Diisobutyl Phthalate (DIBP) Final

Project ID

2320

Category

IRIS

Added on

March 10, 2014, 11:43 a.m.

Search the HERO reference database

Query Builder

Search query
Journal Article

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.

DOI
Journal Article

Abstract  A recent food safety issue involves the contamination of a broad range of food and nutraceutical products from Taiwan with industrial plasticizers. Among the suspected contaminants are selected phthalic acid esters, such as benzyl butyl phthalate, dibutyl phthalate, diisobutyl phthalate, di-2-ethylhexyl phthalate, di-n-octyl phthalate, diisononyl phthalate, and diisodecyl phthalate. Described in this study is an analytical method to rapidly qualitatively analyze these compounds in a wide variety of food and nutraceutical matrices suspected in this crisis. The method utilizes direct analysis in real time (DART) ionization coupled to a Thermo Exactive orbitrap mass spectrometer. The method is shown to be capable of detecting these compounds at levels greater than 1.0 mu g/mL in all food products examined and 0.5 mu g/mL in most of the samples tested. In the nutraceutical samples tested, the compounds were detected at levels of 50 mu g/g for all samples with some detected as low as 1.0 mu g/g. Published by Elsevier Ltd.

Journal Article

Abstract  Endocrine disruptors or endocrine-disrupting chemicals (EDCs) represent a highly heterogeneous group of molecules found in the environment or in consumer products. Toxicology and epidemiology studies have suggested the involvement of diverse EDCs in an increasing number of metabolic disorders, including insulin resistance (IR) and IR-related co morbidities, such as obesity, type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome. Nonalcoholic fatty liver disease (NAFLD), another IR related condition, is emerging as a significant public health concern, affecting 30-45% of the general population in the Western world. To evaluate whether EDCs may also play a role in the pathogenesis of NAFLD, we reviewed the literature on well-studied EDCs, such as dioxins, bisphenol A, phthalates and other persistent organic pollutants, in relation to pathways that might contribute to the pathogenesis of fatty liver / NAFDL. Certain EDCs may be responsible for inducing alterations similar to those encountered in NAFLD either directly through a hepatotoxic effect and/or indirectly by triggering hepatic and systematic IR. Considering these effects, which act in concert with the effects of the epidemics of obesity and T2DM, EDCs may play a significant role in the pathogenesis of fatty liver, thereby increasing the prevalence of NAFLD worldwide. Translational studies and clinical trials investigating the association between EDCs and NAFLD are required to confirm and extent these studies.

WoS
Journal Article

Abstract  In this work, the effects of two silane type external donors, Ph2Si(OCH3)(2) (DPDMS) and dicyclopentyldimethoxysilane (DCPDMS) on propylene slurry polymerization in the presence of hydrogen with a MgCl2/TiCl4/DIBP - Al(C2H5)(3) catalyst system were investigated, and the tacticity distribution and molecular weight distribution (MWD) of polypropylene (PP) were further regulated by using silane/ether (ROCH3, R = n-Bu, i-C8H17) composite external donors. The tacticity distribution of PP, as revealed by successive self-nucleation and annealing (SSA) thermo analysis of the polymer, is markedly changed by the external donors. DCPDMS shows much stronger effects than DPDMS. Addition of the ether as an auxiliary external donor in MgCl2/TiCl4/DIBP-TEA/silane (DPDMS or DCPDMS) lead to further increase in catalytic activity and isotacticity of PP, and changes in tacticity distribution. By using the composite external donors, PP with both higher isotacticity index, lower molecular weight or narrower molecular weight distribution was prepared at high activity. Effects of the external donors on the active center distribution were discussed based on the results of deconvoluting the MWD curve with multiple Flory "most-probable" distributions, and possible mechanism of the external donor effects was proposed.

DOI
Journal Article

Abstract  A MgCl2-supported catalyst containing diisobutyl phthalate (DIBP) and 2,4-pentadiol dibenzoate (PDDB) as internal donors was prepared. Propylene polymerizations were carried out using the catalyst in the absence or presence of an external donor. The resulting polymers were characterized by C-13-NMR, crystallization analysis fraction (CRYSTAF) and gel permeation chromatography (GPC). The performance of the catalyst was compared with that of other catalysts containing donor-free, DIBP and PDDB as internal donors respectively. The results demonstrated that the catalyst containing mixed internal donors not only had high activity and stereospecificity but also produced the polymer with relatively broad molecular weight distribution and the highest [mmmm] value. C-13-NMR analysis results indicated that strongly coordinating donors gave more stereoregular polymers, which was further confirmed by CRYSTAF data. The effects of mixed internal donors on the catalyst properties were discussed systematically. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 120: 36-42, 2011

WoS
Journal Article

Abstract  Two different monoethers, CH3CH2CH2CH2OCH3 (NBME) and (CH3)(2)CHCH2-OCH3 (IBME), and Ph2Si(OCH3)(2) were used as external donors in propylene polymerization using MgCl2/TiCl4/DIBP catalyst (DIBP: diisobutyl phthalate) activated by triethylaluminium (TEA). The monoethers alone showed no improvement in the isotacticity index of polypropylene (PP). When one of the ethers and Ph2Si(OCH3)(2) were added together in the polymerization system as composite external donors, the propylene polymerization activity and isotacticity index were increased as compared to those of the systems with only silane as external donor, though the melting temperature and melting enthalpy of PP decreased. The effects of the external donors on the active center distribution of the catalyst system are demonstrated by deconvolution analysis of the PP molecular weight distribution into multiple Flory components, and the mechanism of external donor regulation effects is discussed. All the results show that adding monoether in MgCl2/TiCl4/DIBP-TEA/silane catalyst system can reduce the stereoregularity of the isotactic chains of the polymer while, it maintains the atactic PP fractions at a very low level.

DOI
Journal Article

Abstract  Prediction of reaction yield as the most important characteristic process of a slurry polymerization industrial process of propylene has been carried out. Stacked neural network as an effective method for modeling of inherently complex and nonlinear systems-especially a system with a limited number of experimental data points-was chosen for yield prediction. Also, effect of operational parameters on propylene polymerization yield was modeled by the use of this method. The catalyst system was Mg(OEt)(2)/DIBP/TiCl(4)/PTES/AlEt(3), where Mg(OEt)(2), DIBP (diisobutyl phthalate), TiCl(4), PTES (phenyl triethoxy silane), and triethyl aluminum (AlEt(3)) (TEAl) were employed as support, internal electron donor (ID), catalyst precursor, external electron donor (ED), and co-catalyst, respectively. The experimental results confirmed the validity of the proposed model. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 116: 1237-1246, 2010

DOI
Journal Article

Abstract  Background: Di-n-butyl phthalate (DBP) and di-iso-butyl phthalate (DiBP) are widely used in consumer products, enteric-coated tablets and as plasticizers for polymers. DnBP and DiBP are metabolized in humans to their monoesters mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP). These primary metabolites are currently used in human biomonitoring approaches to assess internal exposures. However, the simple monoesters are prone to external contamination and have rather short half-times of elimination. These shortcomings could be overcome using oxidized, secondary metabolites, when applicable. Methods: We investigated 160 spot urine samples (partly repeated from 110 volunteers) with no known occupational phthalate exposures for oxidised metabolites of both isomers with oxo-, hydroxy- and carboxy-functional groups. 3-carboxy-MPP (3cxMPP) was detected in 90% of the samples with a median concentration of 0.66 μg/L (95th percentile [95P]: 2.70 μg/L). 3-cxMPP is a metabolite of DnBP but also of other higher molecular weight phthalates, thus not specific to DnBP exposure. Results: 3cxMPP was comparably weakly correlated with MnBP (r = 0.56; P < 0.001) and weaker with MiBP (r = 0.30; P < 0.001). 3-hydroxy-MnBP (3OH-MnBP) was detected in 97% of the samples with a median of 1.73 μg/L (95P: 13.3 μg/L). 3OH-MnBP was highly correlated (r = 0.91; P < 0.001) with MnBP (median: 20.9 μg/L; 95P: 110.7) but excreted at about 10-fold lower concentrations. Regarding oxidised DiBP metabolites we detected OH-MiBP in all samples and at high concentrations (median: 10.5 μg/L; 95P: 119.4 μg/L). OH-MiBP was highly correlated with MiBP (r = 0.90; P < 0.001) and excreted at roughly half the concentration of MiBP (median: 27.3 μg/L; 95P: 193.0 μg/L). Thus, OH-MiBP is an excellent additional biomarker of DiBP exposure, supplementing MiBP. With limits of quantification of 0.1 μg/L for all metabolites, we detected no metabolites with a keto (oxo) functional group. Conclusion: Overall, our findings suggest that there are considerable differences in DiBP and DnBP metabolism which have to be taken account of when interpreting biomonitoring data.

DOI
Journal Article

Abstract  An active model for a Ziegler-Natta propylene polymerization catalyst has been prepared by spin-coating of a MgCl2/cliether donor solution in ethanol on a flat silicon wafer, followed by crystal growth by Ostwald ripening to give well-defined MgCl2 center dot donor center dot nEtOH crystallites. The growth of the crystallites on the flat wafer indicates the formation of only 120 degrees edge angles in the presence of the diether donor, suggesting the preference for the formation of one particular crystallite face for the MgCl2. In contrast, presence of diisobutyl phthalate or ethyl benzoate leads to the formation of both 120 degrees and 90 degrees edge angles, indicating the formation of more than one face for the MgCl2. Subsequent trmtment with TiCl4 generates the catalyst and in propylene polymerization polymer forms on the lateral face of each crystallite. This work represents the first visualization of the effect of an internal donor in controlling the crystallite faces of magnesium chloride formed during a Ziegler-Natta catalyst preparation. (c) 2008 Elsevier Inc. All rights reserved.

DOI
Journal Article

Abstract  The use of triisobutylaluminium and diethyl zinc as cocatalyst and chain transfer agent respectively in ethylene/1-hexene copolymerisation, carried out with a Ziegler-Natta catalyst of type MgCl2/TiCl4/diisobutyl phthalate, has been found to give significantly higher comonomer incorporation than was obtained when triethylaluminium was used in combination with diethyl zinc. Triisobutylaluminium reacts readily with diethyl zinc, yielding metallic zinc, most likely via the formation of intermediate hydride species. In contrast, the use of 2,6-dimethylpyridine as external donor in this system has been found to have relatively little effect on comonomer incorporation and distribution, indicating that a change from tendentially isospecific to syndiospecific propagation in propene polymerisation is not accompanied by a major improvement in comonomer distribution in ethylene/ 1-hexene copolymerisation.

DOI
Journal Article

Abstract  A method based on liquid-liquid extraction (LLE) and automated large volume injection (LVI)GC-MS analysis was developed for the trace determination of phthalate di-esters in water samples at sub-mu g L-1 (ppb) levels. Strategies applied to reduce contamination include (i) careful selection of tools, glassware and solvents, (ii) systematic blank checks of the chromatographic system, glassware and solvents and (iii) frequent verifications of blanks during sequences. Background levels could be reduced to those present in the extraction solvent. For phthalates not present in the extraction solvent the limits of quantitation (LOQ) are 6 ng L-1 for di-methyl phthalate (DMP), 3 ng L-1 for benzylbutyl phthalate (BzBP) and 45 ng L-1 for the isomeric phthalate mixtures di-isononyl phthalate (DiNP) and di-isodecyl phthalate (DOP). For the other phthalates, the LOQ was set at twice the blank (extraction solvent) level and are 20 ng L-1 for di-ethyl phthalate (DEP), 60 ng L-1 for di-isobutyl phthalate (DiBP), 80 ng L-1 for di-n-butyl phthalate (DBP) and 30 ng L-1 for bis-(2-ethylhexyl) phthalate (DEHP).

DOI
Journal Article

Abstract  Hyperbranched polymers were synthesized using anionic self-condensing vinyl polymerization (ASCVP) by forming 'inimer' (initiator within a monomer) in situ from divinylbenzene (DVB) and 1,3-diisopropenylbenzene (DIPB) using anionic initiators in THF at -40 degreesC. The reaction of equimolar amounts of DVB and n BuLi results in the formation of hyperbranched poly(divinylbenzene) through self-condensing vinyl polymerization (SCVP). The hyperbranched polymers were invariably contaminated with small amount of gel (< 15%). No gelation was observed when using DIBP with anionic initiators. The presence of monomer-polymer equilibrium in the SCVP of DIPB restricts the growth of hyperbranched poly(DIPB). The inimer synthesized from DIPB at 35 degreesC undergoes intermolecular self-condensation to different extent depending on the nature of anionic initiator at -40 degreesC. The molecular weight of the hyperbranched polymers was higher when DPHLi was used as initiator. A small amount of styrene ([styrene]/[Li+] = 1) was used to promote the chain growth by inducing cross-over reaction with styrene, and subsequent reaction of styryl anion with isopropenyl groups of inimer/hyperbranched oligomer. The hyperbranched polymers were soluble in organic solvents and exhibited broad molecular weight distribution (2 < M-w/M-n < 17). (C) 2003 Elsevier Science Ltd. All rights reserved.

DOI
Journal Article

Abstract  Several samples taken from Duero River source in Spain have been analysed to evaluate the potential risk of uncontrolled discharges from wood industries located in the surrounding area. Toluene, dodecane, tetradecane, naphthalene, 1- tetradecene, 1-hexadecene, BHT, benzophenone, diisobutylphthalate (DiBP), dibenzofuran and fluoranthene have been selected as representative compounds from solvents and other components of varnishes or coatings, the most likely contamination origin. Solid-phase microextraction (SPME) with further GC-MS has been selected as analytical technique by both its versatility, high process speed, low cost and sensitivity. In order to reach the maximum overall performance, three fibres with different polarity: 100 mu m polydimethylsiloxane (PDMS), 85 mu m polyacrylate, and 65 mu m Carbowax- divinylbenzene have been evaluated. In addition, and due to the high number of involved variables, a two-level full factorial experiment design has been applied for optimisation being sampling time (5-20 min), sorption temperature (room: 50 degree C), desorption temperature (minimum recommended +10%, maximum recommended-10%) and salt concentration (NaCl, 0-1 M) as ionic strength modifier the variables under study. After statistical evaluation of experimental design sampling time proved to be the most significant variable, and a more detailed kinetic study has been carried out. The 85 mu m polyacrylate fibre was shown to be the most efficient one. Optimum conditions as well as quantitative values are shown and discussed. Toluene, dodecane, tetradecane, benzophenone, BHT and DiBP were found in the concentration range from 2 to 141 ng ml super(-1).

WoS
Journal Article

Abstract  Due to various components present in the Ziegler-Natta catalyst system and different interactions, taking place between them during the preparation and polymerization, studying of the system is usually very difficult. In this study mono- and bi-supported catalyst systems Of MgCl2 (ethoxide type)/TiCl4/ID and SiO2/MgCl2 (ethoxide type)/TiCl4/DNBP were prepared for the polymerization of propylene, whilst for polymerization of ethylene, MgCl2 (ethoxide type)/SiO2/TiCl4 was prepared. Di-n-butyl phthalate (DNBP) and diisobutyl phthalate (DIBP) were used as internal donors (ID), whilst triethylaluminium (TEA) was used as the cocatalyst. Structural study was carried out using FTIR, SEM, XRF and BET techniques. The observed shift in vibration of C=O, and C-O bands of the electron donors indicate some interactions between the donors, support and the catalyst itself. Surface area of the mono-supported catalyst having the electron donor and bi-supported catalyst without electron donor were about 230 m(2)/g. For the bi-supported having DNBP as the donor, however, a value of 177 m(2)/g was obtained. SEM study shows that the spherical morphologies Of SiO2 are replicated on catalyst and to a lesser extent on final polyethylene obtained. Dimethoxymethyl cyclohexyl silane (DMMCS) was used as an external donor for the polymerization of propylene.

DOI
Journal Article

Abstract  An i.r. study of MgCl2 supported TiCl4 Ziegler-Natta catalysts for propylene polymerization using Lewis base modifiers has been carried out. Two series of catalysts were prepared, differing mainly by the method used to prepare the MgCl2 support. One was prepared by precipitation and the other by ball-milling. Four different Lewis bases, of which two are diesters (di-2-ethyl phthalate and diisobutyl phthalate) and two are monoesters (ethyl benzoate and 2-ethyl hexyl benzoate), were employed. The i.r. investigation of the catalyst was focused on the identification of complexes formed. It was found that the diester-containing catalysts contain significant amounts of TiCl4 . diester complexes and phthaloyl mono- and di-chlorides complexed to MgCl2, whereas the monoester-containing catalysts are virtually free of these compounds. The chlorides are believed to be formed from the reaction of TiCl4 and diester weakly bonded to MgCl2. The TiCl4 . monoester complex is relatively weak so that the coordination of monoester with MgCl2 is much more favorable. The effects of the complexes, particularly their relative amounts, on the catalyst activity was investigated by carrying out propylene polymerizations with catalysts prepared by precipitation and by ball-milling method at three different activation temperatures.

DOI
Journal Article

Abstract  The effect of di-n-butyl ether (DBE) in the synthesis of a highly active propylene polymerization catalyst was studied. Electron-donors having ester and phosphate groups (ethyl benzoate-EB, diisobutyl phthalate-DIBP and tri-n-butyl phosphate-TBP) were added as second internal bases (IB2) to the catalysts prepared by the reduction of TiCl4 with AlClEt2 (DEAC) in the presence of DBE as a first internal base (IB1). The crystalline forms were examined for all catalyst samples by X-ray method. Special attention has been paid to the delta-TiCl3 samples showing the best catalytic properties. These catalysts were evaluated in propylene polymerization in the absence and presence of external bases (EB, DIBP and DBE). The effects of internal and external bases on the catalyst activity and stereo-specificity are discussed.

Journal Article

Abstract  HEEP COPYRIGHT: BIOL ABS. A comprehensive quality assurance program was applied to the analysis of phthalate esters in sediment. By utilizing the rapid ultrasonic extraction of dried sediment and the detecton capabilities of selected ion monitoring mass spectrometry, the analytical scheme was simplified to reduce systematic errors due to contamination and to improve recoveries. Matrix blank levels were 2.5 ng in 5 g dry samples, and spiked field sample recoveries were 90%. Identification of different phthalate species was accomplished by multiple ion monitoring of characteristic ion fragments and retention time comparisons. Eleven phthalate species were measured in representative samples from various sites in the Chesapeake Bay and Chester River, Maryland (USA).

Technical Report

Abstract  Degradability. DIBP released into the troposphere is photochemically-oxidatively degraded by OH-radicals with a half-life of cat 40 hours. An increase of the atmospheric half-life is expected through the presence of DIBP bound to particles. A direct photolysis is not expected in air and water. The hydrolytic degradation is practically of no importance under environmental conditions. According to existing laboratory studies, DIBP is characterized as being "readily biodegradable" under aerobic conditions. However, the degradation apparently stops at concentrations in an order of magnitude of cat 20-100 ng/l. Accumulation. On hand of the n-octanol/water partition coefficient (log Pow = 4.11) and the bioconcentration factor (BCF = 780) estimated from it, a definite tendency towards bioaccumulation is expected which, however, is not confirmed by recently completed experimental studies of H?ls AG. No information is available about geoaccumulation. However, a soil sorption coefficient value of Koc = 4,100 can be estimated from the n-octanol/water partition coefficient (log Pow = 4.11). According to Blume and Ahlsdorf there is a high tendency towards soil sorption, however, in field tests the potential for accumulation in soils with repeated deposition of sewage sludge was shown to be low. A transport with leachate into groundwater is expected through complex formation, e.g with humic acids. Ecotoxicology. Because a surface adsorption of DIBP in aquatic systems cannot be excluded, a differentiation between nominal and effective concentrations has been made below. In the oxygen consumption test, DIBP in concentrations (nominal) of up to 1.7 mg/l showed no inhibiting effect on microorganisms. In a cell-multiplication inhibition test with the green algae Scenedesmus subspicatus, ECso values (effective concentrations) of 1.0 mg/l (biomass) and 2.2 mg/1 (growth rate) were determined. The 24 h EC50 value for the water flea Daphnia magna and the 96 h EC50 value for the crustacean Nitocra spinipes were 7.4 and 3.0 mg/l, respectively (nominal concentrations). In a 21-day reproduction test with the water flea Daphnia magna, a NOEC of 1.0 mg/l (nominal concentration) was determined based on the mortality of the parent animals and the reproduction. Regarding the toxicity of DIBP in fish, a 96 h LC50 value of 0.9 mg/l (flowthrough test, effective concentration) and a 48 h LC50 value of 4.2 mg/l (static test, nominal concentration) were determined for the fathead minnow (Pimephales promelas) and the golden orfe (Leuciscus idus). At DIBP concentrations of 160-180 ng/l air, a definite toxic effect was found in certain plants (e.g. cruciferous plants), while others were less sensitive or not at all. Toxicological Aspects. Phthalates are readily taken up via all exposure routes and are quickly distributed throughout the organism. Excretion takes place in the urine and faeces, and there is no tendency towards accumulation. Phthalates are not acutely toxic. The lowest LD50 values for rats and mice are 15,000 and 13,000 mg DIBP/kg b.w., respectively. LD50 values for rats and mice following i.p. injection lie in the range of= 1,600 mg DIBP/kg b.w. The dermal LD50 value for guinea pigs is 10,000 mg DIBP/kg b.w. The inhalative exposure (8 hours) of rats to DlBP-saturated air did not cause any deaths. DIBP irritates neither the eyes nor skin of rabbits. No data are available on the skin sensitizing effect of DIBP. In a short-term oral toxicity study (14 days) with female rats, a NOEL of 50 mg DIBP/kg b.w. is specified on the basis of increased liver weights, altered clinical-chemical parameters (serum albumin, cholesterol- and triglyceride values) as well as peroxisome proliferation in hepatic tissue (increase of biochemical parameters). For rats, other NOELs in the range of 50-75 mg DIBP/kg b.w. are described afler oral administration (up to 4 months). Analogous to other phthalates (BUA Reports No. 4, 22, 114), DIBP acts hepatotoxic in the sense of a peroxisome proliferation. The projection of this rodent-specific mode of action to humans is questionable. In vitro mutagenicity studies with various S. typhimurium strains showed no indication of a genotoxic effect. The available studies on reproductive toxicity allow neither a clear evaluation of the fertility-impairing potential nor the specification of NOAELs. By considering the effect of structure-related phthalates (BUA Reports No. 4, 22, 114), a hazard potential, in the sense of fertility impairment or embryonal damage in a non-maternally toxic concentration range, cannot be excluded. Studies on carcinogenicity are not available. However, long-term studies with other phthalates show that they trigger tumors mainly via the mechanism of peroxisome proliferation.

Technical Report

Abstract  DESCRIPTION: (Adapted from the Applicant's Abstract): Many PAHs are potent mammary carcinogens in rodent models, but their role in human breast cancer is poorly understood. We have cloned cytochrome P4501B1 (CYP1B1) and have shown that CYP1B 1-null mice are resistant to several cancers, which are induced by PAHs in normal mice. We will test the hypothesis that CYP1B 1 plays a major role in PAH-induced breast cancer, and that the contribution is greater than for CYP1A1 for one or more of the following reasons: (1) CYP1B1 is constitutively expressed in breast epithelia, whereas CYP1A1 requires induction by the PAH, via the Ah-receptor (AhR); (2) CYP1B1, which is also via the AhR, is expressed in multiple breast cell types, including luminal and basal epithelia and a highly proliferative progenitor cell population that may be very susceptible to transformation. CYP1A1 is primarily expressed in more differentiated luminal epithelia; (3) PAHs are preferentially metabolized to carcinogenic dihydrodiol epoxides (PAHDE) by CYP1B1 relative to CYP1A1. Human primary breast epithelia from reduction mammoplasty tissues will be resolved into the respective cell types. The PAHs to be examined are: dibenzo[a,l]pyrene (diBP), representative of the most potent fjord class; benzo[a]pyrene (BP), a bay-region PAH; and 7,12-dimethylbenz[a]anthracene (DMBA), a pseudo-fjord PAR. Metabolism and PAHIDE-DNA adduct formation will be analyzed in mice (wild type and CYP1B 1-null) in vivo in relation to mammary cancer development following BP, DMBA, and diBP exposure. Similar metabolic analyses will be completed in separated primary human breast epithelia for comparison of CYP1B1 and CYP1A1 expression and AhR activation. The role of CYP1B 1 will be further defined by anti-sense suppression or over-expression in the near normal human breast epithelial cell line, MCF-10F. These metabolically activated PAHs cause growth arrest at low concentrations. We will identify markers of this response, and we will examine the role of CYP1B1 in PAHDE-DNA adduct formation. The transformation of MCF-10F cells (including expression variants) to cells that form anchorage-independent colonies will be used to test the involvement of CYP1B 1 in these changes, which correlate with the early stages of carcinogenesis. This work will examine PAR activation for the first time in well characterized primary human breast cells that are cultured to replicate in vivo ductal morphology. The correlation with CYP1B 1 expression and activity will provide insight into the relationship of the mouse model to human breast cancer.

Technical Report

Abstract  PESTAB. A search for micropollutants confirmed the presence of traces of chlorinated and phosphorous pesticides and of phtalates in atmospheric dust samples collected in 3 districts of Southern France from 1973 through 1975. The dust traps consisted of steel plaques coated at first with vaseline and later with silicon grease and exposed at 3 m and 1.5 m from the ground for 14 days. Extracts obtained from these plaques were analyzed by gas chromatography. The least commonly found pollutants included alpha-HCH (alpha-BHC), dicofol, diazinon, fenithrotion, malathion, methyl parathion, PCB and a phtalate (DIBP). The four most frequently detected were gammaHCH (lindane), (in 95% of the observations), parathion, dibutyl phtalate (DBP) and diethylhexyl phtalate (DEHP). The frequency of gamma-HCH, more prevalent from January to August, seemed to be related to its use in agriculture. No valid correlations could be established between the fluctuations in amounts noted and meteorological factors. In 1976, a special search for hexachlorobenzene (HCB) yielded very few results. There was a total absence of residues of DDT or its metabolites. The discovery, by mass spectrometry, of the off-and-on presence of phtalates in rather high amounts for certain periods (up to 6500 mug for DEHP and 1000 mug for DBP) appeared to warrant further investigation.

Journal Article

Abstract  A predominant PAHs-degraded strain was obtained by the selective enrichment culture from ocean sediment. The microorganisms with ability to degrade anthracene were obtained with anthracene as the solo carbon source for growth. The bacteria were preliminary identified as Flavobacterium based on its morphological and physio-biochemcial characteristics. In a mineral salts medium with initial anthracene concentration of 50mg/L, the microbial population and the strain could degrade anthracene well, and the removal rate of anthracene in the medium was 77.6% in 5 days. The study on selectivity enzyme-degraded of PAHs was found that the degradation efficiency to anthracene was better than that to phenanthrene in a mixture culture with 15mg/L of naphthalene, anthracene and phenanthrene. 1, 2-Benzenedicarboxylic acid-bis (2-methylpropyl) ester, 9, 10-anthracenedione and dibutylphthalate were identified as the major metabolites in the culture by GC/MS analysis. Additional, the phthalic acid pathway to anthracene was detected as a metabolizing process.

Journal Article

Abstract  Phthalates are environmental contaminants used in the production of plastics, cosmetics and medical devices. Studies on the effects of phthalates on female reproductive health are particularly sparse and mostly restricted to high-dose exposure in rats. In the present study, pregnant rats were treated with 100mg/kg-d of di-eta-butyl-phthalate (DBP) or only the vehicle (control group), from GD 12 to GD 20 for evaluation of reproductive outcomes and fetal gonads analysis (F0), and from GD 12 to PND 21 to evaluate reproductive development and function on F1 female offspring. Results showed that all parameters were comparable between groups, although there was a significant increase in the fetal weight after DBP exposure. However, the body weight at birth was normal. Based on these data we can conclude that, in these experimental conditions, DBP did not disturb the reproductive development or function of female rats.

  • <<
  • 2 of 47
  • >>
Filter Results