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Sample records for 2-ethylhexyl phthalate dehp

  1. European Union Risk Assessment Report - bis (2-ethylhexyl) phthalate (DEHP)

    2008-01-01

    This report provides a summary, with conclusions, of the risk assessment report of the substance bis (2-ethylhexyl) phthalate (DEHP) that has been prepared by Sweden in the context of Council Regulation (EEC) No. 793/93 on the evaluation and control of existing substances. For detailed information on the risk assessment principles and procedures followed, the underlying data and the literature references, the reader is referred to the comprehensive Final Risk Assessment Report (Final RAR...

  2. Quantitative Determination of Di (2-Ethylhexyl) Phthalate (DEHP) in Hemodialysis-Related Materials

    Mitra Mahdavi mazdeh; Gholam Reza Jahed Khaniki; Masood Yunesian; Hamid Rajlani; Shahrokh Nazmara; SeyedAhmad SeyedAlinaghi; Noushin Rastkari; Hossain Jabbari; Mostafa Hosseini; Simin Naseri

    2012-01-01

    Introduction: Phthalates are founded in medical devices such as filters and dialysis catheters. Scientific evidences show health disadvantages due to exposure to phthalates. In this study, level of Di (2-ethylhexyl) phthalate (DEHP) in Iranian hemodialysis-related materials was measured. Methods: Ten samples of Iranian dialysis catheters (five samples from SUPA medical devices company (SUPA-MDC) and five samples from Helal Ahmar- MDC) were randomly selected. The level of DEHP for each sample ...

  3. Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites

    Klöting, Nora; Hesselbarth, Nico; Gericke, Martin; Kunath, Anne; Biemann, Ronald; Chakaroun, Rima; Kosacka, Joanna; Kovacs, Peter; Kern, Matthias; Stumvoll, Michael; Fischer, Bernd; Rolle-Kampczyk, Ulrike; Feltens, Ralph; Otto, Wolfgang; Wissenbach, Dirk K.

    2016-01-01

    Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse mo...

  4. European Union Summary Risk Assessment Report - Bis (2-ethylhexyl) Phthalate (DEHP)

    2008-01-01

    This report provides a summary, with conclusions, of the risk assessment report of the substance bis (2-ethylhexyl) phthalate (DEHP) that has been prepared by Sweden in the context of Council Regulation (EEC) No. 793/93 on the evaluation and control of existing substances. For detailed information on the risk assessment principles and procedures followed, the underlying data and the literature references, the reader is referred to the comprehensive Final Risk Assessment Report (Final RAR...

  5. Clinically relevant concentrations of di (2-ethylhexyl) phthalate (DEHP) uncouple cardiac syncytium

    Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer found in a variety of polyvinyl chloride (PVC) medical products. The results of studies in experimental animals suggest that DEHP leached from flexible PVC tubing may cause health problems in some patient populations. While the cancerogenic and reproductive effects of DEHP are well recognized, little is known about the potential adverse impact of phthalates on the heart. This study examined the effects of clinically relevant concentrations of DEHP on neonatal rat cardiomyocytes. It was found that application of DEHP to a confluent, synchronously beating cardiac cell network, leads to a marked, concentration-dependent decrease in conduction velocity and asynchronous cell beating. The mechanism behind these changes was a loss of gap junctional connexin-43, documented using Western blot analysis, dye-transfer assay and immunofluorescence. In addition to its effect on electrical coupling, DEHP treatment also affected the mechanical movement of myocyte layers. The latter was linked to the decreased stiffness of the underlying fibroblasts, as the amount of triton-insoluble vimentin was significantly decreased in DEHP-treated samples. The data indicate that DEHP, in clinically relevant concentrations, can impair the electrical and mechanical behavior of a cardiac cell network. Applicability of these findings to human patients remains to be established

  6. Quantitative Determination of Di (2-Ethylhexyl Phthalate (DEHP in Hemodialysis-Related Materials

    Mitra Mahdavi mazdeh

    2012-07-01

    Full Text Available Introduction: Phthalates are founded in medical devices such as filters and dialysis catheters. Scientific evidences show health disadvantages due to exposure to phthalates. In this study, level of Di (2-ethylhexyl phthalate (DEHP in Iranian hemodialysis-related materials was measured. Methods: Ten samples of Iranian dialysis catheters (five samples from SUPA medical devices company (SUPA-MDC and five samples from Helal Ahmar- MDC were randomly selected. The level of DEHP for each sample was measured by Gas chromatography- Mass spectrometry (GC-MS. Mean concentrations of DEHP (mg per ml for each brand was reported separately.Results: Means of DEHP concentration for SUPA- MDC and Helal Ahmar- MDC were 1.36±0.11 and 0.97±0.11 mg/ml, respectively. Range of measured concentrations differed from 1.47 to 1.21 mg/ml and 1.13 to 0.83 mg/ml, for SUPA- and Helal Ahmar-MDCs respectively. Conclusion: Application of alternative medical products without or with less phthalate could reduce exposure of patients to phthalates.

  7. Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

    Shin, In-Sik; Lee, Mee-Young [Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, 483 Expo-ro, Yusung-gu, Daejeon 305-811 (Korea, Republic of); Cho, Eun-Sang [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Choi, Eun-young [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of); Son, Hwa-Young [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Lee, Kyoung-Youl, E-mail: youl10@hanmail.net [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of)

    2014-02-01

    Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.

  8. Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

    Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue

  9. Histopathological study of Di-(2-ethylhexyl phthalate (DEHP on testes in mouse

    Zohre Zare1

    2009-01-01

    Full Text Available (Received 10 October, 2008 ; Accepted 6 May, 2009AbstractBackground and purpose: Di-(2-ethylhexyl phthalate (DEHP is plasticizer used commonly in a variety of polyvinyl chloride- based consumable products. The purpose of this study was to evaluate the effects of DEHP on body weight, testis weight, seminiferous tubular diameter, seminiferous epithelium height, seminiferous lumen diameter, number of sertoli cells and round spermatids per seminiferous tubule in mice.Materials and methods: The protocol for DEHP administration was that adult male NMRI mice (the age group of 4 weeks received 2g DEHP/100μl corn oil/kg, and vehicle group received 100 μl corn oil/ kg by gavage for 14 days. The control group did not receive DEHP.All animals were weighed on the first and terminal day of the experiment. The left and right without fat testis, weights were recorded for each animal. Left testis was fixed in Bouinś solution, routinely processed for embedding in paraffin and staining of 5 μm sections with hematoxilin and eosin (H&E for histopathological examination.Results: Administration of DEHP induced the reduction of body and testis weight significantly (p<0.05. Furthermore, DEHP decreased the seminiferous tubular diameter, seminiferous epithelium height, and seminiferous lumen diameter. The number of sertoli cells and round spermatids in seminiferous tubule was significantly low, compared with control group.Conclusion: These results demonstrated that DEHP administration has toxicant effects on body and testis weight, spermatogenesis process, along with male reproductive system. J Mazand Univ Med Sci 2009; 19(71: 52-59 (Persian

  10. 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

    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-D4). Concentrations of DEHP-D4, of free ring-deuterated MEHP (MEHP-D4), and the sum of free and glucuronidated MEHP-D4 were measured in blood for up to 24 h; amounts of the monoesters MEHP-D4, ring-deuterated mono(2-ethyl-5-hydroxyhexyl) 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-D4 was surprisingly high with an area under the concentration-time curve until 24 h (AUC) amounting to 50% of that of free MEHP-D4. The AUC of free MEHP-D4 normalized to DEHP-D4 dose and body weight (AUC/D) was 2.1 and 8.1 times, that of DEHP-D4 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-D4 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.

  11. 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

    Kessler, Winfried, E-mail: kessler@helmholtz-muenchen.de [Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, D-85764 Neuherberg (Germany); Numtip, Wanwiwa [Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, D-85764 Neuherberg (Germany); Völkel, Wolfgang; Seckin, Elcim [Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority, Pfarrstrasse 3, D-80538 München (Germany); Csanády, György A. [Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, D-85764 Neuherberg (Germany); Institut für Toxikologie und Umwelthygiene, Technische Universität München, München (Germany); Pütz, Christian [Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, D-85764 Neuherberg (Germany); and others

    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) 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.

  12. Metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) in rats: in vivo and in vitro dose and time dependency of metabolism

    This study investigated the in vivo metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in rats after multiple dosing, the metabolism of MEHP in primary rat hepatocyte cultures for periods of up to 3 days, and the biotransformation of some major metabolites of MEHP. Rats were orally administered [14C]DEHP or [14C]MEHP at doses of 50 and 500 mg/kg body wt for three consecutive days. Urine was collected at 24-hr intervals, and metabolite profiles were determined. After a single dose of either compound, urinary metabolite profiles were similar to those previously reported. However, after multiple administration of both DEHP and MEHP at 500 mg/kg, increases in omega-/beta-oxidation products [metabolites I and V, mono(3-carboxy-2-ethylpropyl) phthalate and mono(5-carboxy-2-ethylpentyl) phthalate, respectively] and decreases in omega - 1-oxidation products [metabolites VI and IX, mono(2-ethyl-5-oxohexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate, respectively] were seen. At the low dose of 50 mg/kg little or no alteration in urinary metabolite profiles was observed. At 500 mg/kg of MEHP a 4-fold stimulation of CN- -insensitive palmitoyl-CoA oxidation (a peroxisomal beta-oxidation marker) was seen after three consecutive daily doses. At the low dose of 50 mg/kg only a 1.8-fold increase was noted. Similar observations were made with rat hepatocyte cultures. MEHP at concentrations of 50 and 500 microM was extensively metabolized in the rat hepatocyte cultures. Similar metabolic profiles to those seen after in vivo administration of MEHP were observed. At the high (500 microM) concentration of MEHP, changes in the relative proportions of omega- and omega- 1-oxidized metabolites were seen

  13. Is peroxisome proliferation an obligatory precursor step in the carcinogenicity of di(2-ethylhexyl)phthalate (DEHP)?

    Melnick, R L

    2001-01-01

    Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, has been listed by the International Agency for Research on Cancer (IARC) and by the National Toxicology Program as a possible or reasonably anticipated human carcinogen because it induces dose-related increases in liver tumors in both sexes of rats and mice. Recently, the suggestion has been advanced that DEHP should be considered unlikely to be a human carcinogen because it is claimed that the carcinogenic effects of this agent in...

  14. Effect of di(2-ethylhexyl) phthalate (DEHP) on lipolysis and lipoprotein lipase activities in adipose tissue of rats.

    Martinelli, Marcela I; Mocchiutti, Norberto O; Bernal, Claudio A

    2010-09-01

    The di(2-ethylhexyl) phthalate (DEHP) is an ubiquitous environmental chemical with detrimental health effects. The present work was designed to asses some potential mechanisms by which DEHP causes, among others, a reduced body fat retention. Since this effect could be related to an alteration of adipocyte triacylglycerol (TG) metabolism, we evaluated the effects of dietary DEHP in adipose tissues upon (1) the number and size of fat cells; (2) the basal and stimulated lipolysis and (3) the lipoprotein lipase (LPL) activity. Groups of male Wistar rats were fed for 21 days a control diet alone (control group) or the same control diet supplemented with 2% (w/w) of DEHP (DEHP group). The LPL activity of DEHP-fed rats was increased in lumbar and epididymal adipose tissues. These rats had significantly reduced weight in epididymal and lumbar tissues, together with reduced size of epididymal adipocytes. These alterations do not seem to be associated with higher lipid mobility because neither basal lipolysis nor 'in vitro' stimulated lipolysis by noradrenaline (NA) showed to be modified by DEHP. Based on these results, we concluded that the adipose tissue size reduction induced by DEHP intake is not due to changes in lipolysis nor to a decreased LPL activity. More research is needed to achieve a comprehensive understanding of the potential mechanisms by which DEHP causes, among others, a reduced body fat retention. PMID:20144957

  15. Follow-Up Study of Adolescents Exposed to Di(2-Ethylhexyl) Phthalate (DEHP) as Neonates on Extracorporeal Membrane Oxygenation (ECMO) Support

    Rais-Bahrami, Khodayar; Nunez, Susan; Revenis, Mary E.; Luban, Naomi L.C.; Short, Billie L.

    2004-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is used to make polyvinyl chloride (PVC) plastic tubing soft and flexible. Animal data show that adverse effects of DEHP exposure may include reduced fertility, reduced sperm production in males, and ovarian dysfunction in females. Known treatments that involve high DEHP exposures are blood exchange transfusions, extracorporeal membrane oxygenation (ECMO), and cardiovascular surgery. Although potential exposure to DEHP in ECMO patients is significant, the exp...

  16. Untersuchung der Di-(2-ethylhexyl)phthalat (DEHP)-Belastung der Allgemeinbevölkerung – Durchführung eines Human-Biomonitorings

    Koch, Holger Martin

    2007-01-01

    i-(2-ethylhexyl)phthalat (DEHP) ist einer der bedeutendsten Weichmacher für PVC-Polymere mit Produktionszahlen im Bereich um 1 Million Tonnen pro Jahr weltweit. Als sog. äußerer Weichmacher ist DEHP nicht kovalent an den Kunststoff gebunden und blutet so mehr oder weniger schnell aus diesem aus und kann so die Umwelt, Nahrungsmittel oder den Menschen belasten. DEHP steht unter dringendem Verdacht, als Endokriner Disruptor/Modulator ins menschliche Hormonsystem einzugreifen und so eine Vielzah...

  17. 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

    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 testicular 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 μM 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.

  18. Toxicity study of di(2-ethylhexyl)phthalate (DEHP) in combination with acetone in rats

    Dalgaard, M.; Østergaard, G.; Lam, Henrik Rye;

    2000-01-01

    measured parameters. In the 4-week study DEHP, at the highest dose level, resulted in severe general toxicity. The group exposed to DEHP in combination with acetone was more affected. Male fertility was decreased. Body weight was decreased, and the relative weight of the liver, kidney, heart, brain and...

  19. Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl) phthalate (DEHP) in rats and marmosets: extrapolation of effects in rodents to man

    Certain phthalate esters and hypolipidemic agents are known to induce morphological and biochemical changes in the liver of rodents, which have been associated with an increased incidence of hepatocellular tumors in these species. There is evidence that hypolipidemic agents do not induce these effects in either subhuman primates or man. The oral and intraperitoneal administration of di(2-ethylhexyl) phthalate (DEHP) to the marmoset monkey at doses up to 5 mmole DEHP/kg body weight/day for 14 days did not induce morphological or biochemical changes in the liver or testis comparable with those obtained in rats given the same amount of DEHP. In the marmoset, the excretion profile of [14C]-DEHP following oral, IP, and IV administration and the lower tissue levels of radioactivity demonstrated a considerably reduced absorption in this species compared to the rat. The urinary metabolite pattern in the marmoset was in many respects qualitatively similar to but quantitatively different from that in the rat. The pharmacokinetic differences between these two species indicate that the tissues of the marmoset are exposed to a level of DEHP metabolites equivalent to the complete absorption of a dose of Ca. 0.1 to 0.25 mmole DEHP/kg body weight/day without significant toxicological effects. The evidence suggests that in some nonrodent species the hepatocellular and testicular response to DEHP is considerably less than that in rodents and is dose-dependent

  20. Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl) phthalate (DEHP) in rats and marmosets: extrapolation of effects in rodents to man

    Rhodes, C.; Orton, T.C.; Pratt, I.S.; Batten, P.L.; Bratt, H.; Jackson, S.J.; Elcombe, C.R.

    1986-03-01

    Certain phthalate esters and hypolipidemic agents are known to induce morphological and biochemical changes in the liver of rodents, which have been associated with an increased incidence of hepatocellular tumors in these species. There is evidence that hypolipidemic agents do not induce these effects in either subhuman primates or man. The oral and intraperitoneal administration of di(2-ethylhexyl) phthalate (DEHP) to the marmoset monkey at doses up to 5 mmole DEHP/kg body weight/day for 14 days did not induce morphological or biochemical changes in the liver or testis comparable with those obtained in rats given the same amount of DEHP. In the marmoset, the excretion profile of (/sup 14/C)-DEHP following oral, IP, and IV administration and the lower tissue levels of radioactivity demonstrated a considerably reduced absorption in this species compared to the rat. The urinary metabolite pattern in the marmoset was in many respects qualitatively similar to but quantitatively different from that in the rat. The pharmacokinetic differences between these two species indicate that the tissues of the marmoset are exposed to a level of DEHP metabolites equivalent to the complete absorption of a dose of Ca. 0.1 to 0.25 mmole DEHP/kg body weight/day without significant toxicological effects. The evidence suggests that in some nonrodent species the hepatocellular and testicular response to DEHP is considerably less than that in rodents and is dose-dependent.

  1. Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms

    The exposure of cultured rat hepatocytes to mono(2-ethyhexyl)phthalate (MEHP) for 72 hr resulted in marked induction of peroxisomal enzyme activity (β-oxidation; cyanide-insensitive palmitoyl CoA oxidase) and concomitant increases in the number of peroxisomes. Similar treatment of cultured guinea pig, marmoset, or human hepatocytes revealed little or no effect of MEHP. In order to eliminate possible confounding influences of biotransformation, the proximate peroxisome proliferator(s) derived from MEHP have been identified. Using cultured hepatocytes these agents were found to be metabolite VI [mono(2-ethyl-5-oxohexyl) phthalate] and metabolite IX [mono(2-ethyl-5-hydroxyhexyl) phthalate]. The addition of these active metabolites to cultured guinea pig, marmoset, or human hepatocytes again revealed little effect upon peroxisomes or related enzyme activities (peroxisomal β-oxidation or microsomal lauric acid hydroxylation). These studies demonstrate a marked species difference in the response of hepatocytes to MEHP-elicited peroxisome proliferation. Preliminary studies have also suggested that peroxisome proliferation due to MEHP may be due to an initial biochemical lesion of fatty acid metabolism

  2. Stereoselectivity and the potential endocrine disrupting activity of di-(2-ethylhexyl)phthalate (DEHP) against human progesterone receptor: a computational perspective.

    Sheikh, Ishfaq Ahmad

    2016-05-01

    Di-(2-ethylhexyl)phthalate (DEHP) is a phthalate plasticizer and is one of the very common endocrine-disrupting chemicals (EDCs) contaminating our ecosystem. It is used for imparting flexibility to plastics and frequently used in personal and industrial products. Clinical and experimental studies have indicated that exposure to DEHP is associated with developmental abnormalities of the reproductive system particularly of male neonates, endometriosis and miscarriage in women, low sperm counts and lower sperm motility and DNA integrity in men, and placental problems with higher rates of low birth weight, premature birth, and fetal loss in laboratory animals. Binding of DEHP to progesterone receptor (PR) represents a potential mechanism of interference in the reproductive functions. DEHP is a chiralmolecule and is available commercially as a racemic mixture of RR, SS and RS stereoisomers. The ability of individual stereoisomers of DEHP to interfere with the reproductive functions of humans and animals is not known and molecular interactions of DEHP stereoisomers with PR are not available. In the present study, in silico approaches were adopted for molecular simulation studies of the three stereoisomers of DEHP with PR. The study suggested that all three stereoisomers of DEHP have the potential to compete with the normal substrate binding of PR. However, the binding of DEHP to PR was stereoselective with RR stereoisomer of DEHP having the best binding characteristics compared with SS, and RS stereoisomers. It has been suggested that stereoselectivity may be employed for improving the safety of the commercial compounds using pure stereoisomers instead of racemic mixtures. PMID:26879776

  3. NTP-CERHR monograph on the potential human reproductive and developmental effects of di (2-ethylhexyl) phthalate (DEHP).

    Shelby, Michael D

    2006-11-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an updated evaluation of the potential for DEHP to cause adverse effects on reproduction and development in humans. The first CERHR expert panel evaluation of DEHP was completed in 2000 by the Phthalates Expert Panel. CERHR selected DEHP for an updated evaluation because of: (1) widespread human exposure, (2) public and government interest in adverse health effects, (3) recently available human exposure studies, and (4) the large number of relevant toxicity papers published since the earlier evaluation. DEHP (CAS RN: 117-81-7) is a high production volume chemical used as a plasticizer of polyvinyl chloride in the manufacture of a wide variety of consumer goods, such as building products, car products, clothing, food packaging, children's products (but not in toys intended for mouthing), and in medical devices made of polyvinyl chloride. The public can be exposed to DEHP by ingesting food, drink or dust that has been in contact with DEHP-containing materials, by inhaling contaminated air or dust, or by undergoing a medical procedure that uses polyvinyl chloride medical tubing or storage bags. It is estimated that the general population of the United States is exposed to DEHP levels ranging from 1 to 30 microg/kg bw/day (micrograms per kilogram body weight per day). The results of this DEHP update evaluation are published in an NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the Expert Panel Update on the Reproductive and Developmental Toxicity of DEHP, and (3) public comments on the expert panel report. The NTP reached the following conclusions on the possible effects of exposure to DEHP on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. There is serious concern that certain intensive medical treatments of

  4. The influence of humidity on the emission of di-(2-ethylhexyl) phthalate (DEHP) from vinyl flooring in the emission cell "FLEC"

    Clausen, Per Axel; Xu, Ying; Kofoed-Sørensen, Vivi; Little, John C.; Wolkoff, Peder

    Asthma in children appears to be associated with both phthalate esters and dampness in buildings. An important question is whether the concentrations of phthalate esters correlate with dampness (expressed as relative humidity—RH) in indoor air. The objective was to study the influence of RH on the specific emission rate (SER) of di-(2-ethylhexyl)phthalate (DEHP) from one type of vinyl flooring in the well characterized Field and Laboratory Emission Cell (FLEC). The vinyl flooring with ca. 17% (w/w) DEHP as plasticizer was tested in 6 FLECs at 22 °C. The RH in the 6 FLECs was 10%, 30%, 50% (in triplicate) and 70%. The RH was changed after 248 d in 2 of the 50%-FLECs to 10% and 70%, and to 50% in the 10%-and 70%-FLECs. The data show that the SER of DEHP from vinyl flooring in FLECs during a 1 yr period is independent of the RH. A new physically based emission model for semivolatile organic compounds was found to be consistent with the experimental data and independent of the RH. The model helps to explain the RH results, because it appears that RH does not significantly influence any of the identified controlling mechanisms.

  5. Influence of temperature on the emission of di-(2-ethylhexyl)phthalate (DEHP) from PVC flooring in the emission cell FLEC.

    Clausen, Per Axel; Liu, Zhe; Kofoed-Sørensen, Vivi; Little, John; Wolkoff, Peder

    2012-01-17

    Emissions of di-(2-ethylhexyl) phthalate (DEHP) from one type of polyvinylchloride (PVC) flooring with approximately 13% (w/w) DEHP as plasticizer were measured in the Field and Laboratory Emission Cell (FLEC). The gas-phase concentrations of DEHP versus time were measured at air flow rate of 450 mL·min(-1) and five different temperatures: 23 °C, 35 °C, 47 °C, 55 °C, and 61 °C. The experiments were terminated two weeks to three months after steady-state was reached and the interior surface of the FLECs was rinsed with methanol to determine the surface concentration of DEHP. The most important findings are (1) DEHP steady-state concentrations increased greatly with increasing temperature (0.9 ± 0.1 μg·m(-3), 10 ± 1 μg·m(-3), 38 ± 1 μg·m(-3), 91 ± 4 μg·m(-3), and 198 ± 5 μg·m(-3), respectively), (2) adsorption to the chamber walls decreased greatly with increasing temperature (measured partition coefficient between FLEC air and interior surface are: 640 ± 146 m, 97 ± 20 m, 21 ± 5 m, 11 ± 2 m, and 2 ± 1 m, respectively), (3) gas-phase DEHP concentration in equilibrium with the vinyl flooring surface is close to the vapor pressure of pure DEHP, and (4) with an increase of temperature in a home from 23 to 35 °C, the amount of DEHP in the gas- and particle-phase combined is predicted to increase almost 10-fold. The amount in the gas-phase increases by a factor of 24 with a corresponding decrease in the amount on the airborne particles. PMID:22191658

  6. Effects of high di(2-ethylhexyl) phthalate (DEHP) exposure due to tainted food intake on pre-pubertal growth characteristics in a Taiwanese population.

    Tsai, Yen-An; Lin, Ching-Ling; Hou, Jia-Woei; Huang, Po-Chin; Lee, Meng-Chih; Chen, Bai-Hsiun; Wu, Ming-Tsang; Chen, Chu-Chih; Wang, Shu-Li; Lee, Ching-Chang; Hsiung, Chao Agnes; Chen, Mei-Lien

    2016-08-01

    On May 23, 2011, a major scandal involving the illegal use of phthalates as clouding agents in food products was reported. Specifically, di(2-ethylhexyl) phthalate (DEHP) was purposefully added to foods as a substitute emulsifier. The purpose of this study was to examine the effects of DEHP exposure on the growth characteristics of the child victims of this scandal. Eighty-eight victims, originating from northern, central, and southern Taiwan and ranging in age from 6.0 to 10.5 years, were invited to participate in this study during clinic visits. The participants underwent follow-up health examinations from August 2012 to February 2013. We collected information on each participant's history of exposure to tainted food products using a questionnaire, and we analyzed their urinary concentrations of DEHP metabolites using high-performance liquid chromatography/tandem mass spectrometry. These data were then used to estimate their daily DEHP intake (DIAll) during the scandal. We also measured physical development parameters (height, weight, and bone age) and hormone levels (thyroid, sex and growth hormones) to evaluate their overall growth characteristics. The average (SD) duration of DEHP intake from tainted nutrition supplements was 1.39 (1.01) years. The median DIAll values were 19.93 and 20.69μg/kg bw/day for boys and girls, respectively. Among the enrolled children, the DIAll values of 46.9% of boys and 51.3% of girls exceeded the reference dose (RfD) of 20μg/kg bw/day established by the US Environmental Protection Agency. Our results demonstrate that DIAll is negatively associated with the height percentile, weight percentile, bone age/chronological age, and insulin-like growth factor 1 (IGF-1) levels but not with IGF binding protein 3 (IGF-BP3) level, IGF-1/IGF-BP3, sex hormones, or thyroid hormone levels. The DEHP DIAll value exceeded the RfD at high rates among children of both genders. Our results suggest that high levels of DEHP exposure due to the

  7. Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death

    Guida, Natascia; Laudati, Giusy [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Galgani, Mario; Santopaolo, Marianna [Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Napoli (Italy); Montuori, Paolo; Triassi, Maria [Department of Preventive Medical Sciences, University Federico II, Via Pansini 5, 80131 Naples (Italy); Di Renzo, Gianfranco [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Canzoniero, Lorella M.T., E-mail: canzon@unisannio.it [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Division of Pharmacology, Department of Science and Technology, University of Sannio, Via Port' Arsa 11, 82100 Benevento (Italy); Formisano, Luigi, E-mail: cformisa@unisannio.it [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Division of Pharmacology, Department of Science and Technology, University of Sannio, Via Port' Arsa 11, 82100 Benevento (Italy)

    2014-10-01

    Phthalates, phthalic acid esters, are widely used as plasticizers to produce polymeric materials in industrial production of plastics and daily consumable products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may cause toxic effects in the rat brain. In the present study, chronic exposure to DEHP (0.1–100 μM) caused dose-dependent cell death via the activation of caspase-3 in neuroblastoma cells. Intriguingly, this harmful effect was prevented by the pan-histone deacetylase (HDAC) inhibitor trichostatin A, by the class II HDAC inhibitor MC-1568, but not by the class I HDAC inhibitor MS-275. Furthermore, DEHP reduced specificity protein 3 (Sp3) gene expression, but not Sp3 mRNA, after 24 and 48 h exposures. However, Sp3 protein reduction was prevented by pre-treatment with MC-1568, suggesting the involvement of class II HDACs in causing this effect. Then, we investigated the possible relationship between DEHP-induced neuronal death and the post-translational mechanisms responsible for the down-regulation of Sp3. Interestingly, DEHP-induced Sp3 reduction was associated to its deacetylation and polyubiquitination. Co-immunoprecipitation studies showed that Sp3 physically interacted with HDAC4 after DEHP exposure, while HDAC4 inhibition by antisense oligodeoxynucleotide reverted the DEHP-induced degradation of Sp3. Notably, Sp3 overexpression was able to counteract the detrimental effect induced by DEHP. Taken together, these results suggest that DEHP exerts its toxic effect by inducing deacetylation of Sp3 via HDAC4, and afterwards, Sp3-polyubiquitination. - Highlights: • Di(2-ethylhexyl)phthalate (DEHP) is cytotoxic to SH-SY5Y cells and cortical neurons. • DEHP-induced cytotoxicity is mediated by apoptosis. • DEHP-induced apoptotic cell death is inhibited by class II HDAC MC-1568. • DEHP neurotoxicity is caused by HDAC4-mediated Sp3 degradation by ubiquitin.

  8. Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death

    Phthalates, phthalic acid esters, are widely used as plasticizers to produce polymeric materials in industrial production of plastics and daily consumable products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may cause toxic effects in the rat brain. In the present study, chronic exposure to DEHP (0.1–100 μM) caused dose-dependent cell death via the activation of caspase-3 in neuroblastoma cells. Intriguingly, this harmful effect was prevented by the pan-histone deacetylase (HDAC) inhibitor trichostatin A, by the class II HDAC inhibitor MC-1568, but not by the class I HDAC inhibitor MS-275. Furthermore, DEHP reduced specificity protein 3 (Sp3) gene expression, but not Sp3 mRNA, after 24 and 48 h exposures. However, Sp3 protein reduction was prevented by pre-treatment with MC-1568, suggesting the involvement of class II HDACs in causing this effect. Then, we investigated the possible relationship between DEHP-induced neuronal death and the post-translational mechanisms responsible for the down-regulation of Sp3. Interestingly, DEHP-induced Sp3 reduction was associated to its deacetylation and polyubiquitination. Co-immunoprecipitation studies showed that Sp3 physically interacted with HDAC4 after DEHP exposure, while HDAC4 inhibition by antisense oligodeoxynucleotide reverted the DEHP-induced degradation of Sp3. Notably, Sp3 overexpression was able to counteract the detrimental effect induced by DEHP. Taken together, these results suggest that DEHP exerts its toxic effect by inducing deacetylation of Sp3 via HDAC4, and afterwards, Sp3-polyubiquitination. - Highlights: • Di(2-ethylhexyl)phthalate (DEHP) is cytotoxic to SH-SY5Y cells and cortical neurons. • DEHP-induced cytotoxicity is mediated by apoptosis. • DEHP-induced apoptotic cell death is inhibited by class II HDAC MC-1568. • DEHP neurotoxicity is caused by HDAC4-mediated Sp3 degradation by ubiquitin

  9. Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach.

    Eveillard, Alexandre; Lasserre, Frédéric; de Tayrac, Marie; Polizzi, Arnaud; Claus, Sandrine; Canlet, Cécile; Mselli-Lakhal, Laïla; Gotardi, Gaëlle; Paris, Alain; Guillou, Hervé; Martin, Pascal G P; Pineau, Thierry

    2009-05-01

    Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbalpha pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbalpha target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbalpha pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations. PMID:19245819

  10. Thyroid Endocrine Disruption in Zebrafish Larvae after Exposure to Mono-(2-Ethylhexyl) Phthalate (MEHP)

    Zhai, Wenhui; Huang, Zhigang; Chen, Li; Feng, Cong; Li, Bei; Li, Tanshi

    2014-01-01

    Phthalates are extensively used as plasticizers in a variety of daily-life products, resulting in widespread distribution in aquatic environments. However, limited information is available on the endocrine disrupting effects of phthalates in aquatic organisms. The aim of the present study was to examine whether exposure to mono-(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di-(2-ethylhexyl) phthalate (DEHP) disrupts thyroid endocrine system in fish. In this study, zebrafish (D...

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

    Lorber, Matthew; 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 respon...

  12. Assay of vtg, ERs and PPARs as endpoint for the rapid in vitro screening of the harmful effect of Di-(2-ethylhexyl)-phthalate (DEHP) and phthalic acid (PA) in zebrafish primary hepatocyte cultures.

    Maradonna, Francesca; Evangelisti, Matteo; Gioacchini, Giorgia; Migliarini, Beatrice; Olivotto, Ike; Carnevali, Oliana

    2013-02-01

    In the last years the concern about the negative effects of phthalates on reproduction significantly increased. Considering that, at date data available dealing with the adverse outcome of Di-(2-ethylhexyl)-phthalate (DEHP) on the reproduction of several species are still contrasting, in this study, the effects induced by DEHP (0.05, 0.1, 1, 10 and 100 nM) and its active metabolite, phthalic acid (PA) (0.01, 0.1, 1 and 10 μM), were analyzed in zebrafish, Danio rerio, primary hepatocyte cultures, using target molecules involved in fish reproduction (vitellogenin--vtg and estrogen receptors--ERα, β1 and β2) and metabolism (peroxisome proliferators activated receptors--PPAR α, β, γ). The use of in vitro culture, in fact, has the potential to significantly reduce the number of animals sacrificed for research allowing a precise control of the physical and chemical parameters that is often not possible in vivo. Moreover, since many toxicological studies revealed a sex specific response to toxicants, male and female primary hepatocyte cultures were set up to elucidate the possible gender specific effects of two common environmental phthalates. The increase of vtg levels observed in the culture media of male or female hepatocytes strongly evidenced the phthalates E2-like action. Moreover, the data obtained suggested that the observed different ERs isoforms modulation is otherwise associated with the vtg increase, depending on fish gender. Regarding PPARs, a similar trend of expression was found in both males and females. In conclusion, this study enforces the role of vtg as biomarker for evaluate the presence of environmental doses of DEHP and PA. Considering the similar gender modulation observed for vtg and PPARs, these molecules could be used for the rapid screening of the presence of DEHP and PA. Noteworthy the gender specific modulation observed for ERs opens a debate on the estrogenic mechanism of action of DEHP and PA and their role on vtg induction. PMID

  13. Di (2-ethylhexyl) Phthalate Exposure Impairs Growth of Antral Follicle in Mice

    Li, Lan; Liu, Jing-Cai; Lai, Fang-Nong; Liu, Huan-Qi; Zhang, Xi-Feng; Dyce, Paul W.; Shen, Wei; Chen, Hong

    2016-01-01

    Di (2-ethylhexyl) phthalate (DEHP) is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-...

  14. In vitro serum protein-binding characteristics of bis-(2-ethylhexyl) phthalate and its principal metabolite, mono-(2-ethylhexyl) phthalate

    The metabolism and toxicity of the ubiquitous plasticizer, bis-(2-ethylhexyl) phthalate (DEHP), and its principal metabolite, mono-(2-ethylhexyl) phthalate (MEHP), have been extensively investigated. In an attempt to understand their disposition in man, the authors studied the in vitro serum protein-binding characteristics of these compounds, using ultracentrifugation and agarose gel electrophoresis. The association of DEHP and lipoproteins was shown to be highly dependent upon, and proportional to, the lipid concentration of the serum. It appears that more than half of the serum DEHP is bound to proteins with density greater than 1.21 g/mL when the concentration of cholesterol is below 300 mg/dL or the cholesterol and triglyceride total concentration is less than 600 mg/dL. As the cholesterol and triglyceride concentrations increase, the percent DEHP bound to VLDL, IDL, and LDL increases. MEHP is bound principally to nonlipoprotein constituents in the serum, and this binding distribution is unaffected by lipid concentration. The percent binding of DEHP and MEHP to individual proteins was also found to be unaffected by their concentrations in serum. These data indicate that the protein-binding characteristics of these compounds, in vitro, is somewhat more complex than previously reported

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

    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 μg/ml) and MEHP (0.1-10 μg/ml) directly inhibit antral follicular growth and 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.

  16. Survey of di-(2-ethylhexyl)phthalate plasticiser contamination of retail Danish milks

    Petersen, Jens Højslev

    1991-01-01

    An investigation of residues of di-(2-ethylhexyl)-phthalate (DEHP) in retail whole milk in samples from one German and 14 Danish dairies is reported. The investigation was performed about six months after the use of DEHP-plasticized milk tubing was banned in Denmark. The results indicate a mean c...

  17. The endocrine disruptor mono-(2-ethylhexyl)phthalate promotes adipocyte differentiation and induces obesity in mice

    Chanjuan Hao; Xuejia Cheng; Hongfei Xia; Xu Ma

    2013-01-01

    The environmental obesogen hypothesis proposes that exposure to endocrine disruptors during developmental ‘window’ contributes to adipogenesis and the development of obesity. MEHP [mono-(2-ethylhexyl) phthalate], a metabolite of the widespread plasticizer DEHP [di-(2-ethylhexyl) phthalate], has been found in exposed organisms and identified as a selective PPARγ (peroxisome-proliferator-activated receptor γ) modulator. However, implication of MEHP on adipose tissue ...

  18. MECHANISTIC CONSIDERATIONS FOR HUMAN RELEVANCE OF CANCER HAZARD OF DI(2-ETHYLHEXYL) PHTHALATE

    Rusyn, Ivan; Corton, J. Christopher

    2011-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator agent that is widely used as a plasticizer to soften polyvinylchloride plastics and non-polymers. Both occupational (e.g., by inhalation during its manufacture and use as a plasticizer of polyvinylchloride) and environmental (medical devices, contamination of food, or intake from air, water and soil) routes of exposure to DEHP are of concern for human health. There is sufficient evidence for carcinogenicity of DEHP in the liver in...

  19. Urinary concentrations of di(2-ethylhexyl) phthalate metabolites and serum reproductive hormones

    Mendiola, Jaime; Meeker, John D; Jørgensen, Niels;

    2012-01-01

    Urinary concentrations of metabolites of the anti-androgenic xenobiotic di-(2-ethylhexyl) phthalate (DEHP) were previously shown to be weakly associated with serum levels of several hormones in 2 disparate US populations: partners of pregnant women participating in the Study for Future Families a...

  20. The Adverse Cardiac Effects of Di(2-ethylhexyl) phthalate and Bisphenol A

    Posnack, Nikki Gillum

    2014-01-01

    The ubiquitous nature of plastics has raised concerns pertaining to continuous exposure to plastic polymers and human health risks. Of particular concern is the use of endocrine-disrupting chemicals (EDCs) in plastic production, including Di(2-ethylhexyl) phthalate (DEHP) and Bisphenol A (BPA). Widespread and continuous exposure to DEHP and BPA occurs through dietary intake, inhalation, dermal and intravenous exposure via consumer products and medical devices. This article reviews the literat...

  1. In Utero Exposure to Di-(2-Ethylhexyl) Phthalate Decreases Mineralocorticoid Receptor Expression in the Adult Testis

    Martinez-Arguelles, D B; Culty, M.; Zirkin, B. R.; Papadopoulos, V.

    2009-01-01

    In utero exposure to di-(2-ethylhexyl) phthalate (DEHP) has been shown to result in decreased androgen formation by fetal and adult rat testes. In the fetus, decreased androgen is accompanied by the reduced expression of steroidogenic enzymes. The mechanism by which in utero exposure results in reduced androgen formation in the adult, however, is unknown. We hypothesized that deregulation of the nuclear steroid receptors might explain the effects of in utero DEHP exposure on adult testosteron...

  2. Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets

    A comparison of the dose-dependent blood burden of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in pregnant and nonpregnant rats and marmosets is presented. Sprague-Dawley rats and marmosets were treated orally with 30 or 500 mg DEHP/kg per day, nonpregnant animals on 7 (rats) and 29 (marmosets) consecutive days, pregnant animals on gestation days 14-19 (rats) and 96-124 (marmosets). In addition, rats received a single dose of 1000 mg DEHP/kg. Blood was collected up to 48 h after dosing. Concentrations of DEHP and MEHP in blood were determined by GC/MS. In rats, normalized areas under the concentration-time curves (AUCs) of DEHP were two orders of magnitude smaller than the normalized AUCs of the first metabolite MEHP. Metabolism of MEHP was saturable. Repeated DEHP treatment and pregnancy had only little influence on the normalized AUC of MEHP. In marmosets, most of MEHP concentration-time courses oscillated. Normalized AUCs of DEHP were at least one order of magnitude smaller than those of MEHP. In pregnant marmosets, normalized AUCs of MEHP were similar to those in nonpregnant animals with the exception that at 500 mg DEHP/kg per day, the normalized AUCs determined on gestation days 103, 117, and 124 were distinctly smaller. The maximum concentrations of MEHP in blood of marmosets were up to 7.5 times and the normalized AUCs up to 16 times lower than in rats receiving the same daily oral DEHP dose per kilogram of body weight. From this toxicokinetic comparison, DEHP can be expected to be several times less effective in the offspring of marmosets than in that of rats if the blood burden by MEHP in dams can be regarded as a dose surrogate for the MEHP burden in their fetuses

  3. Effects of sewage sludge on Di-(2-ethylhexyl) phthalate uptake by plants

    Di-(2-ethylhexyl) phthalate (DEHP) is a priority organic pollutant frequently found in municipal sludges. A greenhouse study was conducted to determine the effect of sludge on plant uptake of 14C-DEHP (carbonyl labeled). Plants grown included three food chain crops, lettuce (Lactuca sativa L.), carrot (Daucus carota L.) and chile pepper (Capsicum annuum L.) and tall fescue (Festuca arundinacea Schreb.). Net 14C concentration in plants grown in soil amended with 14C-DEHP-contaminated sludge was independent of sludge rate (at the same DEHP loading) for lettuce, chile fruit, and carrot roots. Net 14C concentration, however, was inversely related to sludge rate in carrot tops, fescue, and chile plants. Intact DEHP was not detected in plants by gas chromatography/mass spectrometry analysis. Calculated plant DEHP concentrations (based on measured net 14C concentrations and DEHP specific activities) were generally correlated better with DEHP soil solution concentrations than with total DEHP soil concentrations. Net 14C-DEHP bioconcentration factors were calculated from initial soil DEHP concentration and plant fresh weights. Bioconcentration factors ranged from 0.01 to 0.03 for fescue, lettuce, carrots, and chile, suggesting little DEHP uptake. Additionally, because intact DEHP was not detected in any plants, DEHP uptake by plants was of minor importance and would not limit sludge additions to soils used to grow these crops

  4. Presystemic branchial metabolism limits di-2-ethylhexyl phthalate accumulation in fish

    Despite the high lipophilicity of di-2-ethylhexyl phthalate (DEHP), fish do not extensively accumulate this ubiquitous environmental contaminant. Experiments with rainbow trout (Salmo gairdneri) fitted with an indwelling cannula showed that the majority of [14C]DEHP did not reach the systemic circulation of the fish, but was present in the exposure water as metabolites. Pharmacokinetic analysis, using a compartmental model that included the gill as a separate metabolic compartment, indicated that DEHP was extensively metabolized as it diffused from water to blood. Isolated perfused gill arches of trout metabolized DEHP in the exposure bath to monoethylhexyl phthalate, demonstrating the ability of the gill to prevent DEHP entry into the fish. The relationship between metabolic clearance and tissue perfusion further suggests that metabolism in the gill can play an important role in determining the accumulation and toxicity of organic chemical pollutants in fish

  5. [Accumulation of di-(2-ethylhexyl) phthalate in various genotype Ipomoea aquatica-paddy soil system].

    Cai, Quanying; Mo, Cehui; Zeng, Qiaoyun; Li, Yunhui; Xiao, Kai'en; Li, Haiqin; Xu, Guosheng; Wang, Boguang; Wu, Qingzhu

    2004-08-01

    Various genotypes of Ipomoea aquatica were pot-cultured on paddy soils with different pollution level of di-(2-ethylhexyl) phthalate (DEHP), and the concentrations of DEHP in plant and soil were determined by GC/MS. The results showed that the concentration of DEHP in plant varied directly with soil pollution level, and different genotypes of Ipomoea aquatica had significantly different concentrations of DEHP, which varied directly with leaf area. Soils grown with various genotypes of Ipomoea aquatica also had significantly different DEHP concentrations. The soil DEHP bioaccumulation factors (BCFs) of various Ipomoea aquatica genotypes were all under 1.0 and in inverse proportion to soil pollution level. The BCFs varied significantly among the genotypes of Ipomoea aquatica, with a relatively higher value for those genotypes with middle size leaves. PMID:15574007

  6. Di(2-ethylhexyl) phthalate exacerbates non-alcoholic fatty liver in rats and its potential mechanisms.

    Chen, Hao; Zhang, Wang; Rui, Bei-Bei; Yang, Si-Min; Xu, Wei-Ping; Wei, Wei

    2016-03-01

    Di(2-ethylhexyl) phthalate (DEHP) may be responsible for inducing alterations similar to those encountered in nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to investigate the detrimental effects and possible mechanisms of DEHP on fatty liver rats directly through triggering the disorder of liver lipid metabolism or indirectly by hepatotoxic effect. Considering these effects, DEHP may play a significant role in the pathogenesis of NAFLD. In this study, high-fat diet was used to induce NAFLD in rats for eight weeks. DEHP treated groups received (0.05, 5, 500mg/kg daily, respectively) dose by gavage during the whole experiment period. Our results indicated that the detrimental effects of DEHP on high-fat diet induced NAFLDs were mediated via increasing lipid accumulation in the liver and causing lipid peroxidation and inflammation. PMID:26773359

  7. Survey of di-(2-ethylhexyl)phthalate plasticizer contamination of retail Danish milks.

    Petersen, J H

    1991-01-01

    An investigation of residues of di-(2-ethylhexyl)-phthalate (DEHP) in retail whole milk in samples from one German and 14 Danish dairies is reported. The investigation was performed about six months after the use of DEHP-plasticized milk tubing was banned in Denmark. The results indicate a mean concentration of DEHP lower than 50 micrograms/litre in retail whole milk. Based on these data and the Tolerable Daily Intake (TDI) for DEHP of 25 micrograms/kg body weight laid down by the EEC Scientific Committee for Food, it is concluded that the intake of DEHP from milk and milk products does not, even through a whole life, constitute a danger to health for the Danish population. PMID:1812016

  8. Effects of early pubertal exposure to di-(2-ethylhexyl) phthalate on social behavior of mice.

    Wang, Ran; Xu, Xiaohong; Weng, Huifang; Yan, Shengyao; Sun, Yangyang

    2016-04-01

    Di-(2-ethylhexyl) phthalate (DEHP), a main member of phthalates used as plasticizer in PVC plastics, is an environmental endocrine disrupter. The present study investigated the effect of DEHP on social behavior of mice following pubertal exposure (1, 10, 50, and 200mg/kg/d) from postnatal day 28 through postnatal day 42. The results showed that, in pubertal females, DEHP reduced the time spent in social play and social investigation and inhibited sociability, but a contrary effect was found in pubertal males, suggesting that the effect of DEHP on pubertal social behavior displays sex differences. In adults, DEHP reduced sociability in females and inhibited social play and social investigation in males, suggesting that early pubertal exposure to DEHP not only plays a significant role in puberty but also alters social behavior in adults. In addition, the present study showed that the higher dose of DEHP (50, 200mg/kg/d) reduced the relative weight of bilateral testis and anogenital distance of pubertal or adult males, suggesting an anti-androgenic activity of DEHP. These results suggest that early pubertal exposure to DEHP sex- and age- specifically affected the social behaviors of pubertal and even adult mice. PMID:26844866

  9. Health hazards associated with the use of di-(2-ethylhexyl) phthalate (commonly referred to as DOP) in HEPA filter test

    NONE

    1995-01-01

    Di-(2-ethylhexyl) phthalate (DEHP), commonly referred to as di-octyl phthalate, is an important production chemical in the US. In addition to its major use as an additive in plastics, DEHP is widely used to evaluate the effectiveness of high efficiency particulate air (HEPA) filters. Historically, DEHP was also used in quantitative fit testing for respirators. Evaluations of this compound a decade ago showed that it can induce hepatocellular carcinomas in laboratory animals. Although most Department of Energy (DOE) facilities have since discontinued using DEHP in respirator fit testing, DEHP continues to be used for evaluating HEPA filters. This report summarizes available information on the toxicity, mutagenicity, carcinogenicity, and other hazards and problems posed by DEHP, specifically with reference to HEPA filter testing. Information on work practice improvements as well as the availability and suitability of DEHP substitutes are also presented. This material should assist the DOE in the safe use of this material.

  10. Effects of airway exposure to di-(2-ethylhexyl) phthalate on allergic rhinitis.

    He, Miao; Inoue, Ken-Ichiro; Yoshida, Seiichi; Tanaka, Michitaka; Takano, Hirohisa; Sun, Guifan; Ichinose, Takamichi

    2013-06-01

    Recent epidemiological studies have suggested a positive link between atopy morbidity and exposure to phthalate esters, which are environmental chemicals mainly involved in house dust. Nevertheless, experimental studies applying several allergic in vivo models (in addition to epidemiological studies) are needed to prove the precise correlation between phthalates and facilitation of the allergic response/pathophysiology. Among the phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used in flexible polyvinyl chloride products, including vinyl flooring and wall covering, and has been widely suggested to have immunomodulating potential. In the present study, we examined the effects of airway exposure to DEHP on allergen (ovalbumin: OVA)-induced rhinitis in mice. The repeated administration of OVA via an intranasal route induced nasal inflammation characterized by the infiltration of granulocytes (neutrophils and eosinophils) into the nasal cavity. In this experimental setting, DEHP did not exaggerate OVA-related inflammatory pathology. However, local (nasal) IL-13 levels were significantly higher in mice treated with allergen plus DEHP than with allergen alone. Taken together, phthalate esters including DEHP have the potential to exacerbate the allergic milieu in the nasal system, as well as dermal and respiratory systems. PMID:23672524

  11. Maternal exposure to di-(2-ethylhexyl) phthalate disrupts placental growth and development in pregnant mice

    Zong, Teng; Lai, Lidan [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China); Hu, Jia [Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi (China); Guo, Meijun; Li, Mo; Zhang, Lu; Zhong, Chengxue; Yang, Bei; Wu, Lei; Zhang, Dalei; Tang, Min [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China); Kuang, Haibin, E-mail: kuanghaibin@ncu.edu.cn [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China)

    2015-10-30

    Highlights: • The influence of DEHP on the development of placenta was investigated. • DEHP disrupts the growth and development of placenta. • DEHP disrupts the formation of labyrinth vascularization. • DEHP inhibits the proliferation of ectoplacental cone and placenta. • DEHP induces the apoptosis of placenta via activated MAPK signaling pathway. - Abstract: Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and widely dispersed in the environment. DEHP exposure reduces embryo implantations, increases embryonic loss, and decreases fetal body weights. However, no detailed information is available about the effect of DEHP on the placentation during pregnancy. Thus, our aim was to explore the effect of DEHP on the growth and development of placenta in vivo. Mice were administered DEHP by gavages at 125, 250, 500 mg/kg/day from gestational days (GD) 1 until sacrifice. Results showed that DEHP treatment significantly reduced the weight of placenta at GD 13. Histopathologically, in DEHP-treated group, the ectoplacental cones significantly became smaller at GD9, and total area of placenta and area of spongiotrophoblast were significantly reduced at GD 13. Expression levels of Ascl2, Esx1 and Fosl1 mRNA dramatically decreased in DEHP-treated placenta at GD 13. DEHP administration disrupted labyrinth vascularization of placentas, and inhibited proliferation and induced apoptosis of placenta by the activation of caspase-3 and -8, up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein at GD 13. In conclusion, these results suggest that adverse pregnancy outcomes including low birth-weight and pregnancy loss exposed to DEHP are possibly mediated, at least in part, via the suppression of placental growth and development.

  12. Achromobacter denitrificans strain SP1 efficiently remediates di(2-ethylhexyl)phthalate.

    Pradeep, S; Josh, M K Sarath; Binod, P; Devi, R Sudha; Balachandran, S; Anderson, Robin C; Benjamin, Sailas

    2015-02-01

    This study describes how Achromobacter denitrificans strain SP1, a novel isolate from heavily plastics-contaminated sewage sludge efficiently consumed the hazardous plasticizer, di(2-ethylhexyl)phthalate (DEHP) as carbon source supplemented in a simple basal salt medium (BSM). Response surface methodology was employed for the statistical optimization of the process parameters such as temperature (32°C), agitation (200 rpm), DEHP concentration (10 mM), time (72 h) and pH (8.0). At these optimized conditions, experimentally observed DEHP degradation was 63%, while the predicted value was 59.2%; and the correlation coefficient between them was 0.998, i.e., highly significant and fit to the predicted model. Employing GC-MS analysis, the degradation pathway was partially deduced with intermediates such as mono(2-ethylhexyl)phthalate and 2-ethyl hexanol. Briefly, this first report describes A. denitrificans strain SP1 as a highly efficient bacterium for completely remediating the hazardous DEHP (10 mM) in 96 h in BSM (50% consumed in 60 h), which offers great potentials for efficiently cleaning the DEHP-contaminated environments such as soil, sediments and water upon its deployment. PMID:25463861

  13. Toxicity of di-(2-ethylhexyl) phthalate on the anaerobic digestion of wastewater sludge

    Alatriste-Mondragon, Felipe; Iranpour, R.; Ahring, Birgitte Kiær

    2003-01-01

    are considered recalcitrant. Moreover, they inhibit methanogenesis. However, studies have not been made on the effect of feeding a combination of recalcitrant and biodegradable PAEs into anaerobic digesters treating wastewater sludge. The present study was conducted with wastewater sludge from the Los Angeles...... populations in the anaerobic bioreactor. Our results imply that high levels of DEHP or other recalcitrant PAEs in wastewater sludge are likely to compromise methanogenesis and removal of biodegradable PAEs in sludge digesters....... Bureau of Sanitation's Hyperion Treatment Plant. Di (2-ethylhexyl) phthalate (DEHP), the most common persistent PAE found in wastewater, and di-n-butyl phthalate (DBP), a common PAE with short ester chains, were sorbed into the sludge fed to a bench-scale digester for a period of 12 weeks. DEHP...

  14. Applications of isotope differentiation for metabolic studies with di-(2-ethylhexyl) phthalate

    The pervasiveness of the plasticizer di-(2-ethylhexyl) phthalate (DEHP) in the environment and especially in the laboratory results in a background that may cause severe interference with analytical studies. Animal-to-animal variability in the distribution of DEHP metabolites in excreta normally makes it necessary to use large groups of animals when different treatments are compared. Finally, radioactive tracers are usually considered undesirable for metabolic studies involving human subjects. All of these problems can be overcome through the use of multiple isotopic labels, especially 12C/13C/14C. Examples are given involving rats and monkeys, and applicability to humans is discussed. The principles involved are not limited to any particular class of test compounds. In rats, the competing pathways for metabolism of phthalate esters produce a different distribution of metabolites from a small intravenous dose of DEHP than from a large oral dose

  15. Risk assessment of di(2-ethylhexyl) phthalate in the workplace

    2016-01-01

    Objectives A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. Methods Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor (“Survey on the work environment”) and by the Ministry of Environment (“Survey on the circulation amount of chemicals”). Risk was determined according to exposure in workplaces and chemical hazard. Results In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be 0.990 mg/m3, as compared to the threshold exposure level of 5 mg/m3. The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. Conclusions DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the

  16. The Adverse Cardiac Effects of Di(2-ethylhexyl) phthalate and Bisphenol A

    Posnack, Nikki Gillum

    2014-01-01

    The ubiquitous nature of plastics has raised concerns pertaining to continuous exposure to plastic polymers and human health risks. Of particular concern is the use of endocrine-disrupting chemicals (EDCs) in plastic production, including Di(2-ethylhexyl) phthalate (DEHP) and Bisphenol A (BPA). Widespread and continuous exposure to DEHP and BPA occurs through dietary intake, inhalation, dermal and intravenous exposure via consumer products and medical devices. This article reviews the literature examining the relationship between DEHP and BPA exposure and cardiac toxicity. In vitro and in vivo experimental reports are outlined, as well as epidemiological studies which examine the association between these chemicals and cardiovascular outcomes. Gaps in our current knowledge are also discussed, along with future investigative endeavors that may help resolve whether DEHP and/or BPA exposure has a negative impact on cardiovascular physiology. PMID:24811950

  17. In Utero Exposure to the Antiandrogen Di-(2-Ethylhexyl) Phthalate Decreases Adrenal Aldosterone Production in the Adult Rat1

    Martinez-Arguelles, Daniel B.; Guichard, Theodore; Culty, Martine; Zirkin, Barry R.; Papadopoulos, Vassilios

    2011-01-01

    We previously reported that in utero exposure of the male fetus to the plasticizer di-(2-ethylhexyl) phthalate (DEHP) resulted in decreased circulating levels of testosterone in the adult without affecting Leydig cell numbers, luteinizing hormone levels, or steroidogenic enzyme expression. Fetal exposure to DEHP resulted in reduced mineralocorticoid receptor (MR; NR3C2) expression in adult Leydig cells. In the present studies, treatment of pregnant Sprague-Dawley dams from Gestational Day 14 ...

  18. Di-(2-ethylhexyl phthalate and autism spectrum disorders

    Giuseppe Latini

    2012-05-01

    Full Text Available ASDs (autism spectrum disorders are a complex group of neurodevelopment disorders, still poorly understood, steadily rising in frequency and treatment refractory. Extensive research has been so far unable to explain the aetiology of this condition, whereas a growing body of evidence suggests the involvement of environmental factors. Phthalates, given their extensive use and their persistence, are ubiquitous environmental contaminants. They are EDs (endocrine disruptors suspected to interfere with neurodevelopment. Therefore they represent interesting candidate risk factors for ASD pathogenesis. The aim of this study was to evaluate the levels of the primary and secondary metabolites of DEHP [di-(2-ethylhexyl phthalate] in children with ASD. A total of 48 children with ASD (male: 36, female: 12; mean age: 11±5 years and age- and sex-comparable 45 HCs (healthy controls; male: 25, female: 20; mean age: 12±5 years were enrolled. A diagnostic methodology, based on the determination of urinary concentrations of DEHP metabolites by HPLC-ESI-MS (HPLC electrospray ionization MS, was applied to urine spot samples. MEHP [mono-(2-ethylhexenyl 1,2-benzenedicarboxylate], 6-OH-MEHP [mono-(2-ethyl-6-hydroxyhexyl 1,2-benzenedicarboxylate], 5-OH-MEHP [mono-(2-ethyl-5-hydroxyhexyl 1,2-benzenedicarboxylate] and 5-oxo-MEHP [mono-(2-ethyl-5-oxohexyl 1,2-benzenedicarboxylate] were measured and compared with unequivocally characterized, pure synthetic compounds (>98% taken as standard. In ASD patients, significant increase in 5-OH-MEHP (52.1%, median 0.18 and 5-oxo-MEHP (46.0%, median 0.096 urinary concentrations were detected, with a significant positive correlation between 5-OH-MEHP and 5-oxo-MEHP (rs = 0.668, P<0.0001. The fully oxidized form 5-oxo-MEHP showed 91.1% specificity in identifying patients with ASDs. Our findings demonstrate for the first time an association between phthalates exposure and ASDs, thus suggesting a previously unrecognized role for

  19. In vivo immunoamplifying effects of di-(2-ethylhexyl) phthalate on cytokine response.

    Tanaka, Michitaka; Inoue, Ken-ichiro; Momoi, Takashi; Takano, Hirohisa

    2013-02-01

    A recent epidemiological study has revealed the positive association between atopy morbidity in children and phthalate esters, environmental chemicals in house dust. Nonetheless, experimental and molecular evidences regarding the correlation between phthalates and allergic response/pathophysiology are not fully investigated. Among phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used for flexible polyvinyl chloride products including vinyl flooring and wall covering. In the present study, we examined the effects of exposure to DEHP on allergen (ovalbumin: OVA) -induced peritonitis in ICR mice. Repeated administration of OVA via intraperitoneal route induced peritoneal inflammation characterized by infiltration of granulocytes (neutrophils and eosinophils) into the cavity. DEHP synergistically exaggerated the OVA-related neutrophilic inflammation. Furthermore, DEHP + OVA profoundly amplified OVA-elicited inflammation- and allergy-related molecules such as interleukin-5, eotaxin, and keratinocyte-derived chemoattractant production/release in the peritoneal cavity. Taken together, DEHP aggravated OVA-related peritoneal inflammation, which is concomitant with local enhanced production/release of inflammation- and allergy-related molecules. PMID:23098214

  20. Radioimmunoassay for mono-(2-ethylhexyl) phthalate in unextracted plasma

    We report a radioimmunoassay for mono-(2-ethylhexyl) phthalate that has been coupled to a protein carrier as a radioligand. Competitive interference tests with a variety of related compounds indicated the assay to be highly specific. Quantitative comparison of mono-(2-ethylhexyl) phthalate values in plasma and serum samples between the radioimmunoassay and gas chromatographic procedures indicated a high reliability. Because this potentially toxic compound can leach into plasma from polyvinyl plastics, this assay should be particularly useful for those involved in the manufacture or use of medical devices made of them

  1. Data from one test "Semi-Volatile Organic Compound Small Chamber for bis (2-Ethylhexyl) phthalate in Vinyl Flooring Test 2"

    This data was generated from a small chamber bis(2-ethylhexyl) phthalate (DEHP) emission test. It was to participate an interaboratory study of DEHP emissions from vinyl flooring in a SVOC emission chamber organized by Virginia Polytechnic Institute and State University (VT).

  2. Di-(2-ethylhexyl) phthalate affects immune cells from atopic prone mice in vitro

    Phthalate esters as plasticizers have been widespread in the environment and may be associated with development of allergic diseases such as asthma and atopic dermatitis. However, the underlying mechanisms have not been fully elucidated. The present study investigated the effects of di-(2-ethylhexyl) phthalate (DEHP) on immune cells from atopic prone NC/Nga mice in vitro. Bone marrow-derived dendritic cells (BMDC) as a professional antigen-presenting cell and splenocytes as mixture of immune cells were used. BMDC were differentiated by culture with granulocyte macrophage-colony stimulating factor (GM-CSF) in the presence of DEHP (0.1-10 μM) for 6 days. In another experiments, BMDC were differentiated by culture with GM-CSF for 8 days then these BMDC were exposed to DEHP (0.1-100 μM) for 24 h. Splenocytes were exposed to DEHP for 24 h (0.1-100 μM) or 72 h (0.1-1000 nM). After the culture, the phenotypic markers and the function of BMDC and splenocytes were evaluated. BMDC differentiated in the presence of DEHP showed enhancement in the expression of MHC class II, CD86, CD11c and DEC205, and in their antigen-presenting activity. On the other hand, the function of the differentiated BMDC was not activated by DEHP although DEHP partly enhanced their expression of DEC205. DEHP-exposed splenocytes showed increases in their TCR and CD3 expression, interleukin-4 production, and antigen-stimulated proliferation. These results demonstrate that DEHP enhances BMDC differentiation but not activation and also enhances Th2 response in splenocytes from atopic prone mice. The enhancement might contribute to the aggravating effect of DEHP on allergic disorders.

  3. Prepubertal exposure to genistein alleviates di-(2-ethylhexyl) phthalate induced testicular oxidative stress in adult rats.

    Zhang, Lian-Dong; Li, He-Cheng; Chong, Tie; Gao, Ming; Yin, Jian; Fu, De-Lai; Deng, Qian; Wang, Zi-Ming

    2014-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors. PMID:25530965

  4. Altered Hippocampal Lipid Profile Following Acute Postnatal Exposure to Di(2-Ethylhexyl Phthalate in Rats

    Catherine A. Smith

    2015-10-01

    Full Text Available Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl phthalate (DEHP disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females.

  5. Inhibition of human platelet phospholipase A/sub 2/ by mono(2-ethylhexyl)phthalate

    Labow, R.S.; Meek, E.; Adams, G.A.; Rock, G.

    1988-06-01

    There is evidence that the carcinogenic and teratogenic effects attributed to the plasticizer di(2-ethylhexyl)phthalate (DEHP) are due to its major metabolite mono(2-ethylhexyl)phthalate (MEHP). MEHP is also formed ex vivo by a plasma enzyme in blood products stored in polyvinyl chloride (PVC) DEHP plastic containers. People who receive large amounts of blood products, such as hemophiliacs or patients undergoing hemodialysis, cardiopulmonary bypass, or massive transfusion, are exposed to significant levels of plasticizer. In this study, the platelet was used to show that MEHP inhibits phospholipase A/sub 2/ (PLA/sub 2/), one of the enzymes important in the release of arachidonic acid from membrane phospholipids. PLA/sub 2/ was measured by the liberation of /sup 14/C-arachidonic acid from 1-stearoyl-2-(1-/sup 14/C)arachidonyl-L-3-phosphatidylcholine. MEHP inhibits PLA/sub 2/ activity noncompetitively in intact human platelets and lysates with a K/sub i/ of 3.7 x 10/sup -4/ M. DEHP does not inhibit PLA/sub 2/ in whole platelets. Inhibition of PLA/sub 2/ by MEHP occurs at only three times the circulating level of MEHP measured in neonates undergoing exchange transfusion and 20-fold the levels experienced by patients during cardiopulmonary bypass. Therefore, infants and adult patients with multisystem failure who accumulate MEHP in their blood may be at risk for decreased platelet function.

  6. Inhibition of human platelet phospholipase A2 by mono(2-ethylhexyl)phthalate

    There is evidence that the carcinogenic and teratogenic effects attributed to the plasticizer di(2-ethylhexyl)phthalate (DEHP) are due to its major metabolite mono(2-ethylhexyl)phthalate (MEHP). MEHP is also formed ex vivo by a plasma enzyme in blood products stored in polyvinyl chloride (PVC) DEHP plastic containers. People who receive large amounts of blood products, such as hemophiliacs or patients undergoing hemodialysis, cardiopulmonary bypass, or massive transfusion, are exposed to significant levels of plasticizer. In this study, the platelet was used to show that MEHP inhibits phospholipase A2 (PLA2), one of the enzymes important in the release of arachidonic acid from membrane phospholipids. PLA2 was measured by the liberation of 14C-arachidonic acid from 1-stearoyl-2-[1-14C]arachidonyl-L-3-phosphatidylcholine. MEHP inhibits PLA2 activity noncompetitively in intact human platelets and lysates with a K/sub i/ of 3.7 x 10-4 M. DEHP does not inhibit PLA2 in whole platelets. Inhibition of PLA2 by MEHP occurs at only three times the circulating level of MEHP measured in neonates undergoing exchange transfusion and 20-fold the levels experienced by patients during cardiopulmonary bypass. Therefore, infants and adult patients with multisystem failure who accumulate MEHP in their blood may be at risk for decreased platelet function

  7. DI-(2-ETHYLHEXYL PHTHALATE OXIDATIVE DEGRADATION BY FENTON PROCESS IN SYNTHETIC AND REAL PETROCHEMICAL WASTEWATER

    R. Esmaeli

    2011-09-01

    Full Text Available Di-(2-Ethylhexyl phthalate (DEHP belongs to the class of phthalate esters and is used as an additive in many products including plastics, paints and inks or as a solvent in industrial formulations. The degradation of DEHP in aqueous solution using oxidative Fenton reaction (H2O2/Fe2+ was carried out in this study. It was found that H2O2 concentration, Fe2+ concentration, and pH were the three main factors that could significantly influence the degradation rates of DEHP. The highest degradation percentage (85.6 % of DEHP was observed within 60 min at pH 3 in H2O2/Fe2+ system. The results of our study suggested that the concentration with 90 mg/L H2O2, 5 mg/L Fe2+, and 20 mg/L DEHP in the solution at pH 3 were the optimal conditions. The optimized reaction parameters were preceded for treatment of real wastewater obtained from a petrochemical plant.

  8. Association between Maternal Exposure to di(2-ethylhexyl) Phthalate and Reproductive Hormone Levels in Fetal Blood: The Hokkaido Study on Environment and Children's Health

    Atsuko Araki; Takahiko Mitsui; Chihiro Miyashita; Tamie Nakajima; Hisao Naito; Sachiko Ito; Seiko Sasaki; Kazutoshi Cho; Tamiko Ikeno; Katsuya Nonomura; Reiko Kishi

    2014-01-01

    Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23-35 weeks of gestation and the concent...

  9. Association between Maternal Exposure to di(2-ethylhexyl) Phthalate and Reproductive Hormone Levels in Fetal Blood: The Hokkaido Study on Environment and Children's Health

    Araki, Atsuko; Mitsui, Takahiko; Miyashita, Chihiro; NAKAJIMA, TAMIE; Naito, Hisao; Ito, Sachiko; Sasaki, Seiko; Cho, Kazutoshi; Ikeno, Tamiko; Nonomura, Katsuya; Kishi, Reiko

    2014-01-01

    Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23–35 weeks of gestation and the concent...

  10. Adjuvant effects of inhaled mono-2-ethylhexyl phthalate in BALB/cJ mice

    Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.;

    2007-01-01

    Phthalates, including di(2-ethylhexyl) phthalate (DEHP), are widely used and have been linked with the development of wheezing and asthma. The main metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP), was investigated for adjuvant effects in a mouse inhalation model. BALB/cJ mice were exposed to...... aerosols of 0.03 or 0.4 mg/m(3) MEHP 5 days/week for 2 weeks and thereafter weekly for 12 weeks together with a low dose of ovalbumin (OVA) as a model allergen. Mice exposed to OVA alone or OVA+Al(OH)(3) served as negative and positive controls, respectively. Finally, all groups were exposed to a nebulized...... mediated by an IgG1-dependent mechanism. To address implications for humans, a margin-of-exposure was estimated based on the lack of significant effects on IgE production and inflammation after exposures to 0.03 mg/m(3) MEHP observed in the present study and estimated human exposure levels....

  11. Di (2-ethylhexyl) Phthalate Exposure Impairs Growth of Antral Follicle in Mice

    Li, Lan; Liu, Jing-Cai; Lai, Fang-Nong; Liu, Huan-Qi; Zhang, Xi-Feng; Dyce, Paul W.; Shen, Wei; Chen, Hong

    2016-01-01

    Di (2-ethylhexyl) phthalate (DEHP) is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 μg/kg DEHP every 5 days from postnatal day 0 (0 dpp) to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative) related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and γH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox-sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre-pubertal stage in mice. PMID:26845775

  12. Di (2-ethylhexyl) Phthalate Exposure Impairs Growth of Antral Follicle in Mice.

    Li, Lan; Liu, Jing-Cai; Lai, Fang-Nong; Liu, Huan-Qi; Zhang, Xi-Feng; Dyce, Paul W; Shen, Wei; Chen, Hong

    2016-01-01

    Di (2-ethylhexyl) phthalate (DEHP) is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 μg/kg DEHP every 5 days from postnatal day 0 (0 dpp) to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative) related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and γH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox-sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre-pubertal stage in mice. PMID:26845775

  13. Di (2-ethylhexyl Phthalate Exposure Impairs Growth of Antral Follicle in Mice.

    Lan Li

    Full Text Available Di (2-ethylhexyl phthalate (DEHP is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 μg/kg DEHP every 5 days from postnatal day 0 (0 dpp to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and γH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox-sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre-pubertal stage in mice.

  14. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

    Wang, Wei, E-mail: weiwang2@illinois.edu; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbasava2@illinois.edu; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-01-15

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ► DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ► NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ► DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral

  15. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ► DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ► NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ► DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral

  16. Mechanisms of toxicity of di(2-ethylhexyl) phthalate on the reproductive health of male zebrafish

    Uren-Webster, Tamsyn M.; Lewis, Ceri; Filby, Amy L.; Paull, Gregory C. [Hatherly Laboratories, School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS (United Kingdom); Santos, Eduarda M., E-mail: e.santos@exeter.ac.uk [Hatherly Laboratories, School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS (United Kingdom)

    2010-09-01

    Phthalates are ubiquitous in the aquatic environment and are known to adversely affect male reproductive health in mammals through interactions with multiple receptor systems. However, little is known about the risks they pose to fish. This project investigated the effects of di(2-ethylhexyl) phthalate (DEHP), the most commonly used phthalate, on the reproductive health of male zebrafish (Danio rerio). Males were treated with 0.5, 50 and 5000 mg DEHP kg{sup -1} (body weight) for a period of 10 days via intraperitoneal injection. The effects of the exposure were assessed by analysing fertilisation success, testis histology, sperm DNA integrity and transcript profiles of the liver and testis. A significant increase in the hepatosomatic index and levels of hepatic vitellogenin transcript were observed following exposure to 5000 mg DEHP kg{sup -1}. Exposure to 5000 mg DEHP kg{sup -1} also resulted in a reduction in fertilisation success of oocytes spawned by untreated females. However, survival and development of the resulting embryos were unaffected by all treatments, and no evidence of DEHP-induced sperm DNA damage was observed. Exposure to 50 and 5000 mg DEHP kg{sup -1} caused alterations in the proportion of germ cells at specific stages of spermatogenesis in the testis, including a reduction in the proportion of spermatozoa and an increase in the proportion of spermatocytes, suggesting that DEHP may inhibit the progression of meiosis. In parallel, exposure to 5000 mg DEHP kg{sup -1} increased the levels of two peroxisome proliferator-activated receptor (PPAR) responsive genes (acyl-coenzyme A oxidase 1 (acox1) and enoyl-coenzyme A, hydratase/3-hydroxyacyl coenzyme A dehydrogenase (ehhadh). These data demonstrated that exposure to high concentrations of DEHP disrupts spermatogenesis in adult zebrafish with a consequent decrease in their ability to fertilise oocytes spawned by untreated females. Furthermore, our data suggest that the adverse effects caused by

  17. Mechanisms of toxicity of di(2-ethylhexyl) phthalate on the reproductive health of male zebrafish

    Phthalates are ubiquitous in the aquatic environment and are known to adversely affect male reproductive health in mammals through interactions with multiple receptor systems. However, little is known about the risks they pose to fish. This project investigated the effects of di(2-ethylhexyl) phthalate (DEHP), the most commonly used phthalate, on the reproductive health of male zebrafish (Danio rerio). Males were treated with 0.5, 50 and 5000 mg DEHP kg-1 (body weight) for a period of 10 days via intraperitoneal injection. The effects of the exposure were assessed by analysing fertilisation success, testis histology, sperm DNA integrity and transcript profiles of the liver and testis. A significant increase in the hepatosomatic index and levels of hepatic vitellogenin transcript were observed following exposure to 5000 mg DEHP kg-1. Exposure to 5000 mg DEHP kg-1 also resulted in a reduction in fertilisation success of oocytes spawned by untreated females. However, survival and development of the resulting embryos were unaffected by all treatments, and no evidence of DEHP-induced sperm DNA damage was observed. Exposure to 50 and 5000 mg DEHP kg-1 caused alterations in the proportion of germ cells at specific stages of spermatogenesis in the testis, including a reduction in the proportion of spermatozoa and an increase in the proportion of spermatocytes, suggesting that DEHP may inhibit the progression of meiosis. In parallel, exposure to 5000 mg DEHP kg-1 increased the levels of two peroxisome proliferator-activated receptor (PPAR) responsive genes (acyl-coenzyme A oxidase 1 (acox1) and enoyl-coenzyme A, hydratase/3-hydroxyacyl coenzyme A dehydrogenase (ehhadh). These data demonstrated that exposure to high concentrations of DEHP disrupts spermatogenesis in adult zebrafish with a consequent decrease in their ability to fertilise oocytes spawned by untreated females. Furthermore, our data suggest that the adverse effects caused by exposure to DEHP are likely to occur

  18. Quercetin attenuates di-(2-ethylhexyl) phthalate-induced testicular toxicity in adult rats.

    Abd-Ellah, M F; Aly, Haa; Mokhlis, Ham; Abdel-Aziz, A H

    2016-03-01

    The aim of the present study was to investigate the potential oxidative damage of di-(2-ethylhexyl) phthalate (DEHP) in the rat testis and to further elucidate the potential modulatory effect of quercetin. DEHP was diluted in corn oil and given to rats by oral gavage at doses 0, 300, 600, and 900 mg/kg/day (groups I, III, IV, or V, respectively) for 15 consecutive days. Group VI was pretreated with quercetin (90 mg/kg), 24 h before starting the experiment and then treated with DEHP (900 mg/kg/day) for 15 consecutive days. Group II was treated with quercetin (90 mg/kg/day). The relative testes weight and sperm motility were significantly decreased by treatment with 900 mg/kg of DEHP. Both sperm count and daily sperm production were significantly decreased by DEHP treatment at doses of 600 and 900 mg/kg. Serum testosterone level and prostatic acid phosphatase (ACP) activity and testicular lactate dehydrogenase-X (LDH-X) activity were significantly decreased in animals treated with 900 mg/kg. Serum total ACP activity was significantly increased in animals treated with 600 and 900 mg/kg of DEHP. DEHP treatment induced oxidative stress and histopathological abnormality. These abnormalities were effectively normalized by pretreatment with quercetin except for LDH-X near normalcy. In conclusion, the findings of this study demonstrate that DEHP impairs testicular function at least, in part, by inducing oxidative stress and quercetin has a potent protective effect against DEHP-induced testicular toxicity in rats. PMID:25882133

  19. Experimental density measurements of bis(2-ethylhexyl) phthalate at elevated temperatures and pressures

    Highlights: • High-temperature, high-pressure experimental densities of bis(2-ethylhexyl) phthalate are reported. • Modified Tait equation is used to correlate reported experimental density data. • The PC-SAFT EoS is used to model experimental density result of bis(2-ethylhexyl) phthalate. • The Peng–Robinson and a volume translation of the Peng–Robinson EoS are used to model reported experimental results. -- Abstract: Experimental high-temperature, high-pressure (HTHP) density data for bis(2-ethylhexyl) phthalate (DEHP) are reported in this study. DEHP is a popular choice as a reference fluid for viscosity calibrations in the HTHP region. However, reliable HTHP density values are needed for accurate viscosity calculations for certain viscometers (e.g. rolling ball). HTHP densities are determined at T = (373, 424, 476, 492, and 524) K and P to 270 MPa using a variable-volume, high-pressure view cell. The experimental density data are satisfactorily correlated by the modified Tait equation with a mean absolute percent deviation (δ) of 0.15. The experimental data are modeled with the Peng–Robinson (PREoS), volume-translated PREoS (VT-PREoS), and perturbed chain statistical associating fluid theory (PC-SAFT EoS) models. The required parameters for the two PREoS and the PC-SAFT EoS models are determined using group contribution methods. The PC-SAFT EoS performs the best of the three models with a δ of 2.12. The PC-SAFT EoS is also fit to the experimental data to obtain a new set of pure component parameters that yield a δ of 0.20 for these HTHP conditions

  20. Exposure to di-2-ethylhexyl phthalate, di-n-butyl phthalate and bisphenol A through infant formulas.

    Cirillo, Teresa; Latini, Giuseppe; Castaldi, Maria Antonietta; Dipaola, Lucia; Fasano, Evelina; Esposito, Francesco; Scognamiglio, Gelsomina; Francesco, Fabio Di; Cobellis, Luigi

    2015-04-01

    Phthalates and bisphenol A (BPA) are ubiquitous contaminants identified as endocrine disruptors. Phthalates are worldwide used as plasticizers, in particular to improve the mechanical properties of polymers such as polyvinyl chloride. Because they are not chemically bound to the polymer, they tend to leach out with time and use. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP) are the two most common phthalates. BPA is an estrogenic compound used to manufacture polycarbonate containers for food and drink, including baby bottles. It can migrate from container into foods, especially at elevated temperatures. Diet is a predominant source of exposure for phthalates and BPA, especially for infants. The aim of this study was to test the presence of DEHP, DnBP, and BPA in infant formulas. DEHP, DnBP, and BPA concentrations were measured in 22 liquid and 28 powder milks by gas chromatography with flame ionization detection and high performance liquid chromatography with fluorimetric detection, respectively. DEHP concentrations in our samples were between 0.005 and 5.088 μg/g (median 0.906 μg/g), DnBP concentrations were between 0.008 and 1.297 μg/g (median 0.053 μg/g), and BPA concentrations were between 0.003 and 0.375 μg/g (median 0.015 μg/g). Concentrations of the investigated contaminants in liquid and powder milks were not significantly different, even though samples were packed in different types of containers. These data point out potential hazards for infants fed with baby formulas. Contamination seems more related to the production of formulas than to a release from containers. PMID:25730646

  1. Determination and Pharmacokinetics of Di-(2-ethylhexyl Phthalate in Rats by Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry

    Tung-Hu Tsai

    2013-09-01

    Full Text Available Di-(2-ethylhexyl phthalate (DEHP is used to increase the flexibility of plastics for industrial products. However, the illegal use of the plasticizer DEHP in food and drinks has been reported in Taiwan in 2011. In order to assess the exact extent of the absorption of DEHP via the oral route, the aim of this study is to develop a reliable and validated ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS method to evaluate the oral bioavailability of DEHP in rats. The optimal chromatographic separation of DEHP and butyl benzyl phthalate (BBP; used as internal standard were achieved on a C18 column. The mobile phase was consisted of 5 mM ammonium acetate-methanol (11:89, v/v with a flow rate of 0.25 mL/min. The monitoring ion transitions were m/z 391.4 → 149.0 for DEHP and m/z 313.3 → 149.0 for BBP. The mean matrix effects of DEHP at low, medium and high concentrations were 94.5 ± 5.7% and 100.1 ± 2.3% in plasma and feces homogenate samples, respectively. In conclusion, the validated UPLC-MS/MS method is suitable for analyzing the rat plasma sample of DEHP and the oral bioavailability of DEHP was about 7% in rats.

  2. Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

    Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and then measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes. - Highlights: ► MEHP increased reactive oxygen species, oxidative DNA damage, and caspase activity. ► MEHP induced expression of PTGS2, a gene

  3. Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro

    Tetz, Lauren M., E-mail: ltetz@umich.edu [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States); Cheng, Adrienne A.; Korte, Cassandra S. [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States); Giese, Roger W.; Wang, Poguang [Department of Pharmaceutical Sciences, Northeastern University, 360 Huntingon Ave, Boston, MA 02115 (United States); Harris, Craig; Meeker, John D.; Loch-Caruso, Rita [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029 (United States)

    2013-04-01

    Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells have not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and then measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes. - Highlights: ► MEHP increased reactive oxygen species, oxidative DNA damage, and caspase activity. ► MEHP induced expression of PTGS2, a gene

  4. Di-(2-ethylhexyl phthalate mediates glycolysis and the TCA cycle in clam Venerupis philippinarum

    C Li

    2014-06-01

    Full Text Available Di-(2-ethylhexyl phthalate (DEHP has many adverse effects on immunity and metabolic states. However, scarce information is available on its connection with toxicologically relevant proteomics response in marine invertebrates. In this study, GS-MS was employed to determine the bio-accumulated levels of DEHP in clam Venerupis philippinarum. After exposure to 0.4 mg L-1 and 4mg L-1 DEHP, the bio-accumulated DEHP in the clam foot was significantly increased in the first 24 h, and then sharply decreased from 0.203 ± 0.022 μg g-1 to 0.104 ± 0.011 μg g-1 , and from 1.689 ± 0.018 μg g-1 to 1.172 ± 0.012 μg g-1, respectively. Comparative proteomic was conducted to investigate the global protein expression changes towards this contaminant exposure. Twenty-eight proteins with significant differences in abundance were identified and characterized, among them six enzymes related to the glycolysis pathway were suppressed, and two members of TCA cycle were induced. The activity and mRNA expression level of malate dehydrogenase (MDH were further assessed using qPCR and an enzymatic assay. The MDH activity and mRNA transcript levels were both elevated compared to those in the ethanol control group. Our findings indicated that a DEHP-treated clam modulated host toxicological effect through depressing glycogen synthesis and activating TCA cycle.

  5. Resveratrol and curcumin ameliorate di-(2-ethylhexyl) phthalate induced testicular injury in rats.

    Abd El-Fattah, Amal Ahmed; Fahim, Atef Tadros; Sadik, Nermin Abdel Hamid; Ali, Bassam Mohamed

    2016-01-01

    The present study aimed to evaluate the protective role of resveratrol and curcumin on oxidative testicular damage induced by di-(2-ethylhexyl) phthalate (DEHP). Male Wistar rats were divided into six groups; three groups received oral daily doses of DEHP (2g/kgBW) for 45days to induce testicular injury. Two of these groups received either resveratrol (80mg/kgBW) or curcumin (200mg/kgBW) orally for 30days before and 45days after DEHP administration. A vehicle-treated control group was also included. Another two groups of rats received either resveratrol or curcumin alone. Oxidative damage was observed by decreased levels of total antioxidant capacity (TAC) and glutathione (GSH) and increased malondialdehyde (MDA) level in the testes of DEHP-administered rats. Serum testosterone level as well as testicular marker enzymes activities; acid and alkaline phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) showed severe declines. DEHP administration caused significant increases in the testicular gene expression levels of Nrf2, HO-1, HSP60, HSP70 and HSP90 as well as a significant decrease in c-Kit protein when compared with the control group. Histopathological observations provided evidence for the biochemical and molecular analysis. These DEHP-induced pathological alterations were attenuated by pretreatment with resveratrol and curcumin. We conclude that DEHP-induced injuries in biochemical, molecular and histological structure of testis were recovered by pretreatment with resveratrol and curcumin. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties along with boosting Nrf2, HSP 60, HSP 70 and HSP 90 gene expression levels and as such may be useful potential tools in combating DEHP-induced testicular dysfunction. PMID:26361869

  6. Docking study: PPARs interaction with the selected alternative plasticizers to di(2-ethylhexyl) phthalate.

    Kambia, Nicolas; Farce, Amaury; Belarbi, Karim; Gressier, Bernard; Luyckx, Michel; Chavatte, Philippe; Dine, Thierry

    2016-06-01

    Phthalates, used in medical devices (MDs), have been identified as reproductive and developmental toxicants. Their toxicity varies somewhat depending on the specific phthalate and is in part linked to the activation of Peroxisome Proliferating-Activated Receptors (PPARs). So, the use of MDs containing targeted phthalates such as di(2-ethylhexyl) phthalate (DEHP) has been challenged by European directive 2007/47/EC. Therefore, MDs manufacturers were forced to quickly find replacement plasticizers. However, very little toxicological and epidemiological studies are available on human health. So, we proceeded to dock these chemicals in order to identify compounds that are likely to interact with PPARs binding sites. The results obtained are generally very mixed on the harmlessness of these alternatives. Moreover, no data exist on the biological effects of their possible metabolites. As DEHP toxicity resulted mainly from its major metabolites, generalizing the use of these plasticizers without conducting extensive studies on the possible effects on human health of their metabolites seems inconceivable. PMID:25942360

  7. Biodegradation of di(2-ethylhexyl)phthalate in a typical tropical soil

    Castelo de Moura Carrara, Silvia Marta; Morita, Dione Mari [Polytechnic School, University of Sao Paulo (Brazil); Boscov, Maria Eugenia Gimenez, E-mail: meboscov@usp.br [Polytechnic School, University of Sao Paulo (Brazil)

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer Scarce literature on contamination of tropical soils by phthalates. Black-Right-Pointing-Pointer Investigation of mobility of DEHP in a tropical soil by infiltration tests showed that DEHP is retained in the upper layer of the soil. Black-Right-Pointing-Pointer Low air and water permeability indicate that in situ bioremediation is not feasible for this soil. Black-Right-Pointing-Pointer Respirometric tests were inadequate to investigate biodegradation because tropical soils are acidic. Black-Right-Pointing-Pointer Slurry-phase reactor with cement mixer provided significant biodegradation (99% in 49 days). - Abstract: The aim of this research was to evaluate the possibility of biodegradation of di(2-ethylhexyl)phthalate (DEHP), widely used as an industrial plasticizer and considered an endocrine-disrupting chemical included in the U.S. Environmental Protection Agency priority list, in a Brazilian tropical soil, which has not been previously reported in the literature, despite the geographic importance of tropical soils. Preliminary laboratory testing comprised respirometric, air and water permeability, and pilot scale infiltration tests. Standard respirometric tests were found inadequate for studying biodegradation in tropical contaminated soils, due to the effect of the addition of significant amounts of calcium carbonate, necessary to adjust soil pH. Pilot scale infiltration tests performed for 5 months indicated that DEHP was retained in the superficial layer of the soil, barely migrating downwards, whereas air and water permeability tests discarded in situ bioremediation. However, ex situ bioremediation was possible, using a slurry-phase reactor with acclimated microorganisms, in pilot scale tests conducted to remediate a total mass of 150 kg of contaminated soil with 100 mg DEHP/kg. The removal of DEHP in the slurry-phase reactor achieved the percentage of 99% in 49 days, with biodegradation following a first

  8. Biodegradation of di(2-ethylhexyl)phthalate in a typical tropical soil

    Highlights: ► Scarce literature on contamination of tropical soils by phthalates. ► Investigation of mobility of DEHP in a tropical soil by infiltration tests showed that DEHP is retained in the upper layer of the soil. ► Low air and water permeability indicate that in situ bioremediation is not feasible for this soil. ► Respirometric tests were inadequate to investigate biodegradation because tropical soils are acidic. ► Slurry-phase reactor with cement mixer provided significant biodegradation (99% in 49 days). - Abstract: The aim of this research was to evaluate the possibility of biodegradation of di(2-ethylhexyl)phthalate (DEHP), widely used as an industrial plasticizer and considered an endocrine-disrupting chemical included in the U.S. Environmental Protection Agency priority list, in a Brazilian tropical soil, which has not been previously reported in the literature, despite the geographic importance of tropical soils. Preliminary laboratory testing comprised respirometric, air and water permeability, and pilot scale infiltration tests. Standard respirometric tests were found inadequate for studying biodegradation in tropical contaminated soils, due to the effect of the addition of significant amounts of calcium carbonate, necessary to adjust soil pH. Pilot scale infiltration tests performed for 5 months indicated that DEHP was retained in the superficial layer of the soil, barely migrating downwards, whereas air and water permeability tests discarded in situ bioremediation. However, ex situ bioremediation was possible, using a slurry-phase reactor with acclimated microorganisms, in pilot scale tests conducted to remediate a total mass of 150 kg of contaminated soil with 100 mg DEHP/kg. The removal of DEHP in the slurry-phase reactor achieved the percentage of 99% in 49 days, with biodegradation following a first-order kinetic model with a biodegradation coefficient of 0.127 day−1.

  9. Di-(2-ethylhexyl) phthalate induces apoptosis of GC-2spd cells via TR4/Bcl-2 pathway.

    Zhu, Lishan; Lu, Jinchang; Tang, Xiao; Fu, Guoqing; Duan, Peng; Quan, Chao; Zhang, Ling; Zhang, Zhibing; Chang, Wei; Shi, Yuqin

    2016-06-01

    Di-(2-ethylhexyl) phthalate (DEHP) is a widely used environmental endocrine disruptor. Many studies have reported that DEHP exposure causes reproductive toxicity and cells apoptosis. However, the mechanism by which DEHP exposure causes male reproductive toxicity remains unknown. This study investigated the role of the testicular orphan nuclear receptor4 (TR4)/Bcl-2 pathway in apoptosis induced by DEHP, which resulted in reproductive damage. To elucidate the mechanism underpinning the male reproductive toxicity of DEHP, we sought to investigate apoptotic effects, expression levels of TR4/Bcl-2 pathway in GC-2spd cells, including TR4, Bcl-2 and caspase-3. GC-2spd cells were exposed to various concentrations of DEHP (0, 50, 100, or 200μM). The results indicated that, with the increase of the concentrations of DEHP, the survival rate of cell decreased gradually. DEHP exposure at over 100μM significantly induced apoptotic cell death. DEHP decreased SOD and GSH-Px activity in 200μM group. Compared to the control group, the mRNA levels of caspase-3 increased significantly, however, Bcl-2 mRNA decreased (PBcl-2 and procaspase-3 protein levels. Taken together, these results lead us to speculate that in vitro exposure to DEHP might induce apoptosis in GC-2spd cells through the TR4/Bcl-2 pathway. PMID:27084994

  10. Gas chromatographic-mass spectrometric analysis of di(2-ethylhexyl) phthalate and its metabolites in hepatic microsomal incubations

    A method is reported for the determination of di(2-ethylhexyl) phthalate (DEHP) and its metabolites in in vitro metabolism studies. Gas chromatography-mass spectrometry (GC-MS) analysis allows separation of 18 by-products of DEHP metabolism. On the basis of retention time and specific mass spectra m/z values, three classes of compounds can be identified: (i) alcohols as hydrolysis product; (ii) acids produced by alcohol oxidation; (iii) compounds retaining phthalic moiety. The chromatogram can also be acquired in SIM mode at m/z 149 resulting in 13 well-separated chromatographic peaks: from retention time and mass spectra it can be inferred that the main peaks correspond to mono(2-ethylhexyl) phthalate (MEHP) and (ω-1)-hydroxyl-MEHP. The kinetics of DEHP metabolism was studied using an S9 Aroclor-induced liver fraction as in vitro model and following incubation assay after 20, 40, 60 and 90 min. The composition of incubation mixtures can be quantitatively evaluated from selected ion monitoring chromatograms at m/z 149: the by-product concentration increases during the incubation time, as a consequence of DEHP degradation. During the incubation test a significant conversion of DEHP into MEHP is observed: a conversion yield of 10, 13, 16 and 20% of the original DEHP is obtained after 20, 40, 60 and 90 min, respectively. The metabolic conversion of DEHP to MEHP explains the endocrine-disrupting activity of the original DEHP; moreover, it has been demonstrated that MEHP and its (ω-1)-oxidation metabolite induce peroxisome proliferation. This result strengthens the suggestion that the study of DEHP metabolic pathway is fundamental to better understanding its toxicological behavior

  11. Mono-(2-ethylhexyl) phthalate induces injury in human umbilical vein endothelial cells.

    Ban, Jin-Bao; Fan, Xiao-Wu; Huang, Qi; Li, Bin-Feng; Chen, Chen; Zhang, Hua-Chuan; Xu, Shun-Qing

    2014-01-01

    Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a widespread environmental contaminant and has been proved to have potential adverse effects on the reproductive system, carcinogenicity, liver, kidney and developmental toxicities. However, the effect of MEHP on vascular system remains unclear. The main purpose of this study was to evaluate the cytotoxic effects of MEHP on human umbilical endothelial cells (HUVEC) and its possible molecular mechanism. HUVEC cells were treated with MEHP (0, 6.25, 12.5, 25,50 and 100 µM), and the cellular apoptosis and mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In present study, MEHP induced a dose-dependent cell injury in HUVEC cell via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3, -8 and -9, and increased ratio of Bax/bcl-2 mRNA and protein expression as well as cytochrome C releasing. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, could effectively block MEHP-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicated that MEHP induced apoptosis in HUVEC cells through a reactive oxygen species-mediated mitochondria-dependent pathway. PMID:24836450

  12. Mono-(2-Ethylhexyl) Phthalate Induces Injury in Human Umbilical Vein Endothelial Cells

    Huang, Qi; Li, Bin-Feng; Chen, Chen; Zhang, Hua-Chuan; Xu, Shun-Qing

    2014-01-01

    Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a widespread environmental contaminant and has been proved to have potential adverse effects on the reproductive system, carcinogenicity, liver, kidney and developmental toxicities. However, the effect of MEHP on vascular system remains unclear. The main purpose of this study was to evaluate the cytotoxic effects of MEHP on human umbilical endothelial cells (HUVEC) and its possible molecular mechanism. HUVEC cells were treated with MEHP (0, 6.25, 12.5, 25,50 and 100 µM), and the cellular apoptosis and mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In present study, MEHP induced a dose-dependent cell injury in HUVEC cell via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3, -8and -9, and increased ratio of Bax/bcl-2 mRNA and protein expression as well as cytochrome C releasing. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, could effectively block MEHP-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicated that MEHP induced apoptosis in HUVEC cells through a reactive oxygen species-mediated mitochondria-dependent pathway. PMID:24836450

  13. The acute effects of mono(2-ethylhexyl)phthalate (MEHP) on testes of prepubertal Wistar rats

    Dalgaard, M.; Nellemann, Christine Lydia; Lam, Henrik Rye; Sørensen, Ilona Kryspin; Ladefoged, Ole

    2001-01-01

    A single oral dose of 400 mg/kg body weight of mono(2-ethylhexyl)phthalate (MEHP), the testis toxic metabolite of di(2-ethylhexyl)phthalate. was given to 28-day-old male Wistar rats and the testis toxic effects were investigated 3, 6. and 12 h after exposure. Detachment and sloughing of germ cells...

  14. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  15. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  16. In utero exposure to di-(2-ethylhexyl) phthalate induces testicular effects in neonatal rats that are antagonized by genistein cotreatment.

    Jones, Steven; Boisvert, Annie; Francois, Sade; Zhang, Liandong; Culty, Martine

    2015-10-01

    Fetal exposure to endocrine disruptors (EDs) is believed to predispose males to reproductive abnormalities. Although males are exposed to combinations of chemicals, few studies have evaluated the effects of ED mixtures at environmentally relevant doses. Our previous work showed that fetal exposure to a mixture of the phytoestrogen genistein (GEN) and the plasticizer di-(2-ethylhexyl) phthalate (DEHP) induced unique alterations in adult testis. In this follow-up study, we examined Postnatal Day 3 (PND3) and PND6 male offspring exposed from Gestational Day 14 to parturition to corn oil, 10mg/kg GEN, DEHP, or their combination, to gain insight into the early molecular events driving long-term alterations. DEHP stimulated the mRNA and protein expression of the steroidogenic enzyme HSD3B, uniquely at PND3. DEHP also increased the mRNA expression of Nestin, a Leydig progenitor/Sertoli cell marker, and markers of Sertoli cell (Wt1), gonocyte (Plzf, Foxo1), and proliferation (Pcna) at PND3, while these genes were unchanged by the mixture. Redox (Nqo1, Sod2, Sod3, Trx, Gst, Cat) and xenobiotic transporter (Abcb1b, Abcg2) gene expression was also increased by DEHP at PND3, while attenuated when combined with GEN, suggesting the involvement of cellular stress in short-term DEHP effects and a protective effect of GEN. The direct effects of GEN and mono-(2-ethylhexyl) phthalate, the principal bioactive metabolite of DEHP, on testis were investigated in PND3 organ cultures, showing a stimulatory effect of 10 μM mono-(2-ethylhexyl) phthalate on basal testosterone production that was normalized by GEN. These effects contrasted with previous reports of androgen suppression and decreased gene expression in perinatal rat testis by high DEHP doses, implying that neonatal effects are not predictive of adult effects. We propose that GEN, through an antioxidant action, normalizes reactive oxygen species-induced neonatal effects of DEHP. The notion that these EDs do not follow classical

  17. Maximum permissible concentrations and negligible concentrations for phthalates (dibutylphthalate and di(2-ethylhexyl)phthlate), with emphasis on endocrine disruptive properties

    Wezel AP van der; Posthumus R; van Vlaardingen P; Crommentuijn T; Plassche EJ van de; CSR

    1999-01-01

    This report presents maximal permissible concentrations (MPCs) and negligible concentrations (NCs) are derived for di-n-butylphthalate (DBP) and di(2-ethylhexyl)phthalate (DEHP). Phthalates are often mentioned as suspected endocrine disrupters. Data with endpoints related to the endocrine or reproductive system for in vitro as well as in vivo tests were collected. Especially the two-generation reproduction studies were found sensitive in detecting endocrine disruptive effects. None of the tes...

  18. Thyroid endocrine disruption in zebrafish larvae after exposure to mono-(2-ethylhexyl phthalate (MEHP.

    Wenhui Zhai

    Full Text Available Phthalates are extensively used as plasticizers in a variety of daily-life products, resulting in widespread distribution in aquatic environments. However, limited information is available on the endocrine disrupting effects of phthalates in aquatic organisms. The aim of the present study was to examine whether exposure to mono-(2-ethylhexyl phthalate (MEHP, the hydrolytic metabolite of di-(2-ethylhexyl phthalate (DEHP disrupts thyroid endocrine system in fish. In this study, zebrafish (Danio rerio embryos were exposed to different concentrations of MEHP (1.6, 8, 40, and 200 μg/L from 2 h post-fertilization (hpf to 168 hpf. The whole-body content of thyroid hormone and transcription of genes involved in the hypothalamic-pituitary-thyroid (HPT axis were examined. Treatment with MEHP significantly decreased whole-body T4 contents and increased whole-body T3 contents, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (Dio2 and UGT1ab might be responsible for decreased T4 contents. Elevated gene transcription of Dio1 was also observed in this study, which might assist to degrade increased T3 contents. Exposure to MEHP also significantly induced transcription of genes involved in thyroid development (Nkx2.1 and Pax8 and thyroid hormone synthesis (TSHβ, NIS and TG. However, the genes encoding proteins involved in TH transport (transthyretin, TTR was transcriptionally significantly down-regulated after exposure to MEHP. Overall, these results demonstrate that acute exposure to MEHP alters whole-body contents of thyroid hormones in zebrafish embryos/larvae and changes the transcription of genes involved in the HPT axis, thus exerting thyroid endocrine toxicity.

  19. An experimental setup for isobaric heat capacities for viscous fluids at high pressure: Squalane, bis(2-ethylhexyl) sebacate and bis(2-ethylhexyl) phthalate

    Highlights: ► New setup to measure accurate heat capacities under pressure for viscous fluids. ► Highly accurate Cp up to 30 MPa for SQN, DEHS and DEHP are reported. ► A new fitting equation Cp(T, p) obtaining maximum deviations of 0.5% is presented. ► The highest Cp and the most pronounced decrease with pressure are shown for SQN. - Abstract: A high-pressure flow calorimeter has been used to determine highly accurate isobaric heat capacities for different viscous fluids, squalane (SQN), bis(2-ethylhexyl) sebacate (DEHS) and bis(2-ethylhexyl) phthalate (DEHP) from T = (293.15 to 353.15) K and up to 30 MPa. The experimental device was adapted for viscous liquids at high pressure and it can measure heat capacities with an estimated total uncertainty better than 1%. The isobaric heat capacity values were analysed together with their temperature and pressure dependences. In addition, a fitting equation of the experimental molar isobaric heat capacity for these viscous fluids as a function of temperature and pressure was proposed.

  20. DI-2-ETHYLHEXYL PHTHALATE AND DI-N-BUTYL PHTHALATE IN TISSUES OF COMMON CARP (Cyprinus Carpio L.) AFTER HARVEST AND AFTER STORAGE IN FISH STORAGE TANKS

    Vlasta Stancová; Lenka Puškárová; Alžbeta Jarošová

    2011-01-01

    The aim of the present study was to determine whether the influence of fish pond and fish storage tank conditions change the content of phthalic acid esters (di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP)) in the carcass of the Common carp. Samples obtained from the autumn harvest of two fish ponds (R1 and R2) in 2007 and 2010 from the South Moravia and after a seven-week-long storage in fish storage tanks were analyzed. It was found that in the samples (2007) from both fish ...

  1. Performance of electrochemical oxidation process for removal of di (2-ethylhexyl) phthalate.

    Espinoza, Josué Daniel García; Drogui, Patrick; Zolfaghari, Mehdi; Dirany, Ahmad; Ledesma, Maria Teresa Orta; Gortáres-Moroyoqui, Pablo; Buelna, Gerardo

    2016-06-01

    Di (2-ethylhexyl) phthalate (DEHP) is the most detected and concentrated plasticizer in environment and wastewaters, worldwide. In this study, different operating parameters such as current intensity, treatment time, type of anodes, and supporting electrolytes were tested to optimized the electro-oxidation process (EOP) for the removal of DEHP in the presence of methanol as a dissolved organic matter. Among the anodes, the Nb/BDD showed the best degradation rate of DEHP, at low current intensity of 0.2 A after 90 min of treatment time with a percentage of degradation recorded of 81 %, compared to 70 % obtained with the Ti/IrO2-RuO2. Furthermore, due to the combination of direct and indirect oxidation, the removal of DEHP in the presence of 1 g/L Na2SO4 was higher than NaBr, even though the oxidant production of NaBr was 11.7 mmol/L against 3.5 mmol/L recorded in the presence of sulfate at 0.5 A and after 60 min of electrolysis time. Under optimal condition (current intensity = 0.5 A, time = 120 min, using Nb/BDD anode and Na2SO4 as supporting electrolyte), the removal of 87.2 % of DEHP was achieved. The total cost of 0.106 US$/m(3) of treated water was achieved based on economical optimization of reactor with current intensity of 0.2 A and 1 g/L Na2SO4. PMID:26971515

  2. Metabolism of the persistent plasticizer chemical bis(2-ethylhexyl) phthalate in cell suspension cultures of wheat (Triticum aestivum L.). Discrepancy from the intact plant

    Cell suspension cultures of wheat (Triticum aestivum L.) metabolized the persistent plasticizer chemical bis(2-ethylhexyl) phthalate (DEHP; 1 ppm) predominantly to β-D-glucosyl conjugates. After incubation for 48 h at 270C, 23% of the applied radioactively labeled chemical was recovered in the total polar metabolite fraction. Prior heat treatment of freeze-thawing of the wheat cells abolished conjugate formation and led to mono(2-ethylhexyl) phthalate (MEHP)) as the predominant metabolite (up to 10% conversion). Direct feeding of MEHP to native wheat cells led to 93% conversion to polar metabolites, again consisting largely of β-D-glucosyl conjugates. This suggested that MEHP was a metabolic intermediate and that DEHP esterase activity was rate limiting in DEHP metabolism. The rate of cellular DEHP metabolism in fact agreed with the rate of the DEHP esterase reaction determined in crude cell-free extracts. Therefore, no significant permeation barrier between the intracellular enzyme and external DEHP appeared to exist in cell suspension cultures. In contrast, the DEHP esterase activity of intact leaves has previously been found to be inaccessible to external DEHP

  3. Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

    Martinez–Arguelles, D.B. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); McIntosh, M.; Rohlicek, C.V. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Pediatrics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Culty, M. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Zirkin, B.R. [Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Papadopoulos, V., E-mail: vassilios.papadopoulos@mcgill.ca [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States)

    2013-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

  4. ATSDR evaluation of health effects of chemicals. VI. Di(2-ethylhexyl)phthalate. Agency for Toxic Substances and Disease Registry.

    Fay, M; Donohue, J M; De Rosa, C

    1999-12-01

    Di(2-ethylhexyl)phthalate (also known as DEHP, bis(2-ethylhexyl)phthalate, or BEHP; CAS Registry Number 117-81-7) is a widely-used plasticizer. It is found in numerous plastic articles, such as paints, inks, floor tiles, upholstery, shower curtains, footwear, plastic bags, food-packaging materials, toys, and medical tubing. Not surprisingly, DEHP appears at many waste sites. As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals that are of greatest public health concern at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priority List (NPL) sites. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of the bulk of ATSDR's profile for DEHP (ATSDR, 1993) into the mainstream scientific literature. An extensive listing of human and animal health effects, organized by route, duration, and endpoint, is presented. Toxicological information on toxicokinetics, biomarkers, interactions, sensitive subpopulations, reducing toxicity after exposure, and relevance to public health is also included. Environmental information encompasses physical properties, production and use, environmental fate, levels seen in the environment, analytical methods, and a listing of regulations. ATSDR, at the behest of Congress and therefore the citizenry, prepares these profiles to inform the public about site contaminants. PMID:10786378

  5. Complete degradation of the endocrine disruptor di-(2-ethylhexyl) phthalate by a novel Agromyces sp. MT-O strain and its application to bioremediation of contaminated soil.

    Zhao, Hai-Ming; Du, Huan; Lin, Jing; Chen, Xue-Bin; Li, Yan-Wen; Li, Hui; Cai, Quan-Ying; Mo, Ce-Hui; Qin, Hua-Ming; Wong, Ming-Hung

    2016-08-15

    A newly isolated strain Agromyces sp. MT-O could utilize various phthalates and efficiently degraded di-(2-ethylhexyl) phthalate (DEHP). Response surface methodology was successfully employed for the optimization of culture conditions including pH (7.2), temperature (29.6), and inoculum size (OD600 of 0.2), resulting in almost complete degradation of DEHP (200mgL(-1)) within 7days. At different initial concentrations (50-1000mgL(-1)), DEHP degradation curves were fitted well with the first-order kinetic model, and the half-life of DEHP degradation ranged from 0.83 to 2.92days. Meanwhile, the substrate inhibition model was used to describe the special degradation rate with qmax, Ks, and Ki of 0.6298day(-1), 86.78mgL(-1), and 714.3mgL(-1), respectively. The GC-MS analysis indicated that DEHP was degraded into mono-ethylhexyl phthalate and phthalate acid before its complete mineralization. Bioaugmentation of DEHP-contaminated soils with strain MT-O has greatly enhanced DEHP disappearance rate in soils, providing great potential for efficiently remediating DEHP-contaminated environment. PMID:27099998

  6. Lactational Exposure to Di (2-ethylhexyl) Phthalate Impairs the Ovarian and Uterine Function of Adult Offspring Rat.

    Somasundaram, Dinesh Babu; Selvanesan, Benson Chellakkan; Ramachandran, Ilangovan; Bhaskaran, Ravi Sankar

    2016-04-01

    Phthalates, a class of chemicals used as plasticizers, are economically important due to several industrial applications. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate plasticizer, and it has been described as a potent antiandrogen in males. In this study, lactating dams were exposed via oral gavage to corn oil (vehicle) and DEHP (1, 10, and 100 mg/kg body weight) from postnatal day 1 to 21, and the effects were evaluated in the ovary and uterus of F1 progeny. DEHP exposure significantly decreased the body weight and organ weight in a dose-dependent manner. Serum levels of estradiol, testosterone, and progesterone were decreased but anogenital distance was unaffected. The mRNA expressions of luteinizing hormone receptor, follicle-stimulating hormone receptor, androgen receptor, estrogen receptor (ERα and ERβ), progesterone receptor, peroxisome proliferator-activated receptor γ, 3β hydroxysteroid dehydrogenase, aromatase, and steroidogenic acute regulatory protein were altered in the ovary of F1 progeny rats. Our finding suggest that lactational exposure to DEHP has transgenerational effect on female reproductive system. PMID:26482208

  7. Synergistic effect using vermiculite as media with a bacterial biofilm of Arthrobacter sp. for biodegradation of di-(2-ethylhexyl) phthalate.

    Wen, Zhi-Dan; Wu, Wei-Min; Ren, Nan-Qi; Gao, Da-Wen

    2016-03-01

    Vermiculite is one of matrix material used for constructed wetland (CW) for the treatment of municipal wastewater. Arthrobacter sp. strain C21 (CGMCC No. 7671), isolated from a constructed wetland receiving municipal wastewater, forms biofilm on the surface of vermiculite. Di-(2-ethylhexyl) phthalate (DEHP), a typical phthalate pollutant in environment, can be degraded by the biofilm of strain C21 formed on vermiculite. Results of laboratory studies indicated that DEHP was removed from aqueous phase via biodegradation, adsorption by vermiculite, and adsorption by biofilm biomass. Synergistic effect of these three reactions enhanced the overall DEHP removal efficiency. During a batch incubation test with vermiculite and the cell suspension, bacterial adhesion to the media surface occurred within 5h and the phthalate esters (PEs) removal was due to both biodegradation and vermiculite adsorption. As the biofilm developed on surface of vermiculite (5-36 h), biodegradation became the predominance for PEs removal. As mature biofilm was formed (36-54 h), the adsorption of PEs by biofilm biomass became a main driving force for the removal of PEs from aqueous phase. The content of extracellular polymers (EPS) of the biofilm and DEHP removal performance showed a significant positive correlation (rp>0.86). PMID:26547620

  8. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

    Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Verhoef, Aart; Gremmer, Eric R. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Loveren, Henk van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Piersma, Aldert H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences, Veterinary Faculty, Utrecht University, Utrecht (Netherlands)

    2012-04-01

    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 at 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

  9. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

    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 at 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

  10. Di-(2 ethylhexyl phthalate and flutamide alter gene expression in the testis of immature male rats

    Yu Frank H

    2009-09-01

    Full Text Available Abstract We previously demonstrated that the androgenic and anti-androgenic effects of endocrine disruptors (EDs alter reproductive function and exert distinct effects on developing male reproductive organs. To further investigate these effects, we used an immature rat model to examine the effects of di-(2 ethylhexyl phthalate (DEHP and flutamide (Flu on the male reproductive system. Immature male SD rats were treated daily with DEHP and Flu on postnatal days (PNDs 21 to 35, in a dose-dependent manner. As results, the weights of the testes, prostate, and seminal vesicle and anogenital distances (AGD decreased significantly in response to high doses of DEHP or Flu. Testosterone (T levels significantly decreased in all DEHP- treated groups, whereas luteinizing hormone (LH plasma levels were not altered by any of the two treatments at PND 36. However, treatment with DEHP or Flu induced histopathological changes in the testes, wherein degeneration and disorders of Leydig cells, germ cells and dilatation of tubular lumen were observed in a dose-dependent manner. Conversely, hyperplasia and denseness of Leydig, Sertoli and germ cells were observed in rats given with high doses of Flu. The results by cDNA microarray analysis indicated that 1,272 genes were up-regulated by more than two-fold, and 1,969 genes were down-regulated in response to DEHP, Flu or both EDs. These genes were selected based on their markedly increased or decreased expression levels. These genes have been also classified on the basis of gene ontology (e.g., steroid hormone biosynthetic process, regulation of transcription, signal transduction, metabolic process, biosynthetic process.... Significant decreases in gene expression were observed in steroidogenic genes (i.e., Star, Cyp11a1 and Hsd3b. In addition, the expression of a common set of target genes, including CaBP1, Vav2, Plcd1, Lhx1 and Isoc1, was altered following exposure to EDs, suggesting that they may be marker genes to

  11. Experimental density measurements of bis(2-ethylhexyl) phthalate at elevated temperatures and pressures

    Bamgbade, Babatunde A; Wu, Yue; Baled, Hseen O; Enick, Robert M; Burgess, Ward A

    2013-08-01

    Experimental high-temperature, high-pressure (HTHP) density data for bis(2-ethylhexyl) phthalate (DEHP) are reported in this study. DEHP is a popular choice as a reference fluid for viscosity calibrations in the HTHP region. However, reliable HTHP density values are needed for accurate viscosity calculations for certain viscometers (e.g. rolling ball). HTHP densities are determined at T = (373, 424, 476, 492, and 524) K and P to 270 MPa using a variable-volume, high-pressure view cell. The experimental density data are satisfactorily correlated by the modified Tait equation with a mean absolute percent deviation (δ) of 0.15. The experimental data are modeled with the Peng–Robinson (PREoS), volume-translated PREoS (VT-PREoS), and perturbed chain statistical associating fluid theory (PC-SAFT EoS) models. The required parameters for the two PREoS and the PC-SAFT EoS models are determined using group contribution methods. The PC-SAFT EoS performs the best of the three models with a δ of 2.12. The PC-SAFT EoS is also fit to the experimental data to obtain a new set of pure component parameters that yield a δ of 0.20 for these HTHP conditions.

  12. Mycelial fungi completely remediate di(2-ethylhexyl)phthalate, the hazardous plasticizer in PVC blood storage bag

    Highlights: ► Three novel phthalate utilizing fungi: A. parasiticus, F. subglutinans and P. funiculosum. ► Fungi utilize DEHP in PVC plastics in situ, in simple mineral salt medium. ► Employing these fungi, a batch process can remediate phthalates in plastics. ► Phthalate-free PVC can be recycled afresh. ► Mineral salt and phthalate remediated into fungal biomass. - Abstract: This pioneering work describes how simply, inexpensively and efficiently novel fungi utilize the alarming plasticizer, di(2-ethylhexyl)phthalate (DEHP) blended in PVC blood storage bags (BB). In order to quantify total DEHP (33.5%, w/w) present in BB, it was extracted using n-hexane and confirmed by GC–MS. Three mycelial fungi, viz., Aspergillus parasiticus, Fusarium subglutinans and Penicillium funiculosum isolated in our laboratory form heavily plastics-contaminated soil – either singly or in consortium – completely consumed intact DEHP physically bound to BB by static submerged growth (28 °C) in simple basal salt medium (BSM). A two-stage cultivation strategy was adopted for the complete removal of DEHP from BB in situ. During the first growth stage, almost 70% DEHP contained in the BB was consumed in 2 weeks, accompanied by increased fungal biomass (∼0.15–0.35 g/g BB; OD ∼7 at 600 nm) and a sharp declining (3.3) of initial pH (7.2). Spent BSM was replaced at this stagnant growth state (low pH), thus in the second stage, remaining DEHP bound to BB utilized completely (over 99%). Furthermore, A. parasiticus and F. subglutinans also grew well on scrapes of PVC water pipes in BSM. F. subglutinans was as efficient independently as consortium in completely utilizing the DEHP bound to BB, and these fungi offer great potentials for the inexpensive and eco-friendly bioremediation of phthalates in medical and allied PVC wastes on a large scale through a batch process in alleviating the plactics waste management issue.

  13. Mycelial fungi completely remediate di(2-ethylhexyl)phthalate, the hazardous plasticizer in PVC blood storage bag

    Pradeep, S. [Enzyme Technology Laboratory, Biotechnology Division, Department of Botany, University of Calicut, Kerala 673 635 (India); Benjamin, Sailas, E-mail: sailasben@yahoo.co.in [Enzyme Technology Laboratory, Biotechnology Division, Department of Botany, University of Calicut, Kerala 673 635 (India)

    2012-10-15

    Highlights: Black-Right-Pointing-Pointer Three novel phthalate utilizing fungi: A. parasiticus, F. subglutinans and P. funiculosum. Black-Right-Pointing-Pointer Fungi utilize DEHP in PVC plastics in situ, in simple mineral salt medium. Black-Right-Pointing-Pointer Employing these fungi, a batch process can remediate phthalates in plastics. Black-Right-Pointing-Pointer Phthalate-free PVC can be recycled afresh. Black-Right-Pointing-Pointer Mineral salt and phthalate remediated into fungal biomass. - Abstract: This pioneering work describes how simply, inexpensively and efficiently novel fungi utilize the alarming plasticizer, di(2-ethylhexyl)phthalate (DEHP) blended in PVC blood storage bags (BB). In order to quantify total DEHP (33.5%, w/w) present in BB, it was extracted using n-hexane and confirmed by GC-MS. Three mycelial fungi, viz., Aspergillus parasiticus, Fusarium subglutinans and Penicillium funiculosum isolated in our laboratory form heavily plastics-contaminated soil - either singly or in consortium - completely consumed intact DEHP physically bound to BB by static submerged growth (28 Degree-Sign C) in simple basal salt medium (BSM). A two-stage cultivation strategy was adopted for the complete removal of DEHP from BB in situ. During the first growth stage, almost 70% DEHP contained in the BB was consumed in 2 weeks, accompanied by increased fungal biomass ({approx}0.15-0.35 g/g BB; OD {approx}7 at 600 nm) and a sharp declining (3.3) of initial pH (7.2). Spent BSM was replaced at this stagnant growth state (low pH), thus in the second stage, remaining DEHP bound to BB utilized completely (over 99%). Furthermore, A. parasiticus and F. subglutinans also grew well on scrapes of PVC water pipes in BSM. F. subglutinans was as efficient independently as consortium in completely utilizing the DEHP bound to BB, and these fungi offer great potentials for the inexpensive and eco-friendly bioremediation of phthalates in medical and allied PVC wastes on a large

  14. Cytotoxic effects of mono-(2-ethylhexyl) phthalate on human embryonic stem cells

    SHI Cheng; CHEN Xi; CAI Xiao-hui; YU Wei-dong; LIANG Rong; LU Qun; SHEN Huan

    2013-01-01

    Background Mono-(2-ethylhexyl) phthalate (MEHP),the metabolite of di-(2-ethylhexyl) phthalate (DEHP),was suspected to be toxic to human embryos.This study contributes to investigating its toxic effects by an embryonic stem cell test (EST) based on two human embryonic stem cell (hESCs) lines.Methods CH1 established in our own lab and H1,a federally registered cell line were two human embryonic stem cell lines used in this test.Four endpoint measurements were performed consisting of cell viability,proliferation ability,apoptosis as well as changes of gene expression patterns after spontaneous differentiation were determined.For measuring effects on the first three endpoints,the cells were treated with various concentrations of MEHP dissolved in dimethyl sulfoxide (DMSO) and only with DMSO which served as control and harvested after 5 days.For measuring effects during spontaneous differentiation,the RNA of embryoid bodies (EBs) formed after 8 days' MEHP exposure was collected and changes in differentiation specific gene expression patterns were analyzed by quantitative real time RT-PCR.Results As a result the viability and proliferation ability of both cell lines decreased significantly at 1000 μmol/L MEHP,while there was no effect on apoptosis or cell morphology.In addition MEHP also changed the gene expression pattern in the EBs of both cell lines.Conclusion MEHP in a high dose was cytotoxic and affected the development of hESCs,which indicates its embryo toxicity in human embryos.

  15. Mono-(2-Ethylhexyl) Phthalate Induces Oxidative Stress and Inhibits Growth of Mouse Ovarian Antral Follicles1

    Wang, Wei; Craig, Zelieann R.; Basavarajappa, Mallikarjuna S.; Hafner, Katlyn S.; Flaws, Jodi A.

    2012-01-01

    Mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of the most commonly used plasticizer, di-(2-ethylhexyl) phthalate, and is considered to be a reproductive toxicant. However, little is known about the effects of MEHP on ovarian antral follicles. Thus, the present study tested the hypothesis that MEHP inhibits follicle growth via oxidative stress pathways. The data indicate that MEHP increases reactive oxygen species (ROS) levels and inhibits follicle growth in antral follicles, w...

  16. Effects of di-n-butyl phthalate and di (2-ethylhexyl) phthalate on the growth, photosynthesis, and chlorophyll fluorescence of wheat seedlings.

    Gao, Minling; Qi, Yun; Song, Wenhua; Xu, Haoran

    2016-05-01

    Phthalates are commonly used man-made chemicals that can be released into soil, water, and the atmosphere. The potential toxicity of phthalates on wheat seedlings has not been well studied. To better understand the deleterious effects of di-n-butyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) on wheat seedlings, their influences on the following were investigated: plant growth, net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), intercellular CO2 concentration (Ci), chlorophyll content, initial fluorescence (F0), maximal photochemical efficiency (Fv/Fm), photochemical quenching (qP), non-photochemical quenching (qN), effective quantum yield of photosystem II (ΦPSII), and photosynthetic electron transport rate (ETR). Compared with the control, the growth indices (plant height, fresh and dry weights of shoots, fresh and dry weights of roots), Pn, Gs, Tr, Ci, chlorophyll content, Fv/Fm, qP, ΦPSII, and ETR decreased in the 5 μg mL(-1) and 10 μg mL(-1) DBP and DEHP treatments, whereas F0 and qN increased. When wheat seedlings were treated with 20 μg mL(-1) of DBP and DEHP, the growth indices, Pn, Gs, Tr, chlorophyll content, Fv/Fm, qP, qN, ΦPSII, and ETR decreased significantly, whereas Ci and F0 increased. A decrease in the Pn of wheat seedlings was mainly caused by stomatal limitation in the 5 μg mL(-1) and 10 μg mL(-1) DBP and DEHP treatments. However, stomatal and non-stomatal limitations may have caused the reduction in Pn in the 20 μg mL(-1) DBP and DEHP treatments. Notably, the noxious effect of DBP on the wheat seedlings was significantly greater than that of DEHP. PMID:26928333

  17. Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring.

    Lee, Kuan-I; Chiang, Chin-Wei; Lin, Hui-Ching; Zhao, Jin-Feng; Li, Cheng-Ta; Shyue, Song-Kun; Lee, Tzong-Shyuan

    2016-05-01

    Long-term exposure to di-(2-ethylhexyl) phthalate (DEHP) is highly associated with carcinogenicity, fetotoxicity, psychological disorders and metabolic diseases, but the detrimental effects and mechanisms are not fully understood. We investigated the effect of exposing mouse mothers to DEHP, and the underlying mechanism, on blood pressure, obesity and cholesterol metabolism as well as psychological and learning behaviors in offspring. Tail-cuff plethysmography was used for blood pressure measurement; Western blot used was for phosphorylation and expression of protein; hematoxylin and eosin staining, Nissl staining and Golgi staining were used for histological examination. The serum levels of cholesterol, triglycerides and glucose were measured by blood biochemical analysis. Hepatic cholesterol and triglyceride levels were assessed by colorimetric assay kits. Offspring behaviors were evaluated by open-field activity, elevated plus maze, social preference test and Morris water maze. Maternal DEHP exposure deregulated the phosphorylation of endothelial nitric oxide synthase and upregulated angiotensin type 1 receptor in offspring, which led to increased blood pressure. It led to obesity in offspring by increasing the size of adipocytes in white adipose tissue and number of adipocytes in brown adipose tissue. It increased the serum level of cholesterol in offspring by decreasing the hepatic capacity for cholesterol clearance. The impaired social interaction ability induced by maternal DEHP exposure might be due to abnormal neuronal development. Collectively, our findings provide new evidence that maternal exposure to DEHP has a lasting effect on the physiological functions of the vascular system, adipose tissue and nerve system in offspring. PMID:25995009

  18. Estimating Emissions and Environmental Fate of Di-(2-ethylhexyl) Phthalate in Yangtze River Delta, China: Application of Inverse Modeling.

    Zhan, Yu; Sun, Jianteng; Luo, Yuzhou; Pan, Lili; Deng, Xunfei; Wei, Zi; Zhu, Lizhong

    2016-03-01

    A georeferenced multimedia model was developed for evaluating the emissions and environmental fate of di-2-ethylhexyl phthalate (DEHP) in the Yangtze River Delta (YRD), China. Due to the lack of emission inventories, the emission rates were estimated using the observed concentrations in soil as inputs for the multimedia model solved analytically in an inverse manner. The estimated emission rates were then used to evaluate the environmental fate of DEHP with the regular multimedia modeling approach. The predicted concentrations in air, surface water, and sediment were all consistent with the ranges and spatial variations of observed data. The total emission rate of DEHP in YRD was 13.9 thousand t/year (95% confidence interval: 9.4-23.6), of which urban and rural sources accounted for 47% and 53%, respectively. Soil in rural areas and sediment stored 79% and 13% of the total mass, respectively. The air received 61% of the total emissions of DEHP but was only associated with 0.2% of the total mass due to fast degradation and intensive deposition. We suggest the use of an inverse modeling approach under a tiered risk assessment framework to assist future development and refinement of DEHP emission inventories. PMID:26861906

  19. Pubertal exposure to di-(2-ethylhexyl)-phthalate inhibits G9a-mediated histone methylation during spermatogenesis in mice.

    Liu, Chuan; Qian, Peng; Yang, Lingling; Zhang, Lei; Chen, Chunhai; He, Mindi; Lu, Yonghui; Feng, Wei; Li, Min; Zhang, Yanwen; Zhong, Min; Yu, Zhengping; Zhou, Zhou

    2016-04-01

    The increasing incidence of male reproductive impairments has been associated with di-(2-ethylhexyl)-phthalate (DEHP) exposure. However, mechanisms involved are lacking. We exposed 4-week-old male C57BL/6j mice to DEHP by gavage at 0, 125, 250 or 500 mg/kg body weight/day for 28 consecutive days. Our data showed that pubertal exposure to DEHP induces sperm count reduction as well as histological abnormalities in seminiferous epithelium and apoptosis of post-meiotic germ cells, and these effects are concomitant with reduction of testosterone levels and its steroidogenic gene expression. Moreover, the expressions of estrogen receptor ERβ and nuclear receptors Nr0b1, Nr0b2 are increased. The expression of Nr5a2 which is the inducer of steroidogenesis is significantly reduced. Furthermore, spermatogonial stem cell (SSC) self-renewal, differentiation and meiosis were significantly impaired, and the epigenetic regulator G9a-mediated histone methylation was decreased following DEHP exposure. Our results suggest that the DEHP-induced male reproductive impairments may depend on its estrogenic action on estrogen receptor and nuclear receptor, and involve inhibition of steroidogenesis, SSC self-renewal and meiosis, which may be attributed to the down-regulation of G9a-mediated histone methylation. PMID:25975992

  20. Mono-(2-ethylhexyl) phthalate (MEHP) regulates glucocorticoid metabolism through 11β-hydroxysteroid dehydrogenase 2 in murine gonadotrope cells

    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 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), not 11β-HSD1, is strongly expressed in murine gonadotrope LβT2 cells. Interestingly, MEHP inhibited Hsd11b2 mRNA level and 11β-HSD2 enzyme activity in LβT2 cells at as low as 10-7 M. Corticosterone (CORT) at a concentration of 10-6 M significantly inhibited LβT2 cell proliferation after 2-day culture, and 10-6 M RU486, an antagonist of glucocorticoid receptor (GR), reversed this inhibition. However, in the presence of 10-5 or 10-4 M MEHP, the minimal concentration of CORT to inhibit the proliferation of LβT2 cells was lowered to 10-7 M, and 10-6 M RU486 was not able to completely reverse the CORT effect. In conclusion, along with the regulation of GR, 11β-HSD2 may have a key role in glucocorticoid metabolism in LβT2 cells. MEHP may participate in the glucocorticoid metabolism in LβT2 cells through inhibition of 11β-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.

  1. Desensitization of ovalbumin-sensitized mice by repeated co-administrations of di-(2-ethylhexyl phthalate and ovalbumin

    Nielsen Gunnar D

    2009-11-01

    Full Text Available Abstract Background The plasticizer di-(2-ethylhexyl phthalate (DEHP has been shown to stimulate a non-allergy related immune response with increased levels of IgG1 and IgG2a, but not IgE, after co-administration with the model allergen ovalbumin (OVA in mice. In mice, decreased IgG1 and increased IgG2a have been associated with the development of mucosal tolerance towards inhaled allergens. As DEHP selectively promote formations of IgG1 and IgG2a without stimulating the IgE response, it was hypothesized that DEHP may suppress an established IgE mediated allergic response. Mice pre-sensitised to OVA were repeatedly co-exposed to DEHP and OVA and the effects were evaluated on the levels of OVA-specific antibodies, ex vivo cytokine levels and the degree of lung inflammation after challenge with an OVA aerosol. Findings Compared to the OVA-sensitised control mice, multiple co-exposures to DEHP+OVA reduced the IgG1 level and reduced the IgE/IgG2a ratio. This suggests that DEHP may attenuate allergic sensitisation, as the IgE/IgG2a ratio has been shown to correlate with the degree of anaphylaxis. Nevertheless, no effect of DEHP exposures was seen on inflammatory cells in bronchoalveolar lavage fluid and on cytokine levels in spleen cell culture. Conclusion Data from humane and murine studies suggest that DEHP may attenuate the allergic response. More studies are necessary in order to assess the size of this effect and to rule out the underlying mechanism.

  2. The effects of di(2-ethylhexyl) phthalate and/or selenium on trace element levels in different organs of rats.

    Erkekoglu, Pinar; Arnaud, Josiane; Rachidi, Walid; Kocer-Gumusel, Belma; Favier, Alain; Hincal, Filiz

    2015-01-01

    Di(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer for synthetic polymers, is known to have endocrine disruptive potential, reproductive toxicity, and induces hepatic carcinogenesis in rodents. Selenium (Se) is a component of several selenoenzymes which are essential for cellular antioxidant defense and for the functions of mammalian reproductive system. The present study was designed to investigate the effects of DEHP exposure on trace element distribution in liver, testis, and kidney tissues and plasma of Se-deficient and Se-supplemented rats. Se deficiency was produced by feeding 3-week old Sprague-Dawley rats with ≤0.05mg Se/kg diet for 5 weeks, and supplementation group were on 1mg Se/kg diet. DEHP treated groups received 1000mg/kg dose by gavage during the last 10 days of feeding period. Se, zinc (Zn), copper (Cu), iron (Fe) and manganese (Mn) levels were measured by inductively coupled plasma mass spectrometry (ICP-MS). Se supplementation caused significant increases in hepatic, renal, and testicular Se levels. With DEHP exposure, plasma Se and Zn, kidney Se, Cu and Mn levels were significantly decreased. Besides, liver Fe decreased markedly in all the DEHP-treated groups. Liver and kidney Mn levels decreased significantly in DEHP/SeD group compared to both DEHP and SeD groups. These results showed the potential of DEHP exposure and/or different Se status to modify the distribution pattern of essential trace elements in various tissues, the importance of which needs to be further evaluated. PMID:25193691

  3. Mono-(2-Ethylhexyl) Phthalate (MEHP) Promotes Invasion and Migration of Human Testicular Embryonal Carcinoma Cells1

    Yao, Pei-Li; Lin, Yi-Chen; Richburg, John H.

    2012-01-01

    Testicular dysgenesis syndrome refers to a collection of diseases in men, including testicular cancer, that arise as a result of abnormal testicular development. Phthalates are a class of chemicals used widely in the production of plastic products and other consumer goods. Unfortunately, phthalate exposure has been linked to reproductive dysfunction and has been shown to adversely affect normal germ cell development. In this study, we show that mono-(2-ethylhexyl) phthalate (MEHP) induces mat...

  4. Prevention of di (2-ethylhexyl Phthalate-induced Testicular Disturbance in Mice by Co-administration of L-carnitine

    Majid Malekzadeh Shafaroudi

    2011-01-01

    Full Text Available Background: di (2-ethylhexyl phthalate (DEHP is widely used in the plastic industry and caninduce reproductive toxicity. On the other hand, L-carnitine (LC plays a crucial role in spermmetabolism and maturation. This study evaluates the effect of LC on body and testis weight,testis tissue, count, motility, viability, morphology, and chromatin quality of epididymal sperm,testicular spermatid number (TSN per gram testis and daily sperm production (DSP in LCtreatedmice.Materials and Methods: In this experimental study, adult male NMRI mice (mean age: 4weeks were given doses of DEHP and LC by gavaging for 2 weeks. All samples were assessedaccording to World Health Organization (WHO criteria. Sperm morphology was assessed usingPapanicolaou staining and sperm chromatin quality by aniline-blue staining.The left testes were fixed in Bouinś solution for histological examination and the end slices werestained with hematoxylin and eosin (H&E. The right testes were homogenized, and then TSNand DSP were calculated with an improved Neubauer haemocytometer and respective frames.Paired t-test, ANOVA, and Kruskal-Wallis tests were utilized for data analysis.Results: Co-administration of DEHP and LC not only prevented significant gains in testicularweight, but also maintained the sperm’s normal morphology and chromatin quality (p<0.05. Inaddition, LC recovered histological changes, TSN, DSP, and sperm count.Conclusion: These results demonstrated that oral administration of LC partially or generallyprotects spermatogenesis from DEHP-toxicity in mice.

  5. Reduced Hippocampal Dendritic Spine Density and BDNF Expression following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Male Long Evans Rats

    Smith, Catherine A.; Holahan, Matthew R.

    2014-01-01

    Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats. PMID:25295592

  6. The adverse effects of low-dose exposure to Di(2-ethylhexyl) phthalate during adolescence on sperm function in adult rats.

    Hsu, Ping-Chi; Kuo, Ya-Ting; Leon Guo, Yueliang; Chen, Jenq-Renn; Tsai, Shinn-Shyong; Chao, How-Ran; Teng, Yen-Ni; Pan, Min-Hsiung

    2016-06-01

    Di(2-ethylhexyl) phthalate (DEHP) is the most crucial phthalate derivative added to polyvinyl chloride as a plasticizer. This study examined the effects of low-dose exposure to DEHP during adolescence on sperm function in adult rats. The male rats were daily gavaged with 30, 100, 300, and 1000 µg kg(-1) of DEHP or corn oil from postnatal day (PND) 42 until PND 105. The selection of DEHP doses ranged from the mean daily intake by the normal-population exposure levels to no-observed-adverse-effect level of DEHP for the endpoints evaluated until adulthood. Significant increases in the percentage of sperm with tail abnormality, tendency for sperm DNA fragmentation index (DFI) and percentage of sperm with DFI were found in those exposed to 100, 300, and 1000 µg kg(-1) (P control group (P < 0.05). The excessive production of sperm H2 O2 coincided with an increase in sperm DFI. In this study, the lowest-observed-adverse-effect level for sperm toxicity was considered to be 100 µg DEHP/kg/day in sperm morphology and chromatin DNA damage. Further research is necessary to clarify the mechanisms of DEHP-related sperm ROS generation on sperm DNA damage. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 706-712, 2016. PMID:25410017

  7. Vitamin C and resveratrol supplementation to rat dams treated with di(2-ethylhexyl)phthalate: impact on reproductive and oxidative stress end points in male offspring.

    Botelho, Giuliana G K; Bufalo, Aedra C; Boareto, Ana Claudia; Muller, Juliane C; Morais, Rosana N; Martino-Andrade, Anderson J; Lemos, Karen R; Dalsenter, Paulo R

    2009-11-01

    This study was carried out to assess the influence of di(2-ethylhexyl)phthalate (DEHP) alone or associated with antioxidants on the male reproductive system in newborn rats, emphasizing the implications of oxidative stress and hormonal balance during prenatal and early postnatal periods. Wistar females were exposed by oral route to DEHP alone or associated with antioxidants from gestational day 7 to lactational day 2 according to the following treatment regimens: (C) vehicle control (canola oil + 1% Tween-80); (V) vitamin C (200 mg/kg) + canola oil; (R) resveratrol (10 mg/kg) + canola oil; (D) DEHP (500 mg/kg) + 1% Tween-80; (DV) DEHP (500 mg/kg) + vitamin C (200 mg/kg); and (DR) DEHP (500 mg/kg) + resveratrol (10 mg/kg). Two male pups per litter were randomly selected and necropsied on postnatal day 2. The brain and liver were removed and weighed and anogenital distance (AGD) was measured. Additionally, the testes were removed for assessment of intratesticular testosterone levels and histopathology; the liver was used to measure biomarkers of oxidative stress. Vitamin C and resveratrol alone did not affect the reproductive end points and did not induce oxidative stress. Exposure of dams to DEHP alone and associated with antioxidants resulted in hepatomegaly in offspring and significantly increased the incidence of multinucleated gonocytes in seminiferous cords. Testosterone and AGD presented a trend to decrease in DEHP-exposed groups. Catalase activity increased only in groups exposed to DEHP associated with antioxidants, although GST (gluthatione-S-transferase) activity decreased in all DEHP-exposed groups. The levels of hydroperoxides increased only in group exposed to DEHP associated with vitamin C. These results indicate that the association of DEHP with antioxidants was unable to ameliorate DEHP-induced reproductive changes, and the coadministration of DEHP and these antioxidants might even contribute to an overall increase in oxidative stress. PMID:19756843

  8. Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein.

    Zhang, Lian-Dong; Deng, Qian; Wang, Zi-Ming; Gao, Ming; Wang, Lei; Chong, Tie; Li, He-Cheng

    2013-01-01

    Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat offspring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday), GEN(50mg/kg bwday) or GEN(400mg/kg bwday) alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday) together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday). When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday) together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA expression appeared significantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP-GEN mixture on

  9. Reproductive effects of di(2-ethylhexyl)phthalate in immature male rats and its relation to cholesterol, testosterone, and thyroxin levels.

    Botelho, Giuliana G K; Golin, Munisa; Bufalo, Aedra C; Morais, Rosana N; Dalsenter, Paulo R; Martino-Andrade, Anderson J

    2009-11-01

    Phthalates are chemicals employed in several industrial products and there is a growing body of evidence demonstrating that they induce numerous adverse effects on the reproductive system. This study was carried out to assess possible alterations induced by the plasticizer di(2-ethylhexyl phthalate (DEHP) on cholesterol, testosterone, and thyroxine (total T4) levels, as well as to discuss the significance of these data in global changes observed in the reproductive tract of pubertal animals. Wistar rats aged 21 days received DEHP orally at 0, 250, 500, and 750 mg/kg/day for 30 days and were examined for different reproductive endpoints. At the end of the treatment, significant decreases in relative weight of testosterone-dependent organs, delayed preputial separation, and low serum testosterone were observed at the highest DEHP dose. The plot of the relationship between DEHP dose and serum cholesterol revealed a biphasic effect. The concentration of cholesterol in serum was significantly reduced at 250 mg/kg/day DEHP but returned to control values at 750 mg/kg/day. Cholesterol levels measured in testicular tissue increased with DEHP treatment. Serum T4 levels were not affected by DEHP at any dose, indicating the absence of a link between total thyroxin concentration and phthalate effects on cholesterol levels. Taken together these results indicate that effects observed in serum and testicular cholesterol levels may reflect distinct effects of DEHP on cholesterol synthesis and usage. These results confirm and extend previously reported findings showing that alterations in cholesterol balance may play a role in the suppression of steroidogenesis induced by DEHP in rats. PMID:19330368

  10. Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation, and mitochondrial dysfunction in the testis

    Li, Xiaolin; Fang, Evandro Fei; Scheibye-Knudsen, Morten; Cui, Honghua; Qiu, Lu; Li, Jian; He, Yuping; Huang, Jing; Bohr, Vilhelm A.; Ng, Tzi Bun; Guo, Hongwei

    2014-01-01

    Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitously used endocrine disruptor.There is widespread exposure to DEHP in the general population which has raised substantial public concern due to its potential detrimental health effects. It is particularly pertinent to investigate the molecular mechanisms of its testicular toxicity which are largely unknown. By feeding male rats DEHP for 2 weeks, rat spermatogenesis became disrupted, resulting in a decreased number of spermatocytes and spermatids. Since rapidly dividing tissues appeared to be particularly vulnerable to DEHP toxicity we investigated the effect of DEHP on DNA replication. Intriguingly, DEHP appeared to inhibit DNA replication as evidenced by results of fiber tract analysis. This led to induction of the mitochondrial apoptotic pathways and increased ROS production. Furthermore, the toxicity of DEHP led to respiratory chain defects and attenuation of ATP level probably brought about by hyperPARylation and undermined SIRT1 activity. Our findings reveal a previously unknown mitochondrial dysfunction in DEHP-induced testicular toxicity and highlight the importance of SIRT1 in male reproduction. PMID:25242624

  11. Di-(2-ethylhexyl phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood.

    Arianna Smerieri

    Full Text Available Phthalates might be implicated with obesity and insulin sensitivity. We evaluated the levels of primary and secondary metabolites of Di-(2-ethylhexyl phthalate (DEHP in urine in obese and normal-weight subjects both before and during puberty, and investigated their relationships with auxological parameters and indexes of insulin sensitivity.DEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP, were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis using the Auto-CM analysis were able to offer an insight into the complex biological connections between the studied variables.The data showed changes in DEHP metabolites in urine related with obesity, puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity.It remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects.

  12. Adsorption and Fenton regeneration of SBA-15 for di-(2-ethylhexyl) phthalate leached from PVC sheets by Gram-positive strains LHM1 and LHM2

    Hwang, S.; Latorre, I.; Caban, M.; Soto, B.; Montalvo-Rodríguez, R.; Hernández-Maldonado, A.

    2012-12-01

    Bioleaching of Di-(2-ethylhexyl) phthalate (DEHP) from PVC sheets was studied with newly isolated, Gram-positive strains LHM1 and LHM2 capable of growing on DEHP as the sole carbon source. According to 16S rRNA gene analysis, strains LHM1 and LHM2 were closely related (more than 97% similarity) to Chryseomicrobium imtechense MW 10(T) and Lysinibacillus fusiformis NBRC 15717(T), respectively. The biodeteriorated PVC sheets by the strains LHM1 and LHM2 had thicker biofilm development. Despite their metabolic capability of degrading DEHP as the sole carbon source, the strains LHM1 and LHM2 did not metabolize all DEHP leached out of the PVC sheets. Thermogravimetric analysis (TGA) showed that the biodeterioration by strains LHM1 and LHM2 resulted in less amount of and weakly bonded DEHP present in PVC sheets, in comparison to the virgin PVC sheet. Therefore, PVC biodeterioration by strains LHM1 and LHM2 might play an important role in stability of PVC sheets and fate and effect of leached DEHP on the environmental receptors. In response to this, an advanced adsorption with SBA-15 was assessed as a potential alternative DEHP remediation with arsenic as a co-contaminant. SBA-15 had an excellent arsenic adsorption showing >90% arsenic removal when arsenic was present as a singular contaminant. Adsorption effectiveness was irrelevant to the solid/liquid (S/L) ratio. However, when arsenic was present together with DEHP, arsenic adsorption to bare SBA-15 was reduced by 10 - 40%, with lesser S/L ratio having greater arsenic removal. On the contrary, bare SBA-15 only adsorbed ~30% of DEHP on average. When DEHP was present as a co-solute with arsenic, DEHP adsorption to bare SBA-15 was increased. For SBA-15 regeneration, adsorbed arsenic was recovered with EDTA elution, whereas adsorbed DEHP was destructed with Fenton oxidation.

  13. Transplacental transfer of monomethyl phthalate and mono(2-ethylhexyl) phthalate in a human placenta perfusion system

    Mose, Tina; Knudsen, Lisbeth E; Hedegaard, Morten;

    2007-01-01

    The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental perfusion model with simultaneous perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before...... followed analyzing samples from fetal and maternal perfusion media by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS). Four perfusions with mMP indicated a slow transplacental transfer, with a feto-maternal ratio (FM ratio) of 0.30 +/- 0.03 after 150 min of perfusion. Four perfusions...... with mEHP indicated a very slow or nonexisting placental transfer. mEHP was only detected in fetal perfusion media from two perfusions, giving rise to FM ratios of 0.088 and 0.20 after 150 min of perfusion. Detectable levels of mMP, mEHP, monoethylphthalate (mEP), and monobutylphthalate were found in...

  14. Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood: the Hokkaido study on environment and children's health.

    Araki, Atsuko; Mitsui, Takahiko; Miyashita, Chihiro; Nakajima, Tamie; Naito, Hisao; Ito, Sachiko; Sasaki, Seiko; Cho, Kazutoshi; Ikeno, Tamiko; Nonomura, Katsuya; Kishi, Reiko

    2014-01-01

    Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23-35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), was measured. Concentrations of infant reproductive hormones including estradiol (E2), total testosterone (T), and progesterone (P4), inhibin B, insulin-like factor 3 (INSL3), steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates' exposure in humans, as well as

  15. Association between maternal exposure to di(2-ethylhexyl phthalate and reproductive hormone levels in fetal blood: the Hokkaido study on environment and children's health.

    Atsuko Araki

    Full Text Available Prenatal di(2-ethylhexyl phthalate (DEHP exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23-35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl phthalate (MEHP, was measured. Concentrations of infant reproductive hormones including estradiol (E2, total testosterone (T, and progesterone (P4, inhibin B, insulin-like factor 3 (INSL3, steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates' exposure in humans, as

  16. Association between Maternal Exposure to di(2-ethylhexyl) Phthalate and Reproductive Hormone Levels in Fetal Blood: The Hokkaido Study on Environment and Children's Health

    Araki, Atsuko; Mitsui, Takahiko; Miyashita, Chihiro; Nakajima, Tamie; Naito, Hisao; Ito, Sachiko; Sasaki, Seiko; Cho, Kazutoshi; Ikeno, Tamiko; Nonomura, Katsuya; Kishi, Reiko

    2014-01-01

    Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23–35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), was measured. Concentrations of infant reproductive hormones including estradiol (E2), total testosterone (T), and progesterone (P4), inhibin B, insulin-like factor 3 (INSL3), steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates' exposure in humans, as well as

  17. Acute Exposure to Di(2-Ethylhexyl) Phthalate in Adulthood Causes Adverse Reproductive Outcomes Later in Life and Accelerates Reproductive Aging in Female Mice.

    Hannon, Patrick R; Niermann, Sarah; Flaws, Jodi A

    2016-03-01

    Humans are ubiquitously exposed to di(2-ethylhexyl) phthalate (DEHP), which is an environmental toxicant incorporated in consumer products. Studies have shown that DEHP targets the ovary to disrupt essential processes required for reproductive and nonreproductive health. Specifically, 10-day exposure to DEHP accelerates primordial follicle recruitment and disrupts estrous cyclicity in adult mice. However, it is unknown if these effects on folliculogenesis and cyclicity following acute DEHP exposure can have permanent effects on reproductive outcomes. Further, the premature depletion of primordial follicles can cause early reproductive senescence, and it is unknown if acute DEHP exposure accelerates reproductive aging. This study tested the hypothesis that acute DEHP exposure causes infertility, disrupts estrous cyclicity, alters hormone levels, and depletes follicle numbers by inducing atresia later in life, leading to accelerated reproductive aging. Adult CD-1 mice were orally dosed with vehicle or DEHP (20 μg/kg/day-500 mg/kg/day) daily for 10 days, and reproductive outcomes were assessed at 6 and 9 months postdosing. Acute DEHP exposure significantly altered estrous cyclicity compared to controls at 6 and 9 months postdosing by increasing the percentage of days the mice were in estrus and metestrus/diestrus, respectively. DEHP also significantly decreased inhibin B levels compared to controls at 9 months postdosing. Further, DEHP significantly increased the BAX/BCL2 ratio in primordial follicles leading to a significant decrease in primordial and total follicle numbers compared to controls at 9 months postdosing. Collectively, the adverse effects present following acute DEHP exposure persist later in life and are consistent with accelerated reproductive aging. PMID:26678702

  18. Di-(2-ethylhexyl) phthalate and autism spectrum disorders

    Giuseppe Latini; Anna Maria Papini; Paolo Rovero; Mario Chelli; Claudio De Felice; Joussef Hayek; Francesca Nuti; Chiara Testa

    2012-01-01

    ASDs (autism spectrum disorders) are a complex group of neurodevelopment disorders, still poorly understood, steadily rising in frequency and treatment refractory. Extensive research has been so far unable to explain the aetiology of this condition, whereas a growing body of evidence suggests the involvement of environmental factors. Phthalates, given their extensive use and their persistence, are ubiquitous environmental contaminants. They are EDs (endocrine disruptors) suspected to interfer...

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

    G. Rock; 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 ...

  20. Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions.

    Hanioka, Nobumitsu; Isobe, Takashi; Kinashi, Yu; Tanaka-Kagawa, Toshiko; Jinno, Hideto

    2016-07-01

    Mono(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di(2-ethylhexyl) phthalate (DEHP) and has endocrine-disrupting effects. MEHP is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the hepatic and intestinal glucuronidation of MEHP in humans, dogs, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of MEHP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and dogs, and the biphasic model for rats and mice. The K m and V max values of human liver microsomes were 110 µM and 5.8 nmol/min/mg protein, respectively. The kinetics of intestinal microsomes followed the biphasic model for humans, dogs, and mice, and the Michaelis-Menten model for rats. The K m and V max values of human intestinal microsomes were 5.6 µM and 0.40 nmol/min/mg protein, respectively, for the high-affinity phase, and 430 µM and 0.70 nmol/min/mg protein, respectively, for the low-affinity phase. The relative levels of V max estimated by Eadie-Hofstee plots were dogs (2.0) > mice (1.4) > rats (1.0) ≈ humans (1.0) for liver microsomes, and mice (8.5) > dogs (4.1) > rats (3.1) > humans (1.0) for intestinal microsomes. The percentages of the V max values of intestinal microsomes to liver microsomes were mice (120 %) > rats (57 %) > dogs (39 %) > humans (19 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among species, and imply that these species differences are strongly associated with the toxicity of DEHP. PMID:26514348

  1. Mono-(2-ethylhexyl)-phthalate (MEHP) affects ERK-dependent GDNF signalling in mouse stem-progenitor spermatogonia

    Highlights: ► MEHP affects SSC proliferation in a dose- and time-dependent manner. ► MEHP does not increase apoptosis, necrosis or the production of ROS in SSCs. ► MEHP reduces the activity of the GDNF/ERK1/2/FOS signalling pathway in SSCs. ► MEHP does not affect the GDNF/SRC/MYCN signalling pathway in SSCs. -- Abstract: Many commercial and household products such as lubricants, cosmetics, plastics, and paint contain phthalates, in particular bis-(2-ethyhexyl)-phthalate (DEHP). As a consequence, phthalates have been found in a number of locations and foods (streambeds, household dust, bottled water and dairy products). Epidemiological and animal studies analysing phthalate exposure in males provide evidence of degradation in sperm quality, associated to an increase in the incidence of genital birth defects and testicular cancers. In the testis, spermatogenesis is maintained throughout life by a small number of spermatogonial stem cells (SSCs) that self-renew or differentiate to produce adequate numbers of spermatozoa. Disruption or alteration of SSC self-renewal induce decreased sperm count and sperm quality, or may potentially lead to testicular cancer. GDNF, or glial cell-line-derived neurotrophic factor, is a growth factor that is essential for the self-renewal of SSCs and continuous spermatogenesis. In the present study, the SSC-derived cell line C18-4 was used as a model for preliminary assessment of the effects of mono-(2-ethylhexyl)-phthalate (MEHP, main metabolite of DEHP) on spermatogonial stem cells. Our data demonstrate that MEHP disrupts one of the known GDNF signalling pathways in these cells. MEHP induced a decrease of C18-4 cell viability in a time- and dose-dependent manner, as well as a disruption of ERK1/2 activation but not of SRC signalling. As a result, we observed a decrease of expression of the transcription factor FOS, which is downstream of the GDNF/ERK1/2 axis in these cells. Taken together, our data suggest that MEHP exposure

  2. An Estimation of the Daily Intake of Di (2-ethlhexyl) Phthalate (DEHP) among Workers in Flavoring Factories

    LU Jie; ZHANG Jing; WANG Zhu Tian; FAN Yong Xiang

    2014-01-01

    Objective To estimate the daily intake of DEHP among workers in flavoring factories. Methods 71 workers in two flavoring manufacturers, 27 administrators in those factories and 31 laboratory technicians in a research institute were recruited and assigned to exposure group, control group 1 and control group 2 respectively. Their urinary DEHP metabolites, mono(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), were detected by isotope dilution-ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). The urinary metabolites concentrations were converted into DEHP intake levels using two pharmacokinetic models: the urine creatinine-excretion (UCE) one and the urine volume (UV) one. Results No significant differences were found among the three groups. Based on the urinary concentrations ofΣ3MEHP, we got a median daily DEHP intake of 3.22 or 1.85μg/kg body-weight/day applying the UV or UCE models respectively. Depending on the UV model, three subjects (2.34%) exceeded the RfD value given by US EPA and the P50 of estimate daily DEHP intakes accounted for 16.10%of the RfD value. No subjects exceeded the limitation depending on the UCE model. Conclusion The workers in flavoring factories were not supposed to be the high DEHP exposure ones and their exposure level remained at a low risk.

  3. Mono(2-ethylhexyl)phthalate accumulation disturbs energy metabolism of fat cells.

    Chiang, Huai-Chih; Kuo, Ya-Ting; Shen, Chih-Che; Lin, Yi-Hua; Wang, Shu-Li; Tsou, Tsui-Chun

    2016-03-01

    Phthalates are lipophilic and tend to accumulate in adipose tissue, an important regulator of energy balance and glucose homeostasis. The study aimed to determine whether cellular phthalate accumulation influenced fat cell energy metabolism. Following a 3-day treatment with adipogenesis-inducing medium and a 2-day treatment with adipogenesis-maintaining medium, 3T3-L1 cells differentiated into adipocytes in the presence of a phthalate at a clinically relevant concentration (30-300 μM) for another 6 days. Two phthalates, di(2-ethylhexyl)phthalate and di-n-butylphthalate, and their metabolites, mono(2-ethylhexyl)phthalate (MEHP) and mono-n-butylphthalate, were used here. The phthalate treatments caused no marked effect on cytotoxicity and adipogenesis. Only the MEHP-treated adipocytes were found having smaller lipid droplets; MEHP accumulated in cells in a dose- and time-dependent manner. The MEHP-treated adipocytes exhibited significant increases in lipolysis and glucose uptake; quantitative real-time polymerase chain reaction (qPCR) analysis revealed correlated changes in expression of marker genes involved in adipogenesis, lipid metabolism, and glucose uptake. Analysis of oxygen consumption rate (a mitochondrial respiration indicator) and extracellular acidification rate (a glycolysis indicator) indicated a higher energy metabolism in the adipocytes. qPCR analysis of critical genes involved in mitochondrial biogenesis and/or energy metabolism showed that expression of peroxisome proliferator-activated receptor γ coactivator-1α, sirtuin 3, and protein kinase A were significantly enhanced in the MEHP-treated adipocytes. In vitro evidence of MEHP impacts on lipolysis, glucose uptake/glycolysis, and mitochondrial respiration/biogenesis demonstrates that MEHP accumulation disturbs energy metabolism of fat cells. PMID:25543134

  4. Effects of exposure of pre-pubertal boars to di(2-ethylhexyl) phthalate on their frozen-thawed sperm viability post-puberty.

    Spjuth, L; Saravia, F; Johannisson, A; Lundeheim, N; Rodríguez-Martínez, H

    2006-10-01

    Late effects of pre-pubertal oral exposure to di(2-ethylhexyl) phthalate (DEHP), a plastic softener used in, for example, polyvinyl chloride-products, on semen quality in young boars have not been clear-cut. The aim of this study was to determine whether stress imposed on spermatozoa would reveal such effects. Semen was collected from post-pubertal boars (8-9 months of age), which had been exposed to 300 mg kg(-1) body weight of DEHP per os three times a week from 3 to 7 weeks of age and from control siblings given placebo (water). The semen was cryopreserved and examined for plasma membrane integrity post-thaw using the short hypo-osmotic swelling test and flow cytometry (propidium iodide /SYBR-14). Sperm motility was assessed by computer-assisted sperm analysis. No significant difference in plasma membrane integrity could be found between the groups. The DEHP-exposed group had a significantly lower percentage of linearly motile spermatozoa at 30 min (P boars pre-pubertally exposed to low doses of DEHP, showed kinematic deviations post-thaw that could be related to DEHP exposure. PMID:16961572

  5. Di-(2-ethylhexyl) phthalate inhibits testosterone level through disturbed hypothalamic-pituitary-testis axis and ERK-mediated 5α-Reductase 2.

    Ha, Mei; Guan, Xie; Wei, Li; Li, Peng; Yang, Min; Liu, Changjiang

    2016-09-01

    Di-(2-ethylhexyl) phthalate (DEHP) has reproductive toxicity and can affect male reproductive development. In order to clarify adverse effects of DEHP on testicular physiology and testosterone production, Sprague-Dawley (SD) rats were dosed daily with DEHP by gavage for 30days; TM3 cells (mouse Leydig cell line) were treated with DEHP for 24h after pretreatment with vitamin C or U0126. Results indicated that the hypothalamic-pituitary-testis (HPT) axis was disturbed and serum testosterone, LH and FSH levels were decreased following DEHP exposure. Histomorphological changes of rat testes were also observed, such as deformed seminiferous tubules, aggregated chromatin, multiple vacuoles, swollen mitochondria, apoptotic germ cells and Sertoli cells, as well as increased Leydig cell numbers. Moreover, DEHP caused oxidative stress in vivo and in vitro and then induced the ERK pathway, which was required to mediate 5α-Reductase 2 and scavenger receptor class B-1 (SRB1) levels. However, levels of steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), P450 17α-hydroxylase/17.20 lyase (P450c17), and P450 side-chain cleavage enzyme (P450scc) were not significantly altered after DEHP exposure. Taken together, DEHP-disturbed HPT axis and induced 5α-Reductase 2 contribute to the reduction of serum testosterone level. The activated ERK pathway is required to modulate expressions of 5α-Reductase 2 and SRB1. PMID:27155079

  6. Gene expression analysis of the rat testis after treatment with di(2-ethylhexyl) phthalate using cDNA microarray and real-time RT-PCR

    To investigate the effects of di(2-ethylhexyl) phthalate (DEHP) on gene expression in rat testis, 6-week-old male Sprague-Dawley rats were given a single oral dose of 20 or 2000 mg/kg and euthanized 3, 6, 24, or 72 h thereafter. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells were significantly increased in the testis at 24 and 72 h after the exposure to 2000 mg/kg of DEHP. On cDNA microarray analysis, in addition to apoptosis-related genes, genes associated with atrophy, APEX nuclease, MutS homologue (E. coli), testosterone-repressed-prostatic-message-2 (TRPM-2), connective tissue growth factor, collagen alpha 2 type V, and cell adhesion kinase were differentially expressed. To investigate the relationship between histopathological alteration and gene expression, we selected genes associated with apoptosis and analyzed their expression by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). With 20 mg/kg of DEHP treatment, bcl-2, key gene related to apoptosis, was increased. Up-regulation of bcl-2, inhibitor of Apaf-1/caspase-9/caspase-2 cascade of apoptosis, may be related to the fact that no morphological apoptotic change was induced after dosing of 20 mg/kg DEHP. With 2000 mg/kg of DEHP treatment, the apoptotic activator cascade, Fas/FasL, FADD/caspase-8/caspase-3 cascade, and Apaf-1/caspase-9/caspase-2 cascade were increased and bcl-2 was decreased. Thus, these gene regulations might lead the cells into apoptosis in the case of high exposure to DEHP. In contrast, FADD/caspase-10/caspase-6 cascade and caspase-11/caspase-3 cascade were not increased. These results indicate that the cascades of FADD/caspase-10/caspase-6 and caspase-11/caspase-3 are not related to apoptosis with DEHP treatment

  7. Hepatic peroxisome proliferator-activated receptor α may have an important role in the toxic effects of di(2-ethylhexyl)phthalate on offspring of mice

    Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) is associated with adverse effects on offspring, and the metabolites are agonists of peroxisome proliferator-activated receptor (PPAR) α, which exhibits species differences in expression and function. This study aimed to clarify the mechanism of DEHP-induced adverse effects on offspring in relation to maternal mouse and human PPARα. Male and female Sv/129 wild-type (mPPARα), Pparα-null and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% (medium) or 0.1% (high) DEHP. After 4 weeks, males and females were mated. Dams were killed on gestational day 18 and postnatal day (PND) 2. High-dose DEHP decreased the number of total and live fetuses, and increased resorptions in mPPARα mice. In hPPARα mice, resorptions were increased above the medium dose, and the number of births was decreased at the high dose. The number of live pups on PND2 was decreased over the medium dose in mPPARα and at the high dose in hPPARα mice. No such findings were observed in Pparα-null mice. High-dose DEHP decreased plasma triglyceride in pregnant mPPARα mice, but not in Pparα-null and hPPARα ones. Above the medium dose in mPPARα mice significantly reduced hepatic microsomal triglyceride transfer protein (MTP) expression. Medium- and/or high-dose DEHP increased the levels of maternal PPARα target genes in mPPARα and hPPARα mice. Taken together, PPARα expression is required for the toxicity of DEHP in fetuses and pups and altered plasma triglyceride levels, through regulation of MTP may be important in mPPARα mice and not in hPPARα mice.

  8. Assessment of Carcinogenicity of di(2-ethylhexyl) phthalate in a short-term assay using Xpa(-/-) and Xpa(-/-)/p53(+/-) mice

    Mortensen, Alicja; Bertram, Margareta; Aarup, V.;

    2002-01-01

    The potential of Xpa(-/-) and Xpa(-/-)/p53(+/-) mice for short-term carcinogenicity assays was evaluated with di(2-ethylhexyl)phthalate (DEHP). Groups of 15 male and female Xpa(-/-) mice, received diets containing 0, 1,500, 3, 000, or 6,000 ppm DEHP, and wild-type (WT) and Xpa(-/-)/p53(+/-) mice 0...... or 6,000 ppm DEHP for 39 weeks. Xpa(-/-), Xpa(-/-)/p53(+/-), and WT males, fed 2,500 ppm p-cresidine, served as a positive control. In all models, the survival was not altered by DEHP. Increased incidences of nonneoplastic lesions were recorded in testes and kidneys with no apparent difference...... in the liver, urinary bladder, and nasal cavity in all models, and in kidneys in transgenic models. The only tumors with statistically significantly increased incidence were liver adenomas in transgenic models (XPA:1 vs 7; `XPA/p53': 0 vs 12; WT: 0 vs 5, p = 0.053) and urinary bladder carcinomas in...

  9. Long-term effects of maternal exposure to Di (2-ethylhexyl Phthalate on sperm and testicular parameters in Wistar rats offspring

    Ahmad Ali Moazedi

    2012-01-01

    Full Text Available Background: Phthalate esters have been shown to cause reproductive toxicity in both developing and adult animals. Objective: This study was designed to assess long-term effects of maternal exposure to Di (2-ethylhexyl Phthalate (DEHP on reproductive ability of both neonatal and adult male offspring.Materials and Methods: 60 female rats randomly divided in four equal groups; vehicle control and three treatment groups that received 10, 100 and 500 mg/kg/day DEHP via gavage during gestation and lactation. At different ages after birth, the volumes of testes were measured by Cavellieri method, testes weights recorded and epididymal sperm samples were assessed for number and gross morphology of spermatozoa. Following tissue processing, seminiferous tubules diameter and germinal epithelium height evaluated with morphometric techniques.Results: Mean testis weight decreased significantly (p<0.05 in 500 mg/kg/day dose group from 28 to 150 days after birth. Significant decreases were seen in total volumes of testis in 100 (p<0.05 and 500 (p<0.01 mg/kg/day doses groups until 150 days after birth. Seminiferous tubules diameter and germinal epithelium height decreased significantly in 100 (p<0.05 and 500 (p<0.01 mg/kg/day doses groups during postnatal development. Also, mean sperm density in 100 mg/kg/day (p<0.05 and 500 mg/kg/day (p<0.01 doses groups and percent of morphologically normal sperm in highest dose group (p<0.05 decreased significantly until 150 days after birth. Conclusion: Present study showed that maternal exposure to Di (2-ethylhexyl Phthalate during gestation and lactation caused to permanent and dose-related reductions of sperm and testicular parameters in rats offspring

  10. Mono-(2-Ethylhexyl) Phthalate Promotes Pro-Labor Gene Expression in the Human Placenta

    Parobchak, Nataliya; Rosen, Alex; Vetrano, Anna M.; Srinivasan, Aarthi; Wang, Bingbing; Rosen, Todd

    2016-01-01

    Women exposed to phthalates during pregnancy are at increased risk for delivering preterm, but the mechanism behind this relationship is unknown. Placental corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2) are key mediators of parturition and are regulated by the non-canonical NF-kB (RelB/p52) signaling pathway. In this study, we demonstrate that one of the major phthalate metabolites, mono-(2-ethylhexyl)-phthalate (MEHP), increased CRH and COX-2 mRNA and protein abundance in a dose-dependent manner in primary cultures of cytotrophoblast. This was coupled with an increase in nuclear import of RelB/p52 and its association with the CRH and COX-2 promoters. Silencing of NF-kB inducing kinase, a central signaling component of the non-canonical NF-kB pathway, blocked MEHP-induced upregulation of CRH and COX-2. These results suggest a potential mechanism mediated by RelB/p52 by which phthalates could prematurely induce pro-labor gene activity and lead to preterm birth. PMID:26751383

  11. Mono-(2-Ethylhexyl Phthalate Promotes Pro-Labor Gene Expression in the Human Placenta.

    Ximi K Wang

    Full Text Available Women exposed to phthalates during pregnancy are at increased risk for delivering preterm, but the mechanism behind this relationship is unknown. Placental corticotropin-releasing hormone (CRH and cyclooxygenase-2 (COX-2 are key mediators of parturition and are regulated by the non-canonical NF-kB (RelB/p52 signaling pathway. In this study, we demonstrate that one of the major phthalate metabolites, mono-(2-ethylhexyl-phthalate (MEHP, increased CRH and COX-2 mRNA and protein abundance in a dose-dependent manner in primary cultures of cytotrophoblast. This was coupled with an increase in nuclear import of RelB/p52 and its association with the CRH and COX-2 promoters. Silencing of NF-kB inducing kinase, a central signaling component of the non-canonical NF-kB pathway, blocked MEHP-induced upregulation of CRH and COX-2. These results suggest a potential mechanism mediated by RelB/p52 by which phthalates could prematurely induce pro-labor gene activity and lead to preterm birth.

  12. The increased number of Leydig cells by di(2-ethylhexyl) phthalate comes from the differentiation of stem cells into Leydig cell lineage in the adult rat testis

    Highlights: ► DEHP increases rat Leydig cell number. ► DEHP induces the proliferation of stem Leydig cells. ► DEHP induces the formation of progenitor Leydig cells. - Abstract: The objective of the present study is to determine whether di(2-ethylhexyl) phthalate (DEHP) exposure at adulthood increases rat Leydig cell number and to investigate the possible mechanism. 90-day-old Long–Evans rats were randomly divided into 3 groups, and were gavaged with the corn oil (control) or 10 or 750 mg/kg DEHP daily for 7 days, and then received an intraperitoneal injection of 75 mg/kg ethane dimethanesulfonate (EDS) to eliminate Leydig cells. Serum testosterone concentrations were assessed by RIA, and the mRNA levels of Leydig cell genes were measured by qPCR. EDS eliminated all Leydig cells in the control testis on day 4 post-EDS, as judged by undetectable serum testosterone level and no 3β-hydroxysteroid dehydrogenase positive (3β-HSDpos) cells in the interstitium. However, in DEHP-treated groups, there were detectable serum testosterone concentrations and some oval-shaped 3β-HSDpos cells in the interstitium. These 3β-HSDpos cells were not stained by the antibody against 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), a marker for Leydig cells at a more advanced stage. The disappearance of mRNAs of Leydig cell biomarkers including Lhcgr, Cyp11a1, Cyp17a1, Insl3 and Hsd11b1 in the control testis was observed on day 4 post-EDS. However, there were detectable concentrations of Lhcgr, Cyp11a1 and Cyp17a1 mRNAs but undetectable concentrations of Insl3, Hsd17b3 and Hsd11b1 in the DEHP-treated testes, indicating that these 3β-HSDpos cells were newly formed progenitor Leydig cells. The mRNA level for nestin (Nes, biomarker for stem Leydig cells) was significantly increased in the control testis on day 4 post-EDS, but not in the DEHP treated testes, suggesting that these nestin positive stem cells were differentiated into progenitor Leydig cells in the DEHP-treated testes

  13. Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells

    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 μmol L-1). After incubation for 48 h estradiol 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 (IC50 = 105 μmol L-1, 138 μmol L-1, 49 μmol L-1 and 78 μmol L-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 μmol L-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 possible.

  14. Plant-originated glycoprotein (24 kDa) has an inhibitory effect on proliferation of BNL CL.2 cells in response to di(2-ethylhexyl)phthalate.

    Lee, Jin; Lim, Kye-Taek

    2011-08-01

    Di(2-ethylhexyl)phthalate (DEHP) is one of the many environmental chemicals that are widely used in polyvinyl chloride products, vinyl flooring, food packaging and infant toys. They cause cell proliferation or dysfunction of human liver. The purpose of this study is to investigate the inhibitory effect of a glycoprotein (24 kDa) isolated from Zanthoxylum piperitum DC (ZPDC) on proliferation of liver cell in the DEHP-induced BNL CL. 2 cells. [³H]-thymidine incorporation, intracellular reactive oxygen species (ROS), intracellular Ca²⁺ mobilization and activity of protein kinase C (PKC) were measured using radioactivity and fluorescence method respectively. The expression of mitogen-activated protein kinases [extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)], activator protein (AP)-1 (c-Jun and c-Fos), proliferating cell nuclear antigen (PCNA) and cell cycle-related factors (cyclin D1/cyclin-dependent kinase [CDK] 4) were evaluated using Western blotting or electrophoretic mobility shift assay. The results in this study showed that the levels of [³H]-thymidine incorporation, intracellular ROS, intracellular Ca²⁺ mobilization and activity of PKCα were inhibited by ZPDC glycoprotein (100 µg/ml) in the DEHP-induced BNL CL. 2 cells. Also, activities of ERK, JNK and AP-1 were reduced by ZPDC glycoprotein (100 µg/ml). With regard to cell proliferation, activities of PCNA and cyclin D1/CDK4 were significantly suppressed at treatment with ZPDC glycoprotein (100 µg/ml) in the presence of DEHP. Taken together, these findings suggest that ZPDC glycoprotein significantly normalized activities of PCNA and cyclin D1/CDK4, which relate to cell proliferation factors. Thus, ZPDC glycoprotein appears to be one of the compounds derived from natural products that are able to inhibit cell proliferation in the phthalate-induced BNL CL. 2 cells. PMID:21721021

  15. Effect of environmental conditions on the migration of DI (2-Ethylhexyl) Phthalate from PET bottles into yogurt drinks: Influence of time, temperature and food simulant

    Polyethylene terephthalate (PET) is one of the materials that are widely used for packaging of beverages and edible oils. In this study, the migration of di (2-ethylhexyl) phthalate (DEHP) from PET bottles into the Iranian yogurt drink was investigated. According to European Commission regulations, acetic acid (3% w/v) was chosen as stimulant. The acetic acid samples were stored at 4C, 25C and 45Cfor four months and analyzed periodically by gas chromatography. Differential Scanning Calorimetry (DSC) was used to investigate if contact with the food stimulant could affect the PET material. It was concluded that the storage temperature had a large effect on the migration of DEHP. Also, increasing storage time resulted in higher concentrations of migrating DEHP. The concentrations of migrating substance did not exceed its specific migration limit (Economic European Community (EEC) regulations). Determination of glass transition (Tg) and crystallinity percent of PET bottles using DSC method showed that the variations in the amount of migration at different storage condition did not induce any change in the PET material in contact with 3% acetic acid. (author)

  16. Effect of environmental conditions on the migration of di(2-ethylhexyl)phthalate from pet bottles into yogurt drinks: influence of time, temperature, and food simulant

    Polyethylene terephthalate (PET) is one of the materials that are widely used for packaging of beverages and edible oils. In this study, the migration of di(2-ethylhexyl)phthalate (DEHP) from PET bottles into the Iranian yogurt drink was investigated. According to European Commission regulations, acetic acid (3% w/v) was chosen as simulant. The acetic acid samples were stored at 4 degree C, 25 degree C, and 45 degree C for four months and analyzed periodically by gas chromatography. Differential Scanning Calorimetry (DSC) was used to investigate if contact with the food simulant could affect the PET material. It was concluded that the storage temperature had a large effect on the migration of DEHP. Also, increasing storage time resulted in higher concentrations of migrating DEHP. The concentrations of migrating substance did not exceed its specific migration limit (Economic European Community (EEC) regulations). Determination of glass transition (Tg) and crystallinity percent of PET bottles using DSC method showed that the variations in the amount of migration at different storage condition did not induce any change in the PET material in contact with 3% acetic acid. (author)

  17. Re-characterization of mono-2-ethylhexyl phthalate hydrolase belonging to the serine hydrolase family.

    Iwata, Makoto; Imaoka, Takuya; Nishiyama, Takashi; Fujii, Takao

    2016-08-01

    A novel bacterium assimilating di-2-ethylhexyl phthalate as a sole carbon source was isolated, and identified as a Rhodococcus species and the strain was named EG-5. The strain has a mono-2-ethylhexyl phthalate (MEHP) hydrolase (EG-5 MehpH), which exhibits some different enzymatic features when compared with the previously reported MEHP hydrolase (P8219 MehpH) from Gordonia sp. These differences include different pH optimum activity, maximal reaction temperature and heat stability. The Km and Vmax values of EG-5 MehpH were significantly higher than those of P8219 MehpH. The primary structure of EG-5 MehpH showed the highest sequence identity to that of P8219 MehpH (39%) among hydrolases. The phylogenetic tree suggested that EG-5 MehpH and P8219 MehpH were categorized in different groups of the novel MEHP hydrolase family. Mutation of a conserved R(109) residue of EG-5 MehpH to a hydrophobic residue resulted in a dramatic reduction in the Vmax value towards MEHP without affecting the Km value. These results indicate that this residue may neutralize the negative charge of a carboxylate anion of MEHP, and thus inhibit the catalytic nucleophile from attacking the ester bond. In other words, the R residue blocks inhibition from the carboxylate anion of MEHP. Recently, registered hypothetical proteins exhibiting 98% or 99% identities for EG-5 MehpH or for P8219 MehpH were found from some pathogens belonging to Actinomycetes. The protein may have other activities besides MEHP hydrolysis and function in other physiological reactions in some Actinomycetes. PMID:26868518

  18. Possible Mechanisms of Di(2-ethylhexyl Phthalate-Induced MMP-2 and MMP-9 Expression in A7r5 Rat Vascular Smooth Muscle Cells

    Mei-Fen Shih

    2015-12-01

    Full Text Available Proliferation and migration of vascular smooth muscle cells (VSMC are important in the development and/or progression of many cardiovascular diseases, including atherosclerosis. Evidence shows that matrix metalloproteinase (MMP-2 and MMP-9 are related to the pathogenesis of atherosclerosis. The expressions of MMP-2 and MMP-9 in atherosclerosis are regulated via various pathways, such as p38 mitogen activated protein kinase (MAPK, extracellular signal regulated kinase 1 and 2 (ERK1/2, Akt, and nuclear factor kappa (NF-κB. Di(2-ethylhexyl phthalate (DEHP has been shown to induce atherosclerosis by increasing tumor necrosis factor (TNF-α, interleukin (IL-6, and intercellular adhesion molecule (ICAM productions. However, whether DEHP poses any effects on MMP-2 or MMP-9 expression in VSMC has not yet been answered. In our studies, rat aorta VSMC was treated with DEHP (between 2 and 17.5 ppm and p38 MAPK, ERK1/2, Akt, NF-κB, and MMP-2 and MMP-9 proteins and activities were measured. Results showed that the presence of DEHP can induce higher MMP-2 and MMP-9 expression than the controls. Similar results on MMP-regulating proteins, i.e., p38 MAPK, ERK1/2, Akt, and NF-κB, were also observed. In summary, our current results have showed that DEHP can be a potent inducer of atherosclerosis by increasing MMP-2 and MMP-9 expression at least through the regulations of p38 MAPK, ERK1/2, Akt, and NF-κB.

  19. Exposure to Phthalates in Neonatal Intensive Care Unit Infants: Urinary Concentrations of Monoesters and Oxidative Metabolites

    Weuve, Jennifer; Brisa N. Sánchez; Calafat, Antonia M.; Schettler, Ted; Green, Ronald A; Hu, Howard; Hauser, Russ

    2006-01-01

    Objective We previously demonstrated that among 54 infants in neonatal intensive care units, exposure to polyvinyl chloride plastic medical devices containing the plasticizer di(2-ethylhexyl) phthalate (DEHP) is associated with urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP), a DEHP metabolite. In this follow-up report, we studied the neonates’ exposure to DEHP-containing devices in relation to urinary concentrations of two other DEHP metabolites, and to urinary concentrations o...

  20. Increased Serum Phthalates (MEHP, DEHP) and Bisphenol A Concentrations in Children With Autism Spectrum Disorder: The Role of Endocrine Disruptors in Autism Etiopathogenesis.

    Kardas, Fatih; Bayram, Ayse Kacar; Demirci, Esra; Akin, Leyla; Ozmen, Sevgi; Kendirci, Mustafa; Canpolat, Mehmet; Oztop, Didem Behice; Narin, Figen; Gumus, Hakan; Kumandas, Sefer; Per, Huseyin

    2016-04-01

    The aim of this study was to investigate the relationship between autism spectrum disorders development and exposure to mono-(2-ethylhexyl)-phthalate (MEHP), di-(2-ethylhexyl)-phthalate (DEHP), and bisphenol A (BPA), 1 of the endocrine disruptors, among phthalates. The study included 48 children with autism spectrum disorder (27 boys, 21 girls) and 41 healthy subjects (24 boys, 17 girls) as controls. Serum MEHP, DEHP, and BPA levels were measured by using high-performance liquid chromatography. Children with autism spectrum disorder had significantly increased serum MEHP, DEHP, and BPA concentrations (0.47 ± 0.14 µg/ml, 2.70 ± 0.90 µg/ml, 1.25 ± 0.30 ng/ml) compared to healthy control subjects (0.29 ± 0.05 µg/ml, 1.62 ± 0.56 µg/ml, 0.88 ± 0.18 ng/ml) respectively (P = .000). The fact that higher serum MEHP, DEHP, and BPA were found levels in the autism spectrum disorder group compared to healthy controls suggests that endocrine disruptors may have a role in the pathogenesis of autism spectrum disorders. PMID:26450281

  1. Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats

    Boberg, Julie; Ladefoged, Ole; Hass, Ulla;

    2004-01-01

    with DEHA and DINP have led to the hypothesis that similarities inaction may also exist. Pregnant Wistar rats were gavaged during gestation and lactation with vehicle, DEHP (300 or 750 mg/kg bodyweight per day), DINP (750 mg/kg bodyweight per day), DEHP (750 mg/kg bodyweight per day) in combination......The plasticizer di(2-ethylhexyl)phthalate (DEHP) exhibits antiandrogenic effects in perinatally exposed male rats. Di(2-ethylhexyl) adipate (DEHA) and diisononyl phthalate (DINP) are currently being evaluated as potential substitutes for DEHP, but similarities in structure and metabolism of DEHP...

  2. Ant cuticular response to phthalate pollution

    Lenoir, Alain; Axel, Touchard; Devers, Séverine; Christidès, Jean-Philippe; Boulay, Raphaël; Cuvillier-Hot, Virginie

    2014-01-01

    Phthalates are common atmospheric contaminantsused in the plastic industry. Ants have been shown to constitutegood bioindicators of phthalate pollution. Hence,phthalates remain trapped on ant cuticles which are mostlycoated with long-chain hydrocarbons. In this study, we artificiallycontaminated Lasius niger ants with four phthalates:dibutyl phthalate (DBP), diisobutyl phthalate (DiBP), di(2-ethylhexyl) phthalate (DEHP), and benzyl butyl phthalate(BBP). The first three have previously been fo...

  3. Kinetics of the phthalate metabolites mono-2-ethylhexyl phthalate (MEHP) and mono-n-butyl phthalate (MnBP) in male subjects after a single oral dose.

    Mittermeier, Astrid; Völkel, Wolfgang; Fromme, Hermann

    2016-06-11

    Humans have been exposed to dialkyl ortho-phthalates for decades. Due to degradation the phthalate monoesters, responsible for the toxic effects, are additionally found in environmental media as well as food samples. Nevertheless, the toxicokinetic properties of the monoesters are not known. Therefore, metabolism of the phthalate monoesters mono-2-ethylhexyl phthalate (MEHP) and mono-n-butyl phthalate (MnBP) was studied in four male volunteers (23-58 years of age) after ingestion of a single dose of 50μg/kg bw D4-MEHP or 10μg/kg bw D4-MnBP. The main metabolites in urine were determined up to 46h after administration. In the MEHP-study, more than 90% of each metabolite appeared in the urine within the first 22h, and the average excreted amount of D4-MEHP and its four secondary metabolites was 62% of the administered dose. The highest value of 15% was observed for mono-2-ethyl-5-carboxy-pentyl phthalate (D4-5cx-MEPP). The mean elimination half-life of D4-MEHP was estimated to be 3.5±1.4h. In the MnBP-study, the total recovered values of D4-MnBP and its secondary metabolites ranged from 52% to 130%. The monoester itself, with a half-life of 1.9±0.5h, accounted for the majority of the ingested dose (92%), while the secondary metabolites D4-mono-3-hydroxy-n-butyl phthalate (D4-3OH-MnBP) and D4-3-carboxy-mono-propyl phthalate (D4-3cx-MPP) represented only 7.1% and 1.0% of the ingested dose, respectively. Overall, this study determined that the kinetics of the phthalate monoesters MEHP and MnBP after oral dosage are comparable to the properties of their diesters. PMID:27091076

  4. Mono-2-ethylhexyl phthalate (MEHP) alters histiotrophic nutrition pathways and epigenetic processes in the developing conceptus.

    Sant, Karilyn E; Dolinoy, Dana C; Jilek, Joseph L; Shay, Brian J; Harris, Craig

    2016-01-01

    Histiotrophic nutrition pathways (HNPs) are processes by which the organogenesis-stage conceptus obtains nutrients, amino acids, vitamins and cofactors required for protein biosynthesis and metabolic activities. Nutrients are captured from the maternal milieu as whole proteins and cargoes via receptor-mediated endocytosis in the visceral yolk sac (VYS), degraded by lysosomal proteolysis and delivered to the developing embryo (EMB). Several nutrients obtained by HNPs are required substrates for one-carbon (C1) metabolism and supply methyl groups required for epigenetic processes, including DNA and histone methylation. Increased availability of methyl donors has been associated with reduced risk for neural tube defects (NTDs). Here, we show that mono-2-ethylhexyl phthalate (MEHP) treatment (100 or 250μM) alters HNPs, C1 metabolism and epigenetic programming in the organogenesis-stage conceptus. Specifically, 3-h MEHP treatment of mouse EMBs in whole culture resulted in dose-dependent reduction of HNP activity in the conceptus. To observe nutrient consequences of decreased HNP function, C1 components and substrates and epigenetic outcomes were quantified at 24h. Treatment with 100-μM MEHP resulted in decreased dietary methyl donor concentrations, while treatment with 100- or 250-μM MEHP resulted in dose-dependent elevated C1 products and substrates. In MEHP-treated EMBs with NTDs, H3K4 methylation was significantly increased, while no effects were seen in treated VYS. DNA methylation was reduced in MEHP-treated EMB with and without NTDs. This research suggests that environmental toxicants such as MEHP decrease embryonic nutrition in a time-dependent manner and that epigenetic consequences of HNP disruption may be exacerbated in EMB with NTDs. PMID:26507544

  5. Transcriptomic effects of di-(2-ethylhexyl-phthalate in Syrian hamster embryo cells: an important role of early cytoskeleton disturbances in carcinogenesis?

    Atienzar Franck

    2011-10-01

    Full Text Available Abstract Background Di-(2-ethylhexyl-phthalate (DEHP is a commonly used plasticizer in polyvinylchloride (PVC formulations and a potentially non-genotoxic carcinogen. The aim of this study was to identify genes whose level of expression is altered by DEHP by using a global wide-genome approach in Syrian hamster embryo (SHE cells, a model similar to human cells regarding their responses to this type of carcinogen. With mRNA Differential Display (DD, we analysed the transcriptional regulation of SHE cells exposed to 0, 12.5, 25 and 50 μM of DEHP for 24 hrs, conditions which induced neoplastic transformation of these cells. A real-time quantitative polymerase chain reaction (qPCR was used to confirm differential expression of genes identified by DD. Results Gene expression profiling showed 178 differentially-expressed fragments corresponding to 122 genes after tblastx comparisons, 79 up-regulated and 43 down-regulated. The genes of interest were involved in many biological pathways, including signal transduction, regulation of the cytoskeleton, xenobiotic metabolism, apoptosis, lipidogenesis, protein conformation, transport and cell cycle. We then focused particularly on genes involved in the regulation of the cytoskeleton, one of the processes occurring during carcinogenesis and in the early steps of neoplastic transformation. Twenty one cytoskeleton-related genes were studied by qPCR. The down-regulated genes were involved in focal adhesion or cell junction. The up-regulated genes were involved in the regulation of the actin cytoskeleton and this would suggest a role of cellular plasticity in the mechanism of chemical carcinogenesis. The gene expression changes identified in the present study were PPAR-independent. Conclusion This study identified a set of genes whose expression is altered by DEHP exposure in mammalian embryo cells. This is the first study that elucidates the genomic changes of DEHP involved in the organization of the

  6. Mono-(2-ethylhexyl) Phthalate Increases Oxidative Stress Responsive miRNAs in First Trimester Placental Cell Line HTR8/SVneo.

    Meruvu, Sunitha; Zhang, Jian; Choudhury, Mahua

    2016-03-21

    Phthalates, an endocrine disruptor group, cause oxidative stress (OS) in the placenta. However, no studies have reported OS-related miRNAs induced by phthalates. In the present study, we demonstrate that mono-(2-ethylhexyl) phthalate (MEHP) induces OS responsive miR-17-5p, miR-155-5p, and miR-126-3p in HTR8/SVneo in a dose- and time-dependent manner. Furthermore, MEHP altered the expression of phosphoinositide-3-kinase regulatory subunit 1α, phosphatase and tensin homolog, CDKN2A interacting protein, superoxide dismutase 2, and 3β-hydroxysterol-D24 reductase, which are involved in OS and predicted to be regulated by these miRNAs. Our results suggest that placental exposure to MEHP may result in aberrant miRNA expression leading to pregnancy complications. PMID:26871967

  7. 食品塑料包装材料中邻苯二甲酸二(2-乙基己)酯的暴露评估%Exposure Assessment of Di(2-ethylhexyl)phthalate of Plastic Food Packaging Materials

    白艳红; 许珂; 赵电波

    2012-01-01

    This article mainly reviewed the nature, source, toxicity and hazard of di(2-ethylhexyl)phthalate, one of the phthalate plasticizers of food plastics packaging materials. Preventive measures and proposals for this reference were discussed to provide security for plastic food packaging materials, as well as for packed food security research.%文中主要综述了食品塑料包装材料所用邻苯二甲酸酯类增塑剂中,邻苯二甲酸二(2.乙基己)酯(DEHP)的性质、来源、毒性及危害.提出了预防措施和建议,为食品塑料包装材料的安全性以及包装食品的安全性的相关研究提供参考依据.

  8. Pubertal exposure to di-(2-ethylhexyl) phthalate influences social behavior and dopamine receptor D2 of adult female mice.

    Wang, Ran; Xu, Xiaohong; Zhu, Qingjie

    2016-02-01

    DEHP, one of the most commonly phthalates used in plastics and many other products, is an environmental endocrine disruptor (EED). Puberty is another critical period for the brain development besides the neonatal period and is sensitive to EEDs. Social behavior is organized during puberty, so the present study is to investigate whether pubertal exposure to DEHP influenced social behavior of adult female mice. The results showed that pubertal exposure to DEHP for 2 weeks did not change the serum level of 17β-estradiol and the weight of uterus of adult females, but decreased the number of grid crossings and the frequency of rearing, and increased grooming in open field. DEHP reduced the open arm entries and the time spent in open arms in the elevated plus maze. DEHP reduced mutual sniffing and grooming between unfamiliar conspecifics in social play task and reduced the right chamber (containing unfamiliar female mouse) entries and the frequency of sniffing unfamiliar female mouse. DEHP at 1 mg kg(-1) d(-1) reduced the time spent in right chamber. Furthermore, Western blot analyses showed that DEHP decreased the levels of estrogen receptor β (ERβ), dopamine receptor D2, and the phosphorylation of ERKs in striatum. These results suggest that pubertal exposure to DEHP impaired social investigation and sociability and influenced anxiety-like state of adult female mice. The decreased activity of ERK1/2, and the down-regulated D2 and ERβ in striatum may be associated with the DEHP-induced changes of emotional and social behavior in mice. PMID:26524146

  9. Determination of Phthalate Metabolites in Human Serum and Urine as Biomarkers for Phthalate Exposure Using Column-Switching LC-MS/MS

    Jeong, Jee Yeon; Lee, Ji Hyun; Kim, Eun Young; Kim, Pan Gyi; Kho, Young Lim

    2011-01-01

    Objectives Although phthalates like dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are commonly used as plasticizers and their metabolites are especially suspected of reproductive toxicity, little is known about occupational exposure to those phthalates. The aim of this study was to assess the utility of measuring the metabolite concentrations of DBP and DEHP in serum and urine samples as an indicator of occupational exposure to those phthalates. Methods Phthalate metabolites we...

  10. 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

    Bekö, Gabriel; Weschler, Charles J; Langer, Sarka;

    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 a...

  11. Mutagenicity of the peroxisome proliferators clofibrate, Wyeth 14,643 and di-2-ethylhexyl phthalate in the lacZ plasmid-based transgenic mouse mutation assay

    Boerrigter Michaël

    2004-01-01

    Full Text Available Abstract Background Peroxisome proliferators are considered rodent carcinogens that are putative human non-carcinogens based on the presumed absence of direct genetic toxicity in rodent and human cells and the resistance of human cells to the induction of peroxisomes by peroxisome proliferators. The highly sensitive lacZ plasmid-based transgenic mouse mutation assay was employed to investigate the mutagenicity of several peroxisome proliferators based on several lines of evidence suggesting that these agents may in fact exert a genotoxic effect. Methods Male and female lacZ-plasmid based transgenic mice were treated at 4 months of age with 6 doses of 2,333 mg di-2-ethylhexyl phthalate (DHEP, 200 mg Wyeth-14,643, or 90 mg clofibrate per kg of bodyweight, respectively, over a two-week period. Control animals were treated with the respective vehicles only (35% propyl glycol for DEHP and Wyeth-14,643 treatment controls and sterile water for clofibrate treatment controls. The mutant frequency in liver, kidney and spleen DNA was determined as the proportion of retrieved mutant and wild-type lacZ plasmids expressed in Escherichia Coli C host cells employing a positive selection system for mutant plasmids. Results Exposure to DEHP or Wyeth-14,643 significantly increased the mutant frequency in liver, but not in kidney or spleen, of both female and male mice. Treatment with clofibrate did not lead to an increased mutant frequency in any of the organs studied. Conclusion The results indicate that some peroxisome proliferators display an organ-specific mutagenicity in lacZ plasmid-based transgenic mice consistent with historical observations of organ- and compound-specific carcinogenicity.

  12. Bovine Induced Pluripotent Stem Cells Are More Resistant to Apoptosis than Testicular Cells in Response to Mono-(2-ethylhexyl Phthalate

    Ying-Chu Lin

    2014-03-01

    Full Text Available Although the androgen receptor (AR has been implicated in the promotion of apoptosis in testicular cells (TSCs, the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl phthalate (MEHP, the active metabolite of di-(2-ethylhexyl phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.

  13. Comparison of hepatic peroxisome proliferative effect and its implication for hepatocarcinogenicity of phthalate esters, di(2-ethylhexyl) phthalate, and di(2-ethylhexyl) adipate with a hypolipidemic drug.

    Reddy, J K; Reddy, M K; Usman, M. I.; Lalwani, N D; M.S. Rao

    1986-01-01

    Peroxisome proliferation is inducible in hepatocytes of rodent and nonrodent species by structurally dissimilar hypolipidemic drugs and certain phthalate ester plasticizers. The induction of peroxisome proliferation appears to be a tissue specific response limited largely to the hepatocyte. Peroxisome proliferation is associated with increases in the activity of the H2O2-generating peroxisomal fatty acid beta-oxidation system and in the amount of peroxisome proliferation-associated 80,000 MW ...

  14. Human testis steroidogenesis is inhibited by phthalates

    Desdoits-Lethimonier, C.; Albert, O.; Le Bizec, B.; Perdu, E.; Zalko, D.; Courant, F; Lesne, L; Guille, F.; Dejucq-Rainsford, N.; Jegou, B.

    2012-01-01

    Phthalic acid esters are widely used in the manufacture of plastics. Numerous studies have shown that these phthalates impair testicular testosterone production in the rat. However, the scarce and contradictory data concerning humans have cast doubt over whether these compounds are also anti-androgenic in man. We therefore investigated the direct effects of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) on organo-cultured adult human testis and a human cell line A...

  15. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men

    Mendiola, J; Jørgensen, N; Andersson, A-M;

    2011-01-01

    Summary Widely used man-made chemicals, including phthalates, can induce hormonal alterations through a variety of cellular and molecular mechanisms. A number of rodent and observational studies have consistently demonstrated the anti-androgenic effect of several phthalates. However, there are on...

  16. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men

    Mendiola, J; Jørgensen, N; Andersson, A-M;

    2010-01-01

    Summary Widely used man-made chemicals, including phthalates, can induce hormonal alterations through a variety of cellular and molecular mechanisms. A number of rodent and observational studies have consistently demonstrated the anti-androgenic effect of several phthalates. However, there are on...

  17. Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

    The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10−5 M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10−5 M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with 14C-MEHP. A 10−5 M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10−5 M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10−5 M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

  18. Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

    Muczynski, V. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Cravedi, J.P. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Lehraiki, A.; Levacher, C.; Moison, D.; Lecureuil, C.; Messiaen, S. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Perdu, E. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Frydman, R. [Service de Gynécologie-Obstétrique, Hôpital A. Béclère, Université Paris Sud F-92141 Clamart (France); Habert, R. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); and others

    2012-05-15

    The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

  19. Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers.

    Barr, Dana B.; Silva, Manori J.; Kato, Kayoko; Reidy, John A; Malek, Nicole A; Hurtz, Donald; Sadowski, Melissa; Needham, Larry L.; Calafat, Antonia M.

    2003-01-01

    Phthalates are a group of industrial chemicals with many commercial uses, such as solvents, additives, and plasticizers. For example, di-(2-ethylhexyl) phthalate (DEHP) is added in varying amounts to certain plastics, such as polyvinyl chloride, to increase their flexibility. In humans, phthalates are metabolized to their respective monoesters, conjugated, and eliminated. However, despite the high production and use of DEHP, we have recently found that the urinary levels of the DEHP metabolit...

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

    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 adolescents.

  1. Toxicity and Estrogenic Endocrine Disrupting Activity of Phthalates and Their Mixtures

    Xueping Chen; Shisan Xu; Tianfeng Tan; Sin Ting Lee; Shuk Han Cheng; Fred Wang Fat Lee; Steven Jing Liang Xu; Kin Chung Ho

    2014-01-01

    Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity of butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-n-octyl phthalate (DNOP) and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the...

  2. Toxicity of di-(2-ethylhexyl) phthalate on the anaerobic digestion of wastewater sludge

    Alatriste-Mondragon, Felipe; Iranpour, R.; Ahring, Birgitte Kiær

    2003-01-01

    considered recalcitrant. Moreover, they inhibit methanogenesis. However, studies have not been made on the effect of feeding a combination of recalcitrant and biodegradable PAEs into anaerobic digesters treating wastewater sludge. The present study was conducted with wastewater sludge from the Los Angeles...... populations in the anaerobic bioreactor. Our results imply that high levels of DEHP or other recalcitrant PAEs in wastewater sludge are likely to compromise methanogenesis and removal of biodegradable PAEs in sludge digesters....

  3. Effect of DEHP (Di-2-Ethyl Hexyl-Phthalate on Resumption of Meiosis and in-vitro Maturation of Mouse Oocytes and Development of Resulting Embryos

    Hossein Eimani

    2005-01-01

    Full Text Available Introduction: DEHP [di(2-ethylhexyl phthalate] is widely used in plastic industry and some reproductive toxicity has been shown with it. So, this study was designed to evaluate DEHP effects on resumption of meiosis and in vitro maturation of mouse oocytes as well as development of embryos resulted from them. Material and Methods: Mice of 4-6 weeks old were administered daily doses of 50, 100, 200 µl of 2.56 µM DEHP solution for 12 days. Immature mouse oocytes were recovered from all experimental groups and matured in MEM-α medium containing 5% FCS with and without 7.5 IU hCG and 100 mIU rFSH. IVF was performed T6 medium. Results: Resumption of meiosis and in vitro maturation were significantly lower in all experimental groups in culture media without hormones compared to controls. Fertilization and embryo development were also significantly decreased in both culture media (with and without hormones. Conclusions: This study showed the adverse effects of DEHP on in vitro maturation and embryo development in a dose dependent manner.

  4. Chronic Effects of Di (2-ethylhexyl phthalate on Stereological Parameters of Testis in Adult Wistar Rats

    Mehran Dorostghoal

    2010-09-01

    Full Text Available Objective(sIn recent years concerns have been raised regarding the incidence of male reproductive disorders from exposure to endocrine disruptors. So, chronic effects of di(2-ethylhexylphthalate were studied on histological and stereological structure of testis in adult Wistar rats. Materials and MethodsThirty two adult Wistar rats were randomly divided in four equal experiment groups; oil vehicle group and three treated groups which received 10, 100 and 500 mg/kg/day di(2-ethylhexylphthalate by gavage for 90 days, respectively. At the end of exposure period the volume of testes was measured by Cavellieri method, testes weight was recorded and then fixed in Bouin’s solution. Following tissue processing, 5 µm sections were stained with haematoxylin-eosin and evaluated with quantitative techniques. Seminiferous tubule diameter, germinal epithelium height, relative and total volumes of seminiferous tubules, tubular lumen and interstitial tissue were estimated.ResultsThe results showed that mean weight and volume of testis were decreased significantly (35.2% and 23.9% respectively in rats treated with 500 mg/kg/day DEHP for 90 days. Seminiferous tubules diameter reduced, 4.4% and 13.4% in 100 and 500 mg/kg/day DEHP-treated groups, respectively. Relative volumes of tubular lumen and interstitial tissue were increased significantly in 100 (P< 0.05 and 500 (P< 0.01 mg/kg/day doses groups. Also, testosterone serum levels were significantly higher (P< 0.05 in rats exposed to 500 mg/kg/day DEHP. ConclusionPresent study indicated dose-dependent reductions of testicular parameters in adult male rats chronically exposed to di(2-ethylhexylphthalate.

  5. Childhood exposure to DEHP, DBP and BBP under the existing chemical management systems

    Lee, Jihyun; Lee, Jong-Hyeon; Kim, Chan-Kook;

    Since early 20th century, phthalates have been widely used as plasticizers. Due to the potential for adverse health effects - particularly reproductive effects - for vulnerable population such as children, phthalates like Di(2-ethylhexyl) phthalate (DEHP), Di-n-butyl phthalate (DBP) and Benzyl-bu...... environmental impact assessment will be discussed in the context of obtaining a better and equal protection of the environment and human health at a territorial level....

  6. PPARα- and DEHP-Induced Cancers

    Tamie Nakajima; Yuki Ito

    2008-01-01

    Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer and a potentially nongenotoxic carcinogen. Its mechanism had been earlier proposed based on peroxisome proliferator-activated receptor α (PPARα) because metabolites of DEHP are agonists. However, recent evidence also suggests the involvement of non-PPARα multiple pathway in DEHP-induced carcinogenesis. Since there are differences in the function and constitutive expression of PPARα among rodents and humans, species diff...

  7. Mono-ethylhexyl phthalate stimulates prostaglandin secretion in human placental macrophages and THP-1 cells

    Tetz, Lauren M; David M. Aronoff; Loch-Caruso, Rita

    2015-01-01

    Background Diethylhexyl phthalate (DEHP) is widely used as a plasticizer in polyvinyl chloride products. DEHP exposure, which is widespread in the US, increases preterm birth risk; however, the mechanisms driving this relationship are unclear. Because cyclooxygenase-2 (COX-2) dependent prostaglandin synthesis is implicated in preterm birth, we evaluated effects of mono-2-ethylhexyl phthalate (MEHP), the active metabolite of DEHP, on prostaglandin E2 (PGE2) synthesis and COX expression in huma...

  8. Differential cytotoxic effects of mono-(2-ethylhexyl) phthalate on blastomere-derived embryonic stem cells and differentiating neurons

    Potential applications of embryonic stem (ES) cells are not limited to regenerative medicine but can also include in vitro screening of various toxicants. In this study, we established mouse ES cell lines from isolated blastomeres of two-cell stage embryos and examined their potential use as an in vitro system for the study of developmental toxicity. Two ES cell lines were established from 69 blastomere-derived blastocysts (2.9%). The blastomere-derived ES (bm-ES) cells were treated with mono-(2-ethylhexyl) phthalate (MEHP) in an undifferentiated state or after directed differentiation into early neural cell types. We observed significantly decreased cell viability when undifferentiated bm-ES cells were exposed to a high dose of MEHP (1000 μM). The cytotoxic effects of MEHP were accompanied by increased DNA fragmentation, nuclear condensation, and activation of Caspase-3, which are biochemical and morphological features of apoptosis. Compared to undifferentiated bm-ES cells, considerably lower doses of MEHP (50 and 100 μM) were sufficient to induce cell death in early neurons differentiated from bm-ES cells. At the lower doses, the number of neural cells positive for the active form of Caspase-3 was greater than that for undifferentiated bm-ES cells. Thus, our data indicate that differentiating neurons are more sensitive to MEHP than undifferentiated ES cells, and that undifferentiated ES cells may have more efficient defense systems against cytotoxic stresses. These findings might contribute to the development of a new predictive screening method for assessment of hazards for developmental toxicity.

  9. Mono-(2-ethylhexyl) phthalate induces apoptosis through miR-16 in human first trimester placental cell line HTR-8/SVneo.

    Meruvu, Sunitha; Zhang, Jian; Bedi, Yudhishtar Singh; Choudhury, Mahua

    2016-03-01

    Phthalates have been linked to adverse pregnancy complications. Mono-(2-ethylhexyl) phthalate, an active metabolite of di-(2-ethylhexyl) phthalate and an endocrine disruptor, has been shown to induce apoptosis in various cell types including placental cells. However, the mechanism of action of MEHP induced apoptosis is still unknown. We hypothesized that apoptosis may be mediated in part through altered microRNA(s) in placenta under MEHP exposure. In the present study, we report that MEHP increases miR-16 expression in a time- and dose-dependent manner (p<0.05), while inducing apoptosis in HTR-8/SVneo. Cells treated with MEHP showed a dose-dependent increase in cytotoxicity and reactive oxygen species along with decreased cell viability. Consistent with significant increase in apoptosis analyzed by flow cytometry, we detected decreased anti-apoptotic BCL-2 at transcriptional and translational levels with MEHP (p<0.05). Knockdown of miR-16 did not decrease the BCL-2/BAX protein expression ratio in the presence of MEHP when compared to negative control demonstrating that MEHP induces apoptosis directly through miR-16. In conclusion, our study demonstrates for the first time that MEHP induces miR-16, which in turn, alters BCL-2/BAX ratio leading to increased apoptosis. This study provides a novel insight into MEHP induced epigenetic regulation in placental apoptosis which may lead to pregnancy complications. PMID:26597031

  10. Phthalates, perfluoroalkyl acids, metals and organochlorines and reproductive function

    Lenters, Virissa; Portengen, Lützen; Smit, Lidwien A M;

    2015-01-01

    than 70% of blood samples, including metabolites of di(2-ethylhexyl) and diisononyl phthalates (DEHP, DiNP), perfluoroalkyl acids, metals and organochlorines. Twenty-two reproductive biomarkers were assessed, including serum levels of reproductive hormones, markers of semen quality, sperm chromatin...... contaminants provides further indications that some organochlorines and phthalates adversely affect some parameters of male reproductive health....

  11. Evaluation of method for phthalate extraction from milk related to milk dilution ratio

    Milojković Danica S.; Anđelković Darko H.; Kocić Gordana M.; Anđelković Tatjana D.

    2015-01-01

    Liquid-liquid extraction techniques were compared coupled with gas chromatography-mass spectrometry (GC-MS), for the extraction and the determination of four phthalates: dimethyl phthalate (DMP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP) and di-(2-ethylhexyl) phthalate (DEHP) in six different kinds of milk-based samples. Extraction factors: sample preparation, organic solvent type and volume, salt effect, agitation and the extraction time wer...

  12. Identification of Phthalates in Medications and Dietary Supplement Formulations in the United States and Canada

    Kelley, Katherine E.; Hernández-Díaz, Sonia; Chaplin, Erica L.; Hauser, Russ B.; Mitchell, Allen Avrom

    2011-01-01

    Background: In animal studies, some :ortho-phthalates, including di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP), have been shown to be reproductive and developmental toxicants. Human studies show widespread population exposure to background levels of phthalates. Limited evidence suggests that particularly high exposure levels may result from orally ingested medicinal products containing phthalates as excipients (inactive ingredients). Objective: In this study we aimed to ide...

  13. Integrating Biomonitoring Exposure Data into the Risk Assessment Process: Phthalates [Diethyl Phthalate and Di(2-ethylhexyl) Phthalate] as a Case Study

    Calafat, Antonia M.; McKee, Richard H.

    2006-01-01

    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...

  14. Prenatal plus postnatal exposures to phthalates and child health risks

    Latini, G; Massaro, M.; A. Mandich

    2011-01-01

    Phthalates are a class of chemicals predominantly used as plasticizers in many plastics since the 1930's, in a wide variety of manufacturing applications and consumer products. Given their extensive use and their leakage from plastics, they are ubiquitous environmental contaminants with potential detrimental health effects. Di(2-ethylhexyl)phthalate (DEHP) is the most commonly used phthalate plasticizer. There is widespread exposure to phthalates in the general population and therefore it is ...

  15. Consumption of Phthalates Coated Pharmaceutical Tablets: An Unnoticed Threat

    Haji Bahadar; Faheem Maqbool; Mohammad Abdollahi

    2014-01-01

    Phthalates are synthetic chemicals used in many products of both industrial and medical importance. Approximately three million metric tons of phthalates are produced worldwide annually and are used in various sectors. Di-2-ethylhexyl phthalate (DEHP) is one of the most commonly used plasticizers. Chemically, they are loosely attached to Polyvinyl Chloride (PVC) based materials and with passage of time, leach to the surrounding environment. Phthalates are released from various sources and hum...

  16. Low-dose perinatal exposure to di(2-ethylhexyl) phthalate induces anti-androgenic effects in male rats

    Christiansen, Sofie; Boberg, Julie; Petersen, Marta Axelstad;

    2010-01-01

    demasculinizing effects of DEHP as well as investigating low dose effects. Our results demonstrate that DEHP at a relatively low dose of 10 mg/kg causes adverse anti-androgenic effects on male rat development. At this dose level, male anogenital distance was decreased, the incidence of nipple retention was...... increased, weight of levator ani/bulbocavernosus muscle was reduced and mild external genitalia dysgenesis was observed. Higher doses of DEHP, i.e. from 100 mg/kg, additionally induced histopathological effects on the testes, reduced testicular and prostate weight, and reduced expres¬sion of androgen...

  17. Predicting Residential Exposure to Phthalate Plasticizer Emitted from Vinyl Flooring - A Mechanistic Analysis

    A two-room model is developed to estimate the emission rate of di-2-ethylhexyl phthalate (DEHP) from vinyl flooring and the evolving gas-phase and adsorbed surface concentrations in a realistic indoor environment. Adsorption isotherms for phthalates and plasticizers on interior ...

  18. Predicting Residential Exposure to Phthalate Plasticizer Emitted from Vinyl Flooring: Sensitivity, Uncertainty, and Implications for Biomonitoring

    Given the ubiquitous nature of phthalates in the environment and the potential for adverse human health impacts, there is a need to understand the potential human exposure. A three-compartment model is developed to estimate the emission rate of di-2-ethylhexyl phthalate (DEHP) f...

  19. The association between phthalates in dust and allergic diseases among Bulgarian children

    Kolarik, Barbara; Naydenov, Kiril Georgiev; Larsson, Martin;

    2008-01-01

    esters in settled dust collected from children's homes in Sofia and Burgas, Bulgaria. METHODS: Dust samples from the child's bedroom were collected. A total of 102 children (2-7 Years of age) had symptoms of wheezing, rhinitis, and/or eczema in preceding 12 months (cases), and 82 were nonsymptomatic...... (controls). The dust samples were analyzed for their content of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP). RESULTS: A higher concentration of DEHP was found in homes of...... case children than in those of controls (1.24 vs. 0.86 mg/g dust). The concentration of DEHP was significantly associated with wheezing in the preceding 12 months (p = 0.035) as reported by parents. We found a dose-response relationship between DEHP concentration and case status and between DEHP...

  20. Phthalate Exposure Changes the Metabolic Profile of Cardiac Muscle Cells

    Posnack, Nikki Gillum; Swift, Luther M.; Kay, Matthew W.; Lee, Norman H; Sarvazyan, Narine

    2012-01-01

    Background: Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown. Objectives: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction. Methods: N...

  1. Phthalate Esters Used as Plasticizers in Packed Red Blood Cell Storage Bags May Lead to Progressive Toxin Exposure and the Release of Pro-Inflammatory Cytokines

    Rael, Leonard T; Raphael Bar-Or; Ambruso, Daniel R.; Mains, Charles W; Slone, Denetta S.; Michael L. Craun; David Bar-Or

    2009-01-01

    Phthalate esters (PE's) are plasticizers used to soften PVC-based medical devices. PE's are the most abundant man-made pollutants and increase the risk of developing an allergic respiratory disease or a malignancy. The leaching of PE's in donated packed red blood cells (PRBC) during storage was assessed. PRBC transfusion bags containing CPD/AS-1 (ADSOL) buffer were analyzed. Samples were collected on storage day 1 and day 42. Two PE's, di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl...

  2. Early testicular effects in rats perinatally exposed to DEHP in combination with DEHA - apoptosis assessment and immunohistochemical studies

    Borch, Julie; Dalgaard, Majken; Ladefoged, Ole

    2005-01-01

    metabolism, we investigated if the testicular effects of DEHP were modulated by co-administration with DEHA. Wistar rats were gavaged during gestation and lactation with vehicle, DEHP (300 or 750 mg/kg/day), or DEHP (750 mg/kg/day) in combination with DEHA (400 mg/kg/day), and male offspring were examined at......This study aimed to characterize the effects of di(2-ethylhexyl) phthalate (DEHP) on the fetal rat testes and relate them to the effects seen in adults. Histopathological effects in fetal testes were examined with immunohistochemistry for anti-Mullerian hormone (ANTH), 3 beta......-hydroxysteroid dehydrogenase, smooth muscle actin (SMA), proliferating cell nuclear antigen (PCNA), histone H3 and vimentin. Additionally, testicular apoptosis levels were assessed in fetal, prepubertal and adult rats. As the plasticizer di(2-ethylhexyl) adipate (DEHA) has similarities with DEHP in chemical structure and...

  3. Phthalate migration from packaging materials into food

    Soňa Bogdanovičová; Alžbeta Jarošová

    2015-01-01

    The content of dibutylphthalate (DBP) and di- (2-ethylhexyl) phthalate (DEHP) in samples of packages used for packaging meat productsand the phthalate migration from packaging materials to meat products were studied. Five samples of textile packaging intended for cooked meat production were analysed as well asthe final product which was filled into packages. Subsequently an analysis was carried out (after 1, 7, 14, 21, and 28 days of storage) of the finished meat products stored o...

  4. Role of PPARα in mediating the effects of phthalates and metabolites in the liver

    Phthalate esters belong to a large class of compounds known as peroxisome proliferators (PP). PP include chemicals that activate different subtypes of the peroxisome proliferator-activated receptor (PPAR) family. The ability of phthalate esters and their metabolites to activate responses through different PPAR subtypes is not fully characterized. We investigated the ability of two phthalate esters di-(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) and selected metabolites to activate PPAR (α, β/δ, γ) using a transient transfection assay. The monoester of DEHP, mono-(2-ethylhexyl) phthalate (MEHP) activated all three subtypes of PPAR, but preferentially activated PPARα. A second metabolite of DEHP, 2-ethylhexanoic acid (2-EHXA) was a weaker activator of all three subtypes. DBP, but not the primary metabolite mono-n-butyl phthalate weakly activated all three PPAR subtypes. MEHP and DBP but not DEHP and MBP interacted directly with human PPARα and PPARγ as determined by scintillation proximity assays. Both DEHP and DBP activated expression of PP-inducible gene products in wild-type but not PPARα-null mice suggesting that both of these phthalates exert their effects by activation of PPARα in vivo. The preferential activation of PPARα by phthalate ester metabolites suggests that these phthalates mediate their toxic effects in rodent liver in a manner indistinguishable from other PP

  5. Interaction Between DEHP and Particulate in a Eutrophic Lake

    迟杰; 刘华; 季民

    2004-01-01

    Characteristics of interaction between di-2-ethylhexyl phthalate(DEHP) and particulate in a eutrophic lake were studied in this paper. DEHP concentrations ranged from 89.9 to 247 μg/L with an average value of 146 μg/L in subsurface water (SSW) samples, and from 82.0 to 390 μg/L with an average value of 211 μg/L in water surface microlayer (SM) samples. The results indicate that there was only a weak correlation between the DEHP concentrations and suspended particulate material(SPM) concentrations in both SSW and SM, while the significant correlation between DEHP concentrations and chlorophyll a concentrations was found, which suggestes that DEHP was principally bound to phytoplankton in the eutrophic lake. Correlation between DEHP concentrations and total phosphor (TP) concentrations was also found in this investigation.Enrichment factors (EF) of DEHP in SM were in the range of 0.85 to 2.12 with an average value of 1.35. DEHP EFs were significantly related to the enrichment of chlorophyll a in SM. The results suggest that the enrichment of DEHP in SM of this eutrophic lake was mainly due to DEHP accumulation in phytoplankton and was controlled by distribution of phytoplankton between SM and SSW.

  6. Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

    Bornehag, Carl-Gustaf; Carlstedt, Fredrik; Jönsson, Bo A; Lindh, Christian; 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 repro...

  7. Toxic effect of systemic administration of low doses of the plasticizer di-(2-ethyl hexyl) phthalate [DEHP] in rats.

    Nair, K G; Deepadevi, K V; Arun, P; Kumar, V M; Santhosh, A; Lekshmi, L R; Kurup, P A

    1998-03-01

    DEHP [di-(2 ethyl hexyl) phthalate], a widely used plasticizer in blood storage bags, leaches out in appreciable amounts into blood (about 10 mg/100 ml) resulting in exposure of recipients of blood transfusion to this compound. Various reports indicate the toxicity of DEHP, particularly in liver and reproductive organs but all these studies used large doses (up to 2 g or more/Kg body weight) and oral route of administration which are not relevant to the intravenous administration during blood transfusion or the low amounts present in blood. We have studied changes in the activity of some important enzymes-gamma-GT, ALT, CPK, LDH, alkaline phosphatase, acid phosphatase, beta-glucuronidase and few other parameters like vitamin E, glutathione, serum albumin etc in rats administered low doses of DEHP (corresponding to transfusion of 2, 4, 6 and 10 units of blood). Histopathology of the organs has also been carried out. The results obtained indicate no serious toxic effects for DEHP at the level present in blood stored in DEHP plasticized blood bags as evidenced by the lack of any significant alteration in most of the biochemical parameters studied. Even in those cases where there was alteration (for e.g., decrease in the level of vitamin E) 24 hr after administration of DEHP, it returned to near normal level with in 72 hr to 7 days. No histopathological changes were observed in any of the organs at these levels of DEHP. It is concluded that DEHP did not cause any serious toxic effect even at doses corresponding to transfusion of several units of blood in a recipient. PMID:9754059

  8. Effects of Phthalates on the Human Corneal Endothelial Cell Line B4G12

    Krüger, Tanja; Cao, Yi; Kjærgaard, Søren K.; Knudsen, Lisbeth E.; Bonefeld-Jørgensen, Eva Cecilie

    2012-01-01

    Phthalates are industrial chemicals used in many cosmetics. We evaluated an in vitro model for eye irritancy testing using the human corneal endothelial cell line B4G12. Cell proliferation and toxicity were assessed after exposing to di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2......-ethylhexyl phthalate (DEHP), diisodecyl phthalate (DIDP), di-n-octyl phthalate (DnOP), and di-isononyl phthalate (DINP). Gene expression and secretion of inflammatory cytokines were evaluated after exposure to DBP. Decreased cell proliferation was observed for the phthalates DBP, BBP, and DEHP, and cell...... line B4G12 may be a potential model for inflammatory eye irritancy testing of phthalates....

  9. The influence of resource strategy on childhood phthalate exposure

    Lee, Jihyun; Pedersen, Anders Branth; Thomsen, Marianne

    2014-01-01

    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 recycling of 6.3% of DEHP, 20.3% of DBP, and 5.1% of BBP in the percentage of total manufactured amount of these phthalates. To examine the potential influence of the phthalate exposure through recycling, a case study assessing the childhood exposures to phthalates from foods packed in...... recycled paper and plastics has been performed as exemplified by the two countries: Denmark and Korea. The result shows that an increase in recycled paperboard and PET bottles in food packaging causes a significant increase in childhood exposure to DBP corresponding to an additional exposure of 0.355 and 0...

  10. 二乙基己基邻苯二甲酸致小鼠附睾生殖毒性及锌保护作用实验研究%The experimental research on reproductive toxicity of Di(2-ethylhexyl) Phthalate and protective effect of Zinc on mice epididymis

    张超; 宋晓峰; 刘星; 张德迎; 魏光辉

    2008-01-01

    Objective To study reproductive functional lesions of Di (2-ethylhexyl) Phthalate(DEHP) on epididymis, and to find antagon which can repress the toxicity. Methods In vivo study,postnatal day 20 (PND20) and PND50 male KM mice were randomly divided into normal control, cornoil, DEHP and DEHP + Zinc gluconate group. In each stage and group, after been garaged for 10days, epididymal histopathologic changes and androgen receptor (A.R) and estrogen receptor (ER) inepididymis were detected. In vitro study, epididymal epithelial cells of PND20 and PNDS0 mice werecultured. Viability of epididymal epithelial ceils were measured using MTT assay, content of sialic acid(SA) and the activity of α-1,4-glucosidase and lactic acid dehydrogenase (LDH) were investigated. Re-sults DEHP induced epididymis atrophy and conspicuous histopathologic uhrastructure changes, up-regulated AR and down-regulated ER. No conspicuous variations were found in DEHP + Zinc gluco-hate group. Conclusions DEHP can induce lesions of epididymaI structure and function. Zinc is an an-tagon to DEHP toxicity.%目的 探讨二乙基己基邻苯二甲酸(DEHP)埘附睾生殖功能的损害和可能机制,探寻DEHP毒件作用的拮抗剂.方法 出生后20d(PND20)和50d(PND50)雄件KM小鼠分别随机分为正常对照组、玉米油组、DEHP组和DEHP+葡萄糖酸锌组,连续灌胃10d,观察各期各组小鼠附睾组织学改变,检测雄激素受体(AR)、雌激素受体(ER)表达水平;体外培养PND20和PND50小鼠附睾上皮细胞.MTT法测定附睾上皮细胞活性.测定唾液酸(SA)含量、α-1,4-糖苷酶活性及乳酸脱氢酶(LDH)活力.结果 体内实验表明DEHP可导致附睾萎缩等组织病理学改变.并可导致附睾组织AR水平上调和ER水平下调(P0.01);体外实验表明DEHP可导致附睾上皮细胞活性降低.而DEHP+葡萄糖酸锌组附睾的形态、结构及功能均未见明显改变.结论DEHP可使附睾的结构和功能受损.锌对DEHP所致附睾牛殖毒性具有拮抗作用.

  11. Age- and Species-Dependent Infiltration of Macrophages into the Testis of Rats and Mice Exposed to Mono-(2-Ethylhexyl) Phthalate (MEHP)1

    Murphy, Caitlin J.; Stermer, Angela R.; Richburg, John H.

    2014-01-01

    ABSTRACT The mechanism by which noninfectious testicular inflammation results in infertility is poorly understood. Here the infiltration of CD11b+ immunoreactive testicular interstitial cells (neutrophil, macrophages, dendritic cells) in immature (Postnatal Day [PND] 21, 28, and 35) and adult (PND 56) Fischer rats is described at 12, 24, and 48 h after an oral dose of 1 g/kg mono-(2-ethylhexyl) phthalate (MEHP), a well-described Sertoli cell toxicant. Increases of CD11b+ cells are evident 12 h after MEHP exposure in PND 21 and 28 rats. In PND 28 rats, CD11b+ cells remained significantly elevated at 48 h, while in PND 21 rats, it returned to control levels by 24 h. The peak number of CD11b+ cells in PND 35 rat testis is delayed until 24 h, but remains significantly elevated at 48 h. In PND 56 rats, no increase in CD11b+ cells occurs after MEHP exposure. In PND 21, 28, and 35 rats, a significant increase in monocyte chemoattractant protein-1 (MCP-1) by peritubular myoid cells occurs 12 h after MEHP. Interestingly, MEHP treatment of C57BL/6J mice did not incite an infiltration of CD11b+ cells at either PND 21 or 28. The peak level of germ cell apoptosis observed 24 h after MEHP exposure in young rats is not seen in mice at any age or in PND 56 rats. Taken together, these findings implicate MCP-1 released by peritubular myoid cells in provoking the migration of CD11b+ cells into the immature rat testis early after MEHP exposure and point to a role for CD11b+ cells in triggering germ cell apoptosis in an age- and species-dependent manner. PMID:24876407

  12. Toxicity of phthalate esters exposure to carp (Cyprinus carpio) and antioxidant response by biomarker

    Zhao, Xiaoxiang; Gao, Ying; Qi, Mingliang

    2014-01-01

    To study the toxic effects of phthalate esters on the aquatic creatures, carps were exposed to dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) of six different concentrations for 96 h-LC50 measurements. It shows that the 96 h-LC50 is 16.30 and 37.95 mg L−1, thus the safe concentration (1/10LC50) is 1.63 mg L−1. The activities of xanthine oxidase (XOD) and catalase (CAT) were measured in liver to carp exposure for single or combinations of DBP and DEHP. The quantity of malonic dia...

  13. Correlations between phthalate metabolites in urine, serum, and seminal plasma from young Danish men determined by isotope dilution liquid chromatography tandem mass spectrometry

    Frederiksen, Hanne; Jørgensen, Niels; Andersson, Anna-Maria

    2010-01-01

    , correlations between urine and serum levels were only observed for mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(4-methyl-7-carboxyheptyl) phthalate (MCiOP), indicating that these secondary carboxylated metabolites were better serum markers than primary metabolites [mono(2-ethylhexyl) phthalate......Phthalates are suspected of endocrine disrupting effects. We aimed to develop an analytical method for simultaneous determination of several phthalate metabolites in human urine, serum, and seminal plasma and to study correlations between levels of metabolites in these matrices. Thirteen...... metabolites were determined in samples from 60 young Danish men. Metabolites of common di-ester phthalates were detected in most urine samples. Summed di-(2-ethylhexyl) phthalate (DEHP) metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL), followed by monoethyl phthalate (MEP), mono...

  14. Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro

    Hansen, Juliana Frohnert; Brorson, Marianne Møller; Boas, Malene; Frederiksen, Hanne; Nielsen, Claus Henrik; Lindström, Emma Sofie; Hofman-Bang, Jacob; Hartoft-Nielsen, Marie-Louise; Frisch, Thomas; Main, Katharina M.; Bendtzen, Klaus; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla

    2016-01-01

    Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells. PMID:26985823

  15. Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro.

    Juliana Frohnert Hansen

    Full Text Available Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP, di-(2-ethylhexyl phthalate (DEHP and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl phthalate (MEHP on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.

  16. Hepatic effects of a phthalate ester plasticizer leached from poly(vinyl chloride) blood bags following transfusion.

    Kevy, S V; Jacobson, M S

    1982-01-01

    The effects of di(2-ethylhexyl) phthalate (DEHP) on hepatic function and histology were evaluated in the rhesus monkey undergoing platelet and plasma transfusion. The average cumulative amount infused in one year is comparable to that received by patients who undergo chronic transfusion. Abnormalities in hepatic scan and BSP kinetics persisted for up to 26 months after transfusion, as did histologic abnormalities. Patients undergoing maintenance hemodialysis receive a yearly dose of DEHP whic...

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

    Rudel, Ruthann A.; 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...

  18. 增塑剂邻苯二甲酸二(2-乙基己基)酯的危害、分布及生物降解%Occurrence, Hazard and Biodegradation of Di-(2-ethylhexyl) Phthalate in Environment

    孟雪征; 牛贵龙; 曾明; 柳学速; 韩玉伟; 曹相生

    2014-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is widely found in plastics, leather, building materials, personal care products, detergents, paint, pharmaceuticals etc. As one of the synthetic organic compounds, DEHP is used as the most popular plasticizer in the world. This review present the toxic effects, regulations, occurrence and biodegradation of DEHP based on a wide range of papers and articles. The current and future directions in the field of DEHP researches are put forward. DEHP is toxic to immune system, embryo and liver etc. It also has carcinogenicity and is considered as an endocrine disrupter. Studies have shown the positively relation between DEHP and breast cancer, pancreatic cancer, testicular cancer, respiratory cancer and multiple myeloma etc., but there are no sufficient evidences to prove that DEHP can cause these cancers in human bodies. Since the severe lack of data of human beings, the toxicity of DEHP on human bodies has not fully confirmed. That is the reason why WHO suggests DEHP listed in the Group 2B carcinogen. As the toxic of DEHP to human beings is fundamental to other research works related to DEHP, We recommend the DEHP toxicity continuous experiments on human bodies should be performed as soon as possible. DEHP is widely present in water, food containers, air and soil. Data of samples from Songhua River, the Yellow River and the Yangtze River show that the concentrations of DEHP are beyond the limits of Chinese drinking water source standards or Chinese surface water quality standards. DEHP is also a common chemical in effluent of wastewater treatment plants. It is widely found in cheese, cereals and seafood, particularly in high lipid content foods such as milk, meat and fishes. If foods with plastic packages are stored for a long period, it will lead to more DEHP released to the foods. Furniture and decoration materials will also release DEHP to their environment;therefore the indoor air contains a certain amount of DEHP. In some

  19. Occurrence, Hazard and Biodegradation of Di-(2-ethylhexyl) Phthalate in Environment%增塑剂邻苯二甲酸二(2-乙基己基)酯的危害、分布及生物降解

    孟雪征; 牛贵龙; 曾明; 柳学速; 韩玉伟; 曹相生

    2014-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is widely found in plastics, leather, building materials, personal care products, detergents, paint, pharmaceuticals etc. As one of the synthetic organic compounds, DEHP is used as the most popular plasticizer in the world. This review present the toxic effects, regulations, occurrence and biodegradation of DEHP based on a wide range of papers and articles. The current and future directions in the field of DEHP researches are put forward. DEHP is toxic to immune system, embryo and liver etc. It also has carcinogenicity and is considered as an endocrine disrupter. Studies have shown the positively relation between DEHP and breast cancer, pancreatic cancer, testicular cancer, respiratory cancer and multiple myeloma etc., but there are no sufficient evidences to prove that DEHP can cause these cancers in human bodies. Since the severe lack of data of human beings, the toxicity of DEHP on human bodies has not fully confirmed. That is the reason why WHO suggests DEHP listed in the Group 2B carcinogen. As the toxic of DEHP to human beings is fundamental to other research works related to DEHP, We recommend the DEHP toxicity continuous experiments on human bodies should be performed as soon as possible. DEHP is widely present in water, food containers, air and soil. Data of samples from Songhua River, the Yellow River and the Yangtze River show that the concentrations of DEHP are beyond the limits of Chinese drinking water source standards or Chinese surface water quality standards. DEHP is also a common chemical in effluent of wastewater treatment plants. It is widely found in cheese, cereals and seafood, particularly in high lipid content foods such as milk, meat and fishes. If foods with plastic packages are stored for a long period, it will lead to more DEHP released to the foods. Furniture and decoration materials will also release DEHP to their environment;therefore the indoor air contains a certain amount of DEHP. In some

  20. Probabilistic assessment of risks of diethylhexyl phthalate (DEHP) in surface waters of China on reproduction of fish.

    Liu, Na; Wang, Yeyao; Yang, Qi; Lv, Yibing; Jin, Xiaowei; Giesy, John P; Johnson, Andrew C

    2016-06-01

    Diethylhexyl phthalate (DEHP) is considered to be an endocrine disruptor, which unlike other chemicals that have either non-specific (e.g., narcotics) or more generalized reactive modes of action, affect the Hypothalamic-pituitary-gonadal (HPG) axis and tend to have specific interactions with particular molecular targets within biochemical pathways. Responding to this challenge, a novel method for deriving predicted no-effect concentration (PNEC) and probabilistic ecological risk assessment (PERAs) for DEHP based on long-term exposure to potentially sensitive species with appropriate apical endpoints was development for protection of Chinese surface waters. PNECs based on potencies to cause lesions in reproductive tissues of fishes, which ranged from 0.04 to 0.20 μg DEHP L(-1), were significantly less than those derived based on other endpoints or other taxa, such as invertebrates. An assessment of risks posed by DEHP to aquatic organisms in surface waters of China showed that 88.17% and 78.85% of surface waters in China were predicted to pose risks to reproductive fitness of fishes with thresholds of protection for aquatic organisms based on 5% (HC5) and 10% (HC10), respectively. Assessment of risks of effects based on effects mediated by the HPG-axis should consider effects on chronic, non-lethal endpoints for specific taxa, especially for reproductive fitness of fishes. PMID:26970873

  1. Migration of DEHP and DINP into dust from PVC flooring products at different surface temperature.

    Jeon, Seunghwan; Kim, Ki-Tae; Choi, Kyungho

    2016-03-15

    Phthalates are important endocrine disrupting chemicals that have been linked to various adverse human health effects. Phthalates are ubiquitously present in indoor environment and could enter humans. Vinyl or PVC floorings have been recognized as one of important sources of phthalate release to indoor environment including house dust. In the present study, we estimated the migration of di(2-ethylhexyl)phthalate (DEHP) and di-isononyl phthalate (DINP) from the flooring materials into the dust under different heating conditions. For this purpose, a small chamber specifically designed for the present study and a Field and Laboratory Emission Cell (FLEC) were used, and four major types of PVC flooring samples including two UV curing paint coated, an uncoated residential, and a wax-coated commercial type were tested. Migration of DEHP was observed for an uncoated residential type and a wax-coated commercial type flooring. After 14 days of incubation, the levels of DEHP in the dust sample was determined at room temperature on average (standard deviation) at 384 ± 19 and 481 ± 53 μg/g, respectively. In contrast, migration of DINP was not observed. The migration of DEHP was strongly influenced by surface characteristics such as UV curing coating. In the residential flooring coated with UV curing paint, migration of DEHP was not observed at room temperature. But under the heated condition, the release of DEHP was observed in the dust in the FLEC. Migration of DEHP from flooring materials increased when the flooring was heated (50 °C). In Korea, heated flooring system, or 'ondol', is very common mode of heating in residential setting, therefore the contribution of PVC flooring to the total indoor DEHP exposure among general population is expected to be greater especially during winter season when the floor is heated. PMID:26824397

  2. Development of electrochemical impedance spectroscopy based sensing system for DEHP detection

    Zia, Asif I.

    2011-11-01

    This research work presents a real time and non invasive technique to detect Di(2-ethylhexyl) phthalate (DEHP)content in purified water and quantify its concentration by Electrochemical Impedance Spectroscopy(E.I.S.). Planar Inter-digital capacitive sensor is employed to evaluate conductivity, permeability and dielectric properties of material under test. This sensor, consisting of inter-digitated microelectrodes, is fabricated on silicon substrate using thin-film Microelectromechanical system (MEMS) based semiconductor device fabrication technology. Impedance spectrums are obtained with various concentrations of DEHP in purified water by using an electric circuit in order to extract sample conductance. Relationship of sample conductance with DEHP concentration is studied in this research work which enables us to show the ability of E.I.S. to detect DEHP concentration in water and hence can be applied in water treatment process for contamination quantification. © 2011 IEEE.

  3. Simultaneous GC-MS determination of seven phthalates in total and migrated portions of paper cups.

    Park, Yu Na; Choi, Min Sun; Rehman, Shaheed Ur; Gye, Myung Chan; Yoo, Hye Hyun

    2016-05-01

    Phthalate acid esters are widely used as plasticizers to impart plastic flexibility in various industrial applications. In this study, the content of seven phthalates, dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), di-(2-ethylhexyl) adipate (DEHA), di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DNOP), di-isononyl phthalate (DINP), and di-isodecyl phthalate (DIDP) were determined in paper cups using gas chromatography-mass spectrometry (GC-MS). In addition, the potential migration of these seven phthalates from paper cups into various food stimulants under different conditions was evaluated. The levels of DBP, DEHA, DEHP, and DNOP were in the ranges of 0.07-3.14, 0.16-42.69, 0.45-58.56, and 0.3-2.4 mg/kg, respectively. Meanwhile, BBP, DINP, and DIDP were not detected in most of the tested samples. In the migration test, DEHA was released to 50 % ethanol and n-heptane in a time-dependent manner and the maximum migration levels were 65.62 ± 3.61 and 95.56 ± 19.76 μg/L, respectively. The release of other phthalates was very low or negligible. These results demonstrated that paper cups are not a significant source of phthalate exposure; however, DEHA could be released from paper cups into alcoholic beverages or oily liquid beverages in the human diet. PMID:27053047

  4. Simultaneous sonication-assisted extraction, and determination by gas chromatography-mass spectrometry, of di-(2-ethylhexyl)phthalate, nonylphenol, nonylphenol ethoxylates and polychlorinated biphenyls in sludge from wastewater treatment plants

    Di-(2-ethyl-hexyl)phthalate (DEHP), nonylphenol, nonylphenol mono- and diethoxylates (NPEs) and polychlorinated biphenyls (PCBs) are organic pollutants in sewage sludge which have to be monitored in the European Union according to a future Sludge Directive. In the present work, an analytical method for the simultaneous extraction and determination of DEHP, NPEs and PCBs is proposed for the routine analysis of these compounds in sludge from wastewater treatment plants. All the compounds were simultaneously extracted by sonication with hexane and analysed by gas chromatography-mass spectrometry (GC-MS) in electronic impact mode. Recoveries achieved were 105% for DEHP, 61.4-88.6% for NPEs and 55.8-108.3% for PCBs with relative standard deviation bellow 10%. Limits of quantification were 65 μg kg-1 for DEHP, from 630 to 2504 μg kg-1 for NPEs and from 5.4 to 10.6 μg kg-1 for PCBs in dried sludge. The applicability of the proposed method was evaluated by the determination of these compounds in sludge from wastewater treatment plants in Seville (South Spain)

  5. Amniotic fluid phthalate levels and male fetal gonad function

    Jensen, Morten Søndergaard; Anand-Ivell, Ravinder; Nørgaard-Pedersen, Bent;

    2015-01-01

    ) and diisononyl phthalate (DiNP) exposure in relation to cryptorchidism, hypospadias, and human fetal Leydig cell function. METHODS: We studied 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls. Second-trimester amniotic fluid samples were available from a Danish pregnancy......BACKGROUND: Prenatal exposure to phthalates may pose a threat to human male reproduction. However, additional knowledge about the in vivo effect in humans is needed, and reported associations with genital abnormalities are inconclusive. We aimed to study prenatal di(2-ethylhexyl) phthalate (DEHP...

  6. Cumulative risk assessment of phthalate exposure of Danish children and adolescents using the hazard index approach

    Søeborg, T; Frederiksen, H; Andersson, Anna-Maria

    2012-01-01

    Human risk assessment of chemicals is traditionally presented as the ratio between the actual level of exposure and an acceptable level of exposure, with the acceptable level of exposure most often being estimated by appropriate authorities. This approach is generally sound when assessing the risk...... endpoint for the phthalates included in this article. Using the EFSA TDI values, 12 children exceeded the hazard quotient for the sum of di-n-butyl phthalate and di-iso-butyl phthalate (∑DBP((i+n)) ) and one child exceeded the hazard quotient for di-(2-ethylhexyl)phthalate (DEHP). Nineteen children...... exceeded the cumulated hazard index for three phthalates. Using the RfD AA values, one child exceeded the hazard quotient for DEHP and the same child exceeded the cumulated hazard index for four phthalates. The EFSA TDI approach thus is more restrictive and identifies ∑DBP((i+n)) as the compound...

  7. Intake estimates of phthalate esters for South Delhi population based on exposure media assessment

    An indirect estimation method was followed to derive exposure levels of fifteen phthalate congeners in urban population of Delhi, India. The exposure media samples were collected from Jawaharlal Nehru University (JNU) campus and Okhla industrial area. GC–MS analysis of the samples indicated di(2-ethylhexyl) phthalate (DEHP) to be the most abundant congener and its estimated total daily intake level reached upto 70 μg kg−1 d−1. Out of the studied congeners, intake doses for di-n-butyl phthalate (DnBP) and DEHP, reached levels near or above the established exposure limit. In JNU, DEHP, dimethyl phthalate (DMP) and butyl benzyl phthalate (BBP) had 69% share in combined daily intake of Σ15 phthalates (CDI15); whereas, in Okhla, DEHP, diethyl phthalate (DEP), diisobutyl phthalate (DIBP), DnBP and DMP shared 64% of the CDI15. Food was found to be the major source of exposure contributing 67% and 74% of the estimated CDI15 at JNU and Okhla respectively. - Highlights: • A probabilistic model was used to derive exposure values of 15 phthalate congeners. • Food was the major source of exposure contributing up to 74% of daily intake. • Indoor air contained higher concentration of phthalates with respect to outdoor. • DEHP was the most abundant congener and its daily intake reached upto 70 μg kg−1 d−1. • Intake doses of DnBP and DEHP reached levels near or above the exposure limits. - DEHP was the most abundant congener and its daily intake reached upto 70 μg kg−1 d−1. Intake doses of DnBP and DEHP reached levels near or above the exposure limits

  8. Natural Abundance 14C Content of Dibutyl Phthalate (DBP from Three Marine Algae

    Kazuyo Ukai

    2006-11-01

    Full Text Available Abstract: Analysis of the natural abundance 14C content of dibutyl phthalate (DBP from two edible brown algae, Undaria pinnatifida and Laminaria japonica, and a green alga, Ulva sp., revealed that the DBP was naturally produced. The natural abundance 14C content of di-(2-ethylhexyl phthalate (DEHP obtained from the same algae was about 50-80% of the standard sample and the 14C content of the petrochemical (industrial products of DBP and DEHP were below the detection limit.

  9. Toxicity and Estrogenic Endocrine Disrupting Activity of Phthalates and Their Mixtures

    Xueping Chen

    2014-03-01

    Full Text Available Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity of butyl benzyl phthalate (BBP, di(n-butyl phthalate (DBP, bis(2-ethylhexyl phthalate (DEHP, diisodecyl phthalate (DIDP, diisononyl phthalate (DINP, di-n-octyl phthalate (DNOP and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the six phthalates were found to be 0.72, 0.63 and 0.50 ppm, respectively. The other four phthalates did not cause more than 50% exposed embryo mortality even at their highest soluble concentrations. The typical toxicity symptoms caused by phthalates were death, tail curvature, necrosis, cardio edema and no touch response. Using an estrogen-responsive ChgH-EGFP transgenic medaka (Oryzias melastigma eleutheroembryos based 24 h test, BBP demonstrated estrogenic activity, DBP, DEHP, DINP and the mixture of the six phthalates exhibited enhanced-estrogenic activity and DIDP and DNOP showed no enhanced- or anti-estrogenic activity. These findings highlighted the developmental toxicity of BBP and DBP, and the estrogenic endocrine disrupting activity of BBP, DBP, DEHP and DINP on intact organisms, indicating that the widespread use of these phthalates may cause potential health risks to human beings.

  10. Phthalate Exposure and Human Semen Quality in Shanghai A Cross-sectional Study

    YUN-HUI ZHANG; LI-XING ZHENG; BING-HENG CHEN

    2006-01-01

    Objective To monitor the level of phthalates in human semen samples and to analyze the relationship between phthalate levels and semen parameters. Methods Concentrations of three kinds of commonly used phthalates (di-ethyl phthalate, DEP; di-n-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) were measured using reversed-phase HPLC. Semen parameters were measured by computer aided sperm analysis (CASA). Results The three phthalates were detected in most of the biological samples, With median levels of 0.30 mg/L (0.08-1.32 mg/L) in semen specimens. There was a significant positive association between liquefied time of semen and phthalate concentrations of semen. The correlation coefficient was 0.456 for DEP, 0.475 for DBP, and 0.457 for DEHP, respectively. There was no significant difference between phthalate concentrations of semen and sperm density or livability, though the correlation coefficients were negative. Conclusion These results suggest that people who reside in Shanghai are exposed to phthalates, especially to DBP and DEHP. Although the level of phthalates is relatively mild, an association of phthalate levels and reduced quality of human semen has been shown in the present study.

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

    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. PMID:27186877

  12. Phthalate metabolites in urine samples from Danish children and correlations with phthalates in dust samples from their homes and daycare centers

    Langer, S.; Bekö, Gabriel; Weschler, Charles J.; Brive, L. M.; Toftum, Jørn; Callesen, M.; Clausen, Geo

    2013-01-01

    Around the world humans use products that contain phthalates, and human exposure to certain of these phthalates has been associated with various adverse health effects. The aim of the present study has been to determine the concentrations of the metabolites of diethyl phthalate (DEP), di......(n-butyl) phthalate (DnBP), di(iso-butyl) phthalate (DiBP), butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) in urine samples from 441 Danish children (3–6 years old). These children were subjects in the Danish Indoor Environment and Children's Health study. As part of each child's medical...... examination, a sample from his or her first morning urination was collected. These samples were subsequently analyzed for metabolites of the targeted phthalates. The measured concentrations of each metabolite were approximately log-normally distributed, and the metabolite concentrations significantly...

  13. 出生前后DEHP暴露对小鼠神经行为的影响❋%Effects of utero and lactational exposure to di-(2-ethylhexyl) phthalate on neurobehavior of offspring mice

    徐晓虹; 竹庆杰; 杨艳玲; 阮琴

    2015-01-01

    The present study investigated the effects of utero and lactational exposure to DEHP (10, 50, and 200 mg/( kg·d) ) from gestation day 7 through postnatal day 21 on the behavior of offspring mice at age of 6 and 12 weeks. The results showed that DEHP exposure significantly inhibited locomotion but increased anxie-ty-like state of pubertal offspring mice of both sexes, and permanently influenced anxiety-like state of females in adulthood. Utero and lactational exposure to DEHP impaired spatial learning and memory function in puber-tal male mice, but not in pubertal females and adult mice of both sexes. These results suggested that develop-mental DEHP exposure sex specifically influenced a variety of neurobehavior, and anxiety and memory of pu-berty were more susceptible to DEHP.%研究了增塑剂邻苯二甲酸二(2-乙基)己酯(di-(2-ethyl hexyl)phthalate,DEHP)围生期母体暴露对青春期(6周龄)和成年后部(12周龄)子代小鼠行为的影响。母鼠从妊娠第7天至断乳前(产后21 d)灌胃染毒DEHP(10,50和200 mg/(kg·d)),同时设空白对照组及溶媒对照组。出生后第6和第12周时分别检测仔鼠的活动性、焦虑、空间记忆等行为。结果显示:DEHP暴露显著抑制了青春期雌、雄仔鼠的活动性,增加了其焦虑状态,且加剧的焦虑状态可延续到成年后的雌鼠;损伤青春期雄鼠的空间学习记忆能力,但对青春期雌鼠和成年后雌、雄仔鼠的空间记忆能力没有影响。以上结果提示,发育期DEHP暴露性别特异性地影响仔鼠的多种神经行为,青春期的情感和记忆能力更容易受影响。

  14. The therapeutic effects of Vitamin E on urethral development toxicity induced by di (2-ethylhexyl)phthalate%维生素E拮抗邻苯二甲酸二(2-乙基)己酯尿道发育毒性的实验研究

    陈柏林; 刘星; 吴盛德; 袁心刚; 何昀; 徐明灯; 刘东尧; 温晟; 魏光辉

    2011-01-01

    目的 探寻维生素E(Vitamin E,VitE)对邻苯二甲酸二(2-乙基)己酯[Di(2-ethylhexy1)phthlate,DEHP]所致大鼠尿道发育毒性的拮抗作用及其可能机制.方法 GD12(gestation day12)SD孕鼠随机分为4组,每组20只:玉米油对照组、DEHP组(500 mg·kg-1·d-1)、DEHP(500mg·kg-1·d-1)+VitE(200mg·kg-1·d-1)组和VitE组(200mg·kg-1·d-1).各组分别于母鼠孕期12~19d(GD12~19)持续经口灌注给药.各组分别留取10只孕鼠让其正常分娩,出生第一天,即对新生大鼠计数,并在解剖显微镜下测量雄性新生鼠的肛门生殖器距离(anal genital distance,AGD)并称体重;雄性仔鼠70日龄时逐个检查尿道下裂的发生情况.余孕鼠在GD19d行破宫产取仔代鼠,应用逆转录-聚合酶链反应(RT-PCR)的方法检测胎鼠阴茎TGF-β1,TGF-βR3 mRNA的表达水平.DNA末端原位标记染色法(TUNEL法)检测胎鼠阴茎尿道上皮细胞凋亡情况.结果 各组TGF-β1mRNA表达水平分别为:正常组为0.63±0.07、DEHP组为0.96±0.12、DEHP+VitE组为0.65±0.07、VitE组为0.62±0.06,DEHP组表达明显较其他各组增高(P<0.05).各组TGF-βR3mRNA表达水平分别为:正常组为0.47±0.10、DEHP组为0.75±0.10、DEHP+VitE组为0.49±0.09、VitE组为0.46±0.09,DEHP组表达明显较其他各组增高(P<0.05).各组胎鼠阴茎凋亡指数分别为:正常组为(30±2.0)%、DEHP组为(8.8土1.1)%、DEHP+VitE组为(28.9±1.6)%、VitE组为(29.6±2.0)%,DEHP组凋亡细胞数较其他各组相比明显减少,差异有统计学意义(P<0.01).导致大鼠尿道下裂的发生.VitE可降低DEHP上调的胎鼠阴茎TGF-β1,TGF-βR3 mRNA表达水平,恢复胎鼠阴茎尿道上皮细胞的凋亡水平.结论 VitE对DEHP所致尿道发育毒性具有拮抗作用,其机制可能与调控TGF-βs及胎鼠阴茎尿道上皮细胞的凋亡有关.%Objective To study the therapeutic effects of Vitamin E (VitE) on urethral development toxicity induced by di(2-ethylhexyl) phthalate (DEHP). Methods

  15. Exposure to DEHP and MEHP from hatching to adulthood causes reproductive dysfunction and endocrine disruption in marine medaka (Oryzias melastigma).

    Ye, Ting; Kang, Mei; Huang, Qiansheng; Fang, Chao; Chen, Yajie; Shen, Heqing; Dong, Sijun

    2014-01-01

    Concern has increased regarding the adverse effects of di-(2-ethylhexyl)-phthalate (DEHP) on reproduction. However, limited information is available on the effects of DEHP in marine organisms. The aim of the present study was to examine whether long-term exposure to DEHP and its active metabolite mono-(2-ethylhexyl)-phthalate (MEHP) disrupts endocrine function in marine medaka (Oryzias melastigma). Marine medaka larvae were exposed to either DEHP (0.1 and 0.5mg/L) or MEHP (0.1 and 0.5mg/L) for 6 months, and the effects on reproduction, sex steroid hormones, liver vitellogenin (VTG), gonad histology and the expression of genes involved in the hypothalamic-pituitary-gonad (HPG) axis were investigated. Exposure to DEHP, but not MEHP, from hatching to adulthood accelerated the start of spawning and decreased the egg production of exposed females. Moreover, exposure to both DEHP and MEHP resulted in a reduction in the fertilization rate of oocytes spawned by untreated females paired with treated males. A significant increase in plasma 17β-estradiol (E2) along with a significant decrease in testosterone (T)/E2 ratios was observed in males, which was accompanied by the upregulation of ldlr, star, cyp17a1, 17βhsd, and cyp19a transcription in the testis. Increased concentrations of T and E2 were observed in females, which was consistent with the upregulation of ldlr. The expression of brain gnrhr2, fshβ, cyp19b and steroid hormone receptor genes also corresponded well with hormonal and reproductive changes. The liver VTG level was significantly increased after DEHP and MEHP exposure in males. DEHP induced histological changes in the testes and ovaries: the testes displayed a reduced number of spermatozoa, and the ovaries displayed an increased number of atretic follicles. In addition, the tissue concentrations of MEHP, MEHHP and MEOHP in DEHP-exposed groups were much higher than those in MEHP-exposed groups, and there were no dose- or sex-specific effects. Thus, DEHP

  16. Joint Toxicity of Two Phthalates with Waterborne Copper to Daphnia magna and Photobacterium phosphoreum.

    Huang, Boyang; Li, Dinglong; Yang, Yan

    2016-09-01

    Di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are two widely used phthalates, while Cu(II) is a common valence state of copper. They have been ubiquitously detected in the aquatic environment, but information on their joint toxicity to aquatic organisms is scarce. In this study, we evaluated the combined effects of copper and these two phthalates to Daphnia magna and Photobacterium phosphoreum by quantifying the acute toxicity expressed by the EC50 (the concentration causing 50 % of maximal effect) value. The toxicity order was DEHP + Cu(II) > DBP + Cu(II) > Cu(II) > DEHP > DBP for both test species. Antagonism effects were found in the joint toxicity of Cu(II) combined with DBP or DEHP using the toxic unit method. These findings have important implications in environmental risk assessment for phthalates in the aquatic environment in the presence of heavy metals. PMID:27385371

  17. Associations between serum phthalates and biomarkers of reproductive function in 589 adult men

    Specht, Ina Olmer; Toft, Gunnar; Hougaard, Karin S; Lindh, Christian H; Lenters, Virissa; Jönsson, Bo A G; Heederik, Dick; Giwercman, Aleksander; Bonde, Jens Peter E

    Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level....... Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (Di......NP) metabolites in serum are associated with serum concentrations of male reproductive hormones and semen quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP on semen quality and reproductive hormones. A cross-sectional sample of 589 spouses of pregnant women from Greenland, Poland and...

  18. Toxicity of phthalate esters in fish and shellfish from virginia beach using matrix solid phase dispersion (mspd) and gc-ms

    This study presents the outcome of an investigation on the occurrence of phthalates, in eight edible marine fish species from lower James River, Chesapeake Bay along the Virginia Coast of Atlantic ocean. These include shell fish like Crab(Callinectes sapidus), Clam( Merccnaria), Oyster(C.ariakensis), and white shrimp ( Litopenaeus vannamei) from aquaculture center of Virginia Tech. These were analyzed for their content of Dimethyl Phthalate, Diethyl Phthalate, Di-n-butyl Phthalate , butyl benzyl Phthalate , bis(2-ethylhexyl) Phthalate ,and di-n-octyl Phthalate Mean concentrations (range) of Di(2-ethylhexyl) phthalate (DEHP), Butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP) in fish samples were 1.1 (<0.01-1.5), 0.22 (<0.01-1.1) and 0.14 (<0.01-1.3) mu g g-1; those in shell fishery were 1.2 (<0.02-1.3), 0.13 (<0.01-0.27) and 0.09 (<0.02-0.22) mu g g-1, respectively. The highest concentration of bis (2-ethylhexyl) Phthalate in fish samples were found in Atlantic mackerel (Centropristis striate) (1.98+-0.92) mu g/g (wet weight) and Oyster (C.ariakensis) (2.30 mu g/g (wet weight), were higher than those in other fish species. (author)

  19. The effect of di-(-2-ethyl hexyl) phthalate (Dehp) as plasticizer on the thermal and mechanical properties of pvc/pmma blends

    Kamira Aouachria; Guilhem Quintard; Valérie Massardier-Nageotte; Naima Belhaneche-Bensemra

    2014-01-01

    Plasticizers play a key role in the formulation of polymers and in determining their physical properties and processability. This study examines the effect of di(2-ethyl hexyl)phthalate (DEHP) as plasticizer on the thermal and mechanical properties of PVC/PMMA blends. For that purpose, blends of variable composition, from 0 to 100 wt%, were prepared in the presence (15, 30 and 50 wt %) and in the absence of di(2-ethyl hexyl)phthalate. The thermal degradation of the blends was investigated by ...

  20. Role of dissolved humic substances surrogates on phthalate esters migration from sewage sludge.

    Zheng, Z; He, P J; Zhang, H; Shao, L M

    2008-01-01

    The facilitated transport of dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), the priority endocrine disrupting chemicals in sludge, by dissolved humic substances (HS) was evaluated by batch extraction. The DBP, much less hydrophobic than DEHP, was inclined to migrate from sludge matrix into humic substances solutions, while the DEHP could not migrate facilitated by most humic and fulvic acids solutions, except the humic acid surrogate of high humification. This result revealed that the affinity of DEHP in sludge matrix exceeded DBP and was not susceptible by weak HS. The hydrophobic property controlled the association of phthalic acid esters on sludge residual phases. Migration rate of DBP was positively correlated to the weight-average molecular weight of HS surrogates and the aromatic extents of HA. Some functional groups in HS molecules benefited to the facilitated transport of DBP. PMID:18360003

  1. Uptake and Metabolism of Phthalate Esters by Edible Plants.

    Sun, Jianqiang; Wu, Xiaoqin; Gan, Jay

    2015-07-21

    Phthalate esters (PAEs) are large-volume chemicals and are found ubiquitously in soil as a result of widespread plasticulture and waste disposal. Food plants such as vegetables may take up and accumulate PAEs from soil, potentially imposing human health risks through dietary intake. In this study, we carried out a cultivation study using lettuce, strawberry, and carrot plants to determine the potential of plant uptake, translocation, and metabolism of di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) and their primary metabolites mono-n-butyl phthalate (MnBP) and mono(2-ethylhexyl) phthalate (MEHP). All four compounds were detected in the plant tissues, with the bioconcentration factors (BCFs) ranging from 0.16 ± 0.01 to 4.78 ± 0.59. However, the test compounds were poorly translocated from roots to leaves, with a translocation factor below 1. Further, PAEs were readily transformed to their monoesters following uptake. Incubation of PAEs and monoalkyl phthalate esters (MPEs) in carrot cell culture showed that DnBP was hydrolyzed more rapidly than DEHP, while the monoesters were transformed more quickly than their parent precursors. Given the extensive metabolism of PAEs to monoesters in both whole plants and plant cells, metabolism intermediates such as MPEs should be considered when assessing human exposure via dietary intake of food produced from PAE-contaminated soils. PMID:26090545

  2. Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

    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

  3. Phthalates in meat products in dependence on the fat content

    Alžbeta Jarošová; Soňa Bogdanovičová

    2016-01-01

    The content of dibutylphthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) in samples of packages intended for thermally processed meat products and release of phthalates from packages into meat products in dependence on the fat content were observed. 80 samples of packages were analyzed, 5 of them wereselected due to exceeding the specific migration limit. The raw meat was prepared, one type with the fat content of 10% and second one with the fat content of 50%. The both types of raw ...

  4. Assessment of Carcinogenicity of di(2-ethylhexyl) phthalate in a short-term assay using Xpa(-/-) and Xpa(-/-)/p53(+/-) mice

    Mortensen, Alicja; Bertram, Margareta; Aarup, V.; Sørensen, Ilona Kryspin

    2002-01-01

    between the models. The only liver tumors in all models were adenomas in males with no statistically significantly increased incidence. For p-cresidine, the survival was decreased (p <0.05) only in transgenic models. Statistically significantly increased incidences of nonneoplastic lesions were recorded...... in the liver, urinary bladder, and nasal cavity in all models, and in kidneys in transgenic models. The only tumors with statistically significantly increased incidence were liver adenomas in transgenic models (XPA:1 vs 7; `XPA/p53': 0 vs 12; WT: 0 vs 5, p = 0.053) and urinary bladder carcinomas in...... XPA/p53 model (0 vs 7). The negative carcinogenic response to DEHP and the positive response to p-cresidine support the expected sensitivity to genotoxic carcinogens in these transgenic models....

  5. The Inflammation Response to DEHP through PPARγ in Endometrial Cells

    Qiansheng Huang

    2016-03-01

    Full Text Available Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa were recruited to investigate the effects of di-(2-ethylhexyl phthalate (DEHP at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

  6. Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults.

    Lin, Chien-Yu; Hsieh, Chia-Jung; Lo, Shyh-Chyi; Chen, Pau-Chung; Torng, Pao-Ling; Hu, Anren; Sung, Fung-Chang; Su, Ta-Chen

    2016-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) has been used worldwide in various products for many years. In vitro studies have shown that exposure to DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) induces endothelial cell apoptosis. Moreover, exposure to DEHP had been linked to cardiovascular risk factors and cardiovascular diseases in epidemiological studies. Circulating microparticles have been known to be indicators of vascular injury. However, whether DEHP or its metabolites are independently associated with microparticles in humans remains unknown. From 2006 to 2008, we recruited 793 subjects (12-30years) from a population-based sample to participate in this cardiovascular disease prevention examination. Each participant was subjected to interviews and biological sample collection to determine the relationship between concentrations of DEHP metabolites MEHP, mono(ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethly-5-oxoheyl) phthalate in urine and concentrations of endothelial microparticles (CD62E and CD31+/CD42a-), platelet microparticles (CD62P and CD31+/CD42a+), and CD14 in serum. Multiple linear regression analysis revealed that an ln-unit increase in MEHP concentration in urine was positively associated with an increase in serum microparticle counts/μL of 0.132 (±0.016) in CD31+/CD42a- (endothelial apoptosis marker), 0.117 (±0.023) in CD31+/CD42a+ (platelet apoptosis marker), and 0.026 (±0.007) in CD14 (monocyte, macrophage, and neutrophil activation marker). There was no association between DEHP metabolite concentration and CD62E or CD62P. In conclusion, a higher MEHP concentration in urine was associated with an increase in endothelial and platelet microparticles in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to DEHP and atherosclerosis. PMID:27104673

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

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

    2016-04-01

    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. PMID:26754760

  8. Gender-Specific Adverse Effects of Mono-ethylhexyl Phthalate on Steroidogenesis in Immature Granulosa Cells and Rat Leydig Cell Progenitors in vitro

    KonstantinSvechnikov

    2011-04-01

    Full Text Available Di-2-ethylhexyl (DEHP phthalate, one of the phthalates most widely distributed in the environment, causes reproductive toxicity that is attributable to the action of its primary metabolite, mono (2-ethylhexyl phthalate (MEHP. Here, we have investigated the effects of MEHP on steroidogenesis by primary cultures of rat Leydig cell progenitors and immature granulosa cells. This phthalate stimulated basal steroidogenesis and StAR expression in both types of steroidogenic cells. However, when MEHP was incubated with (Bu2cAMP, steroid production was increased in granulosa cells and suppressed in Leydig cell progenitors, a process associated with up-regulation of StAR expression. Our data suggest that MEHP exerts gender-specific adverse effects on the hormonal function of the developing gonads. This may be involved in the development of pathological conditions including disorders of prenatal sex development that may attenuate future reproductive health.

  9. Exposure to phthalates affects calcium handling and intercellular connectivity of human stem cell-derived cardiomyocytes.

    Nikki Gillum Posnack

    Full Text Available The pervasive nature of plastics has raised concerns about the impact of continuous exposure to plastic additives on human health. Of particular concern is the use of phthalates in the production of flexible polyvinyl chloride (PVC products. Di-2-ethylhexyl-phthalate (DEHP is a commonly used phthalate ester plasticizer that imparts flexibility and elasticity to PVC products. Recent epidemiological studies have reported correlations between urinary phthalate concentrations and cardiovascular disease, including an increased risk of high blood pressure and coronary risk. Yet, there is little direct evidence linking phthalate exposure to adverse effects in human cells, including cardiomyocytes.The effect of DEHP on calcium handling was examined using monolayers of gCAMP3 human embryonic stem cell-derived cardiomyocytes, which contain an endogenous calcium sensor. Cardiomyocytes were exposed to DEHP (5 - 50 μg/mL, and calcium transients were recorded using a Zeiss confocal imaging system. DEHP exposure (24 - 72 hr had a negative chronotropic and inotropic effect on cardiomyocytes, increased the minimum threshold voltage required for external pacing, and modified connexin-43 expression. Application of Wy-14,643 (100 μM, an agonist for the peroxisome proliferator-activated receptor alpha, did not replicate DEHP's effects on calcium transient morphology or spontaneous beating rate.Phthalates can affect the normal physiology of human cardiomyocytes, including DEHP elicited perturbations in cardiac calcium handling and intercellular connectivity. Our findings call for additional studies to clarify the extent by which phthalate exposure can alter cardiac function, particularly in vulnerable patient populations who are at risk for high phthalate exposure.

  10. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury

  11. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    Chen, Shiwei [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Dong, Yushu [Department of Neurosurgery, 463rd Hospital of PLA, Shenyang 110042 (China); Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Hou, Wugang, E-mail: gangwuhou@163.com [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Li, Wei, E-mail: liweipepeyato@163.com [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi’an 710032 (China)

    2013-11-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.

  12. Comparison, association, and risk assessment of phthalates in floor dust at different indoor environments in Delaware, USA.

    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. PMID:26327207

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

    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. PMID:27261429

  14. Determination of six phthalates in polypropylene consumer products by sonication-assisted extraction/ GC-MS methods

    Studies on determination of six kinds of phthalates, for example dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP), in three kinds of plastic containers for food use, including food container, instant noodle cup and snack container, by gas chromatography in combination with mass spectrometry detector (GC-MS) in electronic ionization mode with selected-ion monitoring (SIM) acquisition method (GC-MS(EI-SIM)) have been carried out. Extraction, clean-up and analysis methods have been developed and optimized. Determination of samples were performed after sonication-assisted extraction with 1:9 toluene and dichloromethane, clean-up with Bio-Beads S-X8 gel-permeation column and analyzed by GC-MS methods. The characteristic ions, 163, 194 for DMP; 149, 177, 222 for DEP; 149, 233, 251 for DBP; 91, 149, 206 for BBP; 149, 176, 193 for DEHP; 149, 167, 279 for DNOP were chosen for quantitative studies. These techniques are possible to detect phthalates at the level of 1-70 mg/ kg. The overall recoveries were 79.2-91.1 % with relative standard deviation (R.S.D.) values at 3.1-11.3 %. Only DEHP was detected in the studied samples. (author)

  15. Measurement of phthalates in small samples of mammalian tissue

    Acott, P.D.; Murphy, M.G.; Ogborn, M.R.; Crocker, J.F.S.

    1987-03-01

    Di-(2-ethylhexyl)-phthalate (DEHP) is a phthalic acid ester that is used as a plasticizer in polyvinyl chloride products, many of which have widespread medical application. DEHP has been shown to be leached from products used for storage and delivery of blood transfusions during procedures such as plasmaphoresis, hemodialysis and open heart surgery. Results of studies in this laboratory have suggested that there is an association between the absorption and deposition of DEHP (and/or related chemicals) in the kidney and the acquired renal cystic disease (ACD) frequently seen in patients who have undergone prolonged dialysis treatment. In order to determine the relationship between the two, it has been necessary to establish a method for extracting and accurately quantitating minute amounts of these chemicals in small tissue samples. The authors have now established such a method using kidneys from normal rats and from a rat model for ACD.

  16. Measurement of phthalates in small samples of mammalian tissue

    Di-(2-ethylhexyl)-phthalate (DEHP) is a phthalic acid ester that is used as a plasticizer in polyvinyl chloride products, many of which have widespread medical application. DEHP has been shown to be leached from products used for storage and delivery of blood transfusions during procedures such as plasmaphoresis, hemodialysis and open heart surgery. Results of studies in this laboratory have suggested that there is an association between the absorption and deposition of DEHP (and/or related chemicals) in the kidney and the acquired renal cystic disease (ACD) frequently seen in patients who have undergone prolonged dialysis treatment. In order to determine the relationship between the two, it has been necessary to establish a method for extracting and accurately quantitating minute amounts of these chemicals in small tissue samples. The authors have now established such a method using kidneys from normal rats and from a rat model for ACD

  17. Structure-activity relationship of immunostimulatory effects of phthalates

    Nielsen Gunnar D

    2008-10-01

    Full Text Available Abstract Background Some chemicals, including some phthalate plasticizers, have been shown to have an adjuvant effect in mice. However, an adjuvant effect, defined as an inherent ability to stimulate the humoral immune response, was only observed after exposure to a limited number of the phthalates. An adjuvant effect may be due to the structure or physicochemical characteristics of the molecule. The scope of this study was to investigate which molecular characteristics that determine the observed adjuvant effect of the most widely used phthalate plasticizer, the di-(2-ethylhexyl phthalate (DEHP, which is documented as having a strong adjuvant effect. To do so, a series of nine lipophilic compounds with structural and physicochemical relations to DEHP were investigated. Results Adjuvant effect of phthalates and related compounds were restricted to the IgG1 antibody formation. No effect was seen on IgE. It appears that lipophilicity plays a crucial role, but lipophilicity does not per se cause an adjuvant effect. In addition to lipophilicity, a phthalate must also possess specific stereochemical characteristics in order for it to have adjuvant effect. Conclusion The adjuvant effect of phthalates are highly influenced by both stereochemical and physico-chemical properties. This knowledge may be used in the rational development of plasticizers without adjuvant effect as well as in the design of new immunological adjuvants.

  18. Effect of inoculation with arbuscular mycorrhizal fungi on the degradation of DEHP in soil

    WANG Shu-guang; LIN Xian-gui; YIN Rui; HOU Yan-lin

    2004-01-01

    The effect of inoculation with arbuscular mycorrhiza(AM) fungi(Acaulospora lavis) on the degradation of di(2-ethylhexyl) phthalate(DEHP) in soil was studies. Cowpea plants(Pigna sinensis) were used as host plants and grown in a specially designed rhizobox. The experimental results indicated that, both in sterile and non-sterile soil, mycorrhizal colonization rates were much higher in the mycorrhizal plants than in the non-mycorrhizal plants. Addition of 4 mg/kg DEHP slightly affected mycorrhizal colonization, but the addition of 100 mg/kg DEHP significantly decreased mycorrhizal colonization. DEHP degradation in the mycorrhizosphere(Ms) and hyphosphere(Hs), especially in the Hs, increased after inoculation with Acaulospora lavis. It is concluded that mycorrhizal hyphae play an important role in the plant uptake, degradation and translocation of DEHP. The mechanism might be attributed to increased numbers of bacteria and actinomycetes and activity of dehydrogenase, urease and acid phosphatase in the Ms and Hs by mycorrhizal fungi.

  19. Phthalates and food-contact materials: enforcing the 2008 European Union plastics legislation

    Petersen, Jens Højslev; Jensen, Lisbeth Krüger

    2010-01-01

    Commission transformed the tolerable daily intakes established by the Authority into legislative limits for phthalates in both plastic and food simulants, while taking exposure from other sources into consideration. These limits have been into force since 1 July 2008. A detailed interpretation...... producers, FCM importers and importers of packed foodstuffs from third-party countries. Products containing phthalates above the current limits were found in several categories of FCM: conveyor belts (six of six), lids from packed foodstuffs in glasses (eight of 28), tubes for liquid foodstuffs (four...... of five) and gloves (five of 14). More than 20% of the samples analysed contained dibutylphthalate (DBP) or di-(2-ethylhexyl)phthalate (DEHP) above the compositional limits of 0.05% and 0.1%, respectively. Analysis of residual phthalates in metal lid gaskets instead of analysis of phthalates in the food...

  20. Aspects of the testicular toxicity of phthalate esters

    Di(2-ethylhexyl) phthalate (DEHP) produced seminiferous tubular atrophy and reductions in seminal vesicle and prostate weight in 4-week-old, but not in 15 -week-old rats. Di-n-pentyl phthalate (DPP) did produce atrophy in the older rats but this developed more slowly than in young animals. Coadministration of testosterone or gonadotrophins did not protect against phthalate-induced testicular toxicity but did partly reverse the depression of seminal vesicle and prostate weight. Secretion of seminiferous tubule fluid and androgen binding protein by the Sertoli cells was markedly suppressed within 1 hr of a dose of DPP or mono-2-ethylhexyl phthalate (MEHP) in immature rats. This occurred less rapidly in mature rats. [14C]mono-n-pentyl phthalate and [14C]MEHP penetrated the blood testis barrier only to a very limited extent. These findings and the early morphological changes in the Sertoli cells produced by DPP suggest that phthalate esters may act initially to cause Sertoli cell injury, the subsequent loss of germ cells occurring as a consequence of this

  1. Increased levels of phthalates in very low birth weight infants with septicemia and bronchopulmonary dysplasia.

    Strømmen, Kenneth; Lyche, Jan Ludvig; Blakstad, Elin Wahl; Moltu, Sissel Jennifer; Veierød, Marit Bragelien; Almaas, Astrid Nylander; Sakhi, Amrit Kaur; Thomsen, Cathrine; Nakstad, Britt; Brække, Kristin; Rønnestad, Arild Erlend; Drevon, Christian André; Iversen, Per Ole

    2016-01-01

    Very low birth weight infants (VLBW; birth weightphthalates from medical devices during their hospital stay. We measured urinary phthalate concentrations among hospitalized VLBW infants participating in a nutritional study. Possible associations between different phthalates and birth weight (BW), septicemia and bronchopulmonary dysplasia (BPD) were evaluated. Forty-six VLBW infants were enrolled in this randomized controlled nutritional study. The intervention group (n=24) received increased quantities of energy, protein, fat, essential fatty acids and vitamin A, as compared to the control group (n=22). The concentrations of 12 urinary phthalate metabolites were measured, using high-performance liquid chromatography coupled to tandem mass spectrometry, at 3 time points during the first 5weeks of life. During this study, the levels of di (2-ethylhexyl) phthalate (DEHP) metabolites decreased, whereas an increasing trend was seen regarding metabolites of di-iso-nonyl phthalate (DiNP). Significantly higher levels of phthalate metabolites were seen in infants with lower BW and those diagnosed with late onset septicemia or BPD. A significant positive correlation between the duration of respiratory support and DEHP metabolites was observed (p≤0.01) at 2.9weeks of age. Birth weight was negatively associated with urinary phthalate metabolite concentrations. Infants with lower BW and those diagnosed with septicemia or BPD experienced prolonged exposure from medical equipment containing phthalates, with subsequent higher levels of phthalate metabolites detected. Clinical Trial Registration no.: NCT01103219. PMID:26922148

  2. Toxic effects of several phthalate esters on the embryos and larvae of abalone Haliotis diversicolor supertexta

    YANG Zhihui; ZHANG Xiangjing; CAI Zhonghua

    2009-01-01

    As the most widely used plasticizers in the world, phthalate esters (PAEs) are potential endocrine disruption compounds (EDCs). In the present study, the toxicity of dimethyl phthalate (DMP),diethyl phthalate (DEP), dibutyl phthalate (DBP), di (2-ethylhexyl) phthalate (DEHP) on embryogenesis and larvae development of the marine univalve Haliotis diversicolor supertexta was examined in laboratory. The results show that the malformation of embryos appeared during the experiment, such as embryos died or lysed, small transparent flocculent rings studded on the periphery of the embryo, and the larvae could failed to hatch. In embryo toxic test, embryos incubated at the highest concentration of DMP,DEP and DBP solutions showed significantly high abnormal rate compared with the control, while DEHP solutions displayed no significant difference. In larval toxic test, in all concentrations of DMP, DEP and DBP solutions, larval settlement rates were low significantly than that of the control. Similarly, DEHP solutions show nearly no effect on the larval settlement. The order of toxicity on embryos and larvae is DBP>DEP>DMP>DEHP. Being a simple and easy stimulation to indoor spawn, sensitive to environmental factors, and short culture time, the embryos of 1-1. diversicolor supertexta can be used to indicate toxicity of the PAEs.

  3. The concentrations of phthalates in settled dust in Bulgarian homes in relation to building characteristic and cleaning habits in the family

    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.

  4. Phthalate migration from packaging materials into food

    Soňa Bogdanovičová

    2015-08-01

    Full Text Available The content of dibutylphthalate (DBP and di- (2-ethylhexyl phthalate (DEHP in samples of packages used for packaging meat productsand the phthalate migration from packaging materials to meat products were studied. Five samples of textile packaging intended for cooked meat production were analysed as well asthe final product which was filled into packages. Subsequently an analysis was carried out (after 1, 7, 14, 21, and 28 days of storage of the finished meat products stored over the course of their intended shelf life at ambient temperature of 4 °C. Determination of phthalates was conducted by high performance liquid chromatography (HPLC method with UV detection at a wavelength of 224 nm on the Zorbax Eclipse C8 column. The content of phthalates in the final product was below the limit of quantification. According to the Regulation of the Commission (EU No. 10/2011, the specific migration limit of products intended for food contact is 1.5 mg.kg-1of food simulant for DEHP and 0.3 mg.kg-1 for DBP. After filling and the first day of storage of the meat product, four package samples release the said phthalates to an extent that it exceeded the limits of the Commission Regulation (EU No. 10/2011. Already after the seventh day of storage, all samples (with the exception of sample 2 for DBP exceeded SMLs. Monitoring of each phthalate migration in individual samples during storage (for 28 days produced a rising tendency.  In sample 1, DBP increased from 0.40 to 3.37 mg.kg-1, while DEHP from 0.58 to 14.66 mg.kg-1. In sample 2, DBP increased from ≤0.2 mg.kg-1 to 4.34 mg.kg-1, whileDEHP from 1.46 to 28.20 mg.kg-1. In sample 3, DBP increased from ≤0.2 mg.kg-1 to  8.27 mg.kg-1, while DEHP from 1.67 to 14.84 mg.kg-1. In sample 4, DBP increased from 0.27 to 6.12 mg.kg-1, while DEHP from 2.37 to 13.22 mg.kg-1. In sample 5, DBP increased from 0.32 to 11.11 mg.kg-1, while DEHP from 1.91 to 15.42 mg.kg-1.

  5. MEMS based impedimetric sensing of phthalates

    Zia, Asif I.

    2013-05-01

    Phthalate esters are known ubiquitous teratogenic and carcinogenic environmental and food pollutants. Their detection and quantification is strictly laboratory based, time consuming, expensive and professionally handled procedure. Presented research work describes a real time non-invasive detection technique for phthalates detection in ethanol, water and drinks. The new type of inter-digital sensor design incorporating multiple sensing gold electrodes were fabricated on silicon substrate based on thin film micro-electromechanical system (MEMS) using semiconductor device fabrication technology. A passivation layer of Silicon Nitride (Si3N4) was used to functionalize the sensor. Various concentrations (0.1 to 20ppm) of DINP (di-isononyl phthalates) in ethanol and di (2-ethylhexyl) phthalate (DEHP) in deionized MilliQ water were subjected to the testing system by dip testing method. Electrochemical impedance spectroscopy (EIS) technique was used to obtain impedance spectra in order to determine sample conductance for evaluation of its dielectric properties. The impedance spectra so obtained showed that the sensor was able to detect the presence of phthalates in the samples distinctively. Electrochemical Spectrum Analyser was used to model the experimentally obtained impedance spectra by curve fitting technique to figure out Constant Phase Element (CPE) equivalent circuit. Locally available energy drink and juice was added with phthalates in concentrations of 2, 6 and 10ppm to observe the performance of the sensor in such products. Experimental results showed that the new sensor was able to detect different concentrations of phthalates in energy drinks. © 2013 IEEE.

  6. Phthalate pollution in an Amazonian rainforest.

    Lenoir, Alain; Boulay, Raphaël; Dejean, Alain; Touchard, Axel; Cuvillier-Hot, Virginie

    2016-08-01

    Phthalates are ubiquitous contaminants and endocrine-disrupting chemicals that can become trapped in the cuticles of insects, including ants which were recognized as good bioindicators for such pollution. Because phthalates have been noted in developed countries and because they also have been found in the Arctic, a region isolated from direct anthropogenic influence, we hypothesized that they are widespread. So, we looked for their presence on the cuticle of ants gathered from isolated areas of the Amazonian rainforest and along an anthropogenic gradient of pollution (rainforest vs. road sides vs. cities in French Guiana). Phthalate pollution (mainly di(2-ethylhexyl) phthalate (DEHP)) was higher on ants gathered in cities and along road sides than on those collected in the pristine rainforest, indicating that it follows a human-mediated gradient of disturbance related to the use of plastics and many other products that contain phthalates in urban zones. Their presence varied with the ant species; the cuticle of Solenopsis saevissima traps higher amount of phthalates than that of compared species. However, the presence of phthalates in isolated areas of pristine rainforests suggests that they are associated both with atmospheric particles and in gaseous form and are transported over long distances by wind, resulting in a worldwide diffusion. These findings suggest that there is no such thing as a "pristine" zone. PMID:27372101

  7. Consumption of Phthalates Coated Pharmaceutical Tablets: An Unnoticed Threat

    Haji Bahadar

    2014-01-01

    Full Text Available Phthalates are synthetic chemicals used in many products of both industrial and medical importance. Approximately three million metric tons of phthalates are produced worldwide annually and are used in various sectors. Di-2-ethylhexyl phthalate (DEHP is one of the most commonly used plasticizers. Chemically, they are loosely attached to Polyvinyl Chloride (PVC based materials and with passage of time, leach to the surrounding environment. Phthalates are released from various sources and humans are exposed via, ingestion or inhalation. Different types of phthalates are used in the manufacture of coated and sustained releases drug formulations, as approved by FDA. Phthalates have been enlisted as Endocrine Disrupting Chemicals (EDCs with proven toxicity on various hormone controlled functions. Currently, besides medical devices, over the counter and prescription drugs contain certain quantity of phthalate as excipient. In certain chronic diseases, treating patient with such drugs may be an additional direct exposure to phthalates toxicity. So, on the basis of gathered evidences there is a need to seriously consider this type of direct human exposure and prevent already suffering people from being chronically poisoned with phthalates.

  8. Prenatal phthalate exposure and reduced masculine play in boys.

    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

  9. Phthalate intake by infants calculated from biomonitoring data.

    Völkel, Wolfgang; Kiranoglu, Mandy; Schuster, Ralph; Fromme, Hermann

    2014-03-01

    Urine samples (n=207) of 47 infants between 1- and 5-month of age were quantitated for 12 metabolites of 7 phthalates and compared with samples collected from the mothers of the infants at different time points. Median and 95-percentile were lower for all metabolites in urine samples of infants compared to mothers. For di-2-ethylhexyl phthalate (DEHP) the 95-percentile daily intake was 23.3μg/kg b.w. for mothers and 5.4μg/kg b.w. for infants and for di-isobutyl phthalate (DiBP) 10.1μg/kg b.w. and 8.5μg/kg b.w. Some values exceeded the corresponding tolerable daily intake (TDI) for DiBP for infants and mothers and for DEHP and di-n-butyl phthalate (DnBP) only for mothers. Both, infants and mothers are able to efficiently form phase II metabolites but infants with a slightly lower degree. Therefore, a distinguished risk assessment with respect to the formed toxic metabolites of phthalates would be necessary in combination with a reduction of the most toxic phthalates. PMID:24374175

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

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

    2010-01-01

    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...

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

    Jensen, Tina K; Frederiksen, Hanne; Kyhl, Henriette B;

    2016-01-01

    human studies have been conducted but associations between the anti-androgenic phthalates and male AGD have been reported. OBJECTIVE: To study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their infants at 3 months of age (N=273). METHODS......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......: In the Odense child cohort urinary concentrations of 12 phthalate metabolites of di-ethyl, di-n-butyl-, di-iso-butyl-, di-(2-ethylhexyl)-, butyl-benzyl- and di-iso-nonyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP and DiNP, respectively) were measured among 245 mothers to boys at approximately gestational...

  12. Indoor phthalate concentration in residential apartments in Chongqing, China: Implications for preschool children's exposure and risk assessment

    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.

  13. The influence of surface sorption and air flow rate on phthalate emissions from vinyl flooring: Measurement and modeling

    Liang, Yirui; Xu, Ying

    2015-02-01

    This study investigated the influences of surface sorption and air flow rate on the emission of phthalates from building materials. Controlled tests were conducted in specially designed stainless steel and wood chambers, and the steady-state concentration in the stainless steel chamber was about 2-3 times higher than that in the wood chamber for di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP). The emission rate of phthalates increased in the wood chamber due to the diffusion mass flow through the chamber wall (i.e., surface absorption). The adsorption isotherm of phthalates on the stainless steel surface and the absorption parameters (i.e., diffusion and partition coefficients) of phthalates on the wood surface were determined experimentally, and the values were comparable to those in the literature. The equilibration time scale for phthalates absorbed to the sink reservoir in actual indoor environments was estimated and can be substantial (approximately 80 years), indicating that surface absorption may continuously drive phthalates from their indoor sources to various sinks and thus significantly increase the emission rate of phthalates. The gas-phase concentration of DEHP was measured in two stainless steel chambers operated at flow rates of 300 mL/min and 3000 mL/min, respectively, which were both adjusted to 1000 mL/min after steady state was reached. The gas-phase concentration of DEHP in the chamber was very sensitive to the chamber air flow rate, and higher air flow rates resulted in lower concentration levels. However, the increased emission rate compensated for the dilution in the gas phase and made the DEHP concentration not drop substantially with an increase in the air flow rate. Independently measured or calculated parameters were used to validate a semi-volatile organic compounds (SVOCs) emission model that included absorptive surfaces and for a range of air flow rates, with excellent agreement between the model predictions and the

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

    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. PMID:25690585

  15. Assessment of the Extraction Methods for Monitoring Phthalate Emerging Contaminants in Groundwater and Tap Water

    Cotto, I.; Padilla, I. Y.; De Jesús, N. H.; Torres, P. M.

    2015-12-01

    Trace organic contaminants such as phthalates, among other chemicals of emerging concerns, have not historically been considered as pollutants but are being detected in water, posing a potential risk to public health and the environment. One of the most common phthalates of particular concern is di-(2-ethylhexyl) phthalate (DEHP), a plasticizer normally found in plastics and consumer products, including: cosmetics, pharmaceuticals, medical devices, food packages, water bottles, and wiring cables. DEHP has been associated with preterm birth, a major cause of neonatal mortality and health complications. This study aims at monitoring the presence and concentration of DEHP and other phthalates in groundwater and tap water systems in Puerto Rico, which has one of the highest rates of preterm birth in the U.S. The Environmental Protection Agency (EPA) suggests a liquid-liquid extraction method that uses methylene chloride as the preferred organic solvent for the extractions. This work presents modified EPA methods that reduce the volume of sample and solvent used, lower the time of analysis, increase productivity, and decrease hazards and waste. Distribution coefficient of DEHP between methylene chloride and water are estimated and related to sample extraction efficiency. Research results indicate that DEHP is in fact distributed between water and methylene chloride with a distribution coefficient average value of 1.24. The study concludes that the sample and solvent volumes have influence on the efficiency but have not an effect on the distribution coefficient. The tests show higher extraction efficiencies for lower DEHP concentrations and higher extraction volumes. Results from the water analysis show presence of DEHP in 55% of groundwater and 44% of tap water samples, indicating a potential exposure through water.

  16. Presence of phthalate esters in intravenous solution evaluated using gas chromatography-mass spectrometry method.

    Strac, Ivona Vidić; Pušić, Maja; Gajski, Goran; Garaj-Vrhovac, Vera

    2013-03-01

    Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in the production of poly-(vinyl) chloride (PVC) materials. It is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. DEHP is not covalently bound within the PVC molecule, which is why migration into a suitable medium can be expected. Since application of infusion solutions is one of the most common medical treatments, the objective of this study was to determine the migration of phthalates from softened PVC storage bags into infusion solution in different time periods within one year from date of production using a gas chromatography-mass spectrometry method. The measured values of DEHP ranged between 0.22 and 14.00 µg l(-1) , but the unexpected presence of other phthalate esters was also detected. It was concluded that values obtained in infusion solutions match the reference data and represent a minor risk for the patient. The presence of other phthalate esters leads to the conclusion that the pharmacopeic requirement for polymer cleanness was not fully met. Since phthalate esters are among the most extensively used industrial chemicals and are widely distributed in the environment, special precautions and further monitoring should be conducted to minimize any possible health risks. PMID:22034089

  17. Urinary Phthalates and Leukocyte Telomere Length: An Analysis of NHANES 1999–2002

    Scinicariello, Franco; Feroe, Aliya G.; Attanasio, Roberta

    2016-01-01

    The International Agency for Research on Cancer classified the di-2-ethylhexyl phthalate (DEHP) as “possibly carcinogenic to humans”. In vitro studies reported that phthalate exposure resulted in induction of several nuclear transcription factors that are activators of telomerase reverse transcriptase (TERT) and telomerase activity of the human telomerase complex. The objective of this study was to determine whether there is an association between urinary phthalate metabolites [mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-(2-ethyl)-hexyl phthalate (MEHP), and mono-benzyl phthalate (MBzP) and leukocyte telomere length (LTL) in the adult population of the National Health and Nutrition Examination Survey (NHANES) 1999–2002 (n = 2472). After adjustment for potential confounders, participants in the 3rd and 4th quartiles of urinary MEHP had statistically significantly longer LTL (5.34%, 95% CI: 1.31, 9.53; and 7.14%, 95% CI: 2.94, 11.63; respectively) compared to the lowest quartile, with evidence of a dose–response relationship (p-trend = 0.01). The association remained when the analyses were stratified by age groups (20–39 years, 40–59 years, and 60 years and older), and sex. Furthermore, MBP and MBzP were associated with higher LTL in older participants. The age independent association between longer LTL and MEHP (a metabolite of DEHP) might suggest a possible role of MEHP as tumor promoter.

  18. Introducing molecular selectivity in rapid impedimetric sensing of phthalates

    Zia, Asif I.

    2014-05-01

    This research article reports a real-time and non-invasive detection technique for phthalates in liquids by Electrochemical Impedance Spectroscopy (EIS), incorporating molecular imprinting technique to introduce selectivity for the phthalate molecule in the detection system. A functional polymer with Bis (2-ethylhexyl) phthalate (DEHP) template was immobilized on the sensing surface of the inter-digital (ID) capacitive sensor with sputtered gold sensing electrodes fabricated over a native layer of silicon dioxide on a single crystal silicon substrate. Various concentrations (10 to 200 ppm) of DEHP in deionized MilliQ water were exposed to the sensor surface functionalized with molecular imprinted polymer (MIP) in order to capture the analyte molecule, hence introducing molecular selectivity to the testing system. Impedance spectra were obtained using EIS in order to determine sample conductance for evaluation of phthalate concentration in the solution. Electrochemical Spectrum Analyzer algorithm was used to deduce equivalent circuit and equivalent component parameters from the experimentally obtained impedance spectra employing Randle\\'s cell model curve fitting technique. Experimental results confirmed that the immobilization of the functional polymer on sensing surface introduces selectivity for phthalates in the sensing system. The results were validated by testing the samples using High Performance Liquid Chromatography (HPLC-DAD). © 2014 IEEE.

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

    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

  20. Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice

    Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels

  1. Microemulsion electrokinetic chromatography for analysis of phthalates in soft drinks.

    Hsieh, Sung-Yu; Wang, Chun-Chi; Wu, Shou-Mei

    2013-12-15

    Microemulsion electrokinetic chromatography (MEEKC) is proposed for analysis of di-n-butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) in soft drinks. However, the instability of microemulsion is a critical issue. In this research, a novel material, Pluronic® F-127, which has the properties of polymer and surfactant, was added for stabilizing the microemulsion in the MEEKC system. Our data demonstrate that the presence of Pluronic® F-127 (0.05-0.30%) also helps enhance resolution of highly hydrophobic compounds, DBP and DEHP. The electrokinetic injection of sodium dodecyl sulphate (SDS) including sample (-10 kV, 20 s) was introduced in this MEEKC system and this yielded about 25-fold sensitivity enhancement compared with hydrodynamic injection (1 psi, 10 s). During method validation, calibration curves were linear (r≥0.99), within a range of 75-500 ng/mL for DBP and 150-1000 ng/mL for DEHP. As the precision and accuracy assays, absolute values of relative standard deviation (RSD) and relative error (RE) in intraday (n=3) and interday (n=5) observations were less than 4.93%. This method was further applied for analyzing six commercial soft drinks and one was found containing 453.67 ng/mL of DEHP. This method is considered feasible for serving as a tool for analysis of highly hydrophobic molecules. PMID:23993511

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

    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

  3. Neonatal phthalate ester exposure induced placental MTs, FATP1 and HFABP mRNA expression in two districts of southeast China

    Li, Bin; Xu, Xijin; Zhu, Yueqin; Cao, Junjun; Zhang, Yuling; Huo, Xia

    2016-01-01

    Plastic production releases phthalate esters (PAEs), which can alter the expression of metallothioneins (MTs), fatty acid transport protein 1 (FATP1) and heart fatty acid binding protein (HFABP). A total of 187 mother-infant pairs were recruited, 127 from Chenghai (high exposed group) and 60 from Haojiang (low exposed group), to investigate the association between neonatal PAE exposure and mRNA expression of placental MTs, FATP1 and HFABP. Umbilical cord blood and placenta samples were collected for measuring five PAE concentrations and detecting mRNA levels of MTs, FATP1 and HFABP. Butylbenzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP) were significantly higher in the high exposed group compared to the low exposed group. FATP1 and HFABP mRNA in the high exposed group were higher than that in the low exposed group while MT-1A was contrary. Both dimethyl phthalate (DMP) and DEHP were correlated with higher MT and MT-2A expression, while diethyl phthalate (DEP) was also positively correlated with MT-1A and FATP1 expression in female infants. DEHP exposure was negatively correlated with birth weight and gestational age in male infants. These results show that neonatal PAE exposure alters the mRNA expression of placental MTs and FATP1, which are related to fetal growth and development. PMID:26867681

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

    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.

  5. An integrated exposure assessment of phthalates for the general population in China based on both exposure scenario and biomonitoring estimation approaches.

    Cao, Yan; Liu, Jianguo; Liu, Yang; Wang, Jie; Hao, Xuewen

    2016-02-01

    The representativeness of available studies on integrated exposure assessment of phthalates for the general population in China is lacking. Based on an exhaustive review of the extensive monitoring data available for China, this study presents a large-scale estimation of exposure levels to three typical phthalates, di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP) and diisobutyl phthalate (DiBP), by applying both exposure scenario and biomonitoring estimation approaches. The respective median exposure levels from the exposure scenario and biomonitoring estimation approaches were 3.80, 3.02 and 1.00 μg/kg bw/day and 3.38, 3.21 and 3.32 μg/kg bw/day for DEHP, DBP and DiBP, which are acceptable levels of exposure with respect to current international guidelines. Evaluation results from the two approaches showed both similarities and differences among the different phthalates, making the exposure assessment comparable and more comprehensive. In terms of sources of exposure, food intake was the largest contributor, while indoor air exposure had greater contribution to the estimated daily intakes (EDIs) of DiBP than that of the other phthalates. Moreover, more attention should be paid to the higher exposure levels of phthalates in several intensively industrialized and urbanized areas, and the causes of the different exposure levels in the different regions need to be further explored. PMID:26654930

  6. Inflammatory Effects Of Phthalates In Neonatal Neutrophils

    Vetrano, Anna M; Laskin, Debra L.; Archer, Faith; Syed, Kirin; Joshua P Gray; Laskin, Jeffrey D.; Nwebube, Nkiru; Weinberger, Barry

    2010-01-01

    Hospitalized infants are exposed to numerous devices containing the plasticizer di-(2-ethylhexyl) phthalate. Urinary levels of the phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), are markedly elevated in premature infants. Phthalates inactivate PPAR-γ, a nuclear transcription factor that mediates the resolution of inflammation, a process impaired in neonates. We speculate that this increases their susceptibility to MEHP, and this was analyzed. MEHP inhibited neutrophil apoptosis; ...

  7. Effects of prolonged administration of phthalate ester on the liver

    Di(2-ethylhexyl)phthalate (DEHP) was administered to male rats in the diet at concentrations of 2.0, 0.2, and 0.02% for up to 102 weeks. Low doses resulted in moderate increases in certain hepatic enzymes during the initial phase of exposure and in a continuous increase in the activities of these same enzymes throughout the treatment period. An increased level of dolichol and decreased concentration of dolichyl-P were observed. Furthermore, the rate of protein glycosylation diminished. Liver biopsies from patients subjected to hemodialysis demonstrated an increased number of peroxisomes. Phthalate ester seems to interfere with protein turnover, so that the half-life of total mitochondrial and microsomal protein is considerably increased

  8. Phthalate concentrations in personal care products and the cumulative exposure to female adults and infants in Shanghai.

    Bao, Jiaqin; Wang, Min; Ning, Xiaojun; Zhou, Yaobin; He, Yuping; Yang, Jielin; Gao, Xi; Li, Shuguang; Ding, Zhuoping; Chen, Bo

    2015-01-01

    Phthalate esters (PE) are synthetic chemicals widely used in industry, and have been detected in personal care products (PCP). Recent findings of human reports demonstrated endocrine-disrupting action associated with phthalate exposures. The aims of this study were to (1) measure levels of 11 PE in 198 PCP collected from retail markets in Shanghai and (2) assess daily dermal exposure in adult females and infants. The health risk of cumulative exposure to eight PE on reproductive system function derived from dermal PCP use was further assessed by utilizing the hazard index (HI) approach. Diethyl phthalate (DEP) was the most frequently detected compound (29.8%), followed by diisobutyl phthalate (DiBP) (6.6%). The geometric mean (GM) concentrations of daily exposure to DEP, bis(2-methoxyethyl) phthalate (DMEP), DiBP, dibutyl phthalate (DBP), diphenyl phthalate (DPP), and bis(2-ethylhexyl) phthalate (DEHP) in female adults were 0.018, 0.012, 0.002, 0.001, 0.003, and 0.002 μg/kg body weight (bw)/d, respectively. The GM daily exposure levels to PE in infants and adult females were similar except for DEHP, which was higher in infants. DEP exposure was highest in both subpopulations at either GM or maximal level. All HI of 8 PE were far less than 1, ranging from 0.0002 to 0.005, indicating no cumulative reproductive risks to these populations. DBP, DMEP, and DEHP were three major contributors to the cumulative HI. In summary, the level of phthalate in PCP from Shanghai retail markets posed no apparent cumulative risk to adult females and infants in China. PMID:25734628

  9. Evaluation of method for phthalate extraction from milk related to milk dilution ratio

    Milojković Danica S.

    2015-01-01

    Full Text Available Liquid-liquid extraction techniques were compared coupled with gas chromatography-mass spectrometry (GC-MS, for the extraction and the determination of four phthalates: dimethyl phthalate (DMP, di-n-butyl phthalate (DBP, benzyl butyl phthalate (BBP and di-(2-ethylhexyl phthalate (DEHP in six different kinds of milk-based samples. Extraction factors: sample preparation, organic solvent type and volume, salt effect, agitation and the extraction time were optimized. The ion of base peaks (m/z 149 for DBP, BBP and DEHP and m/z 163 for DMP for investigated phthalates were selected for the screening studies. The acquisition was performed at the selected ion monitoring mode. The MSD response for GC-MS phthalate calibration standards was linear between 0.25 and 2.50 μg mL-1 with calculated LODs between 0.01 μg mL-1 to 0.04 μg mL-1 and LOQs of 0.05 μg mL-1 to 0.12 μg mL-1, while repeatability was between 1.7 % to 4.9 % RSD. The study demonstrated an increase of the recovery of less polar phthalates in matrix milk standards by matrix dilution. Recovery for hydrophilic phthalates, like DMP, was not changed by matrix dilution and it was continuously low for the investigated method. Two spiking levels were tested for influence of matrix dilution on phthalate recovery, showed the same trend. [Projekat Ministarstva nauke Republike Srbije, br. 31060

  10. Phthalates pollution in algae of Turkish coast

    Erakın, Sinem; Binark, Neşe; Güven, Kasım Cemal; Coban, Burak; Erduğan, Hüseyin

    2014-01-01

    Abstract In this work phthalates pollution in red, brown and green algae in the Black Sea, Istanbul Starait and Çanakkale Strait were investigated. The detected phthalate derivatives were DEP, DIBP, DBP and DEHP. Very toxic phthalate DEHP was found only in the Istanbul Strait. Phthalates pollution of algae depends on the pollution of sea water.

  11. Validação em laboratório de método analítico para determinação do teor de adipato e ftalato de di-(2-etil-hexila utilizados como plastificantes em filmes flexíveis de PVC Validation in laboratory of the analytical method to determine di-(2-ethylhexyl phthalate and adipate utilized as plasticizers in pvc films

    Andreia Artur Esteves

    2007-02-01

    Full Text Available The validation of analytical methods was carried out for di-(ethylhexyl phthalate (DEHP and adipate (DEHA the determination of in PVC films. The level of DEHP and DEHA in samples was determined by leaving the film in contact with n-heptane during 48 hours and analysis in a gas chromatograph (GC equipped with a flame ionization detector and fused silica column with 5% phenylmethyl silicone in the dimensions 30 m x 0.53 mm x 2.65 mm. The results for detection and the quantification limits were smaller than the restriction limits. The recovery rates of DEHP and DEHA were, respectively, 69.10 and 75.30 %.

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

    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).

  13. Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in Pregnant Women: A Repeated Measures Analysis

    Ferguson, Kelly K.; McElrath, Thomas F.; Chen, Yin-Hsiu; Mukherjee, Bhramar

    2014-01-01

    Background Phthalate exposure occurs readily in the environment and has been associated with an array of health end points, including adverse birth outcomes. Some of these may be mediated by oxidative stress, a proposed mechanism for phthalate action. Objectives In the present study, we explored the associations between phthalate metabolites and biomarkers of oxidative stress measured in urine samples from multiple time points during pregnancy. Methods Women were participants in a nested case–control study of preterm birth (n = 130 cases, n = 352 controls). Each was recruited early in pregnancy and followed until delivery, providing urine samples at up to four visits. Nine phthalate metabolites were measured to assess exposure, and 8-hydroxydeoxyguanosine and 8-isoprostane were also measured in urine as markers of oxidative stress. Associations were assessed using linear mixed models to account for intraindividual correlation, with inverse selection probability weightings based on case status to allow for greater generalizability. Results Interquartile range increases in phthalate metabolites were associated with significantly higher concentrations of both biomarkers. Estimated differences were greater in association with monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), and monoisobutyl phthalate (MiBP), compared with di(2-ethylhexyl) phthalate (DEHP) metabolites. Conclusions Urinary phthalate metabolites were associated with increased oxidative stress biomarkers in our study population of pregnant women. These relationships may be particularly relevant to the study of birth outcomes linked to phthalate exposure. Although replication is necessary in other populations, these results may also be of great importance for a range of other health outcomes associated with phthalates. Citation Ferguson KK, McElrath TF, Chen YH, Mukherjee B, Meeker JD. 2015. Urinary phthalate metabolites and biomarkers of oxidative stress in pregnant women: a repeated measures

  14. Exposure Estimation for Risk Assessment of the Phthalate Incident in Taiwan

    Chen, Chu-Chih; Wang, Shu-Li; Wu, Ming-Tsang; Wang, Yin-Han; Huang, Po-Chin; Chen, Bai-Hsiun; Sun, Chien-Wen; Ho, Chi-Kung; Shih, Yang-Chih; Shiu, Ming-Neng; Pan, Wen-Harn; Chen, Mei-Lien; Lee, Ching-Chang; Hsiung, Chao A.

    2016-01-01

    Background In May 2011, di(2-ethylhexyl) phthalates (DEHP) and, to a lesser extent, di-iso-nonyl phthalate (DiNP) were found to have been illegally used for many years in Taiwan as clouding agents in foods including sports drinks, juice beverages, tea drinks, fruit jam/nectar/jelly, and health or nutrient supplements. Objective To estimate the DEHP exposure for the study participants for the follow-up epidemiological study and health risk assessment. Methods A total of 347 individuals possibly highly exposed to phthalate-tainted foods participated in the study. Exposure assessment was performed based on the participants' responses to a structured questionnaire, self-report of exposure history, urinary metabolite concentrations, and DEHP concentration information in 2449 food records. A Bayesian statistical approach using Markov chain Monte Carlo simulation was employed to deal with the uncertainties in the DEHP concentrations of the contaminated foods and the participants' likelihood of being exposed. Results An estimated 37% and 15% of children younger than 12 years old were exposed to DEHP at medium (20–50 μg / kg_bw / day) and high AvDIs (50–100 μg / kg_bw / day), respectively, prior to the episode (9% and 3% in adults, respectively). Moreover, 11% of children and 1% of adults were highly exposed (> 100 μg / kg_bw / day), with a maximum of 414.1 μg / kg_bw / day and 126.4 μg / kg_bw / day, respectively. Conclusions The phthalate exposure-associated adverse health effects for these participants warrant further investigation. The estimation procedure may be applied to other exposure assessment with various sources of uncertainties. PMID:26960145

  15. Exposure Estimation for Risk Assessment of the Phthalate Incident in Taiwan.

    Chu-Chih Chen

    Full Text Available In May 2011, di(2-ethylhexyl phthalates (DEHP and, to a lesser extent, di-iso-nonyl phthalate (DiNP were found to have been illegally used for many years in Taiwan as clouding agents in foods including sports drinks, juice beverages, tea drinks, fruit jam/nectar/jelly, and health or nutrient supplements.To estimate the DEHP exposure for the study participants for the follow-up epidemiological study and health risk assessment.A total of 347 individuals possibly highly exposed to phthalate-tainted foods participated in the study. Exposure assessment was performed based on the participants' responses to a structured questionnaire, self-report of exposure history, urinary metabolite concentrations, and DEHP concentration information in 2449 food records. A Bayesian statistical approach using Markov chain Monte Carlo simulation was employed to deal with the uncertainties in the DEHP concentrations of the contaminated foods and the participants' likelihood of being exposed.An estimated 37% and 15% of children younger than 12 years old were exposed to DEHP at medium (20-50 μg / kg_bw / day and high AvDIs (50-100 μg / kg_bw / day, respectively, prior to the episode (9% and 3% in adults, respectively. Moreover, 11% of children and 1% of adults were highly exposed (> 100 μg / kg_bw / day, with a maximum of 414.1 μg / kg_bw / day and 126.4 μg / kg_bw / day, respectively.The phthalate exposure-associated adverse health effects for these participants warrant further investigation. The estimation procedure may be applied to other exposure assessment with various sources of uncertainties.

  16. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment

    HSU, YA-LING; HSIEH, CHIA-JUNG; TSAI, EING-MEI; HUNG, JEN-YU; CHANG, WEI-AN; HOU, MING-FENG; KUO, PO-LIN

    2016-01-01

    The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didymin, a dietary flavonoid glycoside present in citrus fruits, was able to reverse phthalate ester-mediated breast cancer aggravation. MDA-MB-231 cells were treated with butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP) or di-2-ethylhexyl phthalate (DEHP). Subsequently, the conditioned medium (CM) was harvested and cultured with monocyte-derived dendritic cells (mdDCs). Cultures of MDA-MB-231 cells with the conditioned medium of BBP-, DBP- or DEHP-MDA-MB-231 tumor-associated mdDCs (BBP-, DBP- or DEHP-MDA-TADC-CM) demonstrated enhanced proliferation, migration and invasion. Exposure of the MDA-MB-231 cells to DBP induced the MDA-TADCs to produce the inflammatory cytokine RANTES, which subsequently induced MDA-MB-231 cell proliferation, migration and invasion. Depleting RANTES reversed the effects of DBP-MDA-TADC-mediated MDA-MB-231 cell proliferation, migration and invasion. In addition, didymin was observed to suppress phthalate-mediated breast cancer cell proliferation, migration and invasion. The present study suggested that didymin was capable of preventing phthalate ester-associated cancer aggravation. PMID:26893687

  17. Influence of air flow rate on emission of DEHP from vinyl flooring in the emission cell FLEC: Measurements and CFD simulation

    Clausen, Per Axel; Liu, Zhe; Xu, Ying; Kofoed-Sørensen, Vivi; Little, John C.

    2010-07-01

    The emission of di-(2-ethylhexyl)phthalate (DEHP) from one type of vinyl flooring with ˜15% (w/w) DEHP as plasticizer was measured at 22 °C in five FLECs + one blank FLEC (Field and Laboratory Emission Cell). Initially, the flow through all FLECs was 450 ml min -1. After 689 days the flows were changed to 1000 ml min -1, 1600 ml min -1, 2300 ml min -1, and 3000 ml min -1, respectively, in four FLECs, and kept at 450 ml min -1 in one FLEC. Air samples were collected from the effluent air at regular intervals. After 1190 days the experiments were terminated and the interior surfaces of all six FLECs were rinsed with methanol to estimate the internal surface concentrations of DEHP. The DEHP air concentration and specific emission rate (SER) at steady state was estimated for the five different flow rates. The steady-state concentrations decreased slightly with increasing air flow with only the two highest flow rates resulting in significantly lower concentrations. In contrast, the SERs increased significantly. Despite large variation, the internal surface concentrations appeared to decrease slightly with increasing FLEC flow. Computational fluid dynamic (CFD) simulations suggest that the interior gas and surface concentrations were roughly uniform for the low flow case (450 ml min -1), under which, the partitioning between the FLEC internal surface and chamber air was examined. Although paired t-tests showed no difference between CFD and experimental results for DEHP air concentrations and SERs at steady-state conditions, CFD indicated that the experimental DEHP surface concentrations in the FLECs were underestimated. In conclusion, the experiments showed that the emission of DEHP from vinyl flooring is subject to "external" control and that the SER is strongly and positively dependent on the air exchange rate. However, the increased SER almost compensates for the decrease in gas-phase concentration caused by the increased air exchange.

  18. Fetal origin of endocrine dysfunction in the adult: the phthalate model.

    Martinez-Arguelles, D B; Campioli, E; Culty, M; Zirkin, B R; Papadopoulos, V

    2013-09-01

    Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer with endocrine disrupting properties that is found ubiquitously in the environment as well as in human amniotic fluid, umbilical cord blood, human milk, semen, and saliva. It is used in the industry to add flexibility to polyvinyl chloride-derived plastics and its wide spread use and presence has resulted in constant human exposure through fetal development and postnatal life. Epidemiological studies have suggested an association between phthalate exposures and human reproductive effects in infant and adult populations. The effects of fetal exposure to phthalates on the male reproductive system were unequivocally shown on animal models, principally rodents, in which short term deleterious reproductive effects are well established. By contrast, information on the long term effects of DEHP in utero exposure on gonadal function are scarce, while its potential effects on other organs are just starting to emerge. The present review focuses on these novel findings, which suggest that DEHP exerts more complex and broader disruptive effects on the endocrine system and metabolism than previously thought. This article is part of a Special Issue entitled "CSR 2013". PMID:23333934

  19. A Longitudinal Study of Urinary Phthalate Excretion in 58 Full-Term and 67 Preterm Infants from Birth through 14 Months

    Kuiri-Hänninen, Tanja; Main, Katharina M.; Dunkel, Leo; Sankilampi, Ulla

    2014-01-01

    Background: Some phthalates have shown antiandrogenic effects in rat offspring. Premature infants may be exposed to high amounts of specific phthalates during hospitalization, and thus are potentially at risk. Objective: We evaluated longitudinal phthalate exposure and metabolism in full-term (FT) and preterm (PT) infants. Methods: Fifty-eight FT and 67 PT (gestational age, 24.7–36.6 weeks) infants were recruited at birth and followed until 14 months (nine times). Urinary concentrations of metabolites of diethyl phthalate (DEP), dibutyl phthalate isomers (DiBP and DnBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and diisononyl phthalate (DiNP) were measured in 894 samples. Daily intake and a hazard index for antiandrogenic effects were estimated, and excretion patterns of DEHP and DiNP metabolites were analyzed. Results: Metabolites of BBzP, DiNP, and DEHP were 5–50 times higher at day 7 (D7) and month 1 (M1) in PT than in FT infants. Thereafter, metabolite concentrations were similar between the two groups. The estimated hazard index for combined DiBP, DnBP, BBzP, and DEHP exposures 7 days after birth exceeded the antiandrogenic threshold in > 80% of PT and > 30% of FT infants, and after M2, in 30% of all infants. The excretion pattern of DEHP and DiNP metabolites changed with age. Conclusion: Most PT infants and approximately one-third of healthy FT newborns were exposed to phthalates during early life at a potentially harmful level according to the European Food Safety Authority’s recommended limits of daily exposure. Changes in the relative proportions of secondary phthalate metabolites over time were consistent with maturation of infant metabolic pathways during the first year of life. Further research is needed on the health effects of phthalate exposures and the influence of changes in metabolic capacity in neonates and infants. Citation: Frederiksen H, Kuiri-Hänninen T, Main KM, Dunkel L, Sankilampi U. 2014. A longitudinal

  20. Phthalates determination in pharmaceutical formulae for parenteral nutrition by LC-ES-MS

    Complete text of publication follows. Phthalates (PAEs) are a group of chemical compounds widely use in industry and commerce due to their large variety of uses. Due to the ability to improve softness and flexibility to plastics, they are used mainly as plastizers in a wide variety of products including medical devices, children's toys and all types of packaging. The main drawback of the use of PAEs is that they can migrate from the material to the environment and pollute water, soil and food products. Furthermore, certain phthalate esters and or their metabolites are suspected to be human carcinogenic agents and endocrine disruptors, which make their trace determination of special importance. A method for determining a group of phthalate esters in pharmaceutical formulae for parenteral nutrition samples (with vitamins and without vitamins) was developed. The PAEs studied were Dimethyl phthalate (DMP), diethyl phthalate (DEP), butyl benzyl phthalate (BBP),dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP) and dioctyl phthalate (DOP). This group of phthalates were determined by high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ES-MS), working in positive mode. The phthalates analysed were extracted from the sample using hexane and sodium hydroxide. Then, the hexane was evaporated and the compounds were redissolved in acetonitrile. The compounds were separated in the HPLC system working in a gradient mode with acetonitrile-ultrapure water starting from 5% to 75% acetonitrile in 5 minutes followed by isocratic elution during 5 minutes. Standard calibration curves were linear for all the analytes over the concentration range 10-250 ng mL-1. The method was precise (with RSD from 3.3 to 10.7%), sensitive and accurate (recovery percentage around 100% for all studied compounds). The proposed analytical method has been applied to the analysis of these compounds in different pharmaceutical formulae (with different composition

  1. Dietary phthalate exposure in pregnant women and the impact of consumer practices.

    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

    2014-06-01

    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

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

    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

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

    Samantha E. Serrano

    2014-06-01

    Full Text Available 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.

  4. 增塑剂DEHP的性能、合成、检测方法及其对人体健康的影响%Properties, Synthesis and Detection of Plasticizer DEHP and Its Impact on Human Health

    张文广

    2012-01-01

    Plasticizers are used to impart flexibility for poly vinyl chloride (PVC) plastics. Di(2-ethylhexyl)phthalate(DEHP) is the most widely used plasticizer in PVC plastics. However, DEHP leaks out from PVC items, and has consequently become a environmental contaminant The composition, structure, properties, uses, synthesis principle, determination methods, ways of going into human body and impacts on human health of DEHP was discussed. It was pointed out that we should modify live habit to low absorption and harm of DEHP.%因PVC塑料在人类生活中被广泛应用,增塑剂邻苯二甲酸二-2-乙基己酯(DEHP)在环境中无处不在,已成为一种公认的环境污染物.讨论了DEHP的组成、结构、性质、用途、合成原理、检测方法及其进入人体的途径和对人体健康的影响.指出人们可以通过改变生活习惯来降低人体对DEHP的吸收,减少其危害.

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

    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

  6. Beyond phthalates: Gas phase concentrations and modeled gas/particle distribution of modern plasticizers

    The ongoing health debate about polymer plasticizers based on the esters of phthalic acid, especially di(2-ethylhexyl) phthalate (DEHP), has caused a trend towards using phthalates of lower volatility such as diisononyl phthalate (DINP) and towards other acid esters, such as adipates, terephthalates, citrates, etc. Probably the most important of these so-called 'alternative' plasticizers is diisononyl cyclohexane-1,2-dicarboxylate (DINCH). In the indoor environment, the continuously growing market share of this compound since its launch in 2002 is inter alia apparent from the increasing concentration of DINCH in settled house dust. From the epidemiological point of view there is considerable interest in identifying how semi-volatile organic compounds (SVOCs) distribute in the indoor environment, especially in air, airborne particles and sedimented house dust. This, however, requires reliable experimental concentration data for the different media and good measurements or estimates of their physical and chemical properties. This paper reports on air concentrations for DINP, DINCH, diisobutyl phthalate (DIBP), diisobutyl adipate (DIBA), diisobutyl succinate (DIBS) and diisobutyl glutarate (DIBG) from emission studies in the Field and Laboratory Emission Cell (FLEC). For DINP and DINCH it took about 50 days to reach the steady-state value: for four months no decay in the concentration could be observed. Moreover, vapor pressures p0 and octanol-air partitioning coefficients KOA were obtained for 37 phthalate and non-phthalate plasticizers from two different algorithms: EPI Suite and SPARC. It is shown that calculated gas/particle partition coefficients Kp and fractions can widely differ due to the uncertainty in the predicted p0 and KOA values. For most of the investigated compounds reliable experimental vapor pressures are not available. Rough estimates can be obtained from the measured emission rate of the pure compound in a microchamber as is shown for di

  7. Beyond phthalates: Gas phase concentrations and modeled gas/particle distribution of modern plasticizers

    Schossler, Patricia [Fraunhofer WKI, Department of Material Analysis and Indoor Chemistry, Bienroder Weg 54E, D-38108 Braunschweig (Germany); Institute of Environmental and Sustainable Chemistry, Technische Universitaet Braunschweig, Hagenring 30, D-38106 Braunschweig (Germany); Schripp, Tobias, E-mail: tobias.schripp@wki.fraunhofer.de [Fraunhofer WKI, Department of Material Analysis and Indoor Chemistry, Bienroder Weg 54E, D-38108 Braunschweig (Germany); Salthammer, Tunga [Fraunhofer WKI, Department of Material Analysis and Indoor Chemistry, Bienroder Weg 54E, D-38108 Braunschweig (Germany); Bahadir, Muefit [Institute of Environmental and Sustainable Chemistry, Technische Universitaet Braunschweig, Hagenring 30, D-38106 Braunschweig (Germany)

    2011-09-01

    The ongoing health debate about polymer plasticizers based on the esters of phthalic acid, especially di(2-ethylhexyl) phthalate (DEHP), has caused a trend towards using phthalates of lower volatility such as diisononyl phthalate (DINP) and towards other acid esters, such as adipates, terephthalates, citrates, etc. Probably the most important of these so-called 'alternative' plasticizers is diisononyl cyclohexane-1,2-dicarboxylate (DINCH). In the indoor environment, the continuously growing market share of this compound since its launch in 2002 is inter alia apparent from the increasing concentration of DINCH in settled house dust. From the epidemiological point of view there is considerable interest in identifying how semi-volatile organic compounds (SVOCs) distribute in the indoor environment, especially in air, airborne particles and sedimented house dust. This, however, requires reliable experimental concentration data for the different media and good measurements or estimates of their physical and chemical properties. This paper reports on air concentrations for DINP, DINCH, diisobutyl phthalate (DIBP), diisobutyl adipate (DIBA), diisobutyl succinate (DIBS) and diisobutyl glutarate (DIBG) from emission studies in the Field and Laboratory Emission Cell (FLEC). For DINP and DINCH it took about 50 days to reach the steady-state value: for four months no decay in the concentration could be observed. Moreover, vapor pressures p{sub 0} and octanol-air partitioning coefficients K{sub OA} were obtained for 37 phthalate and non-phthalate plasticizers from two different algorithms: EPI Suite and SPARC. It is shown that calculated gas/particle partition coefficients K{sub p} and fractions can widely differ due to the uncertainty in the predicted p{sub 0} and K{sub OA} values. For most of the investigated compounds reliable experimental vapor pressures are not available. Rough estimates can be obtained from the measured emission rate of the pure compound in a

  8. Soil contamination by phthalate esters in Chinese intensive vegetable production systems with different modes of use of plastic film

    The concentrations of six priority phthalic acid esters (PAEs) in intensively managed suburban vegetable soils in Nanjing, east China, were analyzed using gas chromatography–mass spectrometry (GC–MS). The total PAE concentrations in the soils ranged widely from 0.15 to 9.68 mg kg−1 with a median value of 1.70 mg kg−1, and di-n-butyl phthalate (DnBP), bis-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP) were the most abundant phthalate esters. Soil PAE concentrations depended on the mode of use of plastic film in which PAEs were incorporated as plasticizing agents and both the plastic film and poultry manure appeared to be important sources of soil PAEs. Vegetables in rotation with flooded rice led to lower concentrations of PAEs in soil. The results indicate that agricultural plastic film can be an important source of soil PAE contamination and further research is required to fully elucidate the mechanisms of PAE contamination of intensive agricultural soils with different use modes of use of plastic film. -- Highlights: •Phthalate esters in soils from suburban intensive vegetable production systems were investigated. •Phthalate levels and risks of the vegetable soils with different plastic film use modes were examined. •Sources of phthalate esters in vegetable production soils were analyzed. -- PAE contamination of intensively managed vegetable soils varied widely depending on the mode of use of plastic film in different production systems

  9. Phthalate exposure associated with self-reported diabetes among Mexican women

    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 (ORT3vs.T1=2.66; 95% CI: 0.97-7.33; p for trend=0.063) and MEOHP (ORT3vs.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: → This study evaluated phthalate exposure and diabetes status among Mexican women. → Urinary phthalates metabolite concentrations were used to determine association

  10. Phthalate exposure associated with self-reported diabetes among Mexican women

    Svensson, Katherine [Graduate School of Public Health, Medical Sciences Campus, University of Puerto Rico, San Juan, PR (Puerto Rico); National Institute of Public Health, Universidad No. 655, Col. Santa Maria Ahuacatitlan, Cerrada los Pinos y Caminera, CP. 62100 Cuernavaca, Morelos (Mexico); Hernandez-Ramirez, Raul U.; Burguete-Garcia, Ana [National Institute of Public Health, Universidad No. 655, Col. Santa Maria Ahuacatitlan, Cerrada los Pinos y Caminera, CP. 62100 Cuernavaca, Morelos (Mexico); Cebrian, Mariano E. [Departamento de Toxicologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Mexico City (Mexico); Calafat, Antonia M.; Needham, Larry L. [Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA (United States); Claudio, Luz [Division of International Health, Department of Preventive Medicine, Mount Sinai School of Medicine, NY (United States); Lopez-Carrillo, Lizbeth, E-mail: lizbeth@insp.mx [National Institute of Public Health, Universidad No. 655, Col. Santa Maria Ahuacatitlan, Cerrada los Pinos y Caminera, CP. 62100 Cuernavaca, Morelos (Mexico)

    2011-08-15

    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 (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

  11. High-Throughput and Low-Cost Analysis of Trace Volatile Phthalates in Seafood by Online Coupling of Monolithic Capillary Adsorbent with GC-MS.

    Insuan, Wimonrut; Khawmodjod, Phatchara; Whitlow, Harry J; Soonthondecha, Peerapong; Malem, Fairda; Chienthavorn, Orapin

    2016-04-27

    A simple, sensitive, and high-throughput method was developed for the determination of six volatile phthalate esters-dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), benzylbutyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP)-in seafood samples by using monolith adsorbent in a capillary coupled to a gas chromatography-mass spectrometry (GC-MS) system. The freeze-dried samples were subjected to an ultrasonication with hexane, followed by vortex mixing. The liquid extract was quantitatively determined by a direct application to an online silica monolith capillary adsorbent coupled with a gas chromatograph with mass spectrometric detection. Method validation in seafood matrix gave recoveries of 72.8-85.4% and a detection limit of 6.8-10.0 ng g(-1) for bivalve samples. Reusability of the monolith capillary for trapping coextracted matrix was up to six times, allowing high-throughput analysis at the parts per billion level. When compared with the Food and Environment Research Agency (FERA) method, no significant difference in the result was observed, confirming the method was valid and applicable for the routine analysis of phthalates in seafood samples for food and environmental laboratories. PMID:27082024

  12. Phthalates and diet: a review of the food monitoring and epidemiology data.

    Serrano, Samantha E; Braun, Joseph; Trasande, Leonardo; Dills, Russell; Sathyanarayana, Sheela

    2014-01-01

    Phthalates are associated with a variety of health outcomes, but sources that may be targeted for exposure reduction messaging remain elusive. Diet is considered a significant exposure pathway for these compounds. Therefore, we sought to identify primary foods associated with increased exposure through a review of the food monitoring survey and epidemiological data. A search in PubMed and Google Scholar for keywords "phthalates" and "diet" "food" "food stuffs" "dietary intake" "food intake" and "food concentration" resulted in 17 studies measuring phthalate concentrations in United States (US) and international foods, three epidemiological association studies, and three interventions. We report on food groups with high (≥300 μg/kg) and low (phthalate body burden. Based on these data, we estimated daily intakes of di-2-ethylhexyl phthalate (DEHP) of US women of reproductive age, adolescents and infants for typical consumption patterns as well as healthy and poor diets. We consistently observed high DEHP concentrations in poultry, cooking oils and cream-based dairy products (≥300 μg/kg) across food monitoring studies. Diethyl phthalate (DEP) levels were found at low concentrations across all food groups. In line with these data, epidemiological studies showed positive associations between consumption of meats, discretionary fat and dairy products and DEHP. In contrast to food monitoring data, DEP was found to be associated with intake of vegetables in two studies. DEHP exposure estimates based on typical diets were 5.7, 8.1, and 42.1 μg/kg-day for women of reproductive age, adolescents and infants, respectively, with dairy as the largest contributor to exposure. Diets high in meat and dairy consumption resulted in two-fold increases in exposure. Estimates for infants based on a typical diet exceeded the Environmental Protection Agency's reference dose of 20 μg/kg-day while diets high in dairy and meat consumed by adolescents also exceeded this threshold

  13. Electrochemical impedance spectroscopy based MEMS sensors for phthalates detection in water and juices

    Zia, Asif I.; Mohd Syaifudin, A. R.; Mukhopadhyay, S. C.; Yu, P. L.; Al-Bahadly, I. H.; Gooneratne, Chinthaka P.; Kosel, Jǘrgen; Liao, Tai-Shan

    2013-06-01

    Phthalate esters are ubiquitous environmental and food pollutants well known as endocrine disrupting compounds (EDCs). These developmental and reproductive toxicants pose a grave risk to the human health due to their unlimited use in consumer plastic industry. Detection of phthalates is strictly laboratory based time consuming and expensive process and requires expertise of highly qualified and skilled professionals. We present a real time, non-invasive, label free rapid detection technique to quantify phthalates' presence in deionized water and fruit juices. Electrochemical impedance spectroscopy (EIS) technique applied to a novel planar inter-digital (ID) capacitive sensor plays a vital role to explore the presence of phthalate esters in bulk fluid media. The ID sensor with multiple sensing gold electrodes was fabricated on silicon substrate using micro-electromechanical system (MEMS) device fabrication technology. A thin film of parylene C polymer was coated as a passivation layer to enhance the capacitive sensing capabilities of the sensor and to reduce the magnitude of Faradic current flowing through the sensor. Various concentrations, 0.002ppm through to 2ppm of di (2-ethylhexyl) phthalate (DEHP) in deionized water, were exposed to the sensing system by dip testing method. Impedance spectra obtained was analysed to determine sample conductance which led to consequent evaluation of its dielectric properties. Electro-chemical impedance spectrum analyser algorithm was employed to model the experimentally obtained impedance spectra. Curve fitting technique was applied to deduce constant phase element (CPE) equivalent circuit based on Randle's equivalent circuit model. The sensing system was tested to detect different concentrations of DEHP in orange juice as a real world application. The result analysis indicated that our rapid testing technique is able to detect the presence of DEHP in all test samples distinctively.

  14. Electrochemical impedance spectroscopy based MEMS sensors for phthalates detection in water and juices

    Phthalate esters are ubiquitous environmental and food pollutants well known as endocrine disrupting compounds (EDCs). These developmental and reproductive toxicants pose a grave risk to the human health due to their unlimited use in consumer plastic industry. Detection of phthalates is strictly laboratory based time consuming and expensive process and requires expertise of highly qualified and skilled professionals. We present a real time, non-invasive, label free rapid detection technique to quantify phthalates' presence in deionized water and fruit juices. Electrochemical impedance spectroscopy (EIS) technique applied to a novel planar inter-digital (ID) capacitive sensor plays a vital role to explore the presence of phthalate esters in bulk fluid media. The ID sensor with multiple sensing gold electrodes was fabricated on silicon substrate using micro-electromechanical system (MEMS) device fabrication technology. A thin film of parylene C polymer was coated as a passivation layer to enhance the capacitive sensing capabilities of the sensor and to reduce the magnitude of Faradic current flowing through the sensor. Various concentrations, 0.002ppm through to 2ppm of di (2-ethylhexyl) phthalate (DEHP) in deionized water, were exposed to the sensing system by dip testing method. Impedance spectra obtained was analysed to determine sample conductance which led to consequent evaluation of its dielectric properties. Electro-chemical impedance spectrum analyser algorithm was employed to model the experimentally obtained impedance spectra. Curve fitting technique was applied to deduce constant phase element (CPE) equivalent circuit based on Randle's equivalent circuit model. The sensing system was tested to detect different concentrations of DEHP in orange juice as a real world application. The result analysis indicated that our rapid testing technique is able to detect the presence of DEHP in all test samples distinctively.

  15. Electrochemical impedance spectroscopy based MEMS sensors for phthalates detection in water and juices

    Zia, Asif I

    2013-06-10

    Phthalate esters are ubiquitous environmental and food pollutants well known as endocrine disrupting compounds (EDCs). These developmental and reproductive toxicants pose a grave risk to the human health due to their unlimited use in consumer plastic industry. Detection of phthalates is strictly laboratory based time consuming and expensive process and requires expertise of highly qualified and skilled professionals. We present a real time, non-invasive, label free rapid detection technique to quantify phthalates\\' presence in deionized water and fruit juices. Electrochemical impedance spectroscopy (EIS) technique applied to a novel planar inter-digital (ID) capacitive sensor plays a vital role to explore the presence of phthalate esters in bulk fluid media. The ID sensor with multiple sensing gold electrodes was fabricated on silicon substrate using micro-electromechanical system (MEMS) device fabrication technology. A thin film of parylene C polymer was coated as a passivation layer to enhance the capacitive sensing capabilities of the sensor and to reduce the magnitude of Faradic current flowing through the sensor. Various concentrations, 0.002ppm through to 2ppm of di (2-ethylhexyl) phthalate (DEHP) in deionized water, were exposed to the sensing system by dip testing method. Impedance spectra obtained was analysed to determine sample conductance which led to consequent evaluation of its dielectric properties. Electro-chemical impedance spectrum analyser algorithm was employed to model the experimentally obtained impedance spectra. Curve fitting technique was applied to deduce constant phase element (CPE) equivalent circuit based on Randle\\'s equivalent circuit model. The sensing system was tested to detect different concentrations of DEHP in orange juice as a real world application. The result analysis indicated that our rapid testing technique is able to detect the presence of DEHP in all test samples distinctively.

  16. The influence of resource strategies on childhood phthalate exposure--the role of REACH in a zero waste society.

    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. PMID:25212603

  17. Canine toys and training devices as sources of exposure to phthalates and bisphenol A: quantitation of chemicals in leachate and in vitro screening for endocrine activity.

    Wooten, Kimberly J; Smith, Philip N

    2013-11-01

    Chewing and mouthing behaviors exhibited by pet dogs are likely to lead to oral exposures to a variety of environmental chemicals. Products intended for chewing and mouthing uses include toys and training devices that are often made of plastics. The goal of the current study was to determine if a subset of phthalates and bisphenol A (BPA), endocrine disrupting chemicals commonly found in plastics, leach out of dog toys and training devices (bumpers) into synthetic canine saliva. In vitro assays were used to screen leachates for endocrine activity. Bumper leachates were dominated by di-2-ethylhexyl phthalate (DEHP) and BPA, with concentrations reaching low μg mL(-1) following short immersions in synthetic saliva. Simulated chewing of bumpers during immersion in synthetic saliva increased concentrations of phthalates and BPA as compared to new bumpers, while outdoor storage had variable effects on concentrations (increased DEHP; decreased BPA). Toys leached substantially lower concentrations of phthalates and BPA, with the exception of one toy which leached considerable amounts of diethyl phthalate. In vitro assays indicated anti-androgenic activity of bumper leachates, and estrogenic activity of both bumper and toy leachates. These results confirm that toys and training devices are potential sources of exposure to endocrine disrupting chemicals in pet dogs. PMID:24007620

  18. Lactational exposure of phthalate causes long-term disruption in testicular architecture by altering tight junctional and apoptotic protein expression in Sertoli cells of first filial generation pubertal Wistar rats.

    Sekaran, S; Balaganapathy, P; Parsanathan, R; Elangovan, S; Gunashekar, J; Bhat, F A; Jagadeesan, A

    2015-06-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant and a well-known endocrine disruptor (ED) that interferes with the reproductive function in both humans and animals. This study aimed to find out the impact of lactational exposure of DEHP in testes of first filial generation (F1) progeny male rat postnatal day (PND)-60. Lactating dams were orally treated with DEHP (0, 1, 10 and 100 mg/kg body weight/day, respectively) from the PND-1 to PND-21. Rats were killed at PND 60. Testes were removed and used for histological analysis and for isolation of Sertoli cells (SCs). The histoarchitecture of DEHP-treated rats showed disturbed testicular structure. DEHP-treated rats also showed increased oxidative stress by decreasing antioxidant levels in the SCs; it disrupted SC tight junctional proteins occludin, claudin, junctional adhesion molecule, zona occludens protein-1 (ZO-1), zona occludens protein-2 (ZO-2), and afadin-6 (AF-6), increased apoptosis by altering the apoptotic genes Bax, cytochrome c, caspase-8, -9, -3 and antiapoptotic gene Bcl-2. It is concluded that early postnatal exposure to DEHP disturbs histoarchitecture of testis and SC function in pubertal Wistar rats. PMID:25352649

  19. Prenatal Exposure to Phthalate Esters and Behavioral Syndromes in Children at 8 Years of Age: Taiwan Maternal and Infant Cohort Study

    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

  20. Rapid and molecular selective electrochemical sensing of phthalates in aqueous solution

    Zia, Asif I.

    2015-05-01

    Reported research work presents real time non-invasive detection of phthalates in spiked aqueous samples by employing electrochemical impedance spectroscopy (EIS) technique incorporating a novel interdigital capacitive sensor with multiple sensing thin film gold micro-electrodes fabricated on native silicon dioxide layer grown on semiconducting single crystal silicon wafer. The sensing surface was functionalized by a self-assembled monolayer of 3-aminopropyltrietoxysilane (APTES) with embedded molecular imprinted polymer (MIP) to introduce selectivity for the di(2-ethylhexyl) phthalate (DEHP) molecule. Various concentrations (1-100. ppm) of DEHP in deionized MilliQ water were tested using the functionalized sensing surface to capture the analyte. Frequency response analyzer (FRA) algorithm was used to obtain impedance spectra so as to determine sample conductance and capacitance for evaluation of phthalate concentration in the sample solution. Spectrum analysis algorithm interpreted the experimentally obtained impedance spectra by applying complex nonlinear least square (CNLS) curve fitting in order to obtain electrochemical equivalent circuit and corresponding circuit parameters describing the kinetics of the electrochemical cell. Principal component analysis was applied to deduce the effects of surface immobilized molecular imprinted polymer layer on the evaluated circuit parameters and its electrical response. The results obtained by the testing system were validated using commercially available high performance liquid chromatography diode array detector system.

  1. Rapid and molecular selective electrochemical sensing of phthalates in aqueous solution.

    Zia, Asif I; Mukhopadhyay, Subhas Chandra; Yu, Pak-Lam; Al-Bahadly, I H; Gooneratne, Chinthaka P; Kosel, J Rgen

    2015-05-15

    Reported research work presents real time non-invasive detection of phthalates in spiked aqueous samples by employing electrochemical impedance spectroscopy (EIS) technique incorporating a novel interdigital capacitive sensor with multiple sensing thin film gold micro-electrodes fabricated on native silicon dioxide layer grown on semiconducting single crystal silicon wafer. The sensing surface was functionalized by a self-assembled monolayer of 3-aminopropyltrietoxysilane (APTES) with embedded molecular imprinted polymer (MIP) to introduce selectivity for the di(2-ethylhexyl) phthalate (DEHP) molecule. Various concentrations (1-100 ppm) of DEHP in deionized MilliQ water were tested using the functionalized sensing surface to capture the analyte. Frequency response analyzer (FRA) algorithm was used to obtain impedance spectra so as to determine sample conductance and capacitance for evaluation of phthalate concentration in the sample solution. Spectrum analysis algorithm interpreted the experimentally obtained impedance spectra by applying complex nonlinear least square (CNLS) curve fitting in order to obtain electrochemical equivalent circuit and corresponding circuit parameters describing the kinetics of the electrochemical cell. Principal component analysis was applied to deduce the effects of surface immobilized molecular imprinted polymer layer on the evaluated circuit parameters and its electrical response. The results obtained by the testing system were validated using commercially available high performance liquid chromatography diode array detector system. PMID:25218198

  2. Application of ozone, UV and ozone/UV processes to reduce diethyl phthalate and its estrogenic activity

    A research study to monitor the micropollutant levels present in the Han River, a major drinking water source for the Seoul Metropolitan district in Korea, was performed over a five-year period from 2000 to 2004, inclusive. Of the detected micropollutants, phthalates were found to be the major contaminants. In this study, the estrogenic activities of the detected phthalates and raw water samples contaminated with the pollutants were assessed by the E-screen assay using the MCF-7 breast cancer cell line. Of the phthalates, diethyl phthalate (DEP) and di(2-ethylhexyl) phthalate (DEHP) showed relatively high cell proliferation. Using DEP as a phthalate probe, three candidate processes, ozone alone, UV alone, and the ozone/UV combined, were evaluated for their efficiency in removing DEP and reducing its estrogenic activity. The ozone/UV process was shown to have the highest efficiency for the elimination of DEP and its by-products, leading to the complete mineralization of DEP. This study also found that the ozone/UV process is the best candidate to reduce the estrogenicity induced by DEP and its by-products

  3. Preparation and Application in Solid-phase Extraction of Di (2-ethylhexyl) phthalate Surface Imprinted Polymers%邻苯二甲酸二异辛酯表面印迹聚合物的制备及其固相萃取应用

    刘玉楠; 张朝晖; 张明磊; 陈星; 陈红军; 聂利华

    2013-01-01

    Surface molecularly imprinted polymer(H-SiO2@MIP) based on hybrid silica microspheres was prepared by using di(2-ethylhexyl)phthalate( DIOP) as the template molecule, methacrylic acid(MAA) as the functional monomer and ethylene glycol dimethacrylate(EGDMA) as the cross-linking agent. The H-SiO2 @ MIP was characterized by scanning electron microscope ( SEM) and infrared spectroscopy(IR). The results showed that DIOP imprinted layer was grafted on particles surface successfully. The H-SiO2@ MIP has uniform spherical structure and the thickness of imprinted shell is about 60 ~ 70 nm. The adsorption properties were investigated by high performance liquid chromatography, and results demonstrated that the H-SiO2@MIP exhibited specific selectivity towards DIOP. The maximum adsorption capacity of H-SiO2 @ MIP was 50.35 mg/g, and the selectivity factor of DIOP towards dibutyl phthalate (DBP) and dimethyl phthalate (DEP) was 2.31 and 2.47, respectively. Packed into a solid-phase extraction ( SPE) column, the H-SiO2@ MIP could separate and enrich DIOP from milk sample.%采用复合二氧化硅微球(H-SiO2)作为载体,以邻苯二甲酸二异辛酯(DIOP)为模板分子,甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(EGDMA)为交联剂,制备了邻苯二甲酸二异辛酯表面印迹聚合物(H-SiO2@MIP).分别采用扫描电子显微镜和红外光谱对该印迹聚合物进行了观察和表征,结果表明,制备出的印迹聚合物呈球形,印迹壳层厚度为60 ~70 nm.采用高效液相色谱技术对该印迹聚合物的吸附性能进行了检测,结果表明,该印迹聚合物对塑化剂DIOP表现出特异性吸附性能,最大吸附容量为50.35 mg/g,DIOP对于邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二乙酯(DEP)的选择因子(β)分别为2.31和2.47.将该印迹聚合物装填于固相萃取柱中,结合液相色谱检测技术,能对牛奶样品中的塑化剂DIOP进行有效分离、富集和检测.

  4. Phthalate Esters Used as Plasticizers in Packed Red Blood Cell Storage Bags May Lead to Progressive Toxin Exposure and the Release of Pro-Inflammatory Cytokines

    Leonard T. Rael

    2009-01-01

    Full Text Available Phthalate esters (PE's are plasticizers used to soften PVC-based medical devices. PE's are the most abundant man-made pollutants and increase the risk of developing an allergic respiratory disease or a malignancy. The leaching of PE's in donated packed red blood cells (PRBC during storage was assessed. PRBC transfusion bags containing CPD/AS-1 (ADSOL buffer were analyzed. Samples were collected on storage day 1 and day 42. Two PE's, di-(2-ethylhexyl phthalate (DEHP and mono-(2-ethylhexyl phthalate (MEHP, were measured by liquid chromatography coupled to mass spectrometry (LCMS. Interleukin-8 (IL-8 was measured by standard ELISA techniques. DEHP significantly increased from 34.3 µM (±20.0 SD on day 1 to 433.2 µM (±131.2 SD on day 42, a 12.6-fold increase. Similarly, MEHP significantly increased from 3.7 µM (±2.8 SD on day 1 to 74.0 µM (±19.1 SD on day 42, a 20.2-fold increase. Also, DEHP and MEHP increased the release of IL-8 from human umbilical vein endothelial cells (HUVEC. The transfusion of older units of PRBC could lead to an accumulation of PE's possibly resulting in inflammation and other effects. This accumulation could be exacerbated due to the decreased metabolism of PE's since trauma patients have a lower esterase activity, the enzymes responsible for metabolizing PE's. The effect of oxidative stress caused by PE's is discussed as a potential mechanism for increases in inflammation caused by older units of PRBC.

  5. Mono-2-ethyhexyl phthalate advancing the progression of prostate cancer through activating the hedgehog pathway in LNCaP cells.

    Yong, Wang; Jiao, Chen; Jianhui, Wu; Yan, Zhao; Qi, Pan; Xiu, Wang; Zuyue, Sun; Yunhui, Zhang

    2016-04-01

    Hedgehog (Hh) pathway plays a critical role in the progression of prostate cancer (PCa), the most commonly diagnosed non-cutaneous cancer in male adults. Studies showed that di-n-butyl phthalate (DBP) could interference with the Hh pathway. Di-2-ethylhexyl phthalate (DEHP), the congener of DBP, is the major plasticizer used in plastic materials that are inevitably exposed by patients with PCa. The aim of this in vitro study was to investigate whether mono-2-ethyhexyl phthalate (MEHP, the active metabolite of DEHP) could activate the Hh pathway of LNCaP cells. Results showed that the expression of the critical gene of Hh pathway PTCH and androgen-regulated gene KLK3 was significantly decreased on 3, 6 and 9days with Hh pathway inhibitor cyclopamine's treatment. MEHP notably up-regulated the expression of PTCH with a dose-response relationship in the presence of cyclopamine, which indicate that MEHP might target on the downstream components of Hh pathway and advance the progression of PCa through activating the Hh pathway. PMID:26710974

  6. Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children.

    Larsson, Kristin; Ljung Björklund, Karin; Palm, Brita; Wennberg, Maria; Kaj, Lennart; Lindh, Christian H; Jönsson, Bo A G; Berglund, Marika

    2014-12-01

    Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood. The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6-11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother-child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors. There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 μg/L; ΣDiNP 37.8 μg/L; MBzP 19.9 μg/L; MnBP 76.9 μg/L) than the mothers (ΣDEHP 38.4 μg/L; ΣDiNP 33.8 μg/L; MBzP 12.8 μg/L; MnBP 63.0 μg/L). Conversely, the mother's levels of parabens (MetP 37.8 μg/L; ProP 13.9 μg/L) and MEP (43.4 μg/L) were higher than the children's levels of parabens (MetP 6.8 μg/L; ProP 2.1 μg/L) and MEP (28.8 μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p=personal care products. PMID:25216151

  7. Intake of phthalate-tainted foods alters thyroid functions in Taiwanese children.

    Ming-Tsang Wu

    Full Text Available BACKGROUND: On April-May, 2011, two Taiwan chemical companies were found to have intentionally added phthalates, Di-(2-ethylhexyl phthalate (DEHP and/or Di-isononyl phthalate, as a substitute of emulsifier to many foodstuffs. This study aimed to investigate whether exposure to these foods altered endocrine functions in children aged ≤10 years and, if so, whether those changes could be reversed by stopping exposure. METHODS: One Phthalates Clinic for Children was established in southern Taiwan between May 31 and June 17, 2011. All eligible children had their exposure information, blood and/or urine specimens collected. Endocrine functions were assessed in serum. The exposure groups were categorized into three (High, >500 ppm, Low, 1-500 ppm, and No, <1 ppm of DEHP. After six months, some children were followed up for the selected endocrine hormones. RESULTS: Sixty children were eligible in this study; all were Tanner stage 1 with no pubic hair. Compared to non-exposed group, both high and low exposure groups had significantly lower serum thyroid-stimulating hormone (TSH levels (P = 0.001 and 0.024. At six months follow-up, serum triiodothyronine (T3 levels was significantly changed (P = 0.034 in high exposure group (n = 13. For serum estradiol (E2, the detectable rate (≥8 pg/mL decreased from 76.9% (10/13 to 30.8% (4/13 (P = 0.070. CONCLUSIONS: This study shows that serum TSH levels can be altered when children were exposed to high concentrations of phthalate-tainted foodstuffs. Serum E2 and T3 may be partially recovered after stopping exposure.

  8. Age and Sex-Specific Relationships between Phthalate Exposures and Obesity in Chinese Children at Puberty

    Li, Dan; Zhao, Lifang; Zhao, Yan; Li, Luxi; Shi, Huijing

    2014-01-01

    Objective To examine the age and sex-specific associations of urine levels of six mono-phthalates with body size and fat distribution in Chinese children at puberty. Materials and Methods Four hundred and ninety-three school-aged children (247 boys, 246 girls) were recruited. Obesity related anthropometric indices were measured and body fat proportion (BF%) was calculated. Spot urine samples were collected and phthalate monoesters were detected by an API 2000 electrospray triple quadrupole mass spectrometer (ESI-MS/MS). Associations between phthalate exposure and overweight/obesity measures and their trends were examined by multiple linear regression and Logistic regression analyses, respectively. Results Di-2-ethylhexyl phthalate (DEHP) metabolites and monobutyl phthalate (MBP) were found to be the most detectable chemicals. In 8–10 years (yrs) group, concentrations of MEHP and MBP were significantly higher in girls than those in boys. However, concentrations of all phthalate monoesters, except for MEP and MEHP, in 11–13 yrs boys were significantly higher than those in girls. After adjusting for confounders including puberty onset, urinary concentrations of MBP and sum of low molecular-weight phthalate metabolites (∑LMP) were positively associated with boys' obesity in a concentration-effect manner, while concentrations of MEHP, MEHHP and sum of DEHP metabolites (∑MEHP) were negatively associated with girls' obesity. Associations between phthalate exposure levels and BMI z-score changes were age- and sex-specific in school-age children. Conclusion There are age and sex-specific concentration-effect associations between phthalate exposure and fat distribution in Chinese children. Urinary phthalate levels in 11–13 yrs boys were about 30 percent higher than those in girls, and ∑MEHP levels in younger boys (10 yrs). Associations were positive for MBP and ∑LMP with both BMI z-score and fat distribution in boys >10 years of age, and negative for

  9. MIGRATION OF PHTHALATES FROM PLASTIC TANK TO VEGETABLE OIL AS A PART OF FEEDING MIXTURES USED FOR CHICKEN BROILERS FATTENING

    Pavel Suchý

    2010-05-01

    Full Text Available The concentrations of phthalic acid esters (PAEs as di-n-butyl phthalate (DBP and di-2-ethylhexyl phthalate (DEHP were measured in samples of rapeseed oil, which was used as a feed. First samples were collected during the production process and second after the storage in plastic tank (21 days. The results of measurements are that there is 2.93-10.10 mg PAEs.kg-1 in the oil before storage and 22.73-61.55 mg PAEs.kg-1 after storage. For the monitoring of distribution and accumulation of PAEs in animal tissues and organs (muscles, adipose tissue, skin and liver broiler chicks ROSS 308 were used. The chicks were divided into 4 groups (50 chicks each. All the chicks were fed by commercial diets (complete feed, KKS for broiler chicks (starter – BR1; grower – BR2 and finisher – BR3. The experimental diets were supplemented with vegetable oil (RO with low (group N or high (group V phthalate content, or animal fat with high phthalate content (group Z. Neither the control diets (K nor the grower (BR1 diets contained vegetable oil or animal fat. DBP and DEHP were found in all tissues of all chicks. The highest concentration of DBP of 1.28 1.00 mg.kg-1 of fresh sample (an average value from 8 chicks was determined in the adipose tissue of V chicks. The highest concentration of DEHP of 3.27 2.87 mg.kg-1 of fresh sample (average of 8 chicks was also determined in the V group. doi:10.5219/49

  10. Organophosphorus flame retardants and phthalate esters in indoor dust from different microenvironments: Bioaccessibility and risk assessment.

    He, Ruiwen; Li, Yunzi; Xiang, Ping; Li, Chao; Zhou, Chunyang; Zhang, Shujun; Cui, Xinyi; Ma, Lena Q

    2016-05-01

    Incidental ingestion of indoor dust is an important pathway for human exposure to organophosphorus flame retardants (OPFRs) and phthalate esters (PAEs). However, little is known about their bioaccessibility in indoor dust. In this study, indoor dust samples were collected from houses, offices, public microenvironments (PMEs), and university dorms, and physiologically based extraction test (PBET) was used to measure the bioaccessibility of OPFRs and PAEs in these dust samples. Total concentrations of OPFRs in dust samples ranged from 0.01 to 63.2 μg g(-1), with significantly lower concentrations in dorm dust (median = 0.30 μg g(-1)) than those in houses (3.12), offices (5.94), and PMEs (11.6). Total PAEs ranged from 5.49 to 2161 μg g(-1) with significantly lower concentrations in dorm dust (379 μg g(-1)) than those in the other three types of dust (767, 515, and 731 μg g(-1)). When subject to PBET, the bioaccessibility of OPFRs ranged from 8.18% (triphenyl phosphate) to 54.5% (Tris(2-chloroisopropyl) phosphate) for OPFRs, and from 1.21% (di-2-ethylhexyl phthalate, DEHP) to 81.1% (dimethyl phthalate) for PAEs. Estimated exposure doses for adults and infants to OPFRs via dust ingestion were much lower than the reference doses (RfD), but intake dose of DEHP for infants was higher than the RfD of 20 μg kg(-1) d(-1). However, the DEHP intake dose did not exceed the RfD after incorporating bioaccessibility into risk assessment. Our data indicated the importance of considering contaminant bioaccessibility during risk assessment of indoor dust. PMID:26585356

  11. Phthalate treatment does not influence levels of IgE or Th2 cytokines in B6C3F1 mice

    Bronchial asthma is mediated, in part, by the immunoregulatory cytokines interleukins 4 and 13 (IL-4 and IL-13). These cytokines stimulate IgE synthesis that in turn is associated with airway hyper-responsiveness. Compounds that stimulate IgE synthesis and elicit bronchial reactivity are generally considered to be respiratory sensitizers. Recently, it has been hypothesized that exposure to phthalates may contribute to childhood asthma. To address this question, di-(2-ethylhexyl) phthalate (DEHP) was tested using a protocol adapted from work by Dearman that involves topical application (and challenge) of test substances to mice followed by measurements of total serum IgE. In addition, auricular lymph nodes were harvested for measurement of IL-4 and IL-13 proteins and their corresponding messenger RNAs. Because skin absorption of high molecular weight phthalates is limited, liver weight increase, a measure of peroxisomal proliferation, was monitored to assure that internal dosing had been achieved. ELISA and RNAse protection assays demonstrated that DEHP treatment did not significantly affect IgE, IL-4, or IL-13 levels. Similarly, IL-4 and IL-13 mRNA levels were not elevated. In contrast, all of these were significantly elevated by trimellitic anhydride (TMA), a respiratory sensitizer used as the positive control in this assay. Liver weights were significantly elevated by DEHP, providing evidence of sufficient percutaneous absorption to induce physiological responses. To extend these observations, three other commercial phthalate ester plasticizers, di-isononyl phthalate (DINP), di-isohexyl phthalate (DIHP), and butyl benzyl phthalate (BBP), were assessed using the same protocol. As above, ELISA and RNAse protection assays showed that IgE, IL-4, and IL-13 proteins, and IL-4 and IL-13 mRNAs in the phthalate-treated animals were all at levels similar to that of control values. The positive control, TMA, produced large, statistically significant increases in all

  12. The effect of di-(-2-ethyl hexyl phthalate (Dehp as plasticizer on the thermal and mechanical properties of pvc/pmma blends

    Kamira Aouachria

    2014-08-01

    Full Text Available Plasticizers play a key role in the formulation of polymers and in determining their physical properties and processability. This study examines the effect of di(2-ethyl hexylphthalate (DEHP as plasticizer on the thermal and mechanical properties of PVC/PMMA blends. For that purpose, blends of variable composition, from 0 to 100 wt%, were prepared in the presence (15, 30 and 50 wt % and in the absence of di(2-ethyl hexylphthalate. The thermal degradation of the blends was investigated by thermogravimetric analysis (TGA in an atmosphere of synthetic air in the temperature range of 50-550°C. The variation of the mechanical properties, such as tensile behavior, hardness and impact resistance, were investigated for all blend compositions. The effect of the plasticizer on the same properties was considered. The results obtained show that a range of properties can be generated according to the blend compositions. Therefore, the addition of PMMA to the blends stabilized PVC, for the initial thermal degradation, and the addition of the plasticizer caused a decrease of stress at break and Young modulus.

  13. Technique for rapid detection of phthalates in water and beverages

    Zia, Asif I.

    2013-05-01

    The teratogenic and carcinogenic effects of phthalate esters on living beings are proven in toxicology studies. These ubiquitous food and environmental pollutants pose a great danger to the human race due to their extraordinary use as a plasticizer in the consumer product industry. Contemporary detection techniques used for phthalates require a high level of skills, expensive equipment and longer analysis time than the presented technique. Presented research work introduces a real time non-invasive detection technique using a new type of silicon substrate based planar interdigital (ID) sensor fabricated on basis of thin film micro-electromechanical system (MEMS) semiconductor device fabrication technology. Electrochemical impedance spectroscopy (EIS) was used in conjunction with the fabricated sensor to detect phthalates in deionized water. Various concentrations of di(2-ethylhexyl) phthalate (DEHP) as low as 2 ppb to a higher level of 2 ppm in deionized water were detected distinctively using new planar ID sensor based EIS sensing system. Dip testing method was used to obtain the conductance and dielectric properties of the bulk samples. Parylene C polymer coating was used as a passivation layer on the surface of the fabricated sensor to reduce the influence of Faradaic currents. In addition, inherent dielectric properties of the coating enhanced the sensitivity of the capacitive type sensor. Electrochemical spectrum analysis algorithm was used to model experimentally observed impedance spectrum to deduce constant phase element (CPE) equivalent circuit to analyse the kinetic processes taking place inside the electrochemical cell. Curve fitting technique was used to extract the values of the circuit components and explain experimental results on theoretical grounds. The sensor performance was tested by adding DEHP to an energy drink at concentrations above and below the minimal risk level (MRL) limit set by the ATSDR (Agency for Toxic Substances & Disease Registry

  14. Assessment of Phthalate-induced Changes in Fetal Rat Testis Gene Expression using an rt-PCR Drug Metabolism Array.

    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 ...

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

    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. Σ16PAEs concentrations ranged from 0.195 to 33.6 μg 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 R2 = 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. - PAEs are determined in agricultural soils at high concentration levels, which imply a potential risk for the food chain

  16. Dissolution and Safety of Plasticizer DEHP during Medical Procedures%医疗途径中增塑剂DEHP的溶出及其安全性研究概况

    陈琳; 钱青; 张喆; 张恩娟

    2011-01-01

    OBJECTIVE: To investigate the dissolution of plasticizer di-(2-ethylhexyl) phthalate (DEHP) during medical procedure and provide reference for its safety evaluation. METHODS: The safety of patients when they used PVC medical device were analyzed from physico-chemical property of DEHP, toxic effect, dissolution, pharmacokinetics, patients intake and tolerable intake (TI), international regulations of DEHP medical device by reviewing pertinent literature. RESULTS: DEHP was easily released from medical devices and produced chronic toxiciry which depended on patient intake and individual sensitivity after entering the body. The infants were at increasing risk from exposing to DEHP undergoing total parenteral nutrition and enteral nutrition, exchange transfusion and ECMO. The adult patients were at increasing risk from exposing to DEHP receiving transfused with large volumes of blood, ECMO, artificial heart transplantation, coronary artery bypass and enteral nutrition. CONCLUSION: Patients are at high risk when the dose of DEHP received by patients exceeds the TI, to which a great attention should be paid.%目的:为了解医疗途径中增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)的溶出及其对人体的安全性提供参考.方法:查阅相关文献,从DEHP的理化性质、毒性作用、溶出及体内药动学、各种医疗途径中人体的摄入量及耐受摄入量、目前国际上对含DEHP医疗器材的规定等方面进行分析.结果:DEHP易从聚氯乙烯医疗器材中溶出,进入人体后产生慢性毒性,毒性大小取决于摄入量和个体敏感性,其中新生儿接受全静脉营养、肠道营养、换血、体外心肺循环以及成人接受肠道营养、大量输血(外伤)、体外心肺循环、冠状动脉绕道、人工心脏移植等医疗途径时,会处于DEHP介导的不良反应的高风险中.结论:部分医疗途径中存在因DEHP释放使人体摄入量超过了耐受摄入量而产生危害的风险,应引起有关方面的高度重视.

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

    Dévier, Marie-Hélène; Le Menach, Karyn [Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC, UMR 5805 CNRS), Laboratoire de Physico- et Toxico-Chimie de l' Environnement (LPTC), Université de Bordeaux, 351 cours de la Libération, 33405 Talence cedex (France); Viglino, Liza [Danone Waters Analytical Center, Aqualab, Place de la Gare, 74500 Evian-Les-Bains (France); Di Gioia, Lodovico [Danone Research, R and D Waters Division, RD 128, 91767 Palaiseau Cedex (France); Lachassagne, Patrick [Danone Waters France, Environment and Water Resources Division, BP 87, 11 av. Général Dupas, 74500 Evian-Les-Bains cedex (France); Budzinski, Hélène, E-mail: h.budzinski@epoc.u-bordeaux1.fr [Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC, UMR 5805 CNRS), Laboratoire de Physico- et Toxico-Chimie de l' Environnement (LPTC), Université de Bordeaux, 351 cours de la Libération, 33405 Talence cedex (France)

    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

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

    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

  19. Prenatal phthalate exposures and anogenital distance in Swedish boys

    Bornehag, Carl-Gustaf; Carlstedt, Fredrik; Jönsson, Bo Ag;

    2015-01-01

    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...... distance in Swedish boys. Environ Health Perspect 123:101-107; http://dx.doi.org/10.1289/ehp.1408163....

  20. Maternal in utero exposure to di-(2-ethylhexyl) phthalate affects the heart of adult female offspring%宫内暴露邻苯二甲酸二酯对子代雌性成年大鼠心脏的影响

    赵青松; 方瑞; 吴德; 都鹏飞

    2014-01-01

    Objective To investigate the cardiac effects of DEHP exposure during pregnancy on female rats off-spring. Methods Pregnant SD rats were gavaged from gestationa day 0 until birth with corn oil, low [ 10 mg/( kg·d) ] dose DEHP and high [100 mg/( kg·d) ] dose DEHP. Each group consists of two pregnant dams. The outcomes of general morphometry( weight) , cardiac histology and cardiac function were studied. Results ①When exposed to DEHP during pregnancy, body weight of female rats offspring increased from PND 0 (Postnatal day 0) to PND 70 . The increase level of weight was significantly higher in high dose group at PND 70 ( P <0.05 ) . ②Compared with control group and low dose DEHP group, the heart rate ( HR) and left ventricular end-diastolic pres-sure ( LVEDP) of female adult rats were deteriorated in the high dose DEHP group, while left ventricular systolic pressure ( LVSP) , maximal rise velocity of left ventricular pressure ( +dp/dtmax ) and maximal fall velocity of left ventricular pressure ( -dp/dtmax) of that were significantly decreased (P<0.05). ③The cardiac histology effects of high dose DEHP exposure as follows:Pathological observation demonstrated cardiac myocyte hypertrophy, myo-cardial fiber disarray, a large number of myocardial cells karyopycnosis and stained;electron microscopy showed a lot of myocardial cells karyopycnosis and stained, myocardial fiber disorder and fracture arrangement, most of mito-chondrial cristae were broken and blurred. However, no obvious change was found in the control group and low dose DEHP group. Conclusion High dose DEHP exposure in utero may lead weight increase, hemodynamic and myocardial abnormalities of female rats offspring.%目的探讨邻苯二甲酸二(2-乙基己基)酯(DEHP)宫内暴露对子代雌性大鼠心脏的影响。方法自妊娠第1天直至分娩,SD妊娠大鼠分别予以灌胃玉米油、低剂量[10 mg/(kg·d)]DEHP、高剂量[100 mg/(kg·d)]DEHP。观察各组子代雌性大鼠一般状况(

  1. Assessment of chemical coexposure patterns based upon phthalate biomonitoring data within the 2007/2008 National Health and Nutrition Examination Survey

    Qian, Hua; Chen, Min; Kransler, Kevin M; Zaleski, Rosemary T

    2014-01-01

    As regulatory initiatives increasingly call for an understanding of the cumulative risks from chemical mixtures, evaluating exposure data from large biomonitoring programs, which may inform these cumulative risk assessments, will improve the understanding of occurrence and patterns of coexposures. Here we have analyzed the urinary metabolite data for six phthalates (di-butyl phthalate; di-isobutyl phthalate; butyl-benzyl phthalate; bis(2-ethylhexyl) phthalate; di-isononyl phthalate; and di-is...

  2. Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis

    Boberg, Julie; Petersen, Marta Axelstad; Vinggaard, Anne;

    2006-01-01

    Phthalates are widely used as plasticizers in various consumer products and building materials. Some of the phthalates are known to interfere with male reproductive development in rats, and di-n-butyl phthalate (DBP), diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP) were recently...... histopathology. DiBP has similar testicular and developmental effects as DBP and DEHP, and although more developmental and especially postnatal studies are needed to clearly identify the reproductive effects of DiBP, this study indicates a reason for concern about the use of DiBP as a substitute for DBP. (c...

  3. Performance and mechanisms for the removal of phthalates and pharmaceuticals from aqueous solution by graphene-containing ceramic composite tubular membrane coupled with the simultaneous electrocoagulation and electrofiltration process.

    Yang, Gordon C C; Chen, Ying-Chun; Yang, Hao-Xuan; Yen, Chia-Heng

    2016-07-01

    In this study, commonly detected emerging contaminants (ECs) in water, including di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), cephalexin (CLX), sulfamethoxazole (SMX) and caffeine (CAF), were selected as the target contaminants. A lab-prepared graphene-containing ceramic composite tubular membrane (TGCCM) coupled with the simultaneous electrocoagulation and electrofiltration process (EC/EF) in crossflow filtration mode was used to remove target contaminants in model solution. Meanwhile, a comparison of the removal efficiency was made among various tubular composite membranes reported, including carbon fibers/carbon/alumina composite tubular membrane (TCCACM), titania/alumina composite tubular membrane (TTACM) and alumina tubular membrane (TAM). The results of this study showed that the removal efficiencies for DnBP and DEHP were 99%, whereas 32-97% for cephalexin (CLX), sulfamethoxazole (SMX) and caffeine (CAF). In this work the mechanisms involved in removing target ECs were proposed and their roles in removing various ECs were also discussed. Further, two actual municipal wastewaters were treated to evaluate the applicability of the aforementioned treatment technology (i.e., TGCCM coupled with EC/EF) to various aqueous solutions in the real world. PMID:27131034

  4. A Study on Effects of DEHP on Infant Health%PVC增塑剂DEHP对婴儿健康的影响研究

    于晋泽; 刘大鹏; 胡云峰; 冯爽

    2007-01-01

    作为最普遍使用的增塑剂Di-(2-ethylhexyl)-phthalate(DEHP,邻苯二甲酸二异辛酯)因Polyvinyl chloride(PVC,聚氯乙烯)在人类生活中被广泛应用而在环境中到处存在,已成为一种公认的环境污染物.阐述了DEHP通过日常生活、饮食、药物、母乳及医疗设备等途径对婴儿健康的危害程度.通过定量数据分析了婴儿接触DEHP的安全尺度.指出研究已经证实婴儿与成人对DEHP有着不同的药物代谢动力学和新陈代谢,婴儿是受DEHP危害最敏感的人群.

  5. Phthalate Metabolites, Consumer Habits and Health Effects

    Peter Wallner

    2016-07-01

    Full Text Available 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.

  6. Phthalate monoesters in association with uterine leiomyomata in Shanghai.

    Sun, Jing; Zhang, Mei-Ru; Zhang, Li-Qian; Zhao, Dong; Li, Shu-Guang; Chen, Bo

    2016-06-01

    Phthalates are ubiquitous environmental pollutants because of the broad use of plastics. We conducted a case-control study to determine whether uterine leiomyomata were related to exposure to phthalates. Urine specimens and questionnaires were collected from 61 cases and 61 age-matched controls. Nine phthalate monoesters were determined by ultra performance liquid chromatography coupled with tandem mass spectroscopy. Cases had significantly higher levels of creatinine-adjusted mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), total di(2-ethylhexyl) phthalate metabolites (∑DEHPmet), and total dibutyl phthalate metabolites (∑DBPmet) than controls. After adjusting for potential confounders, logistic regression analyses demonstrated that leiomyomata were positively associated with MiBP, MnBP, MEHP, MEHHP, MECPP, ∑DEHPmet, and ∑DBPmet. In summary, our data support the hypothesis that uterine leiomyomata are related to phthalate exposure. PMID:26608625

  7. The concentrations of phthalates in settled dust in Bulgarian homes in relation to building characteristic and cleaning habits in the family

    Kolarik, Barbara; Bornehag, Carl-Gustaf; Naydenov, Kiril Georgiev;

    2008-01-01

    . 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...

  8. DEHP诱导的氧化应激致小鼠学习记忆能力的下降和维生素E的保护作用%Decreased Learning and Memory Ability Caused by the Oxidative Stress Induced by DEHP and the Protection Effect of Vitamin E in Mice

    程静菲; 尚帅; 何贵波; 刘晓帆; 唐佳琦; 熊国梅; 廖晓梅; 杨旭

    2012-01-01

    Objective To study the impairment effect of DEHP on the abilities of learning and memory in KM mice and discuss its relationship with oxidative damage induced by DEHP in the brain. Methods Thirty - six male KM mice were randomly divided into 4 groups (n =9 for each group), including control group (Saline), DEHP treatment group (50mg/kg DEHP), vitamin E protection group (50mg/kg DEHP +50mg/kg VitE), VitE control group (50mg/kg VitE). With the constant exposure for ten days, the Morris water maze was used to test the abilities of learning and memory. Then the reactive oxygen species ( ROS) level and malondialdehyde (MDA) content of brains were measured. Results The results of MWM showed that the mice only treated with DEHP had a poorer learning and memory ability compared with the control group (P < 0.05 ) , and VitE could protect the mice from the impairment of DEHP. The DEHP group had a significantly higher ROS and MDA level in their brains compared with the other three groups, and VitE reduced its increase. Meanwhile, the VitE control group had no significant difference. Conclusion These results suggested that VitE could protect Kunming mice from the learning and memory impairment induced by the DEHP, which might result from the oxidative damage in their brain.%目的 研究邻苯二甲酸二乙基己酯(Di -2 - ethylhexyl phthalate,DEHP)对小鼠学习记忆能力的影响与其在脑组织造成氧化损伤的关系.方法 36只雄性昆明小鼠随机分成4组,每组9只,分别为空白对照组(生理盐水)、DEHP染毒组(50mg/kg DEHP)、维生素E(vitamin E)保护组(50mg/kg DEHP +50mg/kg维生素E)、维生素E对照组(50mg/kg维生素E).每天清晨灌胃1次,连续10天.期间进行Morris水迷宫测试,检验小鼠的学习记忆能力变化,10天后将小鼠处死,取出脑组织,检验ROS及MDA含量.结果 Morris水迷宫结果显示,DEHP染毒组小鼠学习记忆能力与对照组相比显著下降(P<0.05),而维生素E作为抗氧化剂在一

  9. Phthalates as developmental reproductive toxicants

    PE are a large family ofcompounds used in a wide array ofconsumer, industrial and medical products. Studies have shown that in utero treatment with PE such as diethyl hexyl phthalate (DEHP) during the critical period offetal reproductive development produced male reproductive mal...

  10. Simulation of DEHP biodegradation and sorption during the anaerobic digestion of secondary sludge

    Fountoulakis, M.S.; Stamatelatou, K.; Batstone, Damien J.;

    2006-01-01

    Di-ethylhexyl phthalate (DEHP) has commonly been found in the sludge of municipal wastewater treatment plants especially during anaerobic processing. It is slowly biodegradable under anaerobic conditions. Due to its high hydrophobicity, sorption-desorption processes can be rate-limiting for the c......Di-ethylhexyl phthalate (DEHP) has commonly been found in the sludge of municipal wastewater treatment plants especially during anaerobic processing. It is slowly biodegradable under anaerobic conditions. Due to its high hydrophobicity, sorption-desorption processes can be rate......-limiting for the compound biodegradation. In this study, the anaerobic biodegradation of DEHP was investigated through batch kinetic experiments and dynamic transitions of a continuous stirred tank reactor (CSTR) fed with secondary sludge contaminated with DEHP. A widely accepted model (ADM1) was used to fit the anaerobic...... digestion of secondary sludge and was properly extended to. account for DEHP removal, in which mass transfer processes are also involved. It was shown that DEHP removal was limited by the transfer of DEHP within the solid fraction. The criterion selected for the distinction of the two sites was whether...

  11. The effect of complexing agent on the extraction of Ce(III) and Nd(III) by 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester

    Liquid-liquid extraction of Ce(III) and Nd(III) has been studied using 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (EHEHPA) in kerosene as the extractant. An improvement in separation factor between these elements has been observed in the presence of the complexing agent, glycine. (author). 6 refs., 1 tab

  12. Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis

    Boberg, Julie; Petersen, Marta Axelstad; Vinggaard, Anne; Dalgaard, M.

    2006-01-01

    Phthalates are widely used as plasticizers in various consumer products and building materials. Some of the phthalates are known to interfere with male reproductive development in rats, and di-n-butyl phthalate (DBP), diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP) were recently...... banned for use in toys in the EU mainly due to their reproductive toxicity. Diisobutyl phthalate (DiBP) has similar structural and application properties as DBP. and is being used as a substitute for DBR However, knowledge on male reproductive effects of DiBP in experimental animals is lacking, Methods...

  13. Obtention of Samarium and Gadolinium concentrates by solvent extraction using mono-2-ethylhexyl ester of 2-ethylhexyl phosphonic acid

    The rare earth chlorides solution employed in this study, which is constituted by medium and heavy fractions, is derived from monazite processing accomplished by NUCLEMON-Mineroquimica (SP). This solution shows an acidity about 1.18 M and 189 g/L of rare earth oxides, containing as main constituents: Sm(34.55%), Gd(23.85%), Dy (6.82%), and Y (24.45%). It was used, as organic phase, 2-ethylhexyl phosphonic acid, mono-2-ethylhexylester diluted to 1 M in isododecane. (author)

  14. DEHP exposure impairs mouse oocyte cyst breakdown and primordial follicle assembly through estrogen receptor-dependent and independent mechanisms

    Mu, Xinyi [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); Department of Histology and Embryology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016 (China); Liao, Xinggui; Chen, Xuemei; Li, Yanli; Wang, Meirong; Shen, Cha; Zhang, Xue; Wang, Yingxiong; Liu, Xueqing [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); He, Junlin, E-mail: hejunlin_11@aliyun.com [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China)

    2015-11-15

    Highlights: • DEHP inhibits primordial folliculogenesis in vivo and in vitro. • Estrogen receptors participate in the effect of DEHP on early ovarian development. • DEHP exposure impairs the expression of Notch2 signaling components. • DEHP exposure disrupts the proliferation of pregranulosa precursor cells. - Abstract: Estrogen plays an essential role in the development of mammalian oocytes, and recent studies suggest that it also regulates primordial follicle assembly in the neonatal ovaries. During the last decade, potential exposure of humans and animals to estrogen-like endocrine disrupting chemicals has become a growing concern. In the present study, we focused on the effect of diethylhexyl phthalate (DEHP), a widespread plasticizer with estrogen-like activity, on germ-cell cyst breakdown and primordial follicle assembly in the early ovarian development of mouse. Neonatal mice injected with DEHP displayed impaired cyst breakdown. Using ovary organ cultures, we revealed that impairment was mediated through estrogen receptors (ERs), as ICI 182,780, an efficient antagonist of ER, reversed this DEHP-mediated effect. DEHP exposure reduced the expression of ERβ, progesterone receptor (PR), and Notch2 signaling components. Finally, DEHP reduced proliferation of pregranulosa precursor cells during the process of primordial folliculogenesis. Together, our results indicate that DEHP influences oocyte cyst breakdown and primordial follicle formation through several mechanisms. Therefore, exposure to estrogen-like chemicals during fetal or neonatal development may adversely influence early ovarian development.

  15. DEHP exposure impairs mouse oocyte cyst breakdown and primordial follicle assembly through estrogen receptor-dependent and independent mechanisms

    Highlights: • DEHP inhibits primordial folliculogenesis in vivo and in vitro. • Estrogen receptors participate in the effect of DEHP on early ovarian development. • DEHP exposure impairs the expression of Notch2 signaling components. • DEHP exposure disrupts the proliferation of pregranulosa precursor cells. - Abstract: Estrogen plays an essential role in the development of mammalian oocytes, and recent studies suggest that it also regulates primordial follicle assembly in the neonatal ovaries. During the last decade, potential exposure of humans and animals to estrogen-like endocrine disrupting chemicals has become a growing concern. In the present study, we focused on the effect of diethylhexyl phthalate (DEHP), a widespread plasticizer with estrogen-like activity, on germ-cell cyst breakdown and primordial follicle assembly in the early ovarian development of mouse. Neonatal mice injected with DEHP displayed impaired cyst breakdown. Using ovary organ cultures, we revealed that impairment was mediated through estrogen receptors (ERs), as ICI 182,780, an efficient antagonist of ER, reversed this DEHP-mediated effect. DEHP exposure reduced the expression of ERβ, progesterone receptor (PR), and Notch2 signaling components. Finally, DEHP reduced proliferation of pregranulosa precursor cells during the process of primordial folliculogenesis. Together, our results indicate that DEHP influences oocyte cyst breakdown and primordial follicle formation through several mechanisms. Therefore, exposure to estrogen-like chemicals during fetal or neonatal development may adversely influence early ovarian development

  16. Simulation of DEHP biodegradation and sorption during the anaerobic digestion of secondary sludge

    Fountoulakis, M.S.; Stamatelatou, K.; Batstone, Damien J.;

    2006-01-01

    Di-ethylhexyl phthalate (DEHP) has commonly been found in the sludge of municipal wastewater treatment plants especially during anaerobic processing. It is slowly biodegradable under anaerobic conditions. Due to its high hydrophobicity, sorption-desorption processes can be rate-limiting for the c...

  17. Phthalate esters (PAEs) in indoor PM10/PM2.5 and human exposure to PAEs via inhalation of indoor air in Tianjin, China

    Zhang, Leibo; Wang, Fumei; Ji, Yaqin; Jiao, Jiao; Zou, Dekun; Liu, Lingling; Shan, Chunyan; Bai, Zhipeng; Sun, Zengrong

    2014-03-01

    In this study, filter samples of six Phthalate esters (PAEs) in indoor PM10 and PM2.5 were collected from thirteen homes in Tianjin, China. The results showed that the concentrations of Σ6PAEs in indoor PM10 and PM2.5 were in the range of 13.878-1591.277 ng m-3 and 7.266-1244.178 ng m-3, respectively. Dibutyl phthalate (DBP) was the most abundant compounds followed by di-2-ethylhexyl phthalate (DEHP) in indoor PM10 and PM2.5. Whereas DBP and dimethyl phthalate (DMP) were the predominant compounds in indoor air (gas-phase + particle-phase), the median values were 573.467 and 368.364 ng m-3 respectively. The earlier construction time, the lesser indoor area, the old decoration, the very crowded items coated with plastic and a lower frequency of dusting may lead to a higher level of PAEs in indoor environment. The six PAEs in indoor PM10 and PM2.5 were higher in summer than those in winter. The daily intake (DI) of six PAEs for five age groups through air inhalation in indoor air in Tianjin was estimated. The results indicated that the highest exposure dose was DBP in every age group, and infants experienced the highest total DIs (median: 664.332 ng kg-bw-1 day-1) to ∑6PAEs, whereas adults experienced the lowest total DIs (median: 155.850 ng kg-bw-1 day-1) to ∑6PAEs. So, more attention should be paid on infants in the aspect of indoor inhalation exposure to PAEs.

  18. Activities of the Environmental Protection Agency concerning phthalate esters

    Newburg-Rinn, Steven D.

    1982-01-01

    EPA's activities concerning phthalate esters have been in four general areas, namely: (1) their status as toxic pollutants under the Clean Water Act; (2) their status as “new chemicals” under Section 5 of TSCA; (3) the potential risk to human beings posed by DEHP; and (4) finally, the need for testing phthalates with respect to their health and environmental effects.

  19. Fetal Phthalate Screen: Assessment of Several Phthalate Esters on Fetal Rodent Testosterone Production and Gene Expression Following In Utero Exposure

    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...

  20. Phthalate Migration Study from PVC Grafted by Gamma Radiation

    PVC is a useful polymer used for many applications, as packaging of food, blood and in contact with body fluids. The most widely-used plasticizer, to make it flexible, is the phthalate DEHP, and its toxicity is a problem. A special radiation grafting of PVC allows an important reduction of thrombogenic properties, and it could cause changes in the DEHP migration too. In this work it is presented the methodology using gas chromatography and numerical simulation for the measurement of DEHP migration from PVC grafted with monomer DMAEMA. The grafting could be an interesting way to reduce DEHP migration

  1. Urinary phthalate monoesters and endometriosis in infertile Japanese women

    Phthalates may act as an estrogen and are a potential risk factor for estrogen-related diseases such as endometriosis. We assessed the association between phthalate exposure and endometriosis in 166 consecutive women who presented at a university hospital for consultation regarding infertility. The subjects were interviewed and provided a urine specimen prior to a laparoscopic diagnosis of endometriosis. They were then categorized by the severity of endometriosis as controls (stages 0-I) and cases (stages II-IV). Urinary concentrations of the phthalate metabolites monoethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate were measured in 57 cases and 80 controls using high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Adjusted odds ratios for endometriosis in relation to dichotomized individual phthalate metabolites (standardized for creatinine) were calculated. No significant association between endometriosis and any urinary creatinine-adjusted phthalate monoester was seen. Adjusted odds ratio (95% confidence interval) for higher dichotomized MEHP by endometriosis was 1.57 (0.74-3.30). No monotonic trend was seen in urinary creatinine-adjusted concentration of phthalate metabolites by endometriosis stage (p = 0.23-0.90). Our results do not support the hypothesis that higher urinary concentrations of phthalate metabolites are associated with the risk of endometriosis in infertile Japanese women.

  2. Urinary phthalate monoesters and endometriosis in infertile Japanese women

    Itoh, Hiroaki [Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Iwasaki, Motoki, E-mail: moiwasak@ncc.go.jp [Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Hanaoka, Tomoyuki [Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Sasaki, Hiroshi; Tanaka, Tadao [Department of Obstetrics and Gynecology, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo 105-8461 (Japan); Tsugane, Shoichiro [Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2009-12-15

    Phthalates may act as an estrogen and are a potential risk factor for estrogen-related diseases such as endometriosis. We assessed the association between phthalate exposure and endometriosis in 166 consecutive women who presented at a university hospital for consultation regarding infertility. The subjects were interviewed and provided a urine specimen prior to a laparoscopic diagnosis of endometriosis. They were then categorized by the severity of endometriosis as controls (stages 0-I) and cases (stages II-IV). Urinary concentrations of the phthalate metabolites monoethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate were measured in 57 cases and 80 controls using high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Adjusted odds ratios for endometriosis in relation to dichotomized individual phthalate metabolites (standardized for creatinine) were calculated. No significant association between endometriosis and any urinary creatinine-adjusted phthalate monoester was seen. Adjusted odds ratio (95% confidence interval) for higher dichotomized MEHP by endometriosis was 1.57 (0.74-3.30). No monotonic trend was seen in urinary creatinine-adjusted concentration of phthalate metabolites by endometriosis stage (p = 0.23-0.90). Our results do not support the hypothesis that higher urinary concentrations of phthalate metabolites are associated with the risk of endometriosis in infertile Japanese women.

  3. Phthalates Induce Neurotoxicity Affecting Locomotor and Thermotactic Behaviors and AFD Neurons through Oxidative Stress in Caenorhabditis elegans

    Tseng, I-Ling; Yang, Ying-Fei; Yu, Chan-Wei; Li, Wen-Hsuan; Liao, Vivian Hsiu-Chuan

    2013-01-01

    Background Phthalate esters are ubiquitous environmental contaminants and numerous organisms are thus exposed to various levels of phthalates in their natural habitat. Considering the critical, but limited, research on human neurobehavioral outcomes in association with phthalates exposure, we used the nematode Caenorhabditis elegans as an in vivo model to evaluate phthalates-induced neurotoxicity and the possible associated mechanisms. Principal Findings Exposure to phthalates (DEHP, DBP, and...

  4. Urinary excretion of phthalate metabolites in 129 healthy Danish children and adolescents: Estimation of daily phthalate intake

    Frederiksen, Hanne; Aksglaede, Lise; Sørensen, Kaspar; Skakkebaek, Niels E; Juul, Anders; Andersson, Anna-Maria

    2011-01-01

    Background Phthalates are a group of chemicals with widespread use in the industrial production of numerous consumer products. They are suspected to be involved in male reproductive health problems and have also been associated with several other health problems in children including obesity and...... children were generally more exposed to phthalates than older children and adolescents (except diethyl phthalate (DEP)). Boys were more exposed than girls. The median estimated daily intake of phthalate diesters was: 4.29 (dibutyl phthalate isoforms (DBP(i+n))), 4.04 (DEHP), 1.70 (DiNP), 1.09 (DEP) and 0...

  5. 邻苯二甲酸二(2-乙基己基)酯、氯氰菊酯单独及联合染毒对青春前期雄性大鼠生殖发育的不良影响%Single and combined toxic effects of di-2-ethylhexyl phthalate and cyperm ethrin on fertility and development in the the prepubertal male rats

    李祥婷; 蔡德培

    2012-01-01

    目的 探讨邻苯二甲酸二(2-乙基己基)酯( DEHP)和氯氰菊酯(CYP)单 独及联合染毒对青春前期雄性大鼠生殖发育的不良影响. 方法 选择SPF级3周龄雄性SD大鼠24只,随机分为4组,分别为对照组(喂饲玉米油)、DEHP染毒组(500mg/kg)、CYP染毒组(80mg/kg);DEHP、CYP联合染毒组(DEHP 500mg/kg+ CYP 80mg/kg),每组6只.采用经口灌胃方式染毒,每天1次,连续染毒30天.于末次染毒24小时后处死动物,测定大鼠体重、睾丸湿重,并计算睾丸系数;测定血清睾酮水平;制备睾丸病理组织切片,光镜观察其组织学改变,电镜观察生殖细胞超微结构;测定睾丸标志酶乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、碱性磷酸酶(ALP)和琥珀酸脱氢酶( SDH)的活性.结果 与对照组相比,DEHP、CYP单独及联合染毒组睾丸下降时间和包皮分离时间明显延迟,肛门生殖器间距明显缩短(P <0.05或0.01);DEHP单独染毒组睾丸重量及睾丸系数明显降低,血清睾酮水平显著下降(P<0.05),睾丸匀浆中ALP、ACP和LDH活性明显增高,SDH活性显著下降(P<0.01);DEHP、CYP单独及联合染毒组睾丸病理组织学、生殖细胞超微结构均可见明显异常.结论 DEHP、CYP单独及联合染毒对青春前期雄性大鼠均具有明显的生殖毒性作用,可引起生精细胞、支持细胞和间质细胞的变性、坏死及功能障碍,从而导致雄性生殖系统发育和功能的显著异常.其中,DEHP单独染毒呈现主效应,DEHP、CYP联合染毒对大鼠的生殖毒性未呈现明显交互影响.%Objective To investigate the separate and combined toxic effects of di-2- ethylhexylphthalate (DEHP) and cypermethrin( CYP) on prepubertal male rats. Methods A total of 24 healthy 3-week-old SPF male Sprague-Dawley rats were randomly divided into four groups. They were control group(fed with corn oil) , DEHP group(500 mg/kg, dissolved in corn oil), CYP group (80mg/kg, dissolved in corn oil), combine

  6. Are Medicinal Plants Polluted with Phthalates?

    Soodabeh Saeidnia

    2013-05-01

    Full Text Available Phthalic acid esters (PAEs have been employed in polymer materials as a plasticizer to form them more flexible, adhesive, and soluble. These compounds are mainly used in paints, varnishes, personal cares, cosmetics, paper coatings, and adhesives even in bottled waters, shampoo, body deodorant, hairspray, and gels. Phthalates are able to possess remarkable toxic variations depending on their structures. So far, Di-(2-EthylHexyl Phthalate DEHP and Di-n- Butyl Phthalate DBP have been found to cause reproductive and developmental toxicities. The U.S. Environmental Protection Agency (EPA classified DEHP as probable human carcinogen. To the best of our knowledge, phthalates showed diverse toxicity profiles according to their structures in the liver, kidneys, thyroid, and testes, which are involved in general toxicity. Furthermore, they are introduced as hormonally-active agents, because they can interfere with the endocrine system in human. Incidence of developmental abnormalities (like skeletal malformations and cleft palate, and undescended testes, lowering testes weight and anogenital distance seems increasing via high exposure to phthalate metabolites. Although, increasing the capacity for phthalate free plasticizer productions is the first step to restrict the distribution of these toxic manmade compounds, finding the new ways for phthalate absorption from the soil in agricultural fields may have benefits. Also, evaluation and examination of diverse sources of medicinal and food plants to determine the level of phthalate accumulation in their organs are extremely recommended to avoid creating toxicity particularly in reproductive systems.

  7. 塑料书套中邻苯二甲酸酯的快速检测及污染现状研究%Rapid Determination and Contamination Situation of Phthalate Ester in Plastic Slipcase

    刘君峰; 祝惠惠; 陈智栋; 邵晨杰; 尹大伟

    2013-01-01

    A rapid determination method of 6 Common phthalate esters (PAEs) in plastic slipcase was developed, which took dichloromethane as extraction solvent, extracted PAEs with ultrasonic, and detected PAEs by gas chromatography-mass spectrometry (GC-MS). Then, contamination situation of PAEs in plastic slipcase of students was studied through determining samples from market. The results showed that high concentration PAEs were generally detected in polyvinyl chloride (PVC) plastic slipcase, and the major PAE was di-2-ethylhexyl phthalate (DEHP).%建立了塑料书套中6种常见邻苯二甲酸酯类增塑剂的快速检测方法。该方法以二氯甲烷为萃取溶剂,通过超声萃取对样品中的邻苯二甲酸酯进行提取,使用气相色谱-质谱联用法进行检测。通过对市场上学生用塑料书套的抽样检测,调研邻苯二甲酸酯污染现状,结果显示市场上所售的聚氯乙烯材质书套中普遍检出高浓度邻苯二甲酸酯,主要种类为邻苯二甲酸二(2-乙基)己酯。

  8. Prenatal Exposure to Phthalates and Infant Development at 6 Months: Prospective Mothers and Children’s Environmental Health (MOCEH) Study

    Kim, Yeni; Ha, Eun–Hee; Kim, Eui–Jung; Park, Hyesook; Ha, Mina; Kim, Ja–Hyeong; Hong, Yun–Chul; Chang, Namsoo; Kim, Bung–Nyun

    2011-01-01

    Background: There are increasing concerns over adverse effects of prenatal phthalate exposure on the neurodevelopment of infants. Objectives: Our goal was to explore the association between prenatal di(2-ethylhexyl) phthalate and dibutyl phthalate exposure and the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) of the Bayley Scales of Infant Development at 6 months, as part of the Mothers and Children’s Environmental Health Study. Methods: Between 2006 and 2009, 460 m...

  9. CO'DETERMINATION OF PHTHALATES AND SEMI'VOLATILE ORGANIC CONTAMINANTS OF OTHER CLASSES IN WATER SAMPLES

    Kholova, A.; Vozhdaeva, M.; Kantor, L.; Trukhanova, N.; Melnitsky, I.; Kantor, E.

    2011-01-01

    Iethod for determination of six phthalates dimethyl-, diethyl-, dibutyl-, benzylbutyl-, di(2ethylhexyl)and di-n-octylphthalates with gas chromatography/mass-spectrometry in drinking and natural water has been developed. Concentration range is 0.0008-0.02 mg/dm3. Phthalates are determined under conditions of total ion current, after preliminary liquid-liquid extraction with methylene chloride and after addition of two substitute standards. This method allows determining phthalates simultaneous...

  10. Cloud point extraction equilibrium of lanthanum(III), europium(III) and lutetium(III) using di(2-ethylhexyl)phosphoric acid and Triton X-100.

    Ohashi, Akira; Hashimoto, Takuma; Imura, Hisanori; Ohashi, Kousaburo

    2007-10-31

    The cloud point extraction behaviors of lanthanoids(III) (Ln(III)=La(III), Eu(III) and Lu(III)) with and without di(2-ethylhexyl)phosphoric acid (HDEHP) using Triton X-100 were investigated. It was suggested that the extraction of Ln(III) into the surfactant-rich phase without added chelating agent was caused by the impurities contained in Triton X-100. The extraction percentage more than 91% for all Ln(III) metals was obtained using 3.0x10(-5)moldm(-3) HDEHP and 2.0% (v/v) Triton X-100. From the equilibrium analysis, it was clarified that Ln(III) was extracted as Ln(DEHP)(3) into the surfactant-rich phase. The extraction constant of Ln(III) with HDEHP and 2.0% (v/v) Triton X-100 were also obtained. PMID:19073117

  11. Radiation induced emulsion polymerization of 2-ethylhexyl acrylate

    The effects of radiation dose rate concentration of emulsifier and monomer content on reaction rate of radiation induced 2-ethylhexyl acrylate (EHA) emulsion polymerization have been studied. Nonionic surfactants, polyoxyethylene alkyl ether peregolo 0 with HLB about 15 and polyoxyethylene nonylphenolether (emulsifier OP) with HLB 15, are used as the emulsifiers in this work. It has been found that the dependence of RP on I (RP proportional to In) is changed with the index n from 0.29 for M/W = 2/8 (monomer/water in volume) to 0.91 for 5/5, where [E] of peregolo 0 is 4%. It has also been found that RP proportional to [E]0.58 for peregolo 0 and RP proportional to [E]0.51 for emulsifier OP. In order to interpret the results sufficiently, both micellar nucleation and micro-droplet nucleation have been taken into account for the emulsion polymerization of the present system irradiated without agitation, especially for the case with a higher M/W value the later may be the main nucleation process

  12. Critical cleaning agents for Di-2-ethylhexyl sebacate.

    Hartley, Mya; Archuleta, Kim M.

    2013-08-01

    It is required that Di-2-ethylhexyl Sebacate oil, also commonly known as Dioctyl Sebacate oil, be thoroughly removed from certain metals, in this case stainless steel parts with narrow, enclosed spaces. Dioctyl Sebacate oil is a synthetic oil with a low compressibility. As such, it is ideally used for high pressure calibrations. The current method to remove the Dioctyl Sebacate from stainless steel parts with narrow, enclosed spaces is a labor-intensive, multi-step process, including a detergent clean, a deionized (DI) water rinse, and several solvent rinses, to achieve a nonvolatile residue of0.04 mg per 50 mL rinse effluent. This study was undertaken to determine a superior detergent/solvent cleaning method for the oil to reduce cleaning time and/or the amount of detergent/solvent used. It was determined that while some detergent clean the oil off the metal better than the current procedure, using only solvents obtained the best result. In addition, it can be inferred, based on elevated temperature test results, that raising the temperature of the oil-contaminated stainless steel parts to approximately 50%C2%B0C will provide for improved cleaning efficacy.

  13. Study on the interaction of phthalate esters to human serum albumin by steady-state and time-resolved fluorescence and circular dichroism spectroscopy

    Xie, Xiaoyun [National Key Laboratory of Organic Chemistry, Lanzhou University, Lanzhou 730000 (China); College of Earth and Environmental Sciences, Lanzhou University, Lanzhou 730000 (China); Wang, Zhaowei [College of Earth and Environmental Sciences, Lanzhou University, Lanzhou 730000 (China); Zhou, Ximin; Wang, Xiaoru [National Key Laboratory of Organic Chemistry, Lanzhou University, Lanzhou 730000 (China); Chen, Xingguo, E-mail: chenxg@lzu.edu.cn [National Key Laboratory of Organic Chemistry, Lanzhou University, Lanzhou 730000 (China); Department of Chemistry, Lanzhou University, Lanzhou 730000 (China)

    2011-09-15

    Highlights: {center_dot} Molecular docking revealed PAEs to be located in the hydrophobic pocket of HSA. {center_dot} HSA-DMP had one class of binding sites while HSA-BBP and HSA-DEHP had two types. {center_dot} Hydrophobic and hydrogen interactions dominated in the association of HSA-PAEs. {center_dot} The lifetime of Trp residue of HSA decreased after the addition of PAEs. {center_dot} The presences of PAEs could alter the second structure of HSA. - Abstract: Phthalate esters (PAEs) are globally pervasive contaminants that are considered to be endocrine disruptor chemicals and toxic environmental priority pollutants. In this paper, the interactions between PAEs and human serum albumin (HSA) were examined by molecular modelling, steady state and time-resolved fluorescence, ultraviolet-visible spectroscopy (UV-vis) and circular dichroism spectroscopy (CD). The association constants between PAEs and HSA were determined using the Stern-Volmer and Scatchard equations. The binding of dimethyl phthalate (DMP) to HSA has a single class of binding site and its binding constants (K) are 4.08 x 10{sup 3}, 3.97 x 10{sup 3}, 3.45 x 10{sup 3}, and 3.20 x 10{sup 3} L mol{sup -1} at 289, 296, 303, and 310 K, respectively. The Stern-Volmer and Scatchard plots both had two regression curves for HSA-butylbenzyl phthalate (BBP) and HSA-di-2-ethylhexyl phthalate (DEHP), which indicated that these bindings were via two types of binding sites: the numbers of binding site for the first type were lower than for the second type. The binding constants of the first type binding site were higher than those of the second type binding site at corresponding temperatures, the results suggesting that the first type of binding site had high affinity and the second binding site involved other sites with lower binding affinity and selectivity. The thermodynamic parameters of the binding reactions ({Delta}G{sup o}, {Delta}H{sup o} and {Delta}S{sup o}) were measured, and they indicated the presences

  14. Study on the interaction of phthalate esters to human serum albumin by steady-state and time-resolved fluorescence and circular dichroism spectroscopy

    Highlights: · Molecular docking revealed PAEs to be located in the hydrophobic pocket of HSA. · HSA-DMP had one class of binding sites while HSA-BBP and HSA-DEHP had two types. · Hydrophobic and hydrogen interactions dominated in the association of HSA-PAEs. · The lifetime of Trp residue of HSA decreased after the addition of PAEs. · The presences of PAEs could alter the second structure of HSA. - Abstract: Phthalate esters (PAEs) are globally pervasive contaminants that are considered to be endocrine disruptor chemicals and toxic environmental priority pollutants. In this paper, the interactions between PAEs and human serum albumin (HSA) were examined by molecular modelling, steady state and time-resolved fluorescence, ultraviolet-visible spectroscopy (UV-vis) and circular dichroism spectroscopy (CD). The association constants between PAEs and HSA were determined using the Stern-Volmer and Scatchard equations. The binding of dimethyl phthalate (DMP) to HSA has a single class of binding site and its binding constants (K) are 4.08 x 103, 3.97 x 103, 3.45 x 103, and 3.20 x 103 L mol-1 at 289, 296, 303, and 310 K, respectively. The Stern-Volmer and Scatchard plots both had two regression curves for HSA-butylbenzyl phthalate (BBP) and HSA-di-2-ethylhexyl phthalate (DEHP), which indicated that these bindings were via two types of binding sites: the numbers of binding site for the first type were lower than for the second type. The binding constants of the first type binding site were higher than those of the second type binding site at corresponding temperatures, the results suggesting that the first type of binding site had high affinity and the second binding site involved other sites with lower binding affinity and selectivity. The thermodynamic parameters of the binding reactions (ΔGo, ΔHo and ΔSo) were measured, and they indicated the presences of hydrophobic forces and hydrogen interactions in the PAEs-HSA interactions, which agreed well with the results

  15. Correlation of phthalate exposures with semen quality

    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 analysis 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

  16. Extraction of lanthanoids with bis(2-ethylhexyl) hydrogenphosphate

    Extraction of lanthanoids (Ln) with bis(2-ethylhexyl) hydrogenphosphate (D2EHPA, (C8H17O)2 POOH) has been investigated in the region of high metal loading. Extracted species are polymerized and form gelatinous materials at high metal loading (R sub(tr) > 0.15) as shown in Fig. 1. Table 1 indicates that the composition of the polymerized species is LnX3 (X: (C8H17O)2POO). Fig. 3-(a) indicates that the extractant dependence of the distribution ratio of a lanthanoid is 2.5 power in benzene, and therefore the extraction reaction is represented as Eq. (2) (Ln sub((a))sup(3+) + 5/2(HX)sub(2(o)) reversible LnX3.2HX sub((o)) + 3H sub((a))sup(+)). Fig. 4-(a) shows that the concentration of a lanthanoid in the organic phase is of first order in the D2EHPA concentration in the presence of gelatinous materials when benzene is a diluent, and therefore the equilibrium between the organic phase and the gelatinous materials is represented as Eq. (3) (1/p(LnX3)sub(p(g)) + (HX)sub(2(o)) reversible LnX3.2HX sub((o))), where p is the degree of polymerization. The dependence on D2EHPA concentration is lower in heptane than in benzene as shown in Fig. 3-(b), 4-(b) and 5-(b). The difference can be explained by the fact that the association number of D2EHPA in heptane is more than 2. (author)

  17. Fourier transform infrared spectroscopic study on microemulsion systems of alkali metal salts of 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester

    Zhou, Weijin; Shi, Nai; Xu, Zhen-hua; Wu, JinGuang

    1994-01-01

    There has recently been a growing interest in the reverse micelle and microemulsion formation in the solvent extraction process. In our previous papers, the formation of W/O type microemulsions in the organic phase of sodium or potassium salt of 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester was investigated by using the subtraction technique on FTIR. In this paper, the conductance and the FTIR spectroscopic study on the microemulsion systems of Li, Na, and K salts of this acidic extractant was reported.

  18. Identification of fatty foods with contamination possibilities by plasticizers when stored in PVC film packaging

    Hilda Duval Barros; Helena Pereira da Silva Zamith; Fábio Silvestre Bazílio; Lucia Jaeger de Carvalho; Shirley de Mello Pereira Abrantes

    2011-01-01

    Poly-(vinyl chloride) (PVC) requires the addition of plasticizers - additives that give flexibility and malleability for its processing into flexible film. The most used ones are: di-(2-ethylhexyl) adipate (DEHA) and di-(2-ethylhexyl) phthalate (DEHP). Toxic effects of DEHP have been observed by several authors. Phthalates are being replaced by alternative substances in PVC flexible products, because of their possible toxicological effects. DEHA is a substitute for phthalates widely used as a...

  19. 40 CFR 180.1274 - Tris (2-ethylhexyl) phosphate; exemption from the requirement of a tolerance.

    2010-07-01

    ... (d) The applications occur no later than the pre-boot stage (prior to formation of edible grain). ...: (a) The use is in accordance with good agricultural practices; (b) Tris (2-ethylhexyl) phosphate...

  20. Extraction equilibria of rare earths by a new reagent (2-ethylhexyl-3-pentadecylphenyl) phosphoric acid.

    Sreelatha, S; Rao, T P; Narayanan, C S; Damodaran, A D

    1994-03-01

    A new reagent (2-ethylhexyl-3-pentadecylphenyl) phosphoric acid (EPPA = HR) was synthesized from cardanol (I, 37300-39-5) and was used to investigate the extraction behaviour of lanthanum(III), europium(III) and lutetium(III) from hydrochloric acid solutions. The species extracted were found to be Ln(HR(2))(3) (where Ln = La(III) or Eu(III) or Lu(III)). The extraction behaviour of the above lanthanides has also been compared with yttrium and other rare earths. It was observed that the extraction increases with increase in atomic number of rare earths. In addition, the extraction efficiency of EPPA has also been compared with well known acidic organophosphorus extractants like di-2-ethylhexyl phosphoric acid (DEHPA), 2-ethylhexyl-mono-2-ethylhexyl phosphoric acid (EHEHPA). PMID:18965945

  1. Dermal absorption of phthalate diesters in rats

    This study examined the extent of dermal absorption of a series of phthalate diesters in the rat. Those tested were dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate. Hair from a skin area (1.3 cm in diameter) on the back of male F344 rats was clipped, the [14C]phthalate diester was applied in a dose of 157 mumol/kg, and the area of application was covered with a perforated cap. The rat was restrained and housed for 7 days in a metabolic cage that allowed separate collection of urine and feces. Urine and feces were collected every 24 hr, and the amount of 14C excreted was taken as an index of the percutaneous absorption. At 24 hr, diethyl phthalate showed the greatest excretion (26%). As the length of the alkyl side chain increased, the amount of 14C excreted in the first 24 hr decreased significantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate, about 50-60% of the applied 14C; and intermediate (20-40%) for dimethyl, benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate. This compound was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate that remained in the body was minimal and showed no specific tissue distribution. Most of the unexcreted dose remained in the area of application. These data show that the structure of the phthalate diester determines the degree of dermal absorption. Absorption maximized with diethyl phthalate and then decreased significantly as the alkyl side chain length increased

  2. Migration of phthalates on culture plates

    Frohnert Hansen, Juliana; Boas, Malene; Møller Brorson, Marianne;

    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...... 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...

  3. Influence of phthalates on cytokine production in monocytes and macrophages

    Hansen, Juliana Frohnert; Bendtzen, Klaus; Boas, Malene; Frederiksen, Hanne; Nielsen, Claus H; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla

    2015-01-01

    BACKGROUND: Phthalates are a group of endocrine disrupting chemicals suspected to influence the immune system. The aim of this systematic review is to summarise the present knowledge on the influence of phthalates on monocyte and macrophage production and secretion of cytokines, an influence which......-α secretion/production from monocytes or macrophages. A summary of cytokine measurements was not possible since few studies were comparable in study design and due to insufficient reporting of raw data for most of the included studies. CONCLUSION: Results from this review have suggested that at least one...... phthalate (di-2-ethylhexyl phthalate) has the ability to enhance tumour necrosis factor-α production/secretion from monocytes/macrophages in vitro, but also observed ex vivo. Influence of other phthalates on other cytokines has only been investigated in few studies. Thus, in vitro studies on primary human...

  4. Oxidative Stress and Phthalate-Induced Down-Regulation of Steroidogenesis in MA-10 Leydig Cells*

    Zhou, Liang; Beattie, Matthew C.; Lin, Chieh-Yin; Liu, June; Traore, Kassim; Papadopoulos, Vassilios; ZIRKIN, BARRY R.; Chen, Haolin

    2013-01-01

    Previous studies have shown that phthalate exposure can suppress steroidogenesis. However, the affected components of the steroidogenic pathway, and the mechanisms involved, remain uncertain. We show that incubating MA-10 Leydig cells with mono-(2-ethylhexyl) phthalate (MEHP) resulted in reductions in luteinizing hormone (LH)-stimulated cAMP and progesterone productions. cAMP did not decrease in response to MEHP when the cells were incubated with cholera toxin or forskolin. Incubation of MEHP...

  5. Biodegradation of 2-ethylhexyl nitrate by Mycobacterium austroafricanum IFP 2173

    Compounds such as 2-ethylhexyl nitrate (2-EHN) are added to diesel fuel to improve ignition and boost cetane number. The production of 2-EHN reaches around 100000 tons per year in France, principally. Risks associated to its utilization are however poorly known because, in case of accidental release in the environment, nothing is known about its biodegradation. In this study, we aimed at (i) identifying bacterial strains able to degrade 2-EHN and compare their capabilities, (ii) elucidating the degradation pathway, and (iii) identifying the enzymes involved. Biodegradation of 2-EHN was first tested in biphasic cultures under conditions that reduce the toxicity and increase the availability of the hydrophobic substrate. Using optimized culture conditions, we showed that several strains of Mycobacterium austroafricanum were able to degrade 2-EHN. One of the most efficient strain (IFP 2173) which could grow at 2-EHN concentrations up to 6 g.L-1, was chosen to investigate the degradation pathway. On the basis of carbon balance determination and gas chromatographic (GC) analysis on the culture medium, I found that the degradation of 2-EHN was incomplete and gave rise to the accumulation of a metabolite. This metabolite was identified as β-methyl-γ-butyrolactone by GC-MS and LC-MS/MS analysis. The structure of the lactone indicated that 2-EHN was degraded through a pathway involving the hydroxylation of the methyl group of the main carbon chain, its oxidation into aldehyde an acid and a subsequent cycle of b-oxidation. Enzymes involved in the 2-EHN biodegradation pathway were looked for by a proteomic approach. Analyses by two-dimensional gel electrophoresis showed that, when exposed to 2-EHN, strain IFP 2173 triggered the synthesis of a bunch of enzymes specialized in fatty acid metabolism such as β-oxidation enzymes, as well as alcohol and aldehyde dehydrogenases. An exhaustive analysis of the IFP 2173 proteome resulted in the identification of more than 200

  6. Occurence of the phthalate esters in soil and street dust samples from the Novi Sad city area, Serbia, and the influence on the children's and adults' exposure.

    Škrbić, Biljana D; Ji, Yaqin; Đurišić-Mladenović, Nataša; Zhao, Jie

    2016-07-15

    This is the first study reporting the presence of 6 phthalic acid esters (PAEs) in 60 composite soil and street dust samples collected in the urban zone of Novi Sad, the second largest city in Serbia. The results were further used to assess children's and adults' PAEs nondietary daily intakes (DIs) through incidental soil and dust ingestion and/or dermal absorption. The study could be regarded as the important baseline for future monitoring of PAEs in the urban environments, particularly as it contributes to the rare data on PAEs occurence in the street dust. All 6 PAEs were detected in every analyzed soil and street dust samples from 0.0002mgkg(-1) to 4.82mgkg(-1), with the highest level obtained for di-(2-ethylhexyl) phthalate (DEHP), which was the most dominant PAE (70-96%). The highest total PAEs (Σ6PAEs) contents in soil (2.12mgkg(-1)) and street dust (5.45mgkg(-1)) samples were obtained for the samples from city parks. In all soil samples, Σ6PAEs exceeded the soil sustainable quality limit sets by the relevant Serbian Regulation, but were much lower than the limit requiring remediation measures. Concerning the estimated DIs, children were more susceptible to PAEs intake than adults regardless of the exposure routes. All the estimated DIs values were far below the known reference values. PMID:27039030

  7. A mixture of an environmentally realistic concentration of a phthalate and herbicide reduces testosterone in male fathead minnow (Pimephales promelas) through a novel mechanism of action

    Several chemicals that are used by humans, such as pesticides and plastics, are released into the aquatic environment through wastewater and runoff and have been shown to be potent disruptors of androgen synthesis at high concentrations. Although many of these chemicals have been studied in isolation, a large amount of uncertainty remains over how fish respond to low concentrations of anti-androgenic mixtures, which more accurately reflects how such chemicals are present in the aquatic environment. In this study male fathead minnows (FHM) (Pimephales promelas) were exposed to environmentally relevant concentrations of two anti-androgens, the herbicide linuron, and the plasticizer di(2-ethylhexyl) phthalate (DEHP) individually and as part of a mixture of the two for a 28-day period. At the end of this period there was a reduction in plasma testosterone (T) concentrations in male FHM exposed to the mixture, but not in FHM exposed individually to linuron or DEHP or the control FHM. There was also a significant reduction in 17β-estradiol (E2) in the DEHP-only and mixture exposed groups as compared to the control. Contrary to what has been previously published for these two chemicals in mammals, the lower plasma T concentrations in male FHM exposed to the mixture was not a result of the inhibition of genes involved in steroidogenesis; nor due to an increase in the expression of genes associated with peroxisome proliferation. Rather, an increase in relative transcript abundance for CYP3A4 in the liver and androgen- and estrogen-specific SULT2A1 and SULT1st2 in the testes provides evidence that the decrease in plasma T and E2 may be linked to increased steroid catabolism. Feedback from the pituitary is not repressed as the relative expression of follicle stimulating hormone β-subunit mRNA transcript levels in the brain was significantly higher in both DEHP and mixture exposed FHM. In addition, luteinizing hormone β-subunit mRNA transcript levels increased but were not

  8. A mixture of an environmentally realistic concentration of a phthalate and herbicide reduces testosterone in male fathead minnow (Pimephales promelas) through a novel mechanism of action.

    Crago, Jordan; Klaper, Rebecca

    2012-04-01

    Several chemicals that are used by humans, such as pesticides and plastics, are released into the aquatic environment through wastewater and runoff and have been shown to be potent disruptors of androgen synthesis at high concentrations. Although many of these chemicals have been studied in isolation, a large amount of uncertainty remains over how fish respond to low concentrations of anti-androgenic mixtures, which more accurately reflects how such chemicals are present in the aquatic environment. In this study male fathead minnows (FHM) (Pimephales promelas) were exposed to environmentally relevant concentrations of two anti-androgens, the herbicide linuron, and the plasticizer di(2-ethylhexyl) phthalate (DEHP) individually and as part of a mixture of the two for a 28-day period. At the end of this period there was a reduction in plasma testosterone (T) concentrations in male FHM exposed to the mixture, but not in FHM exposed individually to linuron or DEHP or the control FHM. There was also a significant reduction in 17β-estradiol (E2) in the DEHP-only and mixture exposed groups as compared to the control. Contrary to what has been previously published for these two chemicals in mammals, the lower plasma T concentrations in male FHM exposed to the mixture was not a result of the inhibition of genes involved in steroidogenesis; nor due to an increase in the expression of genes associated with peroxisome proliferation. Rather, an increase in relative transcript abundance for CYP3A4 in the liver and androgen- and estrogen-specific SULT2A1 and SULT1st2 in the testes provides evidence that the decrease in plasma T and E2 may be linked to increased steroid catabolism. Feedback from the pituitary is not repressed as the relative expression of follicle stimulating hormone β-subunit mRNA transcript levels in the brain was significantly higher in both DEHP and mixture exposed FHM. In addition, luteinizing hormone β-subunit mRNA transcript levels increased but were not

  9. A mixture of an environmentally realistic concentration of a phthalate and herbicide reduces testosterone in male fathead minnow (Pimephales promelas) through a novel mechanism of action

    Crago, Jordan, E-mail: jcrago@uwm.edu [Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53204 (United States); Klaper, Rebecca, E-mail: rklaper@uwm.edu [School of Freshwater Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53204 (United States)

    2012-04-15

    Several chemicals that are used by humans, such as pesticides and plastics, are released into the aquatic environment through wastewater and runoff and have been shown to be potent disruptors of androgen synthesis at high concentrations. Although many of these chemicals have been studied in isolation, a large amount of uncertainty remains over how fish respond to low concentrations of anti-androgenic mixtures, which more accurately reflects how such chemicals are present in the aquatic environment. In this study male fathead minnows (FHM) (Pimephales promelas) were exposed to environmentally relevant concentrations of two anti-androgens, the herbicide linuron, and the plasticizer di(2-ethylhexyl) phthalate (DEHP) individually and as part of a mixture of the two for a 28-day period. At the end of this period there was a reduction in plasma testosterone (T) concentrations in male FHM exposed to the mixture, but not in FHM exposed individually to linuron or DEHP or the control FHM. There was also a significant reduction in 17{beta}-estradiol (E2) in the DEHP-only and mixture exposed groups as compared to the control. Contrary to what has been previously published for these two chemicals in mammals, the lower plasma T concentrations in male FHM exposed to the mixture was not a result of the inhibition of genes involved in steroidogenesis; nor due to an increase in the expression of genes associated with peroxisome proliferation. Rather, an increase in relative transcript abundance for CYP3A4 in the liver and androgen- and estrogen-specific SULT2A1 and SULT1st2 in the testes provides evidence that the decrease in plasma T and E2 may be linked to increased steroid catabolism. Feedback from the pituitary is not repressed as the relative expression of follicle stimulating hormone {beta}-subunit mRNA transcript levels in the brain was significantly higher in both DEHP and mixture exposed FHM. In addition, luteinizing hormone {beta}-subunit mRNA transcript levels increased

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

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

    2016-03-16

    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. PMID:26923228

  11. Current status and historical variations of phthalate ester (PAE) contamination in the sediments from a large Chinese lake (Lake Chaohu).

    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. PMID:26330308

  12. Consumer product exposures associated with urinary phthalate levels in pregnant women.

    Buckley, Jessie P; Palmieri, Rachel T; Matuszewski, Jeanine M; Herring, Amy H; Baird, Donna D; Hartmann, Katherine E; Hoppin, Jane A

    2012-09-01

    Human phthalate exposure is ubiquitous, but little is known regarding predictors of urinary phthalate levels. To explore this, 50 pregnant women aged 18-38 years completed two questionnaires on potential phthalate exposures and provided a first morning void. Urine samples were analyzed for 12 phthalate metabolites. Associations with questionnaire items were evaluated via Wilcoxon tests and t-tests, and r-squared values were calculated in multiple linear regression models. Few measured factors were statistically significantly associated with phthalate levels. Individuals who used nail polish had higher levels of mono-butyl phthalate (P=0.048) than non-users. Mono-benzyl phthalate levels were higher among women who used eye makeup (P=0.034) or used makeup on a regular basis (P=0.004). Women who used cologne or perfume had higher levels of di-(2-ethylhexyl) phthalate metabolites. Household products, home flooring or paneling, and other personal care products were also associated with urinary phthalates. The proportion of variance in metabolite concentrations explained by questionnaire items ranged between 0.31 for mono-ethyl phthalate and 0.42 for mono-n-methyl phthalate. Although personal care product use may be an important predictor of urinary phthalate levels, most of the variability in phthalate exposure was not captured by our relatively comprehensive set of questionnaire items. PMID:22760436

  13. In Utero Exposure to Diethylhexyl Phthalate Affects Rat Brain Development: A Behavioral and Genomic Approach

    Han Lin

    2015-10-01

    Full Text Available Diethylhexyl phthalate (DEHP is one of the most widely utilized phthalate plasticizers. Previous studies have demonstrated that gestational or postnatal DEHP exposure induced adverse effects on rat brain development and function. In this study, we investigated the effects of gestational DEHP exposure on gene expression profiling in neonatal rat brain and cognitive function change at adulthood. Adult Sprague Dawley dams were orally treated with 10 or 750 mg/kg DEHP from gestational day 12 to 21. Some male pups were euthanized at postnatal day 1 for gene expression profiling, and the rest males were retained for water maze testing on postnatal day (PND 56. DEHP showed dose-dependent impairment of learning and spatial memory from PND 56 to 63. Genome-wide microarray analysis showed that 10 and 750 mg/kg DEHP altered the gene expression in the neonatal rat brain. Ccnd1 and Cdc2, two critical genes for neuron proliferation, were significantly down-regulated by DEHP. Interestingly, 750 mg/kg DEHP significantly increased Pmch level. Our study demonstrated the changed gene expression patterns after in utero DEHP exposure might partially contribute to the deficit of cognitive function at adulthood.

  14. Childhood exposure to DEHP, DBP and BBP in Denmark and Korea

    Lee, Jihyun; Lee, Jong-Hyun; Kim, Chan-Kook;

    compounds have been restricted for use in children’s products and they are also listed in Annex XIV of the EU REACH. However, these chemicals are still produced and used in many products. In 2002, approximately 10% of the world’s phthalates demand was produced in South Korea, while Denmark has no phthalate...... Korea. Varying environmental qualities and dietary intake patterns were taken into account using a Monte Carlo Model for calculating childhood aggregate exposure via the environment and food. Additionally, childhood activity related exposure from consumer products were calculated for selected product...... scenarios and by using dust as an indicator of indoor exposure. Total exposure to the three phthalates, DEHP, BBP and DBP, is compared taking into account different activity patterns and life styles of children in Denmark and Korea. Multivariate data analysis verifies the relationships between varying...

  15. Residential exposure to plasticizers and its possible role in the pathogenesis of asthma

    Oie, L; Hersoug, Lars-Georg; Madsen, J O

    1997-01-01

    The plasticizer di(2-ethylhexyl) phthalate (DEHP) is widely used in building materials. DEHP is identified as the major plasticizer exposure in dwellings. We provide evidence that inhalation exposure to DEHP as aerosols adsorbed to particulate matter is as important, or more important, than vapor...

  16. Characterization of Urinary Phthalate Metabolites Among Custodians.

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

    2015-10-01

    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

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

    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

  18. Serum phthalate levels and time to pregnancy in couples from Greenland, Poland and Ukraine.

    Ina Olmer Specht

    Full Text Available 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.

  19. Assessment of phthalate-induced changes in fetal rat testis gene expression using an rt-PCR array

    Lambright, CS’, Sampson, H2, Furr, i1, Evans, N’, Hannas, B’, Gray, LE, Jr.’, VS Wilson1. 1USEPA, NHEERL, RTP, NC, 2USEPA, NHEERL, RTP, NC, ORISE Fellow. Phthalate esters (PE) such as diethyl hexyl phthalate (DEHP) produce reproductive malformations in male rodents by reduction o...

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

    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. PMID:26766535

  1. Environmental phthalate monoesters activate pregnane X receptor-mediated transcription

    Phthalate esters, widely used as plasticizers in the manufacture of products made of polyvinyl chloride, induce reproductive and developmental toxicities in rodents. The mechanism that underlies these effects of phthalate exposure, including the potential role of members of the nuclear receptor superfamily, is not known. The present study investigates the effects of phthalates on the pregnane X receptor (PXR), which mediates the induction of enzymes involved in steroid metabolism and xenobiotic detoxification. The ability of phthalate monoesters to activate PXR-mediated transcription was assayed in a HepG2 cell reporter assay following transfection with mouse PXR (mPXR), human PXR (hPXR), or the hPXR allelic variants V140M, D163G, and A370T. Mono-2-ethylhexyl phthalate (MEHP) increased the transcriptional activity of both mPXR and hPXR (5- and 15-fold, respectively) with EC50 values of 7-8 μM. mPXR and hPXR were also activated by monobenzyl phthalate (MBzP, up to 5- to 6-fold) but were unresponsive to monomethyl phthalate and mono-n-butyl phthalate (M(n)BP) at the highest concentrations tested (300 μM). hPXR-V140M and hPXR-A370T exhibited patterns of phthalate responses similar to the wild-type receptor. By contrast, hPXR-D163G was unresponsive to all phthalate monoesters tested. Further studies revealed that hPXR-D163G did respond to rifampicin, but required approximately 40-fold higher concentrations than wild-type receptor, suggesting that the ligand-binding domain D163G variant has impaired ligand-binding activity. The responsiveness of PXR to activation by phthalate monoesters demonstrated here suggests that these ubiquitous environmental chemicals may, in part, exhibit their endocrine disruptor activities by altering PXR-regulated steroid hormone metabolism with potential adverse health effects in exposed individuals

  2. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers

    Sheikh, Ishfaq A.; Turki, Rola F.; Abuzenadah, Adel M.; Damanhouri, Ghazi A.; Beg, Mohd A.

    2016-01-01

    Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15–31 amino acid residues of SHBG and a commonality of 55–95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates. PMID:26963243

  3. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers.

    Ishfaq A Sheikh

    Full Text Available Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15-31 amino acid residues of SHBG and a commonality of 55-95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates.

  4. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers.

    Sheikh, Ishfaq A; Turki, Rola F; Abuzenadah, Adel M; Damanhouri, Ghazi A; Beg, Mohd A

    2016-01-01

    Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15-31 amino acid residues of SHBG and a commonality of 55-95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates. PMID:26963243

  5. Solvent extraction of La(III) with 2-ethylhexyl phosphoric acid-2-ethylhexyl ester (EHEHPA) by membrane dispersion micro-extractor

    侯海龙; 王运东; 徐建鸿; 陈晋南

    2013-01-01

    The conventional rare earth solvent extraction equipments have many problems such as long mixing time, low processing capacity, large factory area occupation, high energy consumption and so on. In order to solve the problems, many types of equipments were brought out. In this work, studies were carried out on the La(III) extraction process with 2-ethylhexyl phosphoric acid-2-ethylhexyl ester (EHEHPA) by membrane dispersion micro-extractor. Equilibrium studies showed that the initial aqueous pH value 4.15 with the saponification rate 40%was the optimal operation condition. The effects of membrane dispersion micro-extractor operational conditions such as dispersion mode, bulk flow rate and organic phase flow rate on the extraction efficiency were studied. The results showed that when the organic solution was the dispersed phase, the extraction efficiency was higher than that of others. Increasing bulk flow ratio could enhance the extraction efficiency greatly. When the ratio of organic phase flow rate to that of aque-ous phase was 80:80, the extraction efficiency was over 95%. The effect of stripping phase acidity on the La(III) recovery was studied. The results showed that when the stripping phase pH was 2.0, organic phase flow rate to stripping phase flow rate was 20:80;the re-covery efficiency of La(III) can reach 82%.

  6. The influence of antenatal exposure to phthalates on subsequent female reproductive development in adolescence

    Hart, Roger; Doherty, Dorota A; Frederiksen, Hanne;

    2014-01-01

    We hypothesised that antenatal exposure to ubiquitous phthalates may lead to an earlier menarche and a lower prevalence of polycystic ovarian syndrome (PCOS) and polycystic ovarian morphology (PCO) in adolescence. The Western Australian Pregnancy Cohort (Raine) Study recruited 3000 women at 18...... (DEHP) were associated with a non-significant tendency towards an earlier age at menarche (p=0.069). Uterine volume was positively associated with mono-(carboxy-iso-octyl) phthalate (MCiOP) (p=0.018). Exposure to monoethyl phthalate (MEP) and the sum of all phthalate metabolites (Σall phth.m) was...

  7. Separation of scandium(III) and yttrium(III) by tris(2-ethylhexyl)phosphate (TEHP).

    Chhatre, M H; Shinde, V M

    1998-10-01

    Tris(2-ethylhexyl)phosphate is proposed as an extractant for scandium(III) and yttrium(III) from salicylate media. The optimum extraction conditions are evaluated and described. The method permits mutual separation of scandium(III) and yttrium(III) and can be used for the separation and determination of scandium(III) and yttrium(III) from binary and multicomponent mixtures. PMID:18967342

  8. Identification of the Biotransformation Products of 2-Ethylhexyl 4-(N,N-Dimethylamino)benzoate

    Leon, Z.; Vlieger, de, J.J.; Chisvert, A.; A. Salvador; Lingeman, H.; Irth, H.; Giera, M.A.

    2009-01-01

    Nowadays, 2-ethylhexyl 4-(N,N-dimethylamino)benzoate (EDP) is one of the most widely used UV filters in sunscreen cosmetics and other cosmetic products. However, undesirable processes such as percutaneous absorption and biological activity have been attributed to this compound. The in vitro metabolism of EDP was elucidated in the present work. First of all, the phase I biotransformation was studied in rat liver microsomes and two metabolites, N,N-dimethyl-p-aminobenzoic acid (DMP) and N-monom...

  9. Exposure to phthalates among premenstrual girls from rural and urban Gharbiah, Egypt: A pilot exposure assessment study

    Hablas Ahmed

    2011-05-01

    Full Text Available Abstract Background Phthalates have been identified as endocrine active compounds associated with developmental and reproductive toxicity. The exposure to phthalates in premenstrual Egyptian females remains unknown. The objective of this study was to characterize phthalate exposure of a potentially vulnerable population of premenstrual girls from urban and rural Egypt. Materials and methods We collected one spot urine sample from 60 10-13 year old females, 30 from rural Egypt, and 30 from urban Egypt from July to October 2009. Samples were analyzed for 11 phthalate metabolites. Additionally, we collected anthropometrics as well as questionnaire data concerning food storage behaviors, cooking practices, and cosmetic use. Phthalate metabolite concentrations were compared between urban and rural Egyptians as well as to age and gender matched Americans. Results Monoethyl phthalate (MEP, was detected at the highest concentration in urine of Egyptian girls (median: 43.2 ng/mL in rural, 98.8 ng/mL in urban. Concentrations of urinary metabolites of di-(2-ethylhexyl phthalate and dibutyl phthalate were comparable between Egyptians and age matched US girls. Storage of food in plastic containers was a statistically significant predictor of urinary mono-isobutyl phthalate (MiBP concentrations when comparing covariate adjusted means. Conclusions Urinary concentrations of phthalate metabolites were similar in Egyptian and US populations, suggesting that phthalate exposure also occurs in developing nations. Dietary intake is likely an important route of exposure to phthalates in both urban and rural populations.

  10. Organophosphate and phthalate esters in settled dust from apartment buildings in Stockholm.

    Luongo, G; Östman, C

    2016-06-01

    In this study, the occurrence of nine phthalate diesters (phthalates) and 14 organophosphorus flame retardants (PFRs) was investigated in 62 house dust samples collected from 19 buildings in Stockholm area during the year 2008. Eight phthalates were detected in almost all samples, with median concentrations ranging from 0.47 μg/g to 449 μg/g with di(2-ethylhexyl) phthalate being the most abundant compound. Twelve PFRs were detected with median concentrations ranging from 0.19 μg/g to 11 μg/g. Within this class of compounds, the most abundant were tris(2-chloroisopropyl) and tris(2-butoxyethyl) phosphate. Both classes of compounds were also measured in the air of the apartments, but no correlation between air and dust concentrations could be found. Based on these measurements, exposure, via house dust ingestion and air inhalation, was calculated for adults and toddlers, and compared to published limit values in order to estimate potential health risks. In an extreme exposure scenario for toddlers, di(2-ethylhexyl) phthalate, tris(2-chloroethyl) phosphate, tris(2-butoxyethyl) phosphate, and tributyl phosphate were close to the reference dose for chronic oral exposure or the tolerable daily intake. Standard Reference Material SRM 2585 was used as a quality control sample, and the levels of diisononyl and diisodecyl phthalates were determined in this material. PMID:25929991

  11. Determination of phthalates in polymer materials - comparison of GC/MS and GC/ECD methods

    Katarzyna Jaworek

    2013-01-01

    Full Text Available The paper presents two methods for determination of phthalates in polymer materials. The methods compared were gas chromatography combined with the mass spectrometry (GC/MS and gas chromatography with electron capture detector (GC/ECD. The GC/ECD technique was chosen for this comparison, because the ECD detector was one of few capable of detecting phthalates. In both cases the same procedure of sample preparation with ultrasonic extraction was applied. Overall recoveries were 76-100 % with relative of standard deviation (R.S.D. values in the range 0.6-19 %. The values of limit of detection (LOD for GC/MS method ranged from 3.46 µg mL- 1 to 10.10 µg mL- 1, depending on the determined phthalate, while in case of the GC/ECD method they were in the range from 2.97 µg mL- 1 to 4.29 µg mL- 1. The methods were applied for determination of: dimethyl phthalate, diethyl phthalate, di-n-butyl phthalate, benzyl butyl phthalate, bis(2-ethylhexyl phthalate, diisononyl phthalate, diisoocyl phthalate in polymer material. The seventeen kinds of samples were analyzed. Most of the materials selected for the analyses were made from polyethylene (PE, polyvinyl chloride (PVC and polystyrene (PS.

  12. Recycling of plastic waste: Presence of phthalates in plastics from households and industry.

    Pivnenko, K; Eriksen, M K; Martín-Fernández, J A; Eriksson, E; Astrup, T F

    2016-08-01

    Plastics recycling has the potential to substitute virgin plastics partially as a source of raw materials in plastic product manufacturing. Plastic as a material may contain a variety of chemicals, some potentially hazardous. Phthalates, for instance, are a group of chemicals produced in large volumes and are commonly used as plasticisers in plastics manufacturing. Potential impacts on human health require restricted use in selected applications and a need for the closer monitoring of potential sources of human exposure. Although the presence of phthalates in a variety of plastics has been recognised, the influence of plastic recycling on phthalate content has been hypothesised but not well documented. In the present work we analysed selected phthalates (DMP, DEP, DPP, DiBP, DBP, BBzP, DEHP, DCHP and DnOP) in samples of waste plastics as well as recycled and virgin plastics. DBP, DiBP and DEHP had the highest frequency of detection in the samples analysed, with 360μg/g, 460μg/g and 2700μg/g as the maximum measured concentrations, respectively. Among other, statistical analysis of the analytical results suggested that phthalates were potentially added in the later stages of plastic product manufacturing (labelling, gluing, etc.) and were not removed following recycling of household waste plastics. Furthermore, DEHP was identified as a potential indicator for phthalate contamination of plastics. Close monitoring of plastics intended for phthalates-sensitive applications is recommended if recycled plastics are to be used as raw material in production. PMID:27211312

  13. Phthalates and polybrominated diphenyl ethers in retail stores

    Xu, Ying; Liang, Yirui; Urquidi, Jorge R.; Siegel, Jeffrey A.

    2014-04-01

    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, because they are extensively used as additives in consumer products and associated with serious health concerns. This study measured six phthalate and 14 PBDE compounds inside of 12 retail stores in Texas and Pennsylvania, U.S. Phthalates and PBDEs were widely found in the retail environment, indicating that they are ubiquitous indoor air pollutants. DEP, DnBP, and DEHP were the most abundant phthalates, with DnBP showing the highest concentration (0.23 ± 0.36 μg m-3). PBDEs were dominated by BDE-28, -99, and -209, having concentrations as high as 0.85 ± 1.99 ng m-3 (BDE-99). The levels of phthalates and PBDEs measured in this study are comparable to concentrations found in previous investigations of residential buildings, with phthalates showing lower concentrations and PBDEs exhibiting higher concentrations in retail stores. The potential co-occurrence of phthalates was not as strong as that of PBDEs, suggesting that phthalates might have more diverse sources. Whole building emission rates were calculated and showed similar patterns of variations as indoor air concentrations, suggestion the diversity of indoor sources of phthalates and PBDEs in retail environments.

  14. Adsorption of lanthanum (III) from aqueous solution using 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester-grafted magnetic silica nanocomposites

    Highlights: • P507 functionalized magnetic silica nanocomposites were synthesized. • Adsorption behavior of La (III) with P507 functionalized magnetic silica nanocomposite was investigated. • Influencing factors for La (III) adsorption was discussed in batch experiments. • Adsorption mechanism was confirmed by FT-IR and XPS techniques. • Regeneration and repeated use for magnetic adsorbent was studied. -- Abstract: In view of increasing attention of magnetic materials in the field of separation science and technology, we provide an effective route for fabrication of a new magnetic material with high adsorption capacity and selectivity toward metal ions, excellent acid resistance property and long service life. Silica was firstly coated on the magnetic particles, and then silane-coupling agent (3-chloropropyltryethosysilane) was used for grating 2-ethylhexyl phosphonic acid mono-2-ethylhexyl (P507), an organophosphorous acid extractant, on the surface of magnetic silica nanocomposite. The amount of P507 anchored on the particle was estimated to be 0.43 mmol/g. The P507-grafted magnetic silica nanocomposite was stable over pH range of 0–14. The maximum adsorption capacity of La (III) was 55.9 mg/g at the optimized pH 5.5. The adsorption of La (III) on our nanocomposites was found to follow the second order kinetics equation and fit Langmuir isotherm model well. The P=O functional groups took an important role in the coordination and adsorption mechanism, which was confirmed by FTIR and XPS techniques. After 10 adsorption/desorption cycles, no obvious decrease in adsorption capacity or obvious loss in saturation magnetization were observed

  15. Extraction of U(VI), Pu(IV), Am(III) and some fission products by 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester immobilized polyvinyl alcohol hydrogels

    Cross-linked hydrogel matrices immobilized with 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (HA), were prepared to investigate their application in the recovery of radionuclide from acidic waste solutions. Gamma-radiation was used to produce HA immobilized polyvinyl alcohol (PVA) hydrogels (HA-gel). The hydrogels with different characteristics such as: degree of cross-linking (by varying radiation dose) and quantity of extractant immobilized (by starting with aqueous PVA solution containing different amounts of HA), were synthesised. These HA-gels were investigated for solid-liquid phase extraction of U(VI), Pu(IV), Am(III) and some fission products, under various experimental conditions. The concentration of HNO3 in the aqueous phase was found to play an important role in the extraction of these radionuclei. Extraction of U(VI) was more favourable at lower concentration of HNO3 (∼0.001 to 0.5M), while at higher concentrations (∼0.5 to 3M HNO3), more than 90% of Pu(IV) present in the aqueous phase, could be extracted by the HA-gel. The extraction of Am(III) was also found predominant only at lower acidities (at pH∼2 and above). Under optimized conditions, maximum metal loading capacities obtained were 19±0.8 mg, 8±0.4 mg and 11±0.5 mg per gram of swollen HA-gel, for U(VI), Pu(IV) and Am(III), respectively. Under the experimental conditions, extractions of Cs(I) and Sr(II) were observed to be negligible. No leaching out of HA from the HA-gel particles was noted even after its repetitive use for the studied ten cycles of extraction and stripping experiments, as evident from its unchanged extraction efficiency. (author)

  16. Thermal and enzymatic pretreatment of sludge containing phthalate esters prior to mesophilic anaerobic digestion

    Gavala, Hariklia N.; Yenal, U.; Ahring, Birgitte Kiær

    2004-01-01

    The present study aimed at investigating the effect of thermal pretreatment of sludge at 70degreesC on the anaerobic degradation of three commonly found phthalic acid esters (PAE): di-ethyl phthalate (DEP), di-butyl phthalate (DBP), and di-ethylhexyl phthalate (DEHP). Also, the enzymatic treatment...... at 28degreesC with a commercial lipase was studied as a way to enhance PAE removal. Pretreatment at 70degreesC of the sludge containing PAE negatively influenced the anaerobic biodegradability of phthalate esters at 37degreesC. The observed reduction of PAE biodegradation rates after the thermal...... orders of magnitude faster than under normal mesophilic anaerobic conditions. Moreover, the enzymatic treatment resulted in the shortest half-life of DEHP in sludge reported so far. Our study further showed that enzymatic treatment with lipases can be applied to raw sludge and its efficiency does...

  17. Fetal Phthalate Screen: Assessment of Several Phthalate Esters (PE) on Fetal Rodent Testosterone (T) Production and Gene Expressionfollowing In Utero Exposure

    PE are a large family of compounds used in a wide array of products from medical tubing to pharmaceuticals to cables. Studies have shown that in utero treatment with PE such as diethyl hexyl phthalate (DEHP) during the critical period of fetal reproductive development produced ma...

  18. NTP-CERHR EXPERT PANEL UPDATE ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DI(2-ETHYLHEXYL) PHTHALATE.

    The purpose of the Center is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction and development caused by agents to which humans may be exposed.

  19. Association Between Urinary Phthalates and Pubertal Timing in Chinese Adolescents

    Huijing Shi

    2015-09-01

    Full Text Available 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%.

  20. Synergistic solvent extraction of erbium (III) by mixtures of bis-2-ethylhexyl sulphoxide and 2-thenoyltrifluoroacetone

    Synergism in the extraction of Er(III) from thiocyanate solutions has been investigated using mixtures of bis-2-ethylhexyl sulphoxide (B2EHSO) and 2-thenoyltrifluoroacetone (HTTA) in benzene. These extraction data have been analysed theoretically with the aid of a computer by taking into account complexation of the metal in the aqueous phase by inorganic ligands and plausible complexation in the organic phase. The equilibrium constants of the various product species have been deduced by non-linear regression analysis. (author). 6 refs., 2 tab

  1. Distribution of Am and rare earths between acid mixed di-(2-ethylhexyl)phosphate decomposition products

    Reaction of decomposition of acid mixed-ligand complexes of rare earths by water, which are formed in the course of HNO3 interaction with LnA3 (Ln - La, Nd, Eu, Dy, Er, Lu) in the medium of acetone (A - di-(2-ethylhexyl)phosphoric acid) was studied. In the systems comprising complexes of different metals redistribution of metals between decomposition products is observed. This phenomenon can be put at the basis of the method of rare earths and actinide isolation. The dependence of metal distribution between decomposition products on the nature of rare earth elements is observed

  2. Distribution Behavior of Aminobenzoic Acid by Extraction with Di(2-ethylhexyl)phosphoric Acid

    2000-01-01

    A series of extraction equilibrium experiments for aminobenzoic acid with di(2-ethylhexyl)phosphoric acid (D2EHPA) dissolved in n-octane or 1-octanol was carried out. The effects of aminobenzoic acid concentration, D2EHPA concentration and pH on the distribution ratio were discussed in detail. The infrared spectra of the organic phase loaded with solute illustrated that pH had little effect on the structure of the complex formed. There proceed ion association and cation-exchange reaction in the extraction. An expression of the equilibrium distribution was proposed.

  3. Influence of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) on zinc electrodeposition

    Lehr, I.L. [Instituto de Ingenieria Electroquimica y Corrosion (INIEC), Departamento de Ingenieria Quimica, Universidad Nacional del Sur, Av. Alem 1253, 8000 Bahia Blanca (Argentina); Saidman, S.B., E-mail: ssaidman@criba.edu.ar [Instituto de Ingenieria Electroquimica y Corrosion (INIEC), Departamento de Ingenieria Quimica, Universidad Nacional del Sur, Av. Alem 1253, 8000 Bahia Blanca (Argentina)

    2012-03-01

    This work is a study of the electrodeposition of zinc onto SAE 4140 steel electrodes using solutions containing zinc sulfate and bis(2-ethylhexyl) sodium sulfosuccinate (AOT). The influence of different parameters such as electrolyte concentration, electrodeposition time and temperature on the morphology of the electrodeposits was analyzed. The deposits were characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and X-ray diffraction. The variation of open circuit potential over time in chloride solutions was also evaluated. The nucleation-growth process and consequently the morphology of the electrodeposits are modified in the presence of AOT. The surfactant induces the formation of a porous deposit.

  4. 76 FR 64810 - Beverages: Bottled Water Quality Standard; Establishing an Allowable Level for di(2-ethylhexyl...

    2011-10-19

    ... adopting the allowable level for DEHP in the bottled water quality standard as proposed (58 FR 41612... FR 41612), FDA published a proposal (``the 1993 proposed rule'') to revise the bottled water quality... HUMAN SERVICES Food and Drug Administration 21 CFR Part 165 Beverages: Bottled Water Quality...

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

    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.

  6. Variability and predictors of urinary phthalate metabolites in Spanish pregnant women.

    Valvi, Damaskini; Monfort, Nuria; Ventura, Rosa; Casas, Maribel; Casas, Lidia; Sunyer, Jordi; Vrijheid, Martine

    2015-03-01

    Developmental exposure to phthalates may be associated with adverse health outcomes but information on the variability and predictors of urinary phthalate metabolite concentrations during pregnancy is limited. We evaluated in Spanish pregnant women (n=391) the reproducibility of urinary phthalate metabolite concentrations and predictors of exposure. We measured mono-(4-methyl-7-hydroxyoctyl) phthalate (7-OHMMeOP), 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-(2-carboxyhexyl) phthalate (MCMHP), mono-benzyl phthalate (MBzP), mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) in two spot urine samples collected in the first and third pregnancy trimesters. Questionnaires on predictors and food-frequency questionnaires were administered in the first and/or third pregnancy trimesters. Using creatinine-adjusted phthalate metabolite concentrations (log10-trasformed) we calculated intraclass correlation coefficients (ICCs). Linear mixed and regression models assessed the associations between predictors and phthalate metabolites. The ICCs ranged from 0.24 to 0.07 and were higher for MBzP, MEP, MiBP, and lower for MEOHP and MEHHP. Overweight, lower education and social class, and less frequent consumption of organic food were associated with higher levels of some phthalate metabolites. The use of household cleaning products (bleach, ammonia, glass cleaners, oven cleaning sprays and degreasing products) at least once per week during pregnancy was associated with 10-44% higher urinary phthalate metabolites. Bottled-water consumption, consumption of food groups usually stored in plastic containers or cans, use of plastic containers for heating food and cosmetic use were not associated with increased concentrations of phthalate metabolites. This large study with repeated phthalate measurements

  7. Spectral Properties and Solubilization Location of 2'-Ethylhexyl 4-(N,N-Dimethylamino)benzoate in Micelles

    Ning Ding; Xin-zhen Du; Chun Wang; Xiao-quan Lu

    2008-01-01

    Dual fluorescence and UV absorption of 2'-ethylhexyl 4-(N,N-dimethylamino)benzoate (EHDMAB) were investigated in cationic,non-ionic and anionic miceUes.When EHDMAB was solubilized in different micellss, the UV absorption of EHDMAB was enhanced.Twisted intramolecular charge transfer (TICT) emission with longer wavelength was observed in ionic micelles,whereas TICT emission with shorter wavelength was obtained in non-ionic micelles.In particular,dual fluorescence of EHDMAB was significantly quenched by the positively charged pyridinium ions arranged in the Stern layer of cationic micelles.UV radiation absorbed mainly decays via TICT emission and radiationless deactivation.The dimethylamino group of EHDMAB experiences different polar environments in ionic and non-ionic micelles according to the polarity dependence of TICT emission of EHDMAB in organic solvents.In terms of the molecular structures and sizes of EHDMAB and surfactants,each individual EHDMAB molecule should be buried in micelles with its dimethylamino group toward the polar head groups of different micelles and with its 2'-ethylhexyl chain toward the hydrophobic micellar core.Dynamic fluorescence quenching measurements of EHDMAB provide further support for the location of EHDMAB in different micelles.

  8. Screening of phthalate esters in 47 branded perfumes.

    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

  9. Concentrations of phthalate metabolites in breast milk in Korea: estimating exposure to phthalates and potential risks among breast-fed infants.

    Kim, Sunmi; Lee, Jangwoo; Park, Jeongim; Kim, Hai-Joong; Cho, Geumjoon; Kim, Gun-Ha; Eun, So-Hee; Lee, Jeong Jae; Choi, Gyuyeon; Suh, Eunsook; Choi, Sooran; Kim, Sungjoo; Kim, Young Don; Kim, Sung Koo; Kim, Su Young; Kim, Seunghyo; Eom, Soyong; Moon, Hyo-Bang; Kim, Sungkyoon; Choi, Kyungho

    2015-03-01

    Phthalates have been associated with endocrine disruption and developmental effects in many experimental and epidemiological studies. Developing infants are among the most susceptible populations to endocrine disruption. However, limited information is available on phthalate exposure and its associated risks among breast-fed newborn infants. In the present study, breast milk samples were collected from 62 lactating mothers at 1 month post-partum from four cities of Korea in 2012 and were evaluated for six phthalate metabolites (mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono(2-ethyl-hexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and monoethyl phthalate (MEP)). MEP was detected in all breast milk samples, with a median concentration of 0.37 μg/L, and MiBP, MnBP and MEHP were detected in 79-89% of samples, with median concentrations of 1.10, 1.70, and 2.08 μg/L, respectively. However, MEHHP and MEOHP, the oxidized forms of di-ethyl-hexyl phthalate (DEHP), were detected in only one sample. For exposure assessment, the levels of phthalate diesters were estimated based on the parent:metabolite ratios in the breast milk that are reported elsewhere. For risk assessment, the endocrine-related toxicity of the monoester was assumed to be the same as that of its diester form. Median daily intake estimates of phthalates, including both monoester and diester forms, through breast milk consumption ranged between 0.91 and 6.52 μg/kg body weight (bw) for DEHP and between 0.38 and 1.43 μg/kg bw for di-n-butyl phthalate (DnBP). Based on the estimated daily intake, up to 8% of infants exceeded the reference dose of anti-androgenicity (RfD AA) for DEHP, and 6% of infants exceeded the tolerable daily intake (TDI) for DnBP. Breast milk MiBP and MnBP concentrations showed significant positive associations with maternal consumption of whipped cream or purified water. Considering vulnerability of

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

    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. PMID:27177745

  11. Study on the leaching of phthalates from polyethylene terephthalate bottles into mineral water

    Keresztes, Szilvia; Tatár, Enikő [Laboratory of Environmental Chemistry and Bioanalytics, Department of Analytical Chemistry, Institute of Chemistry, Eötvös Loránd University, H-1117 Budapest, Pázmány Péter sétány 1/A (Hungary); Czégény, Zsuzsanna [Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1525 Budapest, P.O. Box 17 (Hungary); Záray, Gyula [Laboratory of Environmental Chemistry and Bioanalytics, Department of Analytical Chemistry, Institute of Chemistry, Eötvös Loránd University, H-1117 Budapest, Pázmány Péter sétány 1/A (Hungary); Mihucz, Victor G., E-mail: vigami72@yahoo.es [Laboratory of Environmental Chemistry and Bioanalytics, Department of Analytical Chemistry, Institute of Chemistry, Eötvös Loránd University, H-1117 Budapest, Pázmány Péter sétány 1/A (Hungary)

    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{sup −1}–0.2 μg L{sup −1}, < 6.6 ng L{sup −1}–0.8 μg L{sup −1}, < 6.0 ng L{sup −1}–0.1 μg L{sup −1} and < 16.0 ng L{sup −1}–1.7 μg L{sup −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 0.5 L 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). - Highlights: • DEHP — most abundant phthalate in bottled mineral water • Temperature and contact surface area influence phthalate leaching. • Phthalate occurrence depends on virgin vs. polymer containing recycled PET. • pH (carbonated vs. non-carbonated samples) affects hydrolysis of phthalate esters.

  12. Study on the leaching of phthalates from polyethylene terephthalate bottles into mineral water

    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: −1–0.2 μg L−1, −1–0.8 μg L−1, −1–0.1 μg L−1 and −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 0.5 L 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). - Highlights: • DEHP — most abundant phthalate in bottled mineral water • Temperature and contact surface area influence phthalate leaching. • Phthalate occurrence depends on virgin vs. polymer containing recycled PET. • pH (carbonated vs. non-carbonated samples) affects hydrolysis of phthalate esters

  13. Phthalate Exposure and Health-Related Outcomes in Specific Types of Work Environment

    Kolena, Branislav; Petrovicova, Ida; Pilka, Tomas; Pucherova, Zuzana; Munk, Michal; Matula, Bohumil; Vankova, Viera; Petlus, Peter; Jenisova, Zita; Rozova, Zdenka; Wimmerova, Sona; Trnovec, Tomas

    2014-01-01

    Many toxic substances in the workplace can modify human health and quality of life and there is still insufficient data on respiratory outcomes in adults exposed to phthalates. The aim of this work was to assess in waste management workers from the Nitra region of Slovakia (n = 30) the extent of exposure to phthalates and health-related outcomes. Four urinary phthalate metabolites mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MnBP), monoethyl phthalate (MEP) and monoisononyl phthalate (MiNP) were determined by high-performance liquid chromatography with mass spectrometry (HPLC-MS/MS). Urinary concentration of MEHP was positively associated with ratio of forced expiratory volume in 1 s to forced vital capacity % (FEV1/FVC) (r = 0.431; p = 0.018) and MiNP with fat free mass index (FFMI) (r = 0.439; p = 0.015). The strongest predictor of pulmonary function was the pack/year index as smoking history that predicted a decrease of pulmonary parameters, the FEV1/FVC, % of predicted values of peak expiratory flow (PEF % of PV) and FEV1 % of PV. Unexpectedly, urinary MEHP and MINP were positively associated with pulmonary function expressed as PEF % of PV and FEV1/FVC. We hypothesize that occupational exposure to phthalates estimated from urinary metabolites (MEHP, MiNP) can modify pulmonary function on top of lifestyle factors. PMID:24865398

  14. Phthalate Exposure and Health-Related Outcomes in Specific Types of Work Environment

    Branislav Kolena

    2014-05-01

    Full Text Available Many toxic substances in the workplace can modify human health and quality of life and there is still insufficient data on respiratory outcomes in adults exposed to phthalates. The aim of this work was to assess in waste management workers from the Nitra region of Slovakia (n = 30 the extent of exposure to phthalates and health-related outcomes. Four urinary phthalate metabolites mono(2-ethylhexyl phthalate (MEHP, monobutyl phthalate (MnBP, monoethyl phthalate (MEP and monoisononyl phthalate (MiNP were determined by high-performance liquid chromatography with mass spectrometry (HPLC-MS/MS. Urinary concentration of MEHP was positively associated with ratio of forced expiratory volume in 1 s to forced vital capacity % (FEV1/FVC (r = 0.431; p = 0.018 and MiNP with fat free mass index (FFMI (r = 0.439; p = 0.015. The strongest predictor of pulmonary function was the pack/year index as smoking history that predicted a decrease of pulmonary parameters, the FEV1/FVC, % of predicted values of peak expiratory flow (PEF % of PV and FEV1 % of PV. Unexpectedly, urinary MEHP and MINP were positively associated with pulmonary function expressed as PEF % of PV and FEV1/FVC. We hypothesize that occupational exposure to phthalates estimated from urinary metabolites (MEHP, MiNP can modify pulmonary function on top of lifestyle factors.

  15. Extraction mechanism of scandium(III) from sulphuric acid solution by di-(2-ethylhexyl) phosphoric acid

    The extraction equilibria of scandium(III) and sulphuric acid extracted by H(DEHP) in n-heptane from sulphuric acid aqueous medium is studied. Extraction mechanisms of scandium(III) and sulphuric acid under different concentrations of sulphuric acid in the aqueous phase are suggested through infrared and NMR measurements and saturation extraction study. The effect of temperature on extraction equilibria is discussed and the thermodynamic functions of the extraction reactions are calculated

  16. Identification and quantification of n-octyl esters of alkanoic and hexanedioic acids and phthalates as urban wastewater markers in biota and sediments from estuarine areas.

    Chaler, Roser; Cantón, Lourdes; Vaquero, Menchu; Grimalt, Joan O

    2004-08-13

    A gas chromatographic method for the identification and quantification of n-octyl esters (from n-octyl tetradecanoate to n-octyl hexa-cosanoate including dioctyl hexanedioate) and phthalates [dibutyl phthalate, benzyl butyl phthalate and di(2-ethylhexyl) phthalate] in sediments and biota from estuarine environments is described. Standards used for identification and quantification of some n-octyl esters were synthesized. The method has allowed the analysis of these compounds in polychaeta (Nereis diversicolor), oysters (Crassostea angulata), crabs (Carcinus maenas) and fish (Chelon labrosus, Platichtys flesus and Chondostroma polylepis) that were collected at different locations of the Urdaibai estuary (Bizkaia, Basque Country, Spain). Total phthalates and n-octyl esters ranged between 0.01 and 12 microg g(-1) and 0.05 and 9.4 microg g(-1), respectively, and were predominantly found in polychaeta and fish. Sediments did not contain these compounds in significant amount, only benzyl butyl phthalate, dioctyl hexanedioate and di(2-ethylhexyl) phthalate were found above limit of detection (0.01-0.05 microg g(-1)). PMID:15387189

  17. Prenatal plus postnatal exposures to phthalates and child health risks

    G. Latini

    2011-01-01

    Full Text Available Phthalates are a class of chemicals predominantly used as plasticizers in many plastics since the 1930's, in a wide variety of manufacturing applications and consumer products. Given their extensive use and their leakage from plastics, they are ubiquitous environmental contaminants with potential detrimental health effects. Di(2-ethylhexylphthalate (DEHP is the most commonly used phthalate plasticizer. There is widespread exposure to phthalates in the general population and therefore it is importat to investigate the toxic potential of these compounds. In particular, phthalate exposure has been shown to cause developmental and reproductive anomalies in animal models, and there is concern that these compounds may be causing adverse effects on human reproductive health. Phthalate effects are suspected to be much more severe after in uterus exposure. Phthalate esters are considered endocrine balance and development of the mammalian testis, thus exerting harmful effects on mammalian reproduction and fertility. Health risk assessments for the phthalate exposure of the general population should be performed and current PVC plasticizers, especially the ones used for infants should be replaces with high quality materials.

  18. Radiochemical extraction of lanthanide thiocyanate complexes with bis-2-ethylhexyl sulphoxide

    The extraction of lanthanides (Ln) such as Nd(III), Eu(III) and Er(III) from thiocyanate solutions by bis-2-ethylhexyl sulphoxide (B2EHSO) in benzene has been studied by tracer techniques. For comparison, extraction studies have been carried out with di-n-octyl sulphoxide (DOSO) and tri-octyl phosphine oxide (TOPO). Extraction studies have also been carried out with mixtures of B2EHSO and DOSO or TOPO. A relatively small synergistic enhancement has been observed with a mixture of extractants, which may be due to the formation of more stable mixed-ligand complexes. The extraction data have been analysed by both graphical and theoretical methods taking into account aqueous phase speciation and all plausible complexes extracted into the organic phase. The equilibrium constants of the extracted species were determined by non-linear regression analysis. (orig.)

  19. Extraction equilibrium of mercury(II) with bis(2-ethylhexyl) sulfoxide

    The extraction of mercury(II) from chloride and thiocyanate solutions has been studied by tracer techniques using bis(2-ethylhexyl)sulphoxide (B2EHSO) in benzene as an extractant. These extraction data have been analyzed theoretically by taking into account complexation of the metal in the aqueous phase by inorganic ligands and plausible complexation in the organic phase.The results demonstrate that Hg(II) is extracted as HgX2 and HgX2 x nB2EHSO (where X=Cl- or SCN- and n=1 or 2). The effect to the foreign ions on the extraction of Hg(II) has also been investigated. (author) 14 refs.; 2 figs.; 1 tab

  20. Study of kinetics of scandium extraction by di(2-ethylhexyl)phosphoric acid

    Kinetics of extracting scandium with (2-ethylhexyl)phosphoric acid (D2EHPA) from 0.5 and 8 mol/l solutions of hydrochloric acid has been studied. At [Sc]:[D2EHPA] ratio equal to 1:2.6 and 1:3.2 equilibrium is attained in strongly acid solutions after 40 and 10 minutes periods of contacting and in weakly acid solutions after 60 and 20 minutes. At [Sc]:[D2EHPA] ratio more than 1:4.6 the equilibrium is attained for less than two minutes. The rate constant of scandium extraction by cation-exchange mechanism is 0.0293 cm/min and by solvate mechanism 0.0415 cm/min. The activation energy upon extracting from weakly acid solutions is 5.4 kcal/mol, from strongly acid solutions - 1.8 kcal/mol

  1. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis

    Boberg, Julie; Metzdorff, Stine Broeng; Vinggaard, Anne;

    2006-01-01

    Diethylhexyl phthalate (DEHP) is widely used as a plasticizer in consumer products and is known to disturb the development of the male reproductive system in rats. The mechanisms by which DEHP exerts these effects are not yet fully elucidated, though some of the effects are related to reduced fetal...... testosterone production. The present study investigated the effects of four different doses of DEHP on fetal testicular histopathology, testosterone production and expression of proteins and genes involved in steroid synthesis in fetal testes. Pregnant Wistar rats were gavaged from GD 7 to 21 with vehicle, 10...... synthesis, and reduced expression of the cryptorchidism-associated Insl-3. Immunohistochemistry showed clear reductions of StAR, PBR, P450scc and PPAR gamma protein levels in fetal Leydig cells, indicating that DEHP affects regulation of certain steps in cholesterol transport and steroid synthesis. The...

  2. Serum phthalate levels and time to pregnancy in couples from Greenland, Poland and Ukraine

    Specht, Ina Olmer; Bonde, Jens Peter; Toft, Gunnar;

    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...... 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....

  3. Maternal and early life exposure to phthalates: The Plastics and Personal-care Products use in Pregnancy (P4) study.

    Arbuckle, Tye E; Fisher, Mandy; MacPherson, Susan; Lang, Carly; Provencher, Gilles; LeBlanc, Alain; Hauser, Russ; Feeley, Mark; Ayotte, Pierre; Neisa, Angelica; Ramsay, Tim; Tawagi, George

    2016-05-01

    Phthalates are a group of chemicals found in a number of consumer products; some of these phthalates have been shown to possess estrogenic activity and display anti-androgenic effects. While a number of biomonitoring studies of phthalates in pregnant women and infants have been published, there is a paucity of data based on both multiple sampling periods and in different matrices. Phthalate metabolites were measured in 80 pregnant women and their infants in Ottawa Canada (2009-2010) in urine, meconium and breast milk collected at various time periods pre- and post-parturition. At least 50% of the women had at least one urine sample greater than the limit of detection (LOD) for the various phthalate metabolites, with the exception of mono-n-octyl phthalate (MnOP), mono-isononyl phthalate (MiNP) and mono(carboxy-isooctyl) phthalate (MCiOP). Four major clusters of maternal urinary metabolites were identified. Among infants (n=61), the following metabolites were rarely (phthalate (MCHP), mono-isononyl phthalate (MiNP), mono-methyl phthalate (MMP), and mono-n-octyl phthalate (MnOP). While mono-benzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), MEHHP, and MEOHP were frequently detected in maternal urines at any time point, these metabolites were rarely detected in breast milk. Maternal urinary concentrations of MEP and the DEHP metabolites were higher in samples collected during pregnancy than postnatally. No statistically significant differences were observed in infant's urinary phthalate concentrations between breast-fed and bottle-fed infants. Significant correlations were observed between maternal urinary MEHHP (r=0.35), MEOHP (r=0.35) and MEP (r=0.37) collected at infant urine collected 2-3months after birth. These results suggest at least some maternal-fetal-infant transfer of phthalates and that meconium may be a useful matrix for measuring in utero exposure to phthalates. PMID:26878646

  4. Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy

    Nina Holland

    2016-03-01

    Full Text Available People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects of exposure in early and late pregnancy. In this study, we examined the relationship of eleven urinary phthalate metabolites with isoprostane, an established marker of oxidative stress, among pregnant Mexican-American women from an agricultural cohort. Isoprostane levels were on average 20% higher at 26 weeks than at 13 weeks of pregnancy. Urinary phthalate metabolite concentrations suggested relatively consistent phthalate exposures over pregnancy. The relationship between phthalate metabolite concentrations and isoprostane levels was significant for the sum of di-2-ethylhexyl phthalate and the sum of high molecular weight metabolites with the exception of monobenzyl phthalate, which was not associated with oxidative stress at either time point. In contrast, low molecular weight metabolite concentrations were not associated with isoprostane at 13 weeks, but this relationship became stronger later in pregnancy (p-value = 0.009 for the sum of low molecular weight metabolites. Our findings suggest that prenatal exposure to phthalates may influence oxidative stress, which is consistent with their relationship with obesity and other adverse health outcomes.

  5. Separation of middle rare earths by solvent extraction using 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester as an extractant

    Danilo; Fontana; Loris; Pietrelli

    2009-01-01

    The extraction of the trivalent middle rare earths from chloride media by kerosene solutions of 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester as an extractant was studied. The separation factors between the elements using solution simulating wastes from NiMH spent batteries have been evaluated: the order of the extractive ability of extractant can be confirmed in ThGdEuSm.

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

    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. PMID:27007912

  7. A longitudinal study of urinary phthalate excretion in 58 full-term and 67 preterm infants from birth through 14 months

    Frederiksen, Hanne; Kuiri-Hänninen, Tanja; Main, Katharina M;

    2014-01-01

    BACKGROUND: Some phthalates have shown antiandrogenic effects in rat offspring. Premature infants may be exposed to high amounts of specific phthalates during hospitalization, and thus are potentially at risk. OBJECTIVE: We evaluated longitudinal phthalate exposure and metabolism in full-term (FT......) and preterm (PT) infants. METHODS: Fifty-eight FT and 67 PT (gestational age, 24.7-36.6 weeks) infants were recruited at birth and followed until 14 months (nine times). Urinary concentrations of metabolites of diethyl phthalate (DEP), dibutyl phthalate isomers (DiBP and DnBP), butylbenzyl phthalate......% of FT infants, and after M2, in 30% of all infants. The excretion pattern of DEHP and DiNP metabolites changed with age. CONCLUSION: Most PT infants and approximately one-third of healthy FT newborns were exposed to phthalates during early life at a potentially harmful level according to the European...

  8. 77 FR 12852 - Draft Guidance for Industry on Limiting the Use of Certain Phthalates as Excipients in Center for...

    2012-03-02

    ... (DEHP). In particular, the draft guidance recommends that the pharmaceutical industry avoid the use of... Products.'' This draft guidance provides the pharmaceutical industry with CDER's current thinking on the... recommends that the pharmaceutical industry avoid the use of these two specific phthalates as excipients...

  9. Statistical study on yttrium recovery by solvent extraction using mono(2-ethylhexyl)2-ethylhexylphosphonic acid

    The scope of this experimental work was to study the yttrium extraction and stripping behavior in a solvent extraction system with mono(2-ethylhexyl)2-ethylhexylphosphonic acid (IONQUEST 801) in a chloride system. The study was performed for only one contact between organic and aqueous phases. The experiments were carried out according to a factorial design. Due to the statistical analysis and its experimental proof, the optimum conditions for maximum yttrium loading into the organic phase of the extraction stage were 16 minutes for time of contact between phases, 980 rpm of stirring intensity and pH = 2.3 for the aqueous phase of the solvent extraction system. The optimized experimental conditions by the statistical approach for the stripping stage were: time of contact between phases equal to 20 minutes, 1,050 rpm of stirring intensity and 1.75 M HCl into the stripping aqueous solution. Some important applications of yttrium and heavy rare earth elements range from fluorescent devices, magnetic substances and hydrogen storage alloys to superconductivity

  10. Mixed-ligand chelate extraction of lanthanides with thenoyltrifluoroacetone and bis-2-ethylhexyl sulphoxide

    Mixed-ligand chelate extraction of lanthanides (Ln) such as Nd(III), Eu(III) and Lu(III) into benzene with mixtures of thenoyltrifluoroacetone (HTTA) and bis-2-ethylhexyl sulphoxide (B2EHSO) from thiocyanate solutions has been studied by tracer techniques. For comparison, extraction studies have also been carried out from perchlorate solutions with mixtures of HTTA and B2EHSO. A very high synergistic enhancement of the order 103 has been observed in the extraction of Nd(III) or Eu(III) and about 102 fold enhancement in the extraction of Lu(III). Lanthanides are found to be extracted from thiocyanate solutions as mixed-ligand species: Ln(SCN)x.(TTA)3-x.yB2EHSO; whereas from perchlorate solutions the complexes extracted into the organic phase are Ln(TTA)3.B2EHSO and Ln(TTA)3.2B2EHSO. The extraction constants of these mixed-ligand chelate systems do not increase monotonically with atomic number but have a maximum at Eu(III). (orig.)

  11. Evaluation of the Phthalate Esters in South Indian Women with Endometriosis

    with Endometriosis

    2008-01-01

    Full Text Available Background: To evaluate the possible association between phthalate esters (PEs and the occurrenceof endometriosis. Blood samples were collected from 99 infertile women with endometriosis (studygroup; 135 age-matched women without endometriosis (control group but with infertility relatedto tubal defects, fibroids, polycystic ovaries, idiopathic infertility and pelvic inflammatory diseasesdiagnosed by laparoscopy with no evidence of endometriosis or other gynecological disordersduring laparoscopic sterilization.Materials and Methods: This is a prospective case-control study, which recruited womenundergoing infertility treatment at three collaborating centers (BMMHRC: Bhagwan MahavirMedical Hospital and Research Centre, MHRT: Maternal Health and Research Trust, and OwaisiHospital and Research Center of Reproductive Medicine Hyderabad, which receives cases fromall over the region of Andhra Pradesh, India. The concentrations of Phthalate Esters were measuredby using the High Performance Liquid Chromatography (HPLC.Evaluation of Phthalate Esters concentrations in women with endometriosis compared with womenwho are free from the disease.Results: Women with endometriosis showed significantly higher concentrations of Phthalate esters(Dimethyl phthalate (DMP, Diethyl phthalate (DEP, Di-n-butyl phthalate (DnBP, Butyl benzylphthalate (BBP and Bis (2-ethylhexyl phthalate (BEHP compared with control group. Wefound that (38% of the cases with endometriosis and (21% of the control group. The correlationbetween the concentrations of Phthalate esters and different severity of endometriosis was strongand statistically significant at p<0.05 for all five compounds (DMP: r=+0.57, p<0.0001; DnBPr=+0.39, p<0.0001; BBP: r=+0.89, p<0.0001; DnOP: r=+0.66, p<0.0001 and BEHP: r=+0.33,p<0.0014.Conclusion: This study for the first time from Indian subcontinent demonstrates that possiblyPhthalate Esters might have a role in etiology of endometriosis.

  12. Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns.

    Martino-Andrade, A J; Liu, F; Sathyanarayana, S; Barrett, E S; Redmon, J B; Nguyen, R H N; Levine, H; Swan, S H

    2016-07-01

    Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS ) and anopenile distance (AGPAP ) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono-2-ethyl-5-oxohexyl (MEOHP, β=-0.48; 95% confidence interval, -0.93, -0.02), MEHHP (-0.48; -0.92, -0.05), mono-2-ethyl-5-carboxypentyl (MECPP, -0.51; -1.01, -0.004), although no appreciable associations were seen between PW and T1 and T3 DEHP metabolite concentrations in this subset. Concentrations of DEHP metabolites in T1 urine samples were inversely related to male AGD. For example, in T1 samples in this subset of women mono-2-ethyl-5-hydroxyhexyl (MEHHP) was inversely associated with male AGDAP (β = -1.73; 95% confidence interval, -3.45, 0.0004). However, no appreciable associations were seen between AGD measures and any DEHP metabolite in T2 and T3 samples. These data suggest that DEHP exposure is inversely associated with AGD and PW, with PW primarily associated with T2 exposure and AGD associations seen only for T1 exposure, but no associations were found between T3 DEHP metabolites and any of these genital endpoints. These findings are consistent with data on critical windows in rodent studies, supporting the biological plausibility of these

  13. SIMULTANEOUS DEGRADATION OF SOME PHTHALATE ESTERS UNDER FENTON AND PHOTO-FENTON OXIDATION PROCESSES

    BELDEAN-GALEA M.S.

    2015-03-01

    Full Text Available In this study the assessment of the degradation efficiency of five phthalates, DEP, BBP, DEHP, DINP and DIDP, found in a mixture in a liquid phase, using the Fenton and Photo Fenton oxidation processes, was conducted. It was observed that the main parameters that influence the Fenton oxidative processes of phthalates were the concentration of the oxidizing agent, H2O2, the concentration of the catalyst used, Fe2+, the pH value, UV irradiation and the reaction time. For the Fenton oxidative process, the highest degradation efficiencies were 19% for DEP, 50% for BBP, 84% for DEHP, 90% for DINP and 48% for DIDP, when the experiments were carried out using concentrations of 20 mg L-1 phthalate mixture, 100 mg L-1 H2O2, 10 mg L-1 Fe2+ at a pH value of 3, with a total reaction time of 30 minutes. For the Photo-Fenton oxidative process carried out in the same conditions as Fenton oxidative process, it was observed that after an irradiation time of 90 minutes under UV radiation the degradation efficiencies of phthalates were improved, being 22% for DEP, 71% for BBP, 97% for DEHP, 97% for DINP and 81% for DIDP.

  14. Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat

    Diethyl hexyl phthalate (DEHP) is an endocrine disruptor, it influences various organ systems in human beings and experimental animals. DEHP reduced the serum testosterone and increased the blood glucose, estradiol, T3 and T4 in rats. However, the effect of DEHP on insulin signaling and glucose oxidation in skeletal muscle is not known. Adult male albino rats were divided into four groups: Group I: Control; Groups II and III: DEHP treated (dissolved in olive oil at a dose of 10 and 100 mg/kg body weight, respectively, once daily through gastric intubation for 30 days); and Group IV: DEHP (100 mg/kg body weight) plus vitamins E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubation for 30 days. On completion of treatment, animals were euthanized and perfused (whole body); gastrocnemius muscle was dissected out and subjected to assessment of various parameters. DEHP treatment increased the H2O2, hydroxyl radical levels and lipid peroxidation which disrupt the membrane integrity and insulin receptor. DEHP impaired the insulin signal transduction, glucose uptake and oxidation through decreased expression of plasma membrane GLUT4, which may partly be responsible for the elevation of fasting blood glucose level. The present study suggests that DEHP exposure affects glucose oxidation in skeletal muscle and is mediated through enhanced lipid peroxidation, impaired insulin signaling and GLUT4 expression in plasma membrane. Antioxidant vitamins (C and E) have a protective role against the adverse effect of DEHP. -- Highlights: ► DEHP treatment significantly decreased serum insulin and testosterone levels. ► Increased ROS and decreased glucose uptake were observed in DEHP treated animals. ► Impaired insulin signaling in gastrocnemius muscle was observed in DEHP treatment. ► Vitamins C and E alter ROS, glucose uptake, oxidation and insulin signaling molecules.

  15. Tris(2-ethylhexyl) phosphate: a new extractant for U(VI) and Pu(IV) from aqueous nitric acid solutions

    The extraction of U(VI) and Pu(IV) by tris(2-ethylhexyl) phosphate (TEHP), a higher homologue of commonly used tributyl phosphate (TBP), is discussed. The distribution data is analysed and the complexes formed have been established. An efficient extraction of both U(VI) and Pu(IV) from 2 M HNO3 is readily accomplished. Stripping of both of these cations is possible from the loaded organic phase by commonly used strippants. (author). 3 refs., 2 tabs

  16. Extraction kinetics of uranium(VI) with di(2-ethylhexyl) phosphoric acid using a hollow fiber membrane extractor

    The kinetics of solvent extraction of U(VI) with di(2-ethylhexyl) phosphoric acid (HDEHP) using a microporous hydrophobic hollow fiber membrane extractor has been investigated. The effects of U(VI) and hydrogen ion concentrations in aqueous phase, HDEHP concentration in organic phase, flow velocities of aqueous and organic phase and temperature on extraction rate of U(VI) were examined. The experimental results suggest that the extraction rate of U(VI) is controlled by diffusion. (author)

  17. Formation of chlorinated breakdown products during degradation of sunscreen agent, 2-ethylhexyl-4-methoxycinnamate in the presence of sodium hypochlorite

    Gackowska, Alicja; Przybyłek, Maciej; Studziński, Waldemar; Gaca, Jerzy

    2015-01-01

    In this study, a new degradation path of sunscreen active ingredient, 2-ethylhexyl-4-methoxycinnamate (EHMC) and 4-methoxycinnamic acid (MCA) in the presence of sodium hypochlorite (NaOCl), was discussed. The reaction products were detected using gas chromatography–mass spectrometry (GC-MS). Since HOCl treatment leads to more polar products than EHMC, application of polar extracting agents, dichloromethane and ethyl acetate/n-hexane mixture, gave better results in terms of chlorinated breakdo...

  18. Prenatal exposure to phthalates is associated with decreased anogenital distance and penile size in male newborns.

    Bustamante-Montes, L P; Hernández-Valero, M A; Flores-Pimentel, D; García-Fábila, M; Amaya-Chávez, A; Barr, D B; Borja-Aburto, V H

    2013-08-01

    Reproductive effects from phthalate exposure have been documented mostly in animal studies. This study explored the association between prenatal exposure to phthalate metabolites, anogenital distance and penile measurements in male newborns in Toluca, State of Mexico. A total of 174 pregnant women provided urine samples for phthalate analysis during their last prenatal visit, and the 73 who gave birth to male infants were included in the study. The 73 male newborns were weighed and measured using standardized methods after delivery. After adjusting for creatinine and supine length at birth, significant inverse associations were observed between an index of prenatal exposure to total phthalate exposure and the distance from the anus to anterior base of the penis (β = -0.191 mm per 1 μg/l, P = 0.037), penile width (β = -0.0414, P = 0.050) and stretched length (β = -0.2137, P = 0.034); prenatal exposure to mono-2-ethylhexyl phthalate exposure was associated with a reduction in the stretched length of the penis (β = -0.2604, P = 0.050). Human exposure to phthalates is a public health concern, and the system most vulnerable to its potential effects seems to be the immature male reproductive tract. PMID:24349678

  19. Concentrations of phthalates and DINCH metabolites in pooled urine from Queensland, Australia.

    Gomez Ramos, M J; Heffernan, A L; Toms, L M L; Calafat, A M; Ye, X; Hobson, P; Broomhall, S; Mueller, J F

    2016-03-01

    Dialkyl phthalate esters (phthalates) are ubiquitous chemicals used extensively as plasticizers, solvents and adhesives in a range of industrial and consumer products. 1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a phthalate alternative introduced due to a more favourable toxicological profile, but exposure is largely uncharacterised. The aim of this study was to provide the first assessment of exposure to phthalates and DINCH in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n=24 pools of 100). Concentrations of free and total species were measured using online solid phase extraction isotope dilution high performance liquid chromatography tandem mass spectrometry. Concentrations ranged from 2.4 to 71.9ng/mL for metabolites of di(2-ethylhexyl)phthalate, and from phthalate metabolites concentrations in Australia were at least two times higher than in the United States and Germany; and may be related to legislative differences among countries. DINCH metabolite concentrations were comparatively low and consistent with the limited data available. Ongoing biomonitoring among the general Australian population may help assess temporal trends in exposure and assess the effectiveness of actions aimed at reducing exposures. PMID:26760715

  20. Extraction and transport of uranium (VI) by polymer inclusion membranes incorporating Di-(2-ethylhexyl) phosphoric acid

    Di-(2-ethylhexyl) phosphoric acid (D2EHPA) is a commonly used extraction reagent for the separation of uranium from aqueous solutions. Previous work showed the suitability of a polymer inclusion membrane (PIM) based on D2EHPA and poly(vinyl chloride) (PVC) for the extraction and transport of uranium (VI) from sulfate solutions. This study investigates the influence of the main system parameters (i.e. stirring rate, percentage of D2EHPA in the membrane, initial U(VI) concentration, membrane thickness, and concentration of sulfuric acid) on the extraction process. A comprehensive mathematical model, describing the extraction of U(VI), was developed, numerically solved and fitted to the experimental extraction data to determine the values of the extraction constant and the diffusion coefficient of the U(VI)-D2EHPA complex in the membrane. The transport properties of the PVC/D2EHPA PIM have been further improved by adding o-nitrophenyloctyl ether as plasticizer. Fluxes of U(VI) as high as 1.5 x 10-6 mol m-2 S-1 were recorded using a membrane composed of 35% D2EHPA, 10% o-nitrophenyloctyl ether and 55% PVC (m/m) from a solution containing 100 mg L-1 U(VI) in 0.1 mol L-1 H2SO4 into a solution containing 6 mol L-1H2SO4. The effect of the counter-ion on the extraction and back extraction of uranium was also investigated and the membranes were tested for durability over repeated cycles of extraction and back-extraction. It was demonstrated that a 45% D2EHPA and 55% PVC PIM (m/m) allowed U(VI) to be completely separated thermodynamically from a range of common metal cations and kinetically from iron (III). (author)

  1. Urinary Phthalate Metabolites Are Associated With Decreased Serum Testosterone in Men, Women, and Children From NHANES 2011–2012

    Ferguson, Kelly K.

    2014-01-01

    Context: There is evidence of declining trends in T levels among men in recent decades, as well as trends in related conditions at multiple life stages and in both sexes. There is also animal and limited human evidence that exposure to phthalates, chemicals found in plastics and personal care products, is associated with reduced androgen levels and associated disorders. Objective: To explore relationships between urinary concentrations of 13 phthalate metabolites and serum total T levels among men, women, and children when adjusting for important confounders and stratifying by sex and age (6–12, 12–20, 20–40, 40–60, and 60–80 y). Design: A cross-sectional study. Setting: US National Health and Nutrition Examination Survey, 2011–2012. Patients or Other Participants: US general population. Interventions: None Main Outcome Measures: Serum total T measured by isotope dilution-liquid chromatography-tandem mass spectrometry. Results: Multiple phthalates were associated with significantly reduced T in both sexes and in differing age groups. In females, the strongest and most consistent inverse relationships were found among women ages 40–60 years. In boys 6–12 years old, an interquartile range increase in metabolites of di-2-ethylhexyl phthalate was associated with a 29% (95% confidence interval, 6, 47) reduction in T. In adult men, the only significant or suggestive inverse associations between phthalates (metabolites of di-2-ethylhexyl phthalate and dibutyl phthalate) and T were observed among men ages 40–60 years. Conclusions: Because T plays an important role in all life stages for both sexes, future efforts should focus on better defining these relationships and their broader impacts. PMID:25121464

  2. 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

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

    2013-01-01

    . 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......'s total intake of certain phthalates. Such exposures, by themselves, may lead to intakes exceeding current limit values....

  3. Investigation of the amount of transdermal exposure of newborn babies to phthalates in paper diapers and certification of the safety of paper diapers.

    Ishii, Satoko; Katagiri, Ritsuko; Minobe, Yasushi; Kuribara, Isamu; Wada, Takeharu; Wada, Mitsuhiro; Imai, Shigeo

    2015-10-01

    A risk assessment study of seven phthalates in paper diapers for newborn babies produced in Japan was performed. The diapers were purchased and the contents of the seven phthalates were determined and estimated amounts of exposure were calculated based on the eluted rate into artificial medium of urine or sweat, average weight of infants, and frequency of use. Di-2-ethylhexyl phthalate and di-n-butyl phthalate were detected in the topsheets and determined to be 0.6 μg/g and 0.2 μg/g, respectively. The daily estimated exposure volume was calculated to be in the range of 1.86 × 10(-10)-2.98 × 10(-6) mg/kg/day as follows: content of seven phthalates in the topsheet (0.1-1 μg/g) × eluted rate of phthalates into artificial sweat (0.0006-2.4%) × weight of the topsheet of a diaper (1.5 g) × the number of diapers used per day (12 sheets) × skin absorption rate (0.005-0.1)/average body weight (2.9 kg). For hazard assessment, we used 0.2-300 mg/kg/day for the seven phthalates based on the data available at international agencies. The margin of exposure to the seven phthalates was 6.71 × 10(4)-1.99 × 10(11), indicating that the risk of exposure to phthalates from the diapers produced in Japan was negligible. PMID:26123074

  4. Food safety involving ingestion of foods and beverages prepared with phthalate-plasticizer-containing clouding agents.

    Yen, Tzung-Hai; Lin-Tan, Dan-Tzu; Lin, Ja-Liang

    2011-11-01

    In May 2011, the illegal use of the phthalate plasticizer di(2-ethylhexyl) phthalate in clouding agents for use in foods and beverages was reported in Taiwan. This food scandal has caused shock and panic among the majority of Taiwanese people and has attracted international attention. Phthalate exposure is assessed by ambient monitoring or human biomonitoring. Ambient monitoring relies on measuring chemicals in environmental media, foodstuff and consumer products. Human biomonitoring determines body burden by measuring the chemicals, their metabolites or specific reaction products in human specimens. In mammalian development, the fetus is set to develop into a female. Because the female phenotype is the default, impairment of testosterone production or action before the late phase may lead to feminizing characteristics. Phthalates disrupt the development of androgen-dependent structures by inhibiting fetal testicular testosterone biosynthesis. The spectrum of effects obtained following perinatal exposure of male rats to phthalates has remarkable similarities with the human testicular dysgenesis syndrome. Epidemiological studies have suggested associations between phthalate exposure and shorter gestational age, shorter anogenital distance, shorter penis, incomplete testicular descent, sex hormone alteration, precocious puberty, pubertal gynecomastia, premature thelarche, rhinitis, eczema, asthma, low birth weight, attention deficit hyperactivity disorder, low intelligence quotient, thyroid hormone alteration, and hypospadias in infants and children. Furthermore, many studies have suggested associations between phthalate exposure and increased sperm DNA damage, decreased proportion of sperm with normal morphology, decreased sperm concentration, decreased sperm morphology, sex hormone alteration, decreased pulmonary function, endometriosis, uterine leiomyomas, breast cancer, obesity, hyperprolactinemia, and thyroid hormone alteration in adults. Finally, the number of

  5. 邻苯二甲酸二(2-乙基)己酯诱导隐睾对SD幼鼠睾丸生殖细胞凋亡的影响%Effect of di-2-(ethylhexy1)phthalate-induced cryptorchidism on apoptosis of germ cells in infant SD rats

    刘东尧; 吴盛德; 华燚; 何文飞; 何昀; 陈柏林; 龙春兰; 魏光辉

    2013-01-01

    Objective To analyze the apoptosis of germ cells and the expression of Bax/Bcl-2 in testes of infant male rats with cryptorchidism induced by maternal exposure to di-2-(ethylhexyl )phthalate (DEHP). Methods Thirty healthy SD rats on day 12. 5 after pregnancy were randomly divided into normal control, coin oil control and DEHP-exposure groups, ten for each. The rats in corn oil and DEHP-exposure groups were treated with corn oil and DEHP by gavage, each at a dosage of 500 mg/kg, once a day on gestation days (GD) 12. 5 ~ 19. 5, respectively, while those in normal control group were untreated. Testes of infant male rats were collected on post-natal day (PND) 20 then determined for expression levels of Bax and Bcl-2 genes by Q-PCR, and for apoptosis of germ cells by flow cytometry. Results The expression level of Bax mRNA in DEHP-exposure group was significantly higher (P < 0. 001), while that of Bcl-2 mRNA was significantly lower, than those in two control groups (P < 0. 01). However, the apoptosis rate of germ cells in DEHP-exposure group was significantly higher than those in two control groups (P < 0. 000 1). Conclusion Maternal exposure to DEHP induced cryptorchidism in male offspring, which promoted the apoptosis of germ cells. Meanwhile, the expressions of Bax and Bcl-2 in testis tissue of rats with cryptorchidism, which was speculated to involve the apoptosis of germ cells and be related to secondary infecundity in future.%目的 探讨环境内分泌干扰物邻苯二甲酸二(2-乙基)己酯[Di(2-ethylhexy1)phthalate,DEHP]作用于SD孕鼠后,对哺乳期雄性幼鼠睾丸组织中生殖细胞凋亡及凋亡基因Bax和Bcl-2表达的影响.方法 将30只妊娠第12.5天的SD孕鼠随机分正常对照组、玉米油对照组和DEHP诱导隐睾组,每组10只.玉米油对照组和DEHP诱导隐睾组自妊娠第12.5~19.5天分别每日灌胃玉米油(2ml)和DEHP(500 mg/kg),正常对照组不给药.取各组出生后第20天的雄性幼鼠睾丸组

  6. PPARα- and DEHP-Induced Cancers

    Tamie Nakajima

    2008-08-01

    Full Text Available Di(2-ethylhexylphthalate (DEHP is a widely used plasticizer and a potentially nongenotoxic carcinogen. Its mechanism had been earlier proposed based on peroxisome proliferator-activated receptor α (PPARα because metabolites of DEHP are agonists. However, recent evidence also suggests the involvement of non-PPARα multiple pathway in DEHP-induced carcinogenesis. Since there are differences in the function and constitutive expression of PPARα among rodents and humans, species differences are also thought to exist in the carcinogenesis. However, species differences were also seen in the lipase activity involved in the first step of the DEHP metabolism, which should be considered in DEHP-induced carcinogenesis. Taken together, it is very difficult to extrapolate the results from rodents to humans in the case of DEHP carcinogenicity. However, PPARα-null mice or mice with human PPARα gene have been developed, which may lend support to make such a difficult extrapolation. Overall, further mechanical study on DEHP-induced carcinogenicity is warranted using these mice.

  7. SIMULTANEOUS DEGRADATION OF SOME PHTHALATE ESTERS UNDER FENTON AND PHOTO-FENTON OXIDATION PROCESSES

    BELDEAN-GALEA M.S.; COZMA A.M.; DIODIU R.

    2015-01-01

    In this study the assessment of the degradation efficiency of five phthalates, DEP, BBP, DEHP, DINP and DIDP, found in a mixture in a liquid phase, using the Fenton and Photo Fenton oxidation processes, was conducted. It was observed that the main parameters that influence the Fenton oxidative processes of phthalates were the concentration of the oxidizing agent, H2O2, the concentration of the catalyst used, Fe2+, the pH value, UV irradiation and the reaction time. For the Fenton oxidative pr...