Concentrations of phthalates and DINCH metabolites in pooled urine from Queensland, Australia

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 71.9 ng/mL for metabolites of di(2-ethylhexyl)phthalate, and from < 0.5 to 775 ng/mL for all other metabolites. Our data suggest that 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.

Water solubility enhancement of phthalates by cetyltrimethylammonium bromide and beta-cyclodextrin

Water solubility enhancements of six phthalates (five aliphatic phthalates and one phenyl phthalate) by cetyltrimethylammonium bromide (CTAB) and beta-cyclodextrin (beta-CD) were studied at 25 degreesC. The solubilities of these plithalates are remarkably enhanced by CTAB solutions above the critical micelle concentration (cmc). Only marginal enhancement of phthalate solubility was observed in solutions containing CTAB below its cmc and beta-CD at low concentrations (less than 5 mM). The solubility enhancements of the plithalates are proportional to the added amount of CTAB and beta-CD. Partition coefficients of the plithalates between monomeric CTAB surfactant and water (K-MN) and between CTAB micelle and water K-MC) were estimated from the experimental data. The mechanisms of solubility enhancements by CTAB and beta-CD were discussed. A log-linear equation was proposed and evaluated for the solubilization by CTAB below cmc, while the previously proposed linear partitioning model was questioned. The structures of the complexes formed between plithalates and beta-CD were proposed, and the formation constants were estimated. The values of log K-MC, log K-MN, and log Kbeta-CD of the plithalates were found to correlate linearly with the log K-OW of plithalates, with the exception of the solid phenyl phthalate.

Efficient synthesis and facile polymerization of some cyclic bisphenol o-phthalates

A series of new macrocyclic aromatic esters have been efficiently synthesized from o-phthaloyl dichloride and various bisphenols, and unambiguously characterized by a combination of GPC, MS(FAB), FTIR and NMR. These macrocyclic oligomers undergo facile ring-opening polymerization in the presence of anionic initiators to give high molecular weight polyarylates.

(Table 1) Concentrations of phthalates in chloroform extracts from waters of the Northwest Indian Ocean and the Red Sea

Chloroform extracts of water-soluble organic matter collected in the water column from the surface to the bottom were studied by C-13 and H-1 NMR chromatographic mass spectrometry, and phthalate concentrations were determined by capillary gas-liquid chromatography. More than 14 compounds were found including diethyl phthalate, ethyl butyl phthalate, dibutyl phthalate, and di-2-ethylhexyl phthalate, phthalates with normal C4-C12 chains, phthalates partially esterified with methanol, and others, at total concentrations up to 0.4 mg/l. Possible reasons for presence of phthalates in oceans, sometimes in high concentrations, are discussed.

Determination of phthalate acid esters plasticizers in plastic by ultrasonic solvent extraction combined with solid-phase microextraction using calix[4]arene fiber

Ultrasonic solvent extraction combined with solid-phase microextraction (SPME) with calix[4]arene/hydroxy-terminated silicone (C[4]/OHTSO) oil coated fiber was used to extract phthalate acid esters (PAEs) plasticizers in plastic, such as blood bags, transfusion tubing, food packaging bag, and mineral water bottle for analysis by gas chromatography (GC). Both extraction parameters (i.e. extraction time, extraction temperature, ionic strength) and conditions of the thermal desorption in a GC injector were optimized by analysis of eight phthalates. The fiber shows wonderful sensitivity and selectivity to the tested compounds. Owing to its high thermal stability (380 degreesC), the carryover effect that often encountered when using conventional fibers can be reduced by appropriately enhancing the injector temperature. The method showed linear response over two to four orders of magnitude with correlation coefficients (r) better than 0.996, and limits of detection (LOD) ranged between 0.006 and 0.084 mug l(-1). The relative standard deviation values obtained were less than or equal to 10%. bis-2-Ethylhexyl phthalate (DEHP) was the sole analyte detected in these plastics and recoveries were in the ranges 95.5-101.4% in all the samples. (C) 2004 Elsevier B.V. All rights reserved.

Effect of plasticizer-polymer compatibility on the response characteristics of optical thin CO2 and O-2 sensing films

A homologous family of dialkyl phthalates has been used to investigate the effect of plasticizer/polymer compatibility on the response characteristics of transparent, plastic, thin optical gas sensing films for CO2 and oxygen. Plasticizer/polymer compatibilities were determined through the value of the difference in solubility parameter, i.e. Delta delta, for the plasticizer and polymer with a Delta delta value of zero indicating high compatibility. A strong correlation was found between plasticizer/polymer compatibility and sensitivity in phenol red/ethyl cellulose CO2-sensitive films and this relationship extended to CO2-sensitive films based on other polymers such as polystyrene and poly(methyl methacrylate). It extended also to optical O-2-sensitive films implying that the relationship is general for thin-film optical sensors. Other results from the CO2-sensitive films in different polymers indicated that the film sensitivity is largely independent of the polymer matrix regardless of its inherent gas permeability, when a sufficient quantity of compatible plasticizer is present. (C) 1998 Elsevier Science B.V.

Endocrine disruptor activity of multiple environmental food chain contaminants

Industrial chemicals, antimicrobials, drugs and personal care products have been reported as global pollutants which enter the food chain. Some of them have also been classified as endocrine disruptors based on results of various studies employing a number of in vitro/. vivo tests. The present study employed a mammalian reporter gene assay to assess the effects of known and emerging contaminants on estrogen nuclear receptor transactivation.Out of fifty-nine compounds assessed, estrogen receptor agonistic activity was observed for parabens (. n= 3), UV filters (. n= 6), phthalates (. n= 4) and a metabolite, pyrethroids (. n= 9) and their metabolites (. n= 3). Two compounds were estrogen receptor antagonists while some of the agonists enhanced 17β-estradiol mediated response.This study reports five new compounds (pyrethroids and their metabolites) possessing estrogen agonist activity and highlights for the first time that pyrethroid metabolites are of particular concern showing much greater estrogenic activity than their parent compounds.

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.

The influence of environmental contaminants on time to pregnancy

Cette thèse porte sur l’évaluation de l’impact de certains composés environnementaux sur la fécondité féminine, tel que mesuré par le délai de conception (« time to pregnancy » en anglais, ou TTP). Cette recherche a été réalisée dans le cadre de l’Étude mère-enfant sur les composés chimiques de l’environnement (MIREC), une cohorte de grossesse de 2001 femmes recrutées durant le premier trimestre dans dix villes canadiennes de 2008 à 2011. Les données des questionnaires et les échantillons biologiques ont servi à évaluer l’effet de deux groupes de composés : les persistants [composés perfluorés – perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA) et perfluorohexane sulfonate (PFHxS)] et les non persistants (bisphénol A, triclosan et phtalates). Cette thèse comprend également une analyse du potentiel du ratio index-annulaire (2D:4D) comme mesure de sensibilité endocrinienne. À ce jour, des mesures anthropométriques ont été collectées sur environ 800 mères-enfants dans le cadre de l’Étude mère-enfant sur les composés chimiques de l’environnement : biomonitoring et neurodéveloppement à la petite enfance (MIREC CD Plus), un suivi de la cohorte MIREC portant sur la croissance et le développement des enfants jusqu’à 5 ans. Sur l’ensemble, les résultats de cette thèse permettent d’étoffer les preuves concernant les effets adverses potentiels de plusieurs contaminants environnementaux sur la fécondité féminine, telle que mesurée par le TTP. Dans le premier article, nous avons montré une association entre les PFOA et les PFHxS et une baisse de fécondité, ce que d’autres recherches avaient déjà révélé. Dans le deuxième article, nous avons évalué l’effet du triclosan sur le TTP, ce qui n’avait jamais été examiné, pour montrer un délai plus élevé chez les femmes du quartile supérieur d’exposition. De plus, nos résultats sont en accord avec ceux de la seule étude ayant évalué l’effet du Bisphénol A sur la fécondité féminine, qui n’avait pas détecté d’effet. Finalement, nos données semblent indiquer une association entre l’exposition des femmes aux phtalates et un TTP plus court, mais ces résultats ne sont pas statistiquement significatifs. En ce qui a trait au potentiel du ratio index-annuaire (2D:4D) pour mesurer la sensibilité endocrinienne chez les femmes, nos données ne permettent pas d’établir une association entre ce ratio et le TTP. Pour ce qui est des enfants, nous n’avons pas trouvé d’effet adverse entre le tabagisme de la mère durant la grossesse et leur ratio 2D:4D. Par conséquent, nos données ne semblent pas justifier l’utilisation du ratio 2D:4D pour mesurer la sensibilité endocrinienne en lien avec le potentiel reproducteur (basé sur le TTP) ou l’exposition des enfants au tabac durant le premier trimestre de grossesse.

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

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.

Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: Proliferative and inflammatory disorders and a possible role of androgens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reproductive development and function of female rats exposed to di-eta-butyl-phthalate (DBP) in utero and during lactation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Caracterização e estudo do comportamento térmico de chorume, de composto maturado e derivados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)