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A New Validated HPLC Method for the Simultaneous Determination of 2-phenoxyethanol, Methylparaben, Ethylparaben and Propylparaben in a Pharmaceutical Gel  

PubMed Central

A novel reversed-phase HPLC method has been developed and validated for the simultaneous determination of 2-phenoxyethanol, methylparaben, ethylparaben and propylparaben preservatives. The method uses a Lichrosorb C8 (150×4.6 mm, 5 µm) column and isocratic elution. The mobile phase consisted of a mixture of acetonitrile, tetrahydrofuran and water (21:13:66, v/v/v), pumped at a flow rate of 1 ml/min. The UV detection was set at 258 nm. The method was validated with respect to accuracy, precision (repeatability and intermediate precision), specificity, linearity and range. All the parameters examined met the current recommendations for bioanalytical method validation. The developed method was successfully applied to the determination of commercially available pharmaceutical gel products for these preservatives. The procedure describes here is simple, selective and reliable for routine quality control analysis and stability tests. PMID:21218050

Shabir, G. A.



Simultaneous determination of methylparaben, propylparaben and thimerosal by high-performance liquid chromatography and electrochemical detection  

Microsoft Academic Search

A reversed-phase high-performance liquid chromatographic method using amperometric detection has been developed for the analysis of methylparaben, propylparaben and thimerosal. The liquid chromatographic separation of the three preservatives was made possible on a C18-bonded silica column with a mixed solvent consisting of methanol and aqueous 0.02 M phosphoric acid (59:41, v\\/v). A potential value of + 1.25 V versus Ag\\/AgCl

Seong Ho Kang; Hasuck Kim



Assay of artemether, methylparaben and propylparaben in a formulated paediatric antimalarial dry suspension.  


Two HPLC-UV methods are described for the separate determination of artemether (AM) and the combined preservatives, methylparaben and propylparaben in a pharmaceutical dosage form. These analytes are contained in a dry suspension with a high amount of non-soluble excipients, some of which can interfere with the analysis. This makes their separation and analysis of the actives complex. Moreover, due to the wide difference in concentrations, the three analytes could not be quantitated simultaneously. Artemether was analysed using a reversed-phase Nucleosil C(18) column [5 microm, 125 mm x 4 mm (i.d.)] with a mixture of acetonitrile: potassium phosphate buffer pH 5.0 (0.05 M): water [48:32:10 (v/v/v)] as mobile phase. Due to the low solubility of the hydroxy benzoic acid esters in water, their sodium salts were used in the formulation. Complete separation of these preservatives was achieved on the same type of column as artemether using as eluent acetonitrile: potassium phosphate buffer pH 5.0 (0.05 M) (30:70, v/v). Quantitation was achieved with UV detection at 215 nm for artemether and 254 nm for the parabens, respectively. And in both methods, pump flow rate was 1.0 ml/min, sample injection volume 20 microl, ambient temperature maintained and no prior sample extraction methods were necessary throughout the experiments. Calibration curves were linear at concentration ranges of 4-16 microg/ml, 1-4 microg/ml and 1-10 mg/ml for methylparaben, propylparaben and artemether respectively. The excipient powder interference could be eliminated by diluting the sample and the analytes eluted at relatively short times using these systems. Both methods were further validated in terms of specificity, linearity, precision and accuracy. The procedures prescribed here are simple, selective and can be used for routine quality control and stability indicating tests involving the analysed compounds formulated in complex matrices. PMID:17074460

Atemnkeng, Magnus A; Marchand, Els; Plaizier-Vercammen, Jacqueline



A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben.  


A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs. PMID:17960329

Talevi, Alan; Bellera, Carolina L; Castro, Eduardo A; Bruno-Blanch, Luis E



Development and Validation of a Stability-Indicating LC-Method for the Simultaneous Estimation of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and Levodropropizine Impurities  

PubMed Central

A simple, fast, and efficient RP-HPLC method has been developed and validated for the simultaneous estimation of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and the quantification of Levodropropizine impurities in the Reswas syrup dosage form. A gradient elution method was used for the separation of all the actives and Levodropropizine impurities by using the X-Bridge C18, 150 mm × 4.6 mm, 3.5 ?m column with a flow rate of 1.0 mL/min and detector wavelength at 223 nm. The mobile phase consisted of a potassium dihydrogen orthophosphate buffer and acetonitrile. All the peaks were symmetrical and well-resolved (resolution was greater than 2.5 for any pair of components) with a shorter run time. The limit of detection for Levodropropizine and its Impurity B was 0.07 ?g/ml & 0.05 ?g/ml, whereas the limit of quantification was 0.19 ?g/ml & 0.15 ?g/ml respectively. The method was validated in terms of precision, accuracy, linearity, robustness, and specificity. Degradation products resulting from the stress studies were well-resolved and did not interfere with the detection of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and Levodropropizine Impurity B, thus the test method is stability-indicating. Validation of the method was carried out as per International Conference on Harmonization (ICH) guidelines. PMID:23641334

Kumar, Palakurthi Ashok; Raju, Thummala Veera Raghava; Thirupathi, Dongala; Kumar, Ravindra; Shree, Jaya



Validated Stability-indicating Reverse-phase Ultra-performance Liquid Chromatography Method for Simultaneous Determination of Sodium Methylparaben, Sodium Propylparaben and Ketorolac Tromethamine in Topical Dosage Forms.  


A sensitive, fast, and stability-indicating isocratic reverse-phase ultra-performance liquid chromatography method was developed and validated for quantitative simultaneous determination of sodium methylparaben, sodium propylparaben and ketorolac tromethamine in topical dosage forms. Separation of all peaks was achieved by using acquity ethylene bridged hybrid C18 (50×2.1 mm, 1.7 ?) as stationary phase, mobile phase used was triethylamine buffer (pH 2.5):tetrahydrofuran:methanol (665:35:300, v/v/v) with isocratic mode at a flow rate of 0.40 ml/min. All component were detected at 252 nm with 10 min run time. The described method was found to be linear in the concentration range of 248-744 ?g/ml for ketorolac tromethamine, 20.8-62.4 ?g/ml for sodium methylparaben and 2.38-7.13 ?g/ml for sodium propylparaben with correlation coefficients more than 0.999. Method was validated in terms of specificity, linearity, accuracy, precision, solution stability, filter equivalency, and robustness as per International Conference on Harmonization guideline. Formulation was exposed to the stress conditions of peroxide, acid, base, thermal, and photolytic degradation and proven all components were well separated in the presence of degradants. PMID:24019569

Roy, C; Chakrabarty, J; Modi, P B



Quality by Design-Based Development of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Methylparaben, Propylparaben, Diethylamino Hydroxybenzoyl Hexyl Benzoate, and Octinoxate in Topical Pharmaceutical Formulation.  


A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of methylparaben (MP), propylparaben (PP), diethylamino hydroxybenzoyl hexyl benzoate (DAHHB), and octinoxate (OCT) in topical pharmaceutical formulation. The desired chromatographic separation was achieved on the Kinetex(TM) C18 (250 × 4.6 mm, 5 ?m) column using gradient elution at 257 nm detection wavelength. The optimized mobile phase consisted of a buffer : acetonitrile : tetrahydrofuran (60 : 30 : 10, v/v/v) as solvent A and acetonitrile : tetrahydrofuran (70 : 30, v/v) as solvent B. The method showed linearity over the range of 0.19-148.4 ?g/mL, 0.23-15.3 ?g/mL, 1.97-600.5 ?g/mL, and 1.85-451.5 ?g/mL for MP, PP, DAHHB, and OCT, respectively. Recovery for all the components was found to be in the range of 98-102%. The stability-indicating capability of the developed method was established by analysing the forced degradation samples in which the spectral purity of MP, PP, DAHHB, and OCT, along with the separation of the degradation products from the analyte peaks, was achieved. The proposed method was successfully applied for the quantitative determination of MP, PP, DAHHB, and OCT in the lotion sample. The design expert with ANOVA software with the linear model was applied and a 2(4) full factorial design was employed to estimate the model coefficients and also to check the robustness of the method. Results of the two-level full factorial design, 2(4) with 20 runs including four centrepoint analysis based on the variance analysis (ANOVA), demonstrated that all four factors, as well as the interactions of resolution between DAHHB and OCT are statistically significant. PMID:25853065

Roy, Chinmoy; Chakrabarty, Jitamanyu



Quality by Design-Based Development of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Methylparaben, Propylparaben, Diethylamino Hydroxybenzoyl Hexyl Benzoate, and Octinoxate in Topical Pharmaceutical Formulation  

PubMed Central

Abstract A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of methylparaben (MP), propylparaben (PP), diethylamino hydroxybenzoyl hexyl benzoate (DAHHB), and octinoxate (OCT) in topical pharmaceutical formulation. The desired chromatographic separation was achieved on the KinetexTM C18 (250 × 4.6 mm, 5 ?m) column using gradient elution at 257 nm detection wavelength. The optimized mobile phase consisted of a buffer : acetonitrile : tetrahydrofuran (60 : 30 : 10, v/v/v) as solvent A and acetonitrile : tetrahydrofuran (70 : 30, v/v) as solvent B. The method showed linearity over the range of 0.19–148.4 ?g/mL, 0.23–15.3 ?g/mL, 1.97–600.5 ?g/mL, and 1.85–451.5 ?g/mL for MP, PP, DAHHB, and OCT, respectively. Recovery for all the components was found to be in the range of 98–102%. The stability-indicating capability of the developed method was established by analysing the forced degradation samples in which the spectral purity of MP, PP, DAHHB, and OCT, along with the separation of the degradation products from the analyte peaks, was achieved. The proposed method was successfully applied for the quantitative determination of MP, PP, DAHHB, and OCT in the lotion sample. The design expert with ANOVA software with the linear model was applied and a 24 full factorial design was employed to estimate the model coefficients and also to check the robustness of the method. Results of the two-level full factorial design, 24 with 20 runs including four centrepoint analysis based on the variance analysis (ANOVA), demonstrated that all four factors, as well as the interactions of resolution between DAHHB and OCT are statistically significant.

Roy, Chinmoy; Chakrabarty, Jitamanyu



Ethylparaben affects lifespan, fecundity, and the expression levels of ERR, EcR and YPR in Drosophila melanogaster.  


Parabens, which mainly include methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP), are widely used as cosmetic and food preservatives. Although these chemicals, when used as preservatives, are thought to be safe for humans, many studies have demonstrated that they have estrogenic effects, and can affect the normal development and functions of the reproductive systems in a number of animal species. By treating fruit flies (Drosophila melanogaster) with EP, here we show that lower concentration of EP (0.02%) enhanced fertility while higher concentration of EP (0.10% and 0.20%) shortened the lifespan and reduced the fecundity of fruit flies. When we analyzed the expression levels of the estrogen-related receptor gene (ERR), ecdysone receptor gene (EcR) and Yolk protein receptor gene (YPR) from control and EP-treated fruit flies by using quantitative real-time PCR, we found that the expression levels of all three genes were significantly changed by EP treatment, and that female fruit flies are more sensitive to EP than males. Our data suggests that the estrogenic and the toxic effects of EP to fruit flies may have a molecular basis through the hormonal effect of EP. PMID:25265034

Liu, Ting; Li, Yajuan; Zhao, Xiaojun; Zhang, Min; Gu, Wei



Fast simultaneous spectrophotometric determination of naphazoline nitrate and methylparaben by sequential injection chromatography.  


Fast simultaneous determination of naphazoline nitrate and methylparaben in pharmaceuticals using separation method based on a novel reversed-phase sequential injection chromatography (SIC) is described in this contribution as an alternative to classical HPLC. A Chromolithtrade mark Flash RP-18e (25mmx4.6mm) column (Merck((R)), Germany) and a FIAlab((R)) 3000 system (USA) with a six-port selection valve and 5.0ml syringe pump were used for sequential injection chromatographic separations in our study. The mobile phase used was methanol/water (40:65, v/v), pH 5.2 adjusted with triethylamine 0.8mulml(-1) and acetic acid, at flow rate 0.9mlmin(-1). UV detection provided by DAD detector and two wavelengths were simultaneously monitored for increasing sensitivity of determination. Detector was set up at 220nm for naphazoline nitrate and 256nm for methylparaben and ethylparaben (IS). There is no necessity to use pre-adjustment of sample of nasal drops (only dilution with mobile phase) so the time of the whole analysis is very short. The validation parameters have shown good results: linearity of determination for both components (naphazoline nitrate and methylparaben), correlation coefficient >0.999; repeatability of determination (R.S.D.) in the range 0.5-1.6% at three different concentration levels, detection limits 0.02mugml(-1) (naphazoline nitrate) and 0.20mugml(-1) (methylparaben and ethylparaben), and recovery from the pharmaceutical preparations in the range 100.06-102.55%. The chromatographic resolution between peaks of compounds was more than 4.0 and analysis time was less than 4min under the optimal conditions. The advantages and drawbacks of SIC against classical HPLC are discussed showing that SIC can be an advantageous alternative in many cases. PMID:18970784

Chocholous, Petr; Satínský, Dalibor; Solich, Petr



Determination of parabens in shampoo using high performance liquid chromatography with amperometric detection on a boron-doped diamond electrode  

Microsoft Academic Search

Methylparaben (MePa), ethylparaben (EtPa) and propylparaben (PrPa) have been widely used, among others, as chemical preservatives in cosmetics, drugs and foods. As these compounds are linked with allergies, dermatitis and estrogenic properties, it is necessary to control the concentration of these substances in different matrices. The aim of this paper are: to evaluate the electrochemical behavior of parabens on the

Isarita Martins; Franciely Cristiani Carreira; Larissa S. Canaes; Francisco Alberto de Souza Campos Junior; Letícia Maria da Silva Cruz; Susanne Rath




Microsoft Academic Search

In the present work an efficient method based on ultrasound-assisted emulsification microextraction was developed for the determination of sodium benzoate (SB), p-hydroxybenzoic acid (PHBA), methyl-paraben (MP), ethyl-paraben (EP) and propyl-paraben (PP) in different samples. In this procedure, 40 µL of (5% w\\/v) aliquat 336 in 1-octanol was injected slowly into a 12 mL home-designed centrifuge glass vial containing an aqueous sample of

Yadollah Yamini; Abolfazl Saleh; Mohammad Rezaee; Leila Ranjbar; Morteza Moradi



Identification of ethylparaben as the antimicrobial substance produced by Brevibacillus brevis FJAT-0809-GLX.  


In this study, crude antimicrobial extract from the culture supernatant of Brevibacillus brevis FJAT-0809-GLX was extracted, and its antimicrobial activity was investigated with the agar diffusion method. The results showed that the antimicrobial activity of the culture supernatant of B. brevis FJAT-0809-GLX increased with the extension of the incubation time of B. brevis FJAT-0809-GLX. The antimicrobial spectrum assays showed that this crude antimicrobial extract from culture supernatant of B. brevis FJAT-0809-GLX could inhibit the growth of both bacteria and fungi. A heat stability test was performed, and different temperatures (30°C, 50°C and 70°C) did not affect the antibiotic activity of this crude antimicrobial extract. The crude antimicrobial extract was also tolerable to changes in pH levels. Its antibiotic activity against Escherichia coli was stable at pH 1 to pH 11, with zone sizes ranging from 18.46mm to 22.19mm. Almost all of the crude extracts extracted using different solvents showed variable degrees of inhibition zones against E. coli, with zone sizes ranging from 17.29mm to 19.62mm, except petroleum ether and butanol extracts, which were found to be completely inactive. Purification of the antimicrobial components was carried out using a column chromatographic technique with column chromatography grade silica gel and analyzed by an Agilent 7890A Network GC system. The separated compound was identified as ethylparaben, with a retention time of 21.980min and a relative amount of 95.50%. The antimicrobial activity of ethylparaben on different types of bacteria and fungi was investigated, and ethylparaben was shown to inhibit different types of microbes to different extents. To the best of our knowledge, this is the first report demonstrating that the bacterium B. brevis could produce ethylparaben. PMID:25542595

Jianmei, Che; Bo, Liu; Zheng, Chen; Huai, Shi; Guohong, Liu; Cibin, Ge



Differential effect of methyl-, butyl- and propylparaben and 17?-estradiol on selected cell cycle and apoptosis gene and protein expression in MCF-7 breast cancer cells and MCF-10A non-malignant cells.  


Parabens are alkyl esters of p-hydroxybenzoic acid used widely as antimicrobial preservatives in consumer products, including pharmaceuticals, foods and cosmetics. We showed previously that methyl-, butyl- and propylparaben parabens, even at low doses, stimulate the proliferation of MCF-7 breast cancer cells and non-transformed MCF-10A breast epithelial cells. The present study was undertaken to determine whether this represents a direct effect on cell cycle and apoptotic gene expression. MCF-7 and MCF-10A cells were exposed to methyl, butyl- and propylparaben (20?nm) or 17?-estradiol (10?nm). Cell cycle and apoptotic gene expression were evaluated by real-time polymerase chain reaction and protein expression by Western blot. 17?-estradiol upregulated G1 /S phase genes and downregulated cell cycle progression inhibitors in both MCF-7 and MCF-10A. Upregulation of Bcl-xL and downregulation of caspase 9 was observed in MCF-7, while upregulation of Bcl-xL, BCL2L2 and caspase 9 was noted in MCF-10A. Cyclins in MCF-7 cells were not affected by any of the parabens. Methyl- and butylparaben had no effect on the expression of selected apoptotic genes in MCF-7. In MCF-10A, all parabens tested increased the expression of G1 /S phase genes, and downregulated cell cycle inhibitors. Methylparaben increased pro-survival gene. Butylparaben increased BCL2L1 gene, as did 17?-estradiol, while propylparaben upregulated both the extrinsic and intrinsic apoptotic pathways. There are differences in cell cycle and apoptosis gene expression between parabens and 17?-estradiol in MCF-7 cells. In MCF-10A cells, most of the genes activated by parabens were comparable to those activated by 17?-estradiol. PMID:24481588

Wróbel, Anna Maria; Gregoraszczuk, Ewa ?ucja



Methylparaben potentiates UV-induced damage of skin keratinocytes  

Microsoft Academic Search

For many years, methylparaben (MP) has been used as a preservative in cosmetics. In this study, we investigated the effects of ultraviolet-B (UVB) exposure on MP-treated human skin keratinocytes. HaCaT keratinocyte was cultured in MP-containing medium for 24h, exposed to UVB (15 or 30mJ\\/cm2) and further cultured for another 24h. Subsequent cellular viability was quantified by MTT-based assay and cell

Osamu Handa; Satoshi Kokura; Satoko Adachi; Tomohisa Takagi; Yuji Naito; Toru Tanigawa; Norimasa Yoshida; Toshikazu Yoshikawa



Photocatalytic degradation of methylparaben by TiO 2: Multivariable experimental design and mechanism  

Microsoft Academic Search

Methylparaben is widely used as a bactericide and as an antimicrobial agent in the formulation of personal care products (PCPs) such as tooth pastes, deodorants, beauty creams, solar filters, and bath gels. Owing to a certain estrogenic activity, a possible relationship with breast cancer has been proved by many researchers. Photocatalytic degradation of methylparaben was carried out in an aqueous

Yixin Lin; Corinne Ferronato; Nansheng Deng; Feng Wu; Jean-Marc Chovelon



Determination of parabens in beverage samples by dispersive liquid-liquid microextraction based on solidification of floating organic droplet.  


A simple and efficient method for dispersive liquid-liquid microextraction of methylparaben, ethylparaben, propylparaben and butylparaben in real beverage samples was developed. It is making use of solidified floating organic droplets of 1-dodecanol which has low density and a proper melting point. Parameters influencing the extraction efficiency, such as the type of extraction and dispersive solvent, the volume of extraction and dispersive solvent, salt effect, pH, extraction time, were optimized and resulted in enrichment factors (EFs) of 84 for methylparaben, 103 for ethylparaben, 115 for propylparaben and 126 for butylparaben. The limits of detection for parabens were 1.52, 1.06, 0.32 and 0.17 ng/mL, respectively. Excellent linearity with coefficients of correlation from 0.9970 to 0.9997 was observed in the concentration range of 5-1,000 ng/mL. The repeatability of the proposed method expressed as relative standard deviations (RSDs) ranged from 2.54 to 3.89% (n = 5). The relative recoveries for parabens in beverage samples were good and in the ranges of 89.8-109.9, 90.2-107.3, 90.9-101.7 and 92.3-118.1%, respectively. Thus, the proposed method has excellent potential for the determination of parabens in beverage samples. PMID:24297525

Hou, Fang; Deng, Xiaoying; Jiang, Xinyu; Yu, Jingang



Influence of methylparaben as a solid-state plasticizer on the physicochemical properties of Eudragit RS PO hot-melt extrudates.  


The purpose of this study was to investigate the properties of methylparaben as a solid-state plasticizer for Eudragit RS PO during a hot-melt extrusion process. Extruded matrices containing different levels of methylparaben and Eudragit RS PO, were prepared by feeding the powder blend through a hot melt extruder. The melt viscosity of the polymer blends was assessed by torque rheometry using a Brabender Plasticorder. The physicochemical properties of the extruded methylparaben-containing polymer matrix were characterized by differential scanning calorimetry and X-ray diffraction. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to study the possible interaction between methylparaben and Eudragit RS PO polymer. The results demonstrated that the glass transition temperature of the Eudragit RS PO decreased with increasing levels of methylparaben in the extrudate, due to an increase in the chain mobility of Eudragit RS PO. The crystallinity of methylparaben was absent following hot-melt processing. At increasing levels of methylparaben in the extrudates, a decrease in the melt viscosity was seen due to a plasticization of the polymer. Rheological properties of the extrudates containing methylparaben were compared with the extrudates containing conventional plasticizers. It was found that methylparaben was as effective as triethyl citrate (TEC) in reducing torque during the extrusion process. Solid state NMR spectra indicated a change in the chemical shift of Eudragit RS PO plasticized with methylparaben, which could be ascribed to an interaction between the hydroxyl group of the methylparaben and the ester group of the Eudragit RS PO polymer. The results of this study demonstrated that methylparaben could be used as a solid-state plasticizer for the Eudragit RS PO polymer when a hot melt extrusion technique was employed in the preparation of sustained release tablets. PMID:12837487

Wu, Chuanbin; McGinity, James W



Influence of methylparaben as a solid-state plasticizer on the physicochemical properties of Eudragit® RS PO hot-melt extrudates  

Microsoft Academic Search

The purpose of this study was to investigate the properties of methylparaben as a solid-state plasticizer for Eudragit® RS PO during a hot-melt extrusion process. Extruded matrices containing different levels of methylparaben and Eudragit® RS PO, were prepared by feeding the powder blend through a hot melt extruder. The melt viscosity of the polymer blends was assessed by torque rheometry

Chuanbin Wu; James W McGinity



A new validated method for the simultaneous determination of benzocaine, propylparaben and benzyl alcohol in a bioadhesive gel by HPLC  

Microsoft Academic Search

A new HPLC-RP method has been developed and validated for the simultaneous determination of benzocaine, two preservatives (propylparaben (nipasol) and benzyl alcohol) and degradation products of benzocaine in a semisolid pharmaceutical dosage form (benzocaine gel). The method uses a Nucleosil 120 C18 column and gradient elution. The mobile phase consisted of a mixture of methanol and glacial acetic acid (10%,

P. Pérez-Lozano; E. García-Montoya; A. Orriols; M. Miñarro; J. R. Ticó; J. M. Suñé-Negre



Degradation of methylparaben in water by corona plasma coupled with ozonation.  


The degradation of methylparaben (MeP) in water was investigated using a pulsed corona discharge generated in oxygen, above the liquid. A comparison was made between results obtained in semi-batch corona (SBC) configuration (stationary solution, continuous gas flow) and results obtained in a semi-batch corona with recirculation combined with ozonation (SBCR?+?O3), where the liquid is continuously circulated between a solution reservoir and the plasma reactor and the effluent gas containing ozone is bubbled through the solution in the reservoir. It was found that MeP was completely degraded after 10-15 min of treatment in both configurations. Oxidation by ozone alone, in the absence of plasma, was a slower process. The energy efficiency for MeP removal (Y MeP) and for mineralization (Y TOC) was significantly higher in the SBCR?+?O3 configuration (Y MeP?=?7.1 g/kWh at 90 % MeP removal and Y TOC?=?0.41 g/kWh at 50 % total organic carbon (TOC) removal) than in the SBC configuration (Y MeP?=?0.6 g/kWh at 90 % MeP removal and Y TOC?=?0.11 g/kWh at 50 % TOC removal). PMID:24801291

Dobrin, D; Magureanu, M; Bradu, C; Mandache, N B; Ionita, P; Parvulescu, V I



Bioanalysis of propylparaben and p-hydroxybenzoic acid, and their sulfate conjugates in rat plasma by liquid chromatography-tandem mass spectrometry.  


Two rugged liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the determination of propylparaben, its major metabolite, p-hydroxybenzoic acid (pHBA), and their sulfate conjugates have been developed and validated in citric acid-treated rat plasma. To prevent propylparaben being hydrolyzed to pHBA ex vivo, rat plasma was first treated with citric acid; then collected and processed at a reduced temperature (ice bath). Stable isotope labeled internal standards, d4-propylparaben, (13)C6-pHBA, and the d4-labeled internal standards of their sulfate conjugates were used in the methods. The analytes were extracted from the matrix using protein precipitation, followed by chromatographic separation on a Waters ACQUITY UPLC HSS T3 column. Quantification using negative ion electrospray was performed on a Sciex API 4000 mass spectrometer. The analytical ranges were established from 2.00 to 200 ng/mL for propylparaben, 50.0-5000 ng/mL for pHBA, 50.0-10,000 ng/mL for the sulfate conjugate of propylparaben (SPP) and 200-40,000 ng/mL for the sulfate conjugate of pHBA (SHBA). Inter- and intra-run precision for the quality control samples were less than 5.3% and 4.4% for all analytes; and the overall accuracy was within ±5.7% of the nominal values. The validated bioanalytical methods demonstrated excellent sensitivity, specificity, accuracy and precision and were successfully applied to a rat toxicology study under the regulations of Good Laboratory Practices (GLP). Strategies have been developed and applied toward overcoming the challenges related to analyte stability, and environmental and endogenous background. PMID:24412689

Zhao, Yue; Liu, Guowen; Shen, Hongwu; Shen, Jim X; Aubry, Anne-Françoise; Sivaraman, Lakshmi; Arnold, Mark E



Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 2: personal care product ingredients.  


An intensive study was conducted to provide data on intra- and inter-individual variation in urinary excretion of a series of ingredients in personal care products (parabens, triclosan, benzophenones) and bisphenol A (BPA, not expected to be an ingredient) in 8 volunteers over 6 days. Exposure diaries recorded use of personal care products with identified target analytes as ingredients. Participants' usual products were replaced with products without the target analytes for 2 of the 6 days. Urine void volumes and times were recorded. Methyl, ethyl, and n-propylparabens, triclosan, benzophenone-3, and BPA were frequently detected (?70% of samples). Urinary concentrations of the parabens and triclosan were lower on product replacement days. First morning void concentrations correlated moderately to highly with 24-h composite concentrations for all analytes. Intraclass correlation coefficients (ICCs) for spot samples collected on days with usual product use were low for BPA (0.15), moderate for n-propylparaben and methylparaben (0.39 and 0.56, respectively), and high for ethylparaben, benzophenone-3, and triclosan (0.76, 0.81, and 0.934, respectively); ICCs were consistently higher on the basis of cr-adjusted concentrations. Hydration status adjustment methods were assessed by comparing unadjusted and adjusted concentrations to urinary excretion rates (ER, ng/kg-h) for all analytes and samples. Specific gravity-adjusted concentrations correlated slightly better with ER than creatinine-adjusted concentrations. Within-individual variation in biomarker concentrations was highest for methyl and ethylparabens (2 orders of magnitude variation in spot sample concentrations) and lower for the other analytes (1-1.5 orders of magnitude). This dataset provides insight into the design and interpretation of urinary biomonitoring studies for non-persistent chemicals. PMID:24956590

Koch, Holger M; Aylward, Lesa L; Hays, Sean M; Smolders, Roel; Moos, Rebecca K; Cocker, John; Jones, Kate; Warren, Nicholas; Levy, Len; Bevan, Ruth



Structural Changes in PEO?PPO?PEO Gels Induced by Methylparaben and Dexamethasone Observed Using Time-Resolved SAXS  

SciTech Connect

Aqueous solutions of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) triblock copolymers (commercially available as Pluronic surfactants) micellize and structurally arrange into cubic quasicrystalline lattices as their temperature is raised. This structural evolution is seen macroscopically as a gelation, and the presence of these ordered phases can be controlled through both polymer concentration and temperature. The presence of added solutes within the dispersions can also affect the onset and kinetics of structure formation. Here we investigate the structures formed in Pluronic F127 solutions ranging from 20 to 30% with two pharmaceutical additives [methylparaben (MP) and dexamethasone (DX)] using small-angle X-ray scattering (SAXS). We observe both the progressive evolution and breakdown of these structures as the temperature is increased from 0 to 80 C. Additionally, we conducted time-resolved SAXS measurements to elucidate the kinetics of the structural evolution. On the basis of the evolution of scattering peaks as the samples were being heated, we suggest that added MP changes the nucleation behavior of fcc phases within the sample from a heterogeneous process to a more homogeneous distribution of nucleated species. MP and DX also stabilize the micelle lattices, allowing them to persevere at higher temperatures. We observed the unusual result that the presence of DX caused the primary peaks of the structure factor to be suppressed, while preserving the higher order peaks. The primary peaks reappeared at the highest temperatures tested.

Meznarich, Norman A.K.; Juggernauth, K. Anne; Batzli, Kiersten M.; Love, Brian J. (Michigan)



Determination of biocides in different environmental matrices by use of ultra-high-performance liquid chromatography-tandem mass spectrometry.  


A sensitive and robust method using solid-phase extraction and ultrasonic extraction for preconcentration followed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) has been developed for determination of 19 biocides: eight azole fungicides (climbazole, clotrimazole, ketoconazole, miconazole, fluconazole, itraconazole, thiabendazole, and carbendazim), two insect repellents (N,N-diethyl-3-methylbenzamide (DEET), and icaridin (also known as picaridin)), three isothiazolinone antifouling agents (1,2-benzisothiazolinone (BIT), 2-n-octyl-4-isothiazolinone (OIT), and 4,5-dichloro-2-n-octyl-isothiazolinone (DCOIT)), four paraben preservatives (methylparaben, ethylparaben, propylparaben, and butylparaben), and two disinfectants (triclosan and triclocarban) in surface water, wastewater, sediment, sludge, and soil. Recovery of the target compounds from surface water, influent, effluent, sediment, sludge, and soil was mostly in the range 70-120%, with corresponding method quantification limits ranging from 0.01 to 0.31 ng L(-1), 0.07 to 7.48 ng L(-1), 0.01 to 3.90 ng L(-1), 0.01 to 0.45 ng g(-1), 0.01 to 6.37 ng g(-1), and 0.01 to 0.73 ng g(-1), respectively. Carbendazim, climbazole, clotrimazole, methylparaben, miconazole, triclocarban, and triclosan were detected at low ng L(-1) (or ng g(-1)) levels in surface water, sediment, and sludge-amended soil. Fifteen target compounds were found in influent samples, at concentrations ranging between 0.4 (thiabendazole) and 372 ng L(-1) (methylparaben). Fifteen target compounds were found in effluent samples, at concentrations ranging between 0.4 (thiabendazole) and 114 ng L(-1) (carbendazim). Ten target compounds were found in dewatered sludge samples, at concentrations ranging between 1.1 (DEET) and 887 ng g(-1) (triclocarban). PMID:23052884

Chen, Zhi-Feng; Ying, Guang-Guo; Lai, Hua-Jie; Chen, Feng; Su, Hao-Chang; Liu, You-Sheng; Peng, Fu-Qiang; Zhao, Jian-Liang



Direct rapid analysis of multiple PPCPs in municipal wastewater using ultrahigh performance liquid chromatography-tandem mass spectrometry without SPE pre-concentration.  


Ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was utilized to develop a rapid, sensitive and reliable method without solid phase extraction (SPE) pre-concentration for trace analysis of 11 pharmaceuticals and personal care products (PPCPs) in in?uent and ef?uent from municipal wastewater treatment plants (WWTPs). This method not only shortened the analysis time but also reduced analysis cost significantly by omitting SPE process and avoiding the consumption of SPE cartridge. Detection parameters for UHPLC-MS/MS analysis were optimized, including sample pH, eluent, mobile phase (solvent and additive), column temperature, and ?ow rate. Under the optimal conditions, all analytes were well separated and detected within 8.0min by UHPLC-MS/MS. The method quantification limits (MQLs) for the 11 PPCPs ranged from 0.040 to 88ngL(-1) and from 0.030 to 90ngL(-1) for influent and effluent, respectively. The matrix effect was systematically investigated and quantified for different types of samples. The analysis of in?uent and ef?uent samples of two WWTPs in Hong Kong revealed the presence of 11 PPCPs, including acyclovir, benzophenone-3, benzylparaben, carbamazepine, ethylparaben, fluconazole, fluoxetine, methylparaben, metronidazole, propylparaben, and ranitidine. Their concentrations ranged from 9.1 to 1810ngL(-1) in influent and from 6.5 to 823ngL(-1) in effluent samples collected from Hong Kong WWTPs. PMID:22790701

Yu, Ke; Li, Bing; Zhang, Tong



Advanced oxidation kinetics and mechanism of preservative propylparaben degradation in aqueous suspension of TiO2 and risk assessment of its degradation products.  


The absolute kinetic rate constants of propylparaben (PPB) in water with different free radicals were investigated, and it was found that both hydroxyl radicals (HO(•)) and hydrated electrons could rapidly react with PPB. The advanced oxidation kinetics and mechanisms of PPB were investigated using photocatalytic process as a model technology, and the degradation was found to be a pseudo-first-order model. Oxidative species, particularly HO(•), were the most important reactive oxygen species mediating photocatalytic degradation of PPB, and PPB degradation was found to be significantly affected by pH because it was controlled by the radical reaction mechanism and was postulated to occur primarily via HO(•)-addition or H-abstraction reactions on the basis of pulse radiolysis measurements and observed reaction products. To investigate potential risk of PPB to humans and aqueous organisms, the estrogenic assays and bioassays were performed using 100 ?M PPB solution degraded by photocatalysis at specific intervals. The estrogenic activity decreased as PPB was degraded, while the acute toxicity at three trophic levels first increased slowly and then decreased rapidly as the total organic carbon decreased during photocatalytic degradation. PMID:23432079

Fang, Hansun; Gao, Yanpeng; Li, Guiying; An, Jibin; Wong, Po-Keung; Fu, Haiying; Yao, Side; Nie, Xiangping; An, Taicheng



Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: using a pig-ear model in vitro.  


Currently, there is a trend to reduce of parabens use due to concern about the safety of their unmetabolised forms. This paper focused on dermal absorption rate and effectiveness of first-pass biotransformation of methylparaben (MP) under in-use conditions of skincare products. 24-h exposure of previously frozen intact and tapestripped (20 strips) pig-ear skin to nine vehicles containing 0.1% MP (AD, applied dose of 10 ?g/cm²), resulted in 2.0-5.8%AD and 2.9-7.6%AD of unmetabolised MP, and 37.0-73.0%AD and 56.0-95.0%AD of p-hydroxybenzoic acid, respectively, in the receptor fluid. The absorption rate of MP was higher from emulsions than from hydrogels, from enhancer-containing vehicles than from enhancer-free vehicles, and when skin was damaged. Experiments confirmed that the freezing of pig-ear skin slightly reduces hydrolysis of MP. After 4-h exposure of intact freshly excised and intact frozen stored skin, amount of

Pažoureková, Silvia; Hojerová, Jarmila; Klimová, Zuzana; Lucová, Marianna



Influence of relative humidity on the mechanical and drug release properties of theophylline pellets coated with an acrylic polymer containing methylparaben as a non-traditional plasticizer.  


The purpose of this study was to investigate the influence of relative humidity (RH) on the mechanical and dissolution properties of theophylline pellets coated with Eudragit((R)) RS 30 D/RL 30 D containing methylparaben (MP) as a non-traditional plasticizer. The coated beads were stored at 23 degrees C and at different relative humidities (0, 29, 51, 75 and 84% RH). The effect of storage conditions on the rate of drug release from coated beads was determined in pH 7.4 phosphate buffer solution. The mechanical properties, including tensile strength and Young's modulus, of individual beads were determined by a diametral compression method with a Chatillon((R)) tension/compression apparatus. The morphology of the intact and fractured beads was investigated using scanning electron microscopy (SEM). The moisture content of the polymeric films was determined using a Karl Fischer coulometric moisture analyzer. The results from the mechanical studies demonstrated that an increase in the relative humidity resulted in a decrease in the tensile strength and Young's modulus of the coated beads. SEM photographs showed that coated beads stored at 0% RH exhibited brittle fracture failure. The coated beads stored at 84% RH showed ductile behavior, which was attributed to the hydroplasticization effect on the acrylic polymer due to the uptake of moisture. The moisture content in the films was also shown to influence the rate of drug release from Eudragit((R)) RS 30 D/RL 30 D coated beads containing MP as the plasticizer. The change in release profiles could be minimized when the relative humidity was reduced to zero. The dissolution rate of theophylline from the coated beads decreased when stored at high relative humidities. This trend was reversed when the coated beads that were stored at 84% RH for 5 weeks, were then equilibrated at 0% RH. PMID:10962239

Wu, C; McGinity, J W



Glucocorticoid-like activity of propylparaben, butylparaben, diethylhexyl phthalate and tetramethrin mixtures studied in the MDA-kb2 cell line.  


Endocrine-disrupting compounds can interfere with the endocrine organs or hormone system and cause tumors, birth defects and developmental disorders in humans. The estrogen-like activity of compounds has been widely studied but little is known concerning their possible modulation of the glucocorticoid receptor. Steroidal (synthetic and natural) and non-steroidal endocrine-active compounds commonly occur as complex mixtures in human environments. Identification of such molecular species, which are responsible for modulating the glucocorticoid receptor are necessary to fully assess their risk. We have used the MDA-kb2 cell line, which expresses endogenous glucocorticoid receptor and a stably transfected luciferase reporter gene construct, to quantify the glucocorticoid-like activity of four compounds present in products in everyday use - propylparaben (PP), butylparaben (BP), diethylhexyl phthalate (DEHP) and tetramethrin (TM). We tested all possible combinations of these compounds at two concentrations (1 ?M and 10 nM) and compared their glucocorticoid-like activity. At the concentration of 1 ?M seven mixtures were identified to have glucocorticoid-like activity except: DEHP+TM, BP+TM, DEHP+PP+TM, BP+PP+TM. At the concentration of 10 nM only three mixtures have glucocorticoid modulatory activity: DEHP+PP, BP+PP, DEHP+BP+PP+TM. Identified glucocorticoid-like activities were between 1.25 and 1.51 fold at the concentration of 1 ?M and between 1.23 and 1.44 fold at the concentration of 10 nM in comparison with the solvent control. Individually BP, PP, and DEHP had glucocorticoid-like activity of 1.60, 1.57 and 1.50 fold over the solvent control at the concentration of 1 ?M. On the other hand PP and DEHP, at the concentration of 10nM, showed no glucocorticoid-like activity, while BP showed 1.44 fold. The assertion that individual glucocorticoid-like compounds do not produce harm because they are present at low, ineffective levels in humans may be irrelevant when we include mixed exposures. This study emphasizes that risk assessment of compounds should take mixture effects into account. PMID:25448277

Klop?i?, Ivana; Kolšek, Katra; Dolenc, Marija Sollner



Determination and temperature effects of lidocaine (lignocaine) hydrochloride, epinephrine, methylparaben, 2,6-dimethylaniline, and p-hydroxybenzoic acid in USP lidocaine injection by ion-pair reversed-phase high pressure liquid chromatography  

SciTech Connect

USP Lidocaine injection was assayed using ion-pair high pressure liquid chromatography with an octylsilane (RP-8) reversed-phase column packing and a mobile phase consisting of D-10-camphorsulfonic acid/methanol/acetic acid/water. The effect of temperature was investigated to determine the optimum temperature for separating the drug components and their degradation products. Lidocaine (lignocaine) hydrochloride, epinephrine, methylparaben, and p-hydroxybenzoic acid were separated at 50 degrees C. 2,6-Dimethylaniline was separated from lidocaine at 15 degrees C. An aliquot of the sample was injected directly into the liquid chromatograph, and after separation the compounds were quantitated by their spectrophotometric response at 254 nm (lidocaine) or 280 nm (lidocaine plus epinephrine).

Smith, D.J.



Simultaneous spectrophotometric determination of four preservatives in foodstuffs by multivariate calibration and artificial neural networks  

Microsoft Academic Search

Benzoic acid (BA), methylparaben (MP), propylparaben (PP) and sorbic acid (SA) are food preservatives, and they have well defined UV spectra. However, their spectra overlap seriously, and it is difficult to determine them individually from their mixtures without preseparation. In this paper, seven different chemometric approaches were applied to resolve the overlapping spectra and to determine these compounds simultaneously. With

Yan Qing Chen; Yong Nian Ni



Application of a validated method in the stability study of colistin sulfate and methylparaben in a veterinary suspension formulation by high-performance liquid chromatography with a diode array detector.  


A methodology following International Cooperation on Harmonization for Veterinary Products (VICH) guidelines for the stability evaluation of colistin sulfate in a nonaqueous suspension pharmaceutical dosage form for veterinary use (via their drinking water) is described. This method monitors the percentage of colistin sulfate during the stability study of the preparation in drinking water and establishes the shelf life of the final product by a new high-performance liquid chromatography method which was developed and validated for the simultaneous determination of colistin sulfate [colistin A (Polymixin E1) and colistin B (Polymixin E2)] and methylparaben (Nipagin) using a diode array detector (DAD). The method uses a Kromasil C18 column and isocratic elution. The mobile phase consisted of an acetonitrile-sodium sulfate anhydrous solution (25 + 75) pumped at a flow rate of 1.5 mL/min. The DAD was set at 215 nm. The validation study was carried out according to the VICH guidelines in order to prove that the new analytical method meets the reliability characteristics, which include the fundamental criteria for validation: selectivity, linearity, precision, accuracy, and sensitivity. The method was applied during the quality control or stability studies of the suspension dosage form in order to quantify the drug (colistin) and preservative, and proved to be suitable for rapid and reliable quality control. PMID:17580623

Pérez-Lozano, Pilar; García-Montoya, Encarna; Orriols, Anna; Miñarro, Montse; Ticó, Josep Ramon; Suñé-Negre, Josep Maria



21 CFR 184.1670 - Propylparaben.  

Code of Federal Regulations, 2012 CFR

...chemical propyl p -hydroxybenzoate. It is produced by the n -propanol esterification of p -hydroxybenzoic acid in the presence of sulfuric acid, with subsequent distillation. (b) The ingredient meets the specifications of...



21 CFR 184.1670 - Propylparaben.  

Code of Federal Regulations, 2010 CFR

...chemical propyl p -hydroxybenzoate. It is produced by the n -propanol esterification of p -hydroxybenzoic acid in the presence of sulfuric acid, with subsequent distillation. (b) The ingredient meets the specifications of...



21 CFR 184.1490 - Methylparaben.  

Code of Federal Regulations, 2014 CFR

...chemical methyl p -hydroxybenzoate. It is produced by the methanol esterification of p -hydroxybenzoic acid in the presence of sulfuric acid, with subsequent distillation. (b) The ingredient meets the specifications of...



21 CFR 184.1490 - Methylparaben.  

Code of Federal Regulations, 2013 CFR

...chemical methyl p -hydroxybenzoate. It is produced by the methanol esterification of p -hydroxybenzoic acid in the presence of sulfuric acid, with subsequent distillation. (b) The ingredient meets the specifications of...



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


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 ?DEHP 65.5 ?g/L; ?DiNP 37.8 ?g/L; MBzP 19.9 ?g/L; MnBP 76.9 ?g/L) than the mothers (?DEHP 38.4 ?g/L; ?DiNP 33.8 ?g/L; MBzP 12.8 ?g/L; MnBP 63.0 ?g/L). Conversely, the mother's levels of parabens (MetP 37.8 ?g/L; ProP 13.9 ?g/L) and MEP (43.4 ?g/L) were higher than the children's levels of parabens (MetP 6.8 ?g/L; ProP 2.1 ?g/L) and MEP (28.8 ?g/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p=<0.001; MnBP p=0.001-0.002), which is probably due to higher presence of PVC in floorings and wall coverings in this area, whereas the levels of parabens were higher among the children in the urban area (MetP p=0.003; ProP p=0.004) than in the rural area. The levels of high molecular weight phthalates were associated with consumption of certain foods (i.e. chocolate and ice cream) whereas the levels of parabens were associated with use of cosmetics and personal care products. PMID:25216151

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



Exposure to parabens at the concentration of maximal proliferative response increases migratory and invasive activity of human breast cancer cells in vitro.  


Alkyl esters of p-hydroxybenzoic acid (parabens) are widely used as preservatives in personal care products, foods and pharmaceuticals. Their oestrogenic activity, their measurement in human breast tissue and their ability to drive proliferation of oestrogen-responsive human breast cancer cells has opened a debate on their potential to influence breast cancer development. As proliferation is not the only hallmark of cancer cells, we have investigated the effects of exposure to parabens at concentrations of maximal proliferative response on migratory and invasive properties using three oestrogen-responsive human breast cancer cell lines (MCF-7, T-47-D, ZR-75-1). Cells were maintained short-term (1?week) or long-term (20?±?2?weeks) in phenol-red-free medium containing 5% charcoal-stripped serum with no addition, 10(-8) ?M 17?-oestradiol, 1-5?×?10(-4) ?M methylparaben, 10(-5) ?M n-propylparaben or 10(-5) ?M n-butylparaben. Long-term exposure (20?±?2?weeks) of MCF-7 cells to methylparaben, n-propylparaben or n-butylparaben increased migration as measured using a scratch assay, time-lapse microscopy and xCELLigence technology: invasive properties were found to increase in matrix degradation assays and migration through matrigel on xCELLigence. Western immunoblotting showed an associated downregulation of E-cadherin and ?-catenin in the long-term paraben-exposed cells which could be consistent with a mechanism involving epithelial to mesenchymal transition. Increased migratory activity was demonstrated also in long-term paraben-exposed T-47-D and ZR-75-1 cells using a scratch assay and time-lapse microscopy. This is the first report that in vitro, parabens can influence not only proliferation but also migratory and invasive properties of human breast cancer cells. PMID:24652746

Khanna, Sugandha; Dash, Philip R; Darbre, Philippa D



Spalling and sorption of tubing for peristaltic pumps.  


Available tubing for peristaltic pumps tend to shed particulates into the solution due to their poor abrasion characteristics. Most commonly used flexible tubing is silicone rubber or polyvinyl chloride (Tygon) tubing. Two newly available tubing are manufactured from a composite of expanded polytetrafluoroethylene (Teflon PTFE) with platinum-cured silicone rubber (Sta-Pure) and a tubing composite of PTFE with fluoroelastomer (Chem-Sure). These are claimed to resist spalling and deliver constant volume when used in peristaltic pumps. The four tubing were compared for spallation. They were also compared for sorption of methylparaben, propylparaben, and benzyl alcohol over a 72 hr study. Spallation studies indicate that Tygon and silicone tubing are prone to damage and shedding of particulates due to abrasion during use in peristaltic pumps while the Chem-Sure and Sta-Pure tubing are resistant to abrasion and spalling and show negligible shedding of particulates over 72 hr use in the peristaltic pump. Chem-Sure shows no spalling after 48 hr. Decrease in volume delivered is expected using Tygon and silicone tubing only. Chem-Sure tubing did not show any preservative losses. Tygon sorbed all preservatives tested to the greatest extent, followed by Silastic and Sta-Pure tubing, in decreasing order of sorption. Propylparaben was sorbed to the greatest extent. The tubing used appear to approach saturation in 24-48 hr. Chem-Sure and Sta-Pure tubing are ideal for use in peristaltic pumps or for general use for any demanding pharmaceutical applications. PMID:12229263

Bahal, Surendra M; Romansky, Jamie M



Hydrolysis of a series of parabens by skin microsomes and cytosol from human and minipigs and in whole skin in short-term culture  

SciTech Connect

Parabens are esters of 4-hydroxybenzoic acid and used as anti-microbial agents in a wide variety of toiletries, cosmetics and pharmaceuticals. It is of interest to understand the dermal absorption and hydrolysis of parabens, and to evaluate their disposition after dermal exposure and their potential to illicit localised toxicity. The use of minipig as a surrogate model for human dermal metabolism and toxicity studies, justifies the comparison of paraben metabolism in human and minipig skin. Parabens are hydrolysed by carboxylesterases to 4-hydroxybenzoic acid. The effects of the carboxylesterase inhibitors paraoxon and bis-nitrophenylphosphate provided evidence of the involvement of dermal carboxylesterases in paraben hydrolysis. Loperamide, a specific inhibitor of human carboxylesterase-2 inhibited butyl- and benzylparaben hydrolysis in human skin but not methylparaben or ethylparaben. These results show that butyl- and benzylparaben are more selective substrates for human carboxylesterase-2 in skin than the other parabens examined. Parabens applied to the surface of human or minipig skin were absorbed to a similar amount and metabolised to 4-hydroxybenzoic acid during dermal absorption. These results demonstrate that the minipig is a suitable model for man for assessing dermal absorption and hydrolysis of parabens, although the carboxylesterase profile in skin differs between human and minipig.

Jewell, Christopher [Toxicology Unit, School of Clinical and Laboratory Sciences, Devonshire Building, Newcastle University, Newcastle upon Tyne, NE2 4EA (United Kingdom); Prusakiewicz, Jeffery J.; Ackermann, Chrisita; Payne, N. Ann; Fate, Gwendolyn; Voorman, Richard [Pfizer Inc., Ann Arbor, MI (United States); Williams, Faith M. [Toxicology Unit, School of Clinical and Laboratory Sciences, Devonshire Building, Newcastle University, Newcastle upon Tyne, NE2 4EA (United Kingdom)], E-mail:



Simultaneous, stability indicating, HPLC-DAD determination of guaifenesin and methyl and propyl-parabens in cough syrup  

Microsoft Academic Search

A stability indicating high performance liquid chromatography procedure has been developed for the simultaneous determination of guaifenesin (GUA), methyl p-hydroxybenzoate (MHB) and propyl p-hydroxybenzoate (PHB) in a commercial cough syrup dosage form. The method was specific and stability indicating as chromatographic conditions were selected to provide adequate separation of GUA, MHB and PHB from the putative degradation products guaiacol (GUAI)

Giorgio Grosa; Erika Del Grosso; Roberta Russo; Gianna Allegrone



Occurrence of acidic pharmaceuticals and personal care products in Turia River Basin: from waste to drinking water.  


The occurrence of 21 acidic pharmaceuticals, including illicit drugs, and personal care products (PPCPs) in waste, surface and drinking water and in sediments of the Turia River Basin (Valencia, Spain) was studied. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the determination of these PPCPs with electrospray (ESI) in negative ionization (NI) mode. Ammonium fluoride in the mobile phase improved ionization efficiency by an average increase in peak area of 5 compared to ammonium formate or formic acid. All studied compounds were detected and their concentration was waste water>surface water>drinking water. PPCPs were in waste water treatment plants (WWTPs) influents up to 7.26?gL(-1), dominated by ibuprofen, naproxen and 11-nor-9-carboxy-?9-tetrahydrocannabinol (THCOOH). WWTPs were highly effective in removing most of them, with an average removal rate of >90%. PPCPs were still detected in effluents in the 6.72-940ngL(-1) range, with the THCOOH, triclocarban, gemfibrozil and diclofenac as most prevalent. Similarly, diclofenac, gemfibrozil, ibuprofen, naproxen and propylparaben were detected quite frequently from the low ngL(-1) range to 7?gL(-1) in the surface waters of Turia River. Ibuprofen, methylparaben, salicylic acid and tetrahydrocannabinol (THC) were at concentrations up to 0.85ngg(-1) d.w. in sediments. The discharge of WWTP as well as of non-treated waters to this river is a likely explanation for the significant amount of PPCPs detected in surface waters and sediments. Mineral and tap waters also presented significant amounts (approx. 100ngL(-1)) of ibuprofen, naproxen, propylparaben and butylparaben. The occurrence at trace levels of several PPCPs in drinking water raises concerns about possible implications for human health. PMID:24686145

Carmona, Eric; Andreu, Vicente; Picó, Yolanda



New sorbent in the dispersive solid phase extraction step of quick, easy, cheap, effective, rugged, and safe for the extraction of organic contaminants in drinking water treatment sludge.  


Recent studies have shown a decrease in the concentration of pesticides, pharmaceuticals and personal care products (PCPs) in water after treatment. A possible explanation for this phenomenon is that these compounds may adhere to the sludge; however, investigation of these compounds in drinking water treatment sludge has been scarce. The sludge generated by drinking water treatment plants during flocculation and decantation steps should get some special attention not only because it has been classified as non-inert waste but also because it is a very complex matrix, consisting essentially of inorganic (sand, argil and silt) and organic (humic substances) compounds. In the first step of this study, three QuEChERS methods were used, and then compared, for the extraction of pesticides (atrazine, simazine, clomazone and tebuconazole), pharmaceuticals (amitriptyline, caffeine, diclofenac and ibuprofen) and PCPs (methylparaben, propylparaben, triclocarban and bisphenol A) from drinking water treatment sludge. Afterwards, the study of different sorbents in the dispersive solid phase extraction (d-SPE) step was evaluated. Finally, a new QuEChERS method employing chitin, obtained from shrimp shell waste, was performed in the d-SPE step. After having been optimized, the method showed limits of quantification (LOQ) between 1 and 50 ?g kg(-1) and the analytical curves showed r values higher than 0.98, when liquid chromatography tandem mass spectrometry was employed. Recoveries ranged between 50 and 120% with RSD?15%. The matrix effect was evaluated and compensated with matrix-matched calibration. The method was applied to drinking water treatment sludge samples and methylparaben and tebuconazole were found in concentration

Cerqueira, Maristela B R; Caldas, Sergiane S; Primel, Ednei G



Preventing sexual transmission of HIV: anti-HIV bioregulatory and homeostatic components of commercial sexual lubricants.  


Certain safe over-the-counter (OTC) sexual lubricants such as Astroglide, KY Liquid, Replens, Vagisil, ViAmor, and Wet Stuff inhibit both cell-free HIV and the production of HIV by infected leukocytes in vitro even in the presence of seminal fluid. To identify which components of the lubricants were active against HIV, we tested five components (glycerin, methylparaben, propylparaben, polyquaternium-32, and propylene glycol). The paraben preservatives and propylene glycol in the lubricants did not inhibit HIV, while the common natural homeostatic metabolite, glycerin, and the thickener polyquaternium-32 did strongly inactivate infectious HIV and HIV-infected leukocytes. Activity against HIV and HIV-infected cells by glycerin was stable through 24 hours at 37 degrees C. Glycerin and polyquaternium-32 were active at minimum concentrations of approximately 2% and 0.01%, respectively--well within the highest FDA safety guidelines. Both active components disrupted infected leukocytes within 5 minutes which resulted in inhibition of infectious HIV production by infected leukocytes of greater than 25 to 100-fold. These components do not disrupt vaginal epithelial cells in vivo. These components also rapidly inactivate cell-free HIV by 10- to 30-fold. Thus, we may conclude that the active components of the OTC lubricants are glycerin and polyquaternium-32. Using these components, OTC sexual lubricants could be reformulated to optimize their anti-HIV activity. Furthermore, clinical trials of these lubricants and components seem to be indicated because of their FDA safety level, wide availability, and low cost. PMID:15786693

Nguyen, D; Lee, H; Poast, J; Cloyd, M W; Baron, S



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

PubMed Central

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

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



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


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

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



Occurrence, fate and behavior of parabens in aquatic environments: a review.  


Parabens are esters of para-hydroxybenzoic acid, with an alkyl (methyl, ethyl, propyl, butyl or heptyl) or benzyl group. They are mainly used as preservatives in foodstuffs, cosmetics and pharmaceutical drugs. Parabens may act as weak endocrine disrupter chemicals, but controversy still surrounds the health effects of these compounds. Despite being used since the mid-1920s, it was only in 1996 that the first analytical results of their occurrence in water were published. Considered as emerging contaminants, it is useful to review the knowledge acquired over the last decade regarding their occurrence, fate and behavior in aquatic environments. Despite treatments that eliminate them relatively well from wastewater, parabens are always present at low concentration levels in effluents of wastewater treatment plants. Although they are biodegradable, they are ubiquitous in surface water and sediments, due to consumption of paraben-based products and continuous introduction into the environment. Methylparaben and propylparaben predominate, reflecting the composition of paraben mixtures in common consumer products. Being compounds containing phenolic hydroxyl groups, parabens can react readily with free chlorine, yielding halogenated by-products. Chlorinated parabens have been detected in wastewater, swimming pools and rivers, but not yet in drinking water. These chlorinated by-products are more stable and persistent than the parent species and further studies are needed to improve knowledge regarding their toxicity. PMID:25462712

Haman, Camille; Dauchy, Xavier; Rosin, Christophe; Munoz, Jean-François



A Rapid, Stability Indicating RP-UPLC Method for Simultaneous Determination of Ambroxol Hydrochloride, Cetirizine Hydrochloride and Antimicrobial Preservatives in Liquid Pharmaceutical Formulation  

PubMed Central

A stability indicating reversed phase ultra performance liquid chromatography (RP-UPLC) method was developed for simultaneous determination of ambroxol hydrochloride (AMB), cetirizine hydrochloride (CTZ), methylparaben (MP) and propylparaben (PP) in liquid pharmaceutical formulation. The desired chromatographic separation was achieved on an Agilent Eclipse plus C18, 1.8 ?m (50 × 2.1 mm) column using gradient elution at 237 nm detector wavelength. The optimized mobile phase consists of a mixture of 0.01 M phosphate buffer and 0.1 % triethylamine as a solvent-A and acetonitrile as a solvent-B. The developed method separates AMB, CTZ, MP and PP in presence of twelve known impurities/degradation products and one unknown degradation product within 3.5 min. Stability indicating capability was established by forced degradation experiments and seperation of known and unknown degradation products. The lower limit of quantification was established for AMB, CTZ, MP and PP. The developed RP-UPLC method was validated according to the International Conference on Harmonization (ICH) guidelines. This validated method is applied for simultaneous estimation of AMB, CTZ, MP and PP in commercially available syrup samples. Further, the method can be extended for estimation of AMB, CTZ, MP, PP and levo-cetirizine (LCTZ) in various commercially available dosage forms. PMID:21886901

Trivedi, Rakshit Kanubhai; Patel, Mukesh C.; Jadhav, Sushant B.



New validated liquid chromatographic and chemometrics-assisted UV spectroscopic methods for the determination of two multicomponent cough mixtures in syrup.  


Multivariate spectrophotometric calibration and liquid chromatographic (LC) methods were applied to the determination of 2 multicomponent mixtures containing diprophylline, guaiphenesin, methylparaben, and propylparaben (Mixture 1), or clobutinol, orciprenaline, saccharin sodium, and sodium benzoate (Mixture 2). For the multivariate spectrophotometric calibration methods, principal component regression (PCR) and partial least-squares regression (PLS-1), a calibration set of the mixtures consisting of the components of each mixture was prepared in 0.1 M HCl. Analytical figures of merit such as sensitivity, selectivity, limit of quantitation, and limit of detection were determined for both PLS-1 and PCR. The LC separation was achieved on a reversed-phase C18 analytical column by using isocratic elution with 20 mM potassium dihydrogen phosphate, pH 3.3-acetonitrile (55 + 45, v/v) as the mobile phase and UV detection at 260 and 220 nm for Mixture 1 and Mixture 2, respectively. The proposed methods were validated and successfully applied to the analysis of pharmaceutical formulations and laboratory-prepared mixtures containing the 2 multicomponent combinations. PMID:18376584

Hadad, Ghada M; El-Gindy, Alaa; Mahmoud, Waleed M M



Antithyroid effect of a food or drug preservative: 4-hydroxybenzoic acid methyl ester  

Microsoft Academic Search

Summary 4-hydroxybenzoic acid methyl ester (methylparaben) inhibits organification of iodide by isolated hog thyroid cells. The concentration which produces a 50% inhibition was about 2.0×10?4M. A similar inhibition was observed in nonstimulated and TSH- or dibutyryl cyclic AMP-stimulated cells. Neither iodide uptake nor cyclic AMP generation were altered by methylparaben.

B. Rousset



76 FR 16290 - Tolerances for Residues of New Animal Drugs in Food; 2-Acetylamino-5-Nitrothiazole; Buquinolate...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Progesterone; Propylparaben; and Salicylic Acid AGENCY: Food and Drug Administration...40 FR 13802 at 13956). 12. Salicylic acid (Sec. 556.590). In 2005...voluntary withdrawal of approval of salicylic acid for use in cattle under NADA...



Mechanism of p-Hydroxybenzoate Ester-induced Mitochondrial Dysfunction and Cytotoxicity in Isolated Rat Hepatocytes  

Microsoft Academic Search

The relationship between the metabolism and the cytotoxic effects of the alkyl esters of p-hydroxybenzoic acid (parabens) has been studied in freshly isolated rat hepatocytes. Incubation of hepatocytes with propyl-paraben (0.5 to 2.0 mM) elicited a concentration- and time-dependent cell death that was enhanced when enzymatic hydrolysis of propyl-paraben to p-hydroxybenzoic acid was inhibited by a carboxylesterase inhibitor, diazinon. The

Yoshio Nakagawa; Peter Moldéus



Non-traditional plasticization of polymeric films.  


The objective of this study was to investigate the influence of methylparaben, ibuprofen, chlorpheniramine maleate and theophylline on the thermal and mechanical properties of polymeric films of Eudragit RS 30 D. The effects of methylparaben and ibuprofen in the film coating on the rate of drug release from Eudragit RS 30 D coated beads were also studied. The physical and mechanical properties of the cast films and coated beads were investigated using thermal analysis, tensile testing, X-ray diffraction analysis and dissolution testing. The results demonstrated that the glass transition temperature of the Eudragit RS 30 D decreased with increasing levels of methylparaben, ibuprofen and chlorpheniramine maleate in the film. Theophylline exerted no influence on the thermal properties of the polymer. The higher levels of the ibuprofen and methylparaben incorporated into the film resulted in a decrease in the tensile strength of the film. The decrease in Young's modulus of Eudragit RS 30 D coated beads was attributed to an increase in the flexibility of the polymeric films when the level of methylparaben or ibuprofen in the polymeric dispersion was increased. The dissolution data demonstrated that the rate of release of the ibuprofen from coated beads was decreased by increasing the amount of ibuprofen and methylparaben in the polymeric film coating. PMID:10205601

Wu, C; McGinity, J W



Antifungal agents against Aspergillus niger for rearing rice leaffolder larvae (Lepidoptera: Pyralidae) on artificial diet.  


Mold contamination is an important issue in insect mass rearing. Frequently used antifungal agents such as sorbic acid and methylparaben have negative impact on many lepidopteran larvae, which might be one of the reasons for the difficulty in rearing rice leaffolder, Cnaphalocrocis medinalis (Güenée). In this study, 19 antifungal agents, including 7 food preservatives, 6 antifungal drugs, and 6 agricultural fungicides, were screened for their inhibitory activities on Aspergillus niger in diets. The results demonstrated that most of the tested chemicals are unsuitable as mold inhibitors in the diets of the rice leaffolder, and the rice leaffolder neonate is sensitive to sorbic acid and methylparaben. These two mold inhibitors at commonly used concentrations were shown to impact the survival of rice leaffolder larvae fed on artificial diets. Among the tested mold inhibitors, natamycin was the safest for the rice leaffolder larvae. Much higher larva survival was observed for the larvae fed on diets containing natamycin as an antifungal agent (59 and 72% at 200 and 400 ppm, respectively). Two agricultural fungicides, tebuconazole and azoxystrobin, are also potent as mold inhibitors when used in insect diets. The mixed use of natamycin and sorbic acid, or methylparaben, and the mixed use of sorbic acid and azoxystrobin resulted in significantly higher larva survival than sorbic acid + methylparaben. Natamycin + azoxystrobin and sorbic acid + tebuconazole resulted in larva survival similar to that of sorbic acid + methylparaben. The ternary combination of natamycin, sorbic acid, and methylparaben was the best combination for the rearing of rice leaffolder. PMID:25026669

Su, Jianya; Wang, Ye-Cheng; Zhang, Shu-Kun; Ren, Xiu-Bei



Assessment of combined antiandrogenic effects of binary parabens mixtures in a yeast-based reporter assay.  


To date, toxicological studies of endocrine disrupting chemicals (EDCs) have typically focused on single chemical exposures and associated effects. However, exposure to EDCs mixtures in the environment is common. Antiandrogens represent a group of EDCs, which draw increasing attention due to their resultant demasculinization and sexual disruption of aquatic organisms. Although there are a number of in vivo and in vitro studies investigating the combined effects of antiandrogen mixtures, these studies are mainly on selected model compounds such as flutamide, procymidone, and vinclozolin. The aim of the present study is to investigate the combined antiandrogenic effects of parabens, which are widely used antiandrogens in industrial and domestic commodities. A yeast-based human androgen receptor (hAR) assay (YAS) was applied to assess the antiandrogenic activities of n-propylparaben (nPrP), iso-propylparaben (iPrP), methylparaben (MeP), and 4-n-pentylphenol (PeP), as well as the binary mixtures of nPrP with each of the other three antiandrogens. All of the four compounds could exhibit antiandrogenic activity via the hAR. A linear interaction model was applied to quantitatively analyze the interaction between nPrP and each of the other three antiandrogens. The isoboles method was modified to show the variation of combined effects as the concentrations of mixed antiandrogens were changed. Graphs were constructed to show isoeffective curves of three binary mixtures based on the fitted linear interaction model and to evaluate the interaction of the mixed antiandrogens (synergism or antagonism). The combined effect of equimolar combinations of the three mixtures was also considered with the nonlinear isoboles method. The main effect parameters and interaction effect parameters in the linear interaction models of the three mixtures were different from zero. The results showed that any two antiandrogens in their binary mixtures tended to exert equal antiandrogenic activity in the linear concentration ranges. The antiandrogenicity of the binary mixture and the concentration of nPrP were fitted to a sigmoidal model if the concentrations of the other antiandrogens (iPrP, MeP, and PeP) in the mixture were lower than the AR saturation concentrations. Some concave isoboles above the additivity line appeared in all the three mixtures. There were some synergistic effects of the binary mixture of nPrP and MeP at low concentrations in the linear concentration ranges. Interesting, when the antiandrogens concentrations approached the saturation, the interaction between chemicals were antagonistic for all the three mixtures tested. When the toxicity of the three mixtures was assessed using nonlinear isoboles, only antagonism was observed for equimolar combinations of nPrP and iPrP as the concentrations were increased from the no-observed-effect-concentration (NOEC) to effective concentration of 80%. In addition, the interactions were changed from synergistic to antagonistic as effective concentrations were increased in the equimolar combinations of nPrP and MeP, as well as nPrP and PeP. The combined effects of three binary antiandrogens mixtures in the linear ranges were successfully evaluated by curve fitting and isoboles. The combined effects of specific binary mixtures varied depending on the concentrations of the chemicals in the mixtures. At low concentrations in the linear concentration ranges, there was synergistic interaction existing in the binary mixture of nPrP and MeP. The interaction tended to be antagonistic as the antiandrogens approached saturation concentrations in mixtures of nPrP with each of the other three antiandrogens. The synergistic interaction was also found in the equimolar combinations of nPrP and MeP, as well as nPrP and PeP, at low concentrations with another method of nonlinear isoboles. The mixture activities of binary antiandrogens had a tendency towards antagonism at high concentrations and synergism at low concentrations. PMID:24469767

Ma, Dehua; Chen, Lujun; Zhu, Xiaobiao; Li, Feifei; Liu, Cong; Liu, Rui



Anaphylactoid skin reactions after intravenous regional anaesthesia using 0.5% prilocaine with or without preservative--a double-blind study.  


Methylparaben, the preservative of various local anaesthetic solutions, is a potential allergen. In a double-blind study, 0.5% prilocaine with (Citanest, n = 100) or without (n = 100) methylparaben were compared for the occurrence of skin reactions after intravenous regional anaesthesia of the arm in surgical patients. Skin reactions were registered after the deflation of the tourniquet cuff, and intradermal tests were performed with 0.5% prilocaine, 0.1% methylparaben and saline in all patients. Seventeen patients in the Citanest group and four patients in the methylparaben-free prilocaine group developed erythematous skin reactions in the exposed arm after deflation of the tourniquet cuff (P < 0.05, between the groups). The skin symptoms disappeared within an hour and were always restricted to the region which had been anaesthetised. None of the affected patients had positive intradermal tests. The observed skin reactions are probably non-IgE-mediated anaphylactoid reactions in which the presence of methylparaben in the local anaesthetic solution plays a major role. PMID:7484034

Kajimoto, Y; Rosenberg, M E; Kyttä, J; Randell, T; Tuominen, M; Reunala, T; Rosenberg, P H



Photodegradation of parabens by Fe(III)-citrate complexes at circumneutral pH: matrix effect and reaction mechanism.  


The photodegradation of four parabens including methyl-, ethyl-, propyl-, and butyl-paraben in the presence of Fe(III)-citrate complexes under simulated sunlight was investigated. The degradation of parabens increased with decreasing pH within the range of 5.0-8.0 at the Fe(III)-to-citrate ratio of 10:150 (?M). The addition of low-molecular-weight carboxylic acids showed different effects on the photodegradation of methylparaben. The low-photoreactive carboxylic acids inhibited the photodegradation of methylparaben in the order of formic acid>succinic acid>acetic acid>malonic acid. In contrast, oxalic acid enhanced the photodegradation and exhibited appreciable synergistic effect with Fe(III)-citrate at concentration higher than 500 ?M. Up to 99.0% of substrate was degraded after 30 min at pH6.0 in the Fe(III)-citrate-oxalate system. The various fractions of fulvic acid inhibited the photodegradation of methylparaben. The inhibition increased with increasing nominal molecular weight of fractionated fulvic acid. Moreover, the photodegradation of methylparaben was inhibited in natural waters in the order of Liangzi Lakemethylparaben were identified by GC-MS analyses and the degradation pathway was proposed. PMID:24291138

Feng, Xiaonan; Chen, Yong; Fang, Yuan; Wang, Xiaoyue; Wang, Zongping; Tao, Tao; Zuo, Yuegang



Essential oils and herbal extracts as antimicrobial agents in cosmetic emulsion.  


The cosmetic industry adapts to the needs of consumers seeking to limit the use of preservatives and develop of preservative-free or self-preserving cosmetics, where preservatives are replaced by raw materials of plant origin. The aim of study was a comparison of the antimicrobial activity of extracts (Matricaria chamomilla, Aloe vera, Calendula officinalis) and essential oils (Lavandulla officinallis, Melaleuca alternifolia, Cinnamomum zeylanicum) with methylparaben. Extracts (2.5 %), essential oils (2.5 %) and methylparaben (0.4 %) were tested against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, Candida albicans ATCC 14053. Essentials oils showed higher inhibitory activity against tested microorganism strain than extracts and methylparaben. Depending on tested microorganism strain, all tested extracts and essential oils show antimicrobial activity 0.8-1.7 and 1-3.5 times stronger than methylparaben, respectively. This shows that tested extracts and essential oils could replace use of methylparaben, at the same time giving a guarantee of microbiological purity of the cosmetic under its use and storage. PMID:24426114

Herman, Anna; Herman, Andrzej Przemys?aw; Domagalska, Beata Wanda; M?ynarczyk, Andrzej



Simultaneous Determination of Tranexamic Acid and Losartan Potassium in Dosage Formulations and Human Serum by RP-LC  

Microsoft Academic Search

Rapid liquid chromatographic procedure for analytical quality control of pharmaceutical preparations and human serum containing\\u000a drugs, tranexamic acid together with losartan potassium are proposed, using acetonitrile: water (50:50), adjusting pH to 2.6\\u000a with phosphoric acid as a mobile phase, UV detection at 205 nm and propylparaben sodium was used as internal standard. The\\u000a results obtained showed a good agreement with the

M. Saeed Arayne; Najma Sultana; Faiza Qureshi; Farhan Ahmed Siddiqui; Agha Zeeshan Mirza; Saima Sher Bahadur; Muhammad Hashim Zuberi



Determination of preservatives in cosmetics, cleaning agents and pharmaceuticals using fast liquid chromatography.  


This paper reports the development of a method for simultaneously determining five preservatives in cosmetics, cleaning agents and pharmaceuticals by fast liquid chromatography. Methylisothiazolinone, methylchloroisothiazolinone, benzyl alcohol, sodium benzoate and methylparaben were separated on a Chromolith Fast Gradient reversed-phase 18e column using gradient elution with acetonitrile and a 0.1% aqueous solution of formic acid, with a run time of 3 min. The preparation of solid and liquid samples included ultrasonic extraction with methanol with recoveries ranging from 69 to 119%. The developed method was used to analyze samples of cosmetics (66 samples), cleaning agents (five samples) and pharmaceutical industry products (17 samples). PMID:23324734

Baranowska, Irena; Wojciechowska, Iwona; Solarz, Natalia; Krutysza, Ewa



Drug-excipient compatibility studies in binary mixtures of avobenzone.  


During preformulation studies of cosmetic/pharmaceutical products, thermal analysis techniques are very useful to detect physical or chemical incompatibilities between the active and the excipients of interest that might interfere with safety and/or efficacy of the final product. Differential scanning calorimetry (DSC) was used as a screening technique for assessing the compatibility of avobenzone with some currently used cosmetic excipients. In the first phase of the study, DSC was used as a tool to detect any interaction. Based on the DSC results alone, cetearyl alcohol, isopropyl myristate, propylparaben, diethylhexyl syringylidene malonate, caprylic capric triglyceride, butylated hydroxytoluene (BHT), glycerin, cetearyl alcohol/ceteareth 20, cetearyl alcohol/sodium lauryl sulfate/sodium cetearyl sulfate, and paraffinum liquidum exhibit interaction with avobenzone. Stressed binary mixtures (stored at 50°C for 15 days) of avobenzone and excipients were evaluated by high-performance liquid chromatography. Binary mixtures were further investigated by infrared (IR) spectroscopy. Based on DSC, isothermal stress testing, and fourier transform infrared results; avobenzone is incompatible with caprylic capric triglyceride, propylparaben, and BHT. PMID:24139431

Ceresole, Rita; Han, Yong K; Rosasco, Maria A; Orelli, Liliana R; Segall, Adriana



Toxicological evaluation of three contaminants of emerging concern by use of the Allium cepa test.  


Di(2-ethylhexyl)phthalate, triclosan and propylparaben are contaminants of emerging concern that have been subjected to extensive toxicological studies, but for which limited information is currently available concerning adverse effects on terrestrial plant systems. The Allium cepa test, which is considered one of the most efficient approaches to assess toxic effects of environmental chemicals, was selected to evaluate the potential risks of these ubiquitous pollutants. Our data demonstrate that all three compounds studied may in some way be considered toxic, but different effects were noted depending on the chemical and the end point analysed. Results derived from the analysis of macroscopic parameters used in testing for general toxicity, revealed that while di(2-ethylhexyl)phthalate had no apparent effects, the other two chemicals inhibited A. cepa root growth in a dose-dependent manner. On the other hand, although all three compounds caused alterations in the mitotic index of root-tip cells, propylparaben was the only one that did not show evidence of genotoxicity in assays for chromosome aberrations and micronuclei. The results of the present study clearly indicate that sensitive plant bioassays are useful and complementary tools to determine environmental impact of contaminants of emerging concern. PMID:22249112

Herrero, O; Pérez Martín, J M; Fernández Freire, P; Carvajal López, L; Peropadre, A; Hazen, M J



Quantitative determination of infinite inhibition concentrations of antimicrobial agents.  


We developed a method to determine the infinite inhibition concentrations (IICs) of antimicrobial agents. This method was based on finding the relative effectiveness of an inhibitor at various concentrations. Benzoic acid and parabens were tested on Saccharomyces bayanus, Hansenula sp., and Pseudomonas fluorescens. The relative effectiveness values of these compounds were established. A plot of the inhibitor concentration versus the reciprocal of relative effectiveness was linear. The chi-axis intercept was the concentration of the inhibitor which gave infinite microbial inhibition. For S. bayanus the IICs were 330, 930, 480, and 220 ppm (330, 930, 480, and 220 ml/liter) for benzoic acid and methyl-, ethyl-, and propylparabens, respectively. For Hansenula sp. the IIC was 180 ppm for benzoic acid. For P. fluorescens the IICs were 1,310, 960, and 670 ppm for methyl-, ethyl-, and propylparabens, respectively. Our results indicated that the IIC is affected by the growth medium. The advantages and applications of this method are discussed. PMID:3083773

Marwan, A G; Nagel, C W



Influence of plasticizer type and level on the properties of Eudragit S100 matrix pellets prepared by hot-melt extrusion.  


Matrix-type pellets with controlled-release properties may be prepared by hot-melt extrusion applying a single-step, continuous process. However, the manufacture of gastric-resistant pellets is challenging due to the high glass transition temperature of most enteric polymers and an unacceptably high, diffusion-controlled drug release from the matrix during the acidic phase. The objective was to investigate the influence of three plasticizers (triethyl citrate, methylparaben and polyethylene glycol 8000) at two levels (10% or 20%) on the properties of hot-melt extruded Eudragit S100 matrix pellets. Extrusion experiments showed that all plasticizers produced similar reductions in polymer melt viscosity. Differential scanning calorimetry and powder X-ray diffraction demonstrated that the solid state plasticizers were present in the amorphous state. The drug release in acidic medium was influenced by the aqueous solubility of the plasticizer. Less than 10% drug was released after 2 h at pH 1.2 when triethyl citrate or methylparaben was used, independent of the plasticizer level. Drug release at pH 7.4 resulted from polymer dissolution and was not influenced by low levels of plasticizer, but increased significantly at the 20% level. Mechanical testing by diametral compression demonstrated the high tensile strength of the hot-melt extruded pellets that decreased when plasticizers were present. PMID:20575612

Schilling, Sandra U; Lirola, Hélène L; Shah, Navnit H; Waseem Malick, A; McGinity, James W



Gas chromatography/mass spectrometric assay of endogenous cellular lipid peroxidation products: quantitative analysis of 9- and 10-hydroxystearic acids.  


A sensitive, specific, accurate and reproducible gas chromatography/mass spectrometry method was developed for the assay of 9- and 10-hydroxystearic acids in samples obtained as cell extracts. The preparation of the samples required specific procedures to allow the analysis of both the free and the conjugated hydroxy acids as the corresponding methyl esters. The quantification used propyl-paraben as the internal standard and monitoring of a specific fragment of each isomeric hydroxy acid methyl ester, and allowed quantification of the conjugate and the free fractions of both 9- and 10-hydroxystearic acids. This method is suitable for identification and quantification (LOQ 1.8 and 4.4 ng, respectively) of these important metabolites of lipid peroxidation. In particular the development of an assay for the free 9-hydroxystearic acid methyl ester makes the method a reliable analytical tool for investigations of the role of this metabolite in the mechanisms of tumour cell proliferation. PMID:11948817

Bertucci, C; Hudaib, M; Boga, C; Calonghi, N; Cappadone, C; Masotti, L



Personal care product preservatives: Risk assessment and mixture toxicities with an industrial wastewater.  


The aquatic toxicity of eight preservatives frequently used in personal care products (PCPs) (iodopropynyl butylcarbamate, bronopol, diazolidinyl urea, benzalkonium chloride, zinc pyrithione, propylparaben, triclosan and a mixture of methylchloroisothiazolinone and methylisothiazolinone) was assessed by means of two different approaches: a battery of bioassays composed of single species tests of bacteria (Vibrio fischeri and Pseudomonas putida) and protozoa (Tetrahymena thermophila), and a whole biological community resazurin-based assay using activated sludge. The tested preservatives showed considerable toxicity in the studied bioassays, but with a marked difference in potency. In fact, all biocides except propylparaben and diazolidinyl urea had EC50 values lower than 1 mg L(-1) in at least one assay. Risk quotients for zinc pyrithione, benzalkonium chloride, iodopropynyl butylcarbamate and triclosan as well as the mixture of the studied preservatives exceeded 1, indicating a potential risk for the process performance and efficiency of municipal sewage treatment plants (STPs). These four single biocides explained more than 95% of the preservative mixture risk in all bioassays. Each individual preservative was also tested in combination with an industrial wastewater (IWW) from a cosmetics manufacturing facility. The toxicity assessment was performed on binary mixtures (preservative + IWW) and carried out using the median-effect principle, which is a special case of the concept of Concentration Addition (CA). Almost 70% of all experiments resulted in EC50 values within a factor of 2 of the values predicted by the median-effect principle (CI values between 0.5 and 2). The rest of the mixtures whose toxicity was mispredicted by CA were assessed with the alternative concept of Independent Action (IA), which showed higher predictive power for the biological community assay. Therefore, the concept used to accurately predict the toxicity of mixtures of a preservative with a complex industrial wastewater depends on degree of biological complexity. PMID:25585550

Carbajo, Jose B; Perdigón-Melón, Jose A; Petre, Alice L; Rosal, Roberto; Letón, Pedro; García-Calvo, Eloy



Analytical control of a pharmaceutical formulation of sodium picosulfate by capillary zone electrophoresis.  


A new procedure for the analytical control of a pharmaceutical formulation by capillary zone electrophoresis (CZE) is proposed. It allows the simultaneous determination of the major compounds in the formulation: active compound (sodium picosulfate) and preservative (methylparaben), and the degradation products of the preservative, which slowly degrades by hydrolysis or by transesterification with sorbitol (sweetener in excess in the formulation) yielding p-hydroxybenzoic acid and sorbitolparaben, respectively. UV-Vis detection in the absorption maxima of the analytes and 20 mM borate solution at pH 10 as background electrolyte are used. Results are compared with those provided by the HPLC procedure. The method has also been validated using the HPLC procedure as the reference method, evaluating selectivity, accuracy, linearity and precision. The CZE procedure developed is sufficiently accurate and the precision achieved is about 1% for major and 3% for minor compounds. PMID:11232853

Blanco, M; Coello, J; Iturriaga, H; Maspoch, S; Romero, M A



Biocides in the Yangtze River of China: Spatiotemporal distribution, mass load and risk assessment.  


Nineteen biocides were investigated in the Yangtze River to understand their spatiotemporal distribution, mass loads and ecological risks. Fourteen biocides were detected, with the highest concentrations up to 166 ng/L for DEET in surface water, and 54.3 ng/g dry weight (dw) for triclocarban in sediment. The dominant biocides were DEET and methylparaben, with their detection frequencies of 100% in both phases. An estimate of 152 t/y of 14 biocides was carried by the Yangtze River to the East China Sea. The distribution of biocides in the aquatic environments was significantly correlated to Gross Domestic Product (GDP), total phosphorus (TP) and total nitrogen (TN), suggesting dominant input sources from domestic wastewater of the cities along the river. Risk assessment showed high ecological risks posed by carbendazim in both phases and by triclosan in sediment. Therefore, proper measures should be taken to reduce the input of biocides into the river systems. PMID:25697474

Liu, Wang-Rong; Zhao, Jian-Liang; Liu, You-Sheng; Chen, Zhi-Feng; Yang, Yuan-Yuan; Zhang, Qian-Qian; Ying, Guang-Guo



Luminescent homo- and hetero-metallic hybrid molecular materials constructed by covalent grafting  

NASA Astrophysics Data System (ADS)

In this paper, 3-(triethoxysilyl)-propyl isocyanate (abbreviated as TESPIC) was modified by ethylparaben (EPB) to produce corresponding organic-inorganic monomers (EPB-TESPIC) with two components equipped with covalent bonds, which not only can coordinate to RE ions (Tb3+ and Eu3+) but also act as a sol-gel precursor. Luminescent hybrid materials consisting of terbium-europium complex, covalently bonded to silica-based network, have been obtained in situ via a sol-gel approach. Proton nuclear magnetic resonance spectroscopy (1HNMR) and Fourier transform infrared spectroscopy (FT-IR) were applied to characterize the structure of EPB-TESPIC. UV-visible, phosphorescence, and luminescence spectra were obtained to characterize the photophysical properties of the obtained hybrid material. Through co-hydrolysis and polycondensation, Tb3+ and Eu3+ can be introduced into the same organic-inorganic hybrid monomer, forming Si-O backbones. The experimental results show that the strong luminescence of rare-earth ions substantiates the optimum energy match and effective intramolecular energy transfer between the triplet state energy of coordination complex and the emissive energy level of the rare-earth ions. The hybrid material systems are expected to have potential applications in photophysical sensors.

Wang, F. F.; Yan, B.



Acute toxicity of parabens and their chlorinated by-products with Daphnia magna and Vibrio fischeri bioassays.  


The acute toxicity of 21 parabens and their chlorinated derivatives was investigated by means of two toxicity bioassays: Daphnia magna immobilization test and the inhibition of bioluminescence of Vibrio fischeri. The median effective concentration (EC(50)) values of the tested parabens ranged from 2.2 to 62 mg l(-1) in the D. magna test and from 0.0038 to 5.9 mg l(-1) in the V. fischeri test at 15 min after exposure. The toxicity of dichlorinated methyl- and n-propylparaben, the most commonly used preservatives in cosmetics, toward D. magna was 3.9- and 2.8-fold that of their corresponding parent compounds. Toxicity toward D. magna showed a linear relationship with log P, indicating that toxicity increases with increasing hydrophobicity. On the other hand, the correlations of toxicity toward V. fischeri with hydrophobicity and with the degree of chlorination were poor. In addition, the results of the present study indicated that the V. fischeri test was more sensitive than the D. magna test for the determination of the acute toxicity of parabens. A complete assessment of the ecological and toxicological risks of parabens may require the examination of chlorinated parabens as well as the parent pollutants, as described in the present study. PMID:19089854

Terasaki, Masanori; Makino, Masakazu; Tatarazako, Norihisa



Electrochemical Sensing and Assessment of Parabens in Hydro-Alcoholic Solutions and Water Using a Boron-Doped Diamond Electrode  

PubMed Central

In this paper, the electrochemical behaviour of several parabens preservatives, i.e. esters of p-hydroxybenzoic acid, methyl-, ethyl- and propyl-4-hydroxybenzoates as methyl-, ethyl- and propyl-parabens (MB, EB, and PB), has been investigated at a commercial boron-doped diamond electrode (BDDE), especially in the anodic potential range, in both hydro-alcoholic and aqueous media. The cyclic voltammetric and chronoamperometric measurements yielded calibration plots with very good linearity (R2 between 0.990 and 0.998) and high sensitivity, useful for detection and analytical applications. The determination of the characteristics of individual compounds, of an “overall paraben index”, the assessment of the stability and the saturation solubility in water, and the amperometric sensing and determination in double distilled, tap and river water matrix of the relatively slightly soluble investigated parabens have been carried out using electrochemical alternative. Estimated water solubility was correlated with the octanol-water partition coefficient. Several ideas regarding stability and persistence of the presumptive eco-toxic investigated preservatives in the environment or water systems have been adjacently discussed.

Radovan, Ciprian; Cinghi??, Dan; Manea, Florica; Mincea, Manuela; Cofan, Codru?a; Ostafe, Vasile



Development and validation of an HPLC–UV method for the quantification of carbamazepine in rabbit plasma  

PubMed Central

An isocratic simple rapid assay has been developed and validated for the determination of carbamazepine (CBZ) in both solution form and rabbit plasma using propylparaben as an internal standard. The assay was performed using a ?-Bondapak C18 (150 mm × 4.6 mm i.d) with a mobile phase consisting of methanol and water (50:50), the flow rate was 1 ml/min and UV detection at 285 nm. The method was found to be specific for CBZ, no interfering peaks were observed with an overall analytical run time of 15 min. Accuracy reported as % recovery were found to be 98.37–100.45% and 97.53–103.58% for inter-day and intra-day accuracies, respectively. Inter-day precision (reproducibility) was found to be 0.53–2.75% RSD, while intra-day precision (repeatability) was found to be 1.06–3.7% RSD for the samples studied. The calibration curve was found to be linear with the equation y = 0.2847x + 0.0138, with a correlation coefficient of 0.9999 (R2) over a concentration range of 0.5–40 ?g/ml. The limit of quantitation was the lowest concentration. The method is simple and rapid and does not require any preliminary treatment of the sample. The method was fully validated. PMID:23960774

Mowafy, Hammam A.; Alanazi, Fars K.; El Maghraby, Gamal M.



A multiclass method for the analysis of endocrine disrupting chemicals in human urine samples. Sample treatment by dispersive liquid-liquid microextraction.  


The population is continuously exposed to endocrine disrupting chemicals (EDCs). This has influenced an increase in diseases and syndromes that are more frequent nowadays. Therefore, it is necessary to develop new analytical procedures to evaluate the exposure with the ultimate objective of establishing, in an accurate way, relationships between EDCs and harmful health effects. In the present work, a new method based on a sample treatment by dispersive liquid-liquid microextraction (DLLME) for the extraction of six parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl and butylparaben), six benzophenones (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8 and 4-hydroxybenzophenone) and two bisphenols (bisphenol A and bisphenol S) in human urine samples, followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis is proposed. An enzymatic treatment allows determining the total content of the target EDCs. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-(13)C6 and bisphenol A-d16 were used as surrogates. Found limits of quantification ranging from 0.2 to 0.5 ng mL(-1) and inter-day variability (evaluated as relative standard deviation) ranging from 2.0% to 14.9%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 94% to 105%. A good linearity, for concentrations up to 300 ng mL(-1) for parabens and 40 ng mL(-1) for benzophenones and bisphenols, respectively, was obtained. The method was satisfactorily applied for the determination of target compounds in human urine samples from 20 randomly selected individuals. PMID:25127586

Vela-Soria, F; Ballesteros, O; Zafra-Gómez, A; Ballesteros, L; Navalón, A



Simplified matrix solid phase dispersion procedure for the determination of parabens and benzophenone-ultraviolet filters in human placental tissue samples.  


In recent decades, the industrial development has resulted in the appearance of a large amount of new chemicals that are able to produce disorders in the human endocrine system. These substances, so-called endocrine disrupting chemicals (EDCs), include many families of compounds, such as parabens and benzophenone-UV filters. Taking into account the demonstrated biological activity of these compounds, it is necessary to develop new analytical procedures to assess the exposure in order to establish, in an accurate way, relationships between EDCs and harmful health effects in population. In the present work, a new method based on a simplified sample treatment by matrix solid phase dispersion (MSPD) followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is validated for the determination of four parabens (methyl-, ethyl-, propyl- and butylparaben) and six benzophenone-UV filters (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8 and 4-hydroxybenzophenone) in human placental tissue samples. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-13C6 and benzophenone-d10 were used as surrogates. The found limits of quantification ranged from 0.2 to 0.4 ng g(-1) and inter-day variability (evaluated as relative standard deviation) ranged from 5.4% to 12.8%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 96% to 104%. The method was satisfactorily applied for the determination of compounds in human placental tissue samples collected at the moment of delivery from 10 randomly selected women. PMID:25456585

Vela-Soria, F; Rodríguez, I; Ballesteros, O; Zafra-Gómez, A; Ballesteros, L; Cela, R; Navalón, A



Assessment of the sensitizing potency of preservatives with chance of skin contact by the loose-fit coculture-based sensitization assay (LCSA).  


Parabens, methylisothiazolinone (MI) and its derivative methylchloroisothiazolinone (MCI), are commonly used as preservatives in personal care products. They can cause hypersensitivity reactions of the human skin. We have tested a set of nine parabens, MI alone and in combination with MCI in the loose-fit coculture-based sensitization assay (LCSA). The coculture of primary human keratinocytes and allogenic dendritic cell-related cells (DC-rc) in this assay emulates the in vivo situation of the human skin. Sensitization potency of the test substances was assessed by flow cytometric analysis of the DC-rc maturation marker CD86. Determination of the concentration required to cause a half-maximal increase in CD86-expression (EC50sens) allowed a quantitative evaluation. The cytotoxicity of test substances as indicator for irritative potency was measured by 7-AAD (7-amino-actinomycin D) staining. Parabens exhibited weak (methyl-, ethyl-, propyl- and isopropylparaben) or strong (butyl-, isobutyl-, pentyl- and benzylparaben) effects, whereas phenylparaben was found to be a moderate sensitizer. Sensitization potencies of parabens correlated with side chain length. Due to a pronounced cytotoxicity, we could not estimate an EC50sens value for MI, whereas MI/MCI was classified as sensitizer and also showed cytotoxic effects. Parabens showed no (methyl- and ethylparaben) or weak irritative potencies (propyl-, isopropyl-, butyl-, isobutyl-, phenyl- and benzylparaben), only pentylparaben was rated to be irritative. Overall, we were able to demonstrate and compare the sensitizing potencies of parabens in this in vitro test. Furthermore, we showed an irritative potency for most of the preservatives. The data further support the usefulness of the LCSA for comparison of the sensitizing potencies of xenobiotics. PMID:25395006

Sonnenburg, Anna; Schreiner, Maximilian; Stahlmann, Ralf



Aggregate exposure approaches for parabens in personal care products: a case assessment for children between 0 and 3 years old  

PubMed Central

In the risk assessment of chemical substances, aggregation of exposure to a substance from different sources via different pathways is not common practice. Focusing the exposure assessment on a substance from a single source can lead to a significant underestimation of the risk. To gain more insight on how to perform an aggregate exposure assessment, we applied a deterministic (tier 1) and a person-oriented probabilistic approach (tier 2) for exposure to the four most common parabens through personal care products in children between 0 and 3 years old. Following a deterministic approach, a worst-case exposure estimate is calculated for methyl-, ethyl-, propyl- and butylparaben. As an illustration for risk assessment, Margins of Exposure (MoE) are calculated. These are 991 and 4966 for methyl- and ethylparaben, and 8 and 10 for propyl- and butylparaben, respectively. In tier 2, more detailed information on product use has been obtained from a small survey on product use of consumers. A probabilistic exposure assessment is performed to estimate the variability and uncertainty of exposure in a population. Results show that the internal exposure for each paraben is below the level determined in tier 1. However, for propyl- and butylparaben, the percentile of the population with an exposure probability above the assumed “safe” MoE of 100, is 13% and 7%, respectively. In conclusion, a tier 1 approach can be performed using simple equations and default point estimates, and serves as a starting point for exposure and risk assessment. If refinement is warranted, the more data demanding person-oriented probabilistic approach should be used. This probabilistic approach results in a more realistic exposure estimate, including the uncertainty, and allows determining the main drivers of exposure. Furthermore, it allows to estimate the percentage of the population for which the exposure is likely to be above a specific value. PMID:23801276

Gosens, Ilse; Delmaar, Christiaan J E; ter Burg, Wouter; de Heer, Cees; Schuur, A Gerlienke



Stability of an extemporaneously compounded levothyroxine sodium oral liquid.  


The stability of levothyroxine sodium in oral liquid dosage forms compounded from commercially available tablets was studied. Levothyroxine sodium oral liquids (25 micrograms/mL) were prepared from tablets and from powder with and without methylparaben preservative and transferred to amber, high-density polyethylene bottles. Five bottles of each tablet-based formulation were stored at 2-8 degrees C, 23-27 degrees C, and 38-42 degrees C, and five bottles of each powder-based formulation were stored at 38-42 degrees C. On days 3, 8, 14, 22, 31, 61, and 90, samples were taken from each bottle and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. There was significant degradation of levothyroxine sodium in all the formulations. However, the tablet-based formulation without preservative stored at 4 degrees C retained at least 90% of its initial concentration for eight days after compounding. Degradation occurred faster in the tablet-based formulation with preservative. None of the formulations retained > or = 90% initial potency by day 14. An extemporaneous oral liquid formulation of levothyroxine sodium 25 micrograms/mL compounded from crushed tablets was stable for eight days when stored in amber bottles at 4 degrees C. PMID:8734676

Boulton, D W; Fawcett, J P; Woods, D J



Thymol nanospheres as an effective anti-bacterial agent.  


Among thymol, carvacrol, citronellal, eugenol and terpinen-4-ol, thymol showed the highest antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Thymol was then encapsulated into water dispersible submicron sized ethylcellulose/methylcellulose spheres, attaining the relatively high thymol loading level of 43.53% (weight of encapsulated thymol to weight of the thymol-loaded spheres). When tested against the same three bacterial strains, the encapsulated thymol gave comparable minimal inhibition concentration (MIC) and minimal bactericidal concentration (MBC) values to the unencapsulated compound while mostly showing lower MIC and MBC values than the conventionally used preservative, methyl-p-hydroxybenzoate (methylparaben). The use of encapsulated thymol at 0.078, 0.156 and 0.625 mg ml(-1) (0.52, 1.04 and 4.16 mmol(-1), respectively) in cosmetic lotion formulations provided total suppression of viable E. coli, S. aureus and P. aeruginosa growth (all initially seeded at 10(5) cfu ml(-1)), respectively, over the three month test period, whereas unencapsulated thymol showed effective suppression for only 2-4 weeks. Effective bacterial suppression by encapsulated thymol was also observed when used in cream and aqueous gel cosmetic formulations. PMID:22698863

Wattanasatcha, Anna; Rengpipat, Sirirat; Wanichwecharungruang, Supason



Occurrence and ecological potential of pharmaceuticals and personal care products in groundwater and reservoirs in the vicinity of municipal landfills in China.  


Pharmaceutical and personal care products (PPCPs), including antibiotics, azole anti-fungals, non-steroid anti-inflammatory drugs, lipid regulators, parabens, antiseptics, and bisphenol A, were investigated in groundwater and reservoirs in the vicinity of two municipal landfills in the metropolis of Guangzhou, South China. Dehydroerythromycin, sulfamethoxazole, fluconazole, salicylic acid, methylparaben, triclosan, and bisphenol A were the mostly frequently detected PPCPs in the groundwater at low ng L(-1) levels. In the reservoirs, the PPCPs were widely detected at higher frequencies and concentrations, especially sulfamethoxazole, propiconazole, and ibuprofen, with maximal concentrations above 1 ?g L(-1). The PPCPs in the groundwater did not show significant seasonal differences or spatial trends. However, in the reservoirs, higher PPCP concentrations were observed in spring than in other seasons. The anti-bacterials in the groundwater posed medium risks to algae. In the reservoirs, the sulfonamides and macrolides posed low to high risks, while ibuprofen, salicylic acid, and clofibric acid presented low to medium risks to aquatic organisms. Overall, the results showed that the PPCP contaminants and subsequent ecological risks in the groundwater and surface water in the vicinity of the landfills may be of serious concern. More research is needed to better correlate the landfill leachates and PPCP contamination in the nearby aquatic environments. PMID:24908648

Peng, Xianzhi; Ou, Weihui; Wang, Chunwei; Wang, Zhifang; Huang, Qiuxin; Jin, Jiabin; Tan, Jianhua



Determination of micropollutants in combined sewer overflows and their removal in a wastewater treatment plant (Seoul, South Korea).  


The present study investigated the occurrence of 29 selected micropollutants such as endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) in surface waters and wastewaters in Seoul (South Korea) during both dry and wet weather conditions. The study area was selected based on the lack of available information regarding the suspected contamination of rivers/creeks by EDCs and PPCPs in the Seoul region and the presence of a wastewater treatment plant (WWTP), which serves approximately 4.1 million inhabitants and has a design capacity of 1,297 × 10(3) m(3)/day. Many target compounds (83 %) were detected in samples collected from wastewater treatment influent/effluent, creek water, and combined sewer overflow (CSO). The total EDC/PPCP concentrations were as follows: WWTP influent (69,903 ng/L)?>?WWTP effluent (50,175 ng/L) >3 creek samples (16,035-44,446 ng/L) during dry weather, and WWTP influent (53,795 ng/L)?>?WWTP bypass (38,653 ng/L) >5 creek samples (15,260-29,113 ng/L) >2 CSO samples (11,109-11,498 ng/L) during wet weather. EDCs and PPCPs were found to be present at high daily loads (65.1 and 69.8 kg/day during dry and wet weather, respectively) in the WWTP effluent. Compound removal by the WWTP varied significantly by compound: caffeine, diclofenac, ibuprofen, naproxen, and propylparaben (>90 %), and acesulfame, DEET, iohexol, iopromide, and iopamidol (<5 %). These findings and literature information support the hypothesis that the efficiency of removal of EDCs and PPCPs is strongly dependent on both removal mechanism (e.g., biodegradation, adsorption to sludge, and oxidation by chlorine) and compound physicochemical properties (e.g., pK a and hydrophobicity). PMID:24415065

Ryu, Jaena; Oh, Jeill; Snyder, Shane A; Yoon, Yeomin



Characterization of the organic contamination pattern of a hyper-saline ecosystem by rapid screening using gas chromatography coupled to high-resolution time-of-flight mass spectrometry.  


In this paper, gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC-TOF MS) has been applied to evaluate organic pollution in a hyper-saline aquatic environment. Firstly, a target screening was made for a list of 150 GC-amenable organic micro-contaminants, including PAHs, octyl/nonyl phenols, PCBs, PBDEs, and a notable number of pesticides, such us insecticides (organochlorines, organophosphorus, carbamates and pyrethroids), herbicides (triazines and chloroacetanilides), fungicides and several transformation products. This methodology was applied to brine samples, with a salt content from 112 g/L to saturation, and to samples from Artemia populations (crustacean Anostraca) collected during 1 year from three sampling stations in saltworks bodies sited in the Ebro river delta. Around 50 target contaminants, belong to chemical families included in the list of priority substances within the framework on European water policy. Additionally, a non-target analysis was performed in both types of samples with the objective of investigating the presence of other non-selected organic compounds taking advantage of the potential of GC-TOF MS (high sensitivity in full-spectrum acquisition mode, accurate mass measurements) for searching unknowns. Organophosphorus pesticides were the contaminants more frequently detected in brine samples. Other compounds usually present in urban and industrial wastewaters, like caffeine, methylparaben, butylated-hydroxytoluene and N-butylbenzenesulfonamide were also detected in brines. The herbicide simazine and the insecticide chlorpyrifos were among the contaminants detected in Artemia samples. Results of this work reveal a potential threat to vulnerable populations inhabiting the hyper-saline ecosystem. The valuable contribution of GC-TOF MS in environmental analysis, allowing the rapid screening of a large number of organic contaminants, is also demonstrated in this paper. PMID:22789816

Serrano, Roque; Portolés, Tania; Blanes, Miguel A; Hernández, Félix; Navarro, Juan C; Varó, Inmaculada; Amat, Francisco



Preparation and evaluation of monolithic poly(N-vinylcarbazole-co-1,4-divinylbenzene) capillary columns for the separation of small molecules.  


Short-term polymerization or the so-called low-conversion polymerization was applied for the preparation of N-vinylcarbazole (NVC) and 1,4-divinylbenzene (DVB) monolithic capillary columns. The synthesis was carried out by thermally initiated free radical copolymerization under the influence of inert micro- (toluene) and macroporogen (1-decanol) and ?,?'-azoisobutyronitrile (AIBN) as radical initiator. The morphological and porous properties were studied by scanning electron microscopy (SEM), nitrogen adsorption, and mercury intrusion porosimetry (MIP). The copolymerization process was studied by monomer conversion measurements. This approach led to increased porosity and specific surface area. A specific surface area above 400 m(2)/g of the monolith and a distinct bimodal pore size distribution were obtained. The chromatographic performance was determined in terms of theoretical plate heights and number of theoretical plates. The lowest plate height value was found to be 3.9 ?m (corresponding to ?256,000 plates per meter) applying methylparaben utilizing an 80 mm?×?0.2 mm i.d. monolithic capillary. The developed NVC/DVB monolithic supports showed high separation efficiency towards small molecules, which was exemplified applying reversed-phase (RP) separation of alkylbenzenes, beta-blockers, flavanoids, parabens, and phenones. The loading capacity was analyzed for isocratic separation of seven alkylbenzenes and was found to be up to 77 ng total mass of alkylbenzenes. Furthermore, a long-term stability test of 1,000 consecutive runs was performed and resulted in a maximum variance of 0.97, 0.85, and 0.16 % RSD for resolution, peak width at half height, and retention times, respectively. The material was proven to have a high permeability of 1.11E-14 m(2), applying water as a mobile phase. PMID:25056873

Koeck, Rainer; Fischnaller, Martin; Bakry, Rania; Tessadri, Richard; Bonn, Guenther K



Simultaneous determination of some water-soluble vitamins and preservatives in multivitamin syrup by validated stability-indicating high-performance liquid chromatography method.  


HPLC stability-indicating method has been developed for the simultaneous determination of some water-soluble vitamins (ascorbic acid, thiamine hydrochloride, riboflavin-5'-phosphate sodium, pyridoxine hydrochloride, nicotinamide, D(+)-panthenol) and two preservatives (methylparaben and sodium benzoate) in multivitamin syrup preparation. Water-soluble vitamins, preservatives and their degradants were separated on Zorbax SB-Aq (C(18)) (250 mm x 4.6 mm, 5 microm) column at an ambient temperature. Combined isocratic and gradient elution was performed with a mobile phase consisting of 0.0125 M hexane-1-sulfonic acid sodium salt in 0.1% (m/v) o-phosphoric acid, pH 2.4-2.5 (solvent A) and acetonitrile (solvent B) at the flow-rate 1 ml min(-1). Starting with solvent A an isocratic elution was performed for 15 min, then the composition was changed to 85% of A and 15% of B during the next 20 min and it was constant for 5 min, then the composition was changed to 70% of A and 30% of B during next 15 min and it was constant for 5 min and finally was changed to 100% of A as at the beginning of the elution. Detection was performed with diode array detector at 210, 230 and 254 nm. Multivitamin syrup preparation was subjected to stress testing (forced degradation) in order to demonstrate that degradants from the vitamins, preservatives and/or product excipients do not interfere with the quantification of vitamins and preservatives. Typical validation characteristics: selectivity, accuracy, precision, linearity, range, limit of quantification and limit of detection were evaluated for vitamins and preservatives. PMID:18644604

Vidovi?, Stojanka; Stojanovi?, Biljana; Veljkovi?, Jelena; Prazi?-Arsi?, Ljiljana; Rogli?, Goran; Manojlovi?, Dragan



A bioprocess for the production of phytase from Schizophyllum commune: studies of its optimization, profile of fermentation parameters, characterization and stability.  


Schizophyllum commune produces phytase through solid-state fermentation using different agroindustrial residues. After optimization of phytase production, a maximal level of phytase (113.7 Units/gram of dry substrate) was obtained in wheat bran based medium containing 5% sucrose, 50% humidity, 7.5% of biomass at 33 °C pH 7.0 during 72 h and a 285% improvement in enzyme titre was achieved. Analysis of fermentation parameters profile for phytase production showed the highest productivity (1.466 Units/gram of dry substrate/hour) in 66 h of fermentation. Phytase has an optimal pH of 5.0, an optimal temperature of 50 °C and K (m) and V (max) values of 0.16 mM and 1.85 ?mol mL(-1) min(-1), respectively. Phytase activity was stimulated essentially in the presence of K(+), Ca(2+), Mg(2+), Mn(2+), Zn(2+), Cu(2+), Fe(2+), Fe(3+), Co(2+), Ni(2+), acetate and citrate at concentrations of 1 mM. Phytase had the best shelf life when stored at a cooling temperature, maintaining 38% of its initial activity after 112 days of storage, and still presenting enzymatic activity after 125 days of storage. Stability studies of phytase performed in aqueous enzyme extracts showed satisfactory results using polyethyleneglycol 3350, carboxymethylcellulose, methylparaben, mannitol and benzoic acid in concentrations of 0.25, 0.025, 0.025, 0.25, and 0.0025%, respectively. PEG 3350 was shown to be the best stabilizing agent, resulting in 109% of phytase activity from the initial crude extract remaining activity in after 90 days. PMID:22349925

Salmon, Denise Naomi Xavier; Piva, Luíza Cesca; Binati, Renato Leal; Rodrigues, Cristine; Vandenberghe, Luciana Porto de Souza; Soccol, Carlos Ricardo; Spier, Michele Rigon



The metal-organic framework HKUST-1 as efficient sorbent in a vortex-assisted dispersive micro solid-phase extraction of parabens from environmental waters, cosmetic creams, and human urine.  


Three metal-organic frameworks (MOFs), specifically HKUST-1, MOF-5, and MIL-53(Al), have been synthetized, characterized, studied and compared in a vortex-assisted dispersive micro-solid-phase extraction (VA-D-µ-SPE) procedure in combination with high-performance liquid chromatography (HPLC) with diode-array detection (DAD) for determining seven parabens in environmental waters (tap water, swimming pool water, and water coming from a spa pool), human urine (from two volunteers), and cosmetic creams (two commercial brands). Experimental parameters, such as nature and amount of MOF, sample volume, nature of elution solvent and its amount, vortex and centrifugation time, among others, were properly optimized. HKUST-1 was the most adequate MOF to work with. Detection limits for the overall method down to 0.1?gL(-1) for butylparaben (BPB) and benzylparaben (BzPB) were obtained, with determination coefficients (R(2)) higher than 0.9966 for a range of 0.5-147?gL(-1) (depending on the paraben), average relative recoveries (RR, in %) of 80.3% at the low spiked level (7?gL(-1)), and relative standard deviation (RSD) values below 10% also at the low spiked level. The strength of the affinity between HKUST-1 and parabens was evaluated, and it ranged from 33.5% for isopropylparaben (iPPB) to 77.0% for isobutylparaben (iBPB). When analyzing complex environmental waters, RR values of 78%, inter-day precision values (as RSD) lower than 15%, and intra-day precision values lower than 7.8% were obtained, despite the observed matrix effect. When analyzing cosmetic creams, parabens were detected, with contents ranging from 0.14±0.01?gg(-1) for EPB in the healing cream analyzed to 1.12±0.07mgg(-1) for MPB in the mask cream analyzed, with precision values (RSD) lower than 12% and RR values from 63.7% for propylparaben (PPB) to 121% for iPPB. When analyzing human urine, no parabens were detected but the method could be performed with RSD values lower than 19%. These results show the adequateness of MOFs as sorbents in VA-D-µ-SPE procedures despite sample complexity. PMID:25882402

Rocío-Bautista, Priscilla; Martínez-Benito, Carla; Pino, Verónica; Pasán, Jorge; Ayala, Juan H; Ruiz-Pérez, Catalina; Afonso, Ana M



Prenatal Exposure to Environmental Phenols: Concentrations in Amniotic Fluid and Variability in Urinary Concentrations during Pregnancy  

PubMed Central

Background: Maternal urinary biomarkers are often used to assess fetal exposure to phenols and their precursors. Their effectiveness as a measure of exposure in epidemiological studies depends on their variability during pregnancy and their ability to accurately predict fetal exposure. Objectives: We assessed the relationship between urinary and amniotic fluid concentrations of nine environmental phenols, and the reproducibility of urinary concentrations, among pregnant women. Methods: Seventy-one women referred for amniocentesis were included. Maternal urine was collected at the time of the amniocentesis appointment and on two subsequent occasions. Urine and amniotic fluid were analyzed for 2,4- and 2,5-dichlorophenols, bisphenol A, benzophenone-3, triclosan, and methyl-, ethyl-, propyl-, and butylparabens using online solid phase extraction–high performance liquid chromatography–isotope dilution tandem mass spectrometry. Results: Only benzophenone-3 and propylparaben were detectable in more than half of the amniotic fluid samples; for these phenols, concentrations in amniotic fluid and maternal urine collected on the same day were positively correlated (? = 0.53 and 0.32, respectively). Other phenols were detected infrequently in amniotic fluid (e.g., bisphenol A was detected in only two samples). The intraclass correlation coefficients (ICCs) of urinary concentrations in samples from individual women ranged from 0.48 and 0.62 for all phenols except bisphenol A (ICC = 0.11). Conclusion: Amniotic fluid detection frequencies for most phenols were low. The reproducibility of urine measures was poor for bisphenol A, but good for the other phenols. Although a single sample may provide a reasonable estimate of exposure for some phenols, collecting multiple urine samples during pregnancy is an option to reduce exposure measurement error in studies regarding the effects of phenol prenatal exposure on health. Citation: Philippat C, Wolff MS, Calafat AM, Ye X, Bausell R, Meadows M, Stone J, Slama R, Engel SM. 2013. Prenatal exposure to environmental phenols: concentrations in amniotic fluid and variability in urinary concentrations during pregnancy. Environ Health Perspect 121:1225–1231;? PMID:23942273

Wolff, Mary S.; Calafat, Antonia M.; Ye, Xiaoyun; Bausell, Rebecca; Meadows, Molly; Stone, Joanne; Slama, Rémy; Engel, Stephanie M.