Abstract  BACKGROUND: Widespread human exposure to phthalates, some of which are developmental and reproductive toxicants in experimental animals, raises concerns about potential human health risks. Underappreciated sources of exposure include phthalates in the polymers coating some oral medications. OBJECTIVE: The objective of this study was to evaluate whether users of phthalate-containing medications have higher urinary concentrations of phthalate metabolites than do nonusers. METHODS: We used publically available files from the National Health and Nutrition Examination Survey for the years 1999-2004. For certain survey periods, participants were asked to recall use of prescription medication during the past 30 days, and for a subsample of individuals, the urinary concentrations of phthalate metabolites were measured. We a priori identified medications potentially containing phthalates as inactive ingredients and then compared the mean urinary concentration of phthalate metabolites between users and nonusers of those medications. RESULTS: Of the 7,999 persons with information on urinary phthalate concentrations, 6 reported using mesalamine formulations, some of which may include dibutyl phthalate (DBP); the mean urinary concentration of monobutyl phthalate, the main DBP metabolite, among these mesalamine users was 50 times higher than the mean for nonusers (2,257 microg/L vs. 46 microg/L; p < 0.0001). Users of didanosine, omeprazole, and theophylline products, some of which may contain diethyl phthalate (DEP), had mean urinary concentrations of monoethyl phthalate, the main DEP metabolite, significantly higher than the mean for nonusers. CONCLUSION: Select medications might be a source of high exposure to some phthalates, one of which, DBP, shows adverse developmental and reproductive effects in laboratory animals. These results raise concern about potential human health risks, specifically among vulnerable segments of the general population and particularly pregnant women and children.

Abstract  Objective: To measure manicurists' exposure to dibutyl phthalate (DBP) at work and to determine whether workplace characteristics influence this exposure. DBP is a reproductive and developmental toxicant in rats and is used in nail polish to hold color and prevent chipping. Methods: Pre- and postshift spot urine samples were collected from 40 manicurists. Linear regression compared the relationship between the log of the cross-shift differences in urinary phthalate monoester metabolite concentrations and use of workplace exposure control methods. Results: There was a statistically significant cross-shift increase of 17.4 ng/mL in the urinary concentration of mono-n-butyl phthalate, the major metabolite of DBP. Use of gloves reduced mono-n-butyl phthalate concentrations by 15.1 ng/mL below the preshift concentration compared with a 20.5 ng/mL increase if gloves were not worn. Conclusions: Manicurists are occupationally exposed to DBP and glove use may minimize this exposure.

Abstract  In order to determine the sources of pollution of surface waters, an investigation into the occurrence of black list substances in two river basins has been made. Both rivers, “Voorste Stroom” and “Mark-Dintel”, are transboundary ones, coming from Belgium, and both rivers of discharge indirectly into the North Sea. The “Voorste Stroom” flows through a rural area with a number of natural parks. The area of the “Mark-Dintel” is more industrialized and the downstream polders are in agricultural use. Over 75,000 samples have been taken throughout a whole year, and have been analyzed on the presence of over one hundred substances, a large number of them belonging to the black list of the European Community. Not only the surface waters and sediments of the “Voorste Stroom” and the “Mark-Dintel” have been sampled in various places but also the surface waters of upstream rivers, flowing to these two basins. The effluents of all the municipal wastewater treatment plants in the area have been analyzed. Furthermore, a number of industries discharging into these sewage systems, were taken into account. In the whole area of the two basins, 82 out of 121 substances have been found to be present once or more in the surface water, leaving 39 that have not been found at all. Only 14 substances were frequently present, i.e. in over 50% of all the surface water samples. Another 17 substances were present in frequencies between 30 and 50%. The substances withe the highest frequencies belong predominantly tot the polycyclic aromatic hydrocarbons (PAH) and to the polychlorobiphenyls (PCB). In spite of the large number of samples it was not possible to trace the real sources of all the substances polluting the surface water of the “Voorste Stroom” and “Mark-Dintel”. In a small number of cases the discharge from a municipal waste water treatment plant was of major importance tot the surface water quality, but within this study it was not possible to trace the discharge into the sewerage system. In all other cases the pollution seems to be from diffuse sources: groundwater, agricultural run-off, transboundary transport, and urban run-off. Nevertheless, more insight into the importance of the loads from the upstream rivers has been gained. The relative importance of the loads within these two areas to the North Sea may be calculated.

Abstract  BACKGROUND: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine-disrupting compounds (EDCs) share a high degree of structural similarity with mild analgesics.

OBJECTIVES AND METHODS: Using cell-based transfection and transduction experiments, mass spectrometry, and organotypic assays together with molecular modeling, we investigated whether inhibition of the PG pathway by known EDCs could be a novel point of endocrine disruption.

RESULTS: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis, and this reduction was correlated with a reduced testosterone production. The inhibition of PG synthesis occurred without involvement of canonical PG receptors or the peroxisome proliferator-activated receptors (PPARs), which have previously been described as targets of EDCs. Instead, our results suggest that the compounds may bind directly into the active site of the cyclooxygenase (COX) enzymes, thereby obstructing the conversion of arachidonic acid to PG precursors without interfering with the expression of the COX enzymes. A common feature of the PG inhibitory EDCs is the presence of aromatic groups that may stabilize binding in the hydrophobic active site of the COX enzymes.

CONCLUSION: Our findings suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades.

Abstract  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 of individual chemicals. However, several chemicals may concurrently target the same receptor, work through the same mechanism or in other ways induce the same effect(s) in the body. In these cases, cumulative risk assessment should be applied. The present study uses biomonitoring data from 129 Danish children and adolescents and resulting estimated daily intakes of four different phthalates. These daily intake estimates are used for a cumulative risk assessment with anti-androgenic effects as the endpoint using Tolerable Daily Intake (TDI) values determined by the European Food Safety Authorities (EFSA) or Reference Doses for Anti-Androgenicity (RfD AA) determined by Kortenkamp and Faust [Int J Androl 33 (2010) 463] as acceptable levels of exposure. United States Environmental Protection Agency Reference Doses (US EPA RfD) could not be used as none of them identifies anti-androgenic effects as the most sensitive 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(s) associated with the greatest risk, while DEHP is the compound associated with the greatest risk when using the RfD AA approach.

Abstract  Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women.Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study.Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001-2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment-estimated insulin resistance, and glycosylated hemoglobin A1c.Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance.Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.

Abstract  OBJECTIVE: Phthalates are ubiquitous industrial high-volume chemicals known as ligands to peroxisome proliferator-activated receptors (PPARs). Because PPAR-γ agonists modulate insulin sensitivity and are used to treat type 2 diabetes, we investigated whether circulating levels of phthalate metabolites are related to prevalent type 2 diabetes.

RESEARCH DESIGN AND METHODS: A total of 1,016 subjects, aged 70 years, were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors Study. Four phthalate metabolites were detected in almost all participant sera by an API 4000 liquid chromatograph/tandem mass spectrometer. Type 2 diabetes was defined as the use of pharmacological hypoglycemic agents or a fasting plasma glucose >7.0 mmol/L.

RESULTS: A total of 114 subjects were shown to have diabetes. Following adjustment for sex, BMI, serum cholesterol and triglycerides, educational level, and smoking and exercise habits, high levels of the phthalate metabolites monomethyl phthalate (MMP) (P < 0.01), monoisobutyl phthalate (MiBP) (P < 0.05), and monoethyl phthalate (MEP) (P < 0.05), but not mono(2-ethylhexyl) phthalate, were associated with an increased prevalence of diabetes. Using the fasting proinsulin-to-insulin ratio as a marker of insulin secretion and the homeostasis model assessment-insulin resistance index as a marker of insulin resistance, MiBP was mainly related to poor insulin secretion, whereas MEP and MMP mainly were related to insulin resistance.

CONCLUSIONS: The findings in this cross-sectional study showed that several phthalate metabolites are related to diabetes prevalence, as well as to markers of insulin secretion and resistance. These findings support the view that these commonly used chemicals might influence major factors that are regulating glucose metabolism in humans at the level of exposure of phthalate metabolites seen in the general elderly population.

Abstract  To study the surface structure of MgCl(2) support and its interaction with other active components in Ziegler-Natta catalyst, such as electron donors, we prepared a thin film analogue for Ziegler-Natta ethylene polymerization catalyst support by spin-coating a solution of MgCl(2) in ethanol, optionally containing a diester internal donor (diisobutyl-ortho-phthalate, DIBP) on a flat Si crystal surface. The donor content of these films was quantified by applying attenuated total internal reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). Changes in the interaction of DIBP with MgCl(2) at various temperatures were monitored by in situ ATR-FTIR. Upon increasing the temperature, a shift in the (C═O) band toward lower wavenumbers was observed together with the depletion of (O-H) stretching band due to the desorption of residual ethanol. We assign this shift to gradual redistribution of adsorbed DIBP from adsorption sites on the MgCl(2) (104) surface toward the more acidic MgCl(2) (110) surface. The morphologies of MgCl(2) and MgCl(2)/DIBP films were studied by transmission electron microscopy (TEM) revealing a preferential orientation of ClMgCl layers (001) parallel to the lateral film dimensions. This orientation becomes more pronounced upon annealing. In the absence of donor, the MgCl(2) grow in to large crystals aligned in large domains upon annealing. Both crystal growth and alignment is impeded by the presence of donor.

Abstract  The orthogonal test and the supercritical carbon dioxide fluid extraction were used for optimizing the extraction of the essential oil from Plumeria rubra var. actifolia for the first time. Compared with the steam distillation, the optimal operation parameter of extraction was as follows: extraction pressure 25 MPa, extraction temperature 45 degrees C; separator I pressure 12 MPa, separator I temperature 55 degrees C; separator II pressure 6 MPa, separator II temperature 30 degrees C. Under this condition the yield of the essential oil was 5.8927%. The components were separated and identified by GC-MS. 53 components of Plumeria rubra var. actifolia measured by SFE method were identified and determined by normalization method. The main components were 1, 6, 10-dodecatrien-3-ol, 3, 7, 11-trimethyl, benzoic acid, 2-hydroxy-, phenylmethyl ester, 1, 2-benzenedicarboxylic acid, bis(2-methylpropyl) ester,etc.. 1, 2-Benzenedicarboxylic acid, bis (2-methylpropyl) este. took up 66.11% of the total amount, and there was much difference of the results from SD method.

Abstract  OBJECTIVE: To study the chemical constituents in the roots of Pueraria lobata.

METHOD: Various chromatographic methods were employed to separate of chemical constituents and the spectroscopic methods were used to elucidate the structure.

RESULT: Twenty-two compounds were isolated and characterized as beta-sitosterol palmitate (1), beta-sitosterol (2), lupeol (3), lupeone (4) , puerarol (5), diisobutyl phthalate (6), bis(2-ethylhexyl) phthalate (7), sophoracoumestan A (8), coumestrol (9), allantion (10), dadzein (11), formononetin (12), 3'-methoxy daidzein (13), ononin (14), 3'-hydroxy dadzein (15), genistin (16), dadzin (17), 8-methoxy ononin (18), sissotorin (19), (-)-puerol B 2-O-glucopyranoside (20), (6S,9R)-roseoside (21) and sucrose (22), respectively.

CONCLUSION: Compounds 1, 5-8, 15, 18, 21 and 22 were isolated from P. lobata for the first time, and componds 1, 5-7, 15, 18, 21 and 22 were isolated from the genus Pueraria for the first time.

Abstract  Bullous pemphigoid (BP) is an acquired autoimmune disease commonly attributed as idiopathic, especially in elderly patients, characterized by subepidermal vesicles and bullae with linear deposits of IgG autoantibodies and complement along the epidermal basement membrane. It also is now commonly accepted that BP can be caused by or associated with drug therapy. We report a case of drug-induced BP (DIBP) likely due to galantamine hydrobromide, a competitive and reversible acetylcholinesterase inhibitor used in the treatment of mild to moderate Alzheimer dementia.

Abstract  N-Isobutyl-phthalimic acid hydrolyzes to the title salt, 2C(4)H(12)N(+)·C(8)H(4)O(4) (-)·H(2)O, which adopts a hydrogen-bonded layer structure. In the anion, the carboxyl-ate groups are twisted with respect to the benzene ring [dihedral angles = 43.8 (1) and 50.9 (1)°].

Abstract  Bullous pemphigoid (BP) is an acquired autoimmune disease characterized by subepidermal vesicles and bullae. The etiology for BP is mostly idiopathic with the highest occurrence in elderly patients; however, it is now well-accepted that BP has been triggered by or associated with drug therapy. We present a case of furosemide-induced bullous pemphigoid and review the literature of drug-induced bullous pemphigoid (DIBP).

Abstract  OBJECTIVE: To study the chemical constituents of Cornus officinalis extracted by supercritical carbon dioxide fluid extraction (SFE).

METHOD: The process was performed at 40 centigrade with pressures of 15 MPa for 2 hours and with CO2 fluid and gas at the flow rate of 22.0 kg x h(-1) and 18.0 kg x h(-1) respectively. The chemical constituents of the SFE extractions were determined by GC-MS.

RESULT: The total amount of extractable substances or yields by SFE is 2.42% (mass). 31 Chemical constituents were identified and their relative contents were determined by normalization method of area.

CONCLUSION: The major components identified in the extractions are 1,2-benzenedicarboxylic acid, butyl 2-methylpropyl ester, isopropyl myristate etc.

Abstract  CH-type catalysts were prepared by reacting MgC12.ROH, where ROH was 2-ethylhexanol(EH), (R)-2-octanol(R-2O) and (S)-2-octanol(S-2O), with titanium tetrachloride in the presence of diisobutyl phthalate (BP) , diisobutyl terephthalate(BT), (-)-dimenthyl phthalate(MP) or (-) -dimenthyl terephthalate(MT). The CH(EH,BP) catalyst was found to be five times more active than the CH(EH,MT) catalysts and to produce PP which was 97% isotactic, as compared with 84.7% for the latter. The catalysts derived from 2-octanols were much less active than the corresponding catalysts prepared with EH due to lack of reactivity with phthalic anhydride which permitted excessive incorporation of titanium tetrachloride to form non-stereospecific catalytic sites as well as inactive Ti species. 11 refs.

Abstract  The effect of internal and external bases on the copolymerisation of propylene with 1-butene was investigated. Catalytic systems used were magnesium chloride/titanium tetrachloride-triethylaluminium, magnesium chloride/titanium tetrachloride-triethylaluminium/tetramethylpiperidine(TMP), magnesium chloride/titanium tetrachloride-triethylaluminium /triethoxyphenylsilane(TPS), magnesium chloride/diisobutyl phthalate(DIBP)/titanium tetrachloride-triethylaluminium/TMP and magnesium chloride/DIBP/titanium tetrachloride-triethylaluminium /TPS. A series of copolymers of different compositions was produced using each catalytic system and the copolymers obtained were fractionated by sequential extraction with boiling solvents and the fractions characterised by means of carbon-13 NMR. The effect of the Lewis bases on the fraction distribution and on composition and the number-average sequence lengths of all fractions were analysed. 15 refs.

Abstract  In Chiba Prefecture, Japan, air samples were collected at 1.5, 5, 30, 50, and 100 m height using a radio-controlled helicopter, and at 150, 300, and 800 m using a regular helicopter, and concentrations of dialkyl phthalates were measured. The analytical methods used are described. Concentrations of dimethyl phthalate, diethyl phthalate, and diisobutyl phthalate were detected only at ground level, and the concentrations of benzyl butyl phthalate, di-n-butyl phthalate, di(2-ethylhexyl) phthalate, and dioctyl adipate decreased with altitude. The concentrations of all dialkyl phthalates were higher in July than in March at the same altitudes. Maximum concentrations of di(2-ethylhexyl) phthalate were highest, followed in decreasing order by di-n-butyl phthalate; dioctyl adipate; diisobutyl phthalate; benzyl butyl phthalate, di-n-nonyl phthalate, and diethyl phthalate; and dimethyl phthalate. All relevant concentration data are tabulated.

Abstract  In order to assess and analyze the pollution level and distribution character of phthalic acid esteis (PAEs) in soils of Leizhou peninsula, south of China, 71 topsoil samples and 3 soil profile samples were collected from 4 functional agriculture areas of Leizhou peninsula, 16 PAEs including dimethyl phthalate(DMP), diethyl phthalate(DEP), diisobutyl phthalate(DIP), di-n-butyl phthalate(DnBP), bis(methoxyethyl) phthalate (BMP), hexy1-2-ethylhexyl phthalate(HEP),Bis(ethoxyethyl)phthalate (BEHP), di-amyl phthalate(DAP), di-n-hexyl phthalate (DHP), butylbenzyl phthalate(BBP), bis(4-methyl,2-pentyl)phthalate(BMPP), bis(2-n-butoxyethyl)phthalate(BnBP), dicyclohexyl phthalate (DCP), di-n-octyl phthalate(DnOP), di-nonyl phthalate(DnP) and di-2-ethylhexyl) phthalate(DEHP) were determined by gas chromatography- FID detector (GC-FID). Total contents of the 16 PAE compounds( capital sigma PAEs) in all top soils ranged from ND to 5452.7 mu g times kg super(-1), with the average 736.5 mu g times kg super(-1). Among 6 U.S.EPA priority pollutants of PAEs, the contents of DMP, DEP and DnBP in all top soils exceeded the control limits of PAEs in American soil by 1.4%, 45.07% and 91.55% respectively, but the contents of DEHP, DnOP and BBP were less than the control limits. The pollution level of PAEs in topsoil of Leizhou peninsula was lower than that reported in the country. The main components of PAE compounds in soils of Leizhou peninsula were DnBP, DEHP, DIP, BEHP and DAP, and their averaged concentrations in soils was 282.3, 140.7, 92.55, 79.63 and 45.94 mu g times kg super(-1) respectively. Although distribution of capital sigma PAEs in the samples was not well defined, the data suggested the order of pollution potential was sugarcane soil>paddy field>pot garden>fruit garden among 4 functional agriculture areas, and that was Leizhou>Xiashan>Chikan>Wuchuan>Xuwen>Lianjiang>Mazhang>Potou>Suixi among 9 districts of Leizhou peninsula. The contents of capital sigma PAEs and DEHP decreased with the depth of soil profile, but when the contents of DnBP were higher, the contents of capital sigma PAEs and DEHPy increased with depth earlier then decreased.

Abstract  The effects of ethers alone and in combination with alkoxysilanes as external donors on propylene polymerisation carried out in the presence of a MgCl"2/TiCl"4/diisobutyl phthalate catalyst system were investigated. It was found that ethers alone did not improve the isotacticity of PP but a combination of the ethers with an alkoxysilane resulted in increased propylene polymerisation activity and isotacticity index but a decrease in melting temperature and melting enthalpy of polypropylene. An analysis of active centre distribution by deconvolution of the MWD curves showed that the ether/silane combinations increased the activity of the active centres and provided PP with medium molecular weight. 22 refs.

Abstract  Supported titanium catalysts were prepared by chlorination of magnesium stearate with silicon tetrachloride or titanium tetrachloride, followed by treatment of the product with diisobutyl phthalate and titanium tetrachloride. The catalysts were used for the polymerisation of propylene and their productivity and isospecificity were examined. 10 refs.

Abstract  The effects of injecting ethylene, propylene, 1-hexene, 2-methylpropene, 3,3-dimethyl-1-butene, cis-2-butene, trans-2-butene, 2,3-dimethyl-2-butene, cyclopentene, styrene, 1,3-butadiene and 1,4-pentadiene during polymerisations of ethylene and propylene were investigated. Catalysts used were a supported magnesium chloride/ethyl benzoate/titanium tetrachloride ballmilled catalyst and precipitated magnesium chloride /2-ethylhexanol/titanium tetrachloride/diisobutyl phthalate catalysts activated with triethylaluminium in the presence of ethyl benzoate. The instantaneous polymerisation rate was observed by continuous monitoring of the monomer consumption, the time resolution of the measurements being less than one second. 40 refs.

Abstract  11 refs.