptors, calculated for 4 year old children, was lower than the corresponding daily intake for 2.5 year old children, which were determined in an earlier study of the same cohort. In some cases the daily intake levels exceeded the U.S. Environmental Protection Agency Tolerable Daily Intake (TDI) values and the EFSA Reference Doses (RfD) (e.g., for di-2-ethyl-hexyl phthalate, 3.6% and 1% of the children exceeded RfD and TDi, respectively). Exposure was linked to three main sources: PEs-BPA to plastic, PBs-diethyl phthalate to personal hygiene products, and OPs to food.

Reducing Phthalate, Paraben, and Phenol Exposure from Personal Care Products in Adolescent Girls: Findings from the HERMOSA Intervention Study.

PubMed

Harley, Kim G; Kogut, Katherine; Madrigal, Daniel S; Cardenas, Maritza; Vera, Irene A; Meza-Alfaro, Gonzalo; She, Jianwen; Gavin, Qi; Zahedi, Rana; Bradman, Asa; Eskenazi, Brenda; Parra, Kimberly L

2016-10-01

Personal care products are a source of exposure to potentially endocrine-disrupting chemicals such as phthalates, parabens, triclosan, and benzophenone-3 (BP-3) for adolescent girls. We enrolled 100 Latina girls in a youth-led, community-based participatory research intervention study to determine whether using personal care products whose labels stated they did not contain these chemicals for 3 days could lower urinary concentrations. Pre- and postintervention urine samples were analyzed for phthalate metabolites, parabens, triclosan, and BP-3 using high-performance liquid chromatography/tandem mass spectrometry. Urinary concentrations of mono-ethyl phthalate (MEP) decreased by 27.4% (95% CI: -39.3, -13.2) on average over the 3-day intervention; no significant changes were seen in urinary concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP). Methyl and propyl paraben concentrations decreased by 43.9% (95% CI: -61.3, -18.8) and 45.4% (95% CI: -63.7, -17.9), respectively. Unexpectedly, concentrations of ethyl and butyl paraben concentrations increased, although concentrations were low overall and not detected in almost half the samples. Triclosan concentrations decreased by 35.7% (95% CI: -53.3, -11.6), and BP-3 concentrations decreased by 36.0% (95% CI: -51.0, -16.4). This study demonstrates that techniques available to consumers, such as choosing personal care products that are labeled to be free of phthalates, parabens, triclosan, and BP-3, can reduce personal exposure to possible endocrine-disrupting chemicals. Involving youth in the design and implementation of the study was key to recruitment, retention, compliance, and acceptability of the intervention. Harley KG, Kogut K, Madrigal DS, Cardenas M, Vera IA, Meza-Alfaro G, She J, Gavin Q, Zahedi R, Bradman A, Eskenazi B, Parra KL. 2016. Reducing phthalate, paraben, and phenol exposure from personal care products in adolescent girls: findings from the HERMOSA Intervention Study. Environ Health Perspect 124:1600-1607; http://dx.doi.org/10.1289/ehp.1510514.

Exposure Assessment Issues in Epidemiology Studies of Phthalates

PubMed Central

Johns, Lauren E.; Cooper, Glinda S.; Galizia, Audrey; Meeker, John D.

2015-01-01

Purpose The purpose of this paper is to review exposure assessment issues that need to be addressed in designing and interpreting epidemiology studies of phthalates, a class of chemicals commonly used in consumer and personal care products. Specific issues include population trends in exposure, temporal reliability of a urinary metabolite measurement, and how well a single urine sample may represent longer-term exposure. The focus of this review is on seven specific phthalates: diethyl phthalate (DEP); di-n-butyl phthalate (DBP); diisobutyl phthalate (DiBP); butyl benzyl phthalate (BBzP); di(2-ethylhexyl) phthalate (DEHP); diisononyl phthalate (DiNP); and diisodecyl phthalate (DiDP). Methods Comprehensive literature search using multiple search strategies Results Since 2001, declines in population exposure to DEP, BBzP, DBP, and DEHP have been reported in the United States and Germany, but DEHP exposure has increased in China. Although the half-lives of various phthalate metabolites are relatively short (3 to 18 hours), the intraclass correlation coefficients (ICCs) for phthalate metabolites, based on spot and first morning urine samples collected over a week to several months, range from weak to moderate, with a tendency toward higher ICCs (greater temporal stability) for metabolites of the shorter-chained (DEP, DBP, DiBP and BBzP, ICCs generally 0.3 to 0.6) compared with those of the longer-chained (DEHP, DiNP, DiDP, ICCs generally 0.1 to 0.3) phthalates. Additional research on optimal approaches to addressing the issue of urine dilution in studies of associations between biomarkers and different type of health effects is needed. Conclusions In conclusion, the measurement of urinary metabolite concentrations in urine could serve as a valuable approach to estimating exposure to phthalates in environmental epidemiology studies. Careful consideration of the strengths and limitations of this approach when interpreting study results is required. PMID:26313703

Dietary sources of cumulative phthalates exposure among the U.S. general population in NHANES 2005-2014.

PubMed

Varshavsky, Julia R; Morello-Frosch, Rachel; Woodruff, Tracey J; Zota, Ami R

2018-06-01

Anti-androgenic phthalates are reproductive toxicants that may have additive effects on male development. Diet is the primary exposure source for most phthalates, which contaminate the food supply through food contact materials and industrialized production. To compare dietary sources of cumulative phthalates exposure between "food at home" (e.g. food consumed from a grocery store) and "food away from home" (e.g. food consumed from fast food/restaurants and cafeterias) in the U.S. general population. We estimated cumulative phthalates exposure by calculating daily intake from metabolite concentrations in urinary spot samples for 10,253 participants (≥6 years old) using National Health and Nutrition Examination Survey (NHANES, 2005-2014) data. We constructed a biologically relevant metric of phthalates daily intake (∑androgen-disruptor, μg/kg/day) by converting phthalates into anti-androgen equivalent terms prior to their summation. Particular foods and the percent of total energy intake (TEI) consumed from multiple dining out sources were ascertained from 24-h recall surveys. Associations with ∑androgen-disruptor levels were estimated for children, adolescents, and adults using multivariable linear regression. We observed a consistent positive association between dining out and Σandrogen-disruptor levels across the study population (p-trend <0.0001). Among adolescents, high consumers of foods outside the home had 55% (95% CI: 35%, 78%) higher Σandrogen-disruptor levels compared to those who only consumed food at home. The contribution of specific dining out sources to Σandrogen-disruptor levels varied by age group. For example, cafeteria food was associated with 15% (95% CI: 4.0%, 28%) and 64% (95% CI: 40%, 92%) higher Σandrogen-disruptor levels in children and adults, respectively. Particular foods, especially sandwiches (i.e. cheeseburgers), were associated with increased Σandrogen-disruptor levels only if they were purchased away from home (p < 0.01). Dining out may be an important source of biologically relevant cumulative phthalates exposure among the U.S. Future studies should evaluate modifiable production practices that remove phthalates from the food supply in addition to the efficacy of interventions that promote eating fresh foods prepared at home. Copyright © 2018 Elsevier Ltd. All rights reserved.

Urinary heavy metals, phthalates, phenols, thiocyanate, parabens, pesticides, polyaromatic hydrocarbons but not arsenic or polyfluorinated compounds are associated with adult oral health: USA NHANES, 2011-2012.

PubMed

Shiue, Ivy

2015-10-01

Links between environmental chemicals and human health have emerged over the last few decades, but the effects on oral health have been less studied. Therefore, it was aimed to study the relationships of different sets of urinary chemical concentrations and adult oral health conditions in a national and population-based setting. Data was retrieved from the United States National Health and Nutrition Examination Surveys, 2011-2012 including demographics, self-reported oral health conditions and urinary environmental chemical concentrations (one third representative sample of the study population). Chi-square test, t test, and survey-weighted logistic and multi-nominal regression modeling were performed. Of 4566 American adults aged 30-80, 541 adults (11.9 %) reported poor teeth health while 1020 adults (22.4 %) reported fair teeth. Eight hundred fifty-five people (19.1 %) claimed to have gum disease, presented with higher levels of urinary cadmium, cobalt and polyaromatic hydrocarbons. Six hundred three adults (13.3 %) had bone loss around the mouth, presented with higher levels of cadmium, nitrate, thiocyanate, propyl paraben and polyaromatic hydrocarbons. Eight hundred forty-five adults (18.5 %) had tooth loose not due to injury, presented with higher level of cadmium, thiocyanate and polyaromatic hydrocarbons. Eight hundred forty-five adults (18.5 %) with higher levels of lead, uranium, polyaromatic hydrocarbons but lower level of triclosan noticed their teeth did not look right. Three hundred fifty-one adults (7.7 %) often had aching in the mouth and 650 (14.3 %) had it occasionally, presented with higher levels of phthalates, pesticides and polyaromatic hydrocarbons. Benzophenone-3 and triclosan elicited protective effects. Regulation of environmental chemicals in prevention of adult oral health might need to be considered in future health and environmental policies.

Medications as a source of human exposure to phthalates.

PubMed Central

Hauser, Russ; Duty, Susan; Godfrey-Bailey, Linda; Calafat, Antonia M

2004-01-01

Phthalates are a group of multifunctional chemicals used in consumer and personal care products, plastics, and medical devices. Laboratory studies show that some phthalates are reproductive and developmental toxicants. Recently, human studies have shown measurable levels of several phthalates in most of the U.S. general population. Despite their widespread use and the consistent toxicologic data on phthalates, information is limited on sources and pathways of human exposure to phthalates. One potential source of exposure is medications. The need for site-specific dosage medications has led to the use of enteric coatings that allow the release of the active ingredients into the small intestine or in the colon. The enteric coatings generally consist of various polymers that contain plasticizers, including triethyl citrate, dibutyl sebacate, and phthalates such as diethyl phthalate (DEP) and dibutyl phthalate (DBP). In this article we report on medications as a potential source of exposure to DBP in a man who took Asacol [active ingredient mesalamine (mesalazine)] for the treatment of ulcerative colitis. In a spot urine sample from this man collected 3 months after he started taking Asacol, the concentration of monobutyl phthalate, a DBP metabolite, was 16,868 ng/mL (6,180 micro g/g creatinine). This concentration was more than two orders of magnitude higher than the 95th percentile for males reported in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). The patient's urinary concentrations of monoethyl phthalate (443.7 ng/mL, 162.6 micro g/g creatinine), mono-2-ethylhexyl phthalate (3.0 ng/mL, 1.1 micro g/g creatinine), and monobenzyl phthalate (9.3 ng/mL, 3.4 micro g/g creatinine) were unremarkable compared with the NHANES 1999-2000 values. Before this report, the highest estimated human exposure to DBP was more than two orders of magnitude lower than the no observable adverse effect level from animal studies. Further research is necessary to determine the proportional contribution of medications, as well as personal care and consumer products, to a person's total phthalate burden. PMID:15121520

Parental Concern about Environmental Chemical Exposures and Children's Urinary Concentrations of Phthalates and Phenols.

PubMed

Pell, Tripler; Eliot, Melissa; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Sathyanarayana, Sheela; Braun, Joseph M

2017-07-01

To examine whether parents' concerns about environmental chemical exposures were associated with urinary phthalate and phenol concentrations in their school-age children. In a prospective cohort of 218 mother-child pairs from Cincinnati, Ohio (2010-2014), we measured 11 phthalate metabolites and 5 phenols in urine samples when children were age 8 years and used questionnaire data from caregivers. We estimated the covariate-adjusted percent difference in phthalates and phenols among children of parents who expressed concern about environmental chemical exposures compared with children whose parents did not. Concentrations of 4 phthalates, bisphenol S, and bisphenol A were lower among children whose parents expressed concern about environmental chemicals (n = 122) compared with those who did not (n = 96). Di-2-ethylhexyl phthalate metabolites, bisphenol S, and bisphenol A concentrations were 23% (95% CI -38, -5), 37% (95% CI -49, -21), and 13% (95% CI -26, 3) lower, respectively, among children whose parents expressed concern compared with those whose parents did not. Triclosan concentrations were 35% greater (95% CI -2, 87) among children whose parents expressed concern compared with children whose parents did not. Parental concern about environmental chemicals was associated with lower childhood urine concentrations of several phthalates and phenols; unexpectedly, parental concern was associated with greater triclosan concentrations. These results suggest that parental concern may be an important factor in mitigating children's phthalate and phenol exposures. Copyright © 2017 Elsevier Inc. All rights reserved.

Prenatal phthalate exposure and reduced masculine play in boys.

PubMed

Swan, S H; Liu, F; Hines, M; Kruse, R L; Wang, C; Redmon, J B; Sparks, A; Weiss, B

2010-04-01

Foetal exposure to antiandrogens alters androgen-sensitive development in male rodents, resulting in less male-typical behaviour. Foetal phthalate exposure is also associated with male reproductive development in humans, but neurodevelopmental outcomes have seldom been examined in relation to phthalate exposure. To assess play behaviour in relation to phthalate metabolite concentration in prenatal urine samples, we recontacted participants in the Study for Future Families whose phthalate metabolites had been measured in mid-pregnancy urine samples. Mothers completed a questionnaire including the Pre-School Activities Inventory, a validated instrument used to assess sexually dimorphic play behaviour. We examined play behaviour scores (masculine, feminine and composite) in relationship to (log(10)) phthalate metabolite concentrations in mother's urine separately for boys (N = 74) and girls (N = 71). Covariates (child's age, mother's age and education and parental attitude towards atypical play choices) were controlled using multivariate regression models. Concentrations of dibutyl phthalate metabolites, mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) and their sum, were associated with a decreased (less masculine) composite score in boys (regression coefficients -4.53,-3.61 and -4.20, p = 0.01, 0.07 and 0.04 for MnBP, MiBP and their sum respectively). Concentrations of two urinary metabolites of di(2-ethylhexyl) phthalate (DEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and the sum of these DEHP metabolites plus mono(2-ethylhexyl) phthalate were associated with a decreased masculine score (regression coefficients -3.29,-2.94 and -3.18, p = 0.02, 0.04 and 0.04) for MEHHP, MEOHP and the sum respectively. No strong associations were seen between behaviour and urinary concentrations of any other phthalate metabolites in boys, or between girls' scores and any metabolites. These data, although based on a small sample, suggest that prenatal exposure to antiandrogenic phthalates may be associated with less male-typical play behaviour in boys. Our findings suggest that these ubiquitous environmental chemicals have the potential to alter androgen-responsive brain development in humans.

Food Packaging and Bisphenol A and Bis(2-Ethyhexyl) Phthalate Exposure: Findings from a Dietary Intervention

PubMed Central

Gray, Janet M.; Engel, Connie L.; Rawsthorne, Teresa W.; Dodson, Robin E.; Ackerman, Janet M.; Rizzo, Jeanne; Nudelman, Janet L.; Brody, Julia Green

2011-01-01

Background: Bisphenol A (BPA) and bis(2-ethylhexyl) phthalate (DEHP) are high-production-volume chemicals used in plastics and resins for food packaging. They have been associated with endocrine disruption in animals and in some human studies. Human exposure sources have been estimated, but the relative contribution of dietary exposure to total intake has not been studied empirically. Objectives: To evaluate the contribution of food packaging to exposure, we measured urinary BPA and phthalate metabolites before, during, and after a “fresh foods” dietary intervention. Methods: We selected 20 participants in five families based on self-reported use of canned and packaged foods. Participants ate their usual diet, followed by 3 days of “fresh foods” that were not canned or packaged in plastic, and then returned to their usual diet. We collected evening urine samples over 8 days in January 2010 and composited them into preintervention, during intervention, and postintervention samples. We used mixed-effects models for repeated measures and Wilcoxon signed-rank tests to assess change in urinary levels across time. Results: Urine levels of BPA and DEHP metabolites decreased significantly during the fresh foods intervention [e.g., BPA geometric mean (GM), 3.7 ng/mL preintervention vs. 1.2 ng/mL during intervention; mono-(2-ethyl-5-hydroxy hexyl) phthalate GM, 57 ng/mL vs. 25 ng/mL]. The intervention reduced GM concentrations of BPA by 66% and DEHP metabolites by 53–56%. Maxima were reduced by 76% for BPA and 93–96% for DEHP metabolites. Conclusions: BPA and DEHP exposures were substantially reduced when participants’ diets were restricted to food with limited packaging. PMID:21450549

The urinary metabolites of DINCH® have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ.

PubMed

Engel, Anika; Buhrke, Thorsten; Kasper, Stefanie; Behr, Anne-Cathrin; Braeuning, Albert; Jessel, Sönke; Seidel, Albrecht; Völkel, Wolfgang; Lampen, Alfonso

2018-05-01

DINCH ® (di-isononyl cyclohexane-1,2-dicarboxylate) is a non-phthalate plasticizer that has been developed to replace phthalate plasticizers such as DEHP (di-2-ethylhexyl phthalate) or DINP (di-isononyl phthalate). DINCH ® is metabolized to its corresponding monoester and subsequently to oxidized monoester derivatives. These are conjugated to glucuronic acid and subject to urinary excretion. In contrast to DINCH ® , there are almost no toxicological data available regarding its primary and secondary metabolites. The present study aimed at the characterization of potential endocrine properties of DINCH ® and five DINCH ® metabolites by using reporter gene assays to monitor the activity of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ in vitro. DINCH ® itself did not have any effect on the activity of these receptors whereas DINCH ® metabolites were shown to activate all these receptors. In the case of AR, DINCH ® metabolites predominantly enhanced dihydrotestosterone-stimulated AR activity. In the H295R steroidogenesis assay, neither DINCH ® nor any of its metabolites affected estradiol or testosterone synthesis. In conclusion, primary and secondary DINCH ® metabolites exert different effects at the molecular level compared to DINCH ® itself. All these in vitro effects of DINCH ® metabolites, however, were only observed at high concentrations such as 10 μM or above which is about three orders of magnitude above reported DINCH ® metabolite concentrations in human urine. Thus, the in vitro data do not support the notion that DINCH ® or any of the investigated metabolites may exert considerable endocrine effects in vivo at relevant human exposure levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Phthalate metabolites related to infertile biomarkers and infertility in Chinese men.

PubMed

Liu, Liangpo; Wang, Heng; Tian, Meiping; Zhang, Jie; Panuwet, Parinya; D'Souza, Priya Esilda; Barr, Dana Boyd; Huang, Qingyu; Xia, Yankai; Shen, Heqing

2017-12-01

Although in vitro and in vivo laboratory studies have demonstrated androgen and anti-androgen effects on male reproduction from phthalate exposures, human studies still remain inconsistent. Therefore, a case-control study (n = 289) was conducted to evaluate the associations between phthalate exposures, male infertility risks, and changes in metabolomic biomarkers. Regional participants consisted of fertile (n = 150) and infertile (n = 139) males were recruited from Nanjing Medical University' affiliated hospitals. Seven urinary phthalate metabolites were measured using HPLC-MS/MS. Associations between levels of phthalate metabolites, infertility risks, and infertility-related biomarkers were statistically evaluated. MEHHP, one of the most abundant DEHP oxidative metabolites was significantly lower in cases than in controls (p = 0.039). When using the 1st quartile range as a reference, although statistically insignificant for odds ratios (ORs) of the 2nd, 3rd, and 4th quartiles (OR (95% CI) = 1.50 (0.34-6.48), 0.70 (0.14-3.52) and 0.42 (0.09-2.00), respectively), the MEHHP dose-dependent trend of infertility risk expressed as OR decreased significantly (p = 0.034). More interestingly, most of the phthalate metabolites, including MEHHP, were either positively associated with fertile prevention metabolic biomarkers or negatively associated with fertile hazard ones. Phthalate metabolism, along with their activated infertility-related biomarkers, may contribute to a decreased risk of male infertility at the subjects' ongoing exposure levels. Our results may be illustrated by the low-dose related androgen effect of phthalates and can improve our understanding of the controversial epidemiological results on this issue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003-2010.

PubMed

Zota, Ami R; Phillips, Cassandra A; Mitro, Susanna D

2016-10-01

Phthalates and bisphenol A (BPA) are widely used industrial chemicals that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of processed or packaged food. To examine associations between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the U.S. We combined data on 8,877 participants from the National Health and Nutrition Examination Survey (NHANES 2003-2010). Using 24-hr dietary recall data, we quantified: a) fast food intake [percent of total energy intake (TEI) from fast food]; b) fast food-derived fat intake (percent of TEI from fat in fast food); and c) fast food intake by food group (dairy, eggs, grains, meat, and other). We examined associations between dietary exposures and urinary chemical concentrations using multivariate linear regression. We observed evidence of a positive, dose-response relationship between fast food intake and exposure to phthalates (p-trend < 0.0001) but not BPA; participants with high consumption (≥ 34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, respectively, than nonconsumers. Fast food-derived fat intake was also positively associated with ΣDEHPm and DiNPm (p-trend < 0.0001). After adjusting for other food groups, ΣDEHPm was associated with grain and other intake, and DiNPm was associated with meat and grain intake. Fast food may be a source of exposure to DEHP and DiNP. These results, if confirmed, could inform individual and regulatory exposure reduction strategies. Zota AR, Phillips CA, Mitro SD. 2016. Recent fast food consumption and bisphenol A and phthalates exposures among the U.S. population in NHANES, 2003-2010. Environ Health Perspect 124:1521-1528; http://dx.doi.org/10.1289/ehp.1510803.

Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity.

PubMed

Tran, V; Tindula, G; Huen, K; Bradman, A; Harley, K; Kogut, K; Calafat, A M; Nguyen, B; Parra, K; Ye, X; Eskenazi, B; Holland, N

2017-04-01

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

Prenatal Phthalate Exposure and 8-Isoprostane among Mexican-American Children with High Prevalence of Obesity

PubMed Central

Tran, Vy; Tindula, Gwen; Huen, Karen; Bradman, Asa; Harley, Kim; Kogut, Katherine; Calafat, Antonia M.; Nguyen, Brian; Parra, Kimberly; Ye, Xiaoyun; Eskenazi, Brenda; Holland, Nina

2016-01-01

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species (ROS) and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5-, 9- and 14-years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year old children. No associations were observed between 8-isoprostane and BMI, BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks gestation [monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates] were negatively associated with 8-isoprostane concentrations among 9 year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates. PMID:28031075

Reducing Phthalate, Paraben, and Phenol Exposure from Personal Care Products in Adolescent Girls: Findings from the HERMOSA Intervention Study

PubMed Central

Harley, Kim G.; Kogut, Katherine; Madrigal, Daniel S.; Cardenas, Maritza; Vera, Irene A.; Meza-Alfaro, Gonzalo; She, Jianwen; Gavin, Qi; Zahedi, Rana; Bradman, Asa; Eskenazi, Brenda; Parra, Kimberly L.

2016-01-01

Background: Personal care products are a source of exposure to potentially endocrine-disrupting chemicals such as phthalates, parabens, triclosan, and benzophenone-3 (BP-3) for adolescent girls. Methods: We enrolled 100 Latina girls in a youth-led, community-based participatory research intervention study to determine whether using personal care products whose labels stated they did not contain these chemicals for 3 days could lower urinary concentrations. Pre- and postintervention urine samples were analyzed for phthalate metabolites, parabens, triclosan, and BP-3 using high-performance liquid chromatography/tandem mass spectrometry. Results: Urinary concentrations of mono-ethyl phthalate (MEP) decreased by 27.4% (95% CI: –39.3, –13.2) on average over the 3-day intervention; no significant changes were seen in urinary concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP). Methyl and propyl paraben concentrations decreased by 43.9% (95% CI: –61.3, –18.8) and 45.4% (95% CI: –63.7, –17.9), respectively. Unexpectedly, concentrations of ethyl and butyl paraben concentrations increased, although concentrations were low overall and not detected in almost half the samples. Triclosan concentrations decreased by 35.7% (95% CI: –53.3, –11.6), and BP-3 concentrations decreased by 36.0% (95% CI: –51.0, –16.4). Discussion: This study demonstrates that techniques available to consumers, such as choosing personal care products that are labeled to be free of phthalates, parabens, triclosan, and BP-3, can reduce personal exposure to possible endocrine-disrupting chemicals. Involving youth in the design and implementation of the study was key to recruitment, retention, compliance, and acceptability of the intervention. Citation: Harley KG, Kogut K, Madrigal DS, Cardenas M, Vera IA, Meza-Alfaro G, She J, Gavin Q, Zahedi R, Bradman A, Eskenazi B, Parra KL. 2016. Reducing phthalate, paraben, and phenol exposure from personal care products in adolescent girls: findings from the HERMOSA Intervention Study. Environ Health Perspect 124:1600–1607; http://dx.doi.org/10.1289/ehp.1510514 PMID:26947464

Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001–2010

PubMed Central

Calafat, Antonia M.; Woodruff, Tracey J.

2014-01-01

Background: Phthalates are ubiquitous environmental contaminants. Because of potential adverse effects on human health, butylbenzyl phthalate [BBzP; metabolite, monobenzyl phthalate (MBzP)], di-n-butyl phthalate [DnBP; metabolite, mono-n-butyl phthalate (MnBP)], and di(2-ethylhexyl) phthalate (DEHP) are being replaced by substitutes including other phthalates; however, little is known about consequent trends in population-level exposures. Objective: We examined temporal trends in urinary concentrations of phthalate metabolites in the general U.S. population and whether trends vary by sociodemographic characteristics. Methods: We combined data on 11 phthalate metabolites for 11,071 participants from five cycles of the National Health and Nutrition Examination Survey (2001–2010). Percent changes and least square geometric means (LSGMs) were calculated from multivariate regression models. Results: LSGM concentrations of monoethyl phthalate, MnBP, MBzP, and ΣDEHP metabolites decreased between 2001–2002 and 2009–2010 [percent change (95% CI): –42% (–49, –34); –17% (–23, –9); –32% (–39, –23) and –37% (–46, –26), respectively]. In contrast, LSGM concentrations of monoisobutyl phthalate, mono(3-carboxypropyl) phthalate (MCPP), monocarboxyoctyl phthalate, and monocarboxynonyl phthalate (MCNP) increased over the study period [percent change (95% CI): 206% (178, 236); 25% (8, 45); 149% (102, 207); and 15% (1, 30), respectively]. Trends varied by subpopulations for certain phthalates. For example, LSGM concentrations of ΣDEHP metabolites, MCPP, and MCNP were higher in children than adults, but the gap between groups narrowed over time (pinteraction < 0.01). Conclusions: Exposure of the U.S. population to phthalates has changed in the last decade. Data gaps make it difficult to explain trends, but legislative activity and advocacy campaigns by nongovernmental organizations may play a role in changing trends. Citation: Zota AZ, Calafat AM, Woodruff TJ. 2014. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001–2010. Environ Health Perspect 122:235–241; http://dx.doi.org/10.1289/ehp.1306681 PMID:24425099

Reducing prenatal phthalate exposure through maternal dietary changes: results from a pilot study

PubMed Central

Barrett, Emily S.; Velez, Marissa; Qiu, Xing; Chen, Shaw-Ree

2016-01-01

Objectives Diet is a major source of exposure to certain phthalates, a class of environmental chemicals associated with endocrine disruption in animal models and humans. Several studies have attempted to lower phthalate exposure through carefully designed dietary interventions, with inconsistent results. We conducted a dietary intervention pilot study with the objective to lower phthalate exposure in low-income pregnant women, a particularly vulnerable population. Methods Ten pregnant women consumed a provided diet consisting of mostly fresh, organic foods for three days. We collected urine samples before, during, and after the intervention and conducted semi-structured interviews to assess the feasibility and acceptability of the intervention. We used repeated measures ANOVA and paired t-tests to assess differences in urinary phthalate metabolite concentrations across the study, focusing on the metabolites of di-2-ethylhexyl phthalate (DEHP), a phthalate of particular interest, and their molar sum (∑DEHP). Results Phthalate metabolite concentrations did not change appreciably during the intervention period. We observed no significant difference in ∑DEHP metabolite concentrations across the three time periods (F=0.21; adjusted p-value=0.65), and no reduction during the intervention as compared to baseline (t=−1.07, adjusted p-value=0.51). Results of interviews indicated that participants were not motivated to make dietary changes to potentially reduce chemical exposures outside of the study. Conclusions Despite the small sample size, our results suggest that promoting dietary changes to lower phthalate exposure may not be an effective public health measure. Reducing the use of phthalates in food processing and packaging may be a better solution to lowering exposure on a population level. PMID:25652062

Impact of phthalate and BPA exposure during in utero windows of susceptibility on reproductive hormones and sexual maturation in peripubertal males.

PubMed

Watkins, Deborah J; Sánchez, Brisa N; Téllez-Rojo, Martha Maria; Lee, Joyce M; Mercado-García, Adriana; Blank-Goldenberg, Clara; Peterson, Karen E; Meeker, John D

2017-06-21

Phthalates and BPA are endocrine disrupting chemicals (EDCs) widely used in consumer products. Evidence suggests that phthalate and BPA exposure alters steroid hormone levels in adults, while in utero exposure has been associated with altered fetal reproductive development in boys. However, the impact of exposure during distinct critical windows of in utero development on hormone concentrations and sexual maturation during the pubertal transition has not been examined. The objective of this study was to assess trimester-specific in utero phthalate and BPA exposure in relation to measures of reproductive development among peripubertal boys in a Mexico City birth cohort. We measured maternal urinary phthalate metabolites and BPA during the first, second, and third trimesters of pregnancy. We measured serum levels of testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation (Tanner staging and testicular volume) among male children at age 8-14 years (n = 109). Linear and logistic regression were used to investigate trimester-specific in utero exposure as predictors of peripubertal hormone levels and sexual maturation, respectively. In sensitivity analyses we evaluated estimated exposure at 7 weeks gestation and rates of change in exposure across pregnancy in relation to outcomes. Exposure to phthalates during the third trimester was associated with reduced odds of having a Tanner stage >1 for pubic hair development (e.g. MBzP OR = 0.18 per interquartile range (IQR) increase; 95% CI:0.03-0.97) and higher peripubertal SHBG levels (e.g. MBzP 15.2%/IQR; 95% CI:3.2-28%), while first and second trimester phthalates were not. In contrast, exposure to DEHP during the first trimester was associated with higher estradiol (11%/IQR; 95% CI:1.5-22%), while second or third trimester DEHP exposure was not. Sensitivity analyses yielded similar findings. Associations between in utero phthalate and BPA exposure and peripubertal measures of male reproductive development are dependent on the timing of that exposure during gestation. These findings suggest that future epidemiological studies relating in utero EDC exposure to pubertal outcomes should consider windows of susceptibility.

Phthalate exposure and semen quality in fertile US men.

PubMed

Thurston, S W; Mendiola, J; Bellamy, A R; Levine, H; Wang, C; Sparks, A; Redmon, J B; Drobnis, E Z; Swan, S H

2016-07-01

Several experimental and observational studies have demonstrated the antiandrogenicity of several phthalates. However, there is limited evidence of an association between phthalate exposure in adult life and semen quality. The aim of this study was to examine phthalate exposure during adulthood in relation to semen quality in fertile US men. This multi-center cross-sectional study included 420 partners of pregnant women who attended a prenatal clinic in one of five US cities during 1999-2001. Nine phthalate metabolites [mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP)], as well as mono-n-butyl phthalate (MBP) and mono-isobutyl phthalate (MiBP), mono (three carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP)] were measured in urine collected at the same time as the semen sample. We regressed natural log-transformed (ln) sperm concentration, ln(total sperm count), ln(total motile sperm count), percent motile spermatozoa, and percent spermatozoa with normal morphology on each of the nine natural log-transformed metabolite concentrations and on the molar-weighted sum of DEHP metabolites in separate models. We fit unadjusted models and models that adjusted for confounders determined a priori. In unadjusted models, ln(MiBP) was significantly and positively associated with motility and ln(MBzP) significantly negatively associated with ln(total sperm count). In adjusted linear models, urinary metabolite concentrations of DEHP, DBP, DEP, and DOP were not associated with any semen parameter. We found an inverse association between ln(MBzP) concentrations and sperm motility (β = -1.47, 95% CI: -2.61, -0.33), adjusted for ln(creatinine concentration), geographic location, age, race, smoking status, stress, recent fever, time from sample collection and time to complete analysis. Several sensitivity analyses confirmed the robustness of these associations. This study and the available literature suggest that impacts of adult exposure to phthalates at environmental levels on classical sperm parameters are likely to be small. © 2015 American Society of Andrology and European Academy of Andrology.

Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003–2010

PubMed Central

Zota, Ami R.; Phillips, Cassandra A.; Mitro, Susanna D.

2016-01-01

Background: Phthalates and bisphenol A (BPA) are widely used industrial chemicals that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of processed or packaged food. Objective: To examine associations between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the U.S. population. Methods: We combined data on 8,877 participants from the National Health and Nutrition Examination Survey (NHANES 2003–2010). Using 24-hr dietary recall data, we quantified: a) fast food intake [percent of total energy intake (TEI) from fast food]; b) fast food-derived fat intake (percent of TEI from fat in fast food); and c) fast food intake by food group (dairy, eggs, grains, meat, and other). We examined associations between dietary exposures and urinary chemical concentrations using multivariate linear regression. Results: We observed evidence of a positive, dose–response relationship between fast food intake and exposure to phthalates (p-trend < 0.0001) but not BPA; participants with high consumption (≥ 34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, respectively, than nonconsumers. Fast food-derived fat intake was also positively associated with ΣDEHPm and DiNPm (p-trend < 0.0001). After adjusting for other food groups, ΣDEHPm was associated with grain and other intake, and DiNPm was associated with meat and grain intake. Conclusion: Fast food may be a source of exposure to DEHP and DiNP. These results, if confirmed, could inform individual and regulatory exposure reduction strategies. Citation: Zota AR, Phillips CA, Mitro SD. 2016. Recent fast food consumption and bisphenol A and phthalates exposures among the U.S. population in NHANES, 2003–2010. Environ Health Perspect 124:1521–1528; http://dx.doi.org/10.1289/ehp.1510803 PMID:27072648

Exposure to environmental chemicals among Korean adults-updates from the second Korean National Environmental Health Survey (2012-2014).

PubMed

Choi, Wookhee; Kim, Suejin; Baek, Yong-Wook; Choi, Kyungho; Lee, Keejae; Kim, Sungkyoon; Yu, Seung Do; Choi, Kyunghee

2017-03-01

National biomonitoring program can offer solid scientific evidence on exposure profiles of environmental chemicals at a national level, and provide a snapshot of changing exposure level over time. Therefore, several countries have maintained such programs for developing environmental health policies. The Korean National Environmental Health Survey (KoNEHS) was designed to understand the level of human exposure to environmental chemicals by time and location, and to identify possible sources of such exposure. The 2nd stage of KoNEHS, which was conducted between 2012 and 2014, examined a total of 6478 adult subjects over 19 years of age, and measured 21 environmental chemicals of major policy concern. Compared to the findings from the first stage monitoring (2009-2011), slightly higher levels of blood lead were observed, while those of mercury remained similar. Blood metal concentrations, however, were higher than those reported from national biomonitoring programs of United States, Germany and Canada. The urinary concentrations of phthalates metabolites were lower, but those of t,t-muconic acid and BPA were higher than those reported in the first stage survey. The urinary cotinine level decreased perhaps reflecting general declining patterns of first- and second-hand smoking. The results of the second stage survey were made available for public use since April 2016. Some policy efforts appear to be at least in part effective on mitigating chemical exposure among people, e.g., urinary phthalate metabolites and cotinine, while further confirmations are warranted. In-depth assessments will be conducted to identify vulnerable groups and important exposure pathways. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Prevalence and predictors of phthalate exposure in pregnant women in Charleston, SC.

PubMed

Wenzel, Abby G; Brock, John W; Cruze, Lori; Newman, Roger B; Unal, Elizabeth R; Wolf, Bethany J; Somerville, Stephen E; Kucklick, John R

2018-02-01

Phthalates are plasticizers commonly detected in human urine due to widespread exposure from PVC plastics, food packaging, and personal care products. Several phthalates are known antiandrogenic endocrine disruptors, which raises concern for prenatal exposure during critical windows of fetal development. While phthalate exposure is ubiquitous, certain demographics are subject to greater or lesser exposure. We sampled urine from 378 pregnant women during the second trimester of gestation living in Charleston, SC, and measured eight urinary phthalate metabolites as biomarkers of phthalate exposure: monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and monomethyl phthalate (MMP). Demographic data was collected from questionnaires administered at the time of specimen collection. All phthalate metabolites were detected in over 93% of urine samples. On average, concentrations were highest for MEP (median = 47.0 ng/mL) and lowest for MMP (median = 1.92 ng/mL). Sociodemographic characteristics associated with elevated phthalate concentrations included being unmarried, less educated, having a low income, high body mass index (BMI), and/or being African American. After racial stratification, age, BMI, education, and income were significantly associated with phthalate concentrations in African American women. Marital status was associated with phthalate concentrations in Caucasian women only, with greater concentrations of MBP, MEHHP, MiBP, and MMP in unmarried versus married women. Results of this cross-sectional study provide evidence for significant racial and demographic variations in phthalate exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased urinary 8-hydroxy-2'-deoxyguanosine levels in workers exposed to di-(2-ethylhexyl) phthalate in a waste plastic recycling site in China.

PubMed

Wang, Qian; Wang, Li; Chen, Xi; Rao, Kai Min; Lu, Shao You; Ma, Sheng Tao; Jiang, Pu; Zheng, Dan; Xu, Shun Qing; Zheng, Hong Yan; Wang, Jian Shu; Yu, Zhi Qiang; Zhang, Rong; Tao, Yong; Yuan, Jing

2011-07-01

Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer used in industrial and diverse consumer products. Animal studies indicate DEHP caused developmental, reproductive, and hepatic toxicities. However, human studies of the potential effects of DEHP are limited. The exposed site with a history of over 20 years of waste plastic recycling was located in Hunan Province, China. The reference site without known DEHP pollution source was about 50 km far away from the exposed site. In this study, 181 workers working in plastic waste recycling and 160 gender-age matched farmers were recruited. DEHP concentrations in water and cultivated soil samples, serum thyroid-stimulating hormone, malondialdehyde (MDA), superoxide dismutase (SOD), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and micronuclei frequency in human capillary blood lymphocytes were analyzed. Mean levels of DEHP were greater in environment at the recycling site than at reference site (industry wastewater for the exposed: 42.43 μg/l; well water: 14.20 vs. 0.79 μg/l, pond water: 135.68 vs. 0.37 μg/l, cultivated soil: 13.07 vs. 0.81 mg/kg, p < 0.05 for all). The workers had higher median levels of MDA (3.80 vs. 3.14 nmol/ml) and urinary 8-OHdG (340.37 vs. 268.18 μmol/mol creatinine) and decreased SOD activities (112.15 vs. 123.82 U/ml) than the reference group (p < 0.01 for all). Multivariate analysis revealed that the history of working in waste plastic recycling was an independent risk factor for the increased urinary 8-OHdG levels in the male workers (p < 0.01). The occupational DEHP exposure might contribute to oxidative deoxyribonucleic acid damage in the male workers.

Prenatal Exposure to Phthalates and the Development of Eczema Phenotypes in Male Children: Results from the EDEN Mother-Child Cohort Study.

PubMed

Soomro, Munawar Hussain; Baiz, Nour; Philippat, Claire; Vernet, Celine; Siroux, Valerie; Nichole Maesano, Cara; Sanyal, Shreosi; Slama, Remy; Bornehag, Carl-Gustaf; Annesi-Maesano, Isabella

2018-02-02

Contradictory results exist regarding the importance of early-life exposure to phthalates for development of childhood eczema. We evaluated the association between maternal urinary concentrations of phthalate metabolites between the 24th and 28th week of gestation and occurrence of eczema in their sons up to 5 y of age, according to allergic sensitization as assessed by total immunoglobulin E (IgE) in a subsample of individuals. Data on health outcomes and background factors were collected using five standardized annual questionnaires completed by parents at the children's ages of 1-5 y, and their associations with phthalate metabolite urinary concentrations were assessed in 604 mother-son pairs with adjusted multiple logistic regression and Cox's survival model. Several eczema phenotypes were considered. Atopic status was assessed at 5 y of age in 293 boys through total IgE assessment. At 5 y of age, the prevalence of ever eczema was 30.4%. Metabolites of di-isobutyl phthalate (DiBP) and di-isononyl phthalate (DiNP) were positively associated with early-onset (0-24 mo of age) eczema (15.7%) and late-onset (24-60 mo of age) eczema (14.7%). Applying the Cox's model showed a significant association of occurrence of eczema in the first 5 y of life with DiBP and DiNP metabolites. Among IgE-sensitized boys, metabolites of di- n -butyl phthalate (DBP) and DiBP were significantly associated with ever eczema {hazard ratio (HR)=1.67 [95% confidence interval (CI): 1.10, 2.54], p =0.01 and HR=1.87 (95% CI: 1.01, 3.48), p =0.04, respectively}. Occurrence of eczema in early childhood may be influenced by prenatal exposure to certain phthalates in boys. Further investigations are needed to confirm this observation. https://doi.org/10.1289/EHP1829.

Di-Isobutyl Phthalate (DIBP) Hazard Identification [Abstract ...

EPA Pesticide Factsheets

The hazard potential for DIBP is being evaluated as part of EPA’s Integrated Risk Information System (IRIS) Toxicological Review. DIBP is a plasticizer that confers flexibility and durability in industrial and consumer products. A literature search identified a relatively small epidemiology and animal toxicology database for DIBP. The epidemiological database includes studies that assessed the relationship between urinary concentrations of the DIBP metabolite mono-isobutyl phthalate (MIBP)and developmental, neurodevelopmental, immunological or breast cancer outcomes. There is limited support for associations between MIBP and inflammatory biomarker levels and decreased masculine play behavior. The animal toxicological database includes studies that assessed “phthalate syndrome” male reproductive developmental endpoints after in utero DIBP exposure. Data from the largest developmental study, Saillenfait et al. (2008), shows changes in anogenital distance, male reproductive organ weights, and litter incidence of phthalate syndrome endpoints in the lower dose range after early gestational exposure. Other studies observed increased fetal mortality, male postnatal and adult growth decrements, decreased fetal testicular testosterone and changes in expression of genes in androgen production pathways. The developmental reproductive effects observed in animal studies are consistent with the reduced testicular testosterone mode of action that is well-characterize

Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010–2012)

PubMed Central

Jensen, Tina Kold; Frederiksen, Hanne; Kyhl, Henriette Boye; Lassen, Tina Harmer; Swan, Shanna H.; Bornehag, Carl-Gustaf; Skakkebaek, Niels E.; Main, Katharina M.; Lind, Dorte Vesterholm; Husby, Steffen; Andersson, Anna-Maria

2015-01-01

Background: Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)—the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported. Objective: We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010–2012 and AGD in their male infants at 3 months of age (n = 273). Methods: In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4–30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score. Results: Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose–response patterns, and associations were not statistically significant (p > 0.05). Conclusion: We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population. Citation: Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM. 2016. Prenatal exposure to phthalates and anogenital distance in male infants from a low-exposed Danish cohort (2010–2012). Environ Health Perspect 124:1107–1113; http://dx.doi.org/10.1289/ehp.1509870 PMID:26672060

Dietary predictors of urinary environmental biomarkers in young girls, BCERP, 2004-7.

PubMed

Mervish, Nancy; McGovern, Kathleen J; Teitelbaum, Susan L; Pinney, Susan M; Windham, Gayle C; Biro, Frank M; Kushi, Lawrence H; Silva, Manori J; Ye, Xiaoyun; Calafat, Antonia M; Wolff, Mary S

2014-08-01

Exposures of children to phthalates, parabens, and bisphenol-A (BPA) are of concern because of their hormonal potential. These agents are found in a wide range of foods and packaging. We investigated whether intake of certain foods predict exposures to these chemicals in young girls. Among 1101 girls (6-8 years at enrollment) from the Breast Cancer and Environment Research Program (BCERP) study, we measured urinary exposure biomarkers for phthalates, parabens, and BPA and assessed dietary intake using 24-h recall 2-4 times. We examined the average daily servings of major and minor food groups categorized as 0 to <0.5, 0.5 to <1 and ≥ 1 servings per day. Items included dairy, eggs, fats, fish, fruit, single grains, meat, non-poultry meats, pasta, poultry and vegetables. Covariate-adjusted least squares geometric means and 95% confidence intervals of creatinine-corrected phthalate and phenol metabolite concentrations in urine were calculated in relation to food intake. Grains, flour and dry mixes and total fish consumption were positively associated with BPA and the sum of four di-2-ethylhexylphthalate (DEHP) urinary metabolite concentrations. Non-fresh vegetables and poultry were both positively associated with BPA and paraben urinary concentrations. Fats, oils and poultry consumption were positively associated with BPA. Whole-fat dairy consumption was associated with ΣDEHP. Some foods may contribute to child exposures to certain chemicals, and this may constitute modifiable means to reduce these environmental exposures. Copyright © 2014 Elsevier Inc. All rights reserved.

Integrating biomonitoring exposure data into the risk assessment process: phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study.

PubMed

Calafat, Antonia M; McKee, Richard H

2006-11-01

The probability of nonoccupational exposure to phthalates is high given their use in a vast range of consumables, including personal care products (e.g., perfumes, lotions, cosmetics), paints, industrial plastics, and certain medical devices and pharmaceuticals. Phthalates are of high interest because of their potential for human exposure and because animal toxicity studies suggest that some phthalates affect male reproductive development apparently via inhibition of androgen biosynthesis. In humans, phthalates are rapidly metabolized to their monoesters, which can be further transformed to oxidative products, conjugated, and eliminated. Phthalate metabolites have been used as biomarkers of exposure. Using urinary phthalate metabolite concentrations allows accurate assessments of human exposure because these concentrations represent an integrative measure of exposure to phthalates from multiple sources and routes. However, the health significance of this exposure is unknown. To link biomarker measurements to exposure, internal dose, or health outcome, additional information (e.g., toxicokinetics, inter- and intraindividual differences) is needed. We present a case study using diethyl phthalate and di(2-ethylhexyl) phthalate as examples to illustrate scientific approaches and their limitations, identify data gaps, and outline research needs for using biomonitoring data in the context of human health risk assessment, with an emphasis on exposure and dose. Although the vast and growing literature on phthalates research could not be covered comprehensively in this article, we made every attempt to include the most relevant publications as of the end of 2005.

Estimated Daily Phthalate Exposures in a Population of Mothers of Male Infants Exhibiting Reduced Anogenital Distance

PubMed Central

Marsee, Kevin; Woodruff, Tracey J.; Axelrad, Daniel A.; Calafat, Antonia M.; Swan, Shanna H.

2006-01-01

Phthalate diesters have been shown to be developmental and reproductive toxicants in animal studies. A recent epidemiologic study showed certain phthalates to be significantly associated with reduced anogenital distance in human male infants, the first evidence of subtle developmental effects in human male infants exposed prenatally to phthalates. We used two previously published methods to estimate the daily phthalate exposures for the four phthalates whose urinary metabolites were statistically significantly associated with developmental effects in the 214 mother–infant pairs [di-n-butyl phthalate (DnBP), diethyl phthalate (DEP), butylbenzyl phthalate (BBzP), diisobutyl phthalate (DiBP)] and for another important phthalate [di-2-ethylhexyl phthalate (DEHP)]. We estimated the median and 95th percentile of daily exposures to DBP to be 0.99 and 2.68 μg/kg/day, respectively; for DEP, 6.64 and 112.3 μg/kg/day; for BBzP, 0.50 and 2.47 μg/kg/day; and for DEHP, 1.32 and 9.32 μg/kg/day. The U.S. Environmental Protection Agency (EPA) reference doses for these chemicals are 100 (DBP), 800 (DEP), 200 (BBzP), and 20 (DEHP) μg/kg/day. The median and 95th percentile exposure estimates for the phthalates associated with reduced anogenital distance in the study population are substantially lower than current U.S. EPA reference doses for these chemicals and could be informative to any updates of the hazard assessments and risk assessments for these chemicals. PMID:16759976

Phthalate exposure, flavonoid consumption and breast cancer risk among Mexican women.

PubMed

Mérida-Ortega, Ángel; Hernández-Alcaraz, César; Hernández-Ramírez, Raúl U; García-Martínez, Angélica; Trejo-Valdivia, Belem; Salinas-Rodríguez, Aarón; Svensson, Katherine; Cebrián, Mariano E; Franco-Marina, Francisco; López-Carrillo, Lizbeth

2016-11-01

To evaluate if selected phthalate exposure and flavonoid intake interact on breast cancer (BC) risk. Interviews and urine samples were obtained from 233 women with histologically confirmed BC and 221 healthy controls matched by age and place of residence, from various states of northern Mexico. Urinary metabolites concentrations of diethyl phthalate (DEP), butyl benzyl phthalate (BBzP) and dioctyl phthalate (DOP) were determined by solid-phase extraction coupled with high-performance liquid chromatography/isotope dilution/tandem mass spectrometry. Using a semiquantitative food frequency questionnaire, consumption of five types of flavonoids (anthocyanidins, flavan-3-ols, flavanones, flavones and flavonols) was estimated according to three food groups: vegetables, fruits and legumes-oil seeds. A higher intake of anthocyanidins and flavan-3-ols (from vegetables), synergistically increased the negative association between BBzP and BC. No other significant flavonoid-phthalate multiplicative interactions on the risk for BC were found. The consumption of some flavonoids may interact with exposure to phthalates on the risk of BC. Epidemiological and underlying mechanisms information is still insufficient and requires further investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phthalate metabolites and bisphenol-A in association with circulating angiogenic biomarkers across pregnancy

PubMed Central

Ferguson, Kelly K.; McElrath, Thomas F.; Cantonwine, David E.; Mukherjee, Bhramar; Meeker, John D.

2015-01-01

Introduction Phthalates and bisphenol-a (BPA) are endocrine disrupting compounds with widespread exposure that have been linked in a number of epidemiologic studies to adverse birth outcomes and developmental effects. We hypothesized that these associations may be mediated in part through altered placental development and function consequent to exposure. To investigate this question, we examined associations between plasma biomarkers of angiogenesis and urinary biomarkers of exposure to phthalates and bisphenol-a (BPA) measured at repeated time points across pregnancy. Methods We utilized a nested case-control population consisting of 130 mothers who delivered preterm and 352 who delivered term from a prospective birth cohort. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured in plasma samples collected from up to four visits during pregnancy (median 10, 18, 26, and 35 weeks). Phthalate metabolites and BPA were measured in urine samples collected at the same visits as indices of exposure. Results In linear mixed effects models adjusted for urine dilution and gestational age at sample collection, oxidized di-2-ethylhexyl phthalate (DEHP) metabolites were associated with decreases in PlGF as well as increases in the sFlt-1 to PlGF ratio. These results were slightly attenuated in fully adjusted models. Other phthalate metabolites did not show consistent relationships with either sFlt-1 or PlGF. BPA, however, was associated with increased sFlt-1 as well as the sFlt-1 to PlGF ratio in both crude and adjusted models. Discussion We observed associations between urinary DEHP metabolites and BPA and biomarkers of angiogenesis during pregnancy that may be indicative of disrupted placental development and/or function during gestation. PMID:25913709

Considering common sources of exposure in association studies - Urinary benzophenone-3 and DEHP metabolites are associated with altered thyroid hormone balance in the NHANES 2007-2008.

PubMed

Kim, Sujin; Kim, Sunmi; Won, Sungho; Choi, Kyungho

2017-10-01

Epidemiological studies have shown that thyroid hormone balances can be disrupted by chemical exposure. However, many association studies have often failed to consider multiple chemicals with possible common sources of exposure, rendering their conclusions less reliable. In the 2007-2008 National Health and Nutrition Examination Survey (NHANES) from the U.S.A., urinary levels of environmental phenols, parabens, and phthalate metabolites as well as serum thyroid hormones were measured in a general U.S. population (≥12years old, n=1829). Employing these data, first, the chemicals or their metabolites associated with thyroid hormone measures were identified. Then, the chemicals/metabolites with possible common exposure sources were included in the analytical model to test the sensitivities of their association with thyroid hormone levels. Benzophenone-3 (BP-3), bisphenol A (BPA), and a metabolite of di(2-ethylhexyl) phthalate (DEHP) were identified as significant determinants of decreased serum thyroid hormones. However, significant positive correlations were detected (p-value<0.05, r=0.23 to 0.45) between these chemicals/metabolites, which suggests that they might share similar exposure sources. In the subsequent sensitivity analysis, which included the chemicals/metabolite with potentially similar exposure sources in the model, we found that urinary BP-3 and DEHP exposure were associated with decreased thyroid hormones among the general population but BPA exposure was not. In association studies, the presence of possible common exposure sources should be considered to circumvent possible false-positive conclusions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Paired Serum and Urine Concentrations of Biomarkers of Diethyl Phthalate, Methyl Paraben, and Triclosan in Rats

PubMed Central

Teitelbaum, Susan L.; Li, Qian; Lambertini, Luca; Belpoggi, Fiorella; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Silva, Manori J.; Ye, Xiaoyun; Calafat, Antonia M.; Chen, Jia

2015-01-01

Background Exposure to environmental chemicals, including phthalates and phenols such as parabens and triclosan, is ubiquitous within the U.S. general population. Objective This proof-of-concept rodent study examined the relationship between oral doses of three widely used personal care product ingredients [diethyl phthalate (DEP), methyl paraben (MPB), and triclosan] and urine and serum concentrations of their respective biomarkers. Methods Using female Sprague-Dawley rats, we carried out two rounds of experiments with oral gavage doses selected in accordance with no observed adverse effect levels (NOAELs) derived from previous studies: 1,735 (DEP), 1,050 (MPB), 50 (triclosan) mg/kg/day. Administered doses ranged from 0.005 to 173 mg/kg/day, 10–100,000 times below the NOAEL for each chemical. Controls for the MPB and triclosan experiments were animals treated with olive oil (vehicle) only; controls for the DEP serum experiments were animals treated with the lowest doses of MPB and triclosan. Doses were administered for 5 days with five rats in each treatment group. Urine and blood serum, collected on the last day of exposure, were analyzed for biomarkers. Relationships between oral dose and biomarker concentrations were assessed using linear regression. Results Biomarkers were detected in all control urine samples at parts-per-billion levels, suggesting a low endemic environmental exposure to the three chemicals that could not be controlled even with all of the precautionary measures undertaken. Among the exposed animals, urinary concentrations of all three biomarkers were orders of magnitude higher than those in serum. A consistently positive linear relationship between oral dose and urinary concentration was observed (R2 > 0.80); this relationship was inconsistent in serum. Conclusions Our study highlights the importance of carefully considering the oral dose used in animal experiments and provides useful information in selecting doses for future studies. Citation Teitelbaum SL, Li Q, Lambertini L, Belpoggi F, Manservisi F, Falcioni L, Bua L, Silva MJ, Ye X, Calafat AM, Chen J. 2016. Paired serum and urine concentrations of biomarkers of diethyl phthalate, methyl paraben, and triclosan in rats. Environ Health Perspect 124:39–45; http://dx.doi.org/10.1289/ehp.1409586 PMID:26047088

Urinary and air phthalate concentrations and self-reported use of personal care products among minority pregnant women in New York city.

PubMed

Just, Allan C; Adibi, Jennifer J; Rundle, Andrew G; Calafat, Antonia M; Camann, David E; Hauser, Russ; Silva, Manori J; Whyatt, Robin M

2010-11-01

Diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) are used extensively in personal care products, including fragrances (DEP) and nail polish (DnBP). Between May 2003 and July 2006, we gathered questionnaire data on the use of seven product categories (deodorant, perfume, hair spray, hair gel, nail polish/polish remover, liquid soap/body wash, and lotion/mist) over 48 h during the third trimester of pregnancy from 186 inner-city women. A 48-h personal air sample was collected and analyzed for DEP and DnBP; a maternal spot urine sample was collected and analyzed for their monoester metabolites, monoethyl phthalate (MEP) and mono-n-butyl phthalate (MnBP), respectively. In all, 97% of air samples and 84% of urine samples were collected within ±2 days of the questionnaire. During the 48 h, 41% of women reported perfume use and 10% reported nail polish/polish remover use. In adjusted analyses, no association was seen between nail product use and air DnBP or urine MnBP concentrations. Women reporting perfume use had 2.3 times higher (95% CI 1.6, 3.3) urinary MEP concentrations. Personal air DEP increased by 7% for each 25% increase in a composite indicator of the six other product categories (P<0.05), but was not associated with perfume use. Air DEP was correlated with urine MEP concentrations only among non-perfume users (r=0.51, P<0.001). Results suggest that perfume use is a significant source of DEP exposure.

Urinary and air phthalate concentrations and self-reported use of personal care products among minority pregnant women in New York City

PubMed Central

Just, Allan C.; Adibi, Jennifer J.; Rundle, Andrew G.; Calafat, Antonia M.; Camann, David E.; Hauser, Russ; Silva, Manori J.; Whyatt, Robin M.

2011-01-01

Diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) are used extensively in personal care products, including fragrances (DEP) and nail polish (DnBP). Between May 2003 and July 2006, we gathered questionnaire data on use of 7 product categories (deodorant, perfume, hair spray, hair gel, nail polish/polish remover, liquid soap/body wash, lotion/mist) over 48 hours during the 3rd trimester of pregnancy from 186 inner-city women. A 48-hour personal air sample was collected and analyzed for DEP and DnBP; a maternal spot urine sample was collected and analyzed for their monoester metabolites, monoethyl phthalate (MEP) and mono-n-butyl phthalate (MnBP), respectively. Ninety-seven percent of air samples and 84% of urine samples were collected within ±2 days of the questionnaire. During the 48 hours, 41% of women reported perfume use and 10% reported nail polish/polish remover use. In adjusted analyses, no association was seen between nail product use and air DnBP or urine MnBP concentrations. Women reporting perfume use had 2.3 times higher (95% CI 1.6, 3.3) urinary MEP concentrations. Personal air DEP increased 7% for each 25% increase in a composite indicator of the 6 other product categories (p<0.05) but was not associated with perfume use. Air DEP was correlated with urine MEP concentrations only among non-perfume users (r=0.51, p<0.001). Results suggest that perfume use is a significant source of DEP exposure. PMID:20354564

Pilot study testing a European human biomonitoring framework for biomarkers of chemical exposure in children and their mothers: experiences in the UK.

PubMed

Exley, Karen; Aerts, Dominique; Biot, Pierre; Casteleyn, Ludwine; Kolossa-Gehring, Marike; Schwedler, Gerda; Castaño, Argelia; Angerer, Jürgen; Koch, Holger M; Esteban, Marta; Schindler, Birgit K; Schoeters, Greet; Den Hond, Elly; Horvat, Milena; Bloemen, Louis; Knudsen, Lisbeth E; Joas, Reinhard; Joas, Anke; Sepai, Ovnair

2015-10-01

Exposure to a number of environmental chemicals in UK mothers and children has been assessed as part of the European biomonitoring pilot study, Demonstration of a Study to Coordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES). For the European-funded project, 17 countries tested the biomonitoring guidelines and protocols developed by COPHES. The results from the pilot study in the UK are presented; 21 school children aged 6-11 years old and their mothers provided hair samples to measure mercury and urine samples, to measure cadmium, cotinine and several phthalate metabolites: mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP), mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP). Questionnaire data was collected on environment, health and lifestyle. Mercury in hair was higher in children who reported frequent consumption of fish (geometric mean 0.35 μg/g) compared to those that ate fish less frequently (0.13 μg/g, p = 0.002). Cadmium accumulates with age as demonstrated by higher levels of urinary cadmium in the mothers (geometric mean 0.24 μg/L) than in the children(0.14 μg/L). None of the mothers reported being regular smokers, and this was evident with extremely low levels of cotinine measured (maximum value 3.6 μg/L in mothers, 2.4 μg/L in children). Very low levels of the phthalate metabolites were also measured in both mothers and children (geometric means in mothers: 5OH-MEHP 8.6 μg/L, 5oxo-MEHP 5.1 μg/L, MEHP 1.2 μg/L, MEP 26.8 μg/L, MiBP 17.0 μg/L, MBzP 1.6 μg/L and MnBP 13.5 μg/L; and in children: 5OH-MEHP 18.4 μg/L, 5oxo-MEHP 11.4 μg/L, MEHP 1.4 μg/L, MEP 14.3 μg/L, MiBP 25.8 μg/L, MBzP 3.5 μg/L and MnBP 22.6 μg/L). All measured biomarker levels were similar to or below population-based reference values published by the US National Health and Nutrition Examination Survey (NHANES) and Germany's GerES surveys. No results were above available health guidance values and were of no concern with regards to health. The framework and techniques learnt here will assist with future work on biomonitoring in the UK.

Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function: a Systematic Review of Human Evidence.

PubMed

Høyer, Birgit Bjerre; Lenters, Virissa; Giwercman, Aleksander; Jönsson, Bo A G; Toft, Gunnar; Hougaard, Karin S; Bonde, Jens Peter E; Specht, Ina Olmer

2018-03-01

The purpose of this review is to systematically review the literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on reproductive health in adult males. Thirty-three papers were included of which 28 were cross-sectional. Twenty-one papers investigated semen samples, 18 investigated reproductive hormones, and three studies investigated time to pregnancy. Studies revealed some but inconsistent indications that higher urinary DEHP metabolite levels are associated with an increase in the proportion of spermatozoa with damaged DNA and to a decrease in sperm concentration and motility. A negative association between DEHP metabolites and testosterone levels was more consistent. DEHP metabolites do not seem to be associated with a delay in time to pregnancy, but data are sparse. The studies on DEHP exposure and reproductive biomarkers in men converge to support the hypothesis that DEHP exposure is related to impaired male reproductive function. Longitudinal studies are needed to establish if the observed associations are causal.

Positive Association between Urinary Concentration of Phthalate Metabolites and Oxidation of DNA and Lipid in Adolescents and Young Adults

NASA Astrophysics Data System (ADS)

Lin, Chien-Yu; Chen, Pau-Chung; Hsieh, Chia-Jung; Chen, Chao-Yu; Hu, Anren; Sung, Fung-Chang; Lee, Hui-Ling; Su, Ta-Chen

2017-03-01

Phthalate has been used worldwide in various products for years. Little is known about the association between phthalate exposure and biomarkers of oxidative stress in adolescents and young adults. Among 886 subjects recruited from a population-based cohort during 2006 to 2008, 751 subjects (12-30 years) with complete phthalate metabolites and oxidation stress measurement were enrolled in this study. Nine urine phthalate metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso prostaglandin F2α (8-isoPGF2α) were measured in urine to assess exposure and oxidative stress to DNA and lipid, respectively. Multiple linear regression analysis revealed that an ln-unit increase in mono-methyl phthalate (MMP) concentration in urine was positively associated with an increase in urine biomarkers of oxidative stress (in μg/g creatinine of 0.098 ± 0.028 in 8-OHdG; and 0.253 ± 0.051 in 8-isoPGF2α). There was no association between other eight phthalate metabolite concentrations and oxidative stress. In conclusion, a higher MMP concentration in urine was associated with an increase in markers of oxidative stress to DNA and lipid in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to phthalate and oxidative stress.

Correcting for the influence of sampling conditions on biomarkers of exposure to phenols and phthalates: a 2-step standardization method based on regression residuals.

PubMed

Mortamais, Marion; Chevrier, Cécile; Philippat, Claire; Petit, Claire; Calafat, Antonia M; Ye, Xiaoyun; Silva, Manori J; Brambilla, Christian; Eijkemans, Marinus J C; Charles, Marie-Aline; Cordier, Sylvaine; Slama, Rémy

2012-04-26

Environmental epidemiology and biomonitoring studies typically rely on biological samples to assay the concentration of non-persistent exposure biomarkers. Between-participant variations in sampling conditions of these biological samples constitute a potential source of exposure misclassification. Few studies attempted to correct biomarker levels for this error. We aimed to assess the influence of sampling conditions on concentrations of urinary biomarkers of select phenols and phthalates, two widely-produced families of chemicals, and to standardize biomarker concentrations on sampling conditions. Urine samples were collected between 2002 and 2006 among 287 pregnant women from Eden and Pélagie cohorts, from which phthalates and phenols metabolites levels were assayed. We applied a 2-step standardization method based on regression residuals. First, the influence of sampling conditions (including sampling hour, duration of storage before freezing) and of creatinine levels on biomarker concentrations were characterized using adjusted linear regression models. In the second step, the model estimates were used to remove the variability in biomarker concentrations due to sampling conditions and to standardize concentrations as if all samples had been collected under the same conditions (e.g., same hour of urine collection). Sampling hour was associated with concentrations of several exposure biomarkers. After standardization for sampling conditions, median concentrations differed by--38% for 2,5-dichlorophenol to +80 % for a metabolite of diisodecyl phthalate. However, at the individual level, standardized biomarker levels were strongly correlated (correlation coefficients above 0.80) with unstandardized measures. Sampling conditions, such as sampling hour, should be systematically collected in biomarker-based studies, in particular when the biomarker half-life is short. The 2-step standardization method based on regression residuals that we proposed in order to limit the impact of heterogeneity in sampling conditions could be further tested in studies describing levels of biomarkers or their influence on health.

Estimated Daily Intake and Cumulative Risk Assessment of Phthalates in the General Taiwanese after the 2011 DEHP Food Scandal

NASA Astrophysics Data System (ADS)

Chang, Jung-Wei; Lee, Ching-Chang; Pan, Wen-Harn; Chou, Wei-Chun; Huang, Han-Bin; Chiang, Hung-Che; Huang, Po-Chin

2017-03-01

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 (HQrep) and hepatic (HQhep) 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 95th percentile (P95) of HQrep values were all >1 in the 7- to 12-year-old and 18- to 40-year-old male groups. The P95 of HQhep values were all >1 in the 7- to 18- year-old male groups. Most of the HQrep was attributable to the HQs of DnBP and DiBP (53.9-84.7%), and DEHP contributed most to HQhep (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.

Plastic toys as a source of exposure to bisphenol-A and phthalates at childcare facilities.

PubMed

Andaluri, Gangadhar; Manickavachagam, Muruganandham; Suri, Rominder

2018-01-06

Infants and toddlers are constantly exposed to toys at childcare facilities. Toys are made of a variety of plastics that often use endocrine-disrupting chemicals such as bisphenol-A (BPA) and phthalates as their building blocks. The goal of this study was to assess the non-dietary exposure of infants and toddlers to BPA and phthalates via leaching. We have successfully developed wipe tests to evaluate the leachability of BPA and phthalates from toys used at several day care facilities in Philadelphia. Our studies have shown an average leaching of 13-280 ng/cm 2 of BPA and phthalates. An estimate of total exposure of infants to BPA and phthalates is reported. The leaching of the chemicals was observed to be dependent on the washing procedures and the location of the day care facilities. Using bleach/water mixture two or more times a week to clean the toys seems to reduce the leaching of chemicals from the toys. There is a huge data gap in the estimated intake amounts and reported urinary concentrations; this is the first study that provides valuable information to address these data gaps in the existing literature.

Relationship between environmental phthalate exposure and the intelligence of school-age children.

PubMed

Cho, Soo-Churl; Bhang, Soo-Young; Hong, Yun-Chul; Shin, Min-Sup; Kim, Boong-Nyun; Kim, Jae-Won; Yoo, Hee-Jung; Cho, In Hee; Kim, Hyo-Won

2010-07-01

Concern over phthalates has emerged because of their potential toxicity to humans. We investigated the relationship between the urinary concentrations of phthalate metabolites and children's intellectual functioning. This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers. We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 microg/L [geometric SD (GSD) = 2.2 microg/L; range, 0.5-445.4], 18.0 microg/L (GSD = 2.4; range, 0.07-291.1), and 48.9 microg/L (GSD = 2.2; range, 2.1-1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children's vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables. Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.

Urinary Phthalate Metabolites Are Associated with Body Mass Index and Waist Circumference in Chinese School Children

PubMed Central

Wang, Hexing; Zhou, Ying; Tang, Chuanxi; He, Yanhong; Wu, Jingui; Chen, Yue; Jiang, Qingwu

2013-01-01

Background Lab studies have suggested that ubiquitous phthalate exposures are related to obesity, but relevant epidemiological studies are scarce, especially for children. Objective To investigate the association of phthalate exposures with body mass index (BMI) and waist circumference (WC) in Chinese school children. Methods A cross-sectional study was conducted in three primary and three middle schools randomly selected from Changning District of Shanghai City of China in 2011–2012. According to the physical examination data in October, 2011, 124 normal weight, 53 overweight, and 82 obese students 8–15 years of age were randomly chosen from these schools on the basis of BMI-based age- and sex-specific criterion. First morning urine was collected in January, 2012, and fourteen urine phthalate metabolites (free plus conjugated) were determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Multiple linear regression was used to explore the associations between naturally log-transformed urine phthalate metabolites and BMI or WC. Results The urine specific gravity-corrected concentrations of nine urine phthalate metabolites and five molar sums were positively associated with BMI or WC in Chinese school children after adjustment for age and sex. However, when other urine phthalate metabolites were included in the models together with age and sex as covariables, most of these significant associations disappeared except for mono (2-ethylhexyl) phthalate (MEHP) and monoethyl phthalate (MEP). Additionally, some associations showed sex- or age-specific differences. Conclusions Some phthalate exposures were associated with BMI or WC in Chinese school children. Given the cross-sectional nature of this study and lack of some important obesity-related covariables, further studies are needed to confirm the associations. PMID:23437242

Selecting Adequate Exposure Biomarkers of Diisononyl and Diisodecyl Phthalates: Data from the 2005–2006 National Health and Nutrition Examination Survey

PubMed Central

Calafat, Antonia M.; Wong, Lee-Yang; Silva, Manori J.; Samandar, Ella; Preau, James L.; Jia, Lily T.; Needham, Larry L.

2011-01-01

Background High-molecular-weight phthalates, such as diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers. Objectives We assessed exposure to DINP and DIDP in a representative sample of persons ≥ 6 years of age in the U.S. general population from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Methods We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography–tandem mass spectrometry. Results We detected monocarboxyisooctyl phthalate (MCOP), a metabolite of DINP, and monocarboxyisononyl phthalate (MCNP), a metabolite of DIDP, in 95.2% and 89.9% of the samples, respectively. We detected monoisononyl phthalate (MNP), a minor metabolite of DINP, much less frequently (12.9%) and at concentration ranges (> 0.8 μg/L–148.1 μg/L) much lower than MCOP (> 0.7 μg/L– 4,961 μg/L). Adjusted geometric mean concentrations of MCOP and MCNP were significantly higher (p < 0.01) among children than among adolescents and adults. Conclusions The general U.S. population, including children, was exposed to DINP and DIDP. In previous NHANES cycles, the occurrence of human exposure to DINP by using MNP as the sole urinary biomarker has been underestimated, thus illustrating the importance of selecting the most adequate biomarkers for exposure assessment. PMID:20870567

Vaginal douching and racial/ethnic disparities in phthalates exposures among reproductive-aged women: National Health and Nutrition Examination Survey 2001-2004.

PubMed

Branch, Francesca; Woodruff, Tracey J; Mitro, Susanna D; Zota, Ami R

2015-07-15

Diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) are industrial chemicals found in consumer products that may increase risk of adverse health effects. Although use of personal care/beauty products is known to contribute to phthalate exposure, no prior study has examined feminine hygiene products as a potential phthalate source. In this study, we evaluate whether vaginal douching and other feminine hygiene products increase exposure to phthalates among US reproductive-aged women. We conducted a cross-sectional study on 739 women (aged 20-49) from the National Health and Nutrition Examination Survey 2001-2004 to examine the association between self-reported use of feminine hygiene products (tampons, sanitary napkins, vaginal douches, feminine spray, feminine powder, and feminine wipes/towelettes) with urinary concentrations of monoethyl phthalate (MEP) and mono-n-butyl phthalate (MnBP), metabolites of DEP and DnBP, respectively. A greater proportion of black women than white and Mexican American women reported use of vaginal douches, feminine spray, feminine powder, and wipes/towelettes in the past month whereas white women were more likely than other racial/ethnic groups to report use of tampons (p < 0.05). Douching in the past month was associated with higher concentrations of MEP but not MnBP. No other feminine hygiene product was significantly associated with either MEP or MnBP. We observed a dose-response relationship between douching frequency and MEP concentrations (p(trend) < 0.0001); frequent users (≥2 times/month) had 152.2% (95% confidence intervals (CI): (68.2%, 278.3%)) higher MEP concentrations than non-users. We also examined whether vaginal douching mediates the relationship between race/ethnicity and phthalates exposures. Black women had 48.4% (95% CI: 16.8%, 88.6%; p = 0.0002) higher MEP levels than white women. Adjustment for douching attenuated this difference to 26.4% (95% CI:-0.9%, 61.2%; p = 0.06). Mediation effects of douching were statistically significant for black-white differences (z = 3.71, p < 0.001) but not for differences between Mexican Americans and whites (z = 1.80, p = 0.07). Vaginal douching may increase exposure to DEP and contribute to racial/ethnic disparities in DEP exposure. The presence of environmental chemicals in vaginal douches warrants further examination.

Bisphenol A, phthalates and lead and learning and behavioral problems in Canadian children 6-11 years of age: CHMS 2007-2009.

PubMed

Arbuckle, Tye E; Davis, Karelyn; Boylan, Khrista; Fisher, Mandy; Fu, Jingshan

2016-05-01

Childhood developmental disorders and related problems such as learning disabilities and attention deficit hyperactivity disorder (ADHD) account for a growing burden on the family, education and health care systems. Exposure to environmental chemicals such as bisphenol A (BPA) and phthalates may play a role in the development of child behavioral problems. Using cross-sectional data from Cycle 1 of the Canadian Health Measures Survey (CHMS), we examined the potential association between urinary concentrations of BPA and various phthalate metabolites and child learning and behavioral problems, considering important covariates such as gender, blood lead and environmental tobacco smoke (ETS). The Strengths and Difficulties Questionnaire (SDQ) outcomes of interest were emotional symptoms, hyperactivity/inattention, and a total difficulties score with borderline and abnormal scores grouped together and compared with children with normal scores. Other outcomes studied included any reported learning disability, a subset of learning disabilities reported as ADD/ADHD (attention deficit disorder) and use of psychotropic medications in the past month. Among children ages 6-11 years, the prevalences of any learning disability, ADD, and ADHD were 8.7%, 1.5% and 2.8%, respectively. Estimated prevalences for SDQ hyperactivity/inattention, emotional symptoms and total difficulties scores were 16.9%, 15.0%, and 13.0%, respectively. Child's urinary BPA was associated with taking psychotropic medications (OR 1.59; 95% CI 1.05-2.40). Urinary MBzP concentration was significantly associated with emotional symptoms in girls (OR 1.38 95% CI 1.09-1.75) but not in boys (OR 1.05 95% CI 0.82-1.36).) Blood lead was significantly associated with several of the outcomes examined, with a significant interaction observed between prenatal smoking and blood lead for the total difficulties score (OR=10.57; 95% CI 2.81-39.69 vs. OR=1.98; 95% CI 1.41-2.79 if mother did not smoke during pregnancy). Although limited by the cross-sectional nature of the study which precludes examining causation, the results suggest that although some indicators of child behavior were significantly associated with their urinary BPA and phthalate concentrations, the major chemical associated with adverse behavioral indicators was lead. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls.

PubMed

Watkins, Deborah J; Sánchez, Brisa N; Téllez-Rojo, Martha Maria; Lee, Joyce M; Mercado-García, Adriana; Blank-Goldenberg, Clara; Peterson, Karen E; Meeker, John D

2017-11-01

Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes. Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester was associated with 25% higher DHEA-S (95%CI: 4.7-47%). In IQR increase in mean mono-2-ethylhexyl phthalate (MEHP) levels across pregnancy was associated with lower odds of having a Tanner Stage >1 for breast development (OR = 0.32, 95%CI: 0.11-0.95), while MEHP in the third trimester was associated with higher odds of having a Tanner Stage >1 for pubic hair development (OR = 3.76, 95%CI: 1.1-12.8). Results from secondary analyses were consistent with findings from our main analysis. These findings suggest that female reproductive development may be more vulnerable to the effects of phthalate or BPA exposure during specific critical periods of in utero development. This highlights the need for comprehensive characterizations of in utero exposure and consideration of windows of susceptibility in developmental epidemiological studies. Future research should consider repeated measures of in utero phthalate and BPA exposure within each trimester and across pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

Prenatal Phthalate, Triclosan, and Bisphenol A Exposures and Child Visual-Spatial Abilities

PubMed Central

Braun, Joseph M.; Bellinger, David C.; Hauser, Russ; Wright, Robert O.; Chen, Aimin; Calafat, Antonia M.; Yolton, Kimberly; Lanphear, Bruce P.

2016-01-01

Introduction During fetal development, sex steroids influence sexually dimorphic behaviors, such as visual-spatial abilities. Thus, endocrine disrupting chemicals that impact sex steroids during gestation may affect these behaviors. Objective We investigated the relationship between prenatal urinary phthalate metabolite, triclosan, and BPA concentrations and visual-spatial abilities in a prospective cohort of 198 mother-child dyads. Methods Data are from a prospective cohort in Cincinnati, OH (HOME Study). We measured nine phthalate metabolites, triclosan, and BPA in maternal urine samples collected at 16 and 26 weeks of gestation. We assessed children’s visual-spatial abilities at 8 years of age using the Virtual Morris Water Maze (VMWM), a computerized version of the rodent Morris Water Maze. We quantified the covariate-adjusted change in the time or distance to complete the VMWM and time spent in the correct quadrant during a probe trial with an interquartile range increase in chemical concentrations using linear mixed models and linear regression, respectively. Results Boys completed the VMWM faster (4.1 seconds; 95% CI:−7.1, −1.2) and in less distance (1.4 units; 95% CI:−2.8, 0) than girls. Overall, children with higher mono-n-butyl (MnBP), mono- benzyl (MBzP), and mono-carboxypropyl phthalate concentrations completed the VMWM in less time and distance than children with lower concentrations. For example, children with higher MnBP concentrations completed the VMWM in 0.9 less distance units (95% CI:−1.8, −0.0). Child sex modified the association between MnBP and VMWM performance. In girls, higher MnBP concentrations were associated with longer time (1.7 seconds; 95% CI: −0.7, 4.1) and shorter distance (−1.7 units; 95% CI: −2.8, −0.5), whereas in boys, it was associated with shorter time (−3.0 seconds; 95% CI:−5.6, −0.4), but not distance (−0.1 units; 95% CI:1.4, 1.0). Other phthalate metabolites, triclosan, and BPA were not associated with VMWM performance, and sex did not consistently modify these associations. Conclusions In this cohort, greater prenatal urinary concentrations of some phthalate metabolites were associated with improved VMWM performance, particularly among boys. Future studies should confirm these findings and determine if phthalates affect other hormonally sensitive aspects of child neurobehavior. PMID:27888119

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

PubMed Central

Cho, Soo-Churl; Bhang, Soo-Young; Hong, Yun-Chul; Shin, Min-Sup; Kim, Boong-Nyun; Kim, Jae-Won; Yoo, Hee-Jung; Cho, In Hee; Kim, Hyo-Won

2010-01-01

Background Concern over phthalates has emerged because of their potential toxicity to humans. Objective We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning. Methods This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers. Results We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables. Conclusion Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations. PMID:20194078

Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study

PubMed Central

Cullen, Elizabeth; Evans, David; Griffin, Chris; Burke, Padraig; Mannion, Rory; Burns, Damien; Flanagan, Andrew; Kellegher, Ann; Schoeters, Greet; Govarts, Eva; Biot, Pierre; Casteleyn, Ludwine; Castaño, Argelia; Kolossa-Gehring, Marike; Esteban, Marta; Schwedler, Gerda; Angerer, Jürgen; Knudsen, Lisbeth E.; Joas, Reinhard; Joas, Anke; Dumez, Birgit; Sepai, Ovnair; Exley, Karen; Aerts, Dominique

2017-01-01

Background: Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the ‘Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale’ (DEMOCOPHES) pilot biomonitoring study. Methods: the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results: Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions: The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood. PMID:29186834

Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study.

PubMed

Cullen, Elizabeth; Evans, David; Griffin, Chris; Burke, Padraig; Mannion, Rory; Burns, Damien; Flanagan, Andrew; Kellegher, Ann; Schoeters, Greet; Govarts, Eva; Biot, Pierre; Casteleyn, Ludwine; Castaño, Argelia; Kolossa-Gehring, Marike; Esteban, Marta; Schwedler, Gerda; Koch, Holger M; Angerer, Jürgen; Knudsen, Lisbeth E; Joas, Reinhard; Joas, Anke; Dumez, Birgit; Sepai, Ovnair; Exley, Karen; Aerts, Dominique

2017-11-25

Background : Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the 'Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale' (DEMOCOPHES) pilot biomonitoring study. Methods : the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results : Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions : The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood.

Exposure to phthalic acid, phthalate diesters and phthalate monoesters from foodstuffs: UK total diet study results.

PubMed

Bradley, Emma L; Burden, Richard A; Bentayeb, Karim; Driffield, Malcolm; Harmer, Nick; Mortimer, David N; Speck, Dennis R; Ticha, Jana; Castle, Laurence

2013-01-01

Phthalates are ubiquitous in the environment and thus exposure to these compounds can occur in various forms. Foods are one source of such exposure. There are only a limited number of studies that describe the levels of phthalates (diesters, monoesters and phthalic acid) in foods and assess the exposure from this source. In this study the levels of selected phthalate diesters, phthalate monoesters and phthalic acid in total diet study (TDS) samples are determined and the resulting exposure estimated. The methodology for the determination of phthalic acid and nine phthalate monoesters (mono-isopropyl phthalate, mono-n-butyl phthalate, mono-isobutyl phthalate, mono-benzyl phthalate, mono-cyclohexyl phthalate, mono-n-pentyl phthalate, mono-(2-ethylhexyl) phthalate, mono-n-octyl phthalate and mono-isononyl phthalate) in foods is described. In this method phthalate monoesters and phthalic acid are extracted from the foodstuffs with a mixture of acidified acetonitrile and dichloromethane. The method uses isotope-labelled phthalic acid and phthalate monoester internal standards and is appropriate for quantitative determination in the concentration range of 5-100 µg kg⁻¹. The method was validated in-house and its broad applicability demonstrated by the analysis of high-fat, high-carbohydrate and high-protein foodstuffs as well as combinations of all three major food constituents. The methodology used for 15 major phthalate diesters has been reported elsewhere. Phthalic acid was the most prevalent phthalate, being detected in 17 food groups. The highest concentration measured was di-(2-ethylhexyl) phthalate in fish (789 µg kg⁻¹). Low levels of mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate were detected in several of the TDS animal-based food groups and the highest concentrations measured corresponded with the most abundant diesters (di-n-butyl phthalate and di-(2-ethylhexyl) phthalate). The UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) considered the levels found and concluded that they did not indicate a risk to human health from dietary exposure alone.

Urinary metabolomic profiling in rats exposed to dietary di(2-ethylhexyl) phthalate (DEHP) using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS).

PubMed

Dong, Xinwen; Zhang, Yunbo; Dong, Jin; Zhao, Yue; Guo, Jipeng; Wang, Zhanju; Liu, Mingqi; Na, Xiaolin; Wang, Cheng

2017-07-01

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental chemical with widespread nonoccupational human exposure through multiple ways. Although considerable efforts have been invested to investigate mechanisms of DEHP toxicity, the key metabolic biomarkers of DEHP toxicity remain to be identified. The aim of this study was to assess the urinary metabonomics of dietary DEHP in rats using the technique of ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). Fourteen female Wistar rats were divided into two groups and given increasing dietary doses of DEHP for 30 consecutive days. The urinary metabolite profile was studied using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) enabled clusters to be clearly separated. Eleven principal urinary metabolites were identified as contributing to the clusters. The clusters in the positive electrospray ionization (ESI) mode were xanthurenic acid, kynurenic acid, nonate, N6-methyladenosine, and L-isoleucyl-L-proline. The clusters in the negative ESI mode were hippuric acid, tetrahydrocortisol, citric acid, phenylpropionylglycine, cPA(18:2(9Z, 12Z)/0:0), and LysoPC(14:1(9Z)). The urinary metabonomic changes indicated that exposure to dietary DEHP can affect energy-related metabolism, liver and renal function, fatty acid metabolism, and cause DNA damage in rats. The findings of this study on the urinary metabolites and metabolic pathways of DEHP may form the basis for future studies on the mechanisms of toxicity of this commonly found environmental chemical.

The Characteristics of Atmospheric Phthalates in Shanghai: a Haze Case Study

NASA Astrophysics Data System (ADS)

Li, Y.; Wang, J.; Ren, B.; Wang, H.; Qiao, L.; Zhu, J.; Li, L.

2017-12-01

While phthalates in indoor environments are extensively studied, reports on phthalates in outdoor air, particularly their associations with haze events are rare. Phthalates, especially dimethyl phthalate, are known to react with criteria air pollutants contributing to the formation of secondary organic aerosols. This study investigated phthalates levels in outdoor air in Shanghai with a focus on their associations with different air quality conditions. The air quality during the study period was classified into three levels: non-haze, light pollution and moderate pollution based on the Air Quality Index. Phthalates levels were found to be lower in non haze (236 ng/m3) and higher in moderate pollution weather (up to 700 ng/m3). Meteorological factors of relative humidity and wind speed had an inverse relationship with phthalates levels. Airborne particulate matter had a positive correlation with phthalates levels. Hydroxyl radical initiated photo-reaction of dimethyl phthalate was observed through its inverse relationship with total atmospheric oxidant (O3 + NO2), indicating that dimethyl phthalate could be one of the precursors of secondary organic aerosol causing haze. This is the first study demonstrating the relationship of phthalates and different air quality conditions. The knowledge contributes to our understanding on the cause of haze events in China and elsewhere.

Associations of phthalate concentrations in floor dust and multi-surface dust with the interior materials in Japanese dwellings.

PubMed

Ait Bamai, Yu; Araki, Atsuko; Kawai, Toshio; Tsuboi, Tazuru; Saito, Ikue; Yoshioka, Eiji; Kanazawa, Ayako; Tajima, Shuji; Shi, Cong; Tamakoshi, Akiko; Kishi, Reiko

2014-01-15

Phthalates are widely used as plasticizers in numerous products. However, there has been some concern about the various effects they may have on human health. Thus, household phthalate levels are an important public health issue. While many studies have assessed phthalate levels in house dust, the association of these levels with building characteristics has scarcely been examined. The present study investigated phthalate levels in house dust samples collected from the living areas of homes, and examined associations between these phthalate levels and the interior materials. Dust was collected from two portions of the living area: floor dust from the entire floor surface, and multi-surface dust from objects more than 35 cm above the floor. The levels of seven phthalates were measured using gas chromatography/mass spectrometry in selective ion monitoring mode. Phthalate levels were higher in multi-surface dust than in floor dust. Among floor dust samples, those from dwellings with compressed wooden flooring had significantly higher levels of di-iso-butyl phthalate compared to those with other floor materials, while polyvinyl chloride (PVC) flooring was associated with higher di-2-ethylhexyl phthalate (DEHP) levels. Among multi-surface dust samples, higher levels of DEHP and di-iso-nonyl phthalate (DINP) were found in samples from homes with PVC wallpaper than without. The number of PVC interior materials was significantly positively correlated with the levels of DEHP and DINP in multi-surface dust. The phthalate levels in multi-surface dust were associated with the interior surface materials, and those in floor dust were directly related to the flooring materials. Our findings show that when using house dust as an exposure assessment, it is very important to note where the samples were collected from. The present report provides useful information about the association between phthalates and dust inside dwellings, which will assist with establishing public health provisions. © 2013. Published by Elsevier B.V. All rights reserved.

Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls.

PubMed

Wolff, Mary S; Teitelbaum, Susan L; Pinney, Susan M; Windham, Gayle; Liao, Laura; Biro, Frank; Kushi, Lawrence H; Erdmann, Chris; Hiatt, Robert A; Rybak, Michael E; Calafat, Antonia M

2010-07-01

Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins. We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6-8 years of age at enrollment (2004-2007). We measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age-specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones. Breast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with pubic hair development [adjusted PR, 0.94 (95% CI, 0.88-1.00), fifth vs. first quintile]. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed for low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23-1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone. Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.

Relationships between urinary biomarkers of phytoestrogens, phthalates, phenols, and pubertal stages in girls

PubMed Central

Chakraborty, Tandra R; Alicea, Eilliut; Chakraborty, Sanjoy

2012-01-01

Phytoestrogens, phthalates, and phenols are estrogen-disrupting chemicals that have a pronounced effect at puberty. They are exogenous chemicals that are either plant-derived or man-made, and can alter the functions of the endocrine system and cause various health defects by interfering with the synthesis, metabolism, binding, or cellular responses of natural estrogens. Phytoestrogens, phthalates, and phenols are some of the potent estrogens detectable in urine. Phytoestrogens are plant-derived xenestrogens found in a wide variety of food products, like soy-based food, beverages, several fruits, and vegetables. Exposure to phytoestrogens can delay breast development and further lead to precocious puberty. The effect of phytoestrogens is mediated through estrogen receptors α and β or by binding with early immediate genes, such as jun and fos. Phthalates are multifunctional synthetic chemicals used in plastics, polyvinyl chloride products, cosmetics, hair spray, and children’s toys. Phthalates have been shown to cause defeminization, thelarche, precocious puberty, and an increase in breast and pubic hair in pubertal girls. However, reports are also available that show no association of phthalates with precocious puberty in girls. Phthalates can act through a receptor-mediated signaling pathway or affect the production of luteinizing hormone and follicle-stimulating hormone that has a direct effect on estrogen formation. Phenols like bisphenol A are industrial chemicals used mainly in the manufacture of polycarbonates and plastic materials. Bisphenol A has been shown to cause precocious puberty and earlier menarche in pubertal girls. Reports suggest that the neurotoxic effect of bisphenol A can be mediated either by competing with estradiol for binding with estrogen receptors or via the ERK/NK-kappa or ERRγ pathway. This review demonstrates the effects of phytoestrogens, phthalates, and phenols on the development of girls during puberty. PMID:24600283

Phthalate exposure, even below US EPA reference doses, was associated with semen quality and reproductive hormones: Prospective MARHCS study in general population.

PubMed

Chen, Qing; Yang, Huan; Zhou, Niya; Sun, Lei; Bao, Huaqiong; Tan, Lu; Chen, Hongqiang; Ling, Xi; Zhang, Guowei; Huang, Linping; Li, Lianbing; Ma, Mingfu; Yang, Hao; Wang, Xiaogang; Zou, Peng; Peng, Kaige; Liu, Taixiu; Shi, Xiefei; Feng, Dejian; Zhou, Ziyuan; Ao, Lin; Cui, Zhihong; Cao, Jia

2017-07-01

Environment-Protection-Agency Reference Doses (EPA RfDs) for phthalate intakes are based on limited evidence, especially regarding low-dose male-reproductive toxicity. This study investigates the association between phthalate exposure and semen parameters and reproductive hormones in a general population with low phthalate exposure compared to the EPA RfDs. The MARHCS (Male-Reproductive-Health-in-Chongqing-College-Students) cohort recruited 796 male students, who experienced a relocation of campuses and shifting environmental exposure. Urine, semen and blood before and after the relocation was collected and investigated for: (1) the associations between 13 urinary phthalate metabolites and 11 semen/hormone outcomes (five semen parameters including semen volume, sperm concentration, total sperm number, progressive motility, normal morphology) and six serum reproductive hormones including estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, testosterone; (2) re-analysis of the metabolite-outcome associations in the subjects with estimated phthalate intakes below the RfDs; (3) a change in phthalate metabolites and change in semen/hormone outcomes after the relocation; (4) the association between these changes. (1) All but two semen/hormone outcomes were associated with at least one phthalate metabolite, e.g., each quartile monoethyl phthalate was associated with a 5.3%, 5.7% and 2.6% decrease of sperm concentration, total sperm number and progressive motility respectively. (2) In the subjects with phthalate intakes below the RfDs, these metabolite-outcome associations remained significant. (3) All metabolites except mono(2-ethylhexyl) phthalate declined after relocation (P<0.001 respectively); at the same time, semen volume, normal morphology, estradiol and luteinizing hormone increased (by 5.9%, 25.0%, 34.2% and 10.0%) and testosterone decreased (by 7.0%). (4) The changes in semen volume, normal morphology, estradiol and testosterone, but not the change in luteinizing hormone after relocation, were associated with the changes in the phthalate metabolites. Phthalate exposure is associated with interrupted semen quality and reproductive hormones in the human population even with a dose given below the RfDs. These effects, however, may only partially revert back when exposure decreases, thus emphasizing the urgency of stricter phthalate administration. Copyright © 2017. Published by Elsevier Ltd.

Phthalate levels in Norwegian indoor air related to particle size fraction.

PubMed

Rakkestad, Kirsten Eline; Dye, Christian Jarle; Yttri, Karl Espen; Holme, Jørn Andreas; Hongslo, Jan Kenneth; Schwarze, Per Everhard; Becher, Rune

2007-12-01

Phthalates are found in numerous consumer products, including interior materials like polyvinyl chloride (PVC). Several studies have identified phthalates in indoor air. A recent case-control study demonstrated associations between allergic symptoms in children and the concentration of phthalates in dust collected from their homes. Here we have analyzed the content of selected phthalates in particulate matter (PM): PM(10) and PM(2.5) filter samples collected in 14 different indoor environments. The results showed the presence of the phthalates di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP), dicyclohexyl phthalate (DCHP) and diethyl hexyl phthalate (DEHP) in the samples. The dominating phthalate in both PM(10) and PM(2.5) samples from all locations was DBP. More than a 10-fold variation in the mean concentration of total phthalates between sampling sites was observed. The highest levels of total phthalates were detected in one children's room, one kindergarten, in two primary schools, and in a computer room. The relative contribution of total phthalates in PM(10) and PM(2.5) was 1.1 +/- 0.3% for both size fractions. The contribution of total phthalates in PM(2.5) to total phthalates in PM(10) ranged from 23-81%, suggesting different sources. Of the phthalates that were analyzed in the PM material, DBP was found to be the major phthalate in rubber from car tyres. However, our analyses indicate that tyre wear was of minor importance for indoor levels of both DBP as well as total phthalates. Overall, these results support the notion that inhalation of indoor PM contributes to the total phthalate exposure.

The characteristics of atmospheric phthalates in Shanghai: A haze case study and human exposure assessment

NASA Astrophysics Data System (ADS)

Li, Yingjie; Wang, Jiahui; Ren, Bainian; Wang, Hongli; Qiao, Liping; Zhu, Jiping; Li, Li

2018-04-01

While phthalates in indoor environments are extensively studied, reports on phthalates in outdoor air, particularly their associations with haze weather events are rare. Phthalates, especially dimethyl phthalate, are known to react with criteria air pollutants contributing to the formation of secondary organic aerosols. This study investigated phthalates levels in the atmosphere in Shanghai with a focus on their associations with different air quality weather events. The air quality during the study period was classified into three levels: non-haze, light pollution and moderate pollution. Phthalates levels were found to be lower in non-haze weather events (236 ng/m3) and higher in moderate pollution weather events (up to 700 ng/m3). Meteorological factors of relative humidity and wind speed had an inverse relationship with phthalates levels. Particulate matter had a positive correlation with phthalates levels. Hydroxyl radical initiated photo-reaction of dimethyl phthalate was evident by its inverse relationship with total atmospheric oxidant (O3 + NO2), indicating that dimethyl phthalate could be one of the precursors of secondary organic aerosol causing haze weather events. Daily intake of phthalates through exposure to outdoor air is estimated to be relatively minor; children intake remains higher on a body weight basis. This is the first study demonstrating the relationship of phthalates and different air quality conditions in haze weather events. The knowledge contributes to our understanding on the cause of haze weather events in China and elsewhere.

Phthalate metabolites in the European eel (Anguilla anguilla) from Mediterranean coastal lagoons.

PubMed

Fourgous, C; Chevreuil, M; Alliot, F; Amilhat, E; Faliex, E; Paris-Palacios, S; Teil, M J; Goutte, A

2016-11-01

The levels and fate of phthalate metabolites have been poorly evaluated in fish, despite their potential ecotoxicological impacts. The present study aims to characterize the levels of phthalate metabolites in muscle tissue of yellow eels (Anguilla anguilla) from two coastal Mediterranean lagoons, during three sampling periods. Nine phthalate metabolites were detected in >70% of the samples. Slightly higher levels of phthalate metabolites were detected in March and June compared to October, suggesting possible seasonal variations in environmental release and/or phthalate metabolization process by eels. The large sample size (N=117) made it possible to explore correlations between phthalate metabolites' levels and individual parameters, such as body length, age, body condition and hepatic histo-pathologies. Body length and estimated age poorly correlated with phthalate metabolites, suggesting that eels did not accumulate phthalates during growth, contrary to persistent compounds. Eels presented different grades of hepatic fibrosis and lipidosis. A negative correlation was found between the severity of these pathologies in the liver and the sum of phthalate metabolites levels, supporting the hypothesis that eels with damaged liver are less able to metabolize xenobiotics. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of race on prenatal phthalate exposure and anogenital measurements among boys and girls.

PubMed

Wenzel, Abby G; Bloom, Michael S; Butts, Celeste D; Wineland, Rebecca J; Brock, John W; Cruze, Lori; Unal, Elizabeth R; Kucklick, John R; Somerville, Stephen E; Newman, Roger B

2018-01-01

Select phthalates have antiandrogenic activity, which raises concern for adverse developmental outcomes given widespread exposure of pregnant women. Investigators have reported associations between maternal urinary phthalates and altered anogenital distance (AGD), a marker of in utero androgen activity, among offspring. However, data assessing the impact of race on these associations is sparse. To evaluate associations between prenatal phthalate exposure and AGD in a racially diverse newborn population. We prospectively collected second trimester urine from 187 African American and 193 white mothers, and used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure eight phthalate metabolites and calculate molar sums. We measured anopenile (APD) and anoscrotal (ASD) distances of 171 boys and anoclitoral (ACD) and anofourchette (AFD) distances of 128 girls at delivery. We collected sociodemographic and clinical data from questionnaires and delivery records. We identified a statistically significant inverse association for mono-2-ethylhexyl phthalate (MEHP) and APD in boys (B=-1.57mm, p=0.02), which was stronger for African Americans (B=-2.07mm, p=0.04) than for whites (B=-1.23mm, p=0.22), although the racial interaction was not statistically significant (p=0.56). We found a longer ASD for higher molar sums of dibutyl phthalate (∑DBP; B=0.99mm, p=0.04), with stronger associations for whites (B=1.30mm, p=0.04) than for African Americans (B=0.39mm, p=0.59), again without a statistically significant racial interaction (p=0.34). Among girls, we found inverse associations for tertiles of MEHP with AFD and ACD, and statistically significant race-based interactions, in which ACD was longer for whites and shorter for African Americans, following exposure to monoethyl phthalate (MEP; p=0.01) and ∑DBP (p=0.08). Our findings suggest race and sex play important roles in phthalate-associated reproductive developmental toxicity, with important implications for designing future investigations and health interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of PAEs with Precocious Puberty in Children: A Systematic Review and Meta-Analysis.

PubMed

Wen, Yi; Liu, Shu-Dan; Lei, Xun; Ling, Yu-Shuang; Luo, Yan; Liu, Qin

2015-12-01

Precocious puberty (PP) currently affects 1 in 5000 children and is 10 times more common in girls. Existing studies have tried to detect an association between phathalic acid esters (PAEs) and PP, but the results did not reach a consensus. To estimate the association between PAEs and children with PP based on current evidence. Databases including PubMed (1978 to March 2015), OVID (1946 to March 2015), Web of Science (1970 to March 2015), EBSCO (1976 to March 2015), CNKI (1979 to March 2015), WANFANG DATA (1987 to March 2015), CBM (1978 to March 2015) and CQVIP (1989 to March 2015) were searched to identify all case-control studies that determined the exposure and concentration of PAEs and their metabolites in children with PP. Meta-analysis of the pooled standard mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI) were calculated. A total of 14 studies involving 2223 subjects were finally included. The pooled estimates showed that PP was associated with di-(2-ethylhexyl)-phthalate (DEHP) exposure (OR: 3.90, 95% CI: 2.77 to 5.49). Besides, the concentration of DEHP (SMD: 1.73, 95% CI: 0.54 to 2.91) and di-n-butyl phthalate (DBP) (SMD: 4.31, 95% CI: 2.67 to 5.95) in the PP group were significantly higher than those in the control group, respectively, while no difference was detected between case and control groups in either serum or urinary concentration of mono-(2-ethylhexyl)-phthalate (MEHP), monobutyl phthalate (MBP), mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), monomethyl phthalate (MMP), monobenzyl phthalate (MBzP) or monoethyl phthalate (MEP). Exposure of DEHP and DBP might be associated with PP risk for girls, however, there is no evidence to show an association between the exposure to most PAE metabolites and PP. Given the moderate strength of the results, well-designed cohort studies with large sample size should be performed in future.

[A cohort study on association between the first trimester phthalates exposure and fasting blood glucose level in the third trimester].

PubMed

Zhang, Y W; Gao, H; Huang, K; Xu, Y Y; Sheng, J; Tao, F B

2017-03-10

Objective: To examine the association between the phthalate exposure in the first trimester and fasting blood glucose level or gestational diabetes mellitus (GDM) in the third trimester in pregnant women. Methods: A total of 3 474 pregnant women, receiving their prenatal examination in Ma' anshan Maternal and Child Health-Care Hospital of Anhui province, were selected from May 2013 to September 2014. Questionnaires were used to collect the information about their socio-demographic characteristics, clinical characteristics and GDM diagnostic results in the first, second and third trimesters. Urine samples and fasting venous blood samples were collected. Concentrations of 7 kinds of phthalate metabolites in urine samples were detected by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS), and multiple linear regression model was used for statistical analyses. Logistic regression analysis on the risk of the first trimester phthalate exposure for GDM in the third trimester was conducted. Results: The prevalence of GDM in this study was 12.8%, monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEHHP) exposure levels were positively correlated with the fasting blood glucose level in the third trimester ( P <0.05), but mono-(2-ethylhexyl) phthalate (MEHP) and mono-(2-ethyl-5-hydroxylhexyl) phthalate (MEOHP) exposure levels were negatively correlated with the fasting blood glucose level in the third trimester ( P <0.05). Stratified analysis showed a positive correlation between MEHHP exposure and the third trimester fasting blood glucose level in both normal group and GDM group. However, MMP, MEP, MBP, MBzP, MEHP and MEOHP exposure levels had influences on the third trimester fasting blood glucose level in normal group but not in GDM group. MMP and MBP exposure might increase the risk of GDM, but MEOHP exposure might reduce the risk of GDM. Conclusion: The phthalate exposure in the first trimester might be associated with the fasting blood glucose level in the third trimester, MMP, MEP, MBP, MBzP and MEHHP concentrations were positively associated with the third trimester blood glucose level, MEHP and MEOHP concentrations were negatively associated with the third trimester blood glucose level. Moreover, the effects of different kinds of phthalates might be different.

Prenatal Phthalates, Maternal Thyroid Function, and Risk of Attention-Deficit Hyperactivity Disorder in the Norwegian Mother and Child Cohort.

PubMed

Engel, Stephanie M; Villanger, Gro D; Nethery, Rachel C; Thomsen, Cathrine; Sakhi, Amrit K; Drover, Samantha S M; Hoppin, Jane A; Zeiner, Pal; Knudsen, Gun Peggy; Reichborn-Kjennerud, Ted; Herring, Amy H; Aase, Heidi

2018-05-10

There is growing concern that phthalate exposures may have an impact on child neurodevelopment. Prenatal exposure to phthalates has been linked with externalizing behaviors and executive functioning defects suggestive of an attention-deficit hyperactivity disorder (ADHD) phenotype. We undertook an investigation into whether prenatal exposure to phthalates was associated with clinically confirmed ADHD in a population-based nested case-control study of the Norwegian Mother and Child Cohort (MoBa) between the years 2003 and 2008. Phthalate metabolites were measured in maternal urine collected at midpregnancy. Cases of ADHD ( n =297) were obtained through linkage between MoBa and the Norwegian National Patient Registry. A random sample of controls ( n =553) from the MoBa population was obtained. In multivariable adjusted coexposure models, the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP) was associated with a monotonically increasing risk of ADHD. Children of mothers in the highest quintile of had almost three times the odds of an ADHD diagnosis as those in the lowest [OR=2.99 (95% CI: 1.47, 5.49)]. When ∑DEHP was modeled as a log-linear (natural log) term, for each log-unit increase in exposure, the odds of ADHD increased by 47% [OR=1.47 (95% CI: 1.09, 1.94)]. We detected no significant modification by sex or mediation by prenatal maternal thyroid function or by preterm delivery. In this population-based case-control study of clinical ADHD, maternal urinary concentrations of DEHP were monotonically associated with increased risk of ADHD. Additional research is needed to evaluate potential mechanisms linking phthalates to ADHD. https://doi.org/10.1289/EHP2358.

Migrated phthalate levels into edible oils.

PubMed

Sungur, Sana; Okur, Ramazan; Turgut, Faruk Hilmi; Ustun, Ihsan; Gokce, Cumali

2015-01-01

The determination of phthalates in edible oils (virgin olive oil, olive oil, canola oil, hazelnut oil, sunflower oil, corn oil) sold in Turkish markets was carried out using gas chromatography-mass spectrometry. Mean phthalate concentrations were between 0.102 and 3.863 mg L(-1) in virgin olive oil; 0.172 and 6.486 mg L(-1) in olive oil; 0.501 and 3.651 mg L(-1) in hazelnut oil; 0.457 and 3.415 mg L(-1) in canola oil; 2.227 and 6.673 mg L(-1) in sunflower oil; and 1.585 and 6.248 mg L(-1) in corn oil. Furthermore, the influence of the types of oil and container to the phthalate migration was investigated. The highest phthalate levels were measured in sunflower oil. The lowest phthalate levels were determined in virgin olive oil and hazelnut oil. The highest phthalate levels were determined in oil samples contained in polyethylene terephthalate.

Low-Level Environmental Phthalate Exposure Associates with Urine Metabolome Alteration in a Chinese Male Cohort.

PubMed

Zhang, Jie; Liu, Liangpo; Wang, Xiaofei; Huang, Qingyu; Tian, Meiping; Shen, Heqing

2016-06-07

The general population is exposed to phthalates through various sources and routes. Integration of omics data and epidemiological data is a key step toward directly linking phthalate biomonitoring data with biological response. Urine metabolomics is a powerful tool to identify exposure biomarkers and delineate the modes of action of environmental stressors. The objectives of this study are to investigate the association between low-level environmental phthalate exposure and urine metabolome alteration in male population, and to unveil the metabolic pathways involved in the mechanisms of phthalate toxicity. In this retrospective cross-sectional study, we studied the urine metabolomic profiles of 364 male subjects exposed to low-level environmental phthalates. Di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are the most widely used phthalates. ∑DEHP and MBP (the major metabolite of DBP) were associated with significant alteration of global urine metabolome in the male population. We observed significant increase in the levels of acetylneuraminic acid, carnitine C8:1, carnitine C18:0, cystine, phenylglycine, phenylpyruvic acid and glutamylphenylalanine; and meanwhile, decrease in the levels of carnitine C16:2, diacetylspermine, alanine, taurine, tryptophan, ornithine, methylglutaconic acid, hydroxyl-PEG2 and keto-PGE2 in high exposure group. The observations indicated that low-level environmental phthalate exposure associated with increased oxidative stress and fatty acid oxidation and decreased prostaglandin metabolism. Urea cycle, tryptophan and phenylalanine metabolism disruption was also observed. The urine metabolome disruption effects associated with ∑DEHP and MBP were similar, but not identical. The multibiomarker models presented AUC values of 0.845 and 0.834 for ∑DEHP and MBP, respectively. The predictive accuracy rates of established models were 81% for ΣDEHP and 73% for MBP. Our results suggest that low-level environmental phthalate exposure associates with urine metabolome disruption in male population, providing new insight into the early molecular events of phthalate exposure.

Using exposure prediction tools to link exposure and ...

EPA Pesticide Factsheets

A few different exposure prediction tools were evaluated for use in the new in vitro-based safety assessment paradigm using di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DnBP) as case compounds. Daily intake of each phthalate was estimated using both high-throughput (HT) prediction models such as the HT Stochastic Human Exposure and Dose Simulation model (SHEDS-HT) and the ExpoCast heuristic model and non-HT approaches based on chemical specific exposure estimations in the environment in conjunction with human exposure factors. Reverse dosimetry was performed using a published physiologically based pharmacokinetic (PBPK) model for phthalates and their metabolites to provide a comparison point. Daily intakes of DEHP and DnBP were estimated based on the urinary concentrations of their respective monoesters, mono-2-ethylhexyl phthalate (MEHP) and monobutyl phthalate (MnBP), reported in NHANES (2011–2012). The PBPK-reverse dosimetry estimated daily intakes at the 50th and 95th percentiles were 0.68 and 9.58 μg/kg/d and 0.089 and 0.68 μg/kg/d for DEHP and DnBP, respectively. For DEHP, the estimated median from PBPK-reverse dosimetry was about 3.6-fold higher than the ExpoCast estimate (0.68 and 0.18 μg/kg/d, respectively). For DnBP, the estimated median was similar to that predicted by ExpoCast (0.089 and 0.094 μg/kg/d, respectively). The SHEDS-HT prediction of DnBP intake from consumer product pathways alone was higher at 0.67 μg/kg/d. The PBPK-reve

Impact of Clothing on Dermal Exposure to Phthalates: Observations and Insights from Sampling Both Skin and Clothing.

PubMed

Gong, Mengyan; Weschler, Charles J; Zhang, Yinping

2016-04-19

Clothing can either retard or accelerate dermal exposure to phthalates. To investigate the impact of clothing on dermal exposure to six phthalates (DMP/DEP/DiBP/DnBP/BBzP/DEHP) in real environments, two sets of experiments have been conducted: (1) Skin wipes were collected from 11 adults to examine the phthalate levels on both bare-skin (hand/forehead) and clothing-covered body locations (arm/back/calf); (2) Five adults were asked to wear just-washed jeans for 1 day (1(st) experiment), 5 days (2(nd) experiment), and 10 days (3(rd) experiment). Phthalate levels on their legs were measured on selected days during the wearing period, and phthalate levels in the jeans were measured at the end of each experiment and again after washing. Measured phthalate levels on body locations covered by clothing were lower than those on uncovered locations, but still substantial. Dermal uptake would be underestimated by a factor of 2 to 5 if absorption through body locations covered by clothing were neglected. Phthalate levels in the jeans and on the legs increased with the wearing time. However, the levels in the jeans and on the legs were not strongly correlated, indicating that other pathways, e.g, contact with bedding or bedclothes, likely contribute to the levels on the legs. The efficiency with which laundering washing removed phthalates from the jeans increased with decreasing Kow; median values ranged from very low (<5%) for DEHP to very high (∼75%) for DMP.

Phthalates in toys available in Indian market.

PubMed

Johnson, Sapna; Saikia, Nirmali; Sahu, Ramakant

2011-06-01

Twenty four children's toys and child care articles available in the local market of India were analyzed for eight phthalates as children toys are plasticized with phthalates. All toy samples showed the presence of one or more phthalates including di-(2-ethylhexyl) phthalate (96% of the samples), di-iso-nonyl phthalate and di-iso-decyl phthalate (42% of the samples) at a concentration ranging from 0.1% to 16.2%. Soft toys contain higher levels of phthalates as compared to hard toys as primary function of phthalates is softening of hard plastic materiel.

Interaction of DRD4 Methylation and Phthalate Metabolites Affects Continuous Performance Test Performance in ADHD.

PubMed

Kim, Johanna Inhyang; Kim, Jae-Won; Shin, Inkyung; Kim, Bung-Nyun

2018-05-01

We investigated the interaction effect between the methylation of dopamine receptor D4 (DRD4) and phthalate exposure in ADHD on continuous performance test (CPT) variables. Urine concentrations of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MBP) were tested. The methylation status was analyzed for CpG sites of DRD4. Multivariable linear regression models were applied to investigate the interaction effects of methylation and phthalate levels. There was a significant interaction effect of the methylation of CpG26 and CpG28 with the MEHHP level on omission errors in ADHD patients, but not in controls. The post hoc analysis revealed a significant correlation between the MEHHP concentration and omission errors in the methylated group, but not in the unmethylated group. The interaction between the methylation status of CpG sites of DRD4, particularly CpG26 and CpG28, and phthalate metabolite levels affects the attention level in ADHD patients.

Prenatal and childhood exposure to phthalate diesters and sex steroid hormones in 2-, 5-, 8-, and 11-year-old children: A pilot study of the Taiwan Maternal and Infant Cohort Study.

PubMed

Wen, Hui-Ju; Sie, Lillian; Su, Pen-Hua; Chuang, Chia-Jui; Chen, Hsiao-Yen; Sun, Chien-Wen; Huang, Li-Hua; Hsiung, Chao Agnes; Julie Wang, Shu-Li

2017-11-01

Phthalate diesters are commonly used and have been well established as environmental endocrine disruptors. However, few studies have examined their effects on sex steroid hormones in children. We followed children over time to examine the association between pre- and post-natal phthalate exposure and sex steroid hormone levels at 2, 5, 8, and 11 years of age. We recruited 430 pregnant women from central Taiwan from 2000 to 2001 and assessed their children at birth, 2, 5, 8, and 11 years of age. We studies children with at least one measurement for both phthalate and hormone levels during each any of the follow-up time point (n = 193). Estradiol, free testosterone, testosterone, and progesterone were measured from venous blood. Three monoesters of di-2-ethylhexyl phthalate (DEHP), mono-benzyl phthalate, mono-n-butyl phthalate, mono-ethyl phthalate, and mono-methyl phthalate were measured in maternal urine collected during the 3rd trimester and child urine collected at each follow-up point. The sum of mono-2-ethylhexyl phthalate (∑MEHP) was calculated by summing the concentrations of the three DEHP monoesters. Generalized estimating equation regression analysis with repeated measures was used to estimate associations between phthalate metabolites and hormone levels. After adjustment for potential confounders, maternal ∑MEHP level was associated with decreased levels of progesterone in girls (β = -0.309 p = 0.001). The child ∑MEHP concentration was associated with decreased levels of progesterone for girls (β = -0.194, p = 0.003) and with decreased levels of free testosterone for boys (β = -0.124, p = 0.004). Early-life DEHP exposure may alter sex steroid hormones of children over time, which may pose potential reproductive health risks. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following in utero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate and diisononyl phthalate

EPA Science Inventory

Several phthalate esters have been linked to the Phthalate Syndrome, affecting male reproductive development when administered to pregnant rats during in utero sexual differentiation. The goal of the current study was to enhance understanding of this class of compounds in the Spr...

Effect of cooking at home on the levels of eight phthalates in foods.

PubMed

Fierens, T; Vanermen, G; Van Holderbeke, M; De Henauw, S; Sioen, I

2012-12-01

Food products can be contaminated with toxic compounds via the environment. Another possibility of food contamination is that toxicants are generated in foods or that chemicals migrate from food contact materials into foods during processing. In this study, the effect of cooking at home on the levels of phthalates - world's most used group of plasticisers - in various food types (starchy products, vegetables and meat and fish) was examined. Eight compounds were considered, namely dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), benzylbutyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), dicyclohexyl phthalate (DCHP) and di-n-octyl phthalate (DnOP). Food products were analysed before as well as after cooking (boiling, steaming, (deep-)frying or grilling). In general, phthalate concentrations in foods declined after cooking, except in vegetables, where almost no effect was seen. Several factors influenced the degree of this decline (e.g. weight difference, fat uptake, etc.). Of all phthalates, DEHP, DiBP and BBP were affected the most. In conclusion, cooking at home definitely affected phthalate concentrations in foods and thus needs to be considered in order to correctly assess humans' dietary exposure to these contaminants. Copyright © 2012 Elsevier Ltd. All rights reserved.

77 FR 19005 - Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-29

... combination with other phthalates; Examine the likely levels of children's, pregnant women's, and others... substitutes. The Commission appointed this CHAP on April 14, 2010, to study the effects on children's health of all phthalates and phthalate alternatives, as used in children's toys and child care articles...

76 FR 75537 - Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-02

... other phthalates; Examine the likely levels of children's, pregnant women's, and others' exposure to... Commission appointed this CHAP on April 14, 2010, to study the effects on children's health of all phthalates and phthalate alternatives, as used in children's toys and child care articles, pursuant to section...

Associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic diseases among children aged 6 and 7 years.

PubMed

Buckley, Jessie P; Quirós-Alcalá, Lesliam; Teitelbaum, Susan L; Calafat, Antonia M; Wolff, Mary S; Engel, Stephanie M

2018-06-01

Prenatal environmental phenol and phthalate exposures may alter immune or inflammatory responses leading to respiratory and allergic disease. We estimated associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic outcomes among children in the Mount Sinai Children's Environmental Health Study. We quantified urinary biomarkers of benzophenone-3, bisphenol A, paradichlorobenzene (as 2,5-dichlorophenol), triclosan, and 10 phthalate metabolites in third trimester maternal samples and assessed asthma, wheeze, and atopic skin conditions via parent questionnaires at ages 6 and 7 years (n = 164 children with 240 observations). We used logistic regression to estimate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per standard deviation difference in natural log biomarker concentrations and examined effect measure modification by child's sex. Associations of prenatal 2,5-dichlorophenol (all outcomes) and bisphenol A (asthma outcomes) were modified by child's sex, with increased odds of outcomes among boys but not girls. Among boys, ORs for asthma diagnosis per standard deviation difference in biomarker concentration were 3.00 (95% CI: 1.36, 6.59) for 2,5-dichlorophenol and 3.04 (95% CI: 1.38, 6.68) for bisphenol A. Wheeze in the past 12 months was inversely associated with low molecular weight phthalate metabolites among girls only (OR: 0.27, 95% CI: 0.13, 0.59) and with benzophenone-3 among all children (OR: 0.65, 95% CI: 0.44, 0.96). Prenatal bisphenol A and paradichlorobenzene exposures were associated with pediatric respiratory outcomes among boys. Future studies may shed light on biological mechanisms and potential sexually-dimorphic effects of select phenols and phthalates on respiratory disease development. Copyright © 2018 Elsevier Ltd. All rights reserved.

Observing phthalate leaching from plasticized polymer films at the molecular level.

PubMed

Zhang, Xiaoxian; Chen, Zhan

2014-05-06

Phthalates, the most widely used plasticizers in poly(vinyl chloride) (PVC), have been extensively studied. In this paper, a highly sensitive, easy, and effective method was developed to examine short-term phthalate leaching from PVC/phthalate films at the molecular level using sum frequency generation vibrational spectroscopy (SFG). Combining SFG and Fourier transform infrared spectroscopy (FTIR), surface and bulk molecular structures of PVC/phthalate films were also comprehensively evaluated during the phthalate leaching process under various environments. The leaching processes of two phthalates, diethyl phthalate (DEP) and dibutyl phthalate (DBP), from the PVC/phthalate films with various weight ratios were studied. Oxygen plasma was applied to treat the PVC/phthalate film surfaces to verify its efficacy on preventing/reducing phthalate leaching from PVC. Our results show that DBP is more stable than DEP in PVC/phthalate films. Even so, DBP molecules were still found to very slowly leach to the environment from PVC at 30 °C, at a rate much slower than DEP. Also, the bulk DBP content substantially influences the DBP leaching. Higher DBP bulk concentration yields less stable DBP molecules in the PVC matrix, allowing molecules to leach from the polymer film more easily. Additionally, DBP leaching is very sensitive to temperature changes; higher temperature can strongly enhance the leaching process. For most cases, the oxygen plasma treatment can effectively prevent phthalate leaching from PVC films (e.g., for samples with low bulk concentrations of DBP-5 and 30 wt %). It is also capable of reducing phthalate leaching from high DBP bulk concentration PVC samples (e.g., 70 wt % DBP in PVC/DBP mixture). This research develops a highly sensitive method to detect chemicals at the molecular level as well as provides surface and bulk molecular structural changes. The method developed here is general and can be applied to detect small amounts of chemical/biological environmental contaminants.

Association between prenatal bisphenol A and phthalate exposures and fetal metabolic related biomarkers: The Hokkaido study on Environment and Children's Health.

PubMed

Minatoya, Machiko; Araki, Atsuko; Miyashita, Chihiro; Ait Bamai, Yu; Itoh, Sachiko; Yamamoto, Jun; Onoda, Yu; Ogasawara, Kazuki; Matsumura, Toru; Kishi, Reiko

2018-02-01

Bisphenol A and phthalates are widely detected in human urine, blood, breast milk, and amniotic fluid. Both bisphenol A and phthalates have been suggested as playing a role in obesity epidemics. Exposure to these chemicals during fetal development, and its consequences should be concerning because they can cross the placenta. Thus, this study aimed to assess the association between prenatal exposure to bisphenol A and phthalates, and cord blood metabolic-related biomarkers. Maternal serum was used during the first trimester, to determine prenatal exposure to bisphenol A and phthalates. Levels of metabolic-related biomarkers in the cord blood were also determined. Linear regression models were applied to the 365 participants with both, exposure and biomarker assessments, adjusted for maternal age, pre-pregnancy body mass index, parity, education, and sex of the child. The level of bisphenol A was negatively associated with the leptin level (β = -0.06, 95% confidence interval [CI]: -0.11, -0.01), but was positively associated with the high-molecular-weight adiponectin level, with marginal significance (β = 0.03, 95%CI: 0.00, 0.06). The mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate (MEHP), and summation of MEHP and MECPP to represent DEHP exposure (∑DEHPm) levels were inversely associated with the leptin levels (β=-0.14, 95%CI: -0.27, -0.01; β = -0.12, 95%CI: -0.24, 0.00 with marginal significance; β=0.08, 95%CI: -0.14, -0.03; and β = -0.09, 95%CI: -0.16, -0.03, respectively). The present study provided some evidence that prenatal exposure to bisphenol A and certain phthalates may modify fetal adiponectin and leptin levels. Copyright © 2017. Published by Elsevier Inc.

Occurrence of phthalate esters in over-the-counter medicines from China and its implications for human exposure.

PubMed

Jia, Lu-Lu; Lou, Xiang-Ying; Guo, Ying; Leung, Kelvin Sze-Yin; Zeng, Eddy Y

2017-01-01

Food, air, personal care products and indoor dust have been recognized as the main routes of exposure to phthalates in Chinese population, but other sources may have been overlooked, e.g., medicines. To fill the knowledge gap, phthalate esters were measured in 96 over-the-counter medicines made in China, including selected 71 Chinese patented medicines and 25 western medicines. It was found that none of the medicines was free of phthalates. The mean concentrations of individual phthalates ranged from 0.001μg/g (dicyclohexyl phthalate) to 5.85μg/g (diethyl phthalate). Among 9 targeted phthalates, di-n-butyl phthalate was the dominant congener, accounting for >65% of the total phthalates in all medicine samples, followed by di-(2-ethylhexyl) phthalate and diethyl phthalate. Phthalates in medicines appeared to derive from gastroresistant film coatings, plastic packing materials or phthalate contaminated rural herbal plants (especially for Chinese patented medicines). Daily human exposure to phthalates was estimated for local patients for one treatment cycle (e.g., one week) based on suggested consumption dosage and phthalate concentrations. Almost all exposure levels were below the guidelines suggested by the United States Environmental Protection Agency or European Food Safety Authority, indicating low health risk with phthalates from consumption of the medicines. In addition, concentration levels of phthalates in patients would increase upon administration but are expected to decrease to the same values as those in patients before they took medicines in several days. Because the number of medicine samples was limited and the concentrations of phthalates varied in a large range, further investigations are needed to acquire more data for better assessment of human health effects for Chinese population. Capsule: Distribution of phthalate esters in over-the-counter medicines and related exposure for Chinese population are examined. Copyright © 2016 Elsevier Ltd. All rights reserved.

77 FR 34028 - Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-08

... combination with other phthalates; Examine the likely levels of children's, pregnant women's, and others... children's health of all phthalates and phthalate alternatives, as used in children's toys and child care... (15 to 17 GMT) on Friday, June 29, 2012. Interested members of the public may listen to the CHAP's...

Using exposure prediction tools to link exposure and dosimetry for risk-based decisions: A case study with phthalates.

PubMed

Moreau, Marjory; Leonard, Jeremy; Phillips, Katherine A; Campbell, Jerry; Pendse, Salil N; Nicolas, Chantel; Phillips, Martin; Yoon, Miyoung; Tan, Yu-Mei; Smith, Sherrie; Pudukodu, Harish; Isaacs, Kristin; Clewell, Harvey

2017-10-01

A few different exposure prediction tools were evaluated for use in the new in vitro-based safety assessment paradigm using di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DnBP) as case compounds. Daily intake of each phthalate was estimated using both high-throughput (HT) prediction models such as the HT Stochastic Human Exposure and Dose Simulation model (SHEDS-HT) and the ExpoCast heuristic model and non-HT approaches based on chemical specific exposure estimations in the environment in conjunction with human exposure factors. Reverse dosimetry was performed using a published physiologically based pharmacokinetic (PBPK) model for phthalates and their metabolites to provide a comparison point. Daily intakes of DEHP and DnBP were estimated based on the urinary concentrations of their respective monoesters, mono-2-ethylhexyl phthalate (MEHP) and monobutyl phthalate (MnBP), reported in NHANES (2011-2012). The PBPK-reverse dosimetry estimated daily intakes at the 50th and 95th percentiles were 0.68 and 9.58 μg/kg/d and 0.089 and 0.68 μg/kg/d for DEHP and DnBP, respectively. For DEHP, the estimated median from PBPK-reverse dosimetry was about 3.6-fold higher than the ExpoCast estimate (0.68 and 0.18 μg/kg/d, respectively). For DnBP, the estimated median was similar to that predicted by ExpoCast (0.089 and 0.094 μg/kg/d, respectively). The SHEDS-HT prediction of DnBP intake from consumer product pathways alone was higher at 0.67 μg/kg/d. The PBPK-reverse dosimetry-estimated median intake of DEHP and DnBP was comparable to values previously reported for US populations. These comparisons provide insights into establishing criteria for selecting appropriate exposure prediction tools for use in an integrated modeling platform to link exposure to health effects. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Reproducibility of urinary biomarkers in multiple 24-h urine samples.

PubMed

Sun, Qi; Bertrand, Kimberly A; Franke, Adrian A; Rosner, Bernard; Curhan, Gary C; Willett, Walter C

2017-01-01

Limited knowledge regarding the reproducibility of biomarkers in 24-h urine samples has hindered the collection and use of the samples in epidemiologic studies. We aimed to evaluate the reproducibility of various markers in repeat 24-h urine samples. We calculated intraclass correlation coefficients (ICCs) of biomarkers measured in 24-h urine samples that were collected in 3168 participants in the NHS (Nurses' Health Study), NHSII (Nurses' Health Study II), and Health Professionals Follow-Up Study. In 742 women with 4 samples each collected over the course of 1 y, ICCs for sodium were 0.32 in the NHS and 0.34 in the NHSII. In 2439 men and women with 2 samples each collected over 1 wk to ≥1 mo, the ICCs ranged from 0.33 to 0.68 for sodium at various intervals between collections. The urinary excretion of potassium, calcium, magnesium, phosphate, sulfate, and other urinary markers showed generally higher reproducibility (ICCs >0.4). In 47 women with two 24-h urine samples, ICCs ranged from 0.15 (catechin) to 0.75 (enterolactone) for polyphenol metabolites. For phthalates, ICCs were generally ≤0.26 except for monobenzyl phthalate (ICC: 0.55), whereas the ICC was 0.39 for bisphenol A (BPA). We further estimated that, for the large majority of the biomarkers, the mean of three 24-h urine samples could provide a correlation of ≥0.8 with true long-term urinary excretion. These data suggest that the urinary excretion of various biomarkers, such as minerals, electrolytes, most polyphenols, and BPA, is reasonably reproducible in 24-h urine samples that are collected within a few days or ≤1 y. Our findings show that three 24-h samples are sufficient for the measurement of long-term exposure status in epidemiologic studies. © 2017 American Society for Nutrition.

Reproducibility of urinary biomarkers in multiple 24-h urine samples123

PubMed Central

Sun, Qi; Bertrand, Kimberly A; Franke, Adrian A; Rosner, Bernard; Curhan, Gary C; Willett, Walter C

2017-01-01

Background: Limited knowledge regarding the reproducibility of biomarkers in 24-h urine samples has hindered the collection and use of the samples in epidemiologic studies. Objective: We aimed to evaluate the reproducibility of various markers in repeat 24-h urine samples. Design: We calculated intraclass correlation coefficients (ICCs) of biomarkers measured in 24-h urine samples that were collected in 3168 participants in the NHS (Nurses’ Health Study), NHSII (Nurses’ Health Study II), and Health Professionals Follow-Up Study. Results: In 742 women with 4 samples each collected over the course of 1 y, ICCs for sodium were 0.32 in the NHS and 0.34 in the NHSII. In 2439 men and women with 2 samples each collected over 1 wk to ≥1 mo, the ICCs ranged from 0.33 to 0.68 for sodium at various intervals between collections. The urinary excretion of potassium, calcium, magnesium, phosphate, sulfate, and other urinary markers showed generally higher reproducibility (ICCs >0.4). In 47 women with two 24-h urine samples, ICCs ranged from 0.15 (catechin) to 0.75 (enterolactone) for polyphenol metabolites. For phthalates, ICCs were generally ≤0.26 except for monobenzyl phthalate (ICC: 0.55), whereas the ICC was 0.39 for bisphenol A (BPA). We further estimated that, for the large majority of the biomarkers, the mean of three 24-h urine samples could provide a correlation of ≥0.8 with true long-term urinary excretion. Conclusions: These data suggest that the urinary excretion of various biomarkers, such as minerals, electrolytes, most polyphenols, and BPA, is reasonably reproducible in 24-h urine samples that are collected within a few days or ≤1 y. Our findings show that three 24-h samples are sufficient for the measurement of long-term exposure status in epidemiologic studies. PMID:28049663

Considerations on ultra-trace analysis of phthalates in drinking water.

PubMed

Serôdio, P; Nogueira, J M F

2006-07-01

Stir bar sorptive extraction with liquid desorption followed by large volume injection and capillary gas chromatography coupled to mass spectrometry (SBSE-LD/LVI-GC-MS), had been applied for the determination of ultra-traces of seven-phthalates (dimethyl phthalate, diethyl phthalate, di-n-butyl phthalate, butyl benzyl phthalate, bis(2-ethylhexyl) adipate, bis(2-ethylhexyl) phthalate and bis(1-octyl) phthalate) in drinking water samples, which are included in the priority lists set by several international regulatory organizations. Instrumental calibration under the selected-ion monitoring mode acquisition (LVI-GC-MS(SIM)), experimental parameters that could affect the SBSE-LD efficiency, as well as, the control of the contamination profile are fully discussed. Throughout systematic assays on 30 mL water samples spiked at the 0.40 microg/L level, it had been established that stir bars coated with 47 microL of polydimethylsiloxane, an equilibrium time of 60 min (1,000 rpm) and methanol as back extraction solvent, allowed the best analytical performance to monitor phthalates in water matrices. From the data obtained, good accuracy and a remarkable reproducibility (< 14.8%) were attained, providing experimental recovery data in agreement with the theoretical equilibrium described by the octanol-water partition coefficients (K(PDMS/W) approximately K(O/W)), with the exception of bis(2-ethylhexyl) adipate, bis(2-ethylhexyl) phthalate and bis(1-octyl) phthalate, for which lower yields were measured. Additionally, a remarkable linear dynamic range between 25 and 2,000 ng/L (r(2)>0.99) and low detection limits (3-40 ng/L) were also achieved for the seven-phthalates studied. The application of the present method to monitor phthalates in tap and bottled mineral water samples, allowed convenient selectivity and high sensitivity up to 1.0 microg/L level, using the standard addition methodology. The proposed method showed to be feasible and sensitive with a low sample volume requirement to monitor phthalates in drinking water matrices at the ultra-trace level, in compliance with international regulatory directives on water quality.

Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smolders, R., E-mail: roel.smolders@vito.be; Den Hond, E.; Koppen, G.

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother–child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality andmore » lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making. - Highlights: • External data was collected to interpret HBM data from DEMOCOPHES. • Hg in hair could be related to fish consumption across different countries. • Urinary cotinine was related to strictness of anti-smoking legislation. • Urinary Cd was borderline significantly related to air and food quality. • Lack of comparable data among countries hampered the analysis.« less

Association between urine phthalate levels and poor attentional performance in children with attention-deficit hyperactivity disorder with evidence of dopamine gene-phthalate interaction.

PubMed

Park, Subin; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Yeni; Kim, Jae-Won; Lee, Ju-Young; Hong, Soon-Beom; Shin, Min-Sup; Yoo, Hee Jeong; Im, Hosub; Cheong, Jae Hoon; Han, Doug Hyun

2014-06-27

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child's urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms.

Tissue Phthalate Levels Correlate With Changes in Immune Gene Expression in a Population of Juvenile Wild Salmon.

PubMed

Martins, Kelly; Hagedorn, Birgit; Ali, Shareen; Kennish, John; Applegate, Ben; Leu, Matthias; Epp, Lidia; Pallister, Chris; Zwollo, Patty

2016-07-01

Phthalates have detrimental effects on health and have been shown to dysregulate the immune system of mammals, birds, and fish. We recently reported that di(2-ethylhexyl) phthalate exposure reduces the abundance and inhibits the proliferation of rainbow trout (Oncorhynchus mykiss) IgM(+) B lymphocytes and expression of secreted immunoglobulin heavy-chain mu transcripts in an in vitro culture system. We proposed that phthalates act as immunomodulators by modifying the normal B cell-activation pathways by accelerating B cell differentiation while suppressing plasmablast expansion, thus resulting in fewer IgM-secreting plasma cells. This hypothesis was tested here in an in vivo field study of juvenile Dolly Varden (Salvelinus malma) from a plastic-polluted lake in the Gulf of Alaska. Fish tissues were analyzed for both phthalate levels using liquid chromatography-coupled tandem mass spectrometry and for changes in immune gene expression using reverse transcriptase-real time polymerase chain reaction. Results showed that fish with higher tissue levels of di(2-ethylhexyl) phthalate, di(n-butyl) phthalate, and/or dimethyl phthalate expressed significantly fewer secreted and membrane-bound immunoglobulin heavy-chain mu and Blimp1 transcripts in their hematopoietic tissue. This suggests that in vivo uptake of phthalates in fish changes the expression of B cell-specific genes. Chronic exposure to phthalates likely dysregulates normal B-lymphoid development and antibody responses in salmonids and may increase susceptibility to infection. Given the conserved nature of B-lineage cells in vertebrate animals, other marine species may be similarly affected by chronic phthalate exposure.

[Analysis of phthalates in aromatic and deodorant aerosol products and evaluation of exposure risk].

PubMed

Sato, Yoshiki; Sugaya, Naeko; Nakagawa, Tomoo; Morita, Masatoshi

2015-01-01

We established an analytical method for the detection of seven phthalates, dimethyl phthalate, diethyl phthalate (DEP), benzyl butyl phthalate, di-i-butyl phthalate, dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP), and di-n-octhyl phthalate, using an ultra high performance liquid chromatograph equipped with a photodiode array detector. This method is quick, with minimal contamination, and was applied to the analysis of aromatic and deodorant aerosol products. Phthalates were detected in 15 of 52 samples purchased from 1999 to 2012 in Yokohama. Three types of phthalate (DEP, DBP, DEHP) were detected, and their concentrations ranged from 0.0085-0.23% DEP in nine samples, 0.012-0.045% DBP in four samples, and 0.012-0.033% DEHP in four samples. No other phthalate esters were detected. Furthermore, we estimated phthalate exposure via breathing in commonly used aromatic and deodorant aerosol products, then evaluated the associated risk. The estimated levels of phthalate exposure were lower than the tolerated daily limit, but the results indicated that aromatic and deodorant aerosol products could be a significant source of phthalate exposure.

MEASUREMENT OF PHTHALATE LEVELS IN HUMAN MILK: CONTRIBUTION FROM PLASTICS IN BREAST PUMPS, STORAGE BOTTLES AND BAGS

EPA Science Inventory

Phthalates are plasticizers used to impart flexibility in products widely used by the general population, including polyvinyl chloride, plastic toys, and medical devices. Some phthalates act as anti-androgens, and prenatal or perinatal exposure to phthalates in laboratory animals...

Phthalates residues in plastic bottled waters.

PubMed

Al-Saleh, Iman; Shinwari, Neptune; Alsabbaheen, Ammar

2011-08-01

This study was conducted to determine the presence of phthalates in 10 different brands of bottled water available in Saudi markets and stored under different conditions. Dimethyl phthalate (DMP), diethylphthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP) and diethyl hexyl phthalate (DEHP) were measured by headspace solid-phase microextraction followed by gas chromatography- mass spectrometer detector. Most of these phthalates were detected in the selected bottled water sample that might be either leached from the plastic packaging materials or contamination during bottling processes. Bottled waters stored at 4°C contained higher levels of DMP, DEP, BBP and DEHP than those stored at room temperature and outdoors. On the other hand, the levels of DMP, DEP and BBP were significantly lower in bottled waters stored at room temperature than those outdoor. It seems that temperature and sunlight play a role in the degradation of phthalates within time. The levels of BBP were the highest at 4°C storage (4.592 ± 3.081 µg/l; range: 1.194-21.128 µg/l) and approximately 76% of the bottled waters had BBP above the limit of quantification (LOQ) of 0.994 µg/l. Apart from DEHP (< 6 µg/l), there are not current legislations for other phthalates. Regardless of storage conditions, all our samples did not exceed the maximum established limit of DEHP. Although, the levels of phthalates in tested bottled waters were low, one should not dismiss that these chemicals may cause endocrine disruption through several mechanisms, especially to potentially vulnerable populations such as infants and pregnant women. Saudi Arabia ranks 12 in bottled water consumption (88 L per capita in 2004) among the 71 reported countries. With this high consumption, a quality assurance scheme for residue monitoring in water is quite important. Although, one cannot avoid phthalates contamination in bottled waters due to manufacturing process but at least special care should be taken regarding their storage conditions.

Association between Urine Phthalate Levels and Poor Attentional Performance in Children with Attention-Deficit Hyperactivity Disorder with Evidence of Dopamine Gene-Phthalate Interaction

PubMed Central

Park, Subin; Kim, Bung-Nyun; Cho, Soo-Churl; Kim, Yeni; Kim, Jae-Won; Lee, Ju-Young; Hong, Soon-Beom; Shin, Min-Sup; Yoo, Hee Jeong; Im, Hosub; Cheong, Jae Hoon; Han, Doug Hyun

2014-01-01

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child’s urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms. PMID:24978879

Association of Exposure to Di-2-Ethylhexylphthalate Replacements With Increased Insulin Resistance in Adolescents From NHANES 2009–2012

PubMed Central

Trasande, Leonardo

2015-01-01

Context: Di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP) are environmental chemicals increasingly used to replace di-2-ethylhexylphthalate (DEHP) and commonly found in processed foods. Phthalate exposures, in particular DEHP, have been associated with insulin resistance in adolescents, but there are no data regarding the two substitutes, DINP and DIDP. Objective: This study aimed to examine associations of DINP, DIDP, and DEHP with insulin resistance outcomes. Design, Setting, and Participants: This was a cross-sectional analysis of 2009–2012 National Health and Nutrition Examination Surveys (NHANES) composed of 356 fasting 12–19-year-olds. Main Outcome Measures: Insulin resistance as a categorical outcome expressed as homeostatic model assessment of insulin resistance (HOMA-IR), using a cut point of 4.39 to define insulin resistance. We also examined continuous HOMA-IR as an outcome in secondary analyses. Results: Controlling for demographic and behavioral factors, diet, age, body mass index, and urinary creatinine, for each log increase in DINP metabolite, a 0.08 (P = .001) increase in HOMA-IR was identified. Compared with the first tertile of DINP (23.4% adjusted prevalence), the third tertile was associated with a 34.4% prevalence (95% confidence interval [CI], 27.3–41.6%; P = .033) of insulin resistance. Similarly, compared with the first tertile of DEHP (20.5% adjusted prevalence), the third tertile had 37.7% prevalence (95% CI 29.8–45.6%; P = .003). Conclusions: Urinary DINP concentrations were associated with increased insulin resistance in this cross-sectional study of adolescents. The previously identified association of DEHP with insulin resistance was also confirmed. Further, longitudinal studies are needed to confirm these associations, with the possibility to assess opportunities for intervention. PMID:25993640

77 FR 2276 - Teleconference and Public Meeting of the Chronic Hazard Advisory Panel on Phthalates and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

... levels of children's, pregnant women's, and others' exposure to phthalates, based upon a reasonable... 2010, and in March, July, and November 2011, at the CPSC's offices in Bethesda, MD, and by... on children's health of all phthalates and phthalate alternatives, as used in children's toys and...

Urinary Cadmium and Cotinine Levels and Hair Mercury Levels in Czech Children and Their Mothers Within the Framework of the COPHES/DEMOCOPHES Projects.

PubMed

Forysová, Kateřina; Pinkr-Grafnetterová, Anna; Malý, Marek; Krsková, Andrea; Mráz, Jaroslav; Kašparová, Lucie; Čejchanová, Mája; Sochorová, Lenka; Rödlová, Sylva; Černá, Milena

2017-10-01

The COPHES/DEMOCOPHES twin project was performed in 2011-2012 in 17 European countries to harmonize all steps of the human biomonitoring survey. Urinary cadmium, cotinine, phthalate metabolites, and hair mercury were measured in children (N = 120, 6-11 years) and their mothers of reproductive age, living in urban or rural areas. Cadmium in mothers' and children's urine was detected at a geometric mean (GM) concentration 0.227 and 0.109 μg/L, respectively; 95th percentile (P95) was 0.655 and 0.280 μg/L in mothers and children, respectively. No age-related, education-related, or urban versus rural differences were observed within the frame of each population group. Cadmium urinary level in mothers was about twofold compared with children. Higher levels were obtained in all smoking mothers but not in occasionally smoking or mothers and children exposed to environmental tobacco smoke (ETS). Mercury values in mothers were significantly higher in urban than in rural populations but not in children. GM and P95 for mercury in children's hair were 0.098 and 0.439 μg/g and in mothers' hair were 0.155 and 0.570 μg/g. Concentrations for mercury in the Czech samples were lower than European average. Hair mercury increased significantly with consumption of fish or seafood and with number of amalgam tooth fillings (in children). A positive association was found with family educational level. No influence of age was observed. Urinary cadmium and hair mercury levels were lower than health-based guidelines with one exception. High levels of urinary cotinine were found in the 12 smoking mothers (GM approximately 500 μg/L); lower levels in occasionally smoking mothers, N = 11 (34.5 μg/L). The mean cotinine levels in nonsmoking mothers who reported daily exposure to ETS was 10.7 μg/L. A similar mean value (10.8 μg/L) was obtained in six children who had daily exposure to ETS. In children without exposure to ETS, the mean cotinine level was 1.39 μg/L urine. Cotinine in the urine of children demonstrates limited protection of the Czech children against exposure to ETS.

Prenatal and Peripubertal Phthalates and Bisphenol-A in Relation to Sex Hormones and Puberty in Boys

PubMed Central

Ferguson, Kelly K.; Peterson, Karen E.; Lee, Joyce M.; Mercado-García, Adriana; Goldenberg, Clara B.; Téllez-Rojo, Martha M.; Meeker, John D.

2014-01-01

Phthalates and BPA are known endocrine disruptors and exposure in pregnant mothers and children is ubiquitous. We explored the relationship of prenatal and childhood exposures with pubertal onset and sex hormones in boys (ages 8–14). Phthalate metabolites and BPA were measured in maternal 3rd trimester or childhood urine. Sex hormones DHEAS, estradiol, inhibin B, SHBG, and total testosterone were measured in serum. Adrenarche and puberty were assessed by pediatrician. Prenatal exposure to some phthalates was associated with decreased DHEAS and inhibin B levels, and with increased SHBG. Prenatal exposure to most phthalates and BPA was associated with greatly reduced odds of adrenarche (odds ratios [OR] = 0.12 to 0.65) and slightly reduced odds of puberty (OR = 0.50 to 0.98). Childhood exposure was not associated with adrenarche or puberty, but some phthalates and BPA were associated with increased SHBG levels and decreased total and free testosterone levels. PMID:24945889

Urine Levels of Phthalate Metabolites and Bisphenol A in Relation to Main Metabolic Syndrome Components: Dyslipidemia, Hypertension and Type 2 Diabetes. A Pilot Study.

PubMed

Piecha, Roman; Svačina, Štěpán; Malý, Marek; Vrbík, Karel; Lacinová, Zdenka; Haluzík, Martin; Pavloušková, Jana; Vavrouš, Adam; Matějková, Dagmar; Müllerová, Dana; Mráz, Miloš; Matoulek, Martin

2016-12-01

Human exposure to organic pollutants (some of them also called endocrine disruptors) can be associated with adverse metabolic health outcomes including type 2 diabetes. The goal of this study was to compare the urine levels of bisphenol A and phthalate metabolites in subgroups of patients with metabolic syndrome composed of patients with and without three important components of metabolic syndrome (hypertension, dyslipidemia and diabetes). We have investigated 24 hr urine samples of 168 patients with metabolic syndrome from the Metabolic Outpatient Department of General University Hospital in Prague. Using standard metabolic syndrome criteria, we classified patients as dyslipidemic (n=87), hypertensive (n=96), and type 2 diabetic (n=58). Bisphenol A and 15 metabolites of phthalates were evaluated in relation to creatinine excretion. Samples were analysed with enzymatic cleavage of glucuronide using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in one laboratory with external quality control. Four metabolites, mono-n-butyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-carboxypentyl) phthalate showed significantly higher levels in diabetic compared to non-diabetic patients (p<0.001, p=0.002, p=0.002, and p=0.005, respectively). The differences remained significant after adjustment to hypertension, dyslipidemia, age, and BMI. No difference was found between either the hypertensive and non-hypertensive or dyslipidemic and non-dyslipidemic patients. There was no significant relation of bisphenol A level to diabetes, hypertension, dyslipidemia, age, and BMI. Urine levels of four phthalate metabolites were significantly higher in type 2 diabetics independently on specified predictors. Phthalate levels can be in relation to beta cell dysfunction in type 2 diabetic patients but this study is not able to show if the relation is causal. Copyright© by the National Institute of Public Health, Prague 2016

Contamination level of four priority phthalates in North Indian wastewater treatment plants and their fate in sequencing batch reactor systems.

PubMed

Gani, Khalid Muzamil; Rajpal, Ankur; Kazmi, Absar Ahmad

2016-03-01

The contamination level of four phthalates in untreated and treated wastewater of fifteen wastewater treatment plants (WWTPs) and their fate in a full scale sequencing batch reactor (SBR) based WWTP was evaluated in this study. The four phthalates were diethyl phthalate (DEP), dibutyl phthalate (DBP), benzylbutyl phthalate (BBP) and diethylhexyl phthalate (DEHP). All compounds were present in untreated wastewater with DEHP being present in the highest mean concentration of 28.4 ± 5.3 μg L(-1). The concentration was in the range of 7.3 μg L(-1) (BBP) to 28.4 μg L(-1) (DEHP) in untreated wastewater and 1.3 μg L(-1) (DBP) to 2.6 μg L(-1) (DEHP) in treated wastewater. The nutrient removal process and advance tertiary treatment based WWTPs showed the highest phthalate removal efficiencies of 87% and 93%, respectively. The correlation between phthalate removal and conventional performance of WWTPs was positive. Fate analysis of these phthalates in a SBR based WWTP showed that total removal of the sum of phthalates in a primary settling tank and SBR was 84% out of which 55% is removed by biodegradation and 29% was removed by sorption to primary and secondary sludge. The percentage removal of four phthalates in primary settling tanks was 18%. Comparison of the diluted effluent DEHP concentration with its environmental quality standards showed that the dilution in an effluent receiving water body can reduce the DEHP emissions to acceptable values.

Interaction of melamine and di-(2-ethylhexyl) phthalate exposure on markers of early renal damage in children: The 2011 Taiwan food scandal.

PubMed

Wu, Chia-Fang; Hsiung, Chao A; Tsai, Hui-Ju; Tsai, Yi-Chun; Hsieh, Hui-Min; Chen, Bai-Hsiun; Wu, Ming-Tsang

2018-04-01

Melamine and phthalate, mainly di-(2-ethylhexyl) phthalate (DEHP), are ubiquitously present in the general environment. We investigated whether urine melamine levels can modify the relationship between DEHP exposure and markers of early renal damage in children. A nationwide health survey for Children aged ≤12 years possibly exposed to phthalates were enrolled between August 2012 and January 2013. They were administered questionnaires to collect details regarding past DEHP exposure to phthalate-tainted foodstuffs. Urine samples were measured melamine levels, phthalate metabolites and biomarkers of renal damage, including urine microalbumin/creatinine ratio (ACR), N-acetyl-beta-d-glucosaminidase (NAG), and β2-microglobulin. The study included 224 children who had a median urine melamine level (μg/mmol creatinine) of 1.61 ranging 0.18-47.42. Positive correlations were found between urine melamine levels and urine ACR as well as urine NAG levels (both Spearman correlation coefficients r = 0.24, n = 224, p < .001). The higher the past DEHP exposure or urine melamine levels, the higher the prevalence of microalbuminuria. An interaction effect was also found between urine melamine levels and past DEHP exposure on urine ACR. Melamine levels may further modify the effect of past DEHP exposure on urine ACR in children. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessing human exposure to phthalic acid and phthalate esters from mineral water stored in polyethylene terephthalate and glass bottles.

PubMed

Montuori, P; Jover, E; Morgantini, M; Bayona, J M; Triassi, M

2008-04-01

Phthalic acid and phthalate esters are of growing interest due to their significant usage and potential toxicity. Polyethylene terephthalate (PET) and glass are both widely used materials for bottled drinking water. In this study, phthalic acid (PhA), bis(2-ethylhexyl) phthalate (DEHP), dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiisoBP) and dibutyl phthalate (DBP) were analysed in a large number of Italian bottled water samples. These samples showed different concentrations of phthalates are nearly 20 times higher in samples bottled in PET than those from glass bottles with total levels of phthalates of 3.52 and 0.19 microg l(-1), respectively. However, the observed levels do not represent a significant exposure pathway when considering the US Environmental Protection Agency (USEPA) reference dose (an estimate of a daily oral exposure to the human population, including sensitive subgroups, that is likely to be without an appreciable risk of deleterious effects during a lifetime). In addition, no significant correlation was found between the phthalate concentrations and the physicochemical properties of the different water samples, apart from the still/sparkling water parameter for the PET samples. In this instance, slightly higher concentrations were observed for the PET bottled still water samples than for the sparkling water samples, although no explanation has been found yet.

Screening of phthalate esters in 47 branded perfumes.

PubMed

Al-Saleh, Iman; Elkhatib, Rola

2016-01-01

In the last few years, the use of phthalates in perfumes has gained attention because these chemicals are sometimes added intentionally as a solvent and a fixative. Five phthalate esters, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and diethyl hexyl phthalate (DEHP), were measured in 47 branded perfumes using headspace solid phase microextraction (SPME) followed by gas chromatography-mass spectrometry (GC-MS). The results revealed considerable amounts of phthalate in all 47 brands with detection frequencies > limit of quantitation in the following order: DEP (47/47) > DMP (47/47) > BBP (47/47) > DEHP (46/47) > DBP (23/45). Of the 47 brands, 68.1, 72.3, 85.1, 36.2, and 6.7 % had DEP, DMP, BBP, DEHP, and DBP levels, respectively, above their reported threshold limits. Of these phthalates, DEP was found to have the highest mean value (1621.625 ppm) and a maximum of 23,649.247 ppm. The use of DEP in the perfume industry is not restricted because it does not pose any known health risks for humans. DMP had the second highest level detected in the perfumes, with a mean value of 30.202 ppm and a maximum of 405.235 ppm. Although DMP may have some uses in cosmetics, it is not as commonly used as DEP, and again, there are no restrictions on its use. The levels of BBP were also high, with a mean value of 8.446 ppm and a maximum of 186.770 ppm. Although the EU banned the use of BBP in cosmetics, 27 of the tested perfumes had BBP levels above the threshold limit of 0.1 ppm. The mean value of DEHP found in this study was 5.962 ppm, and a maximum was 147.536 ppm. In spite of its prohibition by the EU, 7/28 perfumes manufactured in European countries had DEHP levels above the threshold limit of 1 ppm. The DBP levels were generally low, with a mean value of 0.0305 ppm and a maximum value of 0.594 ppm. The EU banned the use of DBP in cosmetics; however, we found three brands that were above the threshold limit of 0.1 ppm, and all were manufactured in European countries. The results of this study are alarming and definitely need to be brought to the attention of the public and health regulators. Although some phthalate compounds are still used in cosmetics, many scientists and environmental activists have argued that phthalates are endocrine-disrupting chemicals that have not been yet proven to be safe for any use, including cosmetics. Phthalates may also have different degrees of estrogenic modes of action. Furthermore, we should not dismiss the widespread use of phthalates in everyday products and exposure to these chemicals from sources such as food, medications, and other personal care products.

Correlation of phthalate exposures with semen quality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pant, Niraj; Shukla, Manju; Kumar Patel, Devendra

2008-08-15

Phthalates are widely used man-made chemical released in the environment and human exposure is mainly through diet. As the phthalate plasticizers are not covalently bound to PVC, they can leach, migrate or evaporate into the environment and as a result have become ubiquitously contaminants. The present study investigates the correlation, if any, between the phthalate esters (DEP, DEHP, DBP, DMP, DOP) and sperm mitochondrial status, ROS, LPO, SCSA, and sperm quality. The study was conducted in the urban/rural population of Lucknow visiting Obstetrics and Gynecology Department, CSMMU, Lucknow. Semen analysis was performed according to the WHO guidelines while phthalate analysismore » by HPLC and LPO by spectrophotometer and the sperm mitochondrial status, ROS, SCSA using flow cytometry. The questionnaire data showed no significant difference in the demographic characteristics among the groups. In general, urban population was found to have statistically significant higher levels of phthalate esters than the rural. Further, infertile men showed statistically significant (p < 0.05) higher levels of pollutants in the semen than fertile men. A negative correlation between semen phthalate level viz DEHP and sperm quality and positive association with depolarized mitochondria, elevation in ROS production and LPO, DNA fragmentation was established. The findings are suggestive that phthalates might be one among the contributing factors associated with the deterioration in semen quality and these adverse effects might be ROS, LPO and mitochondrial dysfunction mediated.« less

Single ingestion of di-(2-propylheptyl) phthalate (DPHP) by male volunteers: DPHP in blood and its metabolites in blood and urine.

PubMed

Klein, D; Kessler, W; Pütz, C; Semder, B; Kirchinger, W; Langsch, A; Gries, W; Otter, R; Gallien, A K E; Wurzenberger, X; Filser, J G

2018-05-11

Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metabolites in blood and urine of 6 male volunteers over time following ingestion of a single DPHP dose (0.7 mg/kg body weight). Concentration-time courses in blood were obtained up to 24 h for DPHP, mono-(2-propylheptyl) phthalate (MPHP), mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP), and mono-(2-propyl-6-oxoheptyl) phthalate (oxo-MPHP); amounts excreted in urine were determined up to 46 h for MPHP, OH-MPHP, oxo-MPHP, and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). All curves were characterized by an invasion and an elimination phase the kinetic parameters of which were determined together with the areas under the concentration-time curves in blood (AUCs). AUCs were: DPHP > MPHP > oxo-MPHP > OH-MPHP. The amounts excreted in urine were: oxo-MPHP > OH-MPHP> > cx-MPHP > MPHP. The AUCs of MPHP, oxo-MPHP, or OH-MPHP could be estimated well from the cumulative amounts of urinary OH-MPHP or oxo-MPHP excreted within 22 h after DPHP intake. Not considering possible differences in species-sensitivity towards unconjugated DPHP metabolites, it was concluded from a comparison of their AUCs in DPHP-exposed humans with corresponding earlier data in rats that there is no increased risk of adverse effects associated with the internal exposure of unconjugated DPHP metabolites in humans as compared to rats when receiving the same dos of DPHP per kg body weight. Copyright © 2018. Published by Elsevier B.V.

Dose Reconstruction of Di(2-ethylhexyl) Phthalate Using a Simple Pharmacokinetic Model

PubMed Central

Calafat, Antonia M.

2012-01-01

Background: Di(2-ethylhexyl) phthalate (DEHP), used primarily as a plasticizer for polyvinyl chloride, is found in a variety of products. Previous studies have quantified human exposure by back calculating intakes based on DEHP metabolite concentrations in urine and by determining concentrations of DEHP in exposure media (e.g., air, food, dust). Objectives: To better understand the timing and extent of DEHP exposure, we used a simple pharmacokinetic model to “reconstruct” the DEHP dose responsible for the presence of DEHP metabolites in urine. Methods: We analyzed urine samples from eight adults for four DEHP metabolites [mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-carboxypentyl) phthalate]. Participants provided full volumes of all voids over 1 week and recorded the time of each void and information on diet, driving, and outdoor activities. Using a model previously calibrated on a single person self-dosed with DEHP in conjunction with the eight participants’ data, we used a simple trial-and-error method to determine times and doses of DEHP that resulted in a best fit of predicted and observed urinary concentrations of the metabolites. Results: The average daily mean and median reconstructed DEHP doses were 10.9 and 5.0 µg/kg-day, respectively. The highest single modeled dose of 60 µg/kg occurred when one study participant reported consuming coffee and a bagel with egg and sausage that was purchased at a gas station. About two-thirds of all modeled intake events occurred near the time of reported food or beverage consumption. Twenty percent of the modeled DEHP exposure occurred between 2200 hours and 0500 hours. Conclusions: Dose reconstruction using pharmacokinetic models—in conjunction with biomonitoring data, diary information, and other related data—can provide a powerful means to define timing, magnitude, and possible sources of exposure to a given contaminant. PMID:23010619

Children’s Phthalate Intakes and Resultant Cumulative Exposures Estimated from Urine Compared with Estimates from Dust Ingestion, Inhalation and Dermal Absorption in Their Homes and Daycare Centers

PubMed Central

Bekö, Gabriel; Weschler, Charles J.; Langer, Sarka; Callesen, Michael; Toftum, Jørn; Clausen, Geo

2013-01-01

Total daily intakes of diethyl phthalate (DEP), di(n-butyl) phthalate (DnBP), di(isobutyl) phthalate (DiBP), butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) were calculated from phthalate metabolite levels measured in the urine of 431 Danish children between 3 and 6 years of age. For each child the intake attributable to exposures in the indoor environment via dust ingestion, inhalation and dermal absorption were estimated from the phthalate levels in the dust collected from the child’s home and daycare center. Based on the urine samples, DEHP had the highest total daily intake (median: 4.42 µg/d/kg-bw) and BBzP the lowest (median: 0.49 µg/d/kg-bw). For DEP, DnBP and DiBP, exposures to air and dust in the indoor environment accounted for approximately 100%, 15% and 50% of the total intake, respectively, with dermal absorption from the gas-phase being the major exposure pathway. More than 90% of the total intake of BBzP and DEHP came from sources other than indoor air and dust. Daily intake of DnBP and DiBP from all exposure pathways, based on levels of metabolites in urine samples, exceeded the Tolerable Daily Intake (TDI) for 22 and 23 children, respectively. Indoor exposures resulted in an average daily DiBP intake that exceeded the TDI for 14 children. Using the concept of relative cumulative Tolerable Daily Intake (TDIcum), which is applicable for phthalates that have established TDIs based on the same health endpoint, we examined the cumulative total exposure to DnBP, DiBP and DEHP from all pathways; it exceeded the tolerable levels for 30% of the children. From the three indoor pathways alone, several children had a cumulative intake that exceeded TDIcum. Exposures to phthalates present in the air and dust indoors meaningfully contribute to a child’s total intake of certain phthalates. Such exposures, by themselves, may lead to intakes exceeding current limit values. PMID:23626820

Prenatal exposure to bisphenol A and phthalates and childhood respiratory tract infections and allergy.

PubMed

Gascon, Mireia; Casas, Maribel; Morales, Eva; Valvi, Damaskini; Ballesteros-Gómez, Ana; Luque, Noelia; Rubio, Soledad; Monfort, Núria; Ventura, Rosa; Martínez, David; Sunyer, Jordi; Vrijheid, Martine

2015-02-01

There is growing concern that prenatal exposure to bisphenol A (BPA) and phthalates, which are widely used in consumer products, might affect susceptibility to infections and the development of allergy and asthma in children, but there are currently very few prospective studies. We sought to evaluate whether prenatal exposure to BPA and phthalates increases the risk of respiratory and allergic outcomes in children at various ages from birth to 7 years. We measured BPA and metabolites of high-molecular-weight phthalates, 4 di-(2-ethylhexyl) phthalate (DEHP) metabolites (Σ4DEHP) and mono-benzyl phthalate (MBzP), and 3 low-molecular-weight phthalate (LMWP) metabolites (Σ3LMWP) in urine samples collected during the first and third trimesters in pregnant women participating in the Infancia y Medio Ambiente-Sabadell birth cohort study. The occurrence of chest infections, bronchitis, wheeze, and eczema in children was assessed at ages 6 and 14 months and 4 and 7 years through questionnaires given to the mothers. Atopy (specific IgE measurement) and asthma (questionnaire) were assessed at ages 4 and 7 years, respectively. The relative risks (RRs) of wheeze (RR, 1.20; 95% CI, 1.03-1.40; P = .02), chest infections (RR, 1.15; 95% CI, 1.00-1.32; P = .05), and bronchitis (RR, 1.18; 95% CI, 1.01-1.37; P = .04) at any age increased for each doubling in concentration of maternal urinary BPA. Σ4DEHP metabolites were associated with the same outcomes (wheeze: RR, 1.25; 95% CI, 1.04-1.50, P = .02; chest infections: RR, 1.15; 95% CI, 0.97-1.35; P = .11; bronchitis: RR, 1.20; 95% CI, 1.01-1.43; P = .04). MBzP was associated with higher risk of wheeze (RR, 1.15; 95% CI, 1.00-1.33; P = .05). The risk of asthma at age 7 years was also increased with increasing prenatal BPA, Σ4DEHP, and MBzP exposure. There were no other exposure-outcome associations. Prenatal exposure to BPA and high-molecular-weight phthalates might increase the risk of asthma symptoms and respiratory tract infections throughout childhood. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Phthalates in dormitory and house dust of northern Chinese cities: Occurrence, human exposure, and risk assessment.

PubMed

Li, Hai-Ling; Song, Wei-Wei; Zhang, Zi-Feng; Ma, Wan-Li; Gao, Chong-Jing; Li, Jia; Huo, Chun-Yan; Mohammed, Mohammed O A; Liu, Li-Yan; Kannan, Kurunthachalam; Li, Yi-Fan

2016-09-15

Phthalates are widely used chemicals in household products, which severely affect human health. However, there were limited studies emphasized on young adults' exposure to phthalates in dormitories. In this study, seven phthalates were extracted from indoor dust that collected in university dormitories in Harbin, Shenyang, and Baoding, in the north of China. Dust samples were also collected in houses in Harbin for comparison. The total concentrations of phthalates in dormitory dust in Harbin and Shenyang samples were significantly higher than those in Baoding samples. The total geometric mean concentration of phthalates in dormitory dust in Harbin was lower than in house dust. Di-(2-ethylhexyl) phthalate (DEHP) was the most abundant phthalate in both dormitory and house dust. The daily intakes of the total phthalates, carcinogenic risk (CR) of DEHP, hazard index (HI) of di-isobutyl phthalate (DiBP), dibutyl phthalate (DBP), and DEHP were estimated, the median values for all students in dormitories were lower than adults who live in the houses. Monte Carlo simulation was applied to predict the human exposure risk of phthalates. HI of DiBP, DBP, and DEHP was predicted according to the reference doses (RfD) provided by the United States Environmental Protection Agency (U.S.EPA) and the reference doses for anti-androgenicity (RfD AA) developed by Kortenkamp and Faust. The results indicated that the risks of some students had exceeded the limitation, however, the measured results were not exceeded the limitation. Risk quotients (RQ) of DEHP were predicted based on China specific No Significant Risk Level (NSRL) and Maximum Allowable Dose Level (MADL). The predicted results of CR and RQ of DEHP suggested that DEHP could pose a health risk through intake of indoor dust. Copyright © 2016 Elsevier B.V. All rights reserved.

Environmental exposure to human carcinogens in teenagers and the association with DNA damage.

PubMed

Franken, Carmen; Koppen, Gudrun; Lambrechts, Nathalie; Govarts, Eva; Bruckers, Liesbeth; Den Hond, Elly; Loots, Ilse; Nelen, Vera; Sioen, Isabelle; Nawrot, Tim S; Baeyens, Willy; Van Larebeke, Nicolas; Boonen, Francis; Ooms, Daniëlla; Wevers, Mai; Jacobs, Griet; Covaci, Adrian; Schettgen, Thomas; Schoeters, Greet

2017-01-01

We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Six hundred 14-15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. This cross-sectional study found associations between current environmental exposure to (potential) human carcinogens in 14-15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex environmental exposures. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma

PubMed Central

Wang, I-Jen; Karmaus, Wilfried J. J.

2017-01-01

Background: Phthalate exposure may increase the risk of asthma. Little is known about whether oxidative-stress related genes may alter this association. First, this motivated us to investigate whether genetic polymorphisms of the oxidative-stress related genes glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase pi 1 (GSTP1), superoxide dismutase 2 (SOD2), catalase (CAT), myeloperoxidase (MPO), and EPHX1 in children are associated with phthalate urine concentrations. Second, we addressed the question whether these genes may affect the influence of phthalates on asthma. Methods: In a case-control study composed of 126 asthmatic children and 327 controls, urine phthalate metabolites (monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP) were measured by UPLC-MS/MS at age 3. Genetic variants were analyzed by TaqMan assay. Information on asthma and environmental exposures was also collected. Analyses of variance and logistic regressions were performed. Results: Urine MEHHP levels were associated with asthma (adjusted OR 1.33, 95% CI (1.11–1.60). Children with the GSTP1 (rs1695) AA and SOD2 (rs5746136) TT genotypes had higher MEHHP levels as compared to GG and CC types, respectively. Since only SOD2 TT genotype was significantly associated with asthma (adjusted OR (95% CI): 2.78 (1.54–5.02)), we estimated whether SOD2 variants modify the association of MEHHP levels and asthma. As MEHHP concentrations were dependent on GSTP1 and SOD2, but the assessment of interaction requires independent variables, we estimated MEHHP residuals and assessed their interaction, showing that the OR for SOD2 TT was further elevated to 3.32 (1.75–6.32) when the residuals of MEHHP were high. Conclusions: Urine phthalate metabolite concentrations are associated with oxidative-stress related genetic variants. Genetic variants of SOD2, considered to be reflect oxidative stress metabolisms, might modify the association of phthalate exposure with asthma. PMID:28208751

Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma.

PubMed

Wang, I-Jen; Karmaus, Wilfried J J

2017-02-08

Background: Phthalate exposure may increase the risk of asthma. Little is known about whether oxidative-stress related genes may alter this association. First, this motivated us to investigate whether genetic polymorphisms of the oxidative-stress related genes glutathione S -transferase Mu 1 ( GSTM1 ), glutathione S -transferase pi 1 ( GSTP1 ), superoxide dismutase 2 ( SOD2 ), catalase ( CAT ), myeloperoxidase ( MPO ), and EPHX1 in children are associated with phthalate urine concentrations. Second, we addressed the question whether these genes may affect the influence of phthalates on asthma. Methods: In a case-control study composed of 126 asthmatic children and 327 controls, urine phthalate metabolites (monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP) were measured by UPLC-MS/MS at age 3. Genetic variants were analyzed by TaqMan assay. Information on asthma and environmental exposures was also collected. Analyses of variance and logistic regressions were performed. Results: Urine MEHHP levels were associated with asthma (adjusted OR 1.33, 95% CI (1.11-1.60). Children with the GSTP1 (rs1695) AA and SOD2 (rs5746136) TT genotypes had higher MEHHP levels as compared to GG and CC types, respectively. Since only SOD2 TT genotype was significantly associated with asthma (adjusted OR (95% CI): 2.78 (1.54-5.02)), we estimated whether SOD2 variants modify the association of MEHHP levels and asthma. As MEHHP concentrations were dependent on GSTP1 and SOD2 , but the assessment of interaction requires independent variables, we estimated MEHHP residuals and assessed their interaction, showing that the OR for SOD2 TT was further elevated to 3.32 (1.75-6.32) when the residuals of MEHHP were high. Conclusions: Urine phthalate metabolite concentrations are associated with oxidative-stress related genetic variants. Genetic variants of SOD2 , considered to be reflect oxidative stress metabolisms, might modify the association of phthalate exposure with asthma.

Serum Phthalate Levels and Time to Pregnancy in Couples from Greenland, Poland and Ukraine

PubMed Central

Specht, Ina Olmer; Bonde, Jens Peter; Toft, Gunnar; Lindh, Christian H.; Jönsson, Bo A. G.; Jørgensen, Kristian T.

2015-01-01

Phthalates are ubiquitous industrial chemicals that have been associated with altered reproductive function in rodents. Several human studies have reported an inverse association between male testosterone and phthalate levels. Our aim was to investigate time to pregnancy (TTP) according to serum levels of diethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in both partners. In 2002-2004 we enrolled 938 pregnant women and 401 male spouses from Greenland, Poland and Ukraine. Six oxidized metabolites of DEHP and DiNP were summarized for each of the two parent compounds to provide proxies of the internal exposure. We used Cox discrete-time models to estimate fecundability ratios (FR) and 95% confidence intervals (95% CIs) for men and women according to their proxy-DEHP or -DiNP serum levels adjusted for a fixed set of covariates. The FR was slightly elevated among women with high levels of DEHP (FR=1.14, 95% CI 1.00;1.30) suggesting a shorter TTP in these women. The FR was unrelated to DiNP in women, whereas the results for men were inconsistent pointing in opposite directions. First-time pregnant women from Greenland with high serum DiNP levels had a longer TTP. This study spanning large contrast in environmental exposure does not indicate adverse effects of phthalates on couple fecundity. The shorter TTP in women with high levels of DEHP metabolites is unexplained and needs further investigation. PMID:25786246

Prenatal phthalate exposure and language development in toddlers from the Odense Child Cohort.

PubMed

Olesen, Trine Staak; Bleses, Dorthe; Andersen, Helle Raun; Grandjean, Philippe; Frederiksen, Hanne; Trecca, Fabio; Bilenberg, Niels; Kyhl, Henriette Boye; Dalsager, Louise; Jensen, Inge Kjær; Andersson, Anna-Maria; Jensen, Tina Kold

Phthalates are a group of chemicals found in a variety of consumer products. They have anti-androgenic properties and human studies have reported associations between prenatal phthalate exposure and neuropsychological development in the offspring despite different cognitive tests, different ages and varying timing of exposure. To investigate the association between prenatal phthalate exposure and language development in children aged 20-36months. In the Odense Child Cohort, we analyzed 3rd trimester urine samples of 518 pregnant women for content of metabolites of diethyl, di-n-butyl, diisobutyl, butylbenzyl, di(2-ethylhexyl), and diisononyl phthalate, adjusted for osmolality. Language development was addressed using the Danish version of the MacArthur-Bates Communicative Development Inventories "Words and Sentences". Associations were assessed using logistic regression models comparing children below and above the 15th percentile while stratifying by sex and adjusting for maternal age and educational level. Phthalate metabolites were detectable in all samples although in lower levels than previous studies. Among boys, increased prenatal phthalate exposure was associated with lower scores in language development; odds ratios for vocabulary score below the 15th percentile with doubling in monoethyl phthalate, and summed di-(2-ethylhexyl) phthalate metabolites were respectively 1.24 (95% confidence interval: 1.05,1.46), and 1.33 (1.01,1.75). Similar associations were found for language complexity. No associations were found for girls. Our findings are notable, as adverse associations were suggested even in this low-level exposed population, with only one spot urine sample for exposure assessment and control for confounders. Lower scores in early language development are of relevance to health as this test predicts later educational success. Copyright © 2017. Published by Elsevier Inc.

Occurrence and environmental risk assessment of PAEs in Weihe River near Xi'an City, China.

PubMed

Guo, Xiaofeng; Wang, Lei; Wang, Xudong; Liu, Hanli

2013-01-01

The occurrence and distribution of phthalate acid esters (PAEs) in surface water of the Weihe River basin (eight mainstream sampling points and 15 tributary sampling points) in the Shaanxi section were investigated during the dry season, level period (spring), wet season and level period (autumn). The PAEs tested for were diethyl phthalate (DEP), di-n-butyl phthalate (DBP), dicyclohexyl phthalate (DCHP) and di-(2-ethylhexyl) phthalate (DEHP). The testing proceeded by millipore filtration, then solid phase extraction and then gas chromatography-mass spectrometry determination for all examined PAEs. The monitoring results indicated that, in terms of seasonal changes, concentration of the PAEs in the mainstream is: Dry season > Level period (spring) > Wet season ≈ Level period (autumn). An environmental risk assessment was then performed on PAE pollution levels of the Weihe River basin. This paper employed a risk assessment methodology to evaluate the potential adverse health effects of the individual PAE compounds according to their carcinogenicities. For DEP, DBP and DEHP, a low Risk Index (all of them were lower than the specified level of 1.0) reveals that small non-carcinogenic risks exist resulting from the presence of trace concentrations in the surface water of the Weihe River basin.

The association between phthalate exposure and atopic dermatitis with a discussion of phthalate induced secretion of interleukin-1β and thymic stromal lymphopoietin.

PubMed

Overgaard, Line E K; Bonefeld, Charlotte M; Frederiksen, Hanne; Main, Katharina M; Thyssen, Jacob P

2016-06-01

Phthalate diesters are widely used as emollients in plastic and cosmetics as well as in food packaging and perfumes, potentially leading to prolonged and repeated dermal, oral and airborne exposure. We here review published articles that have evaluated the putative role of phthalate diesters in the pathogenesis of atopic dermatitis and discuss possible pathogenic pathways. A literature search resulted in 563 articles in Embase and 263 articles in Pubmed. After identification of relevant articles based on screening of titles, abstracts and reference lists, a total of 39 articles were selected and included. While no clear association has been shown between systemic phthalate levels and atopic dermatitis in human studies, animal data suggests that phthalates may worsen dermatitis and in vitro data suggests that interleukin-4 could be upregulated. Moreover, both loss-of-function mutations in the filaggrin gene and atopic dermatitis have been associated with elevated systemic phthalate levels. There is a need for prospective studies to clarify the possible pathogenic role of phthalate diesters in atopic dermatitis and the associated health risk, especially with the general trend towards barrier restoration with emollients in infants at risk of developing atopic dermatitis. In summary, we conclude that the results from published studies are controversial and inconclusive.

Review: UK medicines likely to be affected by the proposed European Medicines Agency's guidelines on phthalates.

PubMed

Jamieson, Lisa; McCully, William

2015-06-13

Phthalates are excipients in drug formulations. However, concerns have been raised about the effects of particular phthalates on reproduction and development. As a result the EMA has introduced guidelines for permitted daily exposure (PDE) limits for certain phthalates. Therefore, the objective of this study was to identify UK licensed medicines that contain the relevant phthalates and determine if they fall within the recommended PDE. The eMC was used to identify which UK licensed medicines contain the phthalates in question. Companies were then contacted for information on the phthalate levels in their products, which was compared with the PDE recommended by the EMA. The eMC search revealed that 54 medicines contained at least one of the phthalates in question. However, only six medicines, namely Asacol 800 mg MR (Warner Chilcott UK), Epilim 200 Gastro-resistant tablets (Sanofi), Prednisolone 2.5 mg and 5 mg Gastro-resistant tablets (Actavis UK), Vivotif (Crucell Italy S.r.l), and Zentiva 200 mg Gastro-resistant tablets (Winthrop Pharmaceuticals UK), were identified as containing levels that exceeded the recommended PDE. These findings indicate that very few UK licensed medicines will be affected by the proposed EMA guidelines. For those medicines identified as exceeding recommendations, these findings highlight the need to instigate a risk-benefit review.

Levels of phthalate esters in settled house dust from urban dwellings with young children in Nanjing, China

NASA Astrophysics Data System (ADS)

Zhang, Qi; Lu, Xiao-Mei; Zhang, Xiao-Ling; Sun, Yong-Gang; Zhu, Dong-Mei; Wang, Bing-Ling; Zhao, Ren-Zheng; Zhang, Zheng-Dong

2013-04-01

To investigate the levels and possible determinants of phthalate esters (PEs) in settled house dust from urban dwellings with young children, dust was collected from 215 urban houses in Nanjing, China, and 145 outdoor settled dust samples were collected nearby. Six PEs were measured by gas chromatography/mass spectrometry. All PEs were detected in the dust from approximately 90% of the houses, with the exception of dioctyl phthalate (DOP), which had only a 59% detection rate. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) were the most abundant PEs, with geometric means of 110 and 16.4 μg g-1, respectively, and maximal concentrations 9950 and 2150 μg g-1. Factor analysis showed that DBP, DEHP and benzyl butyl phthalate (BBP) might come from the same source and were significantly influenced by the use of solid-wood floor wax. High BBP, DEHP, DOP and total PE levels were associated with indices of dampness, and high DOP was associated with humidifier use. In conclusion, six PEs are ubiquitous in urban settled house dust in Nanjing, China, and both plastic materials and cosmetic and personal care products are important sources. Flooring material, dampness and humidifier use potentially influence house dust PE levels.

Human Elimination of Phthalate Compounds: Blood, Urine, and Sweat (BUS) Study

PubMed Central

Genuis, Stephen J.; Beesoon, Sanjay; Lobo, Rebecca A.; Birkholz, Detlef

2012-01-01

Background. Individual members of the phthalate family of chemical compounds are components of innumerable everyday consumer products, resulting in a high exposure scenario for some individuals and population groups. Multiple epidemiological studies have demonstrated statistically significant exposure-disease relationships involving phthalates and toxicological studies have shown estrogenic effects in vitro. Data is lacking in the medical literature, however, on effective means to facilitate phthalate excretion. Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for parent phthalate compounds as well as phthalate metabolites using high performance liquid chromatography-tandem mass spectrometry. Results. Some parent phthalates as well as their metabolites were excreted into sweat. All patients had MEHP (mono(2-ethylhexyl) phthalate) in their blood, sweat, and urine samples, suggesting widespread phthalate exposure. In several individuals, DEHP (di (2-ethylhexl) phthalate) was found in sweat but not in serum, suggesting the possibility of phthalate retention and bioaccumulation. On average, MEHP concentration in sweat was more than twice as high as urine levels. Conclusions. Induced perspiration may be useful to facilitate elimination of some potentially toxic phthalate compounds including DEHP and MEHP. Sweat analysis may be helpful in establishing the existence of accrued DEHP in the human body. PMID:23213291

Migration of phthalates on culture plates - an important challenge to consider for in vitro studies.

PubMed

Frohnert Hansen, Juliana; Boas, Malene; Møller Brorson, Marianne; Frederiksen, Hanne; Hartoft-Nielsen, Marie-Louise; Krogh Rasmussen, Åse; Main, Katharina M; Feldt-Rasmussen, Ulla

2016-01-01

Phthalates are endocrine disruptors of the reproductive system and suspected to influence many other organ and hormone systems. They are also semi-volatile organic compounds present in the gas phase in the environment. Their mode of action has been investigated in numerous in vitro studies. Multi-well culture plates are typically used to study phthalates in cell cultures. In a pilot study, we observed evidence of phthalate migration in 24-well culture plates. As this has not previously been described, we investigated the phenomenon in more detail. Primary human thyroid epithelial cell cultures (n = 8 cultures) were exposed to either di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), mono-n-butyl phthalate (MnBP) or di-(2-ethylhexyl) phthalate (DEHP). Measurement of phthalate metabolites by mass spectrometry demonstrated that the short-branched DEP was able to migrate to adjacent wells when added to cell culture plates. DnBP also seemed to be able to migrate, unlike the long-branched DEHP or the monoester MnBP which did not seem to have this ability. High background levels of phthalate metabolites were also observed, which might compromise results from low dose phthalate studies. In conclusion, the migration of phthalates which is probably caused by their volatile properties might lead to false interpretation of study results.

MEASUREMENT OF PHTHALATE LEVELS IN HUMAN MILK IN THE US EPA MAMA STUDY

EPA Science Inventory

Phthalates are plasticizers used to impart flexibility in products including PVC, plastic toys, and medical devices. These products are widely used by the general population. Phthalates act as anti-androgens and in utero or perinatal exposure in laboratory animal models leads to ...

Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells

EPA Science Inventory

In utero exposure to certain phthalate esters results in testicular toxicity, characterized at the tissue level by induction of multinucleated germ cells (MNGs) in rat, mouse, and human fetal testis. Phthalate exposures also result in a decrease in testicular testosterone in rats...

Semen phthalate metabolites, semen quality parameters and serum reproductive hormones: A cross-sectional study in China.

PubMed

Wang, Yi-Xin; Zeng, Qiang; Sun, Yang; Yang, Pan; Wang, Peng; Li, Jin; Huang, Zhen; You, Ling; Huang, Yue-Hui; Wang, Cheng; Li, Yu-Feng; Lu, Wen-Qing

2016-04-01

Exposure to phthalates has been found to have adverse effects on male reproductive function in animals. However, the findings from human studies are inconsistent. Here we examined the associations of phthalate exposure with semen quality and reproductive hormones in a Chinese population using phthalate metabolite concentrations measured in semen as biomarkers. Semen (n = 687) and blood samples (n = 342) were collected from the male partners of sub-fertile couples who presented to the Reproductive Center of Tongji Hospital in Wuhan, China. Semen quality parameters and serum reproductive hormone levels were determined. Semen concentrations of 8 phthalate metabolites were assessed using high-performance liquid chromatography and tandem mass spectrometry. Associations of the semen phthalate metabolites with semen quality parameters and serum reproductive hormones were assessed using confounder-adjusted linear and logistic regression models. Semen phthalate metabolites were significantly associated with decreases in semen volume [mono-n-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)], sperm curvilinear velocity [monobenzyl phthalate (MBzP), MEHP, the percentage of di-(2-ethylhexyl)-phthalate metabolites excreted as MEHP (%MEHP)], and straight-line velocity (MBzP, MEHP, %MEHP), and also associated with an increased percentage of abnormal heads and tails (MBzP) (all p for trend <0.05). These associations remained suggestive or significant after adjustment for multiple testing. There were no significant associations between semen phthalate metabolites and serum reproductive hormones. Our findings suggest that environmental exposure to phthalates may impair human semen quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concentrations of phthalates and bisphenol A in Norwegian foods and beverages and estimated dietary exposure in adults.

PubMed

Sakhi, Amrit K; Lillegaard, Inger Therese L; Voorspoels, Stefan; Carlsen, Monica H; Løken, Elin B; Brantsæter, Anne L; Haugen, Margaretha; Meltzer, Helle M; Thomsen, Cathrine

2014-12-01

Phthalates and bisphenol A (BPA) are ubiquitous in our environment. These chemicals have been characterized as endocrine disruptors that can cause functional impairment of development and reproduction. Processed and packaged foods are among the major sources of human exposure to these chemicals. No previous report showing the levels of these chemicals in food items purchased in Norway is available. The aim of the present study was to determine the concentration of ten different phthalates and BPA in foods and beverages purchased on the Norwegian market and estimate the daily dietary exposure in the Norwegian adult population. Commonly consumed foods and beverages in Norway were purchased in a grocery store and analysed using gas- and liquid chromatography coupled with mass spectrometry. Daily dietary exposures to these chemicals in the Norwegian adult population were estimated using the latest National dietary survey, Norkost 3 (2010-2011). This study showed that phthalates and BPA are found in all foods and beverages that are common to consume in Norway. The detection frequency of phthalates in the food items varied from 11% for dicyclohexyl phthalate (DCHP) to 84% for di-iso-nonyl phthalate (DiNP), one of the substitutes for bis(2-ethylhexyl) phthalate (DEHP). BPA was found in 54% of the food items analysed. Among the different phthalates, the highest concentrations were found for DEHP and DiNP in the food items. Estimated dietary exposures were also equally high and dominated by DEHP and DiNP (400-500 ng/kg body weight (bw)/day), followed by di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di-n-octyl phthalate (DnOP) and di-iso-decyl phthalate (DiDP) (30-40 ng/kg bw/day). Dimethyl phthalate (DMP), diethylphthalate (DEP) and DCHP had the lowest concentrations and the exposures were around 10-20 ng/kg bw/day. Estimated dietary exposure to BPA was 5 ng/kg bw/day. In general, levels of phthalates and BPA in foods and beverages from the Norwegian market are comparable to other countries worldwide. Grain and meat products were the major contributors of exposure to these chemicals in the Norwegian adult population. The estimated dietary exposures to these chemicals were considerably lower than their respective tolerable daily intake (TDI) values established by the European Food Safety Authority (EFSA). Copyright © 2014 Elsevier Ltd. All rights reserved.

Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells.

PubMed

Spade, Daniel J; Bai, Cathy Yue; Lambright, Christy; Conley, Justin M; Boekelheide, Kim; Gray, L Earl

2018-06-15

In utero exposure to certain phthalate esters results in testicular toxicity, characterized at the tissue level by induction of multinucleated germ cells (MNGs) in rat, mouse, and human fetal testis. Phthalate exposures also result in a decrease in testicular testosterone in rats. The anti-androgenic effects of phthalates have been more thoroughly quantified than testicular pathology due to the significant time requirement associated with manual counting of MNGs on histological sections. An automated counting method was developed in ImageJ to quantify MNGs in digital images of hematoxylin-stained rat fetal testis tissue sections. Timed pregnant Sprague Dawley rats were exposed by daily oral gavage from gestation day 17 to 21 with one of eight phthalate test compounds or corn oil vehicle. Both the manual counting method and the automated image analysis method identified di-n-butyl phthalate, butyl benzyl phthalate, dipentyl phthalate, and di-(2-ethylhexyl) phthalate as positive for induction of MNGs. Dimethyl phthalate, diethyl phthalate, the brominated phthalate di-(2-ethylhexyl) tetrabromophthalate, and dioctyl terephthalate were negative. The correlation between automated and manual scoring metrics was high (r = 0.923). Results of MNG analysis were consistent with these compounds' anti-androgenic activities, which were confirmed in an ex vivo testosterone production assay. In conclusion, we have developed a reliable image analysis method that can be used to facilitate dose-response studies for the reproducible induction of MNGs by in utero phthalate exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

Maternal phthalate exposure during the first trimester and serum thyroid hormones in pregnant women and their newborns.

PubMed

Yao, Hui-Yuan; Han, Yan; Gao, Hui; Huang, Kun; Ge, Xing; Xu, Yuan-Yuan; Xu, Ye-Qing; Jin, Zhong-Xiu; Sheng, Jie; Yan, Shuang-Qin; Zhu, Peng; Hao, Jia-Hu; Tao, Fang-Biao

2016-08-01

Animal and human studies have suggested that phthalate alters thyroid hormone concentrations. This study investigated the associations between phthalate exposure during the first trimester and thyroid hormones in pregnant women and their newborns. Pregnant women were enrolled from the prospective Ma'anshan Birth Cohort study in China. A standard questionnaire was completed by the women at the first antenatal visit. Seven phthalate metabolites were measured in one-spot urine at enrolment (10.0 ± 2.1 gestational weeks), as were thyroid hormone levels in maternal and cord sera. Multivariable linear regression showed that 1-standard deviation (SD) increase in natural log (ln)-transformed mono(2-ethylhexyl) phthalate (MEHP) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with 0.163 μg/dL (p = 0.001) and 0.173 μg/dL (p = 0.001) decreases in maternal total thyroxine (TT4). Both MEHP and MEHHP were negatively associated with maternal free thyroxine (FT4; β: -0.013, p < 0.001 and β: -0.011, p = 0.001, respectively) and positively associated with maternal thyroid-stimulating hormone (β: 0.101, p < 0.001; β: 0.132, p < 0.001, respectively). An inverse association was observed between monobenzyl phthalate and maternal TT4 and FT4. A 1-SD increase in ln-transformed monoethyl phthalate was inversely associated with maternal TT4 (β: -0.151, p = 0.002). By contrast, the concentrations of phthalate metabolites in urine were not associated with those of thyroid hormone in cord serum. Our analysis suggested that phthalate exposure during the first trimester disrupts maternal thyroid hormone levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental exposure to human carcinogens in teenagers and the association with DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franken, Carmen, E-mail: carmen.franken@vito.be

Background: We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods: Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid asmore » a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Results: Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. Conclusion: This cross-sectional study found associations between current environmental exposure to (potential) human carcinogens in 14–15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex environmental exposures. - Highlights: • Exposure to (potential) carcinogens is associated with (oxidative) damage to DNA. • Most associations of exposures are with urinary 8-OHdG. • 1-Hydroxypyrene and chromium are associated with the comet assay and 8-OHdG. • PFOA is associated with higher levels of DNA damage in the alkaline comet assay.« less

Phthalate and PAH concentrations in dust collected from Danish homes and daycare centers

NASA Astrophysics Data System (ADS)

Langer, Sarka; Weschler, Charles J.; Fischer, Andreas; Bekö, Gabriel; Toftum, Jørn; Clausen, Geo

2010-06-01

As part of the Danish Indoor Environment and Children's Health (IECH) study, dust samples were collected from 500 bedrooms and 151 daycare centers of children (ages 3 to 5) living on the island of Fyn. The present paper reports results from the analyses of these samples for five phthalate esters (diethyl phthalate (DEP), di(n-butyl) phthalate (DnBP), di(isobutyl) phthalate (DiBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP)) and three PAHs (pyrene, benz[a]anthracene (B[a]A) and benzo[a]pyrene (B[a]P)). The three PAHs and DEHP were detected in dust samples from all sites, while DEP, DnBP, DiBP and BBzP were detected in more than 75% of the bedrooms and more than 90% of the daycare centers. The dust mass-fractions of both phthalates and PAHs were log-normally distributed. With the exception of DEP, the mass-fractions of phthalates in dust were higher in daycare centers than homes; PAH mass-fractions in dust were similar in the two locations. There was no correlation among the different phthalates in either homes or daycare centers. In contrast, the PAH were correlated with one another - more strongly so in homes ( R2 = 0.80-0.90) than in daycare centers ( R2 = 0.28-0.45). The dust levels of several phthalates (BBzP, DnBP and DEHP) were substantially lower than those measured in a comparable study conducted 6-7 years earlier in Sweden. Although usage patterns in Denmark differ from those in Sweden, the current results may also reflect a change in the plasticizers that are used in common products including toys. PAH levels were roughly an order of magnitude lower than those measured in Berlin and Cape Cod residences, suggesting that the Danish sites are less impacted by motor vehicle emissions.

Ternary complex formation of Eu(III) with o-phthalate in aqueous solutions.

PubMed

Park, K K; Jung, E C; Cho, H-R; Kim, W H

2009-08-15

Ternary hydroxo complex formation of Eu(III) with o-phthalate was investigated by potentiometry and fluorescence spectrophotometry. Curves of the equilibrium pH versus the amount of NaOH added showed that the pH value starting to form a Eu(III) precipitate was decreased due to the formation of a ternary hydroxo complex, EuOHL(s) (L = phthalate). The formation of EuOHL(s) was qualitatively confirmed by the enhancement of the fluorescence intensity of Eu(III) in the precipitate with the light absorbed by phthalate, and was quantitatively confirmed by the measurement of the amounts of Eu(III), OH(-) and phthalate included in the precipitate. The solubility product of EuOHL(s) was determined as pK(sp)(0) = 15.6+/-0.4. Characteristic features in the fluorescence spectra and the solubility product of the Eu(III)-phthalate complex were compared with those of the Eu(III)-PDA (PDA = pyridine-2,6-dicarboxylate) complex. The fluorescence intensity of the EuL(+) complex of L = PDA was about 11 times stronger than that of L = phthalate. The origin of the difference in the fluorescence intensity is discussed based on the intramolecular energy transfer effect from the lowest triplet energy level of the ligand to the resonance energy level of Eu(III).

Effects of prenatal di(2-ethylhexyl) phthalate exposure on childhood allergies and infectious diseases: The Hokkaido Study on Environment and Children's Health.

PubMed

Ait Bamai, Yu; Miyashita, Chihiro; Araki, Atsuko; Nakajima, Tamie; Sasaki, Seiko; Kishi, Reiko

2018-03-15

Phthalates are widely used in consumer products, and experimental studies suggest that exposure to phthalates increase the risk of allergies. However, epidemiologic evidence on the associations between prenatal phthalate exposure and allergies/infectious diseases and cord blood immunoglobulin E (IgE) levels is limited. This study aimed to evaluate the associations between maternal mono(2-ethylhexyl) phthalate (MEHP) levels and cord blood IgE levels at birth (n=127), as well as the risk of allergies/infectious diseases in participants up to 7years of age; the participants were 1.5 (n=248), 3.5 (n=222), 7 (n=184) years of age. Maternal blood MEHP level in the second trimester was measured using gas chromatography-mass spectrometry. Participant characteristics were obtained from the medical birth records and self-administered questionnaires during pregnancy and after delivery. Wheeze and eczema were defined according to the Japanese version of the International Study of Asthma and Allergies in Childhood and the American Thoracic Society-Division of Lung Diseases questionnaire, respectively. Infectious diseases were defined using questionnaires for each specified age. To evaluate the associations between maternal MEHP and allergies or infectious diseases, we used logistic regression analysis and generalized estimating equations analysis. Maternal MEHP levels were negatively associated with cord blood IgE levels and increased risks of allergies and infectious diseases up to 7years of age. This is the first study to investigate the effects of prenatal MEHP exposure on IgE levels at birth and allergies/infectious diseases up to 7years of age. Further epidemiological studies should focus on other phthalate metabolites and their health effects on larger populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Phthalates and perfluorinated alkylated substances in Atlantic bluefin tuna (Thunnus thynnus) specimens from Mediterranean Sea (Sardinia, Italy): Levels and risks for human consumption.

PubMed

Guerranti, Cristiana; Cau, Alessandro; Renzi, Monia; Badini, Simone; Grazioli, Eleonora; Perra, Guido; Focardi, Silvano Ettore

2016-10-02

Atlantic blue fin tuna (Thunnus thynnus) is a species of great importance for Mediterranean Sea area, from both ecological and commercial points of view. The scientific literature reports few data on the contamination of this fish by emerging organic compounds such as perfluorinated alkylated substances(PFASs) and phthalates, being the latter never been studied in tuna. This study therefore investigated the presence of the PFASs perfluorooctane sulphonate (PFOS) and perfluoroctanoic acid (PFOA) and the phthalate di-2-ethylhexyl phthalate (DEHP), also monitored by its metabolite mono-2-ethylhexyl phthalate(MEHP), to assess both the state of contamination of Atlantic bluefin tuna specimen and the risk due to the toxicity of these compounds for human consumption. While PFOA was never found, detectable levels of PFOS (0.4-1.88 ng/g), DEHP (9-14.62 ng/g) and MEHP (1.5-6.30 ng/g) were found. The results were elaborated relating the accumulation to the size and age of the individuals and showed a correlation between the levels of different pollutants investigated.

Determination of phthalates released from paper packaging materials by solid-phase extraction-high-performance liquid chromatography.

PubMed

Gao, Xin; Yang, Bofeng; Tang, Zhixu; Luo, Xin; Wang, Fengmei; Xu, Hui; Cai, Xue

2014-01-01

A solid phase extraction (SPE) high-performance liquid chromatography (HPLC) method was developed for the simultaneous determination of 10 phthalic acid esters (dimethyl phthalate, diethyl phthalate, dipropyl phthalate, benzylbutyl phthalate, diisobutyl phthalate, dicyclohexyl phthalate, diamyl phthalate, di-n-hexyl phthalate, di-n-octyl phthalate and di-2-ethylhexyl phthalate) released from food paper packaging materials. The use of distilled water, 3% acetic acid (w/v), 10% ethanol (v/v) and 95% ethanol (v/v) instead of the different types of food simulated the migration of 10 phthalic acid esters from food paper packaging materials; the phthalic acid esters in four food simulants were enriched and purified by a C18 SPE column and nitrogen blowing, and quantified by HPLC with a diode array detector. The chromatographic conditions and extraction conditions were optimized and all 10 of the phthalate acid esters had a maximum absorbance at 224 nm. The method showed limitations of detection in the range of 6.0-23.8 ng/mL the correlation coefficients were greater than 0.9999 in all cases, recovery values ranged between 71.27 and 106.97% at spiking levels of 30, 60 and 90 ng/mL and relative standard deviation values ranged from 0.86 to 8.00%. The method was considered to be simple, fast and reliable for a study on the migration of these 10 phthalic acid esters from food paper packaging materials into food.

Phthalates in Commercial Chinese Rice Wines: Concentrations and the Cumulative Risk Assessment to Adult Males in Shanghai.

PubMed

Huang, Yue; Lu, Wen Wei; Chen, Bo; You, Jie; Wu, Min; Li, Shu Guang

2014-10-01

The concentrations of 16 phthalates in 164 commercial Chinese rice wines (CRW) were detected by GC-MS, and consumption data on CRW in different packaging types was investigated from 634 adult males in Shanghai using a food frequency questionnaire. Based on the principles of probabilistic modelling and cumulative risk assessment, the exposure and health risk of phthalates from CRW to adult males in Shanghai was evaluated. DMP, DEP, DIBP, DnBP, BBP, and DEHP were detected in the samples, the range of detection frequency of individual phthalates varied from 6.10% for BBP to 15.24% for DIBP, and the detected concentrations were 51.06-200.34 ng/mL. All the respondents consumed CRW, 90.69% of them consumed CRW 0.01-49.9 mL/d, the minimum value of the average daily intake of CRW was 6.25 mL/d, the median was 13.72 mL/d and the maximum was 300 mL/d. The median exposure level of the 6 detected Phthalates to adult males in Shanghai were 6.58-7.10 ng/(d•kg), and the maximum exposure level were 137.38-540.47 ng/(d•kg). The cumulative exposure health risk index (HI) based on the median and maximum exposure level of the 6 Phthalates (DMP, DEP, DIBP, DnBP, BBP, and DEHP) were 0.001147 and 0.063396, both were far less than 1. In conclusion, CRW were generally consumed by the adult males in Shanghai, although multiple phthalates were detected in commercial CRW, health risk of such exposure levels from commercial CRW to the target adult males in Shanghai was very low. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Phthalate esters in the environment: A critical review of their occurrence, biodegradation, and removal during wastewater treatment processes.

PubMed

Gao, Da-Wen; Wen, Zhi-Dan

2016-01-15

Phthalate esters are one of the most frequently detected persistent organic pollutants in the environment. A better understanding of their occurrence and degradation in the environment and during wastewater treatment processes will facilitate the development of strategies to reduce these pollutants and to bioremediate contaminated freshwater and soil. Phthalate esters occur at measurable levels in different environments worldwide. For example, the concentrations of dimethyl phthalate (DMP) in atmospheric particulate matter, fresh water and sediments, soil, and landfills are N.D.-10.4 ng/m(3), N.D.-31.7 μg/L, N.D.-316 μg/kg dry weight, and N.D.-200 μg/kg dry weight, N.D.-43.27 μg/L, respectively. Bis(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) are primary phthalate ester pollutants. Urbanization has increased the discharge of phthalate esters to atmospheric and aquatic environments, and the use of agricultural plastics has exacerbated soil contamination by phthalate esters in rural areas. Aerobic biodegradation is the primary manner of phthalate ester mineralization in the environment, and this process has been widely studied. Phthalate esters can be removed during wastewater treatment processes. The combination of different wastewater treatment technologies showed greater efficiency in the removal of phthalate esters than individual treatment steps, such as the combination of anaerobic wastewater treatment with a membrane bioreactor would increase the efficiency of phthalate ester removal from 65%-71% to 95%-97%. This review provides a useful framework to identify future research objectives to achieve the mineralization and elimination of phthalate esters in the environment. Copyright © 2015 Elsevier B.V. All rights reserved.

FETAL TESTOSTERONE LEVELS ARE DIFFERENTIALLY AFFECTED IN MALE SPRAGUE DAWLEY AND WISTAR RATS AFTER IN UTERO EXPOSURE TO DIETHYLHEXYL PHTHALATE: A DOSE RESPONSE STUDY.

EPA Science Inventory

Exposure to phthalate esters during sexual differentiation disrupts testosterone resulting in malformations of androgen-dependent tissues. We have found that gubernacular lesions are more prevalent in in utero diethylhexyl phthalate (DEHP)-treated Wistar male than in the SD rat o...

Ultrasound assisted extraction combined with dispersive liquid-liquid microextraction (US-DLLME)-a fast new approach to measure phthalate metabolites in nails.

PubMed

Alves, Andreia; Vanermen, Guido; Covaci, Adrian; Voorspoels, Stefan

2016-09-01

A new, fast, and environmentally friendly method based on ultrasound assisted extraction combined with dispersive liquid-liquid microextraction (US-DLLME) was developed and optimized for assessing the levels of seven phthalate metabolites (including the mono(ethyl hexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5-OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5-oxo-MEHP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monoethyl phthalate (MEP), and mono-benzyl phthalate (MBzP)) in human nails by UPLC-MS/MS. The optimization of the US-DLLME method was performed using a Taguchi combinatorial design (L9 array). Several parameters such as extraction solvent, solvent volume, extraction time, acid, acid concentration, and vortex time were studied. The optimal extraction conditions achieved were 180 μL of trichloroethylene (extraction solvent), 2 mL trifluoroacetic acid in methanol (2 M), 2 h extraction and 3 min vortex time. The optimized method had a good precision (6-17 %). The accuracy ranged from 79 to 108 % and the limit of method quantification (LOQm) was below 14 ng/g for all compounds. The developed US-DLLME method was applied to determine the target metabolites in 10 Belgian individuals. Levels of the analytes measured in nails ranged between <12 and 7982 ng/g. The MEHP, MBP isomers, and MEP were the major metabolites and detected in every sample. Miniaturization (low volumes of organic solvents used), low costs, speed, and simplicity are the main advantages of this US-DLLME based method. Graphical Abstract Extraction and phase separation of the US-DLLME procedure.

Phthalates and heavy metals as endocrine disruptors in food: A study on pre-packed coffee products.

PubMed

De Toni, Luca; Tisato, Francesco; Seraglia, Roberta; Roverso, Marco; Gandin, Valentina; Marzano, Cristina; Padrini, Roberto; Foresta, Carlo

2017-01-01

Phthalate plasticizers and heavy metals are widely recognized to be pollutants that interfere with key developmental processes such as masculinization. We investigated the release of phthalates and heavy metals in coffee brewed from coffee packed in single-serve coffee containers made from different types of materials: metal, biodegradable and plastics. We detected with GC-MS small amounts phthalates, below the tolerated daily risks levels, in all the coffees prepared from the different types of capsules. Specifically, Di (2-ethyl-hexyl)-phthalate and DiBP: Diisobuthyl-pthalate were ubiquitously present despite the high variability among the samples (respective range 0.16-1.87 μg/mL and 0.01-0.36 μg/mL). Whereas, diethyl-phthalate (range 0.20-0.26 μg/mL) and di- n -buthyl-phthalate (range 0.02-0.14 μg/mL) were detected respectively in one and three out of the four types of capsule tested. In contrast, we detected by atomic mass spectrometry on mineralized samples heavy metals lead (Pb) and nickel (Ni), in all coffee tested. PB levels (respective range 0.32-211.57 μg/dose) accounted for 42-79%, whereas Ni levels (respective range 166.25-1950.26 μg/dose) accounted for >100% of the tolerable daily intake. These results add to the already present concerns related to the multiple pathways of human exposure and the ubiquitous presence of these pollutants in consumer products and their long-term effect on human health.

Phthalate esters (PAEs): emerging organic contaminants in agricultural soils in peri-urban areas around Guangzhou, China.

PubMed

Zeng, Feng; Cui, Kunyan; Xie, Zhiyong; Wu, Lina; Liu, Min; Sun, Guoquan; Lin, Yujun; Luo, Danling; Zeng, Zunxiang

2008-11-01

This study reports the first data on the concentrations and distribution of phthalate esters (PAEs) in the agricultural soils from the peri-urban areas of Guangzhou city. Sigma(16)PAEs concentrations ranged from 0.195 to 33.6 microg g(-1)-dry weight (dw). Elevated levels of PAEs were recorded in the vegetable fields located next to the urban districts, and a decreasing trend exists following the distance away from the urban center. Diisobutyl phthalate (DiBP), Di-n-butyl phthalate (DnBP), and Di(2-ethylhexyl) phthalate (DEHP) dominated the PAEs in the agricultural soils. Significant relationship (correlation coefficient R(2)=0.85, p<0.01, n=40) was present between the accumulation of PAEs and total organic carbons in agricultural soils. In addition, both pH and texture of soils are found to be important factors affecting the level of PAEs. This study shows that the agricultural soils in the peri-urban area of Guangzhou city were moderately polluted by PAEs.

Concentration and risk assessment of phthalates present in indoor air from newly decorated apartments

NASA Astrophysics Data System (ADS)

Pei, X. Q.; Song, M.; Guo, M.; Mo, F. F.; Shen, X. Y.

2013-04-01

Phthalate esters (PAEs) are ubiquitous in the indoor environment, owing to their use in consumer products. People spend a considerable amount of time indoors. As a result, human exposure to indoor contaminants is of great concern. People are exposed to phthalates through inhalation and dermal absorption of indoor air. In this study, the concentrations, characteristics and carcinogenic risks of gas-phase and particle-phase phthalates in indoor air from bedroom, living room and study room of 10 newly decorated apartments in Hangzhou, China were first investigated. The mean concentration of phthalates (gas-phase and particle-phase) present in household air was 12 096.4 ng m-3, of which diethyl phthalate (DEP), butylbenzyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP) were the most abundant compounds with concentrations of 2290 ng m-3, 3975 ng m-3 and 2437 ng m-3, respectively, totally accounting for 72.0% of ∑6PAEs. Contamination levels of phthalates varied in different compartments. The concentration of phthalates was the highest 17 363.7 ng m-3 in living room, followed with 11 389.5 ng m-3 in study room, and the lowest 9739.1 ng m-3 in bedroom. It was also found that phthalates mainly accumulated in gaseous form in household air. DEHP posed the greatest health risk to children aged 1-2. Carcinogenic risk of DEHP was evaluated to be 3.912 × 10-5, and was 39 times higher than the limit set by the U.S. EPA.

A study on phthalate metabolites, bisphenol A and nonylphenol in the urine of Chinese women with unexplained recurrent spontaneous abortion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, Fanli

Humans are widely exposed to phthalates, bisphenol A and nonylphenol owing to the ubiquitous use of these chemicals in consumer products. Increasing attention has been paid to exposure to phthalates, bisphenol A and nonylphenol because of their potential adverse effects on human fertility. A validated method was developed to investigate the three classes of environmental estrogen, mentioned above, in the urine of Chinese women of Nanjing area with unexplained recurrent spontaneous abortion. Solid-phase extraction coupled with ultra performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used. In this method, amounts of bisphenol A (BPA), nonylphenol (NP) and four phthalate metabolites, mono-n-butylmore » phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono-2-ethylhexyl phthalate (MEHP), along with their isotope labeled internal standards, were measured using UPLC-MS/MS operated in negative electrospray ionization multiple reaction monitoring mode. The limits of detection were 0.3 ng/mL for the four phthalate metabolites, and 0.5 ng/mL for bisphenol A and nonylphenol. For women with unexplained recurrent spontaneous abortion, the mean concentrations of MBP, MiBP, MBzP, MEHP, BPA and 4-n-NP were 6.52±6.04, 5.51±4.19, 0.53±0.42, 10.12±4.16, 7.13±7.42, 0.41±0.49 ng/mL (mean±SD), respectively. For the control group, the mean concentrations of the corresponding analytes were 4.15±3.57, 2.96±3.30, 0.46±0.49, 6.50±2.81, 4.43±2.23,0.48±0.43 ng/mL (mean±SD), respectively. Levels of MiBP and MEHP were significantly different between the two groups, using Wilcoxon rank sum tests. This method can be applied in epidemiological studies to explore the association between exposure to environmental estrogens and relevant adverse outcomes. - Highlights: • Studied on the exposure level of six analytes in Chinese women with unexplained recurrent spontaneous abortion. • Differences in MEHP and MiBP urine levels were found between case and control groups. • A robust UPLC-MS/MS method was established for detecting phthalate monoesters, bisphenol A and nonylphenol. • An excellent solid-phase extraction method was established for urine.« less

An Investigation of the Single and Combined Phthalate Metabolite Effects on Human Chorionic Gonadotropin Expression in Placental Cells

PubMed Central

Zhao, Yaqi; Zhan, Lei V.; Kapidzic, Mirhan; Larocque, Nicholas; Koistinen, Hannu; Huhtaniemi, Ilpo T.; Stenman, Ulf-Håkan

2017-01-01

Background: Observational studies have reported associations between maternal phthalate levels and adverse outcomes at birth and in the health of the child. Effects on placental function have been suggested as a biologic basis for these findings. Objective: We evaluated the effects of phthalates on placental function in vitro by measuring relevant candidate genes and proteins. Materials and Methods: Human trophoblast progenitor cells were isolated at 7–14 wk of pregnancy (two female and three male concepti), and villous cytotrophoblast cells (vCTBs) were isolated at 15–20 wk (three female and four male concepti). Cells were cultured in vitro with four phthalate metabolites and their combination at concentrations based on levels found previously in the urine of pregnant women: mono-n-butyl (MnBP, 200 nM), monobenzyl (MBzP, 3μM), mono-2-ethylhexyl (MEHP, 700 nM), and monoethyl (MEP, 1.5μM) phthalates. mRNA levels of CGA, CGB, PPARG, CYP19A1, CYP11A1, PTGS2, EREG, and the intracellular β subunit of human chorionic gonadotropin (hCGβ) and peroxisome proliferator activated receptor γ (PPARγ) were measured in the cellular extracts, and protein levels for four forms of secreted hCG were measured in the conditioned media. Results: Previously reported associations between maternal phthalates and placental gene expression were reproduced experimentally: MnBP with CGA, MBzP with CYP11A1, and MEHP with PTGS2. CGB and hCGβ were up-regulated by MBzP. In some cases, there were marked, even opposite, differences in response by sex of the cells. There was evidence of agonism in female cells and antagonism in male cells of PPARγ by simultaneous exposure to multiple phthalates. Conclusions: Concentrations of MnBP, MBzP and MEHP similar to those found in the urine of pregnant women consistently altered hCG and PPARγ expression in primary placental cells. These findings provide evidence for the molecular basis by which phthalates may alter placental function, and they provide a preliminary mechanistic hypothesis for opposite responses by sex. https://doi.org/10.1289/EHP1539 PMID:29089286

Intake of Phthalate-tainted Foods and Serum Thyroid Hormones in Taiwanese Children and Adolescents

NASA Astrophysics Data System (ADS)

Tsai, Hui-Ju; Wu, Chia-Fang; Tsai, Yi-Chun; Huang, Po-Chin; Chen, Mei-Lien; Wang, Shu-Li; Chen, Bai-Hsiun; Chen, Chu-Chih; Wu, Wen-Chiu; Hsu, Pi-Shan; Hsiung, Chao A.; Wu, Ming-Tsang

2016-07-01

On April-May, 2011, phthalates, mainly Di-(2-ethylhexyl) phthalate (DEHP), were deliberately added to a variety of foodstuff as a substitute emulsifier in Taiwan. This study investigated the relationship between DEHP-tainted foodstuffs exposure and thyroid function in possibly affected children and adolescents. Two hundred fifty participants <18 years possibly exposed to DEHP were enrolled in this study between August 2012 and January 2013. Questionnaires were used to collect details on their past exposure to DEHP-tainted food items. Blood and urine samples were collected for biochemical workups to measure current exposure derived from three urinary DEHP metabolites using a creatinine excretion-based model. More than half of 250 participants were estimated to be exposed to DEHP-tainted foods found to exceed the recommend tolerable daily intake of DEHP established by the European Food Safety Authority (<50 μg/kg/day). The median daily DEHP intake (DDI) among those 250 participants was 46.52 μg/kg/day after multiple imputation. This value was ~10-fold higher than the current median DEHP intake (4.46 μg/kg/day, n = 240). Neither past nor current DEHP exposure intensity was significantly associated with serum thyroid profiles. Future studies may want to follow the long-term health effects of this food scandal in affected children and adolescents.

Exposure to diethylhexyl phthalate (DEHP) and monoethylhexyl phthalate (MEHP) promotes the loss of alveolar epithelial phenotype of A549 cells.

PubMed

Rafael-Vázquez, L; García-Trejo, Semiramis; Aztatzi-Aguilar, O G; Bazán-Perkins, B; Quintanilla-Vega, B

2018-05-17

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that is metabolized to mono(2-ethylhexyl) phthalate (MEHP). Inhalation is an important exposure route for both phthalates, and their effects on lungs include inflammation, alteration of postnatal maturation (alveolarization), enlarged airspaces and cell differentiation changes, suggesting that alveolar epithelial cells-2 (AEC) are targets of phthalates. This study evaluated the cell progression, epithelial and mesenchymal markers, including surfactant secretion in A549 cells (AEC) that were exposed to DEHP (1-100 μM) or MEHP (1-50 μM) for 24-72 h. The results showed an increased cell proliferation at all concentrations of each phthalate at 24 and 48 h. Cell migration showed a concentration-dependent increase at 24 and 48 h of exposure to either phthalate and enlarged structures were seen. Decreased levels of both surfactants (SP-B/SP-C) were observed after the exposure to either phthalate at 48 h, and of SP-C positive cells exposed to MEHP, suggesting a loss of the epithelial phenotype. While a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal marker fibronectin were observed following exposure to either phthalate. Our results showed that DEHP and MEHP altered the structure and migration of A549 cells and promoted the loss of the epithelial phenotype. Copyright © 2018 Elsevier B.V. All rights reserved.

A study on emission of phthalate esters from plastic materials using a passive flux sampler

NASA Astrophysics Data System (ADS)

Fujii, M.; Shinohara, N.; Lim, A.; Otake, T.; Kumagai, K.; Yanagisawa, Y.

Phthalate esters are used as plasticizer in many plastics, and several studies have shown their toxicity. Phthalate esters are gradually emitted over time, and so it is conceivable that they pose a significant health risk. This study aims to investigate the temperature dependence of the emissions of various phthalate esters and to estimate the health risks of these emissions at various temperatures. A passive-type sampler was developed to measure the flux of phthalate esters from the surface of plastic materials. With this sampler, we examined three widely used plastic materials: synthetic leather, wallpaper and vinyl flooring. The observed maximum emissions of diethyl phthalate, dibutyl phthalate, and diethylhexyl phthalate (DEHP) from these materials at 20°C were 0.89, 0.77, and 14 μg m -2 h -1, respectively. Emissions at 80°C were 2.8, 4.5×10 2, and 1.5×10 3 μg m -2 h -1, respectively. The results showed this temperature dependence is determined primarily by the type of phthalate ester and less so by the type of material. The estimation from the results of temperature dependence indicated the concentration of DEHP in a vehicle left out in the sunshine during the day can exceed the recommended levels of Japan Ministry of Health, Labour and Welfare.

Method development for determination of migrated phthalate acid esters from polyethylene terephthalate (PET) packaging into traditional Iranian drinking beverage (Doogh) samples: a novel approach of MSPE-GC/MS technique.

PubMed

Kiani, Amin; Ahmadloo, Mahsa; Shariatifar, Nabi; Moazzen, Mojtaba; Baghani, Abbas Norouzian; Khaniki, GholamReza Jahed; Taghinezhad, Ali; Kouhpayeh, Amin; Mousavi Khaneghah, Amin; Ghajarbeygi, Peyman

2018-05-01

In the current study, a novel magnetic solid phase extraction (MSPE) technique combined with a gas chromatography/mass spectroscopy (GC/MS) was developed to determine the phthalate ester content of bottled Doogh samples. Doogh is a yogurt-based drinking beverage, which is frequently consumed in Middle East and Balkans. It is produced by stirring yogurt in Chern separation machine and consists of substances such as water, yogurt, and salt in addition to aqueous extracts of native herbs. The magnetic multi-walled carbon nanotubes (MWCNT-Fe 3 O 4 ) were used as adsorbents of phthalate acid esters (PAEs) due to a superior adsorption capability of hydrophobic compounds. In this context, the quantity of the extractable migrated phthalate esters (dibutyl phthalate (DBP), dimethyl phthalate (DMP), butyl benzyl phthalate (BBP), diethyl phthalate (DEP), di-N-octyl phthalate (DNOP), and bis (2-ethylhexyl) phthalate (DEHP)) from polyethylene terephthalate (PET) bottles into Doogh samples was measured. The correlation between the concentration of migrated PAEs and some factors such as the type of Doogh (gaseous and without gas), difference in brand (five brands), volume (1500 and 300 mL), and the storage time also was investigated. The migration level into Doogh samples was increased by incorporating of gas as well as increasing the volume of PET bottles. Also, with elaborating of storage time, the migration of some phthalates such as DEHP (the mean from 2419.85 ng L -1 in the first week to 2716.15 ng L -1 in the second month), DEP, and total phthalate was increased. However, no significant difference in concentrations of migrated phthalate esters among different examined brands was noted. Finally, the concentration of migrated PAEs from bottle into all the examined Doogh samples was below the defined standards by EPA; 6 μg/L for DEHP in drinking water. Graphical abstract ᅟ.

Indoor phthalate concentration and exposure in residential and office buildings in Xi'an, China

NASA Astrophysics Data System (ADS)

Wang, Xinke; Tao, Wei; Xu, Ying; Feng, Jiangtao; Wang, Fenghao

2014-04-01

Indoor phthalate levels were investigated in 28 buildings, including 14 office and 14 residential buildings in Xi'an, China. Phthalate esters in the gas-, particle-, and dust- phase were measured separately. Four phthalates including dimethyl phthalate (DMP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) were detected. The detection frequency of DnBP and DEHP was more than 90%. The concentrations of total phthalate esters ranged from 0.20 to 8.29 μg m-3 for the gas- phase, from 0.09 to 14.77 μg m-3 for the particle- phase and from 123 to 9504 μg g-1 for the dust- phase. The individual phthalate with the highest concentrations of 6.17 μg m-3, 7.97 μg m-3 and 7228 μg g-1 respectively for gas-, particle- and dust- phase in all investigated rooms is all DiBP. The median concentration of the gas- and particle-phase DiBP (0.52 and 0.72 μg m-3) and dust-phase DEHP (582 μg g-1) were the highest. It was also found that the average concentrations of individual phthalates in residential buildings were often higher than in office buildings, and correlation analysis indicated that DiBP, DnBP and DEHP might come from the same sources. Based on the gas- and particle-phase concentrations measured, the particle-air partition coefficients of phthalates were estimated, and their logarithm values were found to be linearly correlated with the logarithm values of their octanol-air partition coefficients. Finally, the total daily exposure to indoor phthalates in air and dust was calculated, and ranged from 2.6 μg kg-1 day-1 (for adults) to 7.4 μg kg-1 day-1 (for toddlers).

Distribution of di(2-ethylhexyl) phthalate and products in blood and blood components.

PubMed Central

Rock, G; Labow, R S; Tocchi, M

1986-01-01

In order to impart flexibility, plastic medical devices incorporate liquid plasticizers into their structure. Data from several laboratories, including ours, have shown that these compounds leach from blood bags and tubing during collection of blood, storage of various blood components and during kidney dialysis and cell and plasma apheresis procedures. After the plasticizer di(2-ethylhexyl) phthalate leaches from poly(vinyl chloride) blood packs, it is converted by a plasma enzyme to a more toxic metabolite, mono(2-ethylhexyl) phthalate. Blood fractionation products from outdated plasma contain mono(2-ethylhexyl) phthalate, the highest level being found in normal serum albumin. Recently, we have reported that di(2-ethylhexyl) phthalate actually binds to the red blood cell membrane and reduces its osmotic fragility. Current methods of red cells storage, which permit utilization up to 35 days after collection, are not possible without this membrane stabilization. Platelets are now stored for 5 days in the Fenwal PL 732 polyolefin bag. Although stated to be essentially free of liquid plasticizers, a significant level of leaching from this bag into the extracts of stored platelet concentrates was observed. PMID:3709456

The risk of missed abortion associated with the levels of tobacco, heavy metals and phthalate in hair of pregnant woman

PubMed Central

Zhao, Ranran; Wu, Yuelian; Zhao, Fangfang; Lv, Yingnan; Huang, Damin; Wei, Jinlian; Ruan, Chong; Huang, Mingli; Deng, Jinghuan; Huang, Dongping; Qiu, Xiaoqiang

2017-01-01

Abstract To assess the association between exposure to the tobacco, heavy metals and phthalate on early pregnancy and missed abortion. 42 women with missed abortion and 57 matched controls (women with normal pregnancies) were recruited between March and May 2012, from the Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangxi Medical University and the People Hospital of Guangxi Zhuang Autonomous Region. The questionnaire survey was carried on to learn about the basic conditions, as well as smoking history of all participants. The levels of tobacco, heavy metal, and phthalate exposure were compared between the 2 groups by measuring nicotine, cocaine, cadmium (Cd), manganese (Mn), plumbum (Pb) and dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), di-2-ethyl hexyl phthalate (DEHP) in the hair samples. Out results showed that significant differences in age (P = .042), premarital examination (P = .041), passive smoking (P = .021), and heavy metal exposure (P = .022) were found in the case group compared to the control. In addition, the concentration of nicotine (P = .037), cotinine (P = .018), Cd (P = .01), Pb (P = .038) and DEHP (P = .001) in the hair were significantly higher in the case group. Furthermore, logistic analysis revealed that age [Odds Ratio (OR) 1.172, 95% confidence interval (CI) 1.036–1.327], Cd (OR 8.931, 95% CI 2.003–39.811), Cotinine (OR 4.376, 95% CI 1.159–16.531), DEHP (OR 1.863, 95% CI 1.103–3.146) were important factors contributing to the missed abortion (P < .05). It was demonstrated that high gestational age, passive smoking, heavy metals, and the phthalate exposure were the risk factors for missed abortion, while the premarital health examination was a protective factor. Avoiding these harmful substances before getting pregnant and during the early stages of pregnancy, might help prevent missed abortions. PMID:29390543

Investigation of the primary plasticisers present in polyvinyl chloride (PVC) products currently authorised as food contact materials.

PubMed

Carlos, Katherine S; de Jager, Lowri S; Begley, Timothy H

2018-03-15

PVC is a common food contact material that is usually plasticised to increase its flexibility. Phthalates are one class of chemical compounds that are often used as plasticisers in PVC in a wide range of industries. They may be used in packaging materials for foods and can also be found in components of certain food processing equipment such as conveyor belts and tubing. Transfer of plasticisers from packaging to foods can occur. In recent years, there has been increased interest in understanding the health effects of phthalates, as well as the possible human exposure levels. However, there is limited information available about the routes of exposure to phthalates. In July 2014, the Chronic Hazard Advisory Panel (CHAP) produced a report for the U.S. Consumer Product Safety Commission detailing the potential health hazards of phthalates and phthalate alternatives. This report listed diet as one factor contributing greater than or equal to 10% of total phthalate exposure. As a result of this report, the U.S. Food and Drug Administration (FDA) is interested in determining the types of the primary plasticiser present in food packaging and processing materials as well as their concentrations. An investigation was conducted of 56 different samples of PVC food packaging and food processing materials available in the US market using a solvent extraction and GC-MS analysis. Nine different plasticisers including three phthalates, di(2-ethylhexyl) phthalate, diisononyl phthalate and diisodecyl phthalate, were identified in the products tested. The plasticiser concentrations ranged from 1 to 53% depending on the types of food contact materials and the type of plasticiser. Overall, it appears that manufacturers are switching away from phthalates as their primary plasticiser to alternate compounds such as ESBO, ATBC, DEHT, DINCH, DEHA and DINA.

Semi-volatile organic compounds in heating, ventilation, and air-conditioning filter dust in retail stores.

PubMed

Xu, Y; Liang, Y; Urquidi, J R; Siegel, J A

2015-02-01

Retail stores contain a wide range of products that can emit a variety of indoor pollutants. Among these chemicals, phthalate esters and polybrominated diphenyl ethers (PBDEs) are two important categories of semi-volatile organic compounds (SVOCs). Filters in heating, ventilation, and air-conditioning (HVAC) system collect particles from large volumes of air and thus potentially provide spatially and temporally integrated SVOC concentrations. This study measured six phthalate and 14 PBDE compounds in HVAC filter dust in 14 retail stores in Texas and Pennsylvania, United States. Phthalates and PBDEs were widely found in the HVAC filter dust in retail environment, indicating that they are ubiquitous indoor pollutants. The potential co-occurrence of phthalates and PBDEs was not strong, suggesting that their indoor sources are diverse. The levels of phthalates and PBDEs measured in HVAC filter dust are comparable to concentrations found in previous investigations of settled dust in residential buildings. Significant correlations between indoor air and filter dust concentrations were found for diethyl phthalate, di-n-butyl phthalate, and benzyl butyl phthalate. Reasonable agreement between measurements and an equilibrium model to describe SVOC partitioning between dust and gas-phase is achieved. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Organophosphorus flame retardants (PFRs) and phthalates in floor and road dust from a manual e-waste dismantling facility and adjacent communities in Thailand.

PubMed

Muenhor, Dudsadee; Moon, Hyo-Bang; Lee, Sunggyu; Goosey, Emma

2018-01-02

This study was undertaken to investigate levels of organophosphorus flame retardants (PFRs) and phthalates in floor and road dust from a manual e-waste dismantling facility and nearby communities in Thailand. Concentrations of Σ10 PFRs and Σ6 phthalates in floor dust from the facility were approximately 36-1,700 and 86,000-790,000 ng g -1 , whereas those from the communities were about 13-9,200 and 44,000-2,700,000 ng g -1 , respectively. The highest content of Σ10 PFRs (9,200 ng g -1 ) and Σ6 phthalates (2,700,000 ng g -1 ) in indoor dust was both detected in the dust sampled from a house with no prevailing winds located 350 m northeast of the facility. Levels of Σ10 PFRs and Σ6 phthalates in road dust from the facility were around 1,100-2,100 and 40,000-670,000 ng g -1 , while those from the residences were about 650-2,000 and 27,000-650,000 ng g -1 , respectively. Concentrations of Σ10 PFRs (2,100 ng g -1 ) and Σ6 phthalates (670,000 ng g -1 ) in road dust were greatest in the dust collected from the facility. For the distributional pattern, TBEP (tris (2-butoxyethyl) phosphate) was the main PFR in residential dust, whereas TPP (triphenyl phosphate) was the major PFR in facility dust. TBEP was also found to be the most prominent PFR in all road dust samples. Furthermore, DEHP (di-2-ethylhexyl phthalate) was the most abundant phthalate congener in both floor and road dust samples. Under realistic high-end scenarios of environmental exposure to DEHP, Thai toddlers (25.29 µg kg -1 bw day -1 ) in the adjacent communities were exposed above the US EPA's (United States Environmental Protection Agency) reference dose (RfD) for this congener (20 µg kg -1 bw day -1 ). Our data reveal that the PFR and phthalate-containing products at the residences are a likely substantial source of PFRs and phthalates to the surrounding indoor environment, and humans can be exposed to PFRs and phthalates in their dwellings via the settled floor dust.

Dipentyl Phthalate F1 Male rat necropsy data, requested by a ...

EPA Pesticide Factsheets

This is a dataset, and it has no abstract. See the manuscript for additional information. Gray LE Jr, Furr J, Tatum-Gibbs KR, Lambright C, Sampson H, Hannas BR, Wilson VS, Hotchkiss A, Foster PM. Establishing the "Biological Relevance" of DipentylPhthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels. Toxicol Sci. 2016 Jan;149(1):178-91. doi: 10.1093/toxsci/kfv224. Epub 2015 Oct 9. PubMed PMID: 26454885; PubMed CentralPMCID: PMC4715258. Dipentyl Phthalate F1 Male rat necropsy data from our 2016 publication. These data were requested by a mathematical statistician in NCEA that is using the data for nested BMD calculations for their ongoing assessment of this phthalate. We continue to provide NCEA and other regulatory groups data on the phthalates for their assessments.

Are urinary polyaromatic hydrocarbons associated with adult hypertension, heart attack, and cancer? USA NHANES, 2011-2012.

PubMed

Shiue, Ivy

2015-11-01

Links between environmental chemicals and human health have emerged over the last few decades, but the effects from polyaromatic hydrocarbons were less studied, compared to other commonly known environmental chemicals such as heavy metals, phthalates, arsenic, phenols and pesticides. Therefore, it was aimed to study the relationships of urinary polyaromatic hydrocarbons and adult cardiovascular disease and cancer using human sample in a national and population-based study in recent years. Data was retrieved from US National Health and Nutrition Examination Surveys, 2011-2012, including demographics, self-reported health conditions and urinary polyaromatic hydrocarbons. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling and population attributable risk (PAR) estimation. Of 5560 American adults aged 20-80 and included in the statistical analysis, urinary polyaromatic hydrocarbons (representatively in one-third sample) were observed to be higher in people with cardiovascular disease and total cancer. In particular, urinary 4-hydroxyphenanthrene was associated with hypertension (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.00-1.76, P = 0.048, PAR 5.1%), urinary 1-hydroxypyrene was significantly associated with heart attack (OR 1.47, 95%CI 1.05-2.06, P = 0.027, PAR 1.7%), and urinary 2-hydroxynapthalene (2-naphthol) was associated with cancer (OR 1.46, 95%CI 1.12-1.90, P = 0.008, PAR 3.9%). Urinary polyaromatic hydrocarbons were associated with adult hypertension, heart attack and cancer, although the causality cannot be established. From the research perspective, future studies with a longitudinal or experimental approach would be suggested. From the law and public health perspectives, regulation on minimizing exposure to polyaromatic hydrocarbons might need to be considered in future health and environmental policies and intervention programs.

Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

PubMed Central

Carlstedt, Fredrik; Jönsson, Bo AG.; Lindh, Christian H.; Jensen, Tina K.; Bodin, Anna; Jonsson, Carin; Janson, Staffan; Swan, Shanna H.

2014-01-01

Background: Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and in a large number of consumer products. Because of reported health risks, diisononyl phthalate (DiNP) has been introduced as a replacement for di(2-ethylhexyl) phthalate (DEHP) in soft PVC. This raises concerns because animal data suggest that DiNP may have antiandrogenic properties similar to those of DEHP. The anogenital distance (AGD)—the distance from the anus to the genitals—has been used to assess reproductive toxicity. Objective: The objective of this study was to examine the associations between prenatal phthalate exposure and AGD in Swedish infants. Methods: AGD was measured in 196 boys at 21 months of age, and first-trimester urine was analyzed for 10 phthalate metabolites of DEP (diethyl phthalate), DBP (dibutyl phthalate), DEHP, BBzP (benzylbutyl phthalate), as well as DiNP and creatinine. Data on covariates were collected by questionnaires. Results: The most significant associations were found between the shorter of two AGD measures (anoscrotal distance; AGDas) and DiNP metabolites and strongest for oh-MMeOP [mono-(4-methyl-7-hydroxyloctyl) phthalate] and oxo-MMeOP [mono-(2-ethyl-5-oxohexyl) phthalate]. However, the AGDas reduction was small (4%) in relation to more than an interquartile range increase in DiNP exposure. Conclusions: These findings call into question the safety of substituting DiNP for DEHP in soft PVC, particularly because a shorter male AGD has been shown to relate to male genital birth defects in children and impaired reproductive function in adult males and the fact that human levels of DiNP are increasing globally. Citation: Bornehag CG, Carlstedt F, Jönsson BA, Lindh CH, Jensen TK, Bodin A, Jonsson C, Janson S, Swan SH. 2015. Prenatal phthalate exposures and anogenital distance in Swedish boys. Environ Health Perspect 123:101–107; http://dx.doi.org/10.1289/ehp.1408163 PMID:25353625

Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats.

PubMed

Clewell, Rebecca A; Sochaski, Mark; Edwards, Kendra; Creasy, Dianne M; Willson, Gabrielle; Andersen, Melvin E

2013-01-01

Pregnant Sprague-Dawley rats received 50, 250, and 500 mg/kg/day diisononyl phthalate (DiNP) from GD 12 to 19 via corn oil gavage to study the dose response for effects on fetal male rat sexual development as well as metabolite disposition in the dam and fetus. Monoisononyl phthalate (MiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxyl-isononyl) phthalate (MHiNP), mono(oxo-isononyl) phthalate (MOiNP), and monoisononyl phthalate glucuronide (MiNP-G) were found in all measured tissues. MCiOP was the major metabolite, followed in decreasing order by MiNP, MHiNP, MOiNP, and MiNP-G. Percentage of dose absorbed decreased at 750 mg/kg/day. Testosterone concentration in the fetal testes was reduced at 250 and 750 mg/kg/day. Multinucleated germ cells were increased in the testes of rats at 250 and 750 mg/kg/day. The no observed effect level (NOEL) for this study was 50 mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat. Copyright © 2012 Elsevier Inc. All rights reserved.

High Plasticizer Levels In Males Linked to Delayed Pregnancy for Female Partners

MedlinePlus

... assessed the concentrations of phthalates and Bisphenol A (BPA) in couples trying to achieve pregnancy. Phthalates, sometimes ... manufacture of plastics, to make them more flexible. BPA is also used in plastics, including in some ...

Impact of ecological doses of the most widespread phthalate on a terrestrial species, the ant Lasius niger.

PubMed

Cuvillier-Hot, Virginie; Salin, Karine; Devers, Séverine; Tasiemski, Aurélie; Schaffner, Pauline; Boulay, Raphaël; Billiard, Sylvain; Lenoir, Alain

2014-05-01

Phthalates are synthetic contaminants released into the environment notably by plastic waste. Semi-volatile, they adsorb to atmospheric particles and get distributed in all ecosystems. Effects of this major anthropogenic pollution in economical species in aquatic habitats have attracted large interest. On the contrary, very few studies have focused on wild terrestrial species. Yet, these lipophilic molecules are easily trapped by insect cuticle; ants and other insects have been shown to permanently bear among their cuticular components a non-negligible proportion of phthalates, meaning that they suffer from chronic exposure to these pollutants. Oral route could also be an additional way of contamination, as phthalates tend to stick to any organic particle. We show here via a food choice experiment that Lasius niger workers can detect, and avoid feeding on, food contaminated with DEHP (DiEthyl Hexyl Phthalate), the most widespread phthalate found in nature. This suggests that the main source of contamination for ants is atmosphere and that doses measured on the cuticle correspond to the chronic exposure levels for these animals. Such an ecologically relevant dose of DEHP was used to contaminate ants in lab and to investigate their physiological impact. Over a chronic exposure (1 dose per week for 5 weeks), the egg-laying rate of queens was significantly reduced lending credence to endocrine disruptive properties of such a pollutant, as also described for aquatic invertebrates. On the contrary, short term exposure (24h) to a single dose of DEHP does not induce oxidative stress in ant workers as expected, but leads to activation of the immune system. Because of their very large distribution, their presence in virtually all terrestrial ecosystems and their representation at all trophic levels, ants could be useful indicators of contamination by phthalates, especially via monitoring the level of activation of their immune state. Copyright © 2014 Elsevier Inc. All rights reserved.

REPRODUCTIVE TOXICITY OF PHTHALATE ESTERS

EPA Science Inventory

Phthalate esters display several modes of toxicity in mammalian species. In the rat, in utero exposure at relatively low dosage levels disrupts development of the reproductive system of the male rat by altering fetal testis hormone production. This presentation is a review of t...

Transgenerational Effects of Di(2-ethylhexyl) Phthalate in the SD Male Rat

EPA Science Inventory

In the rat, some phthalates alter sexual differentiation at relatively low dosage levels by altering fetal Leydig cell development and hormone synthesis, thereby inducing abnormalities of the testis, gubernacular ligaments, epididymis and other androgen-dependent tissues. In ...

Phthalates and type 1 diabetes: is there any link?

PubMed

Castro-Correia, Cíntia; Correia-Sá, Luísa; Norberto, Sónia; Delerue-Matos, Cristina; Domingues, Valentina; Costa-Santos, Cristina; Fontoura, Manuel; Calhau, Conceição

2018-04-21

Phthalates are a group of chemical compounds used as plasticizers in the manufacture of plastic materials. They can be present in many commonly used products. There seems to be a relationship between exposure to phthalates and the occurrence of metabolic dysfunctions, such as a decrease in glucose tolerance, oxidative stress, loss of beta cells, and a decrease in insulin synthesis. As beta cells play a key role in the onset of type 1 diabetes mellitus (T1DM), we sought to investigate the relationship between exposure to phthalates and the diagnosis of T1DM in prepubertal children. Design concentrations of phthalate metabolites were compared in the urine of a population of prepubertal children with new-onset diabetes, patients with T1DM diagnosed more than 6 months previously, and healthy control children. Although the concentrations of DBP and DiBP metabolites were statistically identical in the new-onset diabetes, diabetes, and control groups, there was a clear trend for higher levels of DiBP metabolites in the children with new-onset diabetes. In our sample, there was a trend for higher levels of DiBP metabolites in children with new-onset diabetes.

Solution for blank and matrix difficulties encountered during phthalate analysis of edible oils by high performance liquid chromatography coupled with tandem mass spectrometry.

PubMed

Vavrouš, Adam; Pavloušková, Jana; Ševčík, Václav; Vrbík, Karel; Čabala, Radomír

2016-07-22

Worldwide production of phthalates has led to their undesirable presence in the food chain. Particularly edible oils have become an area of growing concern owing to numerous reported occurrences of phthalates. The analytical methods used in this field face difficulties associated mainly with matrix complexity or phthalate contamination which this study has aimed to describe and resolve. The proposed procedure consisting of liquid-liquid extraction, solid phase extraction and high performance liquid chromatography coupled with tandem mass spectrometry allowed us to analyze simultaneously 6 individual phthalates and 2 phthalate isomeric mixtures. DSC-18 SPE phase was selected for cleanup owing to the most efficient co-extract removal (assessed using high resolution mass spectrometry). Several sources of phthalate contamination were identified, however, the mobile phase was the most serious. The key improvement was achieved by equipping a contamination trap, a 50-mm reverse phase HPLC column, generating a delay between target and mobile phase peaks of the same compounds. RSDs ranging between 2.4 and 16 % confirm good precision and LOQs between 5.5 and 110μgkg(-1) reflect satisfactory blank management. With up to 19 occurrences in 25 analyzed edible oil samples and levels up to 33mgkg(-1), bis(2-ethylhexyl), diisononyl and diisodecyl phthalates were the most important contaminants. Copyright © 2016 Elsevier B.V. All rights reserved.

Establishing the Biological Relevance of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels

EPA Science Inventory

Phthalate esters (PEs) constitute a large class of compounds that are used for many consumer product applications. Many of the C2-C7 di-ortho PEs reduce fetal testicular hormone and gene expression levels in rats resulting in adverse effects seen later in life but it appears that...

[Influence of phthalates from Shaying river on children's intelligence and secretion of thyroid hormone].

PubMed

Li, Anqi; Tang, Chunyu; Hang, Hui; Cheng, Xuemin; Gao, Yalin; Cheng, Hongyang; Huang, Qi; Luo, Yixin; Xue, Yutang; Zuo, Qiting; Ba, Yue; Cui, Liuxin

2013-03-01

To investigate the effect of phthalates exposure from drinking water on children's intelligence and secretion of thyroid hormone. Two villages in S County were selected randomly as polluted area and control area according to the distance from the Shaying river basin. Phthalates including DEP, DBP, DMP, DEHP were measured both in the river water and drinking water using HPLC method. Children aged 8 to 13 years old studying in the village primary school were recruited by cluster sampling (n = 154). The combined Reven Test was used to test children intelligence and ELISA method was used to determined thyroid hormone levels. The concentrations of phthalates (DEP, DBP) were exceeding standards of surface water quality in any of the three sections of the river. Compared to the control area, the concentration of DEP and DBP in drinking water were significant higher in the polluted area than that in control area (P < 0.05). Children from polluted area had significant higher FT4 concentration compared to children from control area (P < 0.05). Intelligence level in children from polluted area was lower than that from control area (P < 0.05). The drinking water has been polluted by Shaying river and thyroid hormones levels of children were affected in the polluted areas. It is necessary to verify if this change is related to the phthalates.

40 CFR 464.21 - Specialized definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72... 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72...-ethylhexyl) phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl...

40 CFR 464.21 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72... 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72...-ethylhexyl) phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl...

The risk of missed abortion associated with the levels of tobacco, heavy metals and phthalate in hair of pregnant woman: A case control study in Chinese women.

PubMed

Zhao, Ranran; Wu, Yuelian; Zhao, Fangfang; Lv, Yingnan; Huang, Damin; Wei, Jinlian; Ruan, Chong; Huang, Mingli; Deng, Jinghuan; Huang, Dongping; Qiu, Xiaoqiang

2017-12-01

To assess the association between exposure to the tobacco, heavy metals and phthalate on early pregnancy and missed abortion.42 women with missed abortion and 57 matched controls (women with normal pregnancies) were recruited between March and May 2012, from the Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangxi Medical University and the People Hospital of Guangxi Zhuang Autonomous Region. The questionnaire survey was carried on to learn about the basic conditions, as well as smoking history of all participants. The levels of tobacco, heavy metal, and phthalate exposure were compared between the 2 groups by measuring nicotine, cocaine, cadmium (Cd), manganese (Mn), plumbum (Pb) and dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), di-2-ethyl hexyl phthalate (DEHP) in the hair samples.Out results showed that significant differences in age (P = .042), premarital examination (P = .041), passive smoking (P = .021), and heavy metal exposure (P = .022) were found in the case group compared to the control. In addition, the concentration of nicotine (P = .037), cotinine (P = .018), Cd (P = .01), Pb (P = .038) and DEHP (P = .001) in the hair were significantly higher in the case group. Furthermore, logistic analysis revealed that age [Odds Ratio (OR) 1.172, 95% confidence interval (CI) 1.036-1.327], Cd (OR 8.931, 95% CI 2.003-39.811), Cotinine (OR 4.376, 95% CI 1.159-16.531), DEHP (OR 1.863, 95% CI 1.103-3.146) were important factors contributing to the missed abortion (P < .05).It was demonstrated that high gestational age, passive smoking, heavy metals, and the phthalate exposure were the risk factors for missed abortion, while the premarital health examination was a protective factor. Avoiding these harmful substances before getting pregnant and during the early stages of pregnancy, might help prevent missed abortions. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Antiandrogenic activity of phthalate mixtures: Validity of concentration addition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christen, Verena; Crettaz, Pierre; Oberli-Schrämmli, Aurelia

2012-03-01

Phthalates and bisphenol A have very widespread use leading to significant exposure of humans. They are suspected to interfere with the endocrine system, including the androgen, estrogen and the thyroid hormone system. Here we analyzed the antiandrogenic activity of six binary, and one ternary mixture of phthalates exhibiting complete antiandrogenic dose–response curves, and binary mixtures of phthalates and bisphenol A at equi-effective concentrations of EC{sub 10}, EC{sub 25} and EC{sub 50} in MDA-kb2 cells. Mixture activity followed the concentration addition (CA) model with a tendency to synergism at high and antagonism at low concentrations. Isoboles and the toxic unit approachmore » (TUA) confirmed the additive to synergistic activity of the binary mixtures BBP + DBP, DBP + DEP and DEP + BPA at high concentrations. Both methods indicate a tendency to antagonism for the EC{sub 10} mixtures BBP + DBP, BBP + DEP and DBP + DEP, and the EC{sub 25} mixture of DBP + BPA. A ternary mixture revealed synergism at the EC{sub 50}, and weak antagonistic activity at the EC{sub 25} level by the TUA. A mixture of five phthalates representing a human urine composition and reflecting exposure to corresponding parent compounds showed no antiandrogenic activity. Our study demonstrates that CA is an appropriate concept to account for mixture effects of antiandrogenic phthalates and bisphenol A. The interaction indicates a departure from additivity to antagonism at low concentrations, probably due to interaction with the androgen receptor and/or cofactors. This study emphasizes that a risk assessment of phthalates should account for mixture effects by applying the CA concept. -- Highlights: ► Antiandrogenic activity of mixtures of 2 and 3 phthalates are assessed in MDA-kb2 cells. ► Mixture activities followed the concentration addition model. ► A tendency to synergism at high and antagonism at low levels occurred.« less

Temporal Variability of Cumulative Risk Assessment on Phthalates in Chinese Pregnant Women: Repeated Measurement Analysis.

PubMed

Gao, Hui; Zhu, Bei-Bei; Tao, Xing-Yong; Zhu, Yuan-Duo; Tao, Xu-Guang; Tao, Fang-Biao

2018-06-05

The assessment of the combined effects of multiple phthalate exposures at low levels is a newly developed concept to avoid underestimating their actual cumulative health risk. A previous study included 3455 Chinese pregnant women. Each woman provided up to three urine samples (in total 9529). This previous study characterized the concentrations of phthalate metabolites. In the present study, the data from 9529 samples was reanalyzed to examine the cumulative risk assessment (CRA) with two models: (1) the creatinine-based and (2) the volume-based. Hazard index (HI) values for three phthalates, dibutyl phthalate, butyl benzyl phthalate, and di(2-ethylhexyl) phthalate, in the first, second, and third trimesters of pregnancy, were calculated, respectively. In creatinine-based model, 3.43%, 14.63%, and 17.28% of women showed HI based on the European Food Safety Authority tolerable daily intake exceeding 1 in the first, second, and third trimester of pregnancy, respectively. The intraclass correlation coefficient of HI was 0.49 (95% confidence interval: 0.46-0.53). Spearman correlations between HI of the creatinine model and ∑androgen disruptor (a developed potency weighted approach) ranged from 0.824 to 0.984. In summary, this study suggested a considerable risk of cumulative exposure to phthalates during the whole gestation in Chinese pregnant women. In addition, moderate temporal reproducibility indicated that single HI, estimated by the phthalate concentration in single spot of urine, seemed representative to describe the throughout pregnancy CRA. Finally, strong correlation between HI of the creatinine model and ∑androgen disruptor revealed that the creatinine-based model was more appropriate to evaluate the CRA.

Pollution characteristics and health risk assessment of phthalate esters in urban soil in the typical semi-arid city of Xi'an, Northwest China.

PubMed

Wang, Lijun; Liu, Mengmei; Tao, Wendong; Zhang, Wenjuan; Wang, Li; Shi, Xingmin; Lu, Xinwei; Li, Xiaoping

2018-01-01

A total of 62 urban soil samples were collected in the city of Xi'an in Northwest China, and analyzed for six U.S. Environmental Protection Agency priority phthalate esters (PAEs). Unlike earlier studies on PAEs in agricultural soil as well as urban soil in humid climates, this paper for the first time comprehensively assessed pollution characteristics and health risks of human exposure to PAEs in urban soil in a typical semi-arid climate. The total concentrations of the six PAEs (Σ6PAEs) in the urban soil varied between 193.0 and 19146.4 μg kg -1 with a mean of 1369.3 μg kg -1 . The PAEs were dominated by di-n-butyl phthalate and di(2-ethylhexyl) phthalate. Magnetic susceptibility and soil texture were controlling factors influencing the concentrations of PAEs in the urban soil. The concentrations of benzyl butyl phthalate, di(2-ethylhexyl) phthalate, and Σ6PAEs increased from the first to third ring roads, while the concentrations of di-n-octyl phthalate decreased. Relatively higher levels of PAEs were observed in industrial, traffic, and residential areas. The PAEs in the urban soil originated mainly from the application of plasticizers or additives, use of cosmetics and personal care products, emissions of construction materials and home furnishings, industrial processes, and atmospheric deposition. The concentrations of some PAEs in the urban soil exceeded soil allowable concentrations and environmental risk levels. The non-cancer and carcinogenic risks of human exposure to the PAEs were relatively low. Copyright © 2017 Elsevier Ltd. All rights reserved.

Curcumin inhibits adipogenesis induced by benzyl butyl phthalate in 3T3-L1 cells.

PubMed

Sakuma, Satoru; Sumida, Maki; Endoh, Yukiko; Kurita, Ayaka; Yamaguchi, Ayana; Watanabe, Tomoki; Kohda, Tetsuya; Tsukiyama, Yui; Fujimoto, Yohko

2017-08-15

Phthalates are a group of endocrine disrupting chemicals and may have contributed to the recent global obesity health crisis. Increased adipogenesis via the peroxisome proliferator-activated receptor γ (PPARγ)-CCAAT-enhancer binding protein α (C/EBPα) pathway could be one critical mechanism responsible for phthalate-induced weight gain. On the other hand, curcumin has been shown to inhibit adipogenesis in cells and animal models. The present study was undertaken to evaluate, for the first time, whether curcumin could reduce adipogenesis induced by benzyl butyl phthalate (BBP) via downregulation of the PPARγ-C/EBPα pathway. 3T3-L1 preadipocytes were differentiated by treating them with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the presence of BBP, with or without curcumin. Cells that were grown in the presence of BBP alone showed a significant increase in triacylglycerol (TG) levels. In addition, the number of Oil Red O-stained cells and the mRNA expression levels of PPARγ, C/EBPα, adiponectin, and tumor necrosis factor-α (TNFα) were significantly increased. However, treatment with BBP in combination with curcumin resulted in major reductions in TG levels, the numbers of Oil Red O-stained cells, and the mRNA expression levels of the four proteins. These results suggest that curcumin might be an inhibitor of BBP-induced weight gain and inflammation via stimulation of adipocyte differentiation and TNFα generation. Curcumin may, therefore, be a potential medication for preventing the harmful effects of phthalates. Copyright © 2017 Elsevier Inc. All rights reserved.

Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Rupesh K., E-mail: drrupesh@illinois.ed; Singh, Jeffery M., E-mail: jsingh20@illinois.ed; Leslie, Tracie C., E-mail: tleslie2@illinois.ed

2010-01-15

Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in a wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) decrease serum estradiol levels and aromatase (Arom) expression, prolong estrous cycles, and cause anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1-100 mug/ml) and MEHP (0.1-10 mug/ml) directly inhibit antral follicular growth andmore » estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 h. During culture, follicle size was measured every 24 h as a measurement of follicle growth. After culture, media were collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at the highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom at the highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.« less

Di(n)butyl phthalate reduces testicular weight, testosterone and associated gene expression in fetal Harlan Sprague Dawley rats.

EPA Science Inventory

Certain phthalate esters (PE) cause reproductive malformations in male rats when exposure occurs during sexual differentiation in utero. Reductions in fetal testosterone levels are causally linked to the induction of these malformations. While reproductive development studies on ...

Man is not a big rat: concerns with traditional human risk assessment of phthalates based on their anti-androgenic effects observed in the rat foetus.

PubMed

Habert, René; Livera, Gabriel; Rouiller-Fabre, Virginie

2014-01-01

Phthalates provide one of the most documented example evidencing how much we must be cautious when using the traditional paradigm based on extrapolation of experimental data from rodent studies for human health risk assessment of endocrine disruptors (EDs). Since foetal testis is known as one of the most sensitive targets of EDs, phthalate risk assessment is routinely based on the capacity of such compounds to decrease testosterone production by the testis or to impair masculinization in the rat during foetal life. In this paper, the well-established inhibiting effects of phthalates of the foetal Leydig cells function in the rat are briefly reviewed. Then, data obtained in humans and other species are carefully analysed. Already in January 2009, using the organotypic culture system named Fetal Testis Assay (FeTA) that we developed, we reported that phthalates might not affect testosterone production in human foetal testes. Several recent experimental studies using xenografts confirm the absence of detectable anti-androgenic effect of phthalates in the human foetal testes. Epidemiological studies led to contradictory results. Altogether, these findings suggest that phthalates effects on foetal Leydig cells are largely species-specific. Consequently, the phthalate threshold doses that disturb foetal steroidogenesis in rat testes and that are presently used to define the acceptable daily intake levels for human health protection must be questioned. This does not mean that phthalates are safe because these compounds have many deleterious effects upon germ cell development that may be common to the different studied species including human. More generally, the identification of common molecular, cellular or/and phenotypic targets in rat and human testes should precede the choice of the toxicological endpoint in rat to accurately assess the safety threshold of any ED in humans.

40 CFR 141.61 - Maximum contaminant levels for organic contaminants.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) adipate X X 117-81-7 Di (2-ethylhexyl) phthalate X 96-12-8 Dibromochloropropane (DBCP) X X 95-50-1 o...-ethylhexyl) adipate 0.4 (22) 117-81-7 Di(2-ethylhexyl) phthalate 0.006 (23) 88-85-7 Dinoseb 0.007 (24) 85-00...

40 CFR 141.61 - Maximum contaminant levels for organic contaminants.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) adipate X X 117-81-7 Di (2-ethylhexyl) phthalate X 96-12-8 Dibromochloropropane (DBCP) X X 95-50-1 o...-ethylhexyl) adipate 0.4 (22) 117-81-7 Di(2-ethylhexyl) phthalate 0.006 (23) 88-85-7 Dinoseb 0.007 (24) 85-00...

40 CFR 141.61 - Maximum contaminant levels for organic contaminants.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) adipate X X 117-81-7 Di (2-ethylhexyl) phthalate X 96-12-8 Dibromochloropropane (DBCP) X X 95-50-1 o...-ethylhexyl) adipate 0.4 (22) 117-81-7 Di(2-ethylhexyl) phthalate 0.006 (23) 88-85-7 Dinoseb 0.007 (24) 85-00...

New insights into the mechanism of phthalate-induced developmental effects.

PubMed

Mu, Xiyan; Huang, Ying; Li, Jia; Yang, Ke; Yang, Wenbo; Shen, Gongming; Li, Xuxing; Lei, Yunlei; Pang, Sen; Wang, Chengju; Li, Xuefeng; Li, Yingren

2018-06-11

To investigate the biological pathways involved in phthalate-induced developmental effects, zebrafish embryos were exposed to different concentrations of di-(2-ethylhexyl) (DEHP) and di-butyl phthalate (DBP) for 96 h. Embryonic exposure to DEHP and DBP induced body length decrease, yolk sac abnormities, and immune responses (up-regulation of immune proteins and genes). The lipidomic results showed that at a concentration of 50 μg/L, DEHP and DBP significantly reduced the levels of fatty acids, triglycerides, diacylglycerol, and cholesterol. These effects are partly explained by biological pathway enrichment based on data from the transcriptional and proteomic profiles. Co-exposure to DBP and ER antagonist did not significantly relieve the toxic symptoms compared with exposure to DBP alone. This indicates that phthalate-induced developmental abnormities in zebrafish might not be mediated by the ER pathway. In conclusion, we identified the possible biological pathways that mediate phthalate-induced developmental effects and found that these effects may not be driven by estrogenic activation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Variation in urinary spot sample, 24 h samples, and longer-term average urinary concentrations of short-lived environmental chemicals: implications for exposure assessment and reverse dosimetry

PubMed Central

Aylward, Lesa L; Hays, Sean M; Zidek, Angelika

2017-01-01

Population biomonitoring data sets such as the Canadian Health Measures Survey (CHMS) and the United States National Health and Nutrition Examination Survey (NHANES) collect and analyze spot urine samples for analysis for biomarkers of exposure to non-persistent chemicals. Estimation of population intakes using such data sets in a risk-assessment context requires consideration of intra- and inter-individual variability to understand the relationship between variation in the biomarker concentrations and variation in the underlying daily and longer-term intakes. Two intensive data sets with a total of 16 individuals with collection and measurement of serial urine voids over multiple days were used to examine these relationships using methyl paraben, triclosan, bisphenol A (BPA), monoethyl phthalate (MEP), and mono-2-ethylhexyl hydroxyl phthalate (MEHHP) as example compounds. Composited 24 h voids were constructed mathematically from the individual collected voids, and concentrations for each 24 h period and average multiday concentrations were calculated for each individual in the data sets. Geometric mean and 95th percentiles were compared to assess the relationship between distributions in spot sample concentrations and the 24 h and multiday collection averages. In these data sets, spot sample concentrations at the 95th percentile were similar to or slightly higher than the 95th percentile of the distribution of all 24 h composite void concentrations, but tended to overestimate the maximum of the multiday concentration averages for most analytes (usually by less than a factor of 2). These observations can assist in the interpretation of population distributions of spot samples for frequently detected analytes with relatively short elimination half-lives. PMID:27703149

Environmental chemicals mediated the effect of old housing on adult health problems: US NHANES, 2009-2010.

PubMed

Shiue, Ivy; Bramley, Glen

2015-01-01

Housing conditions affect occupants continuously, and health interventions have shown a positive association between housing investment or improvement and occupant's health. However, the sources of the housing problems were less understood. Since it was observed that lead dust and chloroanisoles released from housing (materials) as indoor pollutants affected child's health, we now aimed to examine the relationships among built year, environmental chemicals and individual health in adults in a national and population-based setting. Data were retrieved from the US National Health and Nutrition Examination Survey, 2009-2010, including demographics, housing characteristics, self-reported health status, biomarkers and blood and urinary chemical concentrations. Adults aged 20 and above were included for statistical analysis (n = 5,793). Analysis involved chi-square test, t test, and survey-weighted general linear regression and logistic regression modelling. People who resided in older housing built before 1990 tended to report chronic bronchitis, liver problems, stroke, heart failure, diabetes, asthma and emphysema. Higher values in HDL cholesterol, blood lead and blood cadmium and having positive responses of hepatitis A, B, C and E antibodies among occupants were also observed. Furthermore, higher environmental chemical concentrations related to old housing including urinary cadmium, cobalt, platinum, mercury, 2,5-dichlorophenol and 2,4-dichlorophenol concentrations and mono-cyclohexyl phthalate and mono-isobutyl phthalate metabolites were shown in occupants as well. Older housing (≥30 years) seemed to contribute to the amount of environmental chemicals that affected human health. Regular monitoring, upgrading and renovation of housing to remove environmental chemicals and policy to support people in deprived situations against environmental injustice would be needed.

Health risk assessment of phthalate esters (PAEs) in drinking water sources of China.

PubMed

Wang, Wen-Long; Wu, Qian-Yuan; Wang, Chao; He, Tao; Hu, Hong-Ying

2015-03-01

Phthalate esters (PAEs) with endocrine disruption effects and carcinogenicity are widely detected in water environment. Occurrences of PAEs in source water and removal efficiencies of PAEs by drinking water treatment plants (DWTPs) in China were surveyed from publications in the last 10 years. Concentration of diethylhexyl phthalate (DEHP) in source water with median value of 1.3 μg/L was higher than that of dimethyl phthalate (DMP), diethyl phthalate (DEP), and di-n-butyl phthalate (DnBP). If the removal efficiencies of DEHP and DnBP reached 60 and 90 %, respectively, the calculated PAE concentration in drinking water can generally meet Standards for Drinking Water Quality in China. The health risks of PAEs, including non-carcinogenic and carcinogenic risks via the "water source-DWTP-oral ingestion/dermal permeation" pathway, were evaluated with Monte Carlo simulation and sensitivity analysis under certain removal efficiencies from 0 to 95 %. The carcinogenic risk of DEHP was lower than the upper acceptable carcinogenic risk level (10(-4)), while the probability of DEHP's carcinogenic risk between lower (10(-6)) and upper (10(-4)) acceptable carcinogenic risk level decreased from about 21.2 to 0.4 % through increasing DEHP removal efficiency from 0 to 95 %. The non-carcinogenic risk of DEHP was higher than that of DEP and DnBP. In all cases, the total non-carcinogenic risk of DEP, DnBP, and DEHP was lower than 1, indicating that there would be unlikely incremental non-carcinogenic risk to humans. Both carcinogenic risk and non-carcinogenic risk of PAEs in drinking water to female were a little higher than those to male.

Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development.

PubMed Central

Colón, I; Caro, D; Bourdony, C J; Rosario, O

2000-01-01

Premature breast development (thelarche) is the growth of mammary tissue in girls younger than 8 years of age without other manifestations of puberty. Puerto Rico has the highest known incidence of premature thelarche ever reported. In the last two decades since this serious public health anomaly has been observed, no explanation for this phenomenon has been found. Some organic pollutants, including pesticides and some plasticizers, can disrupt normal sexual development in wildlife, and many of these have been widely used in Puerto Rico. This investigation was designed to identify pollutants in the serum of Puerto Rican girls with premature thelarche. A method for blood serum analysis was optimized and validated using pesticides and phthalate esters as model compounds of endocrine-disrupting chemicals. Recovery was > 80% for all compounds. We performed final detection by gas chromatography/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were detected in the serum of the study or control subjects. Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population. PMID:11017896

GC/MS screening method for phthalate esters in children's toys.

PubMed

Ting, Keh-Chuh; Gill, Modan; Garbin, Orlando

2009-01-01

Phthalate esters are commonly added into polyvinyl chloride (PVC) as softeners to make the plastic material flexible. Phthalates are suspected cancer-causing agents and possible teratogens; they have been linked to liver and kidney damage, as well as the underdevelopment of reproductive organs in humans and animals. Public safety concerns about human exposure to phthalates are on the rise because they do not chemically bond to PVC and leach from the material over time. Following the lead of the European Union and Japan in restricting the use of certain phthalates, a legal limit of 0.1% in children's toys was established by the California State Legislature (AB-1108). In addition to its mission to protect public health and the environment from toxic harm, the California Department of Toxic Substances Control (DTSC) has been delegated the role of lead agency for consumer product safety. To support DTSC's Green Chemistry activities, the Environmental Chemistry Laboratory Mobile Laboratory Team has developed an on-site screening method to monitor phthalates in children's toys. This method is simple, fast, and effective, with ample sensitivity to quantify the 6 restricted phthalates in children's toys at 100 ppm (limit of quantitation = 100 microg/g) which is 10 times lower than the legal allowable level of 0.1%. Additionally, the method has a high throughput capability and enables testing of approximately 6-10 samples per day, depending on the complexity of the sample matrix and concentration. This method is designed to survey the 6 phthalates in children's toys and other consumer products for compliance with the threshold of 0.1% (1000 ppm).

Role of Oxidative Stress in Male Reproductive Dysfunctions with Reference to Phthalate Compounds.

PubMed

Sedha, Sapna; Kumar, Sunil; Shukla, Shruti

2015-11-14

A wide variety of environmental chemicals/xenobiotics including phthalates have been shown to cause oxidative stress targeting the endocrine system and cause reproductive anomalies. The present review describes various issues by oxidative stress causing male reproductive dysfunctions. Here in this review, the importance and role of phthalate compounds in male reproductive dysfunction has been well documented. One class of environmental endocrine disruptors is phthalates. Phthalate compounds are mostly used as plasticizers, which increase the flexibility, durability, longevity, and etc. of the plastics. Large-scale use of plastic products in our daily life as well as thousands of workers engaged in the manufacture of plastic and plastic products and recycling plastic industry are potentially exposed to these chemicals. Further, general population as well as vulnerable groups i.e. children and pregnant women are also exposed to these chemicals. Phthalates are among wide variety of environmental toxicants capable of compromising male fertility by inducing a state of oxidative stress in the testes. They may also generate reactive oxygen species (ROS) that may affect various physiological and reproductive functions. The available data points out that phthalate compounds may also induce oxidative stress in the male reproductive organs mainly testis and epididymis. They impair spermatogenic process by inducing oxidative stress and apoptosis in germ cells or target sertoli cells and thereby hamper spermatogenesis. They also impair the Leydig cell function by inducing ROS, thereby decreasing the levels of steroidogenic enzymes. Thus in utero and postnatal exposure to phthalate compounds might lead to decreased sperm count and various other reproductive anomalies in the young male.

Comparative effects of butyl benzyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP) on the aquatic larvae of Chironomus riparius based on gene expression assays related to the endocrine system, the stress response and ribosomes.

PubMed

Planelló, Rosario; Herrero, Oscar; Martínez-Guitarte, José Luis; Morcillo, Gloria

2011-09-01

In this work, the effects of butyl benzyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP), two of the most extensively used phthalates, were studied in Chironomus riparius under acute short-term treatments, to compare their relative toxicities and identify genes sensitive to exposure. The ecotoxicity of these phthalates was assessed by analysis of the alterations in gene expression profiles of selected inducible and constitutive genes related to the endocrine system, the cellular stress response and the ribosomal machinery. Fourth instar larvae, a model system in aquatic toxicology, were experimentally exposed to five increasing concentrations (0.01, 0.1, 1, 10, and 100mg/L) of DEHP and BBP for 24h. Gene expression was analysed by the changes in levels of transcripts, using RT-PCR techniques with specific gene probes. The exposures to DEHP or BBP were able to rapidly induce the hsp70 gene in a concentration-dependent manner, whereas the cognate form hsc70 was not altered by either of these chemicals. Transcription of ribosomal RNA as a measure of cell viability, quantified by the levels of ITS2, was not affected by DEHP, but was slightly, yet significantly, downregulated by BBP at the highest concentrations tested. Finally, as these phthalates are classified as endocrine disruptor chemicals (EDCs), their potential effect on the ecdysone endocrine system was studied by analysing the two genes, EcR and usp, of the heterodimeric ecdysone receptor complex. It was found that BBP provoked the overexpression of the EcR gene, with significant increases from exposures of 0.1mg/L and above, while DEHP significantly decreased the activity of this gene at the highest concentration. These data are relevant as they show for the first time the ability of phthalates to interfere with endocrine marker genes in invertebrates, demonstrating their potential capacity to alter the ecdysone signalling pathway. Overall, the study clearly shows a differential gene-toxin interaction for these two phthalates and adds novel genomic tools for biomonitoring environmental xenobiotics in insects. Copyright © 2011 Elsevier B.V. All rights reserved.

CHRONIC EXPOSURE TO DI(2-ETHYLHEXYL) PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN THE MALE RAT

EPA Science Inventory

DEHP, dibutyl (DBP)-, and benzyl butyl (BBP)- phthalate are plasticizers that cause adverse developmental reproductive effects in laboratory animals. They alter sexual differentiation in the rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels, which in ...

Kinetic evaluation and process performance of a fixed film bioreactor removing phthalic acid and dimethyl phthalate.

PubMed

Pirsaheb, Meghdad; Mesdaghinia, Ali-Reza; Shahtaheri, Seyed Jamaleddin; Zinatizadeh, Ali Akbar

2009-08-15

Phthalate esters are toxic organic contaminants which can enter into the environment through various industrial processes. In this study, a 6-liter fixed film bioreactor was used to examine biodegradation of phthalic acid (PA) and dimethyl phthalate (DMP) in synthetic wastewater. Effect on the process of two operating factors, namely hydraulic retention time (HRT) (at four levels ranging between 6 and 48 h) and initial phthalate concentrations (at six levels ranging from 10mg to 500 mg/l), was investigated. The process was stable at all operating conditions, except for the condition with influent PA and DMP of 500 mg/l and HRT of 6h. More than 95% removal efficiency was achieved for the conditions with HRT longer than 10h. Remarkable amount of DMP (398 mg/kg of sludge) was adsorbed on the biomass due to its higher hydrophobicity compared to PA (171 mg/kg). The kinetic parameters (mu(m,)K(s), Y and K(d)) were determined and compared for both substrates, PA and DMP.

40 CFR 464.11 - Specialized definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (dichloromethane) 65. phenol 66. bis(2-ethylhexyl) phthalate 67. butyl benzyl phthalate 84. pyrene 85... 65. phenol 66. bis(2-ethylhexyl) phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70...) 65. phenol 66. bis (2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 73. benzo...

40 CFR 464.41 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (dichloromethane) 65. phenol 66. bis(2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 85.... naphthalene 65. phenol 66. bis (2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 85...) 55. naphthalene 65. phenol 66. bis(2-ethylhexyl) phthalate 68. di-n-butyl phthalate 85...

40 CFR 464.41 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (dichloromethane) 65. phenol 66. bis(2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 85.... naphthalene 65. phenol 66. bis (2-ethylhexyl) phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 85...) 55. naphthalene 65. phenol 66. bis(2-ethylhexyl) phthalate 68. di-n-butyl phthalate 85...

Association between fetal exposure to phthalate endocrine disruptor and genome-wide DNA methylation at birth.

PubMed

Chen, Chung-Hsing; Jiang, Shih Sheng; Chang, I-Shou; Wen, Hui-Ju; Sun, Chien-Wen; Wang, Shu-Li

2018-04-01

Phthalic acid esters are ubiquitous and antiandrogenic, and may cause systemic effects in humans, particularly with in utero exposure. Epigenetic modification, such as DNA methylation, has been hypothesized to be an important mechanism that mediates certain biological processes and pathogenic effects of in utero phthalate exposure. The aim of this study was to examine the association between genome-wide DNA methylation at birth and prenatal exposure to phthalate. We studied 64 infant-mother pairs included in TMICS (Taiwan Maternal and Infant Cohort Study), a long-term follow-up birth cohort from the general population. DNA methylation levels at more than 450,000 CpG sites were measured in cord blood samples using Illumina Infinium HumanMethylation450 BeadChips. The concentrations of three metabolites of di-(2-ethylhexyl) phthalate (DEHP) were measured using liquid chromatography tandem-mass spectrometry (LC-MS/MS) in urine samples collected from the pregnant women during 28-36 weeks gestation. We identified 25 CpG sites whose methylation levels in cord blood were significantly correlated with prenatal DEHP exposure using a false discovery rate (FDR) of 5% (q-value < 0.05). Via gene-set enrichment analysis (GSEA), we also found that there was significant enrichment of genes involved in the androgen response, estrogen response, and spermatogenesis within those genes showing DNA methylation changes in response to exposure. Specifically, PA2G4, HMGCR, and XRCC6 genes were involved in genes in response to androgen. Phthalate exposure in utero may cause significant alterations in the DNA methylation in cord blood. These changes in DNA methylation might serve as biomarkers of maternal exposure to phthalate in infancy and potential candidates for studying mechanisms via which phthalate may impact on health in later life. Future investigations are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

40 CFR 464.31 - Specialized definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (dichloromethane) 55. naphthalene 64. pentachlorophenol 65. phenol 66. bis(2-ethylhexyl)phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72. benzo (a)anthracene (1,2...-ethylhexyl) phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 72. benzo (a)anthracene (1,2...

Ultra-trace analysis of hormones, pharmaceutical substances, alkylphenols and phthalates in two French natural mineral waters.

PubMed

Dévier, Marie-Hélène; Le Menach, Karyn; Viglino, Liza; Di Gioia, Lodovico; Lachassagne, Patrick; Budzinski, Hélène

2013-01-15

The aim of this work was to investigate the potential presence of a broad range of organic compounds, such as hormones, alkylphenols, bisphenol A and phthalates, as well as pharmaceutical substances in two brands of bottled natural mineral waters (Evian and Volvic, Danone). The phthalates were determined by solid-phase microextraction coupled to gas chromatography-mass spectrometry (SPME-GC-MS) and the other compounds by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or gas chromatography-mass spectrometry (GC-MS) after solid-phase extraction. The potential migration of alkylphenols, bisphenol A and phthalates from polyethylene terephthalate (PET) bottles was also investigated under standardized test conditions. Evian and Volvic natural mineral waters contain none of the around 120 targeted organic compounds. Traces of 3 pharmaceuticals (ketoprofen, salicylic acid, and caffeine), 3 alkylphenols (4-nonylphenol, 4-t-octylphenol, and 4-nonylphenol diethoxylate), and some phthalates including di(2-ethylhexyl)phthalate (DEHP) were detected in the samples, but they were also present in the procedural blanks at similar levels. The additional test procedures demonstrated that the few detected compounds originated from the background laboratory contamination. Analytical procedures have been designed both in the bottling factory and in the laboratory in order to investigate the sources of DEHP and to minimize to the maximum this unavoidable laboratory contamination. It was evidenced that no migration of the targeted compounds from bottles occurred under the test conditions. The results obtained in this study underline the complexity of reaching a reliable measure to qualify the contamination of a sample at ultra-trace level, in the field of very pure matrices. The analytical procedures involving glassware, equipment, hoods, and rooms specifically dedicated to trace analysis allowed us to reach reliable procedural limits of quantification at the ng/L level, by lowering the background laboratory contamination. Copyright © 2012 Elsevier B.V. All rights reserved.

Lifestyle behaviors associated with exposures to endocrine disruptors

PubMed Central

Martina, Camille A.; Weiss, Bernard; Swan, Shanna H.

2013-01-01

Identifying and characterizing sources of exposure to phthalates and bisphenol A (BPA) have proved challenging due to the presence of multiple co-exposures resulting from a wide variety of home environments and lifestyles. We hypothesized that the consistent lifestyle of an Old Order Mennonite (OOM) community would provide an ideal setting in which to characterize sources of exposure to BPA and phthalates. We obtained urine samples from ten mid-term pregnant OOM women (ages-21–39) to determine concentrations of 9 phthalate metabolites and BPA and collected a self-reported survey of participants' household environment, product use, and lifestyle within a 48-h period prior to urine collection. We compared their metabolite concentrations to pregnant women included in the National Health and Nutrition Examination Survey (NHANES 2007–2008). Although OOM participants reported some use of plastic and fragranced household products, concentrations of metabolites were lower and significantly less for BPA (p = 0.002) and phthalate metabolites MEHP (p = 0.0215), MiBP (p = 0.0020) and MEP (p = 0.021), when compared to NHANES pregnant women. Levels of other phthalate metabolites were also lower in this population. Our data suggest three practices that may contribute to these lower levels: (1) consuming mostly homegrown produce (ingestion), (2) no cosmetics and limited use of personal care products, and (3) transportation primarily by sources other than automobiles. PMID:22739065

Determination of contamination pathways of phthalates in food products sold on the Belgian market.

PubMed

Van Holderbeke, Mirja; Geerts, Lieve; Vanermen, Guido; Servaes, Kelly; Sioen, Isabelle; De Henauw, Stefaan; Fierens, Tine

2014-10-01

As numerous studies have indicated that food ingestion is the most important exposure pathway to several phthalates, this study aimed to determine possible contamination pathways of phthalates in food products sold on the Belgian market. To do this, concentrations of eight phthalates (dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), benzylbutyl phthalate (BBP), dicyclohexyl phthalate (DCHP), di(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP)) were determined in 591 foods and 30 packaging materials. In general, the four most prominent phthalates in Belgian food products were DEHP, DiBP, DnBP and BBP. Special attention was given to the origin of these phthalates in bread, since high phthalate concentrations (especially DEHP) were determined in this frequently consumed food product. Phthalates seemed to occur in Belgian bread samples due to the use of contaminated ingredients (i.e. use of contaminated flour) as well as due to migration from phthalate containing contact materials used during production (e.g. coated baking trays). Also the results of the conducted concentration profiles of apple, bread, salami and two cheese types revealed the important role of processing - and not packaging - on phthalate contents in foods. Copyright © 2014 Elsevier Inc. All rights reserved.

Emergent contaminants in the wastewater effluents of two highly populated tropical cities.

PubMed

Soler-Llavina, Sheila M; Ortiz-Zayas, Jorge R

2017-10-01

Exposure to the anthropogenic chemicals known as endocrine disrupting compounds (EDCs) may result in negative biological effects. Low levels of EDCs in the environment aggravate the problem as exposure is constant. Urban areas concentrate pollution as greater volumes are released from human activities. Water for public supply is particularly vulnerable as the sewage treatment facilities may not eliminate EDCs. The goal was to assess estrogenicity and effectiveness of removal of phthalates in primary and tertiary wastewater treatment facilities in urban cities in the tropical island of Puerto Rico. A yeast bioassay used to measure estrogenicity showed higher removal with tertiary treatment. However, results in the picomolar range suggest low doses of estrogenic compounds were being released to receiving waters. For the phthalates, solid phase extraction and gas chromatography-mass spectrometry analyses revealed removals ranging from 42.9% to 92.4% with tertiary treatment. More than 90% removal was achieved for benzylbutyl phthalate, dibutyl phthalate and bis-2-ethylhexyl phthalate. However, concentrations ranging from 0.86 to 1.29 ppm for the phthalates in the outflow were detected even at the tertiary waste water treatment plant effluent implying failure of EDC removal. These results can assist managers in evaluating pollution control technologies to ameliorate the impacts of EDCs in the tropics.

Studies into the transfer and migration of phthalate esters from aluminium foil-paper laminates to butter and margarine.

PubMed

Page, B D; Lacroix, G M

1992-01-01

Retail samples of Canadian butter and margarine wrapped in aluminium foil-paper laminate were found to contain dibutyl, butyl benzyl and/or di-2-ethylhexyl phthalate (DBP, BBP, DEHP) as packaging migrants at levels up to 10.6, 47.8 and 11.9 micrograms/g, respectively. These phthalates were determined by capillary gas chromatography with flame ionization detection (GC-FID) after clean-up of the separated oil by sweep co-distillation. The phthalate esters found in the contacted butter or margarine were also found in the contacting wrappers. They were determined in wrapper extracts by liquid chromatography with diode array detection or by GC-FID. Analysis of unused wrappers showed 76-88% of the total DBP and DEHP to be present on the foil (outer) surface as a component of the protective coating (washcoat). The remainder of the DBP and DEHP was found on the food-contacting paper surface, presumably by transfer from the outer to inner surface during storage in tightly wound rolls, although transfer of phthalate esters, if present in the paper-foil adhesive, cannot be ruled out. Food-contacting surface concentrations of DBP and DEHP were found to be 2.4 to 4.7 and 2.8 to 3.6 micrograms/cm2, respectively. Samples of each packaging component: paper, foil, adhesive, washcoat and inks were analysed for phthalate esters and only the washcoat was found to contain phthalate esters.

40 CFR 433.11 - Specialized definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-propylamine Pentachlorophenol Phenol Bis (2-ethylhexyl) phthalate Butyl benzyl phthalate Di-n-butyl phthalate Di-n-octyl phthalate Diethyl phthalate Dimethyl phthalate 1,2-Benzanthracene (benzo(a)anthracene...

40 CFR 433.11 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-propylamine Pentachlorophenol Phenol Bis (2-ethylhexyl) phthalate Butyl benzyl phthalate Di-n-butyl phthalate Di-n-octyl phthalate Diethyl phthalate Dimethyl phthalate 1,2-Benzanthracene (benzo(a)anthracene...

40 CFR 433.11 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-propylamine Pentachlorophenol Phenol Bis (2-ethylhexyl) phthalate Butyl benzyl phthalate Di-n-butyl phthalate Di-n-octyl phthalate Diethyl phthalate Dimethyl phthalate 1,2-Benzanthracene (benzo(a)anthracene...

40 CFR 413.02 - General definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-nitrosodiphenylamine N-nitrosodi-n-propylamine Pentachlorophenol Phenol Bis (2-ethylhexyl) phthalate Butyl benzyl phthalate Di-n-butyl phthalate Di-n-octyl phthalate Diethyl phthalate Dimethyl phthalate 1,2-benzanthracene...

40 CFR 413.02 - General definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-nitrosodiphenylamine N-nitrosodi-n-propylamine Pentachlorophenol Phenol Bis (2-ethylhexyl) phthalate Butyl benzyl phthalate Di-n-butyl phthalate Di-n-octyl phthalate Diethyl phthalate Dimethyl phthalate 1,2-benzanthracene...

40 CFR 464.21 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... pentachlorophenol 66. bis(2-ethylhexyl)phthalate 71. dimethyl phthalate (2) Dust Collection Scrubbers (§ 464.25(c...-dimethylphenol 55. naphthalene 58. 4-nitrophenol 64. pentachlorophenol 65. phenol 66. bis(2-ethylhexyl)phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72...

40 CFR 464.21 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... pentachlorophenol 66. bis(2-ethylhexyl)phthalate 71. dimethyl phthalate (2) Dust Collection Scrubbers (§ 464.25(c...-dimethylphenol 55. naphthalene 58. 4-nitrophenol 64. pentachlorophenol 65. phenol 66. bis(2-ethylhexyl)phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72...

Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children's Health.

PubMed

Minatoya, Machiko; Naka Jima, Sonomi; Sasaki, Seiko; Araki, Atsuko; Miyashita, Chihiro; Ikeno, Tamiko; Nakajima, Tamie; Goto, Yuko; Kishi, Reiko

2016-09-15

Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study. Maternal blood samples collected between 23 and 41weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18month of age. For the final analysis, 328 participants were included. The median levels of maternal MEHP was 10.6ng/ml, neonatal TSH and FT4 was 2.20 μU/ml and 2.03ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18month. In this study, prenatal DEHP exposure did not show adverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary. Copyright © 2016. Published by Elsevier B.V.

Evaluating the potential genotoxicity of phthalates esters (PAEs) in perfumes using in vitro assays.

PubMed

Al-Saleh, Iman; Al-Rajudi, Tahreer; Al-Qudaihi, Ghofran; Manogaran, Pulicat

2017-10-01

We previously reported high levels of phthalate esters (PAEs) added as solvents or fixatives in 47 brands of perfumes. Diethyl phthalate was the most abundant compound (0.232-23,649 ppm), and 83.3% of the perfumes had levels >1 ppm, the threshold limit cited by a Greenpeace investigation. All samples had dimethyl phthalate levels higher than its threshold limit of 0.1 ppm, and 88, 38, and 7% of the perfumes had benzyl butyl phthalate, di(2-ethylhexyl) phthalate, and dibutyl phthalate levels, respectively, above their threshold limits. The role of PAEs as endocrine disruptors has been well documented, but their effect on genotoxic behavior has received little attention. We used in vitro single-cell gel electrophoresis (comet) and micronucleus (MN) assays with human lymphoblastoid TK6 cells to evaluate the genotoxic potency of 42 of the same perfumes and to determine its association with PAEs. All perfumes induced more DNA damage than a negative control (NEG), ≥ 90% of the samples caused more damage than cells treated with the vehicles possibly used in perfume's preparations such as methanol (ME) and ethanol (ET), and 11.6% of the perfumes caused more DNA damage than a positive control (hydrogen peroxide). Chromosome breakage expressed as MN frequency was higher in cells treated with 71.4, 64.3, 57.1, and 4.8% of the perfumes than in NEG, cells treated with ME or ET, and another positive control (x-rays), respectively. The genotoxic responses in the comet and MN assays were not correlated. The comet assay indicated that the damage in TK6 cells treated with five PAEs at concentrations of 0.05 and 0.2 ppm either individually or as a mixture did not differ significantly from the damage in cells treated with the perfumes. Unlike the comet assay, the sensitivity of the MN assay to PAEs was weak at both low and high concentrations, and MN frequencies were generally low. This study demonstrates for the first time the possible contribution of PAEs in perfumes to DNA damage and suggests that their use as solvents or fixatives should be regulated. Other ingredients with mutagenic/genotoxic properties, however, may also have contributed to the DNA damage. Future studies should focus on applying a series of assays that use different cellular models with various endpoints to identify the spectrum of genotoxic mechanisms involved.

40 CFR Appendix A to Part 423 - 126 Priority Pollutants

Code of Federal Regulations, 2012 CFR

2012-07-01

...-propylamin 064Pentachlorophenol 065Phenol 066Bis(2-ethylhexyl) phthalate 067Butyl benzyl phthalate 068Di-N-Butyl Phthalate 069Di-n-octyl phthalate 070Diethyl Phthalate 071Dimethyl phthalate 0721,2-benzanthracene...

40 CFR Appendix A to Part 423 - 126 Priority Pollutants

Code of Federal Regulations, 2014 CFR

2014-07-01

...-propylamin 064Pentachlorophenol 065Phenol 066Bis(2-ethylhexyl) phthalate 067Butyl benzyl phthalate 068Di-N-Butyl Phthalate 069Di-n-octyl phthalate 070Diethyl Phthalate 071Dimethyl phthalate 0721,2-benzanthracene...

40 CFR Appendix A to Part 423 - 126 Priority Pollutants

Code of Federal Regulations, 2010 CFR

2010-07-01

...-propylamin 064Pentachlorophenol 065Phenol 066Bis(2-ethylhexyl) phthalate 067Butyl benzyl phthalate 068Di-N-Butyl Phthalate 069Di-n-octyl phthalate 070Diethyl Phthalate 071Dimethyl phthalate 0721,2-benzanthracene...

40 CFR Appendix A to Part 423 - 126 Priority Pollutants

Code of Federal Regulations, 2011 CFR

2011-07-01

...-propylamin 064Pentachlorophenol 065Phenol 066Bis(2-ethylhexyl) phthalate 067Butyl benzyl phthalate 068Di-N-Butyl Phthalate 069Di-n-octyl phthalate 070Diethyl Phthalate 071Dimethyl phthalate 0721,2-benzanthracene...

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Changqing; Gao, Liying; Flaws, Jodi A., E-ma

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily frommore » gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. - Highlights: • Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity. • Prenatal exposure to a phthalate mixture induces F1 ovarian cysts. • Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices. • Prenatal exposure to a phthalate mixture induces F1 breeding complications.« less

EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS

EPA Science Inventory

DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

Assessment of fetal testis function and postnatal development of the male rat following in utero exposure to diethylhexyl phthalate, dipentyl phthalate, diisobutyl phthalate, diisoheptyl phthalate and diisononyl phthalate

EPA Science Inventory

Phthalate esters are a large class of plasticizer compounds widely used in many consumer product applications. Some phthalates induce male fetal endocrine toxicity and reproductive malformations through disruption of hormone production during sexual differentiation. Regulatory ag...

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

PubMed Central

Zhou, Changqing; Gao, Liying; Flaws, Jodi A.

2017-01-01

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. PMID:28126412

Current exposure of 200 pregnant Danish women to phthalates, parabens and phenols.

PubMed

Tefre de Renzy-Martin, Katrine; Frederiksen, Hanne; Christensen, Jeppe Schultz; Boye Kyhl, Henriette; Andersson, Anna-Maria; Husby, Steffen; Barington, Torben; Main, Katharina M; Jensen, Tina Kold

2014-01-01

Many phthalates, parabens and phenols are suspected to have endocrine-disrupting properties in humans. They are found in consumer products, including food wrapping, cosmetics and building materials. The foetus is particularly vulnerable and exposure to these chemicals therefore is of concern for pregnant women. We investigated current exposure to several commonly used phthalates, parabens and phenols in healthy, pregnant Danish women. A total of 200 spot urine samples were collected between 8 and 30 weeks of gestation and analysed for metabolites of ten phenols, seven parabens and 16 phthalate by liquid chromatography-tandem mass spectrometry representing 26 non-persistent compounds. The majority of analytes were present in the urine sample collected from most women who participated. Thus, in 174 of the 200 women, metabolites of more than 13 (>50%) of 26 compounds were detected simultaneously. The number of compounds detected per woman (either as the parent compound or its metabolite(s)) ranged from 7 to 21 with a median of 16. The majority of compounds correlated positively with each other within and between chemical groups, suggesting combined exposure sources. Estimated daily intakes (DIs) of phthalates and bisphenol A (BPA) were below their individual tolerable DI (TDI) and with hazard quotients below 1. In conclusion, we found detectable levels of phthalate metabolites, parabens and phenols in almost all pregnant women, suggesting combined multiple exposures. Although the estimated DI of phthalates and BPA for an individual was below TDI, our results still raise concern, as current toxicological risk assessments in humans do not take into account simultaneous exposure. The true cumulative risk for the foetus may therefore be underestimated.

Phthalate induced toxicity in prostate cancer cell lines and effects of alpha lipoic acid.

PubMed

Kismali, G; Yurdakok-Dikmen, B; Kuzukiran, O; Arslan, P; Filazi, A

2017-01-01

The effects of dimethyl phthalate, diethyl phthalate, diisobutyl phthalate, di-n-butyl phthalate, benzylbutyl phthalate, di-2-ethylhexyl phthalate were investigated on human prostate cancer cell lines DU145 and PC3 in vitro. Standards of dimethyl phthalate, diethyl phthalate, di-isobutyl phthalate, dibutyl phthalate, benzyl butyl phthalate, and di-ethyl hexyl phthalate were used. Alpha lipoic acid was used as antioxidant compound. DU145 and PC3 human prostate carcinoma cells were used. MTT assay were used for cytotoxicity assay. A low dose proliferative effect of phthalates in vitro was observed. With the hypothesis of the inhibition of aerobic glycolysis activity in cancer treatment, α-lipoic acid was applied to cells; where as a contrary to previous studies, no change in the cell proliferation was observed. In combination with ALA, at IC50 and lower doses, an increase of the cytotoxic effect was found for DIBP, DBP and BBP; while for DMP, DEP and DEHP, a decrease was observed for DU145 cells. In PC3 cells, a decrease was observed for DMP, DEP and DBPs; while no significant difference were observed for DEHP, DIBP and BBP. The present study demonstrates preliminary information regarding the low dose proliferative effects of phthalates in prostate cancer in vitro (Tab. 2, Fig. 2, Ref. 65).

Dose-Specific Effects of Di-Isononyl Phthalate on the Endocannabinoid System and on Liver of Female Zebrafish.

PubMed

Forner-Piquer, Isabel; Maradonna, Francesca; Gioacchini, Giorgia; Santangeli, Stefania; Allarà, Marco; Piscitelli, Fabiana; Habibi, Hamid R; Di Marzo, Vincenzo; Carnevali, Oliana

2017-10-01

Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, di-isononyl phthalate (DiNP) has been recently used to replace di(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an endocrine-disrupting chemical; however, little is known about its effects on the endocannabinoid system (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage. To do so, adult female zebrafish were exposed to three concentrations (0.42 µg/L, 4.2 µg/L, and 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of the brain and liver as well as liver histology and image analysis, Fourier-transform infrared spectroscopy imaging, and measurement of endocannabinoid levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of the peripheral ECS and lipid metabolism. A decrease in the levels of ECS components at the central level was observed after exposure to the highest DiNP concentration tested. These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms. Copyright © 2017 Endocrine Society.

Classification of phthalates based on an in vitro neurosphere assay using rat mesencephalic neural stem cells.

PubMed

Ishido, Masami; Suzuki, Junko

2014-02-01

Exposure to environmental neurotoxic chemicals both in utero and during the early postnatal period can cause neurodevelopmental disorders. To evaluate the disruption of neurodevelopmental programming, we previously established an in vitro neurosphere assay system using rat mesencephalic neural stem cells that can be used to evaluate. Here, we extended the assay system to examine the neurodevelopmental toxicity of the endocrine disruptors butyl benzyl phthalate, di-n-butyl phthalate, dicyclohexyl phthalate, diethyl phthalate, di(2-ethyl hexyl) phthalate, di-n-pentyl phthalate, and dihexyl phthalate at a range of concentrations (0-100 μM). All phthalates tested inhibited cell migration with a linear or non-linear range of concentrations when comparing migration distance to the logarithm of the phthalate concentrations. On the other hand, some, but not all, phthalates decreased the number of proliferating cells. Apoptotic cells were not observed upon phthalate exposure under any of the conditions tested, whereas the dopaminergic toxin rotenone induced significant apoptosis. Thus, we were able to classify phthalate toxicity based on cell migration and cell proliferation using the in vitro neurosphere assay.

[Emission of volatile components in carpenter's kumylotox into air].

PubMed

Jodynis-Liebert, J; Kiejnowska, M

1991-01-01

Study was made of Carpenter's Kumylotox, a fungicidal preparation containing: p-cumylphenol, dibutyl phthalate, machine oil, chloroparaffin, a 15% solution of ker-1500 rubber in painter's naphta, and petrol for pastas. The preparation was applied onto boards placed in an experimental chamber at 1-week intervals. In air of the chamber, dibutyl phthalate and p-cumylphenol were determined quantitatively by gas chromatography. The presence of hydrocarbons was recorded by the same method, without quantitative determination. Analyses were continued until the disappearance of the investigated from air. It was found that already after 2 weeks the p-cumylphenol level dropped below the allowable concentration amounting to 0.015 mg/dm3. The dibutyl phthalate level decreased to the allowable concentration (0.05 mg/m3) only after 9 weeks of board ageing. According to analysis by the GC-MS method, aromatic hydrocarbons disappeared from the chamber's air already after 5 weeks, and the remaining hydrocarbons--after 9 weeks.

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice.

PubMed

Zhou, Changqing; Gao, Liying; Flaws, Jodi A

2017-03-01

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200μg/kg/day, 200 and 500mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous determination of 22 phthalate esters in polystyrene food-contact materials by ultra performance convergence chromatography with tandem mass spectrometry.

PubMed

Fan, Ying-Li; Ma, Ming; Cui, He-Zhen; Liu, Shu; Yang, Min-Li; Hou, Xiu-Feng

2018-05-29

A method for the determination of 22 phthalate esters in polystyrene food-contact materials has been established using ultra performance convergence chromatography with tandem mass spectrometry. In this method, 22 phthalate esters were analyzed in less than 3.5 min on an ACQUITY Tours 1-AA column by gradient elution. The mobile phase, the compensation solvent, the flow rate of mobile phase, column temperature and automatic back pressure regulator pressure were optimized, respectively. There was a good linearity of 20 phthalate esters with a range of 0.05-10 mg/L, diisodecyl phthalate and diisononyl phthalate were 0.25-10 mg/L, and the correlation coefficients of all phthalates were higher than 0.99 and those of 16 phthalates were higher than 0.999. The limits of detection and the limits of quantification of 15 phthalates were 0.02 and 0.05 mg/kg, meanwhile diallyl phthalate, diisobutyl phthalate, dimethyl phthalate, di-n-butyl phthalate and di(2-ethylhexyl) phthalate were 0.05 and 0.10 mg/kg, diisodecyl phthalate and diisononyl phthalate were 0.10 and 0.25 mg/kg. The spiked recoveries were 76.26-107.76%, and the relative standard deviations were 1.78-12.10%. Results support this method as an efficient alternative to apply for the simultaneous determination of 22 phthalate esters in common polystyrene food-contact materials. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

40 CFR 464.31 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (dichloromethane) 55. naphthalene 64. pentachlorophenol 65. phenol 66. bis(2-ethylhexyl)phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72. benzo (a)anthracene (1,2... (dichloromethane) 66. bis (2-ethylhexyl) phthalate 77. acenaphthylene 84. pyrene (4) Melting Furnace Scrubber...

40 CFR 464.31 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (dichloromethane) 55. naphthalene 64. pentachlorophenol 65. phenol 66. bis(2-ethylhexyl)phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 71. dimethyl phthalate 72. benzo (a)anthracene (1,2... (dichloromethane) 66. bis (2-ethylhexyl) phthalate 77. acenaphthylene 84. pyrene (4) Melting Furnace Scrubber...

40 CFR Appendix - Tables to Part 132

Code of Federal Regulations, 2012 CFR

2012-07-01

...-Bromophenyl phenyl ether Butyl benzyl phthalate Cadmium Carbon tetrachloride; tetrachloromethane Chlorobenzene...) phthalate Diazinon 1,2:5,6-Dibenzanthracene; dibenz[a,h]anthracene Dibutyl phthalate; di-n-butyl phthalate 1...-dichloropropylene Diethyl phthalate 2,4-Dimethylphenol; 2,4-xylenol Dimethyl phthalate 4,6-Dinitro-o-cresol; 2...

40 CFR 464.11 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... fluoranthene 44. methylene chloride (dichloromethane) 65. phenol 66. bis(2-ethylhexyl) phthalate 67. butyl benzyl phthalate 84. pyrene 85. tetrachloroethylene 87. trichloroethylene (2) Die Casting (§ 464.15(c...) phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 72. benzo (a)anthracene...

40 CFR 464.11 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... fluoranthene 44. methylene chloride (dichloromethane) 65. phenol 66. bis(2-ethylhexyl) phthalate 67. butyl benzyl phthalate 84. pyrene 85. tetrachloroethylene 87. trichloroethylene (2) Die Casting (§ 464.15(c...) phthalate 67. butyl benzyl phthalate 68. di-n-butyl phthalate 70. diethyl phthalate 72. benzo (a)anthracene...

Phthalate esters in main source water and drinking water of Zhejiang Province (China): Distribution and health risks.

PubMed

Wang, Xiaofeng; Lou, Xiaoming; Zhang, Nianhua; Ding, Gangqiang; Chen, Zhijian; Xu, Peiwei; Wu, Lizhi; Cai, Jianmin; Han, Jianlong; Qiu, Xueting

2015-10-01

To evaluate the distributions and health risks of phthalate esters in the main source water and corresponding drinking water of Zhejiang Province, the concentrations of 16 phthalate esters in water samples from 19 sites were measured from samples taken in the dry season and wet season. The concentration of the total phthalate ester congeners in source water ranged from 1.07 μg/L to 7.12 μg/L in the wet season, from 0.01 μg/L to 1.58 μg/L in the dry season, from 1.18 μg/L to 15.28 μg/L from drinking water in the wet season, and from 0.16 μg/L to 1.86 μg/L from drinking water in the dry season. Of the 16 phthalate esters, dimethyl phthalate, dibutyl phthalate, di-(2-ethyl-hexyl) phthalate, di-iso-butyl phthalate, bis-2-n-butoxyethyl phthalate, and dicyclohexyl phthalate were present in the samples analyzed, dominated by di-iso-butyl phthalate and di-(2-ethyl-hexyl) phthalate. The concentrations of phthalate esters in the wet season were all relatively higher than those in the dry season, and the drinking water had higher concentrations of phthalate esters than source water. The phthalate ester congeners studied pose little health risk to nearby citizens. Environ Toxicol Chem 2015;34:2205-2212. © 2015 SETAC. © 2015 SETAC.

Phthalates biodegradation in the environment.

PubMed

Liang, Da-Wei; Zhang, Tong; Fang, Herbert H P; He, Jianzhong

2008-08-01

Phthalates are synthesized in massive amounts to produce various plastics and have become widespread in environments following their release as a result of extensive usage and production. This has been of an environmental concern because phthalates are hepatotoxic, teratogenic, and carcinogenic by nature. Numerous studies indicated that phthalates can be degraded by bacteria and fungi under aerobic, anoxic, and anaerobic conditions. This paper gives a review on the biodegradation of phthalates and includes the following aspects: (1) the relationship between the chemical structure of phthalates and their biodegradability, (2) the biodegradation of phthalates by pure/mixed cultures, (3) the biodegradation of phthalates under various environments, and (4) the biodegradation pathways of phthalates.

Phthalates and other additives in plastics: human exposure and associated health outcomes

PubMed Central

Meeker, John D.; Sathyanarayana, Sheela; Swan, Shanna H.

2009-01-01

Concern exists over whether additives in plastics to which most people are exposed, such as phthalates, bisphenol A or polybrominated diphenyl ethers, may cause harm to human health by altering endocrine function or through other biological mechanisms. Human data are limited compared with the large body of experimental evidence documenting reproductive or developmental toxicity in relation to these compounds. Here, we discuss the current state of human evidence, as well as future research trends and needs. Because exposure assessment is often a major weakness in epidemiological studies, and in utero exposures to reproductive or developmental toxicants are important, we also provide original data on maternal exposure to phthalates during and after pregnancy (n = 242). Phthalate metabolite concentrations in urine showed weak correlations between pre- and post-natal samples, though the strength of the relationship increased when duration between the two samples decreased. Phthalate metabolite levels also tended to be higher in post-natal samples. In conclusion, there is a great need for more human studies of adverse health effects associated with plastic additives. Recent advances in the measurement of exposure biomarkers hold much promise in improving the epidemiological data, but their utility must be understood to facilitate appropriate study design. PMID:19528058

Determination of phthalic acid esters in different baby food samples by gas chromatography tandem mass spectrometry.

PubMed

Socas-Rodríguez, Bárbara; González-Sálamo, Javier; Herrera-Herrera, Antonio V; Santana-Mayor, Álvaro; Hernández-Borges, Javier

2018-03-09

In this work, a new method has been developed for the determination of 14 phthalic acid esters (i.e., benzylbutyl phthalate (BBP), bis-2-n-butoxyethyl phthalate (DBEP), dibutyl phthalate (DBP), dicyclohexyl phthalate (DCHP), bis-2-ethoxyethyl phthalate (DEEP), diethyl phthalate (DEP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), bis-isopentyl phthalate (DIPP), bis (2-methoxyethyl) phthalate (DMEP), dimethyl phthalate (DMP), di-n-octyl phthalate (DNOP), bis-n-pentyl phthalate (DNPP), dipropyl phthalate (DPP)) and one adipate (bis (2-ethylhexyl) adipate (DEHA)) in different baby foods. Separation was carried out by gas chromatography triple quadrupole tandem mass spectrometry while the previous extraction of the samples was carried out using the QuEChERS method. The methodology was validated for four baby food samples (two fruit compotes of different compositions and two meat and fish purees with vegetables) using dibutyl phthalate-3,4,5,6-d 4 (DBP-d 4 ) as internal standard. Determination coefficients (R 2 ) of matrix-matched calibration curves were above 0.9922 in all cases while relative recovery values ranged between 70 and 120%, with relative standard deviation values below 19%. The limits of quantification of the method ranged between 0.03 and 1.11 μg/kg. Finally, the analysis of commercially available samples was carried out finding the presence of BBP, DEHA, DEP, DIDP, and DPP in some of the studied samples.

Survey of phthalate pollution in arable soils in China.

PubMed

Hu, Xiao-yu; Wen, Bei; Shan, Xiao-quan

2003-08-01

The problem of pollution by phthalates is of global concern due to their widespread occurrence, toxicity and endocrine disruption properties. The contamination by phthalates such as dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) in 23 arable soils throughout China was investigated to evaluate the present pollution situation. The survey results demonstrated that phthalates were ubiquitous pollutants in soils in China. The total concentrations of phthalates differed from one location to another, and ranged from 0.89 to 10.03 mg kg(-1) with a median concentration of 3.43 mg kg(-1). Among the phthalates, DEHP was dominant and detected in all 23 soils. DEP and DBP were also in abundance, and DMP was rarely detected. Similar contamination patterns were observed in all 23 soils. A distinct feature of phthalate pollution in China was that the average concentration in northern China was higher than that in southern China. In addition, a close relationship was observed between the concentration of phthalates in soils and the consumption of agricultural film. The correlation showed that the application of agriculture film might be a significant pollution source of phthalates in arable soils of China. The potential risk of phthalates in soils was assessed on the basis of current guide values and limits.

In utero exposure to dietheylhexyl phthalate differentially affects fetal testosterone and insl3 levels in the testes of male Sprague Dawley and Wistar rats: A dose response study

EPA Science Inventory

We previously reported that 750 mg/kg/day of diethylhexyl phthalate (DEHP) administered in utero during the period of sex differentiation resulted in a higher prevalence of gubernacular lesions in male Wistar offspring than in the male Sprague Dawley (SD) rat offspring, whereas D...

Exposure to Bisphenol A and Other Phenols in Neonatal Intensive Care Unit Premature Infants

PubMed Central

Calafat, Antonia M.; Weuve, Jennifer; Ye, Xiaoyun; Jia, Lily T.; Hu, Howard; Ringer, Steven; Huttner, Ken; Hauser, Russ

2009-01-01

Objective We previously demonstrated that exposure to polyvinyl chloride plastic medical devices containing di(2-ethylhexyl) phthalate (DEHP) was associated with higher urinary concentrations of several DEHP metabolites in 54 premature infants in two neonatal intensive care units than in the general population. For 42 of these infants, we evaluated urinary concentrations of several phenols, including bisphenol A (BPA), in association with the use of the same medical devices. Measurements We measured the urinary concentrations of free and total (free plus conjugated) species of BPA, triclosan, benzophenone-3, methyl paraben, and propyl paraben. Results The percentage of BPA present as its conjugated species was > 90% in more than three-quarters of the premature infants. Intensity of use of products containing DEHP was strongly associated with BPA total concentrations but not with any other phenol. Adjusting for institution and sex, BPA total concentrations among infants in the group of high use of DEHP-containing products were 8.75 times as high as among infants in the low use group (p < 0.0001). Similarly, after adjusting for sex and DEHP-containing product use category, BPA total concentrations among infants in Institution A were 16.6 times as high as those among infants in Institution B (p < 0.0001). Conclusion BPA geometric mean urinary concentration (30.3 μg/L) among premature infants undergoing intensive therapeutic medical interventions was one order of magnitude higher than that among the general population. Conjugated species were the primary urinary metabolites of BPA, suggesting that premature infants have some capacity to metabolize BPA. The differences in exposure to BPA by intensity of use of DEHP-containing medical products highlight the need for further studies to determine the specific source(s) of exposure to BPA. PMID:19440505

A study on phthalate metabolites, bisphenol A and nonylphenol in the urine of Chinese women with unexplained recurrent spontaneous abortion.

PubMed

Peng, Fanli; Ji, Wenliang; Zhu, Feng; Peng, Danhong; Yang, Miao; Liu, Ran; Pu, Yuepu; Yin, Lihong

2016-10-01

Humans are widely exposed to phthalates, bisphenol A and nonylphenol owing to the ubiquitous use of these chemicals in consumer products. Increasing attention has been paid to exposure to phthalates, bisphenol A and nonylphenol because of their potential adverse effects on human fertility. A validated method was developed to investigate the three classes of environmental estrogen, mentioned above, in the urine of Chinese women of Nanjing area with unexplained recurrent spontaneous abortion. Solid-phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used. In this method, amounts of bisphenol A (BPA), nonylphenol (NP) and four phthalate metabolites, mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono-2-ethylhexyl phthalate (MEHP), along with their isotope labeled internal standards, were measured using UPLC-MS/MS operated in negative electrospray ionization multiple reaction monitoring mode. The limits of detection were 0.3ng/mL for the four phthalate metabolites, and 0.5ng/mL for bisphenol A and nonylphenol. For women with unexplained recurrent spontaneous abortion, the mean concentrations of MBP, MiBP, MBzP, MEHP, BPA and 4-n-NP were 6.52±6.04, 5.51±4.19, 0.53±0.42, 10.12±4.16, 7.13±7.42, 0.41±0.49ng/mL (mean±SD), respectively. For the control group, the mean concentrations of the corresponding analytes were 4.15±3.57, 2.96±3.30, 0.46±0.49, 6.50±2.81, 4.43±2.23,0.48±0.43ng/mL (mean±SD), respectively. Levels of MiBP and MEHP were significantly different between the two groups, using Wilcoxon rank sum tests. This method can be applied in epidemiological studies to explore the association between exposure to environmental estrogens and relevant adverse outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Phthalate concentrations in house dust in relation to autism spectrum disorder and developmental delay in the CHildhood Autism Risks from Genetics and the Environment (CHARGE) study.

PubMed

Philippat, Claire; Bennett, Deborah H; Krakowiak, Paula; Rose, Melissa; Hwang, Hyun-Min; Hertz-Picciotto, Irva

2015-06-26

Phthalates are endocrine-disrupting chemicals that influence thyroid hormones and sex steroids, both critical for brain development. We studied phthalate concentrations in house dust in relation to the risks of developing autism spectrum disorder (ASD) or developmental delay (DD). Participants were a subset of children from the CHARGE (CHildhood Autism Risks from Genetics and the Environment) case-control study. ASD and DD cases were identified through the California Department of Developmental Services system or referrals; general population controls were randomly sampled from state birth files and frequency-matched on age, sex, and broad geographic region to ASD cases. All children (50 ASD, 27 DD, 68 typically developing (TD)) were assessed with Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales (VABS) and Aberrant Behavior Checklist. We measured 5 phthalates in dust collected in the child's home using a high volume small surface sampler. None of the phthalates measured in dust was associated with ASD. After adjustment, we observed greater di(2-ethylhexyl) phthalate (DEHP) and butylbenzyl phthalate (BBzP) concentrations in indoor dust from homes of DD children: Odds ratios (OR) were 2.10 (95% confidence interval (CI); 1.10; 4.09) and 1.40 (95% CI; 0.97; 2.04) for a one-unit increase in the ln-transformed DEHP and BBzP concentrations, respectively. Among TD children, VABS communication, daily living, and adaptive composite standard scores were lower, in association with increased diethyl phthalate (DEP) concentrations in dust. Participants with higher dibutyl phthalate (DBP) concentrations in house dust also trended toward reduced performance on these subscales. Among ASD and DD boys, higher indoor dust concentrations of DEP and DBP were associated with greater hyperactivity-impulsivity and inattention. House dust levels of phthalates were not associated with ASD. The inability to distinguish past from recent exposures in house dust and the fact that house dust does not capture exposure from all sources, limit the interpretation of both positive and null findings and further work is needed. However, the associations observed for DEP and DBP with impairments in several adaptive functions and greater hyperactivity, along with evidence for increased risk of DD raise concerns that these chemicals may affect neurodevelopment in children.

Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erkekoglu, Pinar; Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara; Rachidi, Walid

2010-10-01

Di(2-ethylhexyl)-phthalate (DEHP) is the most abundantly used phthalate derivative, inevitable environmental exposure of which is suspected to contribute to the increasing incidence of testicular dysgenesis syndrome in humans. Oxidative stress and mitochondrial dysfunction in germ cells are suggested to contribute to phthalate-induced disruption of spermatogenesis in rodents, and Leydig cells are one of the main targets of phthalates' testicular toxicity. Selenium is known to be involved in the modulation of intracellular redox equilibrium, and plays a critical role in testis, sperm, and reproduction. This study was aimed to investigate the oxidative stress potential of DEHP and its consequences in testicularmore » cells, and examine the possible protective effects of selenium using the MA-10 mouse Leydig tumor cell line as a model. In the presence and absence of selenium compounds [30 nM sodium selenite (SS), and 10 {mu}M selenomethionine (SM)], the effects of exposure to DEHP and its main metabolite mono(2-ethylhexyl)-phthalate (MEHP) on the cell viability, enzymatic and non-enzymatic antioxidant status, ROS production, p53 expression, and DNA damage by alkaline Comet assay were investigated. The overall results of this study demonstrated the cytotoxicity and genotoxicity potential of DEHP, where MEHP was found to be more potent than the parent compound. SS and SM produced almost the same level of protection against antioxidant status modifying effects, ROS and p53 inducing potentials, and DNA damaging effects of the two phthalate derivatives. It was thus shown that DEHP produced oxidative stress in MA-10 cells, and selenium supplementation appeared to be an effective redox regulator in the experimental conditions used in this study, emphasizing the critical importance of the appropriate selenium status.« less

40 CFR 463.33 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... BAT effluent limitations guidelines for bis(2-ethylhexyl) phthalate, di-n-butyl phthalate, and dimethyl phthalate are reserved. (b) The Agency has determined that, with the exception of bis(2-ethylhexyl) phthalate, di-n-butyl phthalate, and dimethyl phthalate, there are no toxic pollutants in treatable...

40 CFR 463.33 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2014 CFR

2014-07-01

... BAT effluent limitations guidelines for bis(2-ethylhexyl) phthalate, di-n-butyl phthalate, and dimethyl phthalate are reserved. (b) The Agency has determined that, with the exception of bis(2-ethylhexyl) phthalate, di-n-butyl phthalate, and dimethyl phthalate, there are no toxic pollutants in treatable...

75 FR 31426 - Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... health of all phthalates and phthalate alternatives as used in children's toys and child care articles... the CPSIA permanently prohibits the sale of any ``children's toy or child care article'' containing... articles'' containing more than 0.1 percent of each of three additional phthalates-- diisononyl phthalate...

The influence of resource strategies on childhood phthalate exposure--the role of REACH in a zero waste society.

PubMed

Lee, Jihyun; Pedersen, Anders Branth; Thomsen, Marianne

2014-12-01

The present study aims to investigate how resource strategies, which intend to reduce waste and increase recycling, influence on human exposure to hazardous chemicals from material recycling. In order to examine the flows of hazardous chemicals in recycled material, a mass flow analysis of plastics and paper at European level, including the flow of phthalates, i.e. di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and benzyl-butyl phthalate (BBP), has been performed. The result for the year 2012 shows that 26% of plastic wastes and 60% of paper consumed in Europe were recycled. This corresponds to the finding that approximately 4% of DEHP and BBP and 18% of DBP annual demands in Europe as raw material re-enter the product cycle with recycled plastics and paper. To examine the potential contribution of the phthalate exposure through recycled plastics and paper, a case study assessing the childhood exposures to phthalates from foods packed in recycled paper and plastics has been performed for 2-year-old children in Denmark. The result verifies that an increase in recycled paperboard and PET bottles in food packaging material causes a significant increase in childhood exposure to DBP corresponding to an additional exposure of 0.116-0.355 μg/kg bw/day; up to 18% of the total DBP exposure in Danish 2-year-olds. While most of the DEHP exposure can be explained, more than 50% of DBP and 70% of BBP exposure sources still remain to be identified. Finally, a conceptual framework for a circular economy based on sustainable and clean resource flows is proposed in order to increase material recycling without increasing adverse health effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prohibition of Children’s Toys and Child Care Articles Containing Specified Phthalates. Final rule.

PubMed

2017-10-27

The United States Consumer Product Safety Commission (Commission or CPSC) issues this final rule prohibiting children's toys and child care articles that contain concentrations of more than 0.1 percent of diisononyl phthalate (DINP), diisobutyl phthalate (DIBP), di-n-pentyl phthalate (DPENP), di-n-hexyl phthalate (DHEXP), and dicyclohexyl phthalate (DCHP). Section 108 of the Consumer Product Safety Improvement Act of 2008 (CPSIA) established permanent and interim prohibitions on the sale of certain consumer products containing specific phthalates. That provision also directed the CPSC to convene a Chronic Hazard Advisory Panel (CHAP) to study the effects on children's health of all phthalates and phthalate alternatives as used in children's toys and child care articles and to provide recommendations to the Commission regarding whether any phthalates or phthalate alternatives, other than those already permanently prohibited, should be prohibited. The CPSIA requires the Commission to promulgate a final rule after receiving the final CHAP report. This rule fulfills that requirement.

40 CFR Appendix J to Part 122 - NPDES Permit Testing Requirements for Publicly Owned Treatment Works (§ 122.21(j))

Code of Federal Regulations, 2012 CFR

2012-07-01

...-ethylhexyl) phthalate 4-bromophenyl phenyl ether Butyl benzyl phthalate 2-chloronaphthalene 4-chlorophenyl phenyl ether Chrysene Di-n-butyl phthalate Di-n-octyl phthalate Dibenzo(a,h)anthracene 1,2-dichlorobenzene 1,3-dichlorobenzene 1,4-dichlorobenzene 3,3-dichlorobenzidine Diethyl phthalate Dimethyl phthalate...

Growth and antioxidant defense responses of wheat seedlings to di-n-butyl phthalate and di (2-ethylhexyl) phthalate stress.

PubMed

Gao, Minling; Dong, Youming; Zhang, Ze; Song, Wenhua; Qi, Yun

2017-04-01

Phthalate acid esters (PAEs) are vital environmental hormone-like chemicals that are noxious to plants, animals, and human beings. In this study, the influences of di-n-butyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) on the seed germination, root morphology, and various physiological changes of wheat seedlings were investigated by analyzing superoxide anion (O 2 - ) accumulation, antioxidant enzyme activity, and lipid peroxidation. DBP and DEHP were found to obviously inhibit germination only at high concentrations, but significantly affected root morphology even at lower concentrations. Their toxic effects were the most severe on root elongation, followed by shoot elongation, and were the least severe on germination rate, indicating that root elongation was the best index for evaluating DBP and DEHP eco-toxicity. DBP and DEHP also enhanced O 2 - and malondialdehyde levels and membrane permeability, as well as produced changes in the antioxidant status and PAE content in the stem and leaf (combined tissues, hereafter shoot) and root tissues. The activities of superoxide dismutase, catalase, and peroxidase increased at low and medium DBP and DEHP concentrations, but declined at high PAE concentrations. These results indicated that PAEs could exert oxidative damage in the early development stage of wheat, particularly at higher concentrations. DBP and DEHP accumulation was higher in the roots than in the shoot tissues, and their levels in these tissues increased with increasing PAE concentrations, supporting their more-serious toxic effects on roots than those on shoots. Further, the physicochemical properties of DBP rendered it more harmful than DEHP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dibutyl Phthalate (DBP)-Induced Apoptosis and Neurotoxicity are Mediated via the Aryl Hydrocarbon Receptor (AhR) but not by Estrogen Receptor Alpha (ERα), Estrogen Receptor Beta (ERβ), or Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Mouse Cortical Neurons.

PubMed

Wójtowicz, Anna K; Szychowski, Konrad A; Wnuk, Agnieszka; Kajta, Małgorzata

2017-01-01

Dibutyl phthalate (di-n-butyl phthalate, DBP) is one of the most commonly used phthalate esters. DBP is widely used as a plasticizer in a variety of household industries and consumer products. Because phthalates are not chemically bound to products, they can easily leak out to enter the environment. DBP can pass through the placental and blood-brain barriers due to its chemical structure, but little is known about its mechanism of action in neuronal cells. This study demonstrated the toxic and apoptotic effects of DBP in mouse neocortical neurons in primary cultures. DBP stimulated caspase-3 and LDH activities as well as ROS formation in a concentration (10 nM-100 µM) and time-dependent (3-48 h) manner. DBP induced ROS formation at nanomolar concentrations, while it activated caspase-3 and LDH activities at micromolar concentrations. The biochemical effects of DBP were accompanied by decreased cell viability and induction of apoptotic bodies. Exposure to DBP reduced Erα and Pparγ mRNA expression levels, which were inversely correlated with protein expression of the receptors. Treatment with DBP enhanced Ahr mRNA expression, which was reflected by the increased AhR protein level observed at 3 h after exposure. ERα, ERβ, and PPARγ antagonists stimulated DBP-induced caspase-3 and LDH activities. AhR silencing demonstrated that DBP-induced apoptosis and neurotoxicity are mediated by AhR, which is consistent with the results from DBP-induced enhancement of AhR mRNA and protein expression. Our study showed that AhR is involved in DBP-induced apoptosis and neurotoxicity, while the ERs and PPARγ signaling pathways are impaired by the phthalate.

Association of Endocrine Disruptors and Obesity: Perspectives from Epidemiologic Studies

PubMed Central

Hatch, Elizabeth E.; Nelson, Jessica W.; Stahlhut, Richard W.; Webster, Thomas F.

2010-01-01

Although changes in diet and physical activity are undoubtedly key causal factors related to the increase in obesity, there is growing interest in the possibility that endocrine disrupting chemicals (EDCs) may affect obesity-related pathways by altering cell signaling involved in weight and lipid homeostasis. Proposed mechanisms that could underlie associations between EDCs and obesity include effects on thyroid and steroid hormones, and activation of peroxisome proliferator-activated receptors (PPARs) which play a major role in adipocyte differentiation and energy storage. Most evidence supporting the hypothesis that EDCs affect obesity comes from laboratory studies. We summarize the limited epidemiologic literature on the topic, including prospective studies of human prenatal exposure to EDCs. We also present findings from a cross-sectional study of levels of six phthalate metabolites and body mass index (BMI) and waist circumference (WC), using data from the U.S. National Health and Nutrition Examination Survey (NHANES). We found positive associations between BMI and WC among adult males for most phthalate metabolites. For example, in males aged 20–59, the adjusted mean BMI across quartiles of mono-benzyl phthalate (MBzP) was 26.7, 27.2, 28.4, 29.0 (p-trend=0.0002). In females, BMI and WC increased with quartiles of mono-ethyl phthalate (MEP) in 12–19 year olds (adjusted mean BMI=22.9, 23.8, 24.1, 24.7, p-trend =0.03), and a similar but less strong pattern was seen in 20–59 year olds. In contrast, higher levels of mono-2-ethylhexyl phthalate (MEHP) were associated with lower BMI in adolescent girls and females aged 20–59. This exploratory analysis found several associations between phthalate metabolites and obesity, including notable differences by gender. However, the cross-sectional data is a limitation. Additional prospective studies of the association between exposures to EDCs, especially during development, and obesity are warranted. As this field of research advances, there are challenging methodologic questions that must be considered by both epidemiologists and toxicologists. PMID:20113374

biologically relevant effects of dipentyl phthalate

EPA Pesticide Factsheets

metadata sheet, data sheet for each table and figure in the published manuscriptThis dataset is associated with the following publication:Gray , E., J. Furr , K. Tatum-Gibbs, C. Lambright , H. Sampson, B. Hannas, V. Wilson , A. Hotchkiss , and P. Foster. Establishing the Biological Relevance of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels. TOXICOLOGICAL SCIENCES. Society of Toxicology, 149(1): 178-91, (2016).

[Survey of plasticizers in polyvinyl chloride toys].

PubMed

Abe, Yutaka; Yamaguchi, Miku; Mutsuga, Motoh; Hirahara, Yoshichika; Kawamura, Yoko

2012-01-01

Plasticizers in 101 samples of polyvinyl chloride (PVC) toys on the Japanese market were surveyed. No phthalates were detected in designated toys, though bis(2-ethylhexyl)phthalate, diisononyl phthalate, diisobutyl phthalate, dibutyl phthalate, diisodecyl phthalate and benzyl butyl phthalate were detected in more than half of other toys. 2,2,4-Tributyl-1,3-pentanediol diisobutylate, o-acetyl tributyl citrate, adipates and diacetyl lauroyl glycerol, which are alternative plasticizers to phthalates, were detected. The results of structural analysis confirmed the presence of di(2-ethylhexyl)terephthalate, tributyl citrate, diisononyl 1,2-cyclohexanedicarboxylate and neopentyl glycol esters; these have not previonsly been reported in Japan. There appears to be a shift in plasticizers used for designated toys from phthalates to new plasticizers, and the number of different plasticizers is increasing.

Determination of phthalate esters from environmental water samples by micro-solid-phase extraction using TiO2 nanotube arrays before high-performance liquid chromatography.

PubMed

Zhou, Qingxiang; Fang, Zhi; Liao, Xiangkun

2015-07-01

We describe a highly sensitive micro-solid-phase extraction method for the pre-concentration of six phthalate esters utilizing a TiO2 nanotube array coupled to high-performance liquid chromatography with a variable-wavelength ultraviolet visible detector. The selected phthalate esters included dimethyl phthalate, diethyl phthalate, dibutyl phthalate, butyl benzyl phthalate, bis(2-ethylhexyl)phthalate and dioctyl phthalate. The factors that would affect the enrichment, such as desorption solvent, sample pH, salting-out effect, extraction time and desorption time, were optimized. Under the optimum conditions, the linear range of the proposed method was 0.3-200 μg/L. The limits of detection were 0.04-0.2 μg/L (S/N = 3). The proposed method was successfully applied to the determination of six phthalate esters in water samples and satisfied spiked recoveries were achieved. These results indicated that the proposed method was appropriate for the determination of trace phthalate esters in environmental water samples. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

AN ASSESSMENT OF THE TOXICITY OF PHTHALATE ESTERS TO FRESHWATER BENTHOS. 1. AQUEOUS EXPOSURES

EPA Science Inventory

Tests were performed with the freshwater invertebrates, Hyalella azteca, Chironomus tentans, and Lumbriculus variegatus to determine the acute toxicity of six phthalate esters, including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butylbenzyl ph...

Phthalate exposure through food and consumers' risk perception of chemicals in food.

PubMed

Dickson-Spillmann, Maria; Siegrist, Michael; Keller, Carmen; Wormuth, Matthias

2009-08-01

Phthalates have been detected in various types of retail foods. Consumers' exposure to phthalates is common. Consumers are concerned about chemicals in food. Our aim was to investigate the relationships between consumers' exposure to phthalates through food, consumers' interest in a natural and healthy diet, risk perception of food chemicals, and consumers' diet patterns. We collected data through a mail survey in the adult Swiss-German population (N = 1,200). We modeled exposure to di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and diethyl phthalate (DEP) based on a food frequency questionnaire and phthalate concentrations reported from food surveys. Using rating scales, we assessed risk perceptions of chemicals in food and interest in a natural and healthy diet. Higher risk perceptions and higher natural and healthy diet interest were associated with higher daily doses of DEHP, BBP, and DEP. No health risk from phthalates in food was identified for the vast majority of the population. Four consumers' diet clusters were discerned, with differences in phthalate exposure, risk perceptions, and interest in a natural and healthy diet. This study shows that even those consumers who express strong interest in natural food and low acceptance of food chemicals, and who try to make respective food choices, are exposed to contaminants such as phthalates.

Comparison, association, and risk assessment of phthalates in floor dust at different indoor environments in Delaware, USA.

PubMed

Bi, Xiaolong; Yuan, Shoujun; Pan, Xiaojun; Winstead, Cherese; Wang, Qiquan

2015-01-01

This study aimed to compare and assess phthalate contamination in various indoor environments. In this study, 44 floor dust samples from different indoor environments in Delaware, USA were collected and analyzed for 14 phthalates using gas chromatography-mass spectrometry. Phthalates were detected in all dust samples with the total concentration ranging from 84 to 7117 mg kg(-1). DEHP (di-2-ethylhexyl phthalate), BzBP (benzylbutyl phthalate), DBP (dibutyl phthalate), and DiBP (di-isobutyl phthalate) were both the most frequently and abundantly detected phthalates. The average concentration of total phthalates in dust from offices, student dorms, gyms, stores, and daycare centers was found to be significantly or insignificantly (P = 0.05) higher than that in dust from houses and apartments. Plastic flooring materials and the application of floor care chemical products were positively associated with total phthalate concentration in floor dust. Toxicological risk assessment indicated that an investigated daycare center in this study was the only indoor environment that may cause the intake amount of DEHP of infants, toddlers, and children via dust ingestion to exceed the reference dose established by the U.S. Environmental Protection Agency (USEPA). Regular monitoring on phthalate contamination in sensitive indoor environments is recommended.

Current status and historical variations of phthalate ester (PAE) contamination in the sediments from a large Chinese lake (Lake Chaohu).

PubMed

Kang, Lei; Wang, Qing-Mei; He, Qi-Shuang; He, Wei; Liu, Wen-Xiu; Kong, Xiang-Zhen; Yang, Bin; Yang, Chen; Jiang, Yu-Jiao; Xu, Fu-Liu

2016-06-01

The residual levels of phthalate esters (PAEs) in the surface and two core sediments from Lake Chaohu were measured with a gas chromatograph-mass spectrometer (GC-MS). The temporal-spatial distributions, compositions of PAEs, and their effecting factors were investigated. The results indicated that di-n-butyl phthalate (DnBP), diisobutyl phthalate (DIBP), and di(2-ethylhexyl) phthalate (DEHP) were three dominant PAE components in both the surface and core sediments. The residual level of total detected PAEs (∑PAEs) in the surface sediments (2.146 ± 2.255 μg/g dw) was lower than that in the western core sediments (10.615 ± 9.733 μg/g) and in the eastern core sediments (5.109 ± 4.741 μg/g). The average content of ∑PAEs in the surface sediments from the inflow rivers (4.128 ± 1.738 μg/g dw) was an order of magnitude higher than those from the lake (0.323 ± 0.093 μg/g dw), and there were similar PAE compositions between the lake and inflow rivers. This finding means that there were important effects of PAE input from the inflow rivers on the compositions and distributions of PAEs in the surface sediments. An increasing trend was found for the residual levels of ΣPAEs, DnBP, and DIBP from the bottom to the surface in both the western and eastern core sediments. Increasing PAE usage with the population growth, urbanization, and industrial and agricultural development in Lake Chaohu watershed would result in the increasing production of PAEs and their resulting presence in the sediments. The significant positive relationships were also found between the PAE contents and the percentage of sand particles, as well as TOC contents in the sediment cores.

Phthalate Exposure and Children’s Health

PubMed Central

Braun, Joseph M.; Sathyanarayana, Sheela; Hauser, Russ

2013-01-01

Purpose of Review Phthalates are multifunctional chemicals used in personal care products, medications, and plastics. We reviewed the epidemiological literature examining the relationship between early life phthalate exposure and pediatric health outcomes. Recent Findings Five studies from Asia, Europe, and the US suggest that childhood exposure to di-2-ethylhexyl phthalate (DEHP) and butylbenzyl phthalate (BBzP) may increase the risk of allergic diseases including asthma and eczema. Six studies from four different prospective cohorts report that gestational BBzP, DEHP, di-butyl phthalate (DBP), and di-ethyl phthalate (DEP) exposures are associated with alterations in infant/toddler physical development as well as parent-reported externalizing, internalizing, and autistic-like child behavior. However, there are inconsistencies related to the specific phthalates and behavioral domains. Two small studies report shorter anogenital distance among male infants with higher gestational phthalate exposure. Summary Several epidemiological studies suggest fetal and childhood exposure to some phthalates may perturb normal development, with several studies consistently reporting increased risk of allergic diseases with DEHP and BBzP exposure. While anticipatory guidance is not evidence-based at this time, providers can counsel concerned patients to reduce phthalate exposures in order to protect the developing fetus and child from potential adverse health outcomes. PMID:23429708

Findings of 2731 suspected phthalate-tainted foodstuffs during the 2011 phthalates incident in Taiwan.

PubMed

Wu, Chia-Fang; Chang-Chien, Guo-Ping; Su, Sheng-Wen; Chen, Bai-Hsiun; Wu, Ming-Tsang

2014-09-01

This study aims to investigate what kinds of food products were contaminated by phthalates, mainly di-(2-ethylhexyl)phthalate (DEHP) and/or di-isononyl phthalate (DINP), during the 2011 phthalates incident in Taiwan, and whether the DEHP and/or DINP concentrations of some affected foods decreased after this incident. During May-October, 2011, 2731 food items were sent by individual citizens or companies to a government-accredited laboratory for the analyses of six main phthalate chemicals, including DEHP, DINP, di-isodecyl phthalate, di(n-octyl)phthalate, di-n-butyl phthalate, and butyl benzyl phthalate. A concentration of ≥1 ppm for any of the six phthalate chemicals in the foods studied was defined as positive. The overall positive rate was 16.2%. The positive rate of possibly affected foods was similar between sanctioned and non-sanctioned foods categorized as "Others" by the government (16.0% vs. 16.4%). There were 33 food items, most of which belonged to the Others category, sent twice by companies on different dates. Of these, the positive rates of affected foods significantly decreased from 39.4% for DEHP and 72.7% for DINP at the first analyses to 3.0% for DEHP and 9.1% for DINP at the second, respectively (p < 0.0001). Besides the government-sanctioned foods, foods from the Others category were still affected by phthalate contamination. Thus, vigilant scrutiny of food safety in modern life is necessary. Copyright © 2014. Published by Elsevier B.V.

Phthalates and thyroid function in preschool age children: Sex specific associations.

PubMed

Morgenstern, Rachelle; Whyatt, Robin M; Insel, Beverly J; Calafat, Antonia M; Liu, Xinhua; Rauh, Virginia A; Herbstman, Julie; Bradwin, Gary; Factor-Litvak, Pam

2017-09-01

Research relating either prenatal or concurrent measures of phthalate exposure to thyroid function in preschool children is inconclusive. In a study of inner-city mothers and their children, metabolites of di-n-butyl phthalate, butylbenzyl phthalate, di-isobutyl phthalate, di(2-ethylhexyl) phthalate, and diethyl phthalate were measured in a spot urine sample collected from women in late pregnancy and from their children at age 3years. We measured children's serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) at age 3. Linear regression models were used to investigate the associations between phthalate metabolites, measured in maternal urine during late pregnancy and measured in child urine at age 3 and thyroid function measured at age 3. Mean concentrations (ranges) were 1.42ng/dL (1.02-2.24) for FT4, and 2.62uIU/mL (0.61-11.67) for TSH. In the children at age 3, among girls, FT4 decreased with increasing log e mono-n-butyl phthalate [estimated b=-0.06; 95% CI: (-0.09, -0.02)], log e mono-isobutyl phthalate [b=-0.05; 95% CI: (-0.09, -0.01)], log e monoethyl phthalate [b=-0.04; 95% CI: (-0.07, -0.01)], and log e mono(2-ethyl-5-hydroxyhexyl) phthalate [b=-0.04; 95% CI: (-0.07, -0.003)] and log e mono(2-ethyl-5-oxy-hexyl) phthalate [b=-0.04; 95% CI: (-0.07, -0.004)]. In contrast, among boys, we observed no associations between FT4 and child phthalate metabolites at age 3. On the other hand, in late gestation, FT4 increased with increasing log e mono-(2-ethylhexyl) phthalate [estimated b=0.04; 95% CI: (0.02, 0.06)] and no sex difference was observed. We found no associations between phthalate biomarkers measured in either the child or prenatal samples and TSH at age 3. The data show inverse and sex specific associations between specific phthalate metabolites measured in children at age 3 and thyroid function in preschool children. These results may provide evidence for the hypothesis that reductions in thyroid hormones mediate associations between early life phthalate exposure and child cognitive outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phthalate and non-phthalate plasticizers in indoor dust from childcare facilities, salons, and homes across the USA.

PubMed

Subedi, Bikram; Sullivan, Kenneth D; Dhungana, Birendra

2017-11-01

The quality of indoor environment has received considerable attention owing to the declining outdoor human activities and the associated public health issues. The prolonged exposure of children in childcare facilities or the occupational exposure of adults to indoor environmental triggers can be a culprit of the pathophysiology of several commonly observed idiopathic syndromes. In this study, concentrations of potentially toxic plasticizers (phthalates as well as non-phthalates) were investigated in 28 dust samples collected from three different indoor environments across the USA. The mean concentrations of non-phthalate plasticizers [acetyl tri-n-butyl citrate (ATBC), di-(2-ethylhexyl) adipate (DEHA), and di-isobutyl adipate (DIBA)] were found at 0.51-880 μg/g for the first time in indoor dust samples from childcare facilities, homes, and salons across the USA. The observed concentrations of these replacement non-phthalate plasticizer were as high as di-(2-ethylhexyl) phthalate, the most frequently detected phthalate plasticizer at highest concentration worldwide, in most of indoor dust samples. The estimated daily intakes of total phthalates (n = 7) by children and toddlers through indoor dust in childcare facilities were 1.6 times higher than the non-phthalate plasticizers (n = 3), whereas estimated daily intake of total non-phthalates for all age groups at homes were 1.9 times higher than the phthalate plasticizers. This study reveals, for the first time, a more elevated (∼3 folds) occupational intake of phthalate and non-phthalate plasticizers through the indoor dust at salons (214 and 285 ng/kg-bw/day, respectively) than at homes in the USA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exposure to an Environmentally Relevant Phthalate Mixture Causes Transgenerational Effects on Female Reproduction in Mice.

PubMed

Zhou, Changqing; Gao, Liying; Flaws, Jodi A

2017-06-01

Phthalates are used in consumer products and are known endocrine-disrupting chemicals. However, limited information is available on the effects of phthalate mixtures on female reproduction. Previously, we developed a phthalate mixture made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% di-isononyl phthalate, 8% di-isobutyl phthalate, and 5% benzylbutyl phthalate that mimics human exposure. We tested the effects of prenatal exposure to this mixture on reproductive outcomes in first-filial-generation (F1) female mice and found that it impaired reproductive outcomes. However, the impact of this exposure on second-filial-generation (F2) and third-filial-generation (F3) females was unknown. Thus, we hypothesized that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. Pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 µg/kg/d, 200 and 500 mg/kg/d) daily from gestational day 10 to birth. Adult F1 females born to these dams were used to generate the F2 generation and adult F2 females born to F1 females were used to generate the F3 generation. F2 and F3 females were subjected to tissue collections and fertility tests. Prenatal phthalate mixture exposure increased uterine weight, anogenital distance, and body weight; induced cystic ovaries; and caused fertility complications in the F2 generation. It also increased uterine weight, decreased anogenital distance, and caused fertility complications in the F3 generation. These data suggest that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. Copyright © 2017 Endocrine Society.

Exposure to an Environmentally Relevant Phthalate Mixture Causes Transgenerational Effects on Female Reproduction in Mice

PubMed Central

Zhou, Changqing; Gao, Liying

2017-01-01

Phthalates are used in consumer products and are known endocrine-disrupting chemicals. However, limited information is available on the effects of phthalate mixtures on female reproduction. Previously, we developed a phthalate mixture made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% di-isononyl phthalate, 8% di-isobutyl phthalate, and 5% benzylbutyl phthalate that mimics human exposure. We tested the effects of prenatal exposure to this mixture on reproductive outcomes in first-filial-generation (F1) female mice and found that it impaired reproductive outcomes. However, the impact of this exposure on second-filial-generation (F2) and third-filial-generation (F3) females was unknown. Thus, we hypothesized that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. Pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 µg/kg/d, 200 and 500 mg/kg/d) daily from gestational day 10 to birth. Adult F1 females born to these dams were used to generate the F2 generation and adult F2 females born to F1 females were used to generate the F3 generation. F2 and F3 females were subjected to tissue collections and fertility tests. Prenatal phthalate mixture exposure increased uterine weight, anogenital distance, and body weight; induced cystic ovaries; and caused fertility complications in the F2 generation. It also increased uterine weight, decreased anogenital distance, and caused fertility complications in the F3 generation. These data suggest that prenatal exposure to the phthalate mixture induces multigenerational and transgenerational effects on female reproduction. PMID:28368545

Fate of four phthalate plasticizers under various wastewater treatment processes.

PubMed

Armstrong, Dana L; Rice, Clifford P; Ramirez, Mark; Torrents, Alba

2018-05-18

The fate of four phthalate plasticizers during wastewater treatment processes at six different wastewater treatment plants (WWTPs) was investigated. Concentrations of benzyl butyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), and diisodecyl phthalate (DiDP) were determined prior to either aerobic or anaerobic (conventional and advanced) treatment, after treatment, and in final, dewatered solids. Despite their elevated use worldwide, the fate of DiNP and DiDP during wastewater treatment have not been well characterized. DEHP was readily degraded during aerobic treatments while anaerobic digestion resulted in either no significant change in concentrations or an increase in concentration, in the case of more advanced anaerobic processes (thermal hydrolysis pretreatment and a two-phase acid/gas process). Impacts of the various treatment systems on DiNP, DiDP, and BBP concentrations were more varied - anaerobic digestion led to significant decreases, increases, or no significant change for these compounds, depending on the treatment facility, while aerobic treatment was generally effective at degrading the compounds. Additionally, thermal hydrolysis pretreatment of sludge prior to anaerobic digestion resulted in increases in DiNP, DiDP, and BBP concentrations. The predicted environmental concentrations for all four compounds in soils after a single biosolids application were calculated and the risk quotients for DEHP in soils were determined. The estimated toxicity risk for DEHP in soils treated with a single application of sludge from any of the six studied WWTPs is lower than the level of concern for acute and chronic risk, as defined by the US EPA.

Transgenerational Effects of Di (2-Ethylhexyl) Phthalate in the Male CRL:CD(SD) Rat: Added Value of Assessing Multiple Offspring per Litter

PubMed Central

Gray, Leon Earl; Barlow, Norman J.; Howdeshell, Kembra L.; Ostby, Joseph S.; Furr, Johnathan R.; Gray, Clark L.

2009-01-01

In the rat, some phthalates alter sexual differentiation at relatively low dosage levels by altering fetal Leydig cell development and hormone synthesis, thereby inducing abnormalities of the testis, gubernacular ligaments, epididymis, and other androgen-dependent tissues. In order to define the dose-response relationship between di(2-ethylhexyl) phthalate (DEHP) and the Phthalate Syndrome of reproductive alterations in F1 male rats, Sprague-Dawley (SD) rat dams were dosed by gavage from gestational day 8 to day 17 of lactation with 0, 11, 33, 100, or 300 mg/kg/day DEHP (71–93 males per dose from 12 to 14 litters per dose). Some of the male offspring continued to be exposed to DEHP via gavage from 18 days of age to necropsy at 63–65 days of age (PUB cohort; 16–20/dose). Remaining males were not exposed after postnatal day 17 (in utero-lactational [IUL] cohort) and were necropsied after reaching full maturity. Anogenital distance, sperm counts and reproductive organ weights were reduced in F1 males in the 300 mg/kg/day group and they displayed retained nipples. In the IUL cohort, seminal vesicle weight also was reduced at 100 mg/kg/day. In contrast, serum testosterone and estradiol levels were unaffected in either the PUB or IUL cohorts at necropsy. A significant percentage of F1 males displayed one or more Phthalate Syndrome lesions at 11 mg/kg/day DEHP and above. We were able to detect effects in the lower dose groups only because we examined all the males in each litter rather than only one male per litter. Power calculations demonstrate how using multiple males versus one male/litter enhances the detection of the effects of DEHP. The results at 11 mg/kg/day confirm those reported from a National Toxicology Program multigenerational study which reported no observed adverse effect levels-lowest observed adverse effect levels of 5 and 10 mg/kg/day DEHP, respectively, via the diet. PMID:19482887

CUMULATIVE EFFECTS OF DIBUTYL PHTHALATE AND DIETHYLHEXYL PHTHALATE ON MALE RAT REPRODUCTIVE TRACT DEVELOPMENT: ALTERED FETAL STEROID HORMONES AND GENES.

EPA Science Inventory

Exposure to the plasticizers diethylhexyl phthalate (DEHP) and di(n-butyl) phthalate (DBP) during sexual differentiation causes male reproductive tract malformations in rats and rabbits. In the fetal male rat, these two phthalate esters decrease testosterone (T) production and i...

Cathepsin B inhibitory activities of three new phthalate derivatives isolated from seahorse, Hippocampus Kuda Bleeler.

PubMed

Li, Yong; Qian, Zhong-Ji; Kim, Se-Kwon

2008-12-01

Three new phthalate acid derivatives, 2,12-diethyl-11-methylhexadecyl 2-ethyl-11-methylhexadecyl phthalate (1), 2-ethyldecyl 2-ethylundecyl phthalate (2), and bis(2-ethyldodecyl) phthalate (3), were isolated from seahorse, Hippocampus Kuda Bleeler, together with a known natural analog bis(2-ethylheptyl) phthalate (4). The structures of these compounds were elucidated mainly by means of the comprehensive analysis of their NMR spectroscopic data. The four phthalate derivatives showed dose-dependent cathepsin B inhibitions activities with IC(50) values of 0.13 mM (1), 0.21 mM (2), 0.18 mM (3), and 0.29 mM (4), respectively.

Simultaneous determination of organophosphorus pesticides and phthalates in baby food samples by ultrasound-vortex-assisted liquid-liquid microextraction and GC-IT/MS.

PubMed

Notardonato, Ivan; Salimei, Elisabetta; Russo, Mario Vincenzo; Avino, Pasquale

2018-05-01

Baby foods are either a soft, liquid paste or an easily chewed food since babies lack developed muscles and teeth to chew effectively. Babies typically move to consuming baby food once nursing or formula is not sufficient for the child's appetite. Some commercial baby foods have been criticized for their contents. This article focuses on the simultaneous determination of organophosphorus pesticides and phthalates by means of a method based on ultrasound-vortex-assisted liquid-liquid microextraction coupled with gas chromatography-ion trap mass spectrometry (GC-IT/MS). The protocol developed allowed the determination of six phthalates [dimethyl phthalate, diethyl phthalate, dibutyl phthalate, isobutyl cyclohexyl phthalate, benzyl butyl phthalate, bis(2-ethylhexyl) phthalate] and 19 organophosphorus pesticides. Freeze-dried product samples (0.1-0.2 g) were dissolved in 10 mL of warm distilled water along with 5 μL of an internal standard (anthracene at 10 mg mL -1 in acetone): the choice of extraction solvent was studied, with the most suitable being n-heptane, which is used for phthalate determination in similar matrices. The solution, held for 5 min in a vortex mixer and for 6 min in a 100-W ultrasonic bath to favor solvent dispersion and consequently analyte extraction, was centrifuged at 4000 rpm for 30 min. Then 1 μL was injected into the GC-IT/MS system (SE-54 capillary column; length 30 m, inner diameter 250 μm, film thickness 0.25 μm). All analytical parameters investigated are discussed in depth. The method was applied to real commercial freeze-dried samples: significant contaminant concentrations were not found. Graphical abstract Simultaneous and sensitive determination of organophosphorus pesticides and phthalates in baby foods by the ultrasound-vortex-assisted liquid-liquid microextraction ֪gas chromatography-ion trap mass spectrometry procedure. 1 methacrifos, 2 pirofos, 3 phorate, 4 seraphos, 5 diazinon, 6 etrimphos, 7 dichlofenthion, 8 chlorpyrifos-methyl, 9 pirimiphos-methyl, 10 malathion, 11 chlorpyrifos, 12 parathion-ethyl, 13 pirimiphos-ethyl, 14 bromophos, 15 chlorfenvinphos, 16 bromophos-ethyl, 17 stirophos, 18 diethion, 19 coumaphos, A dimethyl phthalate, B diethyl phthalate, C dibutyl phthalate, D butyl cyclohexyl phthalate, E benzyl butyl phthalate, F bis(2-ethylhexyl) phthalate, IS internal standard.

Alkyl Phenols and Diethylhexyl Phthalate in Tissues of Sheep Grazing Pastures Fertilized with Sewage Sludge or Inorganic Fertilizer

PubMed Central

Rhind, Stewart M.; Kyle, Carol E.; Telfer, Gillian; Duff, Elizabeth I.; Smith, Alistair

2005-01-01

We studied selected tissues from ewes and their lambs that were grazing pastures fertilized with either sewage sludge (treated) or inorganic fertilizer (control) and determined concentrations of alkylphenols and phthalates in these tissues. Mean tissue concentrations of alkylphenols were relatively low (< 10–400 μg/kg) in all animals and tissues. Phthalates were detected in tissues of both control and treated animals at relatively high concentrations (> 20,000 μg/kg in many tissue samples). The use of sludge as a fertilizer was not associated with consistently increased concentrations of either alkylphenols or phthalates in the tissues of animals grazing treated pastures relative to levels in control animal tissues. Concentrations of the two classes of chemicals differed but were of a similar order of magnitude in liver and muscle as well as in fat. Concentrations of each class of compound were broadly similar in tissues derived from ewes and lambs. Although there were significant differences (p < 0.01 or p < 0.001) between years (cohorts) in mean tissue concentrations of both nonylphenol (NP) and phthalate in each of the tissues from both ewes and lambs, the differences were not attributable to either the age (6 months or 5 years) of the animal or the duration of exposure to treatments. Octylphenol concentrations were generally undetectable. There was no consistent cumulative outcome of prolonged exposure on the tissue concentrations of either class of pollutant in any ewe tissue. Mean tissue concentrations of phthalate were higher (p < 0.001) in the liver and kidney fat of male compared with female lambs. We suggest that the addition of sewage sludge to pasture is unlikely to cause large increases in tissue concentrations of NP and phthalates in sheep and other animals with broadly similar diets and digestive systems (i.e., domestic ruminants) grazing such pasture. PMID:15811823

Differential effects of phthalates on the testis and the liver.

PubMed

Bhattacharya, Nandini; Dufour, Jannette M; Vo, My-Nuong; Okita, Janice; Okita, Richard; Kim, Kwan Hee

2005-03-01

Phthalates have been shown to elicit contrasting effects on the testis and the liver, causing testicular degeneration and promoting abnormal hepatocyte proliferation and carcinogenesis. In the present study, we compared the effects of phthalates on testicular and liver cells to better understand the mechanisms by which phthalates cause testicular degeneration. In vivo treatment of rats with di-(2-ethylhexyl) phthalate (DEHP) caused a threefold increase of germ cell apoptosis in the testis, whereas apoptosis was not changed significantly in livers from the same animals. Western blot analyses revealed that peroxisome proliferator-activated receptor (PPAR) alpha is equally abundant in the liver and the testis, whereas PPAR gamma and retinoic acid receptor (RAR) alpha are expressed more in the testis. To determine whether the principal metabolite of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), or a strong peroxisome proliferator, 4-chloro-6(2,3-xylindino)-2-pyrimidinylthioacetic acid (Wy-14,643), have a differential effect in Sertoli and liver cells by altering the function of RAR alpha and PPARs, their nuclear trafficking patterns were compared in Sertoli and liver cells after treatment. Both MEHP and Wy-14,643 increased the nuclear localization of PPAR alpha and PPAR gamma in Sertoli cells, but they decreased the nuclear localization of RAR alpha, as previously shown. Both PPAR alpha and PPAR gamma were in the nucleus and cytoplasm of liver cells, but RAR alpha was predominant in the cytoplasm, regardless of the treatment. At the molecular level, MEHP and Wy-14,643 reduced the amount of phosphorylated mitogen-activated protein kinase (activated MAPK) in Sertoli cells. In comparison, both MEHP and Wy-14,643 increased phosphorylated MAPK in liver cells. These results suggest that phthalates may cause contrasting effects on the testis and the liver by differential activation of the MAPK pathway, RAR alpha, PPAR alpha, and PPAR gamma in these organs.

Organophosphate and phthalate esters in indoor air: a comparison between multi-storey buildings with high and low prevalence of sick building symptoms.

PubMed

Bergh, Caroline; Magnus Åberg, K; Svartengren, Magnus; Emenius, Gunnel; Östman, Conny

2011-07-01

An extensive study has been conducted on the prevalence of organophosphorous flame retardants/plasticizers and phthalate ester plasticizers in indoor air. The targeted substances were measured in 45 multi-storey apartment buildings in Stockholm, Sweden. The apartment buildings were classified as high or low risk with regard to the reporting of sick building symptoms (SBS) within the project Healthy Sustainable Houses in Stockholm (3H). Air samples were taken from two to four apartments per building (in total 169 apartments) to facilitate comparison within and between buildings. Association with building characteristics has been examined as well as association with specific sources by combining chemical analysis and exploratory uni- and multivariate data analysis. The study contributes to the overall perspective of levels of organophosphate and phthalate ester in indoor air enabling comparison with other studies. The results indicated little or no difference in the concentrations of the target substances between the two risk classifications of the buildings. The differences between the apartments sampled within (intra) buildings were greater than the differences between (inter) buildings. The concentrations measured in air ranged up to 1200 ng m(-3) for organophosphate esters and up to 11 000 ng m(-3) for phthalate esters. Results in terms of sources were discerned e.g. PVC flooring is a major source of benzylbutyl phthalate in indoor air.

Direct sample introduction gas chromatography and mass spectrometry for the determination of phthalate esters in cleaning products.

PubMed

Cacho, J I; Campillo, N; Viñas, P; Hernández-Córdoba, M

2015-02-06

A method using direct sample introduction (DSI) coupled to gas chromatography-mass spectrometry (GC-MS) is developed for the determination of six phthalate esters (dimethyl, diethyl, dibutyl, butylbenzyl, diethylhexyl and dioctyl phthalate) in cleaning products. The different variables involved in the DSI step, including venting time and temperature, vaporisation time and temperature, injector heating temperature and gas flow rate and pressure, were evaluated and optimised using Taguchi orthogonal arrays. The proposed method, using calibration against methanolic standards, showed good linearity in the 0.05-15 μg g(-1) range and good repeatability, with RSD values ranging from 3.5% to 5.7%. Quantification limits between 0.010 and 0.041 μg g(-1), depending on the compound, were attained, while recovery assays provided values from 83% to 115%. Twenty-seven cleaning products were analysed using the DSI-GC-MS method, being four phthalates (dimethyl, diethyl, dibutyl and diethylhexyl phthalate) found in fourteen of them at concentration levels in the 0.1-21 μg g(-1) range. Compared with the most common GC injection technique, which uses the split/splitless injector, the proposed DSI procedure provided larger peak areas and lower detection limits, as result of the greater injected volume and reduction in noise. Copyright © 2014 Elsevier B.V. All rights reserved.

77 FR 15101 - Results From Inert Ingredient Test Orders Issued Under EPA's Endocrine Disruptor Screening...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-14

... Federal Register document provides further notice. To help companies avoid formulating new product with methyl ethyl ketone, butyl benzyl phthalate, dibutyl phthalate, diethyl phthalate, and dimethyl phthalate...

Assessing the concentration of phthalate esters (PAEs) and bisphenol A (BPA) and the genotoxic potential of treated wastewater (final effluent) in Saudi Arabia.

PubMed

Al-Saleh, Iman; Elkhatib, Rola; Al-Rajoudi, Tahreer; Al-Qudaihi, Ghofran

2017-02-01

Plasticizers such as phthalate esters (PAEs) and bisphenol A (BPA) are highly persistent organic pollutants that tend to bio-accumulate in humans through the soil-plant-animal food chain. Some studies have reported the potential carcinogenic and teratogenic effects in addition to their estrogenic activities. Water resources are scarce in Saudi Arabia, and several wastewater treatment plants (WTPs) have been constructed for agricultural and industrial use. This study was designed to: (1) measure the concentrations of BPA and six PAEs, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), bis (2-ethylhexyl) phthalate (DEHP) and dioctyl phthalate (DOP), in secondary- and tertiary-treated wastewater collected from five WTPs in three Saudi cities for four to five weeks and (2) test their potential genotoxicity. Three genotoxicological parameters were used: % tail DNA (%T), tail moment (TM) and percentage micronuclei (%MN). Both DBP and DEHP were detected in all treated wastewater samples. DMP, DEP, BBP, DOP, and BPA were found in 83.3, 84.2, 79, 73.7 and 97.4% of the samples, respectively. The levels of DMP (p<0.001), DOP (p<0.001) and BPA (p=0.001) were higher in tertiary- treated wastewater than secondary-treated wastewater, perhaps due to the influence of the molecular weight and polarity of the chemicals. Both weekly sampling frequency and WTP locations significantly affected the variability in our data. Treated wastewater from Wadi Al-Araj was able to induce DNA damage (%T and TM) in human lymphoblastoid TK6 cells that was statistically higher than wastewater from all other WTPs and in untreated TK6 cells (negative control). %MN in samples from both Wadi Al-Araj and Manfouah did not differ statistically but was significantly higher than in the untreated TK6 cells. This study also showed that the samples of tertiary-treated wastewater had a higher genotoxicological potential to induce DNA damage than the samples of secondary-treated wastewater. BPA and some PAEs in the treated wastewater might have the potential to induce genetic damage, despite their low levels. Genotoxicity, however, may also have been due to the presence of other contaminants. Our preliminary findings should be of concern to Saudi agriculture because long-term irrigation with treated wastewater could lead to the accumulation of PAEs and BPA in the soil and ultimately reach the human and animal food chain. WTPs need to remove pollutants more efficiently. Until then, a cautious use of treated wastewater for irrigation is recommended to avoid serious health impacts on local populations. Copyright © 2016 Elsevier B.V. All rights reserved.

Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates

PubMed Central

Singh, Sher; Li, Steven Shoei-Lung

2012-01-01

The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis. PMID:22949852

Epigenetic effects of environmental chemicals bisphenol A and phthalates.

PubMed

Singh, Sher; Li, Steven Shoei-Lung

2012-01-01

The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis.

Survey of phthalates, alkylphenols, bisphenol A and herbicides in Spanish source waters intended for bottling.

PubMed

Bono-Blay, Francisco; Guart, Albert; de la Fuente, Boris; Pedemonte, Marta; Pastor, Maria Cinta; Borrell, Antonio; Lacorte, Silvia

2012-09-01

Groundwaters and source waters are exposed to environmental pollution due to agricultural and industrial activities that can enhance the leaching of organic contaminants. Pesticides are among the most widely studied compounds in groundwater, but little information is available on the presence of phthalates, alkylphenols and bisphenol A. These compounds are used in pesticide formulations and represent an emerging family of contaminants due to their widespread environmental presence and endocrine-disrupting properties. Knowledge on the occurrence of contaminants in source waters intended for bottling is important for sanitary and regulatory purposes. So the aim of the present study was to evaluate the presence of phthalates, alkylphenols, triazines, chloroacetamides and bisphenol A throughout 131 Spanish water sources intended for bottling. Waters studied were spring waters and boreholes which have a protection diameter to minimize environmental contamination. Waters were solid-phase extracted (SPE) and analysed by gas chromatography coupled to mass spectrometry (GC-MS). Quality control analysis comprising recovery studies, blank analysis and limits of detection were performed. Using SPE and GC-MS, the 21 target compounds were satisfactorily recovered (77-124 %) and limits of quantification were between 0.0004 and 0.029 μg/L for pesticides, while for alkylphenols, bisphenol A and phthalates the limits of quantification were from 0.0018 μg/L for octylphenol to 0.970 μg/L for bis(2-ethylhexyl) phthalate. Among the 21 compounds analysed, only 9 were detected at levels between 0.002 and 1.115 μg/L. Compounds identified were triazine herbicides, alkylphenols, bisphenol A and two phthalates. Spring waters or shallow boreholes were the sites more vulnerable to contaminants. Eighty-five percent of the samples did not contain any of the target compounds. Target compounds were detected in a very low concentration and only in very few samples. This indicates the good quality of source waters intended for bottling and the effectiveness of the protection measures adopted in Spain. None of the samples analysed exceeded the maximum legislated levels for drinking water both in Spain and in the European Union.

Plasticizer contamination of firefighter personal protective clothing--a potential factor in increased health risks in firefighters.

PubMed

Lacey, Steven; Alexander, Barbara M; Baxter, C Stuart

2014-01-01

Chemical exposures may be responsible for firefighters' elevated incidences of cancer and cardiovascular disease. This study characterized semivolatile chemical contamination on firefighter personal protective clothing to assess exposure of firefighters to these chemicals. Samples from used firefighter protective clothing, including gloves, hood, and one coat wristlet, were extracted with methylene chloride and analyzed by EPA method 8270 for semivolatile contaminants, including 20 polycyclic aromatic hydrocarbons (PAHs) and 6 phthalate diesters. Twenty-two of the chemicals of interest were found on at least one clothing swatch. Only di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, added to polyvinyl chloride (PVC) to increase flexibility, was found on every swatch. DEHP concentrations were the highest of any chemical measured, and were 52 to 875 times higher than any PAH concentration measured. DEHP was also detected on most items of unused firefighter personal protective clothing, although at much lower levels. These findings suggest that firefighters are exposed to high levels of DEHP, a probable human carcinogen, and at levels much higher than PAHs, the semivolatile toxic combustion products most extensively studied historically. Firefighter exposure to DEHP and other phthalate diesters therefore merits further study.

Dietary exposure and human risk assessment of phthalate esters based on total diet study in Cambodia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Zhang; Li, Han-Han

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 human to phthalates are limited. In this study, to assess the daily intakes of phthalate esters and the possible adverse health impacts, different food samples were collected from three areas of Cambodia, one of the poorest countries in the world. The ∑phthalate ester concentrations in Kampong Cham, Kratie and Kandal provinces ranged from 0.05 to 2.34 (median 0.88) μg g{sup −1}, 0.19–1.65 (median 0.86) μg g{sup −1} and 0.24–3.05 (median 0.59) μg g{supmore » −1} wet weight (ww), respectively. Di-2-Ethylhexyl phthalate (DEHP) and diisobutyl phthalate (DiBP) were the predominant compounds among all foodstuffs. The estimated daily intake (EDI) of phthalate esters for the general population in Kampong Cham, Kratie and Kandal was 34.3, 35.6 and 35.8 μg kg{sup −1} bw d{sup −1}, respectively. The dietary daily intake of DEHP, benzylbutyl phthalate (BBP) and di-n-butyl phthalate (DBP) in Kampong Cham, Kratie and Kandal were below the tolerable daily intakes (TDI) imposed by the European Food Safety Authority (EFSA) and reference doses (RfD) imposed by The United States Environmental Protection Agency (USEPA). Rice contributed the greatest quantity of DEHP to the daily intake in Cambodia so may deserve further exploration. To our knowledge, this is the first study to investigate the occurrence and the daily intakes of phthalate esters in Cambodia. - Highlights: • Phthalate esters concentration in daily foodstuffs collected from Cambodia. • Investigate the bioaccessbility of phthalate esters via the foodstuffs consumption. • Health risk evaluation of dietary exposure to phthalate esters.« less

Enzymes involved in the anaerobic degradation of ortho-phthalate by the nitrate-reducing bacterium Azoarcus sp. strain PA01.

PubMed

Junghare, Madan; Spiteller, Dieter; Schink, Bernhard

2016-09-01

The pathway of anaerobic degradation of o-phthalate was studied in the nitrate-reducing bacterium Azoarcus sp. strain PA01. Differential two-dimensional protein gel profiling allowed the identification of specifically induced proteins in o-phthalate-grown compared to benzoate-grown cells. The genes encoding o-phthalate-induced proteins were found in a 9.9 kb gene cluster in the genome of Azoarcus sp. strain PA01. The o-phthalate-induced gene cluster codes for proteins homologous to a dicarboxylic acid transporter, putative CoA-transferases and a UbiD-like decarboxylase that were assigned to be specifically involved in the initial steps of anaerobic o-phthalate degradation. We propose that o-phthalate is first activated to o-phthalyl-CoA by a putative succinyl-CoA-dependent succinyl-CoA:o-phthalate CoA-transferase, and o-phthalyl-CoA is subsequently decarboxylated to benzoyl-CoA by a putative o-phthalyl-CoA decarboxylase. Results from in vitro enzyme assays with cell-free extracts of o-phthalate-grown cells demonstrated the formation of o-phthalyl-CoA from o-phthalate and succinyl-CoA as CoA donor, and its subsequent decarboxylation to benzoyl-CoA. The putative succinyl-CoA:o-phthalate CoA-transferase showed high substrate specificity for o-phthalate and did not accept isophthalate, terephthalate or 3-fluoro-o-phthalate whereas the putative o-phthalyl-CoA decarboxylase converted fluoro-o-phthalyl-CoA to fluoro-benzoyl-CoA. No decarboxylase activity was observed with isophthalyl-CoA or terephthalyl-CoA. Both enzyme activities were oxygen-insensitive and inducible only after growth with o-phthalate. Further degradation of benzoyl-CoA proceeds analogous to the well-established anaerobic benzoyl-CoA degradation pathway of nitrate-reducing bacteria. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Recent progress in safety evaluation studies on plasticizers and plastics and their controlled use in Japan.

PubMed Central

Omori, Y

1976-01-01

Recent experimental studies in Japan on the evaluation of potential health hazards from phthalate esters used in manufacturing poly (vinyl chloride) as well as several plastics for medical devices and for food containers and packages were introduced. Development of pulmonary granuloma formation after intravenous injection of diethylhexyl phthalate was assumed to be dependent on the particle size of the phthalate in vehicle used. Dietary administration of large amount of diethylhexyl phthalate and dibutyl phthalate produced renal cysts in mothers and in descendants in reproduction studies in mice. Cytotoxicity and mutagenicity of the phthalates and several plastics and resins were also examined by in vivo and in vitro studies. Hematological parameters examined in rabbits after repeated intravenous injection of diethylhexyl phthalate and after implantation of plastics in aorta for 3--6 months did not show any significant change. A slow decrease of radioactivity was observed in adipose tissue of rats following oral administration of 14C-labeled diethylhexyl phthalate. tthe administrative action on phthalates by the Japanese Ministry of Health and Welfare is briefly reviewed. PMID:1026406

40 CFR 463.33 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... limitations guidelines for bis(2-ethylhexyl) phthalate, di-n-butyl phthalate, and dimethyl phthalate are reserved. (b) The Agency has determined that, with the exception of bis(2-ethylhexyl) phthalate, di-n-butyl...

Comparative Time Course Profiles of Phthalate Stereoisomers in Mice

EPA Science Inventory

ABSTRACT More efficient models are needed to assess potential carcinogenicity hazard of environmental chemicals. Here we evaluated time course profiles for two reference phthalates, di(2-ethylhexyl) phthalate (DEHP) and its stereoisomer di-n-octyl phthalate (DNOP), to identify...

40 CFR 437.42 - Effluent limitations attainable by the application of the best practicable control technology...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Acetophenone 0.114 0.0562 Bis(2-ethylhexyl) phthalate 0.215 0.101 2-Butanone 4.81 1.85 Butylbenzyl phthalate 0... 0.641 Organic Parameters Bis(2-ethylhexyl) phthalate 0.215 0.101 Butylbenzyl phthalate 0.188 0.0887....2 7.97 Acetophenone 0.114 0.0562 Bis(2-ethylhexyl) phthalate 0.215 0.101 2-Butanone 4.81 1.85...

A monograph on the remediation of hazardous phthalates.

PubMed

Benjamin, Sailas; Pradeep, Selvanesan; Josh, Moolakkariyil Sarath; Kumar, Sunil; Masai, Eiji

2015-11-15

Phthalates or phthalic acid esters are a group of xenobiotic and hazardous compounds blended in plastics to enhance their plasticity and versatility. Enormous quantities of phthalates are produced globally for the production of plastic goods, whose disposal and leaching out into the surroundings cause serious concerns to the environment, biota and human health. Though in silico computational, in vitro mechanistic, pre-clinical animal and clinical human studies showed endocrine disruption, hepatotoxic, teratogenic and carcinogenic properties, usage of phthalates continues due to their cuteness, attractive chemical properties, low production cost and lack of suitable alternatives. Studies revealed that microbes isolated from phthalate-contaminated environmental niches efficiently bioremediate various phthalates. Based upon this background, this review addresses the enumeration of major phthalates used in industry, routes of environmental contamination, evidences for health hazards, routes for in situ and ex situ microbial degradation, bacterial pathways involved in the degradation, major enzymes involved in the degradation process, half-lives of phthalates in environments, etc. Briefly, this handy module would enable the readers, environmentalists and policy makers to understand the impact of phthalates on the environment and the biota, coupled with the concerted microbial efforts to alleviate the burden of ever increasing load posed by phthalates. Copyright © 2015 Elsevier B.V. All rights reserved.

Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016.

PubMed

Silva, Manori J; Wong, Lee-Yang; Samandar, Ella; Preau, James L; Calafat, Antonia M; Ye, Xiaoyun

2017-10-01

Di-2-ethylhexyl terephthalate (DEHTP), a structural isomer of di-2-ethylhexyl phthalate (DEHP), is a plasticizer used in a variety of commercial applications, but data on Americans' exposure to DEHTP do not exist. We investigated the exposure to DEHTP in a convenience group of U.S. adults by analyzing urine collected anonymously in 2000 (N = 44), 2009 (N = 61), 2011 (N = 81), 2013 (N = 92), and 2016 (N = 149) for two major DEHTP oxidative metabolites: mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP). For comparison, we also quantified the analogous DEHP metabolites mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). We detected MECPTP, MEHHP, and MECPP in all samples collected in 2016 with geometric means of 13.1, 4.1, and 6.7 ng/mL, respectively; we detected MEHHTP in 91% of the samples (geometric mean = 3.1 ng/mL). Concentrations of MECPTP correlated well with those of MEHHTP (R 2  = 0.8, p < 0.001), but did not significantly correlate with those of MEHHP (p > 0.05) suggesting different sources of exposure to DEHP and DEHTP. We also evaluated the fraction of the metabolites eliminated in their free (i.e., unconjugated) form. The median percent of unconjugated species was lower for the DEHP metabolites (MECPP [45.5%], MEHHP [1.9%]) compared to the DEHTP metabolites (MECPTP [98.8%], MEHHTP [21.2%]). Contrary to the downward trend from 2000 to 2016 in urinary concentrations of MEHHP and MECPP, we observed an upward trend for MEHHTP and MECPTP. These preliminary data suggest that exposure to DEHTP may be on the rise. Nevertheless, general population exposure data using MEHHTP and MECPTP as exposure biomarkers would increase our understanding of exposure to DEHTP, one of the known DEHP alternatives.

Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016

PubMed Central

Wong, Lee-Yang; Samandar, Ella; Preau, James L.; Calafat, Antonia M.; Ye, Xiaoyun

2017-01-01

Di-2-ethylhexyl terephthalate (DEHTP), a structural isomer of di-2-ethylhexyl phthalate (DEHP), is a plasticizer used in a variety of commercial applications, but data on Americans’ exposure to DEHTP do not exist. We investigated the exposure to DEHTP in a convenience group of U.S. adults by analyzing urine collected anonymously in 2000 (N = 44), 2009 (N = 61), 2011 (N = 81), 2013 (N = 92), and 2016 (N = 149) for two major DEHTP oxidative metabolites: mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP). For comparison, we also quantified the analogous DEHP metabolites mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). We detected MECPTP, MEHHP, and MECPP in all samples collected in 2016 with geometric means of 13.1, 4.1, and 6.7 ng/mL, respectively; we detected MEHHTP in 91% of the samples (geometric mean = 3.1 ng/mL). Concentrations of MECPTP correlated well with those of MEHHTP (R2= 0.8, p < 0.001), but did not significantly correlate with those of MEHHP (p > 0.05) suggesting different sources of exposure to DEHP and DEHTP. We also evaluated the fraction of the metabolites eliminated in their free (i.e., unconjugated) form. The median percent of unconjugated species was lower for the DEHP metabolites (MECPP [45.5%], MEHHP [1.9%]) compared to the DEHTP metabolites (MECPTP [98.8%], MEHHTP [21.2%]). Contrary to the downward trend from 2000 to 2016 in urinary concentrations of MEHHP and MECPP, we observed an upward trend for MEHHTP and MECPTP. These preliminary data suggest that exposure to DEHTP may be on the rise. Nevertheless, general population exposure data using MEHHTP and MECPTP as exposure biomarkers would increase our understanding of exposure to DEHTP, one of the known DEHP alternatives. PMID:28314884

Anaerobic Degradation of Phthalate Isomers by Methanogenic Consortia

PubMed Central

Kleerebezem, Robbert; Pol, Look W. Hulshoff; Lettinga, Gatze

1999-01-01

Three methanogenic enrichment cultures, grown on ortho-phthalate, iso-phthalate, or terephthalate were obtained from digested sewage sludge or methanogenic granular sludge. Cultures grown on one of the phthalate isomers were not capable of degrading the other phthalate isomers. All three cultures had the ability to degrade benzoate. Maximum specific growth rates (μSmax) and biomass yields (YXtotS) of the mixed cultures were determined by using both the phthalate isomers and benzoate as substrates. Comparable values for these parameters were found for all three cultures. Values for μSmax and YXtotS were higher for growth on benzoate compared to the phthalate isomers. Based on measured and estimated values for the microbial yield of the methanogens in the mixed culture, specific yields for the phthalate and benzoate fermenting organisms were calculated. A kinetic model, involving three microbial species, was developed to predict intermediate acetate and hydrogen accumulation and the final production of methane. Values for the ratio of the concentrations of methanogenic organisms, versus the phthalate isomer and benzoate fermenting organisms, and apparent half-saturation constants (KS) for the methanogens were calculated. By using this combination of measured and estimated parameter values, a reasonable description of intermediate accumulation and methane formation was obtained, with the initial concentration of phthalate fermenting organisms being the only variable. The energetic efficiency for growth of the fermenting organisms on the phthalate isomers was calculated to be significantly smaller than for growth on benzoate. PMID:10049876

Study on the leaching of phthalates from polyethylene terephthalate bottles into mineral water.

PubMed

Keresztes, Szilvia; Tatár, Enikő; Czégény, Zsuzsanna; Záray, Gyula; Mihucz, Victor G

2013-08-01

Carbonated and non-carbonated mineral water samples bottled in 0.5-L, 1.5-L and 2.0-L polyethylene terephthalate (PET) containers belonging to three different water brands commercialized in Hungary were studied in order to determine their phthalate content by gas chromatography-mass spectrometry. Among the six investigated phthalates, diisobutyl phthalate, di-n-butyl-phthalate, benzyl-butyl phthalate and di(2-ethyl-hexyl) phthalate (DEHP) were determined in non-carbonated samples as follows: <3.0 ng L(-1)-0.2 μg L(-1), <6.6 ng L(-1)-0.8 μg L(-1), <6.0 ng L(-1)-0.1 μg L(-1) and <16.0 ng L(-1)-1.7 μg L(-1), respectively. Any of the above-mentioned phthalate esters could be detected in carbonated mineral water samples. DEHP was the most abundant phthalate in the investigated samples. It could be detected after 44 days of storage at 22 °C and its leaching was the most pronounced when samples were stored over 1200 days. Mineral water purchased in PET bottles of 0.5L had the highest phthalate concentrations compared to those obtained for waters of the identical brand bottled in 1.5-L or 2.0-L PET containers due to the higher surface/volume ratio. No clear trend could be established for phthalate leaching when water samples were kept at higher temperatures (max. 60 °C) showing improper storage conditions. Phthalate determination by pyrolysis-gas chromatography/mass spectrometric measurements in the plastic material as well as in the aqueous phase proved the importance of the quality of PET raw material used for the production of the pre-form (virgin vs. polymer containing recycled PET). Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibition of UDP-glucuronosyltransferases (UGTs) by phthalate monoesters.

PubMed

Du, Zuo; Cao, Yun-Feng; Li, Sai-Nan; Hu, Cui-Min; Fu, Zhi-Wei; Huang, Chun-Ting; Sun, Xiao-Yu; Liu, Yong-Zhe; Yang, Kun; Fang, Zhong-Ze

2018-04-01

Phthalate monoesters are important metabolites of phthalate esters (PAEs) which have been extensively utilized in industry. This study aims to investigate the inhibition of phthalate monoesters on the activity of various isoforms of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of environmental endocrine disruptors from the new perspectives. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed to evaluate 8 kinds of phthalate monoesters on 11 sorts of main human UGT isoforms. 100 μM phthalate monoesters exhibited negligible inhibition towards the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A10, UGT2B4, UGT2B7, UGT2B15 and UGT2B17. The activity of UGT1A7 was strongly inhibited by monoethylhexyl phthalate (MEHP), but slightly inhibited by all the other phthalate monoesters. UGT1A9 was broadly inhibited by monobenzyl phthalate (MBZP), monocyclohexyl phthalate (MCHP), MEHP, monohexyl phthalate (MHP) and monooctyl phthalate (MOP), respectively. MEHP exhibited competitive inhibition towards UGT1A7, and MBZP, MCHP, MEHP, MHP and MOP showed competitive inhibition towards UGT1A9. The inhibition kinetic parameters (K i ) were calculated to be 11.25 μM for MEHP-UGT1A7, and 2.13, 0.09, 1.17, 7.47, 0.16 μM for MBZP-UGT1A9, MCHP-UGT1A9, MEHP-UGT1A9, MHP-UGT1A9, MOP-UGT1A9, respectively. Molecular docking indicated that both hydrogen bonds formation and hydrophobic interactions significantly contributed to the interaction between phthalate monoesters and UGT isoforms. All these information will be beneficial for understanding the adverse effects of PAEs. Copyright © 2018 Elsevier Ltd. All rights reserved.

40 CFR 721.10501 - Tridecyl phthalate (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tridecyl phthalate (generic). 721... Substances § 721.10501 Tridecyl phthalate (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as tridecyl phthalate (PMN P-06-542...

Sources of Propylene Glycol and Glycol Ethers in Air at Home

PubMed Central

Choi, Hyunok; Schmidbauer, Norbert; Spengler, John; Bornehag, Carl-Gustaf

2010-01-01

Propylene glycol and glycol ether (PGE) in indoor air have recently been associated with asthma and allergies as well as sensitization in children. In this follow-up report, sources of the PGEs in indoor air were investigated in 390 homes of pre-school age children in Sweden. Professional building inspectors examined each home for water damages, mold odour, building’s structural characteristics, indoor temperature, absolute humidity and air exchange rate. They also collected air and dust samples. The samples were analyzed for four groups of volatile organic compounds (VOCs) and semi-VOCs (SVOCs), including summed concentrations of 16 PGEs, 8 terpene hydrocarbons, 2 Texanols, and the phthalates n-butyl benzyl phthalate (BBzP), and di(2-ethylhexyl)phthalate (DEHP). Home cleaning with water and mop ≥ once/month, repainting ≥ one room prior to or following the child’s birth, and “newest” surface material in the child’s bedroom explained largest portion of total variability in PGE concentrations. High excess indoor humidity (g/m3) additionally contributed to a sustained PGE levels in indoor air far beyond several months following the paint application. No behavioral or building structural factors, except for water-based cleaning, predicted an elevated terpene level in air. No significant predictor of Texanols emerged from our analysis. Overall disparate sources and low correlations among the PGEs, terpenes, Texanols, and the phthalates further confirm the lack of confounding in the analysis reporting the associations of the PGE and the diagnoses of asthma, rhinitis, and eczema, respectively. PMID:21318004

Sources of propylene glycol and glycol ethers in air at home.

PubMed

Choi, Hyunok; Schmidbauer, Norbert; Spengler, John; Bornehag, Carl-Gustaf

2010-12-01

Propylene glycol and glycol ether (PGE) in indoor air have recently been associated with asthma and allergies as well as sensitization in children. In this follow-up report, sources of the PGEs in indoor air were investigated in 390 homes of pre-school age children in Sweden. Professional building inspectors examined each home for water damages, mold odour, building's structural characteristics, indoor temperature, absolute humidity and air exchange rate. They also collected air and dust samples. The samples were analyzed for four groups of volatile organic compounds (VOCs) and semi-VOCs (SVOCs), including summed concentrations of 16 PGEs, 8 terpene hydrocarbons, 2 Texanols, and the phthalates n-butyl benzyl phthalate (BBzP), and di(2-ethylhexyl)phthalate (DEHP). Home cleaning with water and mop ≥ once/month, repainting ≥ one room prior to or following the child's birth, and "newest" surface material in the child's bedroom explained largest portion of total variability in PGE concentrations. High excess indoor humidity (g/m³) additionally contributed to a sustained PGE levels in indoor air far beyond several months following the paint application. No behavioral or building structural factors, except for water-based cleaning, predicted an elevated terpene level in air. No significant predictor of Texanols emerged from our analysis. Overall disparate sources and low correlations among the PGEs, terpenes, Texanols, and the phthalates further confirm the lack of confounding in the analysis reporting the associations of the PGE and the diagnoses of asthma, rhinitis, and eczema, respectively.

Analysis of the influencing factors of PAEs volatilization from typical plastic products.

PubMed

Chen, Weidong; Chi, Chenchen; Zhou, Chen; Xia, Meng; Ronda, Cees; Shen, Xueyou

2018-04-01

The primary emphasis of this research was to investigate the foundations of phthalate (PAEs) pollutant source researches and then firstly confirmed the concept of the coefficient of volatile strength, namely phthalate total content in per unit mass and unit surface area of pollutant sources. Through surveying and evaluating the coefficient of volatile strength of PAEs from typical plastic products, this research carried out reasonable classification of PAEs pollutant sources into three categories and then investigated the relationship amongst the coefficient of volatile strength as well as other environmental factors and the concentration level of total PAEs in indoor air measured in environment chambers. Research obtained phthalate concentration results under different temperature, humidity, the coefficient of volatile strength and the closed time through the chamber experiment. In addition, this study further explored the correlation and ratio of influencing factors that affect the concentration level of total PAEs in environment chambers, including environmental factors, the coefficient of volatile strengths of PAEs and contents of total PAEs in plastic products. The research created an improved database system of phthalate the coefficient of volatile strengths of each type of plastic goods, and tentatively revealed that the volatile patterns of PAEs from different typical plastic goods, finally confirmed that the coefficient of volatile strengths of PAEs is a major factor that affects the indoor air total PAEs concentration, which laid a solid foundation for further establishing the volatile equation of PAEs from plastic products. Copyright © 2017. Published by Elsevier B.V.

Phthalates in plastic bottled non-alcoholic beverages from China and estimated dietary exposure in adults.

PubMed

Yang, Ji-Feng; Yang, Li-Ming; Zheng, Li-Ying; Ying, Guang-Guo; Liu, Cheng-Bin; Luo, Sheng-Lian

2017-03-01

Concentrations of six phthalates were determined in 69 plastic bottled non-alcoholic beverages collected from marketplaces in China. Di-n-butyl phthalate (DBP) and di-(2-ethylhexyl)-phthalate (DEHP) were the most detected compounds with frequencies of 100%. Dimethyl phthalate was found less, with a mean frequency of almost 34%. The samples were divided into seven groups. The frequencies of phthalates in these groups ranged from 6.67% to 100%, which indicated that different types of beverages were differently contaminated by phthalates. DEHP contained the highest mean and median concentrations (1.60 ng g -1 and 0.62 ng g -1 ), followed by DBP (1.34 ng g -1 and 0.27 ng g -1 ). For DBP, the highest phthalate concentration of 14.3 ng g -1 was measured. The results of estimated daily intake (EDI) showed that the risk of Chinese adults exposed to these 6 phthalates in beverages examined was lower than the reference doses as suggested by the United States Environmental Protection Agency. The range of EDI values was between 1.77 × 10 - 4 μg kg-bw -1 day -1 and 0.478 μg kg-bw -1 day -1 .

Biodegradation of endocrine disruptor dibutyl phthalate (DBP) by a newly isolated Methylobacillus sp. V29b and the DBP degradation pathway.

PubMed

Kumar, Vinay; Maitra, S S

2016-12-01

Bacteria of the genus Methylobacillus are methanotrophs, a metabolic feature that is widespread in the phylum Proteobacteria. The study demonstrates the isolation and characterization of a newly isolated Methylobacillus sp. V29b. which grows on methanol, protocatechuate, monobutyl phthalate, dibutyl phthalate, diethyl phthalate, benzyl butyl phthalate, dioctyl phthalate and diisodecyl phthalate. Methylobacillus sp. V29b was characterized with scanning electron microscopy, transmission electron microscopy, Gram staining, antibiotics sensitivity tests and biochemical characterization. It degrades 70 % of the initial DBP in minimal salt medium and 65 % of the initial DBP in samples contaminated with DBP. DBP biodegradation kinetics was explained by the Monod growth inhibition model. Values for maximum specific growth rate (µ max ) and half-velocity constant (K s ) are 0.07 h -1 and 998.2 mg/l, respectively. Stoichiometry for DBP degradation was calculated for Methylobacillus sp. V29b. Four metabolic intermediates, dibutyl phthalate (DBP), monobutyl phthalate, phthalic acid and pyrocatechol, were identified. Based on the metabolic intermediates identified, a chemical pathway for DBP degradation was proposed. Six genes for phthalic acid degradation were identified from the genome of Methylobacillus sp. V29b.

Downsides of the recycling process: harmful organic chemicals in children's toys.

PubMed

Ionas, Alin C; Dirtu, Alin C; Anthonissen, Tim; Neels, Hugo; Covaci, Adrian

2014-04-01

Most of the materials used in consumer goods contain a number of additives which are meant to improve key properties like plasticity or flame resistance. At the end-of-life of the product, many polymeric materials are recycled and the additives they contain, such as flame retardants (FRs) and plasticizers, are transferred to the newly manufactured goods. We have investigated the occurrence and profiles of FRs, such as polybrominated diphenyl ethers (PBDEs) and phosphate FR (PFRs) and of plasticisers, such as phthalate esters, in 106 toys samples. Low levels and detection frequencies of components of the technical Penta-BDE and Deca-BDE mixtures were found, with BDE 209 being the dominant PBDE in all samples (maximum value was 0.14mg/g or 0.014%). The levels of PFRs and phthalates were up to 10,000 times higher than those of the PBDEs, with triphenyl phosphate and diethylhexyl phthalate being the major representatives of these classes. Maximum values were 1.3 and 6.9%, respectively. The detection frequencies were up to 50% for PFRs and 98% for phthalates. All but one of the toys produced after the REACH regulation went into force complied with its provisions. The samples were grouped according to relevant selection criteria to assess the risk for children of different age groups. Using models in the literature, exposure to these chemicals was tentatively assessed. It is clear that at the levels found in the investigated toys, these additives do not contribute to the intended characteristics of the materials, but in some cases may pose a health hazard to the children. Most likely, recycled materials are an important source of these additives in toys and therefore, their (re)use in products for children should be subject to stricter restrictions. Copyright © 2014 Elsevier Ltd. All rights reserved.

COMBINATION DOSE OF TWO PHTHALATES ADDITIVELY DEPRESSES TESTOSTERONE PRODUCTION AND INSL3 GENE EXPRESSION IN MALE RAT FETUSES

EPA Science Inventory

Diethylhexyl phthalate (DEHP) and di(n-butyl) phthalate (DBP) are phthalate esters used to modify plastic and polymer textures. Individually,DEHP and DBP reduce testosterone production, inhibit reproductive tract development, andinduce reproductive organ malformationsin male rats...

40 CFR 721.10043 - Dineopentyl-4-substituted phthalate (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Dineopentyl-4-substituted phthalate... Specific Chemical Substances § 721.10043 Dineopentyl-4-substituted phthalate (generic). (a) Chemical... as dineopentyl-4-substituted phthalate (PMN P-02-697) is subject to reporting under this section for...

40 CFR 721.10043 - Dineopentyl-4-substituted phthalate (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Dineopentyl-4-substituted phthalate... Specific Chemical Substances § 721.10043 Dineopentyl-4-substituted phthalate (generic). (a) Chemical... as dineopentyl-4-substituted phthalate (PMN P-02-697) is subject to reporting under this section for...

40 CFR Appendix - Tables to Part 132

Code of Federal Regulations, 2014 CFR

2014-07-01

... ether Butyl benzyl phthalate Cadmium Carbon tetrachloride; tetrachloromethane Chlorobenzene p-Chloro-m... Copper Cyanide 2,4-D; 2,4-Dichlorophenoxyacetic acid DEHP; di(2-ethylhexyl) phthalate Diazinon 1,2:5,6-Dibenzanthracene; dibenz[a,h]anthracene Dibutyl phthalate; di-n-butyl phthalate 1,2-Dichlorobenzene 1,3...

40 CFR 721.10043 - Dineopentyl-4-substituted phthalate (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Dineopentyl-4-substituted phthalate... Specific Chemical Substances § 721.10043 Dineopentyl-4-substituted phthalate (generic). (a) Chemical... as dineopentyl-4-substituted phthalate (PMN P-02-697) is subject to reporting under this section for...

40 CFR 721.10043 - Dineopentyl-4-substituted phthalate (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Dineopentyl-4-substituted phthalate... Specific Chemical Substances § 721.10043 Dineopentyl-4-substituted phthalate (generic). (a) Chemical... as dineopentyl-4-substituted phthalate (PMN P-02-697) is subject to reporting under this section for...

Biodegradation of phthalic acid esters (PAEs) and in silico structural characterization of mono-2-ethylhexyl phthalate (MEHP) hydrolase on the basis of close structural homolog.

PubMed

Singh, Neha; Dalal, Vikram; Mahto, Jai Krishna; Kumar, Pravindra

2017-09-15

Three bacterial strains capable of degrading phthalates namely Pseudomonas sp. PKDM2, Pseudomonas sp. PKDE1 and Pseudomonas sp. PKDE2 were isolated and characterized for their degradative potential. These strains efficiently degraded 77.4%-84.4% of DMP, 75.0%-75.7% of DEP and 71.7%-74.7% of DEHP, initial amount of each phthalate is 500mgL -1 of each phthalate, after 44h of incubation. GC-MS results reveal the tentative DEHP degradation pathway, where hydrolases mediate the breakdown of DEHP to phthalic acid (PA) via an intermediate MEHP. MEHP hydrolase is a serine hydrolase which is involved in the reduction of the MEHP to PA. The predicted 3D model of MEHP hydrolase from Pseudomonas mosselii was docked with phthalate monoesters (PMEs) such as MEHP, mono-n-hexyl phthalate (MHP), mono-n-butyl phthalate (MBP) and mono-n-ethyl phthalate (MEP), respectively. Docking results show the distance between the carbonyl carbon of respective phthalate monoester and the hydroxyl group of catalytic serine lies in the range of 2.9 to 3.3Å, which is similar to the ES complex of other serine hydrolases. This structural study highlights the interaction and the role of catalytic residues of MEHP hydrolase involved in the biodegradation of PMEs to phthalate. Copyright © 2017 Elsevier B.V. All rights reserved.

Status of phthalate esters contamination in agricultural soils across China and associated health risks.

PubMed

Niu, Lili; Xu, Yang; Xu, Chao; Yun, Lingxiang; Liu, Weiping

2014-12-01

The extensive utilization of phthalate-containing products has lead to ubiquitous contamination of phthalate esters (PAEs) in various matrices. However, comprehensive knowledge of their pollution in Chinese farmland and associated risks is still limited. In this study, 15 PAEs were determined in soils from agricultural fields throughout the Mainland China. The concentrations of Σ15PAEs were in the range of 75.0-6369 μg kg(-1). Three provinces (i.e., Fujian, Guangdong and Xinjiang, China) showed the highest loadings of PAEs. Bis(2-Ethylhexyl) phthalate (DEHP) was found as the most abundant component and contributed 71.5% to the ∑15PAEs. The major source of PAEs in arable soils was associated with the application of agricultural plastic films, followed by the activities for soil fertility. Furthermore, the non-cancer and carcinogenic risks of target PAEs were estimated. The hazard indexes (HIs) of PAEs in all samples were below 1 and the carcinogenic risk levels were all within 10(-4). Results from this study will provide valuable information for Chinese agricultural soil management and risk avoidance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Indoor phthalate concentration in residential apartments in Chongqing, China: Implications for preschool children's exposure and risk assessment

NASA Astrophysics Data System (ADS)

Bu, Zhongming; Zhang, Yinping; Mmereki, Daniel; Yu, Wei; Li, Baizhan

2016-02-01

Six phthalates - dimethyl phthalate (DMP), diethyl phthalate (DEP), di(isobutyl) phthalate (DiBP), di(n-butyl) phthalate (DnBP), butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) - in indoor gas-phase and dust samples were measured in thirty residential apartments for the first time in Chongqing, China. Monte-Carlo simulation was used to estimate preschool children's exposure via inhalation, non-dietary ingestion and dermal absorption based on gas-phase and dust concentrations. Risk assessment was evaluated by comparing the modeled exposure doses with child-specific benchmarks specified in California's Proposition 65. The detection frequency for all the targeted phthalates was more than 80% except for BBzP. DMP was the most predominant compound in the gas-phase (median = 0.91 μg/m3 and 0.82 μg/m3 in living rooms and bedrooms, respectively), and DEHP was the most predominant compound in the dust samples (median = 1543 μg/g and 1450 μg/g in living rooms and bedrooms, respectively). Correlation analysis suggests that indoor DiBP and DnBP might come from the same emission sources. The simulations showed that the median DEHP daily intake was 3.18-4.28 μg/day/kg-bw in all age groups, suggesting that it was the greatest of the targeted phthalates. The risk assessment indicated that the exposure doses of DnBP and DEHP exceeded the child-specific benchmarks in more than 90% of preschool children in Chongqing. Therefore, from a children's health perspective, efforts should focus on controlling indoor phthalate concentrations and exposures.

Phthalate esters in soil, plastic film, and vegetable from greenhouse vegetable production bases in Beijing, China: Concentrations, sources, and risk assessment.

PubMed

Li, Cheng; Chen, Jiayi; Wang, Jihua; Han, Ping; Luan, Yunxia; Ma, Xupu; Lu, Anxiang

2016-10-15

The increased use of plastic film in greenhouse vegetable production (GVP) could result in phthalate ester (PAE) contamination in vegetables. However, limited information is currently available on their occurrence and associated potential risks in GVP systems. The present study documents the occurrence and composition of 15 PAEs in soil, plastic film, and vegetable samples from eight large-scale GVP bases in Beijing, China. Results showed that PAEs are ubiquitous contaminants in these GVP bases. Total PAE concentrations ranged from 0.14 to 2.13mg/kg (mean 0.99mg/kg) in soils and from 0.15 to 6.94mg/kg (mean 1.49mg/kg) in vegetables. Di (2-ethylhexyl) phthalate, di-n-butyl phthalate, and diisobutyl phthalate were the most abundant components, which accounted for >90% of the total PAEs. This investigation also indicated that the widespread application of plastic film in GVP systems may be the primary source of these PAEs. The non-cancer and carcinogenic risks of target PAEs were estimated based on the exposures of vegetable intake. The hazard quotients of PAE in all vegetable samples were lower than 1 and the carcinogenic risks were also at acceptable levels for consumers. The data in this study can provide valuable information to understand the status of potential pollutants, specifically PAEs, in GVP systems. Copyright © 2016 Elsevier B.V. All rights reserved.

COMBINATION DOSE OF TWO PHTHALATES ADDITIVELY DEPRESSES TESTOSTERONE PRODUCTION AND INSL3 GENE EXPRESSION IN MALE RAT FETUSES

EPA Science Inventory

Diethylhexyl phthalate (DEHP) and di(n-butyl) phthalate (DBP) are phthalate esters used to modify plastic and polymer textures. Individually,in uteroexposure to DEHP and DBP inhibit reproductive tract development,induce reproductive organ malformations, and reduce testosterone (T...

40 CFR 721.3085 - Brominated phthalate ester.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Brominated phthalate ester. 721.3085... Substances § 721.3085 Brominated phthalate ester. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as brominated phthalate ester (PMN P-90-581) is...

40 CFR 721.3085 - Brominated phthalate ester.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Brominated phthalate ester. 721.3085... Substances § 721.3085 Brominated phthalate ester. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as brominated phthalate ester (PMN P-90-581) is...

40 CFR 721.3085 - Brominated phthalate ester.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Brominated phthalate ester. 721.3085... Substances § 721.3085 Brominated phthalate ester. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as brominated phthalate ester (PMN P-90-581) is...

75 FR 67692 - Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-03

... Product Safety Improvement Act of 2008 (CPSIA) (Pub. L. 110- 314). The CHAP will discuss possible risk... CONSUMER PRODUCT SAFETY COMMISSION Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes AGENCY: Consumer Product Safety Commission. ACTION: Notice of...

76 FR 57024 - Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... Product Safety Improvement Act of 2008 (CPSIA) (Pub. L. 110- 314). The CHAP will discuss its progress... CONSUMER PRODUCT SAFETY COMMISSION Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes AGENCY: Consumer Product Safety Commission. ACTION: Notice of...

MONO-(3-CARBOXYPROPYL) PHTHALATE, A METABOLITE OF DI-N-OCTYL PHTHALATE

EPA Science Inventory

Di-n-octyl phthalate (DnOP) is found as a component of mixed C6–C10 linear-chain phthalates used as plasticizers in various polyvinyl chloride applications, including flooring and carpet tiles. Following exposure and absorption, DnOP is metabolized to its hydrolytic monoester, mo...

Assessment of Phthalate-induced Changes in Fetal Rat Testis Gene Expression using an rt-PCR Drug Metabolism Array.

EPA Science Inventory

Phthalate esters are a large family of compounds used in many industrial and commercial products. Based on numerous studies, phthalates such as diethyl hexyl phthalate (DEHP) produce reproductive malformations in male rodents through reduction of testosterone production and gene ...

Occurrence of phthalates in aquatic environment and their removal during wastewater treatment processes: a review.

PubMed

Gani, Khalid Muzamil; Tyagi, Vinay Kumar; Kazmi, Absar Ahmad

2017-07-01

Phthalates are plasticizers and are concerned environmental endocrine-disrupting compounds. Due to their extensive usage in plastic manufacturing and personal care products as well as the potential to leach out from these products, phthalates have been detected in various aquatic environments including drinking water, groundwater, surface water, and wastewater. The primary source of their environmental occurrence is the discharge of phthalate-laden wastewater and sludge. This review focuses on recent knowledge on the occurrence of phthalate in different aquatic environments and their fate in conventional and advanced wastewater treatment processes. This review also summarizes recent advances in biological removal and degradation mechanisms of phthalates, identifies knowledge gaps, and suggests future research directions.

Temporal trends of cumulative risks to phthalate mixtures in the United States from 2005 to 2014

EPA Science Inventory

Phthalates are used in a wide range of consumer goods resulting in widespread exposures among the general population. Exposures to specific phthalates are expected to vary over time with changes in the patterns of phthalate use. We investigated the existence of trends in estimate...

75 FR 69662 - Workshop: Cumulative Mixtures Risk of Six Selected Phthalates in Support of Summary Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

...: Cumulative Mixtures Risk of Six Selected Phthalates in Support of Summary Information on the Integrated Risk... Workshop on the Cumulative Mixtures Risk of Six Selected Phthalates; Request for Public Comments. SUMMARY...) Review the recommendations for evaluation of the cumulative mixtures risk of phthalates as set forth in...

OCTANOL/WATER PARTITION COEFFICIENTS AND WATER SOLUBILITIES OF PHTHALATE ESTERS

EPA Science Inventory

Measurements of the octanol/water partition coefficients (K-ow) and water solubilities of di-n-octyl phthalate (DnOP) and di-n-decyl phthalate (DnDP) by the slow-stirring method are reported. The water solubility was also measured for di-n-hexyl phthalate (DnHP). The log K-ow val...

Using exposure prediction tools to link exposure and dosimetry for risk-based decisions: A case study with phthalates

EPA Science Inventory

A few different exposure prediction tools were evaluated for use in the new in vitro-based safety assessment paradigm using di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DnBP) as case compounds. Daily intake of each phthalate was estimated using both high-throughput (HT...

76 FR 38116 - Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... Product Safety Improvement Act of 2008 (CPSIA) (Pub. L. 110- 314). DATES: The meeting will be held on... CONSUMER PRODUCT SAFETY COMMISSION Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes AGENCY: Consumer Product Safety Commission. ACTION: Notice of meeting...

75 FR 73048 - Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-29

..., pursuant to section 108 of the Consumer Product Safety Improvement Act of 2008 (CPSIA) (Pub. L. 110- 314... CONSUMER PRODUCT SAFETY COMMISSION Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes AGENCY: Consumer Product Safety Commission. ACTION: Notice of meeting...

76 FR 63610 - Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-13

... Product Safety Improvement Act of 2008 (CPSIA) (Pub. L. 110- 314). DATES: The meeting will be held on... CONSUMER PRODUCT SAFETY COMMISSION Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes AGENCY: Consumer Product Safety Commission. ACTION: Notice of meeting...

76 FR 13988 - Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... Product Safety Improvement Act of 2008 (CPSIA) (Pub. L. 110- 314). DATES: The meeting will be held on... CONSUMER PRODUCT SAFETY COMMISSION Notice of Meeting of Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes AGENCY: Consumer Product Safety Commission. ACTION: Notice of meeting...

Barium alginate caged Fe3O4@C18 magnetic nanoparticles for the pre-concentration of polycyclic aromatic hydrocarbons and phthalate esters from environmental water samples.

PubMed

Zhang, Shengxiao; Niu, Hongyun; Cai, Yaqi; Shi, Yali

2010-04-30

The hydrophobic octadecyl (C(18)) functionalized Fe(3)O(4) magnetic nanoparticles (Fe(3)O(4)@C(18)) were caged into hydrophilic barium alginate (Ba(2+)-ALG) polymers to obtain a novel type of solid-phase extraction (SPE) sorbents, and the sorbents were applied to the pre-concentration of polycyclic aromatic hydrocarbons (PAHs) and phthalate esters (PAEs) pollutants from environmental water samples. The hydrophilicity of the Ba(2+)-ALG cage enhances the dispersibility of sorbents in water samples, and the superparamagnetism of the Fe(3)O(4) core facilitates magnetic separation. With the magnetic SPE technique based on the Fe(3)O(4)@C(18)@Ba(2+)-ALG sorbents, it requires only 30 min to extract trace levels of analytes from 500 mL water samples. After the eluate is condensed to 0.5 mL, concentration factors for both phenanthrene and di-n-propyl-phthalate are over 500, while for other analytes are about 1000. The recoveries of target compounds are independent of salinity and solution pH under testing conditions. Under optimized conditions, the detection limits for phenanthrene, pyrene, benzo[a]anthracene, and benzo[a]pyrene are 5, 5, 3, and 2 ng L(-1), and for di-n-propyl-phthalate, di-n-butyl-phthalate, di-cyclohexyl-phthalate, and di-n-octyl-phthalate are 36, 59, 19, and 36 ng L(-1), respectively. The spiked recoveries of several real water samples for PAHs and PAEs are in the range of 72-108% with relative standard deviations varying from 1% to 9%, showing good accuracy of the method. The advantages of the new SPE method include high extraction efficiency, short analysis time and convenient extraction procedure. To the best of our knowledge, it is unprecedented that hydrophilic Ba(2+)-ALG polymer caged Fe(3)O(4)@C(18) magnetic nanomaterial is used to extract organic pollutants from large volumes of water samples. Copyright 2010 Elsevier B.V. All rights reserved.

Phthalates impact human health: Epidemiological evidences and plausible mechanism of action.

PubMed

Benjamin, Sailas; Masai, Eiji; Kamimura, Naofumi; Takahashi, Kenji; Anderson, Robin C; Faisal, Panichikkal Abdul

2017-10-15

Disregarding the rising alarm on the hazardous nature of various phthalates and their metabolites, ruthless usage of phthalates as plasticizer in plastics and as additives in innumerable consumer products continues due low their cost, attractive properties, and lack of suitable alternatives. Globally, in silico computational, in vitro mechanistic, in vivo preclinical and limited clinical or epidemiological human studies showed that over a dozen phthalates and their metabolites ingested passively by man from the general environment, foods, drinks, breathing air, and routine household products cause various dysfunctions. Thus, this review addresses the health hazards posed by phthalates on children and adolescents, epigenetic modulation, reproductive toxicity in women and men; insulin resistance and type II diabetes; overweight and obesity, skeletal anomalies, allergy and asthma, cancer, etc., coupled with the description of major phthalates and their general uses, phthalate exposure routes, biomonitoring and risk assessment, special account on endocrine disruption; and finally, a plausible molecular cross-talk with a unique mechanism of action. This clinically focused comprehensive review on the hazards of phthalates would benefit the general population, academia, scientists, clinicians, environmentalists, and law or policy makers to decide upon whether usage of phthalates to be continued swiftly without sufficient deceleration or regulated by law or to be phased out from earth forever. Copyright © 2017. Published by Elsevier B.V.

Thermoreversible gelation of poly(vinylidene fluoride) in phthalates: the influence of aliphatic chain length of solvents.

PubMed

Yadav, P Jaya Prakash; Ghosh, Goutam; Maiti, Biswajit; Aswal, Vinod K; Goyal, P S; Maiti, Pralay

2008-04-17

Thermoreversible gelation of poly(vinylidene fluoride) (PVDF) has been studied in a new series of solvents (phthalates), for example, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), and dihexyl phthalate (DHP) as a function of temperature and polymer concentration, both by test tube tilting and dynamic light scattering (DLS) method. The effect of aliphatic chain length (n) of diesters on the gelation kinetics, structure/microstructure and morphology of PVDF gels has been examined. Gelation rate was found to increase with increasing aliphatic chain length of diester. DLS results indicate that the sol-gel transformation proceeds via two-steps: first, microgel domains were formed, and then the infinite three-dimensional (3D) network is established by connecting microgels through polymer chains. The crystallites are responsible for 3D network for gelation in phthalates, and alpha-polymorph is formed during gelation producing higher amount of crystallinity with increasing aliphatic chain length of diester. Morphology of the networks of dried gels in different phthalates showed that fibril thickness and lateral dimensions decrease with higher homologues of phthalates. The scattering intensity is fitted with Debye-Bueche model in small-angle neutron scattering and suggested that both the correlation length and interlamellar spacing increases with n. A model has been proposed, based on electronic structure calculations, to explain the conformation of PVDF chain in presence of various phthalates and their complexes, which offer the cause of higher gelation rate for longer aliphatic chain length.

Fate and transport modeling of phthalate esters from biosolid amended soil under corn cultivation.

PubMed

Sayyad, G; Price, G W; Sharifi, M; Khosravi, K

2017-02-05

Phthalate esters (PAEs) are prevalent in the environment due to the broad range of industrial, agriculture and domestic applications. The ubiquitous use of PAEs has resulted in their potential to reach groundwater sources through application of agri-chemicals and municipal biosolids. A study was conducted to monitor the fate and transport of seven commonly detected PAEs in the environment including: dimethyl phthalate (DMP), diethyl phthalate (DEP), benzyl butyl phthalate (BBP), bis(di-ethyl hexyl) phthalate (DEHP), di-n-octyl phthalate (DnOP), dipentyl phthalate (DPP), and di-n-butyl phthalate (DnBP). Biosolids sourced from the Halifax Regional Municipality were applied at three rates on field-based lysimeter cells which were cropped to corn (Zea mays) for one growing season. In the present study, breakthrough curves (BTCs) were established for phthalates leaching from a corn-cultivated agricultural soil profile. The HYDRUS-1D model and a two-site sorption model were applied to predict transport parameters of PAEs using an inverse solution approach. Results of our research revealed that higher PAE adsorption was observed based on increasing carbon chain number. In addition, higher values of F (i.e. the fraction of type-1 sorption sites assumed to be in equilibrium with the solution phase) and lower values of D (i.e. dispersion coefficient) were observed for PAEs with large carbon chains which was validated both through the empirical dataset and the model simulations. Copyright © 2016. Published by Elsevier B.V.

[Analysis of phthalates in plastic food-packaging bags by thin layer chromatography].

PubMed

Chen, Hui; Wang, Yuan; Zhu, Ruohua

2006-01-01

The method for simultaneous determination of four phthalates, namely dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) in plastic food-packaging bags by thin layer chromatography (TLC) was developed. The plastic food-packaging bags were extracted with ethanol by ultrasonication, then the mixture was filtrated through membrane (0.45 microm). The mixture of ethyl acetate-anhydrous ether-isooctane (1 : 4 : 15, v/v) was used as developing agent on the TLC silica gel plate for development. The filtered liquid was spotted on the TLC plate dealt by acetone, and detected with scanning wavelength of 275 nm and reference wavelength of 340 nm. The qualitative analysis of the phthalates was performed using the R(f) values of the chromatogram. The quantitative analysis was performed with external standard method. Good linearities were obtained for DMP, DEP, DBP and DEHP. The detection limits were 2.1 ng for DMP, 2.4 ng for DEP, 3.4 ng for DBP and 4.0 ng for DEHP. The relative standard deviations (RSDs) of the four phthalates were 2.8% - 3.5%. The recoveries of the four phthalate standards in real sample were 78.58% - 111.04%. The method presented has the advantages of high precision, high sensitivity, small sample size, and simple pretreatment . The method was used to detect the four phthalates in the food-packaging bags. The contents in real samples were close to the results by gas chromatography.

Dietary exposure and human risk assessment of phthalate esters based on total diet study in Cambodia.

PubMed

Cheng, Zhang; Li, Han-Han; Wang, Hong-Sheng; Zhu, Xue-Mei; Sthiannopkao, Suthipong; Kim, Kyoung-Woong; Yasin, Mohamed Salleh Mohamed; Hashim, Jamal Hisham; Wong, Ming-Hung

2016-10-01

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 human to phthalates are limited. In this study, to assess the daily intakes of phthalate esters and the possible adverse health impacts, different food samples were collected from three areas of Cambodia, one of the poorest countries in the world. The ∑phthalate ester concentrations in Kampong Cham, Kratie and Kandal provinces ranged from 0.05 to 2.34 (median 0.88) μgg(-1), 0.19-1.65 (median 0.86) μgg(-1) and 0.24-3.05 (median 0.59) μgg(-1) wet weight (ww), respectively. Di-2-Ethylhexyl phthalate (DEHP) and diisobutyl phthalate (DiBP) were the predominant compounds among all foodstuffs. The estimated daily intake (EDI) of phthalate esters for the general population in Kampong Cham, Kratie and Kandal was 34.3, 35.6 and 35.8μgkg(-1) bw d(-1), respectively. The dietary daily intake of DEHP, benzylbutyl phthalate (BBP) and di-n-butyl phthalate (DBP) in Kampong Cham, Kratie and Kandal were below the tolerable daily intakes (TDI) imposed by the European Food Safety Authority (EFSA) and reference doses (RfD) imposed by The United States Environmental Protection Agency (USEPA). Rice contributed the greatest quantity of DEHP to the daily intake in Cambodia so may deserve further exploration. To our knowledge, this is the first study to investigate the occurrence and the daily intakes of phthalate esters in Cambodia. Copyright © 2016 Elsevier Inc. All rights reserved.

Determination of phthalic acid esters in water samples using core-shell poly(dopamine) magnetic nanoparticles and gas chromatography tandem mass spectrometry.

PubMed

González-Sálamo, Javier; Socas-Rodríguez, Bárbara; Hernández-Borges, Javier; Rodríguez-Delgado, Miguel Ángel

2017-12-29

In this work, the first application of core-shell poly(dopamine) magnetic nanoparticles as sorbent for the extraction of a group of eleven phthalic acid esters of interest (i.e. diethyl phthalate (DEP), dipropyl phthalate (DPP), dibutyl phthalate (DBP), bis-isopentyl phthalate (DIPP), bis-n-pentyl phthalate (DNPP), benzylbutyl phthalate (BBP), dicyclohexyl phthalate (DCHP), di-(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP)) and one adipate (bis (2-ethylhexyl) adipate, DEHA) from different water samples (Milli-Q, mineral, tap, pond and waste water) is proposed. Analysis were carried out by gas chromatography triple quadrupole tandem mass spectrometry. Parameters that affect the extraction performance were optimized following a step by step approach, being the optimum conditions the extraction of water at pH 6, with 60mg of sorbent and the elution with 6mL of dichloromethane. The methodology was validated for the five selected water samples using DBP-d 4 as internal standard. Determination coefficients of matrix-matched calibration curves were above 0.9904 in all cases while relative recovery values ranged between 71 and 120%, with relative standard deviation values below 19%. The limits of quantification of the method ranged between 9 and 20ng/L. Matrix effects were found for most analytes and water samples. Real water samples were also analyzed, finding DEP and DBP at concentrations below 4.20 and 1.23μg/L, respectively, in mineral, tap and waste water. DCHP, DEHP and BBP were also found in some of the samples at concentrations below the LOQs of the method. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of phthalate esters in autism development: A systematic review.

PubMed

Jeddi, Maryam Zare; Janani, Leila; Memari, Amir Hossein; Akhondzadeh, Shahin; Yunesian, Masud

2016-11-01

Available evidence implicates environmental factors in the pathogenesis of autism spectrum disorders (ASD). However, the role of specific environmental chemicals such as phthalate esters that influence ASD risk remains elusive. This paper systematically reviews published evidences on association between prenatal and/or childhood exposure to phthalate and ASD. Studies pertaining to systematic literature search from Scopus, PubMed, PsycInfo and Web of Science prior to December 2015 were identified. The authors included studies which assessed the effect of exposure to phthalates on occurrence of ASD. This comprehensive bibliographic search identified five independent studies. Each eligible paper was summarized with respect to its methods and results with particular attention to study design and exposure assessment. Because of the heterogeneity in the type of included studies, different methods of assessing exposure to phthalates and the use of different statistics for summarizing the results, meta-analysis could not be used to combine the results of included studies. The results of this systematic review have revealed the limited number of studies conducted and assessed phthalate exposure. Seven studies were regarded as relevant to the objectives of this review. Two of them did not measure phthalate exposure directly and did not result in quantitative results. Out of the five studies in which phthalate exposure was mainly measured by the examining biomarkers in biological samples, two were cohort studies (one with positive results and another one with not clear association). Among the three case control studies, two of them showed a significant relation between exposure to phthalate and ASD and the last case control study had negative results. Indeed, this case control studies showed a compromised phthalate metabolite glucuronidation pathway, as a probable explanation of mechanism of the relation between phthalate exposure and ASD. This review reveals evidence showing a connection between exposure to phthalates and ASD. Nevertheless, further research is needed with appropriate attention to exposure assessment and relevant pre and post-natal cofounders. Copyright © 2016 Elsevier Inc. All rights reserved.

Neonatal intensive care unit phthalate exposure and preterm infant neurobehavioral performance.

PubMed

Stroustrup, Annemarie; Bragg, Jennifer B; Andra, Syam S; Curtin, Paul C; Spear, Emily A; Sison, Denise B; Just, Allan C; Arora, Manish; Gennings, Chris

2018-01-01

Every year in the United States, more than 300,000 infants are admitted to neonatal intensive care units (NICU) where they are exposed to a chemical-intensive hospital environment during a developmentally vulnerable period. The neurodevelopmental impact of environmental exposure to phthalates during the NICU stay is unknown. As phthalate exposure during the third trimester developmental window has been implicated in neurobehavioral deficits in term-born children that are strikingly similar to a phenotype of neurobehavioral morbidity common among children born premature, the role of early-life phthalate exposure on the neurodevelopmental trajectory of premature infants may be clinically important. In this study, premature newborns with birth weight <1500g were recruited to participate in a prospective environmental health cohort study, NICU-HEALTH (Hospital Exposures and Long-Term Health), part of the DINE (Developmental Impact of NICU Exposures) cohort of the ECHO (Environmental influences on Child Health Outcomes) program. Seventy-six percent of eligible infants enrolled in the study. Sixty-four of 81 infants survived and are included in this analysis. 164 urine specimens were analyzed for phthalate metabolites using high-performance liquid chromatography/tandem mass spectrometry. The NICU Network Neurobehavioral Scale (NNNS) was performed prior to NICU discharge. Linear and weighted quantile sum regression quantified associations between phthalate biomarkers and NNNS performance, and between phthalate biomarkers and intensity of medical intervention. The sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) was associated with improved performance on the Attention and Regulation scales. Specific mixtures of phthalate biomarkers were also associated with improved NNNS performance. More intense medical intervention was associated with higher ∑DEHP exposure. NICU-based exposure to phthalates mixtures was associated with improved attention and social response. This suggests that the impact of phthalate exposure on neurodevelopment may follow a non-linear trajectory, perhaps accelerating the development of certain neural networks. The long-term neurodevelopmental impact of NICU-based phthalate exposure needs to be evaluated.

Bisphenol and phthalate concentrations and its determinants among pregnant women in a population-based cohort in the Netherlands, 2004-5.

PubMed

Philips, Elise M; Jaddoe, Vincent W V; Asimakopoulos, Alexandros G; Kannan, Kurunthachalam; Steegers, Eric A P; Santos, Susana; Trasande, Leonardo

2018-02-01

Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring. To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants. In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004-2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1-14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns. Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73nmol/l [95% CI 14.56-93.72] and 1.03nmol/l [0.31-2.06]). Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004-5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust. Copyright © 2017 Elsevier Inc. All rights reserved.

Bisphenol and phthalate concentrations and its determinants among pregnant women in a population-based cohort in the Netherlands, 2004–5

PubMed Central

Philips, Elise M.; Jaddoe, Vincent W.V.; Asimakopoulos, Alexandros G.; Kannan, Kurunthachalam; Steegers, Eric A.P.; Santos, Susana; Trasande, Leonardo

2018-01-01

Background Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring. Objective To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants. Methods In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004–2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1–14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns. Results Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73 nmol/l [95% CI 14.56–93.72] and 1.03 nmol/l [0.31–2.06]). Conclusion Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004–5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust. PMID:29245124

Mono-(2-ethylhexyl) phthalate (MEHP) regulates glucocorticoid metabolism through 11{beta}-hydroxysteroid dehydrogenase 2 in murine gonadotrope cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Dun; Department of Orthopedics, Taizhou Hospital, Wenzhou Medical College, Lin Hai, ZJ 317000; Li, Xing-Wang

2009-11-13

Di-(2-ethylhexyl) phthalate (DEHP) and its metabolite mono-(2-ethylhexyl) phthalate (MEHP) have been classified as toxicants to the reproductive system at the testis level and DEHP may also impair reproductive axis function at the pituitary levels. However, MEHP is 10-fold more potent than DEHP in toxicity and little is known about the toxicological effect of MEHP on pituitary. In this study, we demonstrated that 11{beta}-hydroxysteroid dehydrogenase type 2 (11{beta}-HSD2), not 11{beta}-HSD1, is strongly expressed in murine gonadotrope L{beta}T2 cells. Interestingly, MEHP inhibited Hsd11b2 mRNA level and 11{beta}-HSD2 enzyme activity in L{beta}T2 cells at as low as 10{sup -7} M. Corticosterone (CORT) atmore » a concentration of 10{sup -6} M significantly inhibited L{beta}T2 cell proliferation after 2-day culture, and 10{sup -6} M RU486, an antagonist of glucocorticoid receptor (GR), reversed this inhibition. However, in the presence of 10{sup -5} or 10{sup -4} M MEHP, the minimal concentration of CORT to inhibit the proliferation of L{beta}T2 cells was lowered to 10{sup -7} M, and 10{sup -6} M RU486 was not able to completely reverse the CORT effect. In conclusion, along with the regulation of GR, 11{beta}-HSD2 may have a key role in glucocorticoid metabolism in L{beta}T2 cells. MEHP may participate in the glucocorticoid metabolism in L{beta}T2 cells through inhibition of 11{beta}-HSD2 enzyme activity. Such perturbation may be of pathological significance as MEHP may interfere with the reproductive system at pituitary level through regulation of glucocorticoid metabolism, especially in neonates with higher risk of phthalates exposure.« less

Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinsberg, Jochen; Wegener-Toper, Petra; Ven, Katrin van der

2009-08-15

The phthalate ester mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of di-(2-ethylhexyl) phthalate, a high-production-volume chemical used as a plasticizer and solvent in numerous consumer products. MEHP has been demonstrated to be a reproductive toxicant in rodents decreasing estradiol and progesterone production in preovulatory granulosa cells. In the present study, we examined the effect of MEHP on steroid production of human granulosa-lutein (GL) cells. Human GL cells collected from women undergoing in vitro fertilization were cultured in medium containing FSH, hCG and 8-Br-cAMP, respectively, together with various concentrations of MEHP (0-500 {mu}mol L{sup -1}). After incubation for 48 h estradiolmore » and progesterone were assayed in the spent culture medium. Furthermore, aromatase activity and mRNA levels of GL cells were determined. Basal as well as FSH-, hCG- and 8-Br-cAMP-stimulated estradiol production of GL cells was suppressed by MEHP in a dose-dependent manner (IC{sub 50} = 105 {mu}mol L{sup -1}, 138 {mu}mol L{sup -1}, 49 {mu}mol L{sup -1} and 78 {mu}mol L{sup -1}). Furthermore aromatase activity and mRNA levels were reduced in GL cells cultured with MEHP. In contrast, MEHP did not alter the production of progesterone up to a concentration of 167 {mu}mol L{sup -1}. The present data indicate that MEHP is a specific inhibitor of estradiol production in human GL cells with a post-cAMP site of action. The inhibition of estradiol production obviously results from a reduction of aromatase activity on the transcript level. As the in vitro effective doses of MEHP are within the range of real environmental exposure levels an inhibitory effect on estrogen production in vivo seems to be possi0009b.« less

Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl; Laboratory for Health Protection Research, National Institute for Public Health and the Environment; Verhoef, Aart

The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 atmore » doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the developing immune system for DEHP.« less

Food Emulsifier Glycerin Monostearate Increases Internal Exposure Levels of Six Priority Controlled Phthalate Esters and Exacerbates Their Male Reproductive Toxicities in Rats.

PubMed

Gao, Hai-Tao; Xu, Run; Cao, Wei-Xin; Zhou, Xu; Yan, Ye-Hui-Mei; Lu, Lingeng; Xu, Qian; Shen, Yang

2016-01-01

Human beings are inevitably exposed to ubiquitous phthalate esters (PAEs). Processed, packaged foods are popular nowadays, in which emulsifiers are frequently added as food additives. It is unclear how emulsifiers affect the bioavailability of ingested PAEs contaminants and their toxicities. The purposes of our study were to explore whether food emulsifier Glycerin Monostearate (GMS) could increase the internal exposure levels of six priority controlled PAEs and affect their reproductive toxicities when male rats are exposed to PAEs mixture (MIXPs). The male rats were exposed to MIXPs by gavage for thirty days in combination with or without given GMS. Phthalate monoesters (MPAEs), primary metabolites of PAEs, in rat urine were used as biomarkers to predict the internal exposure levels of the six PAEs, and their concentrations were determined using UPLC-MS. The reproductive toxicity was evaluated using serum testosterone levels test and histopathology of testes. Results showed that compared to PAEs exposure alone, the internal exposure levels of PAEs increased by 30%-49% in the presence of GMS. PAEs exposure led to the reduction of testosterone level by 23.4%-42.1% in the presence and absence of GMS, respectively, compared to the baseline. Testosterone levels in MIXPs+GMS and DEHP+GMS group were decreased by 9.1% and 13.6%, respectively, compared with MIXPs and DEHP group. Histopathology showed that injuries of testis (deciduous spermatids) were observed, and GMS exacerbated the injuries. The results indicated food emulsifiers chronically taken up might increase safety risks of food PAEs contaminants.

Impact of endocrine disrupting compounds in sewage impacted coastal area on seabream.

PubMed

Al-Jandal, Noura; Saeed, Talat; Azad, Ismail; Al-Subiai, Sherain; Al-Zekri, Waleed; Hussain, Sumaiah; Al-Hasan, Enas

2018-04-15

The pollution of coastal regions worldwide has been of a great concern due to the presence of endocrine disrupting chemicals (EDCs). These chemicals find their way to the marine environment via the sewage treatment plants (STPs). Hence, this study was designed to investigate the status and sources of EDCs and their effect on fish in Kuwait's coastal areas, from the chemical and biological perspectives. The assessment of three STPs indicated the presence of significant levels of phthalates (19 and 31µg/l), alkylphenols (85 and 159ng/l), and estrogens (30 and 368ng/l) in both inflow and outflow samples. The analysis of samples from field exposure sites revealed significant levels of EDCs in seawater (phthalates: 2.1-4.6µg/l; alkylphenols: 1.2-16.4ng/l; estrogens: 0-36.2ng/l) and sediment (phthalates: 2.1-15.7mg/kg dry wt; alkyphenols: 2.5-15.1µg/kg dry wt.; estrogens: 4.1-214.2µg/kg dry wt.) samples. The biological perspective investigated through the exposure of fish to sewage outlets at five sites. The hepatosomatic index (HSI) revealed a higher level in winter samples 0.48-0.79%) in comparison to summer samples 1-1.5%). Histological observation of hepatic tissue of fish exposed during winter months in all sites, showed much less necrotic changes and hepatic vacuolation in the hepatic tissue of summer exposed fish. Imunnohistochemistry evidences revealed a significant level of positive signals and Vtg localization in the hepatic tissue as the results support the histopathological alterations observed. Results of enzyme-linked immunosorbent assay (ELISA) showed no significant difference between the plasma protein content of winter and summer samples. Overall, the study suggest that there is possible local source or a chronic input of untreated and/or partially treated water due to the significant levels of phthalates, alkyphenols, and estrogens detected in the Kuwait Bay. These levels were enough to initiate alteration in the hepatic tissue of fish exposed to the sewage outlets in Kuwait for two weeks. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinetics of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate in blood and of DEHP metabolites in urine of male volunteers after single ingestion of ring-deuterated DEHP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kessler, Winfried, E-mail: kessler@helmholtz-muenchen.de; Numtip, Wanwiwa; Völkel, Wolfgang

2012-10-15

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is suspected to induce antiandrogenic effects in men via its metabolite mono(2-ethylhexyl) phthalate (MEHP). However, there is only little information on the kinetic behavior of DEHP and its metabolites in humans. The toxikokinetics of DEHP was investigated in four male volunteers (28–61 y) who ingested a single dose (645 ± 20 μg/kg body weight) of ring-deuterated DEHP (DEHP-D{sub 4}). Concentrations of DEHP-D{sub 4}, of free ring-deuterated MEHP (MEHP-D{sub 4}), and the sum of free and glucuronidated MEHP-D{sub 4} were measured in blood for up to 24 h; amounts of the monoesters MEHP-D{sub 4}, ring-deuterated mono(2-ethyl-5-hydroxyhexyl)more » phthalate and ring-deuterated mono(2-ethyl-5-oxohexyl) phthalate were determined in urine for up to 46 h after ingestion. The bioavailability of DEHP-D{sub 4} was surprisingly high with an area under the concentration-time curve until 24 h (AUC) amounting to 50% of that of free MEHP-D{sub 4}. The AUC of free MEHP-D{sub 4} normalized to DEHP-D{sub 4} dose and body weight (AUC/D) was 2.1 and 8.1 times, that of DEHP-D{sub 4} even 50 and 100 times higher than the corresponding AUC/D values obtained earlier in rat and marmoset, respectively. Time courses of the compounds in blood and urine of the volunteers oscillated widely. Terminal elimination half-lives were short (4.3–6.6 h). Total amounts of metabolites in 22-h urine are correlated linearly with the AUC of free MEHP-D{sub 4} in blood, the parameter regarded as relevant for risk assessment. -- Highlights: ► After DEHP intake, DEHP and MEHP in blood show oscillating time courses. ► Dose-related blood levels of DEHP are 50 times higher in humans than in rats. ► Dose-related blood levels of free MEHP are 2 times higher in humans than in rats. ► Elimination of DEHP and its metabolites is short with half-lives of 4.3-6.6 h.« less

Alternatives to Certain Phthalates Partnership

EPA Pesticide Factsheets

The alternatives assessment partnership project on alternatives to certain phthalates seeks to eplore the human health and environmental profiles of eight action plan phthalates and functional alternatives

A mixture of five phthalate diesters cummulatively inhibit fetal testicular testoserone production in a manner consisent with their predicted reporduction toxicity in the Sprague Dawley rat.

EPA Science Inventory

Phthalate diesters are commonly-used plasticizers in intravenous bags, plastic food wrap and children’s toys, and the metabolites of multiple phthalates are detected in humans. In utero exposure to certain phthalates during sexual differentiation causes male reproductive tract m...

Fetal Phthalate Screen: Assessment of Several Phthalate Esters on Fetal Rodent Testosterone Production and Gene Expression Following In Utero Exposure

EPA Science Inventory

Phthalate esters(PE) are a large family of compounds used in a wide array of common products from medical tubing to pharmaceuticals to cables, and wall/floor coverings. Laboratory studies have demonstrated that in utero treatment with PE such as di-ethyl hexyl phthalate (DEHP) du...

A mixture of five phthalate esters inhibits fetal testicular testosterone production in a cummulative manner consistent with their predicted reproductive toxicity in the Sprague Dawley rat

EPA Science Inventory

Phthalate diesters are plasticizers to which humans are ubiquitously exposed. Exposure to certain phthalates during sexual differentiation causes reproductive tract malformations in male rats. In the fetal rat, exposure to the phthalates benzylbutyl (BBP), di(n)butyl (DBP), and...

27 CFR 21.106 - Diethyl phthalate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Diethyl phthalate. 21.106....106 Diethyl phthalate. (a) Refractive index at 25 °C. 1.497 to 1.502. (b) Color. Colorless. (c) Odor... °/25 °C. 1.115 to 1.118. (f) Ester content (as diethyl phthalate). Not less than 99 percent by weight...

27 CFR 21.106 - Diethyl phthalate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Diethyl phthalate. 21.106....106 Diethyl phthalate. (a) Refractive index at 25 °C. 1.497 to 1.502. (b) Color. Colorless. (c) Odor... °/25 °C. 1.115 to 1.118. (f) Ester content (as diethyl phthalate). Not less than 99 percent by weight...

27 CFR 21.106 - Diethyl phthalate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Diethyl phthalate. 21.106....106 Diethyl phthalate. (a) Refractive index at 25 °C. 1.497 to 1.502. (b) Color. Colorless. (c) Odor... °/25 °C. 1.115 to 1.118. (f) Ester content (as diethyl phthalate). Not less than 99 percent by weight...

27 CFR 21.106 - Diethyl phthalate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Diethyl phthalate. 21.106....106 Diethyl phthalate. (a) Refractive index at 25 °C. 1.497 to 1.502. (b) Color. Colorless. (c) Odor... °/25 °C. 1.115 to 1.118. (f) Ester content (as diethyl phthalate). Not less than 99 percent by weight...

Determination of phthalate ester plasticizers in the aquatic environment using hollow fibre supported liquid membranes

NASA Astrophysics Data System (ADS)

Mtibe, A.; Msagati, Titus A. M.; Mishra, Ajay K.; Mamba, Bhekie B.

Phthalates are known to be carcinogenic, teratogenic as well as endocrine disruptors. The potential risk to human and animals health generated from them has drawn great attention all over the world. Hollow fibre supported liquid membrane (HFSLM) online with high pressure liquid chromatography (HPLC) was used to determine benzyl butyl phthalate (BBP), dibutyl phthalate (DBP) and Diethylhexyl phthalate (DEHP) in wastewater. Toluene, di-n-hexyl ether and undecane were used as liquid barriers separating both donor (sample) and acceptor phase. Toluene performed much better than undecane and was used in sample preparation. The presence of toluene showed the potential for the enrichment and removal of phthalates to the concentrations ranges from 0 to 1.7 mg L-1.

Direct determination of trace phthalate esters in alcoholic spirits by spray-inlet microwave plasma torch ionization tandem mass spectrometry.

PubMed

Miao, Meng; Zhao, Gaosheng; Xu, Li; Dong, Junguo; Cheng, Ping

2018-03-01

A direct analytical method based on spray-inlet microwave plasma torch tandem mass spectrometry was applied to simultaneously determine 4 phthalate esters (PAEs), namely, benzyl butyl phthalate, diethyl phthalate, dipentyl phthalate, and dodecyl phthalate with extremely high sensitivity in spirits without sample treatment. Among the 4 brands of spirit products, 3 kinds of PAE compounds were directly determined at very low concentrations from 1.30 to 114 ng·g -1 . Compared with other online and off-line methods, the spray-inlet microwave plasma torch tandem mass spectrometry technique is extremely simple, rapid, sensitive, and high efficient, providing an ideal screening tool for PAEs in spirits. Copyright © 2017 John Wiley & Sons, Ltd.

21 CFR 181.27 - Plasticizers.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Butylphthalyl butyl glycolate. Dibutyl sebacate. Di-(2-ethylhexyl) phthalate (for foods of high water content only). Diethyl phthalate. Diisobutyl adipate. Diisooctyl phthalate (for foods of high water content...

Urinary parabens and polyaromatic hydrocarbons independent of health conditions are associated with adult emotional support needs: USA NHANES, 2005-2008.

PubMed

Shiue, Ivy

2015-09-01

Everyone needs emotional support at some point in life, but the needs might not always be met. The present study was aimed to investigate the prevalence of unmet needs of emotional support in adults and to identify social, environmental and health attributes in a national and population-based setting in recent years. Data was retrieved from the US National Health and Nutrition Examination Surveys, 2005-2008, including demographics, blood pressure readings, self-reported emotional support needs in the last 12 months, self-reported ever health conditions and urinary environmental chemical concentrations. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling and population attributable risk (PAR) estimation. Of 6733 American adults aged 40-80, 1273 (21.0 %) needed more emotional support in the past year. They tended to be aged 40-60, female, Mexican American, other Hispanic, education less than high school, or poverty income ratio 5+. People with higher levels of butyl paraben, ethyl paraben, methyl paraben, 1-hydroxynaphthalene, 2-hydroxynaphthalene, or 9-hydroxyfluorene (but not heavy metals, arsenic, phenols, phthalates, pesticides, or phytoestrogens) or historical diabetes, asthma, arthritis, stroke, thyroid disorder, chronic bronchitis, sleep complaint/disorder, or trouble seeing needed more emotional support. Significant risk associations from environmental chemicals mentioned above have remained after adjusting for historical health conditions as potential mediators. This is the first time examining prevalence of the unmet emotional support in adults and identifying the social, environmental and health attributes. Removal of parabens and polyaromatic hydrocarbons and increasing healthcare for people with health conditions to accommodate emotional support should be considered.

IgE antibodies and urinary trimethylarsine oxide accounted for 1-7% population attributable risks for eczema in adults: USA NHANES 2005-2006.

PubMed

Shiue, Ivy

2015-12-01

Population attributable risks from serum IgE and dust miteallergen concentrations and environmental chemicals for eczema are unclear. Therefore, it was aimed to examine serum IgE and allergen concentrations and environmental chemicals for eczema in adults and to calculate population attributable risks in a national and population-based setting. Data retrieved from the National Health and Nutrition Examination Survey, 2005-2006, was analyzed. Information on demographics and self-reported ever eczema was obtained by household interview. Bloods and urines (sub-sample) were also collected during the interview. Adults aged 20-85 were included. Statistical analyses were using chi-square test, t test, survey-weighted logistic regression modeling, and population attributable risk (PAR) estimation. Of all the included American adults (n = 4979), 310 (6.2%) reported ever eczema. Moreover, more eczema cases were observed in female adults but fewer cases in people born in Mexico. There were no significant associations observed between commonly known biomarkers (including vitamin D) and eczema or between dust mite allergens and eczema. Serum D. Farinae (PAR 1.0%), D. Pteronyssinus (PAR 1.1%), cat (PAR 1.8%), dog (PAR 1.6%), and muse (PAR 3.2%) IgE antibodies were associated with eczema. Adults with ever eczema were found to have higher levels of urinary trimethylarsine oxide concentrations (PAR 7.0%) but not other speciated arsenic concentrations. There were no clear associations between other environmental chemicals including heavy metals, phthalates, phenols, parabens, pesticides, nitrate, perchlorate, polycyclic hydrocarbons and eczema as well. Elimination of environmental risks might help delay or stop eczema up to 7% in the adult population.

21 CFR 181.27 - Plasticizers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... sebacate. Di-(2-ethylhexyl) phthalate (for foods of high water content only). Diethyl phthalate. Diisobutyl adipate. Diisooctyl phthalate (for foods of high water content only). Diphenyl-2-ethylhexyl phosphate...

Human Fetal Testis Xenografts Are Resistant to Phthalate-Induced Endocrine Disruption

PubMed Central

Heger, Nicholas E; Hall, Susan J; Sandrof, Moses A; McDonnell, Elizabeth V; Hensley, Janan B; McDowell, Erin N; Martin, Kayla A; Gaido, Kevin W; Johnson, Kamin J

2012-01-01

Background: In utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypospadias, cryptorchidism, hypospermatogenesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multinucleated germ cell (MNG) induction and suppressed steroidogenic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypospadias and cryptorchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroidogenesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates. Objectives: In this study, we aimed to develop and validate a rat and mouse testis xenograft bioassay of phthalate exposure and examine the human fetal testis response. Methods: Fetal rat, mouse, and human testes were xenografted into immunodeficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points. Results: Consistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xenografts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xenografts exhibited MNG induction but were resistant to suppression of steroidogenic gene expression. Conclusions: Phthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis. PMID:22511013

Partitioning of phthalates among the gas phase, airborne particles and settled dust in indoor environments

NASA Astrophysics Data System (ADS)

Weschler, Charles J.; Salthammer, Tunga; Fromme, Hermann

A critical evaluation of human exposure to phthalate esters in indoor environments requires the determination of their distribution among the gas phase, airborne particles and settled dust. If sorption from the gas phase is the dominant mechanism whereby a given phthalate is associated with both airborne particles and settled dust, there should be a predictable relationship between its particle and dust concentrations. The present paper tests this for six phthalate esters (DMP, DEP, DnBP, DiBP, BBzP and DEHP) that have been measured in both the air and the settled dust of 30 Berlin apartments. The particle concentration, CParticle, of a given phthalate was calculated from its total airborne concentration and the concentration of airborne particles (PM 4). This required knowledge of the particle-gas partition coefficient, Kp, which was estimated from either the saturation vapor pressure ( ps) or the octanol/air partition coefficient ( KOA). For each phthalate in each apartment, the ratio of its particle concentration to its dust concentration ( CParticle/ CDust) was calculated. The median values of this ratio were within an order of magnitude of one another for five of the phthalate esters despite the fact that their vapor pressures span four orders of magnitude. This indicates that measurements of phthalate ester concentrations in settled dust can provide an estimate of their concentration in airborne particles. When the latter information is coupled with measurements of airborne particle concentrations, the gas-phase concentrations of phthalates can also be estimated and, subsequently, the contribution of each of these compartments to indoor phthalate exposures.

Assessment of phthalates/phthalate alternatives in children's toys and childcare articles: Review of the report including conclusions and recommendation of the Chronic Hazard Advisory Panel of the Consumer Product Safety Commission.

PubMed

Lioy, Paul J; Hauser, Russ; Gennings, Chris; Koch, Holger M; Mirkes, Philip E; Schwetz, Bernard A; Kortenkamp, Andreas

2015-01-01

The Consumer Product Safety Commission (CPSC) convened a Chronic Hazard Advisory Panel (CHAP) on Phthalates found in children's toys, and childcare products, and in products used by women of childbearing age. The CHAP conducted a risk assessment on phthalates and phthalate substitutes, and made recommendations to either ban, impose an interim ban, or allow the continued use of phthalates and phthalate substitutes in the above products. After a review of the literature, the evaluation included toxic end points of primary concern, biomonitoring results, extant exposure reconstruction, and epidemiological results. The health end points chosen were associated with the rat phthalate syndrome, which is characterized by malformations of the epididymis, vas deferens, seminal vesicles, prostate, external genitalia (hypospadias), and by cryptorchidism (undescended testes), retention of nipples/areolae, and demasculinization (~incomplete masculinization) of the perineum, resulting in reduced anogenital distance. Risk assessment demonstrated that some phthalates should be permanently banned, removed from the banned list, or remain interim banned. Biomonitoring and toxicology data provided the strongest basis for a mixture risk assessment. In contrast, external exposure data were the weakest and need to be upgraded for epidemiological studies and risk assessments. Such studies would focus on routes and sources. The review presents recommendations and uncertainties.

DI(N-BUTYL) PHTHALATE AND DIETHYLHEXYL PHTHALATE IN COMBINATION ALTER SEXUAL DIFFERENTIATION IN A CUMULATIVE MANNER AS A RESULT OF DEPRESSED FETAL TESTOSTERONE PRODUCTION AND INSL3 GENE EXPRESSION IN MALE RATS

EPA Science Inventory

Plasticizers di(n-butyl) phthalate (DBP) and diehtylhexyl phthalate (DEHP) have similar modes of action: in utero exposure reduces testosterone (T) production in fetal male rats, inhibits reproductive tract differentiation, and induces reproductive organ malformations. In utero e...

16 CFR 1109.13 - Component part testing for phthalates in children's toys and child care articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Component part testing for phthalates in..., Component Parts, and Chemicals § 1109.13 Component part testing for phthalates in children's toys and child... children's toy or child care article for phthalate content provided that the requirements in § 1109.5 are...

40 CFR 799.5000 - Testing consent orders for substances and mixtures with Chemical Abstract Service Registry Numbers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... March 4, 1992. 84-74-2 Di-n-butyl phthalate Environmental effects January 9, 1989. 84-75-3 Di-n-hexyl phthalate Environmental effects January 9, 1989. Chemical fate January 9, 1989. 100-40-3 4-Vinylcyclohexene...-ethylhexyl phthalate Chemical fate January 9, 1989. 119-06-2 Ditridecyl phthalate Chemical fate January 9...

40 CFR 799.5000 - Testing consent orders for substances and mixtures with Chemical Abstract Service Registry Numbers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... March 4, 1992. 84-74-2 Di-n-butyl phthalate Environmental effects January 9, 1989. 84-75-3 Di-n-hexyl phthalate Environmental effects January 9, 1989. Chemical fate January 9, 1989. 100-40-3 4-Vinylcyclohexene...-ethylhexyl phthalate Chemical fate January 9, 1989. 119-06-2 Ditridecyl phthalate Chemical fate January 9...

16 CFR 1109.13 - Component part testing for phthalates in children's toys and child care articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Component part testing for phthalates in..., Component Parts, and Chemicals § 1109.13 Component part testing for phthalates in children's toys and child... children's toy or child care article for phthalate content provided that the requirements in § 1109.5 are...

Di-n-butyl Phthalate (DNBP) and Diisobutyl Phthalate (DiBP) Metabolism in a Human Volunteer after Single Oral Doses [Journal Article

EPA Science Inventory

An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 µg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 hours post dos...

Accuracy investigation of phthalate metabolite standards.

PubMed

Langlois, Éric; Leblanc, Alain; Simard, Yves; Thellen, Claude

2012-05-01

Phthalates are ubiquitous compounds whose metabolites are usually determined in urine for biomonitoring studies. Following suspect and unexplained results from our laboratory in an external quality-assessment scheme, we investigated the accuracy of all phthalate metabolite standards in our possession by comparing them with those of several suppliers. Our findings suggest that commercial phthalate metabolite certified solutions are not always accurate and that lot-to-lot discrepancies significantly affect the accuracy of the results obtained with several of these standards. These observations indicate that the reliability of the results obtained from different lots of standards is not equal, which reduces the possibility of intra-laboratory and inter-laboratory comparisons of results. However, agreements of accuracy have been observed for a majority of neat standards obtained from different suppliers, which indicates that a solution to this issue is available. Data accuracy of phthalate metabolites should be of concern for laboratories performing phthalate metabolite analysis because of the standards used. The results of our investigation are presented from the perspective that laboratories performing phthalate metabolite analysis can obtain accurate and comparable results in the future. Our findings will contribute to improving the quality of future phthalate metabolite analyses and will affect the interpretation of past results.

NTP Carcinogenesis Bioassay of Diallyl Phthalate (CAS No. 131-17-9) in B6C3F1 Mice (Gavage Study).

PubMed

1983-04-01

Diallyl phthalate is a widely used crosslinking agent for unsaturated polyesters. Diallyl phthalate or diallyl phthalate polyester blends are used primarily as plasticizers and carriers for adding catalysts and pigments to polyesters and in molding, electrical parts, laminating compounds, and impregnation of metal castings. Rubber compounds, epoxy formulations, and polyurethane foams may also contain diallyl phthalate. Annual production of diallyl phthalate in the United States exceeds 5,000 pounds; precise figures are not available. A NTP Carcinogenesis bioassay of diallyl phthalate (99% pure) was conducted by administering 0 (vehicle control), 150, or 300 mg/kg diallyl phthalate in corn oil by gavage, 5 days per week for 103 weeks, to groups of 50 male and 50 female B6C3F1 mice. Survival rates and mean body weights of dosed mice were not different from those of the controls, and pathological lesions unrelated to proliferative changes were not observed. Therefore, a maximally tolerated dose for the purposes of carcinogenicity testing may not have been achieved. The incidences of lymphoma and either lymphoma or leukemia in dosed male mice were no significantly greater than those in the controls according to pairwise comparisons (P=0.051 to P=0.096), but the trend tests were statistically significant by either life table or incidental tumor analysis (P=0.031 to P=0.045). The incidence of lymphomas in the high-dose male mice was 12/50 (24%) in comparison with 6/50 (12%) in the controls. Recent historical incidences at the performing laboratory and in the NTP Bioassay Program were 18/120 (15%) and 71/661 (11%), respectively. Since the incidence of high-dose male mice with leukemia was not significantly greater than that of concurrent or historical controls at the performing laboratory by pairwise comparisons, this marginal increase was considered only to be equivocally related to diallyl phthalate administration. Increased incidences of squamous cell papillomas, hyperplasia, and inflammatory lesions of the forestomach were observed in diallyl phthalate-dosed mice of both sexes in a dose-related manner. Papillomas of the forestomach were observed in 0%, 2%, and 4% of the control, low-dose, and high-dose mice of both sexes. The recent historical incidence of this tumor in gavage control mice from both the performing laboratory and other laboratories within the Bioassay Program was less than 1%. Forestomach hyperplasia was diagnosed in 0%, 15%, and 18%, and in 8%, 2%, and 29% of the control, low-dose, and high-dose male and female mice, respectively; chronic inflammation of the forestomach was diagnosed in 0%, 9%, and 16% and in 4%, 2%, and 18% of the control, low-dose, and high-dose male and female mice, respectively. Because of the numerical elevation of the forestomach papillomas in the high-dose mice of both sexes, the concomitant observation of dose related forestomach hyperplasia, and the rarity of this tumor in corn oil (gavage) control B6C3F1 mice, the development of squamous cell papillomas of the forestomach may have been related to diallyl phthalate administration. Under the conditions of this bioassay, the development of chronic inflammation and hyperplasia of the forestomach in both male and female B6C3F1 mice was considered to be related to the administration of diallyl phthalate. The development of squamous cell papillomas of the forestomach may also have been related to chemical administration, but the available data are insufficient to indicate a clear cause and effect relationship. An increase in the incidence of male mice with lymphomas was observed, but this increase was considered only to be equivocally related to diallyl phthalate administration. The results of this bioassay, therefore, do not indicate that diallyl phthalate is carcinogenic in B6C3F1 mice, although a maximum tolerated dose may not have been achieved. A carcinogenicity study by the National Toxicology Program of diallyl phthalate in male and female Fisher 344/N rats, employing daily gavage doses of 0 (vehicle control), 50, or 100 mg/kg boicology Program of diallyl phthalate in male and female Fisher 344/N rats, employing daily gavage doses of 0 (vehicle control), 50, or 100 mg/kg body weight is currently being evaluated. Levels of Evidence of Carcinogenicity: Male Mice: Equivocal Female Mice: Equivocal

Rapid and sensitive analysis of phthalate metabolites, bisphenol A, and endogenous steroid hormones in human urine by mixed-mode solid-phase extraction, dansylation, and ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

PubMed

Wang, He-xing; Wang, Bin; Zhou, Ying; Jiang, Qing-wu

2013-05-01

Steroid hormone levels in human urine are convenient and sensitive indicators for the impact of phthalates and/or bisphenol A (BPA) exposure on the human steroid hormone endocrine system. In this study, a rapid and sensitive method for determination of 14 phthalate metabolites, BPA, and ten endogenous steroid hormones in urine was developed and validated on the basis of ultra-performance liquid chromatography coupled with electrospray ionization triple quadrupole mass spectrometry. The optimized mixed-mode solid phase-extraction separated the weakly acidic or neutral BPA and steroid hormones from acidic phthalate metabolites in urine: the former were determined in positive ion mode with a methanol/water mobile phase containing 10 mM ammonium formate; the latter were determined in negative ion mode with a acetonitrile/water mobile phase containing 0.1 % acetic acid, which significantly alleviated matrix effects for the analysis of BPA and steroid hormones. Dansylation of estrogens and BPA realized simultaneous and sensitive analysis of the endogenous steroid hormones and BPA in a single chromatographic run. The limits of detection were less than 0.84 ng/mL for phthalate metabolites and less than 0.22 ng/mL for endogenous steroid hormones and BPA. This proposed method had satisfactory precision and accuracy, and was successfully applied to the analyses of human urine samples. This method could be valuable when investigating the associations among endocrine-disrupting chemicals, endogenous steroid hormones, and relevant adverse outcomes in epidemiological studies.

Use of Monte Carlo analysis in a risk-based prioritization of toxic constituents in house dust.

PubMed

Ginsberg, Gary L; Belleggia, Giuliana

2017-12-01

Many chemicals have been detected in house dust with exposures to the general public and particularly young children of potential health concern. House dust is also an indicator of chemicals present in consumer products and the built environment that may constitute a health risk. The current analysis compiles a database of recent house dust concentrations from the United States and Canada, focusing upon semi-volatile constituents. Seven constituents from the phthalate and flame retardant categories were selected for risk-based screening and prioritization: diethylhexyl phthalate (DEHP), butyl benzyl phthalate (BBzP), diisononyl phthalate (DINP), a pentabrominated diphenyl ether congener (BDE-99), hexabromocyclododecane (HBCDD), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroethyl) phosphate (TCEP). Monte Carlo analysis was used to represent the variability in house dust concentration as well as the uncertainty in the toxicology database in the estimation of children's exposure and risk. Constituents were prioritized based upon the percentage of the distribution of risk results for cancer and non-cancer endpoints that exceeded a hazard quotient (HQ) of 1. The greatest percent HQ exceedances were for DEHP (cancer and non-cancer), BDE-99 (non-cancer) and TDCIPP (cancer). Current uses and the potential for reducing levels of these constituents in house dust are discussed. Exposure and risk for other phthalates and flame retardants in house dust may increase if they are used to substitute for these prioritized constituents. Therefore, alternative assessment and green chemistry solutions are important elements in decreasing children's exposure to chemicals of concern in the indoor environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taxvig, Camilla, E-mail: camta@food.dtu.dk; Olesen, Pelle Thonning; Nellemann, Christine

2011-02-01

Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenousmore » metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects.« less

Rapid and sensitive determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in human urine samples using UHPLC-MS/MS.

PubMed

Yao, Yuan; Shao, Yijun; Zhan, Ming; Zou, Xiaoli; Qu, Weidong; Zhou, Ying

2018-06-01

Bisphenol analogues, amphenicol antibiotics, and phthalate have widely aroused public concerns due to their adverse effects on human health. In this study, a rapid and sensitive method for determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in the urine based on ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was developed and validated. The sample pretreatment condition on the base of mixed-mode anion-exchange (Oasis MAX) SPE was optimized to separate bisphenol analogues and amphenicol antibiotics from phthalate metabolites: the former were detected with a mobile phase of 0.1% ammonium water solution/methanol containing 0.1% ammonium water solution in negative mode, whereas the latter were determined with a mobile phase of 0.1% acetic acid solution/acetonitrile containing 0.1% acetic acid in negative mode. The limits of detection were less than 0.26 ng/mL for bisphenol analogues, 0.12 ng/mL for amphenicol antibiotics, and 0.14 ng/mL for phathalate metabolites. The recoveries of all target analytes in three fortification levels ranged from 72.02 to 117.64% with the relative standard deviations of no larger than 14.51%. The matrix effect was adjusted by isotopically labeled internal standards. This proposed method was successfully applied to analyze 40 actual urines and 13 out of 18 studied compounds were detected. Graphical abstract Simultaneous determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in human urine samples.

Phthalates and alkylphenols in industrial and domestic effluents: case of Paris conurbation (France).

PubMed

Bergé, A; Gasperi, J; Rocher, V; Gras, L; Coursimault, A; Moilleron, R

2014-08-01

Phthalates and alkylphenols are toxics classified as endocrine disrupting compounds (EDCs). They are of particular concern due to their ubiquity and generally higher levels found in the environment comparatively to other EDCs. Industrial and domestic discharges might affect the quality of receiving waters by discharging organic matter and contaminants through treated waters and combined sewer overflows. Historically, industrial discharges are often considered as the principal vector of pollution in urban areas. If this observation was true in the past for some contaminants, no current data are today available to compare the quality of industrial and domestic discharges as regards EDCs. In this context, a total of 45 domestic samples as well as 101 industrial samples were collected from different sites, including 14 residential and 33 industrial facilities. This study focuses more specifically on 4 phthalates and 2 alkylphenols, among the most commonly studied congeners. A particular attention was also given to routine wastewater quality parameters. For most substances, wastewaters from the different sites were heavily contaminated; they display concentrations up to 1200 μg/l for di-(2-ethylhexyl) phthalate and between 10 and 100 μg/l for diethyl phthalate and nonylphenol. Overall, for the majority of compounds, the industrial contribution to the flux of contaminant reaching the wastewater treatment plants ranges between 1 and 3%. The data generated during this work constitutes one of the first studies conducted in Europe on industrial fluxes for a variety of sectors of activity. The study of the wastewater contribution was used to better predict the industrial and domestic contributions at the scale of a huge conurbation heavily urbanized but with a weak industrial cover, illustrated by Paris. Our results indicate that specific investigations on domestic discharges are necessary in order to reduce the release of phthalates and alkylphenols in the sewer systems for such conurbations. Copyright © 2014 Elsevier B.V. All rights reserved.

Isolation and characterization of marine bacteria capable of utilizing phthalate.

PubMed

Iwaki, Hiroaki; Nishimura, Ayaka; Hasegawa, Yoshie

2012-03-01

Eleven phthalate-degrading bacterial strains were isolated from seawater collected off the coast of Japan. The isolates were found to be most closely related to the marine bacterial genera Alteromonas, Citreicella, Marinomonas, Marinovum, Pelagibaca, Rhodovulum, Sulfitobacter, Thalassobius, Thalassococcus, Thalassospira, and Tropicibacter. For the first time, members of these genera were shown to be capable of growth on phthalate. The plate assay for visual detection of phthalate dioxygenase activity and PCR detection of a possible gene encoding 4,5-dihydroxyphthalate decarboxylase indicated that phthalate is degraded via 4,5-dihydroxyphthalate to protocatechuate in all the isolates.

[Monograph on di-2-propylheptyl phthalate (DPHP) - human biomonitoring (HBM) values for the sum of metabolites oxo-mono-propylheptyl phthalate (oxo-MPHP) and hydroxy-mono-propylheptyl phthalate (OH MPHP) in adult and child urine. Opinion of the Commission "Human Biomonitoring" of the Federal Environment Agency, Germany].

PubMed

2015-07-01

1,2-benzenedicarboxylic acid, bis(2-propylheptyl)ester (bis(2-propylheptyl)phthalate, DPHP) is used as plasticizer for the manufacture of plastics, i.e. mainly polyvinylchloride (PVC). A subchronic feeding study with rats revealed a NOAEL (no observed adverse effect level) of 40 mg/(kg bw · d), which can be used as a point of departure (POD) for the derivation of an HBM-I value. Application of a total assessment factor of 200 leads to an estimation of 200 µg/kg bw as a tolerable daily intake of DPHP. On the basis of the results of metabolism studies with humans it is possible to calculate from the tolerable daily intake of DPHP to the tolerable concentration of specific metabolites in urine. Thus an HBM-I value of 1 mg/L morning urine for children and 1.5 mg/L morning urine for adults was derived for the sum of the oxidized monoesters oxo-MPHP and OH-MPHP, which were identified as robust and conclusive biomarkers for DPHP.

Phthalates

EPA Pesticide Factsheets

EPA is concerned about phthalates because of their toxicity and the evidence of pervasive human and environmental exposure to these chemicals.Phthalates are used in many industrial and consumer products, many of which pose potentially high exposure.

40 CFR 437.45 - New source performance standards (NSPS).

Code of Federal Regulations, 2012 CFR

2012-07-01

... Organic Parameters Acetone 30.2 7.97 Acetophenone 0.114 0.0562 Bis(2-ethylhexyl) phthalate 0.215 0.101 2-Butanone 4.81 1.85 Butylbenzyl phthalate 0.188 0.0887 Carbazole 0.598 0.276 o-Cresol 1.92 0.561 p-Cresol 0... Organic Parameters Bis(2-ethylhexyl) phthalate 0.215 0.101 Butylbenzyl phthalate 0.188 0.0887 Carbazole 0...

40 CFR 437.45 - New source performance standards (NSPS).

Code of Federal Regulations, 2014 CFR

2014-07-01

... Organic Parameters Acetone 30.2 7.97 Acetophenone 0.114 0.0562 Bis(2-ethylhexyl) phthalate 0.215 0.101 2-Butanone 4.81 1.85 Butylbenzyl phthalate 0.188 0.0887 Carbazole 0.598 0.276 o-Cresol 1.92 0.561 p-Cresol 0... Organic Parameters Bis(2-ethylhexyl) phthalate 0.215 0.101 Butylbenzyl phthalate 0.188 0.0887 Carbazole 0...

40 CFR 437.45 - New source performance standards (NSPS).

Code of Federal Regulations, 2011 CFR

2011-07-01

... Parameters Acetone 30.2 7.97 Acetophenone 0.114 0.0562 Bis(2-ethylhexyl) phthalate 0.215 0.101 2-Butanone 4.81 1.85 Butylbenzyl phthalate 0.188 0.0887 Carbazole 0.598 0.276 o-Cresol 1.92 0.561 p-Cresol 0.698 0... Organic Parameters Bis(2-ethylhexyl) phthalate 0.215 0.101 Butylbenzyl phthalate 0.188 0.0887 Carbazole 0...

40 CFR 414.91 - Toxic pollutant effluent limitations and standards for direct discharge point sources that use...

Code of Federal Regulations, 2012 CFR

2012-07-01

...(k)fluoranthene 59 22 Benzo(a)pyrene 61 23 Bis(2-ethylhexyl) phthalate 279 103 Carbon Tetrachloride... Di-n-butyl phthalate 57 27 1,2-Dichlorobenzene 163 77 1,3-Dichlorobenzene 44 31 1,4-Dichlorobenzene... phthalate 203 81 2,4-Dimethylphenol 36 18 Dimethyl phthalate 47 19 4,6-Dinitro-o-cresol 277 78 2,4...

40 CFR 414.91 - Toxic pollutant effluent limitations and standards for direct discharge point sources that use...

Code of Federal Regulations, 2014 CFR

2014-07-01

...(k)fluoranthene 59 22 Benzo(a)pyrene 61 23 Bis(2-ethylhexyl) phthalate 279 103 Carbon Tetrachloride... Di-n-butyl phthalate 57 27 1,2-Dichlorobenzene 163 77 1,3-Dichlorobenzene 44 31 1,4-Dichlorobenzene... phthalate 203 81 2,4-Dimethylphenol 36 18 Dimethyl phthalate 47 19 4,6-Dinitro-o-cresol 277 78 2,4...

Prenatal Exposure to Phthalate Esters and Behavioral Syndromes in Children at 8 Years of Age: Taiwan Maternal and Infant Cohort Study

PubMed Central

Lien, Yin-Ju; Ku, Hsiu-Ying; Su, Pen-Hua; Chen, Suh-Jen; Chen, Hsiao-Yen; Liao, Pao-Chi; Chen, Wei-J.

2014-01-01

Background: Few studies have shown an association between prenatal phthalate exposure and adverse effects on neurodevelopment and behavior in young children. Objectives: We aimed to assess the relationship between prenatal exposure to phthalate esters and behavior syndromes in children at 8 years of age. Methods: A total of 122 mother–child pairs from the general population in central Taiwan were studied from 2000 to 2009. Mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and three di-(2-ethylhexyl) phthalate (DEHP) metabolites—mono-2-ethylhexyl, mono-2-ethyl-5-hydroxyhexyl, and mono-2-ethyl-5-oxohexyl phthalates (MEHP, MEHHP, and MEOHP)—were measured in maternal urine collected during the third trimester of pregnancy using liquid chromatography–electrospray ionization–tandem mass spectrometry. Behavioral syndromes of children at 8 years of age were evaluated using the Child Behavior Checklist (CBCL). Associations between log10-transformed creatinine-corrected phthalate concentrations and standardized scores of the CBCL were estimated using linear regression models or multinomial logistic regressions with adjustments for potential confounders. Results: Externalizing problem scores were significantly higher in association with a 1-unit increase in log10-transformed creatinine-corrected concentrations of maternal MBP (β = 4.29; 95% CI: 0.59, 7.99), MEOHP (β = 3.74; 95% CI: 1.33, 6.15), and MEHP (β = 4.28 ; 95% CI: 0.03, 8.26) after adjusting for the child’s sex, intelligence, and family income. Meanwhile, MBP and MEOHP were significantly associated with Delinquent Behavior and Aggressive Behavior scores. The same pattern was found for borderline and/or clinical ranges. Conclusions: Our findings suggest positive associations between maternal DEHP and dibutyl phthalate (DBP) exposure and externalizing domain behavior problems in 8-year-old children. Citation: Lien YJ, Ku HY, Su PH, Chen SJ, Chen HY, Liao PC, Chen WJ, Wang SL. 2015. Prenatal exposure to phthalate esters and behavioral syndromes in children at 8 years of age: Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 123:95–100; http://dx.doi.org/10.1289/ehp.1307154 PMID:25280125

40 CFR 463.34 - New source performance standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

....34 New source performance standards. (a) NSPS for bis(2-ethylhexyl) phthalate, di-n-butyl phthalate, and dimethyl phthalate are reserved. (b) Any new source subject to this subpart must achieve...

Endocrine disruptors and human reproductive failure: the in vitro effect of phthalates on human luteal cells.

PubMed

Romani, Federica; Tropea, Anna; Scarinci, Elisa; Federico, Alex; Dello Russo, Cinzia; Lisi, Lucia; Catino, Stefania; Lanzone, Antonio; Apa, Rosanna

2014-09-01

To evaluate the influence of phthalates on human luteal cell function. Laboratory study. University hospital. Twenty-three normally menstruating patients in the midluteal phase. Human luteal cells isolated from corpora lutea for primary cultures. Progesterone (P4) and prostaglandin release assayed by enzyme immunoassay, vascular endothelial growth factor (VEGF) secretion by enzyme-linked immunosorbent assay (ELISA), and VEGF mRNA expression by real-time polymerase chain reaction. We investigated the effect of di(2-ethylhexyl)phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBP) on basal and hCG-induced progesterone (P4) release, as well as DEHP effect on the balance between prostaglandin (PG) E2, vascular endothelial growth factor (VEGF)-luteotrophic factors, and the luteolitic PGF2α in isolated human steroidogenc cells. Phthalates influence on VEGF expression has been also evaluated. DEHP, DBP, and BBP were able to reduce both basal and hCG-stimulated P4 as well as PGE2 release. PGF2α release was reduced after DEHP incubation. VEGF protein release was decreased by the incubation with the tested phthalates. VEGF mRNA expression was not affected by DEHP, DBP, and BBP. As expected, both hCG and cobalt chloride were able to induce P4 release and VEGF release and mRNA expression in human luteal cells respectively. The results show the ability of phthalates to affect luteal steroidogenesis as well as the balance between luteotrophic and luteolytic factors suggesting an interference of phthalates in human luteal function. These data may contribute to clarify the classically known impaired reproductive health observed after phthalates exposure. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The concentrations of phthalates in settled dust in Bulgarian homes in relation to building characteristic and cleaning habits in the family

NASA Astrophysics Data System (ADS)

Kolarik, Barbara; Bornehag, Carl-Gustaf; Naydenov, Kiril; Sundell, Jan; Stavova, Petra; Nielsen, Ole Faurskov

Phthalate esters are chemical compounds with a broad range of applications. Recently, we have shown that significantly higher dust concentration of di(2-ethylhexyl) phthalate (DEHP) was found in Bulgarian homes of children with asthma or allergies compared to healthy children. The concentration of DEHP was found to be significantly associated with wheezing in the last 12 months as reported by parents. The objective of the current study was to examine the associations between concentrations of phthalates in settled dust collected in Bulgarian homes and building characteristics and cleaning habits. Dust samples from the child's bedroom were collected in 177 homes and analysed for the content of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di- n-octyl phthalate (DnOP) and DEHP. Information on building characteristics and family habits were collected from parental reports in questionnaires and from inspectors' observations in the homes. Significantly higher concentrations of BBzP, DEHP and DnOP in indoor dust were found in homes where polishing agents were used, compared to homes where such products were not used. The highest concentrations of DEHP, BBzP and DnOP were found in homes with the combination of a low frequency of dusting and the use of polish. There was no difference in phthalate concentrations between inspector-observed balatum flooring (PVC or linoleum) and wood flooring as well as between PVC, as determined by Raman spectra, and wood flooring. However, in a sub-group of homes with no use of polish, the concentration of DEHP was higher in homes with inspector-observed balatum compared with wood flooring but the difference was not significant may be due to a too small sample size.

Correlation of Spatio-Temporal Contaminant Distribution, Land Use, and Hydrogeological Factors in the Karst Aquifers of Northern Puerto Rico

NASA Astrophysics Data System (ADS)

Torres Torres, N. I.; Padilla, I. Y.

2015-12-01

Karst aquifers are characterized by caves, springs, and sinkholes, and typified by interconnected fissures, fractures and conduits. These characteristics make these aquifers highly productive, and vulnerable to contamination. Previous studies in the northern karst aquifers of Puerto Rico have shown significant distribution of contaminants, including volatile organic compounds, phthalates and other contaminants of emerging concern, beyond demarked sources of contamination. This study develops spatial-temporal distributions of phthalate contaminants in the karst system of northern Puerto Rico and assesses statistical correlations between hydrogeologic factors and groundwater contamination with phthalates. Geographic Information Systems (GIS) tools and technologies, and statistical models are applied to attain these objectives. Results show that there is an extensive contamination with phthalates that varies with time. Contamination is present in the confined and shallow aquifers. Di-(2-ethylhexyl) phthalate (DEHP) is the most detected contaminant (20.6% of the sites). Diethyl phthalate and and dibutyl phthalate are also detected in 6.7% and 8.24% of the sites, respectively. Phthalates detected as mixtures components are significantly detected in areas of high urban and industrial development. They are also detected in areas within 5 miles of superfund sites and landfills. The results indicate that phthalate contamination is highly related to land use. Statistical models show that the hydraulic conductivity of the aquifers, sinkholes density, and time are significantly related to the presence of phthalates in groundwater. The extensive spatio-temporal contamination suggests that contaminants can persist in the environment for long periods of time, and that land use and hydrogeological factors are important factors contributing to the presence of emerging contaminants in karst systems.

Distribution of phthalate esters in agricultural soil with plastic film mulching in Shandong Peninsula, East China.

PubMed

Li, Kankan; Ma, Dong; Wu, Juan; Chai, Chao; Shi, Yanxi

2016-12-01

The content of phthalate esters (PAEs) was investigated in 36 vegetable fields with plastic film mulching in Shandong Peninsula, East China. Soils at depths of 0-10 cm, 10-20 cm, and 20-40 cm were collected, and 16 PAEs were analyzed by gas chromatography-mass spectrometry. PAEs were detected in all the analyzed samples. The total contents of the 16 PAEs (Σ 16 PAEs) ranged from 1.374 to 18.810 mg/kg, with an average of 6.470 mg/kg. Among the four areas of Shandong Peninsula, including Qingdao, Weihai, Weifang, and Yantai, the highest Σ 16 PAE in the soil was observed in Weifang district (9.786 mg/kg), which is famous for large-scale vegetable production. Despite the significant differences among the Σ 16 PAEs, the PAE compositions in soils with plastic film mulching in Shandong Peninsula were comparable. Diethyl phthalate (DEP), diisobutyl phthalate, and di(4-methyl-2-pentyl) phthalate were present in all the samples, whereas di-n-hexyl phthalate was detected only in Qingdao (∼1%) and dicyclohexyl phthalate was observed only in Weifang (5.7-8.2%) in low proportions. The ratios of dimethyl phthalate, DEP, and di-n-butyl phthalate, which exceeded allowable concentrations, were 63.9-100% at different soil depths, indicating high PAE pollution. The concentration of butyl benzyl phthalate detected only in Weifang exceeded the recommended allowable soil concentration. Overall, the high PAE content in the soil with plastic film mulching in Shandong Peninsula is an issue of concern because of the large amounts of plastic film used. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

PubMed

Sheikh, Ishfaq A; Beg, Mohd A

2017-12-01

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

[Toxicity effects of phthalate substitute plasticizers used in toys].

PubMed

Hirata-Koizumi, Mutsuko; Takahashi, Mika; Matsumoto, Mariko; Kawamura, Tomoko; Ono, Atsushi; Hirose, Akihiko

2012-01-01

Phthalate esters are widely used as plasticizers in polyvinyl chloride products. Because of human health concerns, regulatory authorities in Japan, US, Europe and other countries control the use of di(2-ethylhexyl) phthalate, diisononyl phthalate, di-n-butyl phthalate, butylbenzyl phthalate, diisodecyl phthalate and di-n-octyl phthalate for the toys that can be put directly in infants' mouths. While these regulatory actions will likely reduce the usage of phthalate esters, there is concern that other plasticizers that have not been sufficiently evaluated for safety will be used more frequently. We therefore collected and evaluated the toxicological information on di(2-ethylhexyl) terephthalate (DEHT), 1,2-cyclohexanedicarboxylic acid, diisononyl ester (DINCH), diisononyl adipate (DINA), 2,2,4-trimetyl-1,3-pentanediol diisobutyrate (TXIB), tri-n-butyl citrate (TBC) and acetyl tri-n-butyl citrate (ATBC) which were detected at a relatively high frequency in toys. The collected data have shown that chronic exposure to DEHT affects the eye and nasal turbinate, and DINCH exerts effects on the thyroid and kidney in rats. DINA and TXIB have been reported to have hepatic and renal effects in dogs or rats, and ATBC slightly affected the liver in rats. The NOAELs for repeated dose toxicity are relatively low for DINCH (40 mg/kg bw/day) and TXIB (30 mg/kg bw/day) compared with DEHT, DINA and ATBC. DEHT, TXIB and ATBC have been reported to have reproductive/developmental effects at relatively high doses in rats. For DINA and TBC, available data are insufficient for assessing the hazards, and therefore, adequate toxicity studies should be conducted. In the present review, the toxicity information on 6 alternatives to phthalate plasticizers is summarized, focusing on the effects after oral exposure, which is the route of most concern.

Webinar Presentation: Phthalates Exposures through Diet: Lessons Learned

EPA Pesticide Factsheets

This presentation, Phthalates Exposures through Diet: Lessons Learned, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Phthalates in the Diet and in our Homes held on June 10, 2015.

40 CFR 463.36 - Pretreatment standards for new sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

....36 Pretreatment standards for new sources. (a) PSNS for bis(2-ethylhexyl) phthalate, di-n-butyl phthalate, and dimethyl phthalate are reserved. (b) Any new source subject to this subpart that introduces...

40 CFR 463.35 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Subcategory § 463.35 Pretreatment standards for existing sources. (a) PSES for bis(2-ethylhexyl) phthalate, di-n-butyl phthalate, and dimethyl phthalate are reserved. (b) Any existing source subject to this...

Occurrence of phthalate diesters (phthalates), p-hydroxybenzoic acid esters (parabens), bisphenol A diglycidyl ether (BADGE) and their derivatives in indoor dust from Vietnam: Implications for exposure.

PubMed

Tran, Tri Manh; Minh, Tu Binh; Kumosani, Taha A; Kannan, Kurunthachalam

2016-02-01

Phthalate diesters (phthalates), esters of p-hydroxybenzoic acid (parabens), and bisphenol A diglycidyl ether (BADGE) are used in personal care products, food packages, household products, or pharmaceuticals. These compounds possess endocrine-disrupting potentials and have been reported to occur in the environment. Nevertheless, no previous studies have reported the occurrence of these compounds in indoor dust from Vietnam. In this study, nine phthalates, six parabens, and four BADGEs were determined in indoor dust samples collected from Hanoi, Hatinh, Hungyen, and Thaibinh, in Vietnam. Total concentrations of phthalates, parabens, and BADGEs in indoor dust ranged from 3440 to 106,000 ng/g (median: 22,600 ng/g), 40-840 ng/g (median: 123 ng/g), and 23 to 1750 ng/g (median: 184 ng/g), respectively. Based on the measured median concentration of phthalates, parabens, and BADGEs in indoor dust, we estimated human exposure doses to these compounds through indoor dust ingestion for various age groups. The exposure doses to phthalates, parabens, and BADGEs decreased with age and ranged from 19.4 to 90.4 ng/kg-bw/d, 0.113-0.528 ng/kg-bw/d, and 0.158-0.736 ng/kg-bw/d, respectively. This is the first study on the occurrence and human exposure of phthalates, parabens, and BADGEs in indoor dust from Vietnam. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of six priority controlled phthalate esters with long-term low-dose integrated exposure on male reproductive toxicity in rats.

PubMed

Gao, Hai-Tao; Xu, Run; Cao, Wei-Xin; Qian, Liang-Liang; Wang, Min; Lu, Lingeng; Xu, Qian; Yu, Shu-Qin

2017-03-01

Human beings are inevitably exposed to ubiquitous phthalate esters (PEs) surroundings. The purposes of this study were to investigate the effects of long-term low-dose exposure to the mixture of six priority controlled phthalate esters (MIXPs): dimethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DBP), butyl benzyl phthalate (BBP), di(2-ethyhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), on male rat reproductive system and further to explore the underlying mechanisms of the reproductive toxicity. The male rats were orally exposed to either sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses by gavage for 15 weeks. Testosterone and luteinizing hormone (LH) in serum were analyzed, and pathological examinations were performed for toxicity evaluation. Steroidogenic proteins (StAR, P450scc, CYP17A1 and 17β-HSD), cell cycle and apoptosis-related proteins (p53, Chk1, Cdc2, CDK6, Bcl-2 and Bax) were measured for mechanisms exploration. MIXPs with long-term low-dose exposure could cause male reproductive toxicity to the rats, including the decrease of both serum and testicular testosterone, and the constructional damage of testis. These effects were related to down-regulated steroidogenic proteins, arresting cell cycle progression and promoting apoptosis in rat testicular cells. The results indicate that MIXPs with long-term low-dose exposure may pose male reproductive toxicity in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dummy molecularly imprinted microbeads as solid-phase extraction material for selective determination of phthalate esters in water.

PubMed

Özer, Elif Tümay; Osman, Bilgen; Yazıcı, Tuğçe

2017-06-02

The aim of this study was to investigate the usability of newly synthesized dummy molecularly imprinted microbeads (DMIMs) as a solid phase extraction (SPE) material to determine six phthalate esters (PEs) in water by GC-MS analysis. Diethyl phthalate (DEP) was used as a dummy template to prepare poly(ethylene glycol dimethacrylate N-methacryloyl-l-tryptophan methyl ester) [PEMATrp)] DMIMs by using suspension polymerization. The PEMATrp DMIMs were characterized by using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Firstly, the adsorption capacities of the DMIMs prepared in different template molecule (DEP) to functional monomer (MATrp) ratios were investigated by using DEP solutions in the concentration range of 1-500mg/L at pH 3.0. Styrene and vanillic acid were used to evaluate the selectivity of the prepared DMIMs towards the template molecule (DEP). Then, the best analytical conditions were investigated for the simultaneous determination of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), benzylbutyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP) in aqueous media by using the PEMATrp DMIMs as SPE material. Validation experiments showed that the PEMATrp DMIMs-SPE method had good linearity at 12.5-250.0μg/L (0.988-0.999), good precision (1.2-5.9%), and limits of detection in a range of 0.31-0.41μg/L. Copyright © 2017 Elsevier B.V. All rights reserved.