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Sample records for methylparaben ethylparaben propylparaben

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

    PubMed Central

    Shabir, G. A.

    2010-01-01

    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

  2. Final amended report on the safety assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in cosmetic products.

    PubMed

    2008-01-01

    Parabens is the name given to a group of p-hydroxybenzoic acid (PHBA) esters used in over 22,000 cosmetics as preservatives at concentrations up to 0.8% (mixtures of parabens) or up to 0.4% (single paraben). The group includes Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben. Industry estimates of the daily use of cosmetic products that may contain parabens were 17.76 g for adults and 378 mg for infants. Parabens in cosmetic formulations applied to skin penetrate the stratum corneum in inverse relation to the ester chain length. Carboxylesterases hydrolyze parabens in the skin. Parabens do not accumulate in the body. Serum concentrations of parabens, even after intravenous administration, quickly decline and remain low. Acute toxicity studies in animals indicate that parabens are not significantly toxic by various routes of administration. Subchronic and chronic oral studies indicate that parabens are practically nontoxic. Numerous genotoxicity studies, including Ames testing, dominant lethal assay, host-mediated assay, and cytogenic assays, indicate that the Parabens are generally nonmutagenic, although Ethylparaben and Methylparaben did increase chromosomal aberrations in a Chinese Hamster ovary cell assay. Ethylparaben, Propylparaben, and Butylparaben in the diet produced cell proliferation in the forestomach of rats, with the activity directly related to chain length of the alkyl chain, but Isobutylparaben and Butylparaben were noncarcinogenic in a mouse chronic feeding study. Methylparaben was noncarcinogenic when injected subcutaneously in mice or rats, or when administered intravaginally in rats, and was not cocarcinogenic when injected subcutaneously in mice. Propylparaben was noncarcinogenic in a study of transplacental carcinogenesis. Methylparaben was nonteratogenic in rabbits, rats, mice, and hamsters, and Ethylparaben was nonteratogenic in rats. Parabens, even at levels that produce maternal

  3. Comparative studies of aerobic and anaerobic biodegradation of methylparaben and propylparaben in activated sludge.

    PubMed

    Wu, Yang; Sun, Qian; Wang, Yu-Wen; Deng, Cheng-Xun; Yu, Chang-Ping

    2017-04-01

    The biodegradability of two typical parabens (methylparaben and propylparaben) in activated sludge, at initial concentrations of 1mgL(-1) or 10mgL(-1), was investigated under aerobic and anaerobic conditions. The results showed that microorganisms played a key role in degradation of parabens in WWTPs, especially in aerobic systems. The half-lives of methylparaben and propylparaben under aerobic conditions have been estimated to range between 15.8 and 19.8min, and benzoic acid was found to be one of the major biodegradation products. The calculated biodegradation efficiency of methylparaben and propylparaben in activated sludge under aerobic conditions was significantly higher than that observed under anaerobic (nitrate, sulfate, and Fe (III) reducing) conditions, as methylparaben and propylparaben exhibited comparatively higher persistence in anaerobic systems, with half-lives ≥43.3h and ≥8.6h, respectively. Overall, the results of this study imply that the majority of these parabens can be eliminated by aerobic biodegradation during conventional wastewater treatment processes, whereas minor removal is possible in anaerobic systems if an insufficient hydraulic retention time was maintained.

  4. The estrogenicity of methylparaben and ethylparaben at doses close to the acceptable daily intake in immature Sprague-Dawley rats

    PubMed Central

    Sun, Libei; Yu, Tong; Guo, Jilong; Zhang, Zhaobin; Hu, Ying; Xiao, Xuan; Sun, Yingli; Xiao, Han; Li, Junyu; Zhu, Desheng; Sai, Linlin; Li, Jun

    2016-01-01

    The estrogenicity of parabens at human exposure levels has become a focus of concern due to the debate over whether the estrogenicity of parabens is strong enough to play a role in the increased incidence of breast cancer. In this study, the uterotrophic activities of methylparaben (MP) and ethylparaben (EP) at doses close to the acceptable daily intake as allocated by JECFA were demonstrated in immature Sprague-Dawley rats by intragastric administration, and up-regulations of estrogen-responsive biomarker genes were found in uteri of the rats by quantitative real-time RT–PCR (Q-RT-PCR). At the same time, the urinary concentrations of MP and EP, as measured by gas chromatography–mass spectrometry (GC-MS) in rats that received the same doses of MP and EP, were found to be near the high urinary levels reported in human populations in recent years. These results show the in vivo estrogenicity of MP and EP at human exposure levels, and indicate that populations exposed to large amounts of MP and EP may have a high burden of estrogenicity-related diseases. In addition, a molecular docking simulation showed interaction between the parabens and the agonist-binding pocket of human estrogen receptor α (hERα). PMID:27121550

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

    NASA Astrophysics Data System (ADS)

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

    2007-09-01

    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.

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

    PubMed Central

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

    2013-01-01

    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 μm 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 μg/ml & 0.05 μg/ml, whereas the limit of quantification was 0.19 μg/ml & 0.15 μg/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

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

    PubMed

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

    2013-01-01

    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 μm 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 μg/ml & 0.05 μg/ml, whereas the limit of quantification was 0.19 μg/ml & 0.15 μg/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.

  8. Development and Validation of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Phenoxyethanol, Methylparaben, Propylparaben, Mometasone Furoate, and Tazarotene in Topical Pharmaceutical Dosage Formulation

    PubMed Central

    Roy, Chinmoy; Chakrabarty, Jitamanyu

    2013-01-01

    A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of phenoxyethanol (PE), methylparaben (MP), propylparaben (PP), mometasone furoate (MF), and tazarotene (TA) in topical pharmaceutical dosage formulation. The desired chromatographic separation was achieved on the Waters X-Bridge™ C18 (50×4.6mm, 3.5μ) column using gradient elution at 256 nm detection wavelength. The optimized mobile phase consisted of 0.1%v/v orthophosphoric acid in water as solvent-A and acetonitrile as solvent-B. The method showed linearity over the range of 5.88–61.76 μg/mL, 0.18–62.36 μg/mL, 0.17–6.26 μg/mL, 0.47–31.22 μg/mL, and 0.44–30.45 μg/mL for PE, MP, PP, MF, and TA, respectively. The recovery for all of the components was 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 PE, MP, PP, MF, and TA along with the separation of degradation products from the analyte peaks was achieved. The proposed method was successfully applied for the quantitative determination of PE, MP, PP, MF, and TA in a cream sample. PMID:24482766

  9. 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

    Roy, Chinmoy; Chakrabarty, Jitamanyu

    2014-01-01

    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 μm) 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 μg/mL, 0.23–15.3 μg/mL, 1.97–600.5 μg/mL, and 1.85–451.5 μg/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. PMID:25853065

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

    PubMed

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

    2014-12-01

    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.

  11. Development of a selective and sensitive voltammetric sensor for propylparaben based on a nanosized molecularly imprinted polymer-carbon paste electrode.

    PubMed

    Gholivand, Mohammad Bagher; Shamsipur, Mojtaba; Dehdashtian, Sara; Rajabi, Hamid Reza

    2014-03-01

    The design and construction of a selective voltammetric sensor for propylparaben (PP) in cosmetics by using a molecularly imprinted polymer (MIP) as recognition element was introduced. The MIP was synthesized by using PP as template and methacrylic acid as functional monomer and then incorporated in the carbon paste electrode as PP sensor. The molecularly imprinted polymer-carbon paste electrode (MIP-CPE) showed very high recognition ability in comparison to non-imprinted polymer-carbon paste electrode (NIP-CPE). It was shown that electrode washing after PP extraction, led to enhanced selectivity, without noticeably decreasing the sensitivity. Some parameters affecting sensor response were optimized, and a calibration curve was then plotted using differential pulse voltammetric (DPV) technique. A dynamic linear range of 1 nM to 100 nM was obtained. The detection limit of the sensor was calculated to be equal to 0.32 nM. The imprinted electrode also displayed good selectivity for PP and selectivity coefficients were 2.29 and 1.66 for methylparaben (MP) and ethylparaben (EP) respectively. Structural analogs, such as phenol and p-hydroxybenzoic acid had almost no response. This sensor was used successfully for propylparaben determination in cosmetic sample.

  12. 21 CFR 184.1670 - Propylparaben.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Substances Affirmed as GRAS § 184.1670 Propylparaben. (a) Propylparaben is the chemical propyl p-hydroxybenzoate. It is produced by the n-propanol esterification of p-hydroxybenzoic acid in the presence...

  13. 21 CFR 184.1670 - Propylparaben.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Substances Affirmed as GRAS § 184.1670 Propylparaben. (a) Propylparaben is the chemical propyl p-hydroxybenzoate. It is produced by the n-propanol esterification of p-hydroxybenzoic acid in the presence...

  14. 21 CFR 184.1670 - Propylparaben.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Substances Affirmed as GRAS § 184.1670 Propylparaben. (a) Propylparaben is the 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 the...

  15. 21 CFR 184.1670 - Propylparaben.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Substances Affirmed as GRAS § 184.1670 Propylparaben. (a) Propylparaben is the 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 the...

  16. 21 CFR 184.1490 - Methylparaben.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Substances Affirmed as GRAS § 184.1490 Methylparaben. (a) Methylparaben is the 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 the...

  17. 21 CFR 184.1490 - Methylparaben.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Substances Affirmed as GRAS § 184.1490 Methylparaben. (a) Methylparaben is the 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 the...

  18. Heat-activated persulfate oxidation of methyl- and ethyl-parabens: Effect, kinetics, and mechanism.

    PubMed

    Chen, Yiqun; Deng, Pinya; Xie, Pengchao; Shang, Ran; Wang, Zongping; Wang, Songlin

    2017-02-01

    We evaluated the degradation of methylparaben (MeP) and ethylparaben (EtP), two representative parabens, using the heat-activated persulfate system in a laboratory. Both sulfate and hydroxyl radicals contributed to the removal of the two parabens. The degradations of both MeP and EtP were improved by increasing the heating temperature or persulfate dose in accordance with a pseudo-first-order reaction model. The oxidation efficiency of parabens was found to be pH-dependent; decreasing in the order pH 5.0 > 7.0 > 9.0. The presence of chloride, bicarbonate, or humic acid was found to inhibit the degradation of the two parabens to some extent because of competition for the reactive radicals, with humic acid having the most serious effect. Dealkylation of the methyl unit, decarboxylation of the carboxylic group, and subsequent hydrolysis are proposed to be involved in the degradation pathway of MeP. The results suggest that the heat-activated persulfate system might be efficiently applied in the treatment of paraben-containing water samples. This was also supported by the results of applying this system to treat a real water sample containing both MeP and EtP.

  19. The Combined Effect of Methyl- and Ethyl-Paraben on Lifespan and Preadult Development Period of Drosophila melanogaster (Diptera: Drosophilidae).

    PubMed

    Chen, Qi; Pan, Chenguang; Li, Yajuan; Zhang, Min; Gu, Wei

    2016-01-01

    Parabens are widely used as preservative substances in foods, pharmaceuticals, industrial products, and cosmetics. But several studies have cautioned that parabens have estrogenic or endocrine-disrupting properties. Drosophila melanogaster is an ideal model in vivo to detect the toxic effects of chemistry. The study was designed to assess the potential additive toxic effects of methylparaben (MP) and ethylparaben (EP) mixture (MP + EP) on lifespan and preadult development period in D. melanogaster The data revealed that the MP + EP can reduce the longevity of flies compared with the control group, consistent with a significant reduction in malondialdehyde levels and an increase in superoxide dismutase activities. Furthermore, MP + EP may have a greater toxic effect on longevity of flies than separate using with the same concentration. Additionally, parabens had a nonmonotonic dose-response effect on D. melanogaster preadult development period, showing that MP + EP delayed preadult development period compared with control group while individual MP or EP significantly shortened (P < 0.01) at low concentration (300 mg/l). In conclusion, MP + EP had the potential additive toxicity on lifespan and preadult development period for D. melanogaster.

  20. Degradation of ethylparaben under simulated sunlight using photo-Fenton.

    PubMed

    Zúñiga-Benítez, Henry; Peñuela, Gustavo A

    2016-01-01

    Ethylparaben (EPB) has been classified by different research groups as a potential endocrine-disrupting chemical, implying that it can potentially interfere with the normal balance of the endocrine system of living beings, which with its presence in different effluents, including drinking water, generates the need to seek methods that allow its removal from different water bodies. Advanced oxidation processes have been employed widely to remove organic compounds from different matrices. In this way, Fenton technology (process based on the reaction between ferrous ions and hydrogen peroxide) has been able to degrade different substrates, but due to the Fe(2+) requirements to carry out the reaction optimally, combination of the conventional Fenton process with visible light radiation (photo-Fenton) is an alternative used in the treatment of pollution due to the presence of chemicals. In this way, the effectiveness of photo-Fenton on EPB degradation was assessed using a face-centered central composite experimental design that allowed assessment of the effects of Fe(2+) and H2O2 initial concentrations on process. In general, results indicated that after 180 min of reaction almost all EPB was eliminated, the dissolved organic carbon in solution was reduced and the sample biodegradability index was increased.

  1. Methylparaben concentration in commercial Brazilian local anesthetics solutions

    PubMed Central

    da SILVA, Gustavo Henrique Rodriguez; BOTTOLI, Carla Beatriz Grespan; GROPPO, Francisco Carlos; VOLPATO, Maria Cristina; RANALI, José; RAMACCIATO, Juliana Cama; MOTTA, Rogério Heládio Lopes

    2012-01-01

    Objective To detect the presence and concentration of methylparaben in cartridges of commercial Brazilian local anesthetics. Material and methods Twelve commercial brands (4 in glass and 8 in plastic cartridges) of local anesthetic solutions for use in dentistry were purchased from the Brazilian market and analyzed. Different lots of the commercial brands were obtained in different Brazilian cities (Piracicaba, Campinas and São Paulo). Separation was performed using high performance liquid chromatography (HPLC) with UV-Vis detector. The mobile phase used was acetonitrile:water (75:25 - v/v), pH 4.5, adjusted with acetic acid at a flow rate of 1.0 ml.min-1. Results When detected in the solutions, the methylparaben concentration ranged from 0.01% (m/v) to 0.16% (m/v). One glass and all plastic cartridges presented methylparaben. Conclusion 1. Methylparaben concentration varied among solutions from different manufacturers, and it was not indicated in the drug package inserts; 2. Since the presence of methylparaben in dental anesthetics is not regulated by the Brazilian National Health Surveillance Agency (ANVISA) and this substance could cause allergic reactions, it is important to alert dentists about its possible presence. PMID:23032206

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

    PubMed

    Wróbel, Anna Maria; Gregoraszczuk, Ewa Łucja

    2014-09-01

    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 17β-estradiol (10 nm). Cell cycle and apoptotic gene expression were evaluated by real-time polymerase chain reaction and protein expression by Western blot. 17β-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 17β-estradiol, while propylparaben upregulated both the extrinsic and intrinsic apoptotic pathways. There are differences in cell cycle and apoptosis gene expression between parabens and 17β-estradiol in MCF-7 cells. In MCF-10A cells, most of the genes activated by parabens were comparable to those activated by 17β-estradiol.

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

    PubMed

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

    2015-03-01

    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.

  4. Methylparaben isolated in solid argon: structural characterization and UV-induced conversion into methylparaben radical and isomeric ketenes.

    PubMed

    Kuş, Nihal; Bayarı, Sevgi H; Fausto, Rui

    2013-10-31

    Methylparaben (methyl p-hydroxybenzoic acid; MP) is a widely used antimicrobial preservative, being the most frequently used antimicrobial preservative in cosmetics. The generalized use of MP has become controversial, with several recent reports of dangerous side effects. For example, the presence of MP in human breast tumors and its harmful effects on human skin exposed to the sunlight have been demonstrated. In spite of the important practical relevance of the compound and of the controversy about its practical use, its structural and photochemical characterization had not been undertaken hitherto. To fill this gap, in the present study, MP was isolated in solid argon (T = 15 K) and structurally characterized by a combined infrared spectroscopy/quantum chemistry approach. The potential energy surface (PES) of the molecule was investigated in detail, revealing the existence of two almost isoenergetic (ΔE(0) = 0.37 kJ mol(-1)) s-cis carboxylic ester low-energy conformers, with an estimated population ratio in the gas phase at room temperature (∼298 K) of ca. 0.83. The calculations also predicted the existence of two high-energy (ΔE(0) = ∼50 kJ mol(-1)) s-trans carboxylic ester conformers of MP. Upon isolation of the compound in an argon matrix, only the lowest energy conformer was found to survive, due to occurrence of extensive conformational cooling during matrix deposition. The infrared spectrum of this conformer was obtained and interpreted. In addition, the chemical processes resulting from in situ irradiation of the matrix-isolated MP with a broadband UV source (λ > 234 nm) were investigated, revealing extensive conversion of MP into highly reactive methylparaben radical and isomeric ketenes. These observations support the recent concerns regarding uses of MP, in particular when the compound has to be exposed to UV light.

  5. Anticonvulsant effect of sodium cyclamate and propylparaben on pentylenetetrazol-induced seizures in zebrafish.

    PubMed

    Pisera-Fuster, Antonella; Otero, Sofía; Talevi, Alan; Bruno-Blanch, Luis; Bernabeu, Ramón

    2017-04-01

    Screening for novel anticonvulsant drugs requires appropriate animal seizure models. Zebrafish provide small, accessible, and cost-efficient preclinical models applicable to high-throughput small molecule screening. Based on previous results in rodents, we have here examined the effects of artificial sweetener sodium cyclamate and antimicrobial agent sodium propylparaben on a model of pentylenetetrazole (PTZ)-induced seizures in zebrafish. Sodium cyclamate reduced the bursts of hyperactivity, the spasms, increased the latency to spasms, and the latency to seizure, while propylparaben increased the latency to spasms. The results show the potential of zebrafish to detect novel anticonvulsant compounds while they also demonstrate the ability of two commonly ingested chemical compounds to modify the seizure threshold when were administrated at low concentration.

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

    PubMed

    Wu, Chuanbin; McGinity, James W

    2003-07-01

    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.

  7. Screening the Toxicity of Selected Personal Care Products Using Embryo Bioassays: 4-MBC, Propylparaben and Triclocarban.

    PubMed

    Torres, Tiago; Cunha, Isabel; Martins, Rosário; Santos, Miguel M

    2016-10-21

    Recently, several emerging pollutants, including Personal Care Products (PCPs), have been detected in aquatic ecosystems, in the ng/L or µg/L range. Available toxicological data is limited, and, for certain PCPs, evidence indicates a potential risk for the environment. Hence, there is an urgent need to gather ecotoxicological data on PCPs as a proxy to improve risk assessment. Here, the toxicity of three different PCPs (4-Methylbenzylidene Camphor (4-MBC), propylparaben and triclocarban) was tested using embryo bioassays with Danio rerio (zebrafish) and Paracentrotus lividus (sea urchin). The No Observed Effect Concentration (NOEC) for triclocarban was 0.256 µg/L for sea urchin and 100 µg/L for zebrafish, whereas NOEC for 4-MBC was 0.32 µg/L for sea urchin and 50 µg/L for zebrafish. Both PCPs impacted embryo development at environmentally relevant concentrations. In comparison with triclocarban and 4-MBC, propylparaben was less toxic for both sea urchin (NOEC = 160 µg/L) and zebrafish (NOEC = 1000 µg/L). Overall, this study further demonstrates the sensitivity of embryo bioassays as a high-throughput approach for testing the toxicity of emerging pollutants.

  8. Screening the Toxicity of Selected Personal Care Products Using Embryo Bioassays: 4-MBC, Propylparaben and Triclocarban

    PubMed Central

    Torres, Tiago; Cunha, Isabel; Martins, Rosário; Santos, Miguel M.

    2016-01-01

    Recently, several emerging pollutants, including Personal Care Products (PCPs), have been detected in aquatic ecosystems, in the ng/L or µg/L range. Available toxicological data is limited, and, for certain PCPs, evidence indicates a potential risk for the environment. Hence, there is an urgent need to gather ecotoxicological data on PCPs as a proxy to improve risk assessment. Here, the toxicity of three different PCPs (4-Methylbenzylidene Camphor (4-MBC), propylparaben and triclocarban) was tested using embryo bioassays with Danio rerio (zebrafish) and Paracentrotus lividus (sea urchin). The No Observed Effect Concentration (NOEC) for triclocarban was 0.256 µg/L for sea urchin and 100 µg/L for zebrafish, whereas NOEC for 4-MBC was 0.32 µg/L for sea urchin and 50 µg/L for zebrafish. Both PCPs impacted embryo development at environmentally relevant concentrations. In comparison with triclocarban and 4-MBC, propylparaben was less toxic for both sea urchin (NOEC = 160 µg/L) and zebrafish (NOEC = 1000 µg/L). Overall, this study further demonstrates the sensitivity of embryo bioassays as a high-throughput approach for testing the toxicity of emerging pollutants. PMID:27775672

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

    PubMed

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

    2014-01-01

    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.

  10. Comparison of antimicrobial activity of essential oils, plant extracts and methylparaben in cosmetic emulsions: 2 months study.

    PubMed

    Herman, Anna

    2014-09-01

    The aim of the study was to compare the preservative effectiveness of plant extracts (Matricaria chamomilla, Aloe vera, Calendula officinalis) and essential oils (Lavandulla officinalis, Melaleuca alternifolia, Cinnamomum zeylanicum) with methylparaben in cosmetic emulsions against skin microflora during 2 months of application by volunteers. Cosmetic emulsions with extracts (2.5 %), essential oils (2.5 %), methylparaben (0.4 %) or placebo were tested by 40 volunteers during 2 months of treatment. In order to determine microbial purity of the emulsions, the samples were taken after 0, 2, 4, 6 and 8 weeks of application. Throughout the trial period it was revealed that only cinnamon oil completely inhibited the growth of bacteria, yeast and mould, as compared to all other essential oils, plant extracts and methylparaben in the tested emulsions. This result shows that cinnamon oil could successfully replace the use of methylparaben in cosmetics, at the same time ensuring microbiological purity of a cosmetic product under its in-use and storage conditions.

  11. Influence of fat addition on the antimicrobial activity of sodium lactate, lauric arginate and methylparaben in minced meat.

    PubMed

    Magrinyà, Núria; Terjung, Nino; Loeffler, Myriam; Gibis, Monika; Bou, Ricard; Weiss, Jochen

    2015-12-23

    A minced meat model system containing three different fat levels (0, 15, and 50 wt.%) was used to evaluate the antimicrobial efficacy of three antimicrobials with different aqueous solubilities (sodium lactate>lauric arginate (Nα-lauroyl-L-arginine ethyl ester, LAE)>methylparaben). Various concentrations of sodium lactate (20, 40, and 60 mg/g), lauric arginate (0.5, 1, 1.5, 2.0, and 2.5 mg/g) and methylparaben (0.1, 0.5, 1.0, and 2.0 mg/g) were used to evaluate the antimicrobial activity against natural meat microbiota (total aerobic mesophilic colony counts, coliform bacteria, and lactic acid bacteria). The results indicate that the three antimicrobials tested are influenced at different strengths by the changes of the fat addition of the minced meat. The antimicrobial efficacy of LAE and methylparaben is increased by a higher fat content in the meat batter, whereas for lactate no clear lactate proportionality relationship can be seen. This structure sensitivity is most strongly pronounced with lauric arginate, which we attributed to the amphiphilic character of the molecule.

  12. Influence of inorganic ions and selected emerging contaminants on the degradation of Methylparaben: A sonochemical approach.

    PubMed

    Sasi, Subha; Rayaroth, Manoj P; Devadasan, Dineep; Aravind, Usha K; Aravindakumar, Charuvila T

    2015-12-30

    The study on the possible pathway of hydroxyl radicals mediated sonolytic degradation of paraben in water is reported. Methylparaben (MPB) which is the most utilized of paraben family is selected as a model emerging pollutant. The influence of common anions and some selected emerging contaminants that may coexist in typical water matrix on the degradation pattern is analyzed alongside. Among the anions, carbonate presents a negative influence which is attributed to the competition for OH radical. Some emerging contaminants also showed negative impact on degradation as was clear from HPLC data. The intermediates, analyzed by LC-Q-TOF-MS include hydroxylated and hydrolytic products. Three major steps (aromatic hydroxylation, hydroxylation at the ester chain and hydrolysis) are proposed to involve in the reaction of OH radical with MPB which ultimately leads to mineralization. The intensity of formation and decay of mono and dihydroxy products of MPB in the presence of additives have also been evaluated. COD analysis indicates a percentage reduction of 98% at 90 min of sonolysis and further increase in the degradation time resulted complete mineralization, which became evident from the mass spectrometric data. MTT assay revealed considerable decrease in the potential cytotoxicity.

  13. Removal of methylparaben from synthetic aqueous solutions using polyacrylonitrile beads: kinetic and equilibrium studies.

    PubMed

    Forte, Maurizio; Mita, Luigi; Perrone, Rosa; Rossi, Sergio; Argirò, Mario; Mita, Damiano Gustavo; Guida, Marco; Portaccio, Marianna; Godievargova, Tzonka; Ivanov, Yavour; Tamer, Mahmoud T; Omer, Ahmed M; Mohy Eldin, Mohamed S

    2017-01-01

    The removal of methylparaben (MP), a well-known endocrine disruptor, from aqueous solutions using polyacrylonitrile (PAN) beads has been studied under batch conditions, at room temperature and at different initial MP concentrations. The kinetic and equilibrium results have been analyzed. Kinetic modeling analysis has been carried out with three different types of adsorption models: pseudo-first-order, pseudo-second-order, and Elovich model. Kinetic data analysis indicated that the adsorption was a second-order process. The MP adsorption by PAN was also quantitatively evaluated by using the equilibrium adsorption isotherm models of Langmuir, Freundlich, Dubinin-Radushkevich (D-R), and Temkin and the applicability of the respective isotherm equations has been compared through the correlation coefficients. Adsorption data resulted well fitted by the Freundlich isotherm model. Data of MP adsorption have also been used to test different adsorption diffusion models. The diffusion rate equations inside particulate of Dumwald-Wagner and the intraparticle diffusion model have been used to calculate the diffusion rate. The actual rate-controlling step involved in the MB adsorption process was determined. The kinetic expression by Boyd gave the right indications. All together, our results indicate that PAN beads are a useful tool to remediate water bodies polluted by endocrine disruptors.

  14. Methylparaben removal using heterogeneous photocatalysis: effect of operational parameters and mineralization/biodegradability studies.

    PubMed

    Zúñiga-Benítez, Henry; Peñuela, Gustavo A

    2016-03-18

    Methylparaben (MePB) is an organic compound employed mainly in the manufacture of different personal care products. However, it has been recently listed as a potential endocrine disrupter chemical. Therefore, the main objective of this work was to evaluate the degradation of MePB in aqueous solutions using heterogeneous photocatalysis with TiO2 and hydrogen peroxide. In this way, effects of pH and the initial concentrations of catalyst, H2O2, and pollutant on treatment were analyzed. A face centered, central composite design was used for determination of the influence of each parameter in the process and the conditions under which the pollutant suffers the highest rates of degradation were selected. In general, results indicate that combination TiO2/H2O2/light irradiation leads to ∼90 % of substrate removal after 30 min of reaction and that hydroxyl free radicals are the main specie responsible for organic matter elimination. Finally, in terms of mineralization and biodegradability, experimental results indicated that part of the organic matter was transformed into CO2 and water and the photo-treatment promoted an increase in samples biodegradability.

  15. Oral propylparaben administration to juvenile male Wistar rats did not induce toxicity in reproductive organs.

    PubMed

    Gazin, Vincent; Marsden, Edward; Marguerite, Fabien

    2013-12-01

    Parabens are in widespread use as preservatives in drugs. In the late 1990 s, concerns were raised about their capacity to disrupt endocrine function based on in vitro data and in vivo uterotrophic tests. Studies in juvenile male rats provided conflicting results on pospubertal sperm production. In an exploratory pharmacokinetic study, Wistar male rats received a single dose of propylparaben (PP) at 3, 10, 100, or 1000 mg/kg, orally on postnatal day (PND) 31. Plasma PP concentrations were quantifiable up 8h after dosing with a mean T max value of 15 min. Distribution was 4.8 l/kg, the plasma elimination half-life was 47 min, and clearance was 4.20 (l/h)/kg at 10mg/kg. A sulfoconjugated metabolite was detected. In the juvenile toxicology study, PP was orally administered by gavage to 20 Wistar male rats at doses of 3, 10, 100, or 1000 mg/kg/day in 1% hydroxyethylcellulose for 8 weeks starting on PND21. A first subgroup of 10 males/dose was necropsied immediately after the 8-week exposure period; a second subgroup of 10 males/dose was necropsied after a 26-week washout period. Blood samples were taken from additional satellite animals after dosing on PND21 and PND77 for toxicokinetic analysis. There was no evidence of an effect of PP on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels, or histopathology. The dose of 1000 mg/kg/day was the no-observed adverse effect level, corresponding to a maximum plasma concentration of 12,030 ng/ml and exposure to 47 760 ng · h/ml (AUC0-8 h) at the end of the treatment.

  16. Spectral characterization of the binding and conformational changes of bovine serum albumin upon interaction with an anti-fungal drug, methylparaben

    NASA Astrophysics Data System (ADS)

    Naik, Keerti M.; Nandibewoor, Sharanappa T.

    2013-03-01

    The binding of methylparaben with bovine serum albumin (BSA) was investigated by spectroscopic methods viz., fluorescence, FT-IR and UV-vis absorption techniques under physiological conditions i.e., pH 7.4. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of bovine serum albumin by methylparaben shows a dynamic quenching. The binding sites number n and binding constants, K were obtained at various temperatures. The distance, r between methylparaben and BSA was evaluated according to the theory of Förster energy transfer. The result of FT-IR spectra and UV-vis absorption spectra showed that the conformation of bovine serum albumin has been changed in the presence of methylparaben. The thermodynamic parameters, enthalpy change (ΔH0) and entropy change (ΔS0) were calculated according to van't Hoff equation, which indicated that the hydrophobic interaction was the predominant intermolecular force stabilizing the complex. The effect of common ions and site probes were also carried on the binding of methylparaben to BSA.

  17. Thermodynamic properties of aqueous PEO-PPO-PEO micelles with added methylparaben determined by differential scanning calorimetry.

    PubMed

    Thompson, Andre Lamont; Love, Brian James

    2013-05-15

    DSC experiments were performed on aqueous solutions of PEO-PPO-PEO (P105) amphiphiles in the low concentration regime (0-1%) to resolve the critical micelle concentration (cmc) both neat and co-formulated with methylparaben (MP). Further work was done at 10% amphiphilic copolymer concentrations and co-formulated with MP to resolve the variations in enthalpy. The compensation temperature, T(compensation), was determined from the analyses for neat P105 as 293.9 K; adding MP raises this to 328.43 K.

  18. Determination of ambroxol hydrochloride, methylparaben and benzoic acid in pharmaceutical preparations based on sequential injection technique coupled with monolithic column.

    PubMed

    Satínský, Dalibor; Huclová, Jitka; Ferreira, Raquel L C; Montenegro, Maria Conceição B S M; Solich, Petr

    2006-02-13

    The porous monolithic columns show high performance at relatively low pressure. The coupling of short monoliths with sequential injection technique (SIA) results in a new approach to implementation of separation step to non-separation low-pressure method. In this contribution, a new separation method for simultaneous determination of ambroxol, methylparaben and benzoic acid was developed based on a novel reversed-phase sequential injection chromatography (SIC) technique with UV detection. A Chromolith SpeedROD RP-18e, 50-4.6 mm column with 10 mm precolumn and a FIAlab 3000 system with a six-port selection valve and 5 ml syringe were used for sequential injection chromatographic separations in our study. The mobile phase used was acetonitrile-tetrahydrofuran-0.05M acetic acid (10:10:90, v/v/v), pH 3.75 adjusted with triethylamine, flow rate 0.48 mlmin(-1), UV-detection was at 245 nm. The analysis time was <11 min. A new SIC method was validated and compared with HPLC. The method was found to be useful for the routine analysis of the active compounds ambroxol and preservatives (methylparaben or benzoic acid) in various pharmaceutical syrups and drops.

  19. Dissociation constants of parabens and limiting conductances of their ions in water.

    PubMed

    Kroflič, Ana; Apelblat, Alexander; Bešter-Rogač, Marija

    2012-02-02

    Precise measurements of electrical conductivities of methylparaben, ethylparaben, propylparaben, and butylparaben sodium salts in dilute aqueous solutions were performed from 278.15 to 313.15 K in 5 K intervals. Experimental conductivity data were analyzed applying the Quint-Viallard conductivity equations by taking into account the salt hydrolysis in aqueous solutions. These evaluations yield the limiting conductances of paraben anions and the dissociation constants of the investigated parabens in water. From temperature dependence of dissociation constants, the thermodynamic functions associated with the dissociation process were estimated. It was discovered that the contributions of enthalpy and entropy to the Gibbs free energy are quite similar. The Walden products of paraben anions in water are independent of temperature, indicating that the hydrodynamic radii are not significantly affected by temperature.

  20. Determination of dexamethasone and two excipients (creatinine and propylparaben) in injections by using UV-spectroscopy and multivariate calibrations.

    PubMed

    Collado, M S; Robles, J C; De Zan, M; Cámara, M S; Mantovani, V E; Goicoechea, H C

    2001-10-23

    The use of multivariate spectrophotometric calibration for the simultaneous determination of dexamethasone and two typical excipients (creatinine and propylparaben) in injections is presented. The resolution of the three-component mixture in a matrix of excipients has been accomplished by using partial least-squares (PLS-1). Notwithstanding the elevated degree of spectral overlap, they have been rapidly and simultaneously determined with high accuracy and precision (comparable to the HPLC pharmacopeial method), with no interference, and without resorting to extraction procedures using non-aqueous solvents. A simple and fast method for wavelength selection in the calibration step is used, based on the minimisation of the predicted error sum of squares (PRESS) calculated as a function of a moving spectral window.

  1. Demonstration of synergy with fluconazole and either ibuprofen, sodium salicylate, or propylparaben against Candida albicans in vitro.

    PubMed Central

    Scott, E M; Tariq, V N; McCrory, R M

    1995-01-01

    The combination of fluconazole with either ibuprofen, sodium salicylate, or propylparaben resulted in synergistic activity (fractional inhibitory index, < 0.5) against Candida albicans NCYC 620 in a microdilution checkerboard assay. Synergism between miconazole and ibuprofen was also demonstrated. In three or four clinical isolates of C. albicans from AIDS patients, the combination of fluconazole and ibuprofen was synergistic. Preparation of the inoculum and the growth conditions used were those recommended by the National Committee for Clinical Laboratory Standards for susceptibility testing. A visual estimation of total inhibition of growth and determination of an 80% reduction in the optical density at 492 nm compared with those for the control were taken as endpoints for the calculation of synergy, and a good correlation between both estimates was demonstrated. PMID:8592988

  2. Simultaneous spectrophotometric-multivariate calibration determination of several components of ophthalmic solutions: phenylephrine, chloramphenicol, antipyrine, methylparaben and thimerosal.

    PubMed

    Collado, M S; Mantovani, V E; Goicoechea, H C; Olivieri, A C

    2000-08-16

    The use of multivariate spectrophotometric calibration for the simultaneous determination of several active components and excipients in ophthalmic solutions is presented. The resolution of five-component mixtures of phenylephrine, chloramphenicol, antipyrine, methylparaben and thimerosal has been accomplished by using partial least-squares (PLS-1) and a variant of the so-called hybrid linear analysis (HLA). Notwithstanding the presence of a large number of components and their high degree of spectral overlap, they have been determined simultaneously with high accuracy and precision, with no interference, rapidly and without resorting to extraction procedures using non aqueous solvents. A simple and fast method for wavelength selection in the calibration step is presented, based on the minimisation of the predicted error sum of squares (PRESS) calculated as a function of a moving spectral window.

  3. Ultra-high-performance liquid chromatography-tandem mass spectrometry for determining the presence of eleven personal care products in surface and wastewaters.

    PubMed

    Pedrouzo, Marta; Borrull, Francesc; Marcé, Rosa Maria; Pocurull, Eva

    2009-10-16

    Personal care products (PCPs) are widely used emerging contaminants which can cause adverse environmental effects. This paper reports the development and validation of a method based on solid-phase extraction (SPE) and ultra-high-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (UHPLC-(ESI)MS-MS) for simultaneously determining eleven PCPs: 4 preservatives (methylparaben; ethylparaben; benzylparaben; propylparaben); 2 antimicrobial agents (triclocarban and triclosan) and 5 UV filters (2,4-dihydroxybenzophenone; 2,2-dihydroxy-4-methoxybenzophenone; benzophenone-3; octocrylene and octyldimethyl-p-aminobenzoic acid) in environmental waters in only 9 run minutes of chromatographic separation. The SPE was carried out with two polymeric cartridges (Oasis HLB and Bond Elut Plexa). The recoveries obtained with Bond Elut Plexa were between 69% and 101% for 500 mL of river waters, with the exception of octyldimethyl-p-aminobenzoic acid (46%). Limits of detection for 500 mL of river water were in the range of 1-5 ng/L. Oasis HLB was chosen for wastewater samples with recoveries between 38% and 92% (250 mL of effluents) and 36-89% (100mL of influents). In both wastewater samples, octyldimethyl-p-aminobenzoic acid and methylparaben showed the lowest recoveries (20% and 27%). The method revealed benzophenone-3 as having the highest concentration levels ( 7 ng/L) in river waters. Most of PCPs determined were found in influent waters being methylparaben and propylparaben the ones found at highest concentration with values of 5613 and 1945 ng/L, respectively. In effluent waters, significant lower levels of some PCPs were found, being benzophenone-3 the one found at the highest concentration (100 ng/L).

  4. Embryonic exposure of medaka (Oryzias latipes) to propylparaben: effects on early development and post-hatching growth.

    PubMed

    González-Doncel, Miguel; García-Mauriño, José Enrique; San Segundo, Laura; Beltrán, Eulalia M; Sastre, Salvador; Fernández Torija, Carlos

    2014-01-01

    Here we proposed a battery of non-invasive biomarkers and a histological survey to examine physiological/anatomical features in embryos, eleutheroembryos (13 days post-fertilization, dpf), and larvae (28-42 dpf) of medaka to investigate the effects of embryonic exposure to propylparaben (PrP). Concentrations <1000 μg PrP/L didn't exert early or late toxic effects. However, survivorship was affected at 4000 μg/L in eleutheroembryos and at ≥1000 μg/L in larvae. Histological alterations were found in 37.5% of eleutheroembryos exposed to 4000 μg PrP/L. Morphometric analysis of the gallbladder revealed significant dilation at ≥400 μg/L throughout embryo development. Ethoxyresorufin-O-deethylase (EROD), as indicator of cytochrome P4501A activity, didn't reveal induction/inhibition although its combination with a P4501A agonist (i.e. β-naphthoflavone) resulted in a synergic EROD response. Results suggest a low toxicity of PrP for fish and support the use of fish embryos and eleutheroembryos as alternatives of in vivo biomarkers indicative of exposure/toxicity.

  5. Experimental and theoretical insights into photochemical transformation kinetics and mechanisms of aqueous propylparaben and risk assessment of its degradation products.

    PubMed

    An, Taicheng; Fang, Hansun; Li, Guiying; Wang, Shilong; Yao, Side

    2014-08-01

    The kinetics and mechanisms of ultraviolet photochemical transformation of propylparaben (PPB) were studied. Specific kinetics scavenging experiments coupled with quantum yield determinations were used to distinguish the roles of various reactive species induced by self-sensitized and direct photolysis reactions, and the excited triplet state of PPB ((3) PPB*) was identified as the most important species to initiate the photochemical degradation of PPB in aquatic environments. The computational results of time-resolved absorption spectra proved that (3) PPB* is a highly reactive electron acceptor, and a head-to-tail hydrogen transfer mechanism probably occurs through electron coupled with proton transfer. Physical quenching by, or chemical reaction of (3) PPB* with, O2 was confirmed as a key step affecting the initial PPB transformation pathways and degradation mechanisms. The transformation products were identified and the toxicity evolutions of PPB solutions during photochemical degradation under aerobic and anaerobic conditions were compared. The results indicate that anaerobic conditions are more likely than aerobic conditions to lead to the elimination and detoxification of PPB but less likely to lead to PPB mineralization.

  6. Computational consideration on advanced oxidation degradation of phenolic preservative, methylparaben, in water: mechanisms, kinetics, and toxicity assessments.

    PubMed

    Gao, Yanpeng; An, Taicheng; Fang, Hansun; Ji, Yuemeng; Li, Guiying

    2014-08-15

    Hydroxyl radicals ((•)OH) are strong oxidants that can degrade organic pollutants in advanced oxidation processes (AOPs). The mechanisms, kinetics, and toxicity assessment of the (•)OH-initiated oxidative degradation of the phenolic preservative, methylparaben (MPB), were systematically investigated using a computational approach, as the supplementary information for experimental data. Results showed that MPB can be initially attacked by (•)OH via OH-addition and H-abstraction routes. Among these routes, the (•)OH addition to the C atom at the ortho-position of phenolic hydroxyl group was the most significant route. However, the methyl-H-abstraction route also cannot be neglected. Further, the formed transient intermediates, OH-adduct ((•)MPB-OH1) and dehydrogenated radical ((•)MPB(-H)α), could be easily transformed to several stable degradation products in the presence of O2 and (•)OH. To better understand the potential toxicity of MPB and its products to aquatic organisms, both acute and chronic toxicities were assessed computationally at three trophic levels. Both MPB and its products, particularly the OH-addition products, are harmful to aquatic organisms. Therefore, the application of AOPs to remove MPB should be carefully performed for safe water treatment.

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

    SciTech Connect

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

    2011-11-17

    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.

  8. Physical properties of parabens and their mixtures: solubility in water, thermal behavior, and crystal structures.

    PubMed

    Giordano, F; Bettini, R; Donini, C; Gazzaniga, A; Caira, M R; Zhang, G G; Grant, D J

    1999-11-01

    The peculiar solubility behavior of propylparaben (propyl ester of 4-hydroxybenzoic acid) in aqueous solution, when tested separately and together with methyl-, ethyl-, and butyl-parabens, has been investigated in detail. The results clearly indicate that the decrease in solubility (approximately 50% compared to the solubility value of propylparaben alone) is typical of those mixtures containing also ethylparaben, as demonstrated by solubility experiments on binary, ternary, and quaternary mixtures of the parabens. Phase diagrams of all the six binaries show that propylparaben and ethylparaben are the only pair that form almost ideal solid solutions near the melting temperatures. Moreover, phase-solubility analysis shows that propylparaben and ethylparaben, at room temperature, can also form solid solutions whose solubility is related to the composition of the solid phase at equilibrium. To achieve an independent confirmation of the possible solid solution formation that supports the above interpretation of the solubility behavior, the crystal structures of the four parabens have been examined and isostructurality has been found to exist only between ethylparaben and propylparaben. Powder X-ray diffraction has also been performed on ethylparaben, propylparaben, and their solid solutions obtained by recrystallization from water. The progressive shift of distinctive diffraction peaks with phase composition clearly indicates that propylparaben and ethylparaben form substitutional solid solutions. The small value (<1) of the disruption index provides thermodynamic support for substitutional solid solutions based on isostructural crystals.

  9. Estrogenic activity of cosmetic components in reporter cell lines: parabens, UV screens, and musks.

    PubMed

    Gomez, E; Pillon, A; Fenet, H; Rosain, D; Duchesne, M J; Nicolas, J C; Balaguer, P; Casellas, C

    2005-02-27

    In this work, the estrogenic effects of three classes of substances included in cosmetic formulations-parabens, ultraviolet (UV) screens, and musk fragrances-were studied. Their estrogenic activity was measured with the use of three reporter cell lines: HELN, HELN ERalpha, and HELN ERbeta. These three cell lines allowed for the measurement of estrogenic activity toward estrogen receptors alpha and beta (ERalpha and ERbeta, while taking nonspecific interactions into account. Eight of the 15 substances tested showed specific estrogenic activity with the following degree of potency on ERalpha butylparaben > propylparaben > homosalate = octyl-dimethyl-PABA = 4-methyl-benzylidenecamphor = octyl-methoxycinnamate > ethylparaben = galaxolide. Among these active substances, parabens activated ERalpha and ERbeta similarly, UV screens activated ERalpha moderately and had almost no effect on ERbeta, and fragrances did not activate ERbeta. Methylparaben, ethylparaben, musk moskene, celestolide, and cashmeran did not activate estrogenic responses up to 10(-5) M. Musk ketone and benzophenone-3 were not considered estrogenic at 10(-5) M.

  10. Propylparaben sensitizes heat-resistant Salmonella Enteritidis and Salmonella Oranienburg to thermal inactivation in liquid egg albumen.

    PubMed

    Gurtler, Joshua B; Jin, Tony Z

    2012-03-01

    Propyl p-hydroxybenzoic acid (propylparaben [PRPA]) is a phenolic antioxidant, known to occur in nature and used as a microbiostat in foods, feeds, pharmaceuticals, cosmetics, and medications. The U.S. Department of Agriculture, Food Safety and Inspection Service (FSIS) requires that liquid egg white (LEW) be pasteurized at 56.7°C for 3.5 min. This study evaluated the effects of PRPA on the pasteurization sensitivity of Salmonella in LEW. When LEW (pH 7.8) was pasteurized under FSIS conditions, salmonellae declined by 0.5, 4.6, 4.5, > 7.0, and > 7.0 log CFU/ml, with 0, 125, 250, 500, or 1,000 ppm of PRPA, respectively, and D(56.7°C)-values were 2.99, 1.05, 0.68, 0.26 and ≤0.16 min. Albumen (pH 8.9) pasteurized under FSIS standards incurred salmonellae reductions of 3.3, 2.8, 5.2, > 7.0, and > 7.0 log CFU/ml, with 0, 125, 250, 500, or 1,000 ppm of PRPA, respectively, while D(56.7°C)-values were 0.87, 0.99, 0.66, 0.22, and 0.09 min. Adding 500 ppm of PRPA to albumen (pH 7.8) reduced D(56.7°C)-values more than 11-fold, and reduced the time to achieve a 5-log reduction from 15.0 to only 1.3 min. A 7-log reduction in plain LEW (pH 7.8) at 56.7°C required 20.9 min, versus only 1.8 and 1.1 min with 500 and 1,000 ppm of PRPA, respectively. Furthermore, a 7-log reduction in plain LEW (pH 8.9) required 6.1 min, versus only 1.5 and 0.6 min with 500 and 1,000 ppm of PRPA, respectively. This study is the first to report the efficacy of PRPA (pK(a) = 8.4) in sensitizing Salmonella in LEW to thermal pasteurization, while documenting that PRPA retains its antibacterial efficacy at pH levels as high as 8.9.

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

    PubMed

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

    2012-12-01

    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).

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

    PubMed

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

    2013-03-19

    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 μM 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.

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

    PubMed

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

    2013-09-01

    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 μg/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

  14. Application of Fenton oxidation to reduce the toxicity of mixed parabens.

    PubMed

    Martins, Rui C; Gmurek, Marta; Rossi, André F; Corceiro, Vanessa; Costa, Raquel; Quinta-Ferreira, M Emília; Ledakowicz, Stanislaw; Quinta-Ferreira, Rosa M

    2016-10-01

    The aims of the present work were to assess the application of a chemical process to degrade a mixture of parabens and determine the influence of a natural river water matrix on toxicity. Model effluents containing either a single compound, namely methylparaben, ethylparaben, propylparaben, butylparaben, benzylparaben or p-hydroxybenzoic acid, or to mimic realistic conditions a mixture of the six compounds was used. Fenton process was applied to reduce the organic charge and toxic properties of the model effluents. The efficiency of the decontamination has been investigated using a chemical as well as a toxicological approach. The potential reduction of the effluents' toxicity after Fenton treatment was evaluated by assessing (i) Vibrio fischeri luminescence inhibition, (ii) lethal effects amongst freshwater Asian clams (Corbicula fluminea), and (iii) the impact on mammalian neuronal activity using brain slices. From the environmental point of view such a broad toxicity analysis has been performed for the first time. The results indicate that Fenton reaction is an effective method for the reduction of chemical oxygen demand of a mixture of parabens and their toxicity to V. fischeri and C. fluminea. However, no important differences were found between raw and treated samples in regard to mammalian neuronal activity.

  15. Parabens in male infertility-is there a mitochondrial connection?

    PubMed

    Tavares, Renata S; Martins, Fátima C; Oliveira, Paulo J; Ramalho-Santos, João; Peixoto, Francisco P

    2009-01-01

    Parabens are widely used as preservatives in many foods, cosmetics, toiletries, and pharmaceuticals due to their relatively low toxicity profile and to a long history of safe use. Parabens are alkyl esters of p-hydroxybenzoic acid and typically include methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben and benzylparaben. These compounds are known to have a null or very weak estrogenic activity in estrogen receptor assays in vitro. In recent years, an increasing concern has emerged regarding possible adverse effects of chemicals in food and in cosmetics on human reproduction outcomes. In developed countries about 15% of human couples are affected by infertility, almost half of these cases attributed to men, through low sperm motility or/and sperm count. It is known that a significant number of cases of male infertility results from exposure to xenobiotics, and also that testis mitochondria are particularly affected by drug-induced toxicity. The present review discusses evidence that parabens may not be as safe as initially thought, and suggests that the interaction between parabens and mitochondrial function in the testis may be key in explaining the contribution of parabens for a decrease in reproductive potential.

  16. Combining MOSCED with molecular simulation free energy calculations or electronic structure calculations to develop an efficient tool for solvent formulation and selection

    NASA Astrophysics Data System (ADS)

    Cox, Courtney E.; Phifer, Jeremy R.; Ferreira da Silva, Larissa; Gonçalves Nogueira, Gabriel; Ley, Ryan T.; O'Loughlin, Elizabeth J.; Pereira Barbosa, Ana Karolyne; Rygelski, Brett T.; Paluch, Andrew S.

    2017-02-01

    Solubility parameter based methods have long been a valuable tool for solvent formulation and selection. Of these methods, the MOdified Separation of Cohesive Energy Density (MOSCED) has recently been shown to correlate well the equilibrium solubility of multifunctional non-electrolyte solids. However, before it can be applied to a novel solute, a limited amount of reference solubility data is required to regress the necessary MOSCED parameters. Here we demonstrate for the solutes methylparaben, ethylparaben, propylparaben, butylparaben, lidocaine and ephedrine how conventional molecular simulation free energy calculations or electronic structure calculations in a continuum solvent, here the SMD or SM8 solvation model, can instead be used to generate the necessary reference data, resulting in a predictive flavor of MOSCED. Adopting the melting point temperature and enthalpy of fusion of these compounds from experiment, we are able to predict equilibrium solubilities. We find the method is able to well correlate the (mole fraction) equilibrium solubility in non-aqueous solvents over four orders of magnitude with good quantitative agreement.

  17. Ozonation of parabens in aqueous solution: kinetics and mechanism of degradation.

    PubMed

    Tay, Kheng Soo; Rahman, Noorsaadah Abd; Abas, Mhd Radzi Bin

    2010-12-01

    This study investigated the reaction kinetics and degradation mechanism of parabens (methylparaben, ethylparaben, propylparaben and butylparaben) during ozonation. Experiments were performed at pH 2, 6 and 12 to determine the rate constants for the reaction of protonated, undissociated and dissociated paraben with ozone. The rate constants for the reaction of ozone with dissociated parabens (3.3 × 10(9)-4.2 × 10(9)M(-1)s(-1)) were found to be 10(4) times higher than the undissociated parabens (2.5 × 10(5)-4.4 × 10(5)M(-1)s(-1)) and 10(7) times higher than with the protonated parabens (1.02 × 10(2)-1.38 × 10(2)M(-1)s(-1)). The second-order rate constants for the reaction between parabens with hydroxyl radicals were found to vary from 6.8 × 10(9) to 9.2 × 10(9)M(-1)s(-1). Characterization of degradation by-products (DBPs) formed during the ozonation of each selected parabens has been carried out using GCMS after silylation. Twenty DBPs formed during ozonation of selected parabens have been identified. Hydroxylation has been found to be the major reaction for the formation of the identified DBPs. Through the hydroxylation reaction, a variety of hydroxylated parabens was formed.

  18. Theoretical investigation on the kinetics and mechanisms of hydroxyl radical-induced transformation of parabens and its consequences for toxicity: Influence of alkyl-chain length.

    PubMed

    Gao, Yanpeng; Ji, Yuemeng; Li, Guiying; An, Taicheng

    2016-03-15

    As emerging organic contaminants (EOCs), the ubiquitous presence of preservative parabens in water causes a serious environmental concern. Hydroxyl radical ((•)OH) is a strong oxidant that can degrade EOCs through photochemistry in surface water environments as well as in advanced oxidation processes (AOPs). To better understand the degradation mechanisms, kinetics, and products toxicity of the preservative parabens in aquatic environments and AOPs, the (•)OH-initiated degradation reactions of the four parabens were investigated systematically using a computational approach. The four studied parabens with increase of alkyl-chain length were methylparaben (MPB), ethylparaben (EPB), propylparaben (PPB), and dibutylparaben (BPB). Results showed that the four parabens can be initially attacked by (•)OH through (•)OH-addition and H-abstraction routes. The (•)OH-addition route was more important for the degradation of shorter alkyl-chain parabens like MPB and EPB, while the H-abstraction route was predominant for the degradation of parabens with longer alkyl-chain for example PPB and BPB. In assessing the aquatic toxicity of parabens and their degradation products using the model calculations, the products of the (•)OH-addition route were found to be more toxic to green algae than original parabens. Although all degradation products were less toxic to daphnia and fish than corresponding parental parabens, they could be still harmful to these aquatic organisms. Furthermore, as alkyl-chain length increased, the ecotoxicity of parabens and their degradation products was found to be also increased.

  19. Porous-membrane-protected polyaniline-coated SBA-15 nanocomposite micro-solid-phase extraction followed by high-performance liquid chromatography for the determination of parabens in cosmetic products and wastewater.

    PubMed

    Ara, Katayoun Mahdavi; Pandidan, Sara; Aliakbari, Azam; Raofie, Farhad; Amini, Mostafa M

    2015-04-01

    A SBA-15/polyaniline para-toluenesulfonic acid nanocomposite supported micro-solid-phase extraction procedure has been developed for the extraction of parabens (methylparaben, ethylparaben, and propylparaben) from wastewater and cosmetic products. The variables of interest in the extraction process were pH of sample, sample and eluent volumes, sorbent amount, salting-out effect, extraction and desorption time, and stirring rate. A Plackett-Burman design was performed for the screening of variables in order to determine the significant variables affecting the extraction efficiency. Then, the significant factors were optimized by using a central composite design. The optimum experimental conditions found at 50 mL sample solution, extraction and desorption times of 40 and 20 min, respectively, 500 μL of 3% v/v acetic acid in methanol as eluent, 0.01 M salt addition, and 10 mg of the sorbent. Under the optimum conditions, the developed method provided detection limits in the range of 0.08-0.4 ng/mL with good repeatability (RSD% < 7) and linearity (r(2) = 0.997-0.999) for the three parabens. Finally, this fast and efficient method was employed for the determination of target analytes in cosmetic products and wastewater, and satisfactory results were obtained.

  20. A proposed study on the transplacental transport of parabens in the human placental perfusion model.

    PubMed

    Mathiesen, Line; Zuri, Giuseppina; Andersen, Maria H; Knudsen, Lisbeth E

    2013-12-01

    Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim to determine the transport kinetics of these parabens across the human placenta, and to investigate placental metabolism, including differences in transport due to molecular characteristics. This will facilitate assessment of the risks associated with the use of paraben-containing products during pregnancy.

  1. Parabens determination in cosmetic and personal care products exploiting a multi-syringe chromatographic (MSC) system and chemiluminescent detection.

    PubMed

    Rodas, Melisa; Portugal, Lindomar A; Avivar, Jessica; Estela, José Manuel; Cerdà, Víctor

    2015-10-01

    Parabens are widely used in dairy products, such as in cosmetics and personal care products. Thus, in this work a multi-syringe chromatographic (MSC) system is proposed for the first time for the determination of four parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) in cosmetics and personal care products, as a simpler, practical, and low cost alternative to HPLC methods. Separation was achieved using a 5mm-long precolumn of reversed phase C18 and multi-isocratic separation, i.e. using two consecutive mobile phases, 12:88 acetonitrile:water and 28:72 acetonitrile:water. The use of a multi-syringe buret allowed the easy implementation of chemiluminescent (CL) detection after separation. The chemiluminescent detection is based on the reduction of Ce(IV) by p-hydroxybenzoic acid, product of the acid hydrolysis of parabens, to excite rhodamine 6G (Rho 6G) and measure the resulting light emission. Multivariate designs combined with the concepts of multiple response treatments and desirability functions have been employed to simultaneously optimize and evaluate the responses. The optimized method has proved to be sensitive and precise, obtaining limits of detection between 20 and 40 µg L(-1) and RSD <4.9% in all cases. The method was satisfactorily applied to cosmetics and personal care products, obtaining no significant differences at a confidence level of 95% comparing with the HPLC reference method.

  2. Rapid determination of parabens in seafood sauces by high-performance liquid chromatography: A practical comparison of core-shell particles and sub-2 μm fully porous particles.

    PubMed

    Ye, Jing; Cao, Xiaoji; Cheng, Zhuo; Qin, Ye; Lu, Yanbin

    2015-12-01

    In this work, the chromatographic performance of superficially porous particles (Halo core-shell C18 column, 50 mm × 2.1 mm, 2.7 μm) was compared with that of sub-2 μm fully porous particles (Acquity BEH C18 , 50 mm × 2.1 mm, 1.7 μm). Four parabens, methylparaben, ethylparaben, propylparaben, and butylparaben, were used as representative compounds for calculating the plate heights in a wide flow rate range and analyzed on the basis of the Van Deemter and Knox equations. Theoretical Poppe plots were constructed for each column to compare their kinetic performance. Both phases gave similar minimum plate heights when using nonreduced coordinates. Meanwhile, the flat C-term of the core-shell column provided the possibilities for applying high flow rates without significant loss in efficiency. The low backpressure of core-shell particles allowed this kind of column, especially compatible with conventional high-performance liquid chromatography systems. Based on these factors, a simple high-performance liquid chromatography method was established and validated for the determination of parabens in various seafood sauces using the Halo core-shell C18 column for separation.

  3. Application of vesicular coacervate phase for microextraction based on solidification of floating drop.

    PubMed

    Moradi, Morteza; Yamini, Yadollah

    2012-03-16

    A new, efficient and environmentally friendly method for the analysis of parabens as model compounds was developed using solidified floating vesicular coacervative drop microextraction (SFVCDME). A supramolecular solvent consisting of vesicles of decanoic acid in the nano- and microscale regimes was firstly used as the solvent in solidification of floating drop microextraction. The solvent was produced from the coacervation of decanoic acid aqueous vesicles in the presence of tetrabutylammonium (Bu(4)N(+)). Methylparaben (MP), ethylparaben (EP), and propylparaben (PP) were extracted on the basis of hydrophobic and π-cation interactions and the formation of hydrogen bonds. Microliter volume of vesicular coacervative droplet was delivered to the surface of the aqueous sample, and the sample was stirred for a desired time. The sample vial was cooled by immersing it into an ice bath for 3 min. The solidified solvent was transferred into a suitable vial and melted immediately. Twenty microliter of the vesicular coacervative solvent was directly injected to high-performance liquid chromatography-ultraviolet detection, with no need to dilution or solvent evaporation. Several parameters affecting the microextraction efficiency including sample temperature, stirring rate, pH, salt effect, volume of the solvent and extraction time were investigated and optimized. Under optimum conditions, preconcentration factors and relative recoveries of the studied compounds were obtained in the range of 81-174 and 91-108%, respectively; and the performance of the method was comparable with that of solid-phase extraction as the reference method.

  4. Determination of personal care products and hormones in leachate and groundwater from Polish MSW landfills by ultrasound-assisted emulsification microextraction and GC-MS.

    PubMed

    Kapelewska, Justyna; Kotowska, Urszula; Wiśniewska, Katarzyna

    2016-01-01

    Determination of the endocrine disrupting compounds (EDCs) in leachate and groundwater samples from the landfill sites is very important because of the proven harmful effects of these compounds on human and animal organisms. A method combining ultrasound-assisted emulsification microextraction (USAEME) and gas chromatography-mass spectrometry (GC-MS) was developed for simultaneous determination of seven personal care products (PCPs): methylparaben (MP), ethylparaben (EP), propylparaben (PP), buthylparaben (BP), benzophenone (BPh), 3-(4-methylbenzylidene)camphor (4-MBC), N,N-diethyltoluamide (DEET), and two hormones: estrone (E1) and β-estradiol (E2) in landfill leachate and groundwater samples. The limit of detection (LOD)/limit of quantification (LOQ) values in landfill leachate and groundwater samples were in the range of 0.003-0.083/0.009-0.277 μg L(-1) and 0.001-0.015/0.002-0.049 μg L(-1), respectively. Quantitative recoveries and satisfactory precision were obtained. All studied compounds were found in the landfill leachates from Polish municipal solid waste (MSW) landfills; the concentrations were between 0.66 and 202.42 μg L(-1). The concentration of pollutants in groundwater samples was generally below 0.1 μg L(-1).

  5. Antifungal activity of food additives in vitro and as ingredients of hydroxypropyl methylcellulose-lipid edible coatings against Botrytis cinerea and Alternaria alternata on cherry tomato fruit.

    PubMed

    Fagundes, Cristiane; Pérez-Gago, María B; Monteiro, Alcilene R; Palou, Lluís

    2013-09-16

    The antifungal activity of food additives or 'generally recognized as safe' (GRAS) compounds was tested in vitro against Botrytis cinerea and Alternaria alternata. Radial mycelial growth of each pathogen was measured in PDA Petri dishes amended with food preservatives at 0.2, 1.0, or 2.0% (v/v) after 3, 5, and 7 days of incubation at 25 °C. Selected additives and concentrations were tested as antifungal ingredients of hydroxypropyl methylcellulose (HPMC)-lipid edible coatings. The curative activity of stable coatings was tested in in vivo experiments. Cherry tomatoes were artificially inoculated with the pathogens, coated by immersion about 24 h later, and incubated at 20 °C and 90% RH. Disease incidence and severity (lesion diameter) were determined after 6, 10, and 15 days of incubation and the 'area under the disease progress stairs' (AUDPS) was calculated. In general, HPMC-lipid antifungal coatings controlled black spot caused by A. alternata more effectively than gray mold caused by B. cinerea. Overall, the best results for reduction of gray mold on cherry tomato fruit were obtained with coatings containing 2.0% of potassium carbonate, ammonium phosphate, potassium bicarbonate, or ammonium carbonate, while 2.0% sodium methylparaben, sodium ethylparaben, and sodium propylparaben were the best ingredients for coatings against black rot.

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

    PubMed

    Klopčič, Ivana; Kolšek, Katra; Dolenc, Marija Sollner

    2015-01-22

    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 μM and 10 nM) and compared their glucocorticoid-like activity. At the concentration of 1 μM 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 μM 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 μM. 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

  7. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum.

    PubMed

    Barr, L; Metaxas, G; Harbach, C A J; Savoy, L A; Darbre, P D

    2012-03-01

    The concentrations of five esters of p-hydroxybenzoic acid (parabens) were measured using HPLC-MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n-propylparaben [16.8 (range 0-2052.7)] and methylparaben [16.6 (range 0-5102.9)]; levels were lower for n-butylparaben [5.8 (range 0-95.4)], ethylparaben [3.4 (range 0-499.7)] and isobutylparaben 2.1 (range 0-802.9). The overall median value for total paraben was 85.5 ng g(-1) tissue (range 0-5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37-91 years), length of breast feeding (0-23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n-propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA).

  8. 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

    Smith, D.J.

    1981-05-01

    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).

  9. 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.

    PubMed

    Smith, D J

    1981-05-01

    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).

  10. 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.

    PubMed

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

    2007-01-01

    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.

  11. Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol A, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry.

    PubMed

    Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

    2016-11-16

    In this paper, a method for the determination of four groups of endocrine-disrupting compounds in human hair is proposed. Target compounds were a plastic monomer (bisphenol A), three parabens commonly used as preservatives (methylparaben, ethylparaben and propylparaben), six perfluoroalkyl compounds commonly used as water, oil and dirt repellents (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, with alkyl chains from four to eight carbon atoms) and a brominated flame retardant (hexabromocyclododecane). All of them are of especial concern to human health because they are utilized in many everyday products. The method is based on hair incubation with methanol/acetic acid solution (85:15, v/v), extraction with acetone for 15 min in an ultrasonic bath and analysis by liquid chromatography-electrospray-tandem mass spectrometry in negative ionization mode. Limits of quantification in hair samples ranged from 0.6 ng g(-1) to 6.1 ng g(-1), except for hexabromocyclododecane (36 ng g(-1)). Recoveries were higher than 69%. Intra-day and inter-day precision, expressed as relative standard deviation, were lower than 15% and 10%, respectively. The applicability of the method was proven by analyzing the target compounds in hair samples from six volunteers. High frequencies of detection and concentrations were obtained for bisphenol A (83% of samples; concentrations up to 158 ng g(-1)) and parabens (100% of samples; concentrations up to 624 ng g(-1)). Lower concentrations were detected for the perfluoroalkyl compounds (up to 13 ng g(-1)). Hexabromocyclododecane was not detected.

  12. Effects of parabens on adipocyte differentiation.

    PubMed

    Hu, Pan; Chen, Xin; Whitener, Rick J; Boder, Eric T; Jones, Jeremy O; Porollo, Aleksey; Chen, Jiangang; Zhao, Ling

    2013-01-01

    Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. However, research on the effects of parabens on health is limited, and the effects of parabens on adipogenesis have not been systematically studied. Here, we report that (1) parabens promote adipogenesis (or adipocyte differentiation) in murine 3T3-L1 cells, as revealed by adipocyte morphology, lipid accumulation, and mRNA expression of adipocyte-specific markers; (2) the adipogenic potency of parabens is increased with increasing length of the linear alkyl chain in the following potency ranking order: methyl- < ethyl- < propyl- < butylparaben. The extension of the linear alkyl chain with an aromatic ring in benzylparaben further augments the adipogenic ability, whereas 4-hydroxybenzoic acid, the common metabolite of all parabens, and the structurally related benzoic acid (without the OH group) are inactive in promoting 3T3-L1 adipocyte differentiation; (3) parabens activate glucocorticoid receptor and/or peroxisome proliferator-activated receptor γ in 3T3-L1 preadipocytes; however, no direct binding to, or modulation of, the ligand binding domain of the glucocorticoid receptor by parabens was detected by glucocorticoid receptor competitor assays; and lastly, (4) parabens, butyl- and benzylparaben in particular, also promote adipose conversion of human adipose-derived multipotent stromal cells. Our results suggest that parabens may contribute to obesity epidemic, and the role of parabens in adipogenesis in vivo needs to be examined further.

  13. Chlorination of parabens: reaction kinetics and transformation product identification.

    PubMed

    Mao, Qianhui; Ji, Feng; Wang, Wei; Wang, Qiquan; Hu, Zhenhu; Yuan, Shoujun

    2016-11-01

    The reactivity and fate of parabens during chlorination were investigated in this work. Chlorination kinetics of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were studied in the pH range of 4.0 to 11.0 at 25 ± 1 °C. Apparent rate constants (k app) of 9.65 × 10(-3) M(-0.614)·s(-1), 1.77 × 10(-2) M(-1.019)·s(-1), 2.98 × 10(-2) M(-0.851)·s(-1), and 1.76 × 10(-2) M(-0.860)·s(-1) for MeP, EtP, PrP, and BuP, respectively, were obtained at pH 7.0. The rate constants depended on the solution pH, temperature, and NH4(+) concentration. The maximum k app was obtained at pH 8.0, and the minimum value was obtained at pH 11.0. The reaction rate constants increased with increasing temperature. When NH4(+) was added to the solution, the reaction of parabens was inhibited due to the rapid formation of chloramines. Two main transformation products, 3-chloro-parabens and 3,5-dichloro-parabens, were identified by GC-MS and LCMS-IT-TOF, and a reaction pathway was proposed. Dichlorinated parabens accumulated in solution, which is a threat to human health and the aqueous environment.

  14. Urinary levels of bisphenol A, benzophenones and parabens in Tunisian women: A pilot study.

    PubMed

    Jiménez-Díaz, I; Artacho-Cordón, F; Vela-Soria, F; Belhassen, H; Arrebola, J P; Fernández, M F; Ghali, R; Hedhili, A; Olea, N

    2016-08-15

    Bisphenol A (BPA), benzophenones and parabens are commonly used in the production of polycarbonate plastics, as UV-filters and as antimicrobial preservatives, respectively, and they are thought to exhibit endocrine disrupting properties. Exposure to these compounds remains poorly characterized in developing countries, despite the fact that certain behaviors related to westernization have the potential to influence exposure. The aim of this pilot study was to measure urinary concentrations of BPA, six different benzophenones and four parabens in 34 Tunisian women. In addition, we identified some socio-demographic and dietary predictors of exposure to these compounds. Chemical analyses were carried out by dispersive liquid-liquid microextraction (DLLME) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Detection frequencies of methylparaben (MP), ethylparaben (EP) and propylparaben (PP) ranged between 67.6 and 94.1%. Butylparaben (BP) was found in 38.2% of the analyzed samples; BPA in 64.7%; and benzophenone-1 (BP-1) and benzophenone-3 (BP-3) were detected in 91.2 and 64.7% of the analyzed samples, respectively. Urinary geometric mean concentrations of MP, EP, PP, and BP were 30.1, 1.4, 2.0 and 0.5ngmL(-1), respectively. Geometric mean concentrations of BPA, BP-1, and BP-3 were 0.4, 1.3 and 1.1ngmL(-1), respectively. Our results suggest that Tunisian women are widely exposed to BPA, parabens and some benzophenones. Further studies on the general Tunisian population are needed in order to assess the levels of exposure to these compounds and to identify sources of exposure and population groups at higher risk.

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

    PubMed

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

    2011-07-15

    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 boron-doped diamond (BDD) electrode and the development of a chromatographic method, with electrochemical detection (HPLC-ED), for determination of parabens in shampoo. A BDD (8000 ppm) electrode was adapted in a thin layer mode analytical cell consisting of a stainless steel and a platinum wire as reference and auxiliary electrodes, respectively. Chromatographic separations were obtained with a reversed phase C8 analytical column and a mobile phase of 0.025 molL(-1) disodium phosphate, pH 7.0, and acetonitrile (40:60, v/v), delivered at a flow rate of 1.0 mL min(-1). Sample preparation was performed by solid phase extraction using C18 cartridges and acetonitrile for elution. Benzylparaben was employed as internal standard. The HPLC-ED method developed, using the BDD electrode, was validated for the determination of parabens in shampoos and presented adequate linearity (>0.999), in the range of 0.0125-0.500% (w/w), detectability 0.01% (w/w), precision (RSD of 2.3-9.8%) and accuracy (93.1-104.4%) and could be applied for routine quality control of shampoos containing MePa, EtPa and PrPa.

  16. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  17. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  18. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  19. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  20. 21 CFR 582.3670 - Propylparaben.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 582.3670... recognized as safe for use at a level not exceeding 0.1 percent in accordance with good manufacturing...

  1. 21 CFR 582.3490 - Methylparaben.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 582.3490... recognized as safe for use at a level not exceeding 0.1 percent in accordance with good manufacturing...

  2. Sorption of parabens by flexible tubings.

    PubMed

    Bahal, S M; Romansky, J M

    2001-08-01

    Flexible tubings are extensively used in pharmaceuticals, food industry, and in hospitals. This study was undertaken to compare various flexible tubings to determine their sorption characteristics, using methyl and propyl parabens. After 24 h, some tubings showed 100% sorption of propylparaben and over 40% for methylparaben. Significant losses were observed within a few hours using several tubings. For methylparaben, the losses were in the following decreasing order of sorption: Tygon, Clearflo, silicone, Nylotube, and Newtex. For propylparaben, the losses were in the following order: Tygon, Clearflo, silicone, Newtex, and Nylotube. Teflon, Zelite, and Vitube showed little to no losses of methyl and propylparaben over 120 h of study. The silicone tubing, refilled after 120 h with fresh methylparaben or propylparaben solutions, again showed significant losses within a few hours. The tubings show slow desorption when filled with the buffer vehicle. For Silastic tubing, increase in temperature from 25 to 40 degrees C, increase in pH from 3.5 to 6.5, tubing lot to lot variation, or curing with peroxide or platinum had little or no effect on paraben sorption. As expected, the sorption of parabens increased with increasing surface area of Silastic tubing. Results provided can be used to select the best tubings and to minimize paraben losses during production and filling of liquid pharmaceuticals andfood products containing these antimicrobial preservatives.

  3. In vivo and in vitro estrogen bioactivities of alkyl parabens.

    PubMed

    Lemini, Cristina; Jaimez, Ruth; Avila, María Estela; Franco, Yanira; Larrea, Fernando; Lemus, Ana Elena

    2003-07-01

    The alkyl esters of p-hydroxybenzoic acid known as parabens (Pbens) are used as preservatives in food, pharmaceutical and cosmetic formulations. They have been reported as estrogenic. Here, we present evidence for the in vivo and in vitro bioactivities and receptor binding affinities of methylparaben (MePben), ethylparaben (EtPben), propylparaben (PrPben), and butylparaben (BuPben) compared with those of estradiol (E2). Estrogenicity was studied using the uterotrophic assay in immature (Im) and adult ovariectomized (Ovx) CD1 mice, and in immature female Wistar rats (IW). Animals were subcutaneously (sc) treated for three consecutive days with different molar equivalent doses ranging from 3.62 to 1086 micromol/kg body weight of Pbens, E2 (0.036 micromol/kg), or vehicle. Pbens increased uterine weight in Im and Ovx animals and their relative uterotrophic effect to E2 (100) (RUEE2) were from 34 to 91. The relative uterotrophic potencies related to E2 (100) (RUPE2) of these compounds were from 0.003 to 0.007. The E2 ED50 for CD1 animals able to increase the uterine weight was 7 microg/kg (0.9-55 confidence limits); and that of Pbens ranged from 18 to 74 mg/kg. In IW rats, the ED50 were from 33 to 338 mg/kg. All Pbens, except MePb, competed with [3H]E2 for the estrogen receptor binding sites. The uterotrophic effects of Pbens in Im mice have a positive correlation with the side-chain length of the ester group of these compounds. The E2 and Pbens relative binding affinities (RBA) and Ki values correlated to their estrogenic activity. The NOELs values for Pbens uterotrophic activity in Im were from 0.6 to 6.5 mg/kg per day; and Ovx from 6 to 55 mg/kg. The NOELs IW ranged from 16.5 to 70 mg/kg indicating that Im were more susceptible than Ovx and IW to these effects. The data shown here confirm the estrogenicity of Pbens.

  4. Hydrolysis of 4-hydroxybenzoic acid esters (parabens) and their aerobic transformation into phenol by the resistant Enterobacter cloacae strain EM.

    PubMed

    Valkova, N; Lépine, F; Valeanu, L; Dupont, M; Labrie, L; Bisaillon, J G; Beaudet, R; Shareck, F; Villemur, R

    2001-06-01

    Enterobacter cloacae strain EM was isolated from a commercial dietary mineral supplement stabilized by a mixture of methylparaben and propylparaben. It harbored a high-molecular-weight plasmid and was resistant to high concentrations of parabens. Strain EM was able to grow in liquid media containing similar amounts of parabens as found in the mineral supplement (1,700 and 180 mg of methyl and propylparaben, respectively, per liter or 11.2 and 1.0 mM) and in very high concentrations of methylparaben (3,000 mg liter(-1), or 19.7 mM). This strain was able to hydrolyze approximately 500 mg of methyl-, ethyl-, or propylparaben liter(-1) (3 mM) in less than 2 h in liquid culture, and the supernatant of a sonicated culture, after a 30-fold dilution, was able to hydrolyze 1,000 mg of methylparaben liter(-1) (6.6 mM) in 15 min. The first step of paraben degradation was the hydrolysis of the ester bond to produce 4-hydroxybenzoic acid, followed by a decarboxylation step to produce phenol under aerobic conditions. The transformation of 4-hydroxybenzoic acid into phenol was stoichiometric. The conversion of approximately 500 mg of parabens liter(-1) (3 mM) to phenol in liquid culture was completed within 5 h without significant hindrance to the growth of strain EM, while higher concentrations of parabens partially inhibited its growth.

  5. A review of the endocrine activity of parabens and implications for potential risks to human health.

    PubMed

    Golden, Robert; Gandy, Jay; Vollmer, Guenter

    2005-06-01

    Parabens are a group of the alkyl esters of p-hydroxybenzoic acid and typically include methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben, and benzylparaben. Parabens (or their salts) are widely used as preservatives in cosmetics, toiletries, and pharmaceuticals due to their relatively low toxicity profile and a long history of safe use. Testing of parabens has revealed to varying degrees that individual paraben compounds have weakly estrogenic activity in some in vitro screening tests, such as ligand binding to the estrogen receptor, regulation of CAT gene expression, and proliferation of MCF-7 cells. Reported in vivo effects include increased uterine weight (i.e., butyl-, isobutyl-, and benzylparaben) and male reproductive-tract effects (i.e., butyl- and propylparaben). However, in relation to estrogen as a control during in vivo studies, the parabens with activity are many orders of magnitude less active than estrogen. While exposure to sufficient doses of exogenous estrogen can increase the risk of certain adverse effects, the presumption that similar risks might also result from exposure to endocrine-active chemicals (EACs) with far weaker activity is still speculative. In assessing the likelihood that exposure to weakly active EACs might be etiologically associated with adverse effects due to an endocrine-mediated mode of action, it is paramount to consider both the doses and the potency of such compounds in comparison with estrogen. In this review, a comparative approach involving both dose and potency is used to assess whether in utero or adult exposure to parabens might be associated with adverse effects mediated via an estrogen-modulating mode of action. In utilizing this approach, the paraben doses required to produce estrogenic effects in vivo are compared with the doses of either 17beta-estradiol or diethylstilbestrol (DES) that are well established in their ability to affect endocrine activity. Where possible

  6. Mechanism of p-hydroxybenzoate ester-induced mitochondrial dysfunction and cytotoxicity in isolated rat hepatocytes.

    PubMed

    Nakagawa, Y; Moldéus, P

    1998-06-01

    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 cytotoxicity was accompanied by losses of cellular ATP, total adenine nucleotide pools, and reduced glutathione, independently of lipid peroxidation and protein thiol oxidation. In the comparative toxic effects based on cell viability, ATP level, and rhodamine 123 retention, butyl- and isobutyl-parabens were more toxic than propyl- and isopropyl-parabens, and ethyl- and methyl-parabens and p-hydroxybenzoic acid were less toxic than propyl-paraben. The addition of propyl-paraben to isolated hepatic mitochondria reduced state 3 respiration with NAD+-linked substrates (pyruvate plus malate) and/or with an FAD-linked substrate (succinate plus rotenone), whereas state 3 respiration with ascorbate plus tetramethyl-p-phenylenediamine (cytochrome oxidase-linked respiration) was not affected significantly by propyl-paraben. Further, the addition of these parabens caused a concentration-dependent increase in the rate of state 4 oxygen consumption, indicating an uncoupling effect. The rate of state 3 oxygen consumption was inhibited by propyl-paraben, butyl-paraben, and their chain isomers. These results indicate that a) propyl-paraben-induced cytotoxicity is mediated by the parent compound rather than by its metabolite p-hydroxybenzoic acid; b) the toxicity is associated with ATP depletion via impairment of mitochondrial function related to membrane potential and/or oxidative phosphorylation; and c) the toxic potency of parabens to hepatocytes or mitochondria depends on the relative elongation of alkyl side-chains esterified to the carboxyl

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

    PubMed Central

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

    2014-01-01

    Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood. The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6–11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother–child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors. There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 μg/L; ΣDiNP 37.8 μg/L; MBzP 19.9 μg/L; MnBP 76.9 μg/L) than the mothers (ΣDEHP 38.4 μg/L; ΣDiNP 33.8 μg/L; MBzP 12.8 μg/L; MnBP 63.0 μg/L). Conversely, the mother's levels of parabens (MetP 37.8 μg/L; ProP 13.9 μg/L) and MEP (43.4 μg/L) were higher than the children's levels of parabens (MetP 6.8 μg/L; ProP 2.1 μg/L) and MEP (28.8 μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p = < 0.001; MnBP p = 0.001–0.002), which is probably due to higher presence of PVC in floorings and wall

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

    PubMed

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

    2014-12-01

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

  9. Occurrence and analysis of parabens in municipal sewage sludge from wastewater treatment plants in Madrid (Spain).

    PubMed

    Albero, Beatriz; Pérez, Rosa Ana; Sánchez-Brunete, Consuelo; Tadeo, José Luis

    2012-11-15

    A rapid method for determination of seven parabens and two chlorinated by-products in sewage sludge was developed based on matrix solid-phase dispersion and gas chromatography-tandem mass spectrometry. The analytical procedure showed good recoveries that ranged from 80 to 125%, with relative standard deviations lower than 12% and low detection limits, ranging from 0.1 to 2.0 ng g(-1) dry weight. The developed method was applied to the analysis of sewage sludge collected during 2010 in 19 wastewater treatment plants (WWTPs) located in various urban, industrial or rural zones in Madrid (Spain). Methylparaben was found in most of the WWTPs sampled (95%) at levels between 5.1 and 26.2 ng g(-1) dry weight and propylparaben was detected in 74% of the WWTPs at levels up to 44.1 ng g(-1) dry weight. In order to study the temporal variation of parabens and two chlorinated parabens during a four-year period, sludge samples were collected from 3 selected WWTPs. The levels of methylparaben encountered were rather constant throughout the sampling period whereas propylparaben levels slightly increased. In one of the WWTPs monitored, isopropylparaben was found at the beginning of the sampling period but its content decreased and was not detected in the 2010 sampling.

  10. Aquatic toxicity and ecological risk assessment of seven parabens: Individual and additive approach.

    PubMed

    Yamamoto, Hiroshi; Tamura, Ikumi; Hirata, Yoshiko; Kato, Jun; Kagota, Keiichiro; Katsuki, Shota; Yamamoto, Atsushi; Kagami, Yoshihiro; Tatarazako, Norihisa

    2011-12-01

    In the present study, aquatic concentrations of seven parabens were determined in urban streams highly affected by treated or untreated domestic sewage in Tokushima and Osaka, Japan. The detected highest concentrations were 670, 207, and 163ngl(-1) for methylparaben, n-propylparaben, and n-butylparaben, respectively in sampling sites with watershed area of no sewer system in Tokushima. Conventional acute/chronic toxicity tests were conducted using medaka (Oryzias latipes), Daphnia magna, and Psuedokirchneriella subcapitata for four parabens, which was consistent with our previous study on three parabens, n-butylparaben, i-butylparaben, and benzylparaben. The aquatic toxicity on fish, daphnia, and algae was weaker for the parabens with a shorter alkyl chain than those with a longer alkyl chain as predicted by their hydrophobicity. Medaka vitellogenin assays and DNA microarray analysis were carried out for methylparaben and found induction of significant vitellogenin in male medaka at 630μgl(-1) of methylparaben, while the expression levels of genes encoding proteins such as choriogenin and vitellogenin increased for concentrations at 10μgl(-1) of methylparaben. Measured environmental concentrations (MECs) of seven parabens in Tokushima and Osaka were divided by predicted no effect concentrations (PNECs) and hazard quotient (MEC/PNEC) was determined for individual parabens. The MEC/PNEC was highest for n-propylparaben and was 0.010 followed by n-butylparaben (max. of 0.0086) and methylparaben (max. of 0.0042). The sum of the MEC/PNEC for the seven parabens was 0.0049. Equivalence factors were assigned for each paraben on the basis of the toxicity of n-butylparaben for each species, and n-butylparaben equivalence was calculated for the measured environmental concentrations. The MEC/PNEC approach was also conducted for the n-butylparaben-based equivalence values. The maximum MEC/PNEC was 0.018, which is lower than the trigger level for further detailed study such as

  11. "Parabenoia" Debunked, or "Who's Afraid of Parabens?".

    PubMed

    Sasseville, Denis; Alfalah, Maisa; Lacroix, Jean-Philip

    2015-01-01

    Parabens have been used as preservatives in foods, injectables, and topical preparations for nearly 10 decades. Present in nature, rapidly metabolized by skin and liver enzymes, they have an excellent safety record. However, in the past 15 years, they have been under scrutiny for their alleged estrogenic and antiandrogenic effects, as well as their putative role in promoting cancerogenesis through endocrine disruption. Scientific articles supporting these assertions have led the European Community to ban or restrict the use of some parabens. Despite that methylparaben and ethylparaben have negligible endocrine disruption activity, the food, pharmaceutical, and cosmetic industries are under pressure from scare campaigns in the media and are responding by replacing parabens with other biocides that cause multiple cases, and even worldwide epidemics, of allergic contact sensitization. In the present review, we present a balanced account of the published literature about the metabolism and potential toxicology of parabens.

  12. Surfactant and temperature effects on paraben transport through silicone membranes.

    PubMed

    Waters, Laura J; Dennis, Laura; Bibi, Aisha; Mitchell, John C

    2013-08-01

    This study investigates the effects of two surfactants (one anionic and one non-ionic) and controlled modifications in temperature (298-323K) on the permeation of two structurally similar compounds through a silicone membrane using a Franz diffusion cell system. In all cases the presence of an anionic surfactant, namely sodium dodecyl sulphate (SDS), reduced the permeation of both compounds (methylparaben and ethylparaben) over a period of 24h. The degree of permeation reduction was proportional to the concentration of surfactant with a maximum effect observed, with an average reduction of approximately 50%, at the highest surfactant concentration of 20mM. Differences were seen around the critical micelle concentration (CMC) of SDS implying the effect was partially connected with the favoured formation of micelles. In contrast, the presence of non-ionic surfactant (Brij 35) had no effect on the permeation of methylparaben or ethylparaben at any of the concentrations investigated, both above and below the CMC of the surfactant. From these findings the authors conclude that the specific effects of SDS are a consequence of ionic surfactant-silicone interactions retarding the movement of paraben through the membrane through indirect modifications to the surface of the membrane. As expected, an increase in experimental temperature appeared to enhance the permeation of both model compounds, a finding that is in agreement with previously reported data. Interestingly, in the majority of cases this effect was optimum at the second highest temperature studied (45°C) which suggests that permeation is a temperature-dependent phenomenon.

  13. Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells.

    PubMed

    Khanna, Sugandha; Darbre, Philippa D

    2013-05-01

    Parabens (alkyl esters of p-hydroxybenzoic acid) are used extensively as preservatives in consumer products, and intact esters have been measured in several human tissues. Concerns of a potential link between parabens and breast cancer have been raised, but mechanistic studies have centred on their oestrogenic activity and little attention has been paid to any carcinogenic properties. In the present study, we report that parabens can induce anchorage-independent growth of MCF-10A immortalized but non-transformed human breast epithelial cells, a property closely related to transformation and a predictor of tumour growth in vivo. In semi-solid methocel suspension culture, MCF-10A cells produced very few colonies and only of a small size but the addition of 5 × 10(-4) M methylparaben, 10(-5) M n-propylparaben or 10(-5) M n-butylparaben resulted in a greater number of colonies per dish (P < 0.05 in each case) and an increased average colony size (P < 0.001 in each case). Dose-responses showed that concentrations as low as 10(-6) M methylparaben, 10(-7) M n-propylparaben and 10(-7) M n-butylparaben could increase colony numbers (P = 0.016, P = 0.010, P = 0.008, respectively): comparison with a recent measurement of paraben concentrations in human breast tissue samples from 40 mastectomies (Barr et al., 2012) showed that 22/40 of the patients had at least one of the parabens at the site of the primary tumour at or above these concentrations. To our knowledge, this is the first study to report that parabens can induce a transformed phenotype in human breast epithelial cells in vitro, and further investigation is now justified into a potential link between parabens and breast carcinogenesis.

  14. Development, Validation and Application of RP-HPLC Method: Simultaneous Determination of Antihistamine and Preservatives with Paracetamol in Liquid Formulations and Human Serum

    PubMed Central

    Hasan, Najmul; Chaiharn, Mathurot; Toor, Umair Ali; Mirani, Zulfiqar Ali; Sajjad, Ghulam; Sher, Nawab; Aziz, Mubashir; Siddiqui, Farhan Ahmed

    2016-01-01

    In this article we describe development and validation of stability indicating, accurate, specific, precise and simple Ion-pairing RP-HPLC method for simultaneous determination of paracetamol and cetirizine HCl along with preservatives i.e. propylparaben, and methylparaben in pharmaceutical dosage forms of oral solution and in serum. Acetonitrile: Buffer: Sulfuric Acid (45:55:0.3 v/v/v) was the mobile phase at flow rate 1.0 mL min-1 using a Hibar® Lichrosorb® C18 column and monitored at wavelength of 230nm. The averages of absolute and relative recoveries were found to be 99.3%, 99.5%, 99.8% and 98.7% with correlation coefficient of 0.9977, 0.9998, 0.9984, and 0.9997 for cetirizine HCl, paracetamol, methylparaben and Propylparaben respectively. The limit of quantification and limit of detection were in range of 0.3 to 2.7 ng mL-1 and 0.1 to 0.8 ng mL-1 respectively. Under stress conditions of acidic, basic, oxidative, and thermal degradation, maximum degradation was observed in basic and oxidative stress where a significant impact was observed while all drugs were found almost stable in the other conditions. The developed method was validated in accordance with ICH and AOAC guidelines. The proposed method was successfully applied to quantify amount of paracetamol, cetirizine HCl and two most common microbial preservatives in bulk, dosage form and physiological fluid. PMID:27651840

  15. Design Space Approach for Preservative System Optimization of an Anti-Aging Eye Fluid Emulsion.

    PubMed

    Lourenço, Felipe Rebello; Francisco, Fabiane Lacerda; Ferreira, Márcia Regina Spuri; Andreoli, Terezinha De Jesus; Löbenberg, Raimar; Bou-Chacra, Nádia

    2015-01-01

    The use of preservatives must be optimized in order to ensure the efficacy of an antimicrobial system as well as the product safety. Despite the wide variety of preservatives, the synergistic or antagonistic effects of their combinations are not well established and it is still an issue in the development of pharmaceutical and cosmetic products. The purpose of this paper was to establish a space design using a simplex-centroid approach to achieve the lowest effective concentration of 3 preservatives (methylparaben, propylparaben, and imidazolidinyl urea) and EDTA for an emulsion cosmetic product. Twenty-two formulae of emulsion differing only by imidazolidinyl urea (A: 0.00 to 0.30% w/w), methylparaben (B: 0.00 to 0.20% w/w), propylparaben (C: 0.00 to 0.10% w/w) and EDTA (D: 0.00 to 0.10% w/w) concentrations were prepared. They were tested alone and in binary, ternary and quaternary combinations. Aliquots of these formulae were inoculated with several microorganisms. An electrochemical method was used to determine microbial burden immediately after inoculation and after 2, 4, 8, 12, 24, 48, and 168 h. An optimization strategy was used to obtain the concentrations of preservatives and EDTA resulting in a most effective preservative system of all microorganisms simultaneously. The use of preservatives and EDTA in combination has the advantage of exhibiting a potential synergistic effect against a wider spectrum of microorganisms. Based on graphic and optimization strategies, we proposed a new formula containing a quaternary combination (A: 55%; B: 30%; C: 5% and D: 10% w/w), which complies with the specification of a conventional challenge test. A design space approach was successfully employed in the optimization of concentrations of preservatives and EDTA in an emulsion cosmetic product.

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

    PubMed

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

    2014-09-01

    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 17β-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 β-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.

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

    PubMed

    Carmona, Eric; Andreu, Vicente; Picó, Yolanda

    2014-06-15

    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 7.26μgL(-1), dominated by ibuprofen, naproxen and 11-nor-9-carboxy-Δ9-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 7μgL(-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.

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

    PubMed

    Jewell, Christopher; Prusakiewicz, Jeffery J; Ackermann, Chrisita; Payne, N Ann; Fate, Gwendolyn; Voorman, Richard; Williams, Faith M

    2007-12-01

    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.

  19. 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

    Jewell, Christopher; Prusakiewicz, Jeffery J.; Ackermann, Chrisita; Payne, N. Ann; Fate, Gwendolyn; Voorman, Richard; Williams, Faith M.

    2007-12-01

    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.

  20. Metabolism of parabens (4-hydroxybenzoic acid esters) by hepatic esterases and UDP-glucuronosyltransferases in man.

    PubMed

    Abbas, Suzanne; Greige-Gerges, Hélène; Karam, Nancy; Piet, Marie-Hélène; Netter, Patrick; Magdalou, Jacques

    2010-01-01

    Parabens (alkyl esters of 4-hydroxybenzoic acid) are widely used as preservatives in drugs, cosmetic products, and foodstuffs. Safety concerns have recently increased due to the potential health risks associated to exposure to large amounts of these substances. Biotransformation of parabens mainly includes hydrolysis of the ester bond and glucuronidation reactions. The hydrolysis and glucuronidation of a series of six parabens differing by the nature of the alkyl group were investigated in human liver microsomes and plasma, and the major human UDP-glucuronosyltransferase (UGT) isoforms involved in the reaction were identified. Methyl- and ethylparaben were stable in human plasma, with 95% of the initial concentration remaining after 24 h. On the other hand, propyl-, butyl- and benzylparaben concentrations decreased by 50% under similar conditions. In contrast, rapid hydrolysis was measured with human liver microsomes depending on the alkyl chain length, with t(1/2) varying from 22 min for methylparaben to 87 min for butylparaben. All parabens were actively glucuronidated by liver microsomes, in comparison to 4-hydroxybenzoic acid. They were mainly substrates of human recombinant UGT1A1, UGT1A8, UGT1A9, UGT2B7, UGT2B15 and UGT2B17. In conclusion, the parabens were readily metabolized in human liver through esterase hydrolysis and glucuronidation by several UGT isoforms. These results suggest that these parabens do not accumulate in human tissue.

  1. 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.

    PubMed

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

    2014-04-04

    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 μg 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

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

    PubMed Central

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

    2011-01-01

    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 μm (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

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

    PubMed

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

    2015-01-01

    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.

  4. Investigation of parabens in commercial cosmetics for children in Beijing, China.

    PubMed

    Wang, Ping; Li, Jie; Tian, Hanmei; Ding, Xiaojing

    2013-01-01

    Parabens are one of the most common preservatives in cosmetics. Because allergenicity and cytotoxicity potential values are major aspects of preservative safety and parabens are xenoestrogens, safety levels of parabens have been restricted in "Hygienic Standard for Cosmetics" (2007 edition) by the Ministry of Public Health of China, and a high-performance liquid chromatography (HPLC) for the simultaneous determination of parabens is recommended. To investigate whether the commonly used parabens in children's cosmetics were at a safety level, 105 cosmetics for children were randomly purchased from the local market in Beijing and analyzed by the proposed HPLC method. The detection rate of methylparaben was the highest and the next was propylparaben. Among the 105 samples, two or more kinds of parabens were detected in 72 samples with concentrations ranging from 0.02% to 0.75%; 18 samples contained one kind of paraben with concentrations ranging from 0.002% to 0.06%. In this study, the contents of parabens in the 105 samples were all below the restricted levels.

  5. Determination of parabens in serum by liquid chromatography-tandem mass spectrometry: Correlation with lipstick use.

    PubMed

    Tahan, Gabriella Padovani; Santos, Nayara de Kássia Souza; Albuquerque, Ana Carolina; Martins, Isarita

    2016-08-01

    Parabens are the most widely used preservative and are considered to be relatively safe compounds. However, studies have demonstrated that they may have estrogenic activity, and there is ongoing debate regarding the safety and potential cancer risk of using products containing these compounds. In the present work, liquid chromatography-tandem mass spectrometry was applied to determine methylparaben and propylparaben concentrations in serum, and the results were correlated with lipstick application. Samples were analyzed using liquid-liquid extraction, followed by liquid chromatography-tandem mass spectrometry. The validation results demonstrated the linearity of the method over a range of 1-20 ng/mL, in addition to the method's precision and accuracy. A statistically significant difference was demonstrated between serum parabens in women who used lipstick containing these substances compared with those not using this cosmetic (p = 0.0005 and 0.0016, respectively), and a strong association was observed between serum parabens and lipstick use (Spearman correlation = 0.7202).

  6. Ecological risk assessment associated to the removal of endocrine-disrupting parabens and benzophenone-4 in wastewater treatment.

    PubMed

    Molins-Delgado, Daniel; Díaz-Cruz, M Silvia; Barceló, Damià

    2016-06-05

    The occurrence of four widely used and endocrine disrupting parabens (PBs) (methylparaben, propylparaben, butylparaben and benzylparaben) and a polar UV filter (benzophenone-4) were determined in influent and effluent wastewater from the 19 major wastewater treatment plants (WWTPs) of Catalonia, Spain. For their analysis an on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method was developed and validated. Laboratory analysis revealed high levels for both PBs and BP4, with maximum concentrations of 5700ngL(-1) and 1806ngL(-1), respectively, in influent samples, and 137ngL(-1) and 1080ngL(-1), respectively in effluent wastewaters. Removal rates (RE%) for the target compounds in each WWTPs were calculated. RE% for parabens were almost 100%, whereas for BP4 values where in the range 5-91%. The half-life time (t1/2), hydraulic retention time (HRT), and annual mass load (ML) for each facility was estimated. Results indicated that there was no clear influence of HRT on the RE% of BP4. MLs for BP4 were in the range 0.9-110.1kgy(-1), with the highest values in the most populated areas. Finally, a risk assessment, estimated in terms of hazard quotients (HQs), was carried out for aquatic biota. HQs for the target compounds in effluent wastewaters indicated a negligible effect, whereas for some influent wastewaters' HQs pointed out that some species are at risk.

  7. Analysis of parabens in dentifrices and the oral cavity.

    PubMed

    Park, Yong-Duk; Jang, Jong-Hwa; Park, Jung-Eun; Kim, Ji Hyun; Kim, Eun-Cheol; Song, Yun-Jung; Kwon, Ha-Jeong

    2014-12-01

    This study analyzed levels of parabens in commercial dentifrices and saliva. HPLC was performed using 35% acetonitrile and measuring absorbance at 254 nm. Thirteen toothpastes and five mouthwashes were analyzed. Of these, volunteers used three toothpastes and two mouthwashes, and levels of parabens were analyzed in saliva and water used for mouth rinsing. In toothpastes, the highest concentrations of methylparaben (MP), propylparaben (PP) and n-butylparaben (nBP) were 1.86, 1.42 and 1.87 mg/g, respectively. In mouthwashes, the highest concentrations of MP and PP were 0.97 and 0.11 mg/mL, respectively. After volunteers used 500 mg toothpaste T-1, which contained 895 µg MP, the first and tenth mouth rinse samples contained means of 64.63 and 1.89 µg MP, respectively. After rinsing the mouth three or five times, 37 µg or 18 µg MP was calculated to remain in the oral cavity, respectively. After using 20 mL mouthwash S-1, which contained 19 mg MP, 1.53 mg MP was calculated to remain in the oral cavity. Immediately after using this mouthwash, the mean salivary concentration of MP was 237 µg/mL. The daily intake of parabens from dentifrices was predicted to be insignificant compared with the intake from food; however, parabens can be ingested from dentifrices.

  8. Stir bar sorptive extraction of parabens, triclosan and methyl triclosan from soil, sediment and sludge with in situ derivatization and determination by gas chromatography-mass spectrometry.

    PubMed

    Ferreira, Ana María Casas; Möder, Monika; Laespada, M E Fernández

    2011-06-24

    The aim of this research work was the evaluation of stir-bar sorptive extraction (SBSE) in combination with an in situ derivatization to determine parabens (methylparaben, isopropylparaben, n-propylparaben, butylparaben and benzylparaben), triclosan and methyltriclosan in soil samples. This is the first time that this approach has been applied to the determination of these compounds in soil samples, providing important advantages over conventional extraction techniques, such as minimization of sampling handling, complete elimination of the use of organic solvents and simplification of the analytical procedure with reduced time consumption. The enriched target analytes were desorbed thermally using a thermodesorption system coupled to a gas chromatograph and a mass spectrometer. The optimized derivatization and SBSE extraction conditions, as well as the analytical characteristics of the method were obtained using spiked soil samples. The proposed methodology proved to be easy to use and sensitive, with limits of detection between 80 ng/kg and 1.06 μg/kg, and reproducibility values below 13%. The accuracy of the method was evaluated at two concentration levels, obtaining apparent recoveries between 91% and 110%. The matrix composition significantly influenced the extraction procedure, and a need to adopt a standard additions protocol is apparent. The analytes assayed were determined successfully in different environmental soil samples.

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

    PubMed Central

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

    2014-01-01

    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

  10. Simultaneous determination of phenylephrine hydrochloride, guaifenesin, and chlorpheniramine maleate in cough syrup by gradient liquid chromatography.

    PubMed

    Amer, Sawsan M; Abbas, Samah S; Shehata, Mostafa A; Ali, Nahed M

    2008-01-01

    A simple and reliable high-performance liquid chromatographic method was developed for the simultaneous determination of mixture of phenylephrine hydrochloride (PHENYL), guaifenesin (GUAIF), and chlorpheniramine maleate (CHLO) either in pure form or in the presence of methylparaben and propylparaben in a commercial cough syrup dosage form. Separation was achieved on a C8 column using 0.005 M heptane sulfonic acid sodium salt (pH 3.4 +/- 0.1) and acetonitrile as a mobile phase by gradient elution at different flow rates, and detection was done spectrophotometrically at 210 nm. A linear relationship in the range of 30-180, 120-1800, and 10-60 microg/mL was obtained for PHENYL, GUAIF, and CHLO, respectively. The results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2002) method and showed that the proposed method is precise, accurate, and can be easily applied for the determination of the drugs under investigation in pure form and in cough syrup formulations.

  11. Minimizing Hemodialysis Catheter Dysfunction: An Ounce of Prevention

    PubMed Central

    Lee, Timmy; Lok, Charmaine; Vazquez, Miguel; Moist, Louise; Maya, Ivan; Mokrzycki, Michele

    2012-01-01

    The maintenance of tunneled catheter (TC) patency is critical for the provision of adequate hemodialysis in patients who are TC-dependent. TC dysfunction results in the need for costly and inconvenient interventions, and reduced quality of life. Since the introduction of TCs in the late 1980s, heparin catheter lock has been the standard prophylactic regimen for the prevention of TC dysfunction. More recently, alternative catheter locking agents have emerged, and in some cases have shown to be superior to heparin lock with respect to improving TC patency and reducing TC-associated infections. These include citrate, tissue plasminogen activator, and a novel agent containing sodium citrate, methylene blue, methylparaben, and propylparaben. In addition, prophylaxis using oral anticoagulants/antiplatelet agents, including warfarin, aspirin, ticlodipine, as well as the use of modified heparin-coated catheters have also been studied for the prevention of TC dysfunction with variable results. The use of oral anticoagulants and/or antiplatelet agents as primary or secondary prevention of TC dysfunction must be weighed against their potential adverse effects, and should be individualized for each patient. PMID:22518310

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

    PubMed

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

    2014-01-01

    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.

  13. [Studies for analyzing the prohibited ingredients such as cyproheptadine hydrochloride in cosmetics].

    PubMed

    Tokunaga, Hiroshi; Uchino, Tadashi

    2005-01-01

    Cyproheptadine hydrochloride (CH) is nominated as the prohibited ingredients in cosmetics in Japanese Pharmaceutical Affairs Act. So the analytical method for CH was investigated by HPLC. The lotion or milky lotion of 0.5 g was put into a 10-ml volumetric flask. After adding 1.0ml of CH solution at 50 microg/ml into the volumetric flask, the mixture was made up to 10ml with methanol as the test solution. Creams were procedured as follows; 0.5 g of cream was put into a 10-ml volumetric flask. After adding 1.0 ml of tetrahydrofuran into the volumetric flask, the mixture was stirred for several minutes and the ingredients of the creams were dissolved. After adding 1.0 ml of CH solution at 50 microg/ml into the volumetric flask, the mixture was made up to 10ml with methanol. This mixture was transferred to a centrifuging tube with a cap and then the tube was centrifuged for 5 minutes at 3000 rpm. The supernatant was used as the test solution. The test solution of 20 microl was analyzed by HPLC using the ODS column (CAPCELL PAK C18 column, 4.6 x 250 mm), the mixture of 1% acetic acid with 10 mmol/l sodium octanesulfonate and acetonitrile (11:9) and the detection wavelength of 286 nm. The working curve from 0.5 to 6.0 microg/ml showed a linear line between the concentrations of CH and the peak areas. There was no interference of peak of CH with the ingredients such as methylparaben, ethylparaben in the lotions, milky lotion and creams.

  14. Evaluating food additives as antifungal agents against Monilinia fructicola in vitro and in hydroxypropyl methylcellulose-lipid composite edible coatings for plums.

    PubMed

    Karaca, Hakan; Pérez-Gago, María B; Taberner, Verònica; Palou, Lluís

    2014-06-02

    Common food preservative agents were evaluated in in vitro tests for their antifungal activity against Monilinia fructicola, the most economically important pathogen causing postharvest disease of stone fruits. Radial mycelial growth was measured in Petri dishes of PDA amended with three different concentrations of the agents (0.01-0.2%, v/v) after 7 days of incubation at 25 °C. Thirteen out of fifteen agents tested completely inhibited the radial growth of the fungus at various concentrations. Among them, ammonium carbonate, ammonium bicarbonate and sodium bicarbonate were the most effective while sodium acetate and sodium formate were the least effective. The effective agents and concentrations were tested as ingredients of hydroxypropyl methylcellulose (HPMC)-lipid edible coatings against brown rot disease on plums previously inoculated with M. fructicola (curative activity). 'Friar' and 'Larry Ann' plums were inoculated with the pathogen, coated with stable edible coatings about 24h later, and incubated at 20 °C and 90% RH. Disease incidence (%) and severity (lesion diameter) were determined after 4, 6, and 8 days of incubation and the 'area under the disease progress stairs' (AUDPS) was calculated. Coatings containing bicarbonates and parabens significantly reduced brown rot incidence in plums, but potassium sorbate, used at 1.0% in the coating formulation, was the most effective agent with a reduction rate of 28.6%. All the tested coatings reduced disease severity to some extent, but coatings containing 0.1% sodium methylparaben or sodium ethylparaben or 0.2% ammonium carbonate or ammonium bicarbonate were superior to the rest, with reduction rates of 45-50%. Overall, the results showed that most of the agents tested in this study had significant antimicrobial activity against M. fructicola and the application of selected antifungal edible coatings is a promising alternative for the control of postharvest brown rot in plums.

  15. Analysis of multi-class preservatives in leave-on and rinse-off cosmetics by matrix solid-phase dispersion.

    PubMed

    Sanchez-Prado, Lucia; Alvarez-Rivera, Gerardo; Lamas, J Pablo; Lores, Marta; Garcia-Jares, Carmen; Llompart, Maria

    2011-12-01

    Matrix solid-phase extraction has been successfully applied for the determination of multi-class preservatives in a wide variety of cosmetic samples including rinse-off and leave-on products. After extraction, derivatization with acetic anhydride, and gas chromatography-mass spectrometry analysis were performed. Optimization studies were done on real non-spiked and spiked leave-on and rinse-off cosmetic samples. The selection of the most suitable extraction conditions was made using statistical tools such as ANOVA, as well as factorial experimental designs. The final optimized conditions were common for both groups of cosmetics and included the dispersion of the sample with Florisil (1:4), and the elution of the MSPD column with 5 mL of hexane/acetone (1:1). After derivatization, the extract was analyzed without any further clean-up or concentration step. Accuracy, precision, linearity and detection limits were evaluated to assess the performance of the proposed method. The recovery studies on leave-on and rinse-off cosmetics gave satisfactory values (>78% for all analytes in all the samples) with an average relative standard deviation value of 4.2%. The quantification limits were well below those set by the international cosmetic regulations, making this multi-component analytical method suitable for routine control. The analysis of a broad range of cosmetics including body milk, moisturizing creams, anti-stretch marks creams, hand creams, deodorant, shampoos, liquid soaps, makeup, sun milk, hand soaps, among others, demonstrated the high use of most of the target preservatives, especially butylated hydroxytoluene, methylparaben, propylparaben, and butylparaben.

  16. Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse

    PubMed Central

    2010-01-01

    Background Several active ingredients proposed as vaginal microbicides have been shown paradoxically to increase susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models. Methods Excipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility. Results The following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML) formulated in K-Y® Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol. Conclusions As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility. PMID:21087496

  17. Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model

    PubMed Central

    Lee, Jae-Hwan; Lee, Myeongho; Ahn, Changhwan; Kang, Hee Young; Tran, Dinh Nam; Jeung, Eui-Bae

    2017-01-01

    Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF). Methylparaben (MP, 100 mg/kg), propylparaben (PP, 100 mg/kg), and butylparaben (BP, 100 mg/kg) dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (Foxl2, Kitl and Amh). All parabens significantly increased the Amh mRNA level but unchanged Foxl2 and Kitlg acting in primordial follicles. VCD and MP slightly increased Star and Cyp11a1 levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles. PMID:28208728

  18. Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model.

    PubMed

    Lee, Jae-Hwan; Lee, Myeongho; Ahn, Changhwan; Kang, Hee Young; Tran, Dinh Nam; Jeung, Eui-Bae

    2017-02-08

    Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF). Methylparaben (MP, 100 mg/kg), propylparaben (PP, 100 mg/kg), and butylparaben (BP, 100 mg/kg) dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (Foxl2, Kitl and Amh). All parabens significantly increased the Amh mRNA level but unchanged Foxl2 and Kitlg acting in primordial follicles. VCD and MP slightly increased Star and Cyp11a1 levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles.

  19. Electrochemical sensor for parabens based on molecular imprinting polymers with dual-templates.

    PubMed

    Wang, Yang; Cao, Yuhua; Fang, Cheng; Gong, Qianqian

    2010-07-19

    A selective, sensitive, rapid and reliable method based on molecularly imprinted polymers (MIPs) with dual templates to determine total content of parabens in cosmetics was developed. With methylparaben (MP) and propylparaben (PP) as dual-templates, methacrylic acid (MAA) as a functional monomer and tripropylene glycol diacrylate (TPGDA) as a cross-linker, MIPs film on a glassy carbon electrode was constructed as paraben sensor. At oxidation potential of 0.94 V (vs. SCE), the peak currents on the MIPs sensor were proportional to the concentration of parabens with square wave voltammetry. As the ratio of MP to PP in the MIPs was 1:1.25, the regression equations for four parabens were almost the same. The linear range was 20-100 microM for MP and EP, 5-100 microM for PP, and 5-80 microM for BP, with detection limit of 0.4 microM for MP and EP, 0.2 microM for the others. The total content of parabens could be calculated according to the average of these four regress equations. At least 10 times of structural analogs, such as p-hydroxybenzoic acid, p-aminobenzoic acid and phenol would not interfere with the determination of parabens. Nonanalogous coexistences such as vitamin C had no response on the sensor at all. Rapid response of the MIPs sensor was obtained within 1 min. MIPs sensor had been used to determine total content of parabens in cosmetic samples with recoveries between 98.7% and 101.8%. It reveals that the MIPs sensor with multi-templates has a potential to determine the total content of a group of homologous compounds.

  20. In-sample acetylation-non-porous membrane-assisted liquid-liquid extraction for the determination of parabens and triclosan in water samples.

    PubMed

    Villaverde-de-Sáa, Eugenia; González-Mariño, Iria; Quintana, José Benito; Rodil, Rosario; Rodríguez, Isaac; Cela, Rafael

    2010-07-01

    A procedure for the determination of seven parabens (esters of 4-hydroxybenzoic acid), including the distinction between branched and linear isomers of propyl- and butyl-parabens and triclosan in water samples, was developed and evaluated. The procedure includes in-sample acetylation-non-porous membrane-assisted liquid-liquid extraction and large volume injection-gas chromatography-ion trap-tandem mass spectrometry. Different derivatisation strategies were considered, i.e. post-extraction silylation with N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide and in situ acylation with acetic anhydride (Ac(2)O) and isobutylchloroformate. Moreover, acceptor solvent and the basic catalyser of the acylation reaction were investigated. Thus, in situ derivatisation with Ac(2)O and potassium hydrogenphosphate (as basic catalyser) was selected. Potassium hydrogenphosphate overcomes some drawbacks of other basic catalysers, e.g. toxicity and bubble formation, while leads to higher responses. Subsequently, other experimental variables affecting derivatisation-extraction yield such as pre-stirring time, salt addition and volume of Ac(2)O were optimised by an experimental design approach. Under optimised conditions, the proposed method achieved detection limits from 0.1 to 1.4 ng L(-1) for a sample volume of 18 mL and extraction efficiencies, estimated by comparison with liquid-liquid extraction, between 46% (for methyl- and ethyl-parabens) and 110% (for benzylparaben). The reported sample preparation approach is free of matrix effects for parabens but affected for triclosan with a reduction of approximately 40% when wastewater samples are analysed; therefore, both internal and external calibration can be used as quantification techniques for parabens, but internal standard calibration is mandatory for triclosan. The application of the method to real samples revealed the presence of these compounds in raw wastewater at concentrations up to 26 ng mL(-1), the prevalence of the

  1. Chronic toxicity of parabens and their chlorinated by-products in Ceriodaphnia dubia.

    PubMed

    Terasaki, Masanori; Abe, Ryoko; Makino, Masakazu; Tatarazako, Norihisa

    2015-01-01

    The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC50 values for mortality, offspring number, and first brood production ranged between 0.30-3.1, 0.047-12, and 1.3-6.3 mg L(-1) , respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg L(-1) and from 1.2 to 19 mg L(-1) , respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl2 BnP) elicited a significant decrease in offspring numbers even at their lowest concentration tested; the NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg L(-1) for MP, BnP, and Cl2 BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent response; their NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0

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

    PubMed

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

    2014-05-01

    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

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

    PubMed

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

    2014-02-15

    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 (μM). 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 μM. 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.

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

    PubMed

    Herman, Anna; Herman, Andrzej Przemysław; Domagalska, Beata Wanda; Młynarczyk, Andrzej

    2013-06-01

    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.

  5. Antimicrobial lubricant formulations containing poly(hydroxybenzene)-trimethoprim conjugates synthesized by tyrosinase.

    PubMed

    Gonçalves, Idalina; Botelho, Cláudia M; Teixeira, Ana; Abreu, Ana S; Hilliou, Loïc; Silva, Carla; Cavaco-Paulo, Artur

    2015-05-01

    Poly(hydroxybenzene)-trimethoprim conjugates were prepared using methylparaben as substrate of the oxidative enzyme tyrosinase. MALDI-TOF MS analysis showed that the enzymatic oxidation of methylparaben alone leads to the poly(hydroxybenzene) formation. In the presence of trimethoprim, the methylparaben tyrosinase oxidation leads poly(hydroxybenzene)-trimethoprim conjugates. All of these compounds were incorporated into lubricant hydroxyethyl cellulose/glycerol mixtures. Poly(hydroxybenzene)-trimethoprim conjugates were the most effective phenolic structures against the bacterial growth reducing by 96 and 97% of Escherichia coli and Staphylococcus epidermidis suspensions, respectively (after 24 h). A novel enzymatic strategy to produce antimicrobial poly(hydroxybenzene)-antibiotic conjugates is proposed here for a wide range of applications on the biomedical field.

  6. 76 FR 16290 - Tolerances for Residues of New Animal Drugs in Food; 2-Acetylamino-5-Nitrothiazole; Buquinolate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ...; Prednisolone; Prednisone; Progesterone; Propylparaben; and Salicylic Acid AGENCY: Food and Drug Administration...) and as Sec. 556.550 (40 FR 13802 at 13956). 12. Salicylic acid (Sec. 556.590). In 2005, FDA acknowledged the voluntary withdrawal of approval of salicylic acid for use in cattle under NADA 010-481...

  7. 77 FR 26706 - Food Ingredients and Sources of Radiation Listed and Approved for Use in the Production of Meat...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... Inspection Service (FSIS) is proposing to remove sodium benzoate, sodium propionate, and benzoic acid from... potassium sorbate, propylparaben (propyl p- hydroxybenzoate), calcium propionate, sodium propionate, benzoic acid, and sodium benzoate. The regulations provide that these substances ``* * * may be used in or...

  8. Action of methyl-, propyl- and butylparaben on GPR30 gene and protein expression, cAMP levels and activation of ERK1/2 and PI3K/Akt signaling pathways in MCF-7 breast cancer cells and MCF-10A non-transformed breast epithelial cells.

    PubMed

    Wróbel, Anna Maria; Gregoraszczuk, Ewa Łucja

    2015-10-14

    In the present study, we examined cAMP levels and activation of the MAPK/ERK1/2 and PI3K/Akt signaling pathways in response to the actions of parabens on GPR30 in MCF-7 and MCF-10A cells. Cells were exposed to methyl-, propyl- or butylparaben at a concentration of 20nM; 17-β-estradiol (10nM) was used as a positive control. 17β-estradiol and all tested parabens increased GPR30 gene and protein expression in MCF-7 and MCF-10A cells. No parabens affected cAMP levels in either cell line, with the exception of propylparaben in MCF-10A cells. 17β-estradiol, propylparaben, and butylparaben increased phosphorylation of ERK1/2 in MCF-7 cells, whereas 17β-estradiol, methyl- and butylparaben, but not propylparaben, increased phosphorylation of ERK1/2 in MCF-10A cells. Akt activation was noted only in MCF-7 cells and only with propylparaben treatment. Collectively, the data presented here point to a nongenomic mechanism of action of parabens in activation GPR30 in both cancer and non-cancer breast cell lines through βγ dimer-mediated activation of the ERK1/2 pathway, but not the cAMP/PKA pathway. Moreover, among investigated parabens, propylparaben appears to inhibit apoptosis in cancer cells through activation of Akt kinases, confirming conclusions suggested by our previously published data. Nevertheless, continuing research on the carcinogenic action of parabens is warranted.

  9. Chemical constituents from the roots of Ranunculus ternatus.

    PubMed

    Tian, Jing-Kui; Sun, Feng; Cheng, Yi-Yu

    2006-01-01

    Two new glycosides named as ternatoside A (1) and ternatoside B (2), with four known constituents sternbin (3), methylparaben (4), 4-O-D-glucopyranosyl-p-coumaric acid (5) and linocaffein (6) were isolated from the roots of Ranunculus ternatus, The structures of new compounds were determined by 1D and 2D NMR, MS techniques, and chemical methods.

  10. Transplacental passage of antimicrobial paraben preservatives.

    PubMed

    Towers, Craig V; Terry, Paul D; Lewis, David; Howard, Bobby; Chambers, Wesley; Armistead, Casey; Weitz, Beth; Porter, Stephanie; Borman, Christopher J; Kennedy, Rebekah C M; Chen, Jiangang

    2015-01-01

    Parabens are widely used preservatives suspected of being endocrine disruptors, with implications for human growth and development. The most common paraben found in consumer products is methylparaben. To date, no study has examined whether these substances cross the human placenta. A total of 100 study subjects (50 mother-child pairs) were enrolled at two medical institutions, serving primarily African-American and Caucasian women, respectively. A maternal blood sample was drawn on admission and a paired cord blood sample was obtained at delivery. Of the 50 mothers, 47 (94%) showed methylparaben in their blood (mean level 20.41 ng/l), and 47 in cords bloods (mean level 36.54 ng/l). There were 45 mother-child pairs where methylparaben was found in both samples. Of these, the fetal level was higher than the maternal level in 23 (51%). For butylparaben, only 4 mothers (8%) showed detectable levels (mean 40.54 ng/l), whereas 8 cord blood samples (16%) were positive (mean 32.5 ng/l). African-American mothers and infants showed higher prevalence of detectable levels (P=0.017). Methylparaben and butylparaben demonstrate transplacental passage. Additional studies are needed to examine potential differences in exposure by geography and demographics, what products are used by pregnant women that contain these preservatives, as well as any potential long-term effects in the growth and development of exposed children.

  11. Hypersensitivity dermatitis following suction-assisted lipectomy: a complication of local anesthetic.

    PubMed

    Fine, P G; Dingman, D L

    1988-06-01

    We report a case of severe dermatitis involving the abdomen and thighs following suction-assisted lipectomy of these areas wherein local anesthetic containing the preservative methylparaben was used for infiltrative anesthesia. This use of local anesthetics with epinephrine can be of value in the performance of suction-assisted lipectomy to reduce blood loss, serve as an adjunct to other intraoperative anesthetic techniques, and for postoperative analgesia. Local anesthetic solutions commonly contain additives, which serve as antioxidants and antimicrobials. The most common of these preservatives is methylparaben, which can cause delayed hypersensitivity reactions. These reactions may be neither recognized nor clinically significant in small areas of infection, whereas in large body surface infiltrative procedures, such as suction-assisted lipectomy, these reactions may be of considerable consequence. This article reviews the pathophysiology and treatment of these reactions and gives recommendations for avoiding them.

  12. Effect of Ternary Solutes on the Evolution of Structure and Gel Formation in Amphiphilic Copolymer Solutions

    NASA Astrophysics Data System (ADS)

    Meznarich, Norman Anthony Kang

    Aqueous solutions of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) amphiphilic triblock copolymers (commercially known as Pluronic surfactants) undergo reversible and temperature-dependent micellization and arrangement into cubic ordered lattices known as "micelle gels". The macroscopic behavior of the ordering is a transition from a liquid to a gel. While the phase behavior and gel structure of pure Pluronic surfactant solutions have been well studied, less is known about the effects of added ternary solutes. In this dissertation, a comprehensive investigation into the effects of the added pharmaceutical methylparaben on solutions of F127 ranging from 10 to 30 wt% was conducted in order to better understand the behavior of F127 in multicomponent pharmaceutical formulations. The viscoelastic properties of F127 gel formation were studied using rheometry, where heating rates of 0.1, 1, and 10 degrees C/min were also used to probe the kinetics of the gel transition. In solutions containing methylparaben, F127 gelation occurred at up to 15 degrees C lower temperatures and was accelerated by a factor of three to four. Small angle x-ray scattering (SAXS) was used to characterize the structure of the ordered domains, and how they were affected by the presence of dissolved pharmaceuticals. It was found that ordered domain formation changed from heterogeneous nucleation and growth to possible homogeneous nucleation and growth. A roughly 2% reduction in the cubic lattice parameter was also observed for solutions containing methylparaben. Differential scanning calorimetry (DSC) experiments were performed on a series of different Pluronic surfactants in order to characterize the micellization behavior as a function of PPO center block length and PEO/PPO ratio. Added methylparaben suppressed the micellization endotherm, the degree of suppression depending linearly on the amount of added methylparaben, as well as the length of the PPO center block and PEO

  13. Effects of parabens on apoptosis induced by serum-free medium.

    PubMed

    Egawa, Mari; Aoki, Kentaro; Sun, Yongkun; Hosokawa, Toshiyuki; Saito, Takeshi; Kurasaki, Masaaki

    2012-01-01

    Alkyl esters of p-hydroxybenzoic acids (parabens), an endocrine disrupter, are used as preservatives in cosmetics and foods. In this study, to understand the relationship between parabens and differentiation in infants, the effects of parabens on apoptosis induced by serum deprivation in PC12 cells were investigated. In addition, apoptosis-related factors were assayed. As results, a tendency toward enhancement of apoptosis was observed in the cells cultured in the serum-free medium with methylparaben, and this tendency was suggested to be related to the contents of BAD, a pro-apoptotic protein. Butylparaben did not show any tendency to enhance apoptosis.

  14. Actions of methyl-, propyl- and butylparaben on estrogen receptor-α and -β and the progesterone receptor in MCF-7 cancer cells and non-cancerous MCF-10A cells.

    PubMed

    Wróbel, Anna Maria; Gregoraszczuk, Ewa Łucja

    2014-11-04

    Numerous studies have shown that widely used parabens possess estrogenic properties. In the present study, we examined the effects of methyl-, propyl- and butylparaben on the mRNA and protein expression of estrogen receptor (ER)-α (ESR1) and -β (ESR2) and the progesterone receptor (PGR). Human MCF-7 breast cancer cells and MCF-10A non-transformed breast epithelial cells were exposed to parabens at a concentration of 20nM; 17β-estradiol at a concentration of 10nM, was used as a positive control. Both propyl- and butylparaben stimulated PGR mRNA expression in MCF-7 cells, whereas methyl- and propylparaben PGR protein expression. In MCF-10A cells, butyl- and propylparaben increased only PGR mRNA expression. All parabens increased ESR1 gene and protein expression in MCF-7 and with the exception of butylparaben in MCF-10A cells. All parabens significantly increased ESR2 mRNA and protein expression in MCF-7 cells, but in MCF-10A cells only ESR2 protein expression. In summary, by virtue of their stimulatory action on the expression of ESR1, ESR2 and PGR in cancer cells, parabens can be viewed as potential contributors to breast cancer progression. Extension, the actions of these parabens on the expression of ERs and PGR in non-cancerous cells point to possible actions on breast cancer initiation.

  15. Drug-excipient compatibility studies in binary mixtures of avobenzone.

    PubMed

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

    2013-01-01

    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.

  16. Formation of organic nanoparticles by electrospinning of volatile microemulsions.

    PubMed

    Dvores, Michelle P; Marom, Gad; Magdassi, Shlomo

    2012-05-01

    This study presents a method for one-step formation of poly(ethylene oxide) nanofibers incorporating nanoparticles of a poorly water-soluble compound. Using the new method reported here, nanofiber-nanoparticle composites are fabricated in one step by electrospinning of an oil-in-water microemulsion, in which a model material, propylparaben, has been dissolved within the volatile dispersed phase in the presence of a high-molecular-weight polymer. The approach is based on nanoscale confinement to the dispersed phase of an oil-in-water microemulsion with a volatile oil phase, in which the poorly water-soluble materials are dissolved. Thus, when the thermodynamically stable oil-in-water microemulsion is combined with the rapid evaporation of solvent inherent in the electrospinning process, the droplets are converted into organic nanoparticles embedded within a polymeric nanofiber. In addition to possessing process simplicity, this method exhibits a very high percentage of nanoparticle loading with desirable active material properties. Specifically, the diameter of the nanofibers is in the range of 60-185 nm, and propylparaben exists within the nanofiber as nanocrystals of 30-120 nm. These dimensions suggest that the nanofiber-nanocrystal composites could serve as a delivery system for water-insoluble materials.

  17. Quantitative determination of infinite inhibition concentrations of antimicrobial agents.

    PubMed Central

    Marwan, A G; Nagel, C W

    1986-01-01

    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

  18. Processes involved in sweeping as sample enrichment method in cyclodextrin-modified micellar electrokinetic chromatography of hydrophobic basic analytes.

    PubMed

    El-Awady, Mohamed; Pyell, Ute

    2014-03-01

    Sweeping is an enrichment method in MEKC, which includes following steps: stacking/destacking of the micelles, sweeping of analyte by the stacked/destacked micelles, destacking/stacking of the swept analyte zone and additional focusing/defocusing due to the retention factor gradient effect (RFGE). In this study, we investigate additional processes, regarding online focusing in cyclodextrin-modified MEKC (CD-MEKC) of hydrophobic basic analytes: dynamic pH junction (sample with pH different from that of BGE) and adsorption of analyte onto the capillary wall within the sample zone. It is demonstrated that the developed method for the assessment of the sweeping efficiency is also applicable to CD-MEKC taking ethylparaben as an example of acidic analytes and desloratadine as an example of basic analytes using different types of β-cyclodextrin. Our previous results regarding RFGE as an additional focusing/defocusing effect in sweeping-MEKC are confirmed for the case that the apparent distribution coefficient differs for the sample and the BGE due to a different content of the complex-forming agent cyclodextrin and due to a pH difference between the sample and the BGE. Despite being significantly more hydrophobic than ethylparaben, desloratadine shows an unexpectedly low enrichment factor. This enrichment factor is nearly unaffected by the addition of CD to the BGE. This unexpected behavior is attributed to wall adsorption of the protonated hydrophobic basic analyte within the sample zone, which significantly counteracts the sweeping process. This assumption is corroborated by an improvement in the enrichment factor achieved via addition of a dynamic coating agent (triethylamine) to the sample solution.

  19. Impact of microbial growth inhibition and proteolytic activity on the stability of a new formulation containing a phytate-degrading enzyme obtained from mushroom.

    PubMed

    Spier, Michele R; Siepmann, Francieli B; Staack, Larissa; Souza, Priscila Z; Kumar, Vikas; Medeiros, Adriane B P; Soccol, Carlos R

    2016-10-02

    The development of stable enzymes is a key issue in both the food and feed industries. Consequently, the aim of the current study is to evaluate the impact of various additives (sodium chloride, sodium citrate, mannitol, methylparaben, polyethylene glycol 3350, ethylenediaminetetraacetic acid disodium salt, and a serine protease inhibitor) on the stability of a mushroom phytase produced by solid-state cultivation and recovery. Also observed was the effect of the additives on microbial growth inhibition by monitoring both the change in optical density over 30 days of storage and proteolytic activity. Initially, eight experimental formulations were prepared along with a control. After screening, a 3(2) factorial design was applied to define suitable concentrations of the selected additives. Among the eight formulations tested, the formulation containing NaCl, PEG 3350, and methylparaben retained all of the initial phytase activity after 50 days of storage, with no detected interference from protease activity. Sodium citrate, a metal chelation agent, presented the unusual effect of reducing protease activity in the formulations. Although all formulations presented better phytase stability when compared to the control, NaCl and PEG were both able to prolong the stability of the enzyme activity and also to inhibit microbial growth during storage, making them favorable for application as food and feed additives.

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

    PubMed

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

    2010-01-01

    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.

  1. Structure-activity relationship of a series of 17 parabens and related compounds for histamine release in rat peritoneal mast cells and skin allergic reaction in guinea pigs.

    PubMed

    Uramaru, Naoto; Inoue, Toshio; Watanabe, Yoko; Shigematsu, Hidenari; Ohta, Shigeru; Kitamura, Shigeyuki

    2014-02-01

    Parabens, which are a homologous series of esters of p-hydroxybenzoic acid, have been used as preservatives in cosmetics, medicines and foods because of their antimicrobial activity. However, parabens in cosmetics have been suspected to cause allergic contact dermatitis. In this study, we examined paraben-induced histamine release from rat peritoneal mast cells and skin reaction in guinea pigs using a series of 17 parabens with different alcohol side chains, ranging from methylparaben to dodecylparaben. Octylparaben showed the greatest histamine release-inducing activity from mast cells, and the activity was decreased in shorter- and longer-side-chain parabens. Octyl benzoate, octyl o-hydroxybenzoate and phenyloctane caused no significant degranulation of mast cells, whereas octyl m-hydroxybenzoate, octyl p-hydroxybenzoate and octyl phenol induced concentration-related degranulation. Metabolites of these parabens (p-hydroxybenzoic acid and alcohols) did not show histamine release-inducing activity. In the guinea pig skin reaction test, heptylparaben induced a typical strong skin reaction, while butylparaben induced a typical weak skin reaction, and methylparaben and dodecylparaben were inactive. Metabolites of parabens (p-hydroxybenzoic acid and alcohols) were also inactive. These results indicate that interaction of parabens with rat mast cells requires a minimum length and adequate lipophilicity of the alkyl side chain. Since metabolites of parabens were inactive, parabens appear to be direct-acting allergens.

  2. Simultaneous determination of pseudoephdrine, pheniramine, guaifenisin, pyrilamine, chlorpheniramine and dextromethorphan in cough and cold medicines by high performance liquid chromatography.

    PubMed

    Louhaichi, M R; Jebali, S; Loueslati, M H; Adhoum, N; Monser, L

    2009-05-15

    A new simple, rapid and sensitive liquid chromatographic method has been developed and validated for the simultaneous determination of pseudoephdrine, pheniramine, guaifenisin, pyrilamine, chlorpheniramine and dextromethorphan in cough and cold pharmaceuticals. The separation of these compounds was achieved within 13 min on a Kromasil C18 column using an isocratic mobile phase consisting of methanol-dihydrogenphosphate buffer at pH 3 (45:55, v/v). The analysis was performed at a flow rate of 1 mL min(-1) and at a detection wavelength of 220 nm. The selectivity, linearity of calibration, accuracy, within and between-days precision and recovery were examined as parts of the method validation. The concentration-response relationship was linear over a concentration range of 5-50 microg mL(-1) for pseudoephdrine, pheniramine, chlorpheniramine and 50-600 microg mL(-1) for guaifenisin, pyrilamine, dextromethorphan, methylparaben and sodium benzoate with correlation coefficients better than 0.998. The standard deviations of the intraday and interday were all less than 2%. The proposed liquid chromatographic method was successfully applied for the routine analysis of these compounds in different cough and cold pharmaceutical preparations such as syrups, capsules, tablets and sachets. The presence of preservatives (sodium benzoate and methylparaben) and other excipients did not show any significant interference on the determination of these compounds.

  3. Properties of melt extruded enteric matrix pellets.

    PubMed

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

    2010-02-01

    The objective of this study was to investigate the properties of enteric matrix pellets that were prepared by hot-melt extrusion in a one-step, continuous process. Five polymers (Eudragit) L100-55, L100 and S100, Aqoat grades LF and HF) were investigated as possible matrix formers, and pellets prepared with Eudragit S100 demonstrated superior gastric protection and acceptable processibility. Extruded pellets containing Eudragit S100 and up to 40% theophylline released less than 10% drug over 2h in acid, however, the processibility and yields were compromised by the high amounts of the non-melting drug material in the formulation. Efficient plasticization of Eudragit S100 was necessary to reduce the polymer's glass transition temperature and melt viscosity. Five compounds including triethyl citrate, methylparaben, polyethylene glycol 8000, citric acid monohydrate and acetyltributyl citrate were investigated in terms of plasticization efficiency and preservation of the delayed drug release properties. The aqueous solubility of the plasticizer and its plasticization efficiency impacted the drug release rate from the matrix pellets. The use of water-soluble plasticizers resulted in a loss of gastric protection, whereas low drug release rates in acid were found for pellets containing insoluble plasticizers or no plasticizer, independent of the extent of Eudragit S100 plasticization. The release rate of theophylline in buffer pH 7.4 was faster for pellets that were prepared with efficient plasticizers. The microstructure and solid-state properties of plasticized pellets were further investigated by scanning electron microscopy and powder X-ray diffraction. Pellets prepared with efficient plasticizers (TEC, methylparaben, PEG 8000) exhibited matrices of low porosity, and the drug was homogeneously dispersed in its original polymorphic form. Pellets containing ATBC or citric acid monohydrate had to be extruded at elevated temperature and showed physical instabilities in

  4. Possible endocrine disrupting effects of parabens and their metabolites.

    PubMed

    Boberg, Julie; Taxvig, Camilla; Christiansen, Sofie; Hass, Ulla

    2010-09-01

    Parabens are preservatives used in a wide range of cosmetic products, including products for children, and some are permitted in foods. However, there is concern for endocrine disrupting effects. This paper critically discusses the conclusions of recent reviews and original research papers and provides an overview of studies on toxicokinetics. After dermal uptake, parabens are hydrolyzed and conjugated and excreted in urine. Despite high total dermal uptake of paraben and metabolites, little intact paraben can be recovered in blood and urine. Paraben metabolites may play a role in the endocrine disruption seen in experimental animals and studies are needed to determine human levels of parabens and metabolites. Overall, the estrogenic burden of parabens and their metabolites in blood may exceed the action of endogenous estradiol in childhood and the safety margin for propylparaben is very low when comparing worst-case exposure to NOAELs from experimental studies in rats and mice.

  5. Determination of gentiopicroside, mangiferin, palmatine, berberine, baicalin, wogonin and glycyrrhizin in the traditional Chinese medicinal preparation sann-joong-kuey-jian-tang by high-performance liquid chromatography.

    PubMed

    Lin, S J; Tseng, H H; Wen, K C; Suen, T T

    1996-04-12

    High-performance liquid chromatography was employed to determine the contents of several marker substances such as gentiopicroside, mangiferin, palmatine, berberine, baicalin, wogonin and glycyrrhizin in Sann-Joong-Kuey-Jian-Tang. The separation was performed on a Cosmosil 5C18-AR column by gradient elution with 0.03% (v/v) phosphoric acid-acetonitrile (0 min, 90:10; 10 min, 87:13; 17-27 min, 77:23; 40 min, 62:38; 50 min, 55:45) as the mobile phase at a flow-rate of 1.0 ml/min, with detection at 254 nm. n-Propylparaben was used as the internal standard and seven regression equations revealed linear relationships between the peak-area ratios (marker substances/internal standard) and concentrations. The repeatability and reproducibility (relative standard deviation) of the method were in the ranges 0.02-1.78% and 1.44-4.95%, respectively.

  6. Estrogenicity of parabens revisited: impact of parabens on early pregnancy and an uterotrophic assay in mice.

    PubMed

    Shaw, Jordan; deCatanzaro, Denys

    2009-07-01

    Parabens, a class of preservatives routinely added to cosmetics, pharmaceuticals, and foods, have estrogenic properties. Given that intrauterine implantation of fertilized ova in inseminated females can be disrupted by minute levels of exogenous estrogens, we assessed the impact of parabens upon early gestation. In Experiment 1, butylparaben was administered subcutaneously in several doses ranging from 0.05 to 35 mg/animal/day to inseminated CF-1 mice on days 1-4 of pregnancy. Butylparaben exposure did not affect litter size, the number of pups born, postnatal day 3 litter weights, or the number of pups surviving to postnatal day 5. In contrast, administration of 500 ng/animal/day 17beta-estradiol terminated all pregnancies. In Experiment 2, propylparaben was subcutaneously administered to inseminated CF-1 mice on gestational days 1-4. Dams were sacrificed on gestation day 6 and the number of implantation sites was counted. Propylparaben had no impact on the number of implantation sites observed. Since Experiments 1 and 2 did not yield the anticipated results, an uterotrophic assay was conducted in Experiment 3 to re-evaluate the in vivo estrogenicity of parabens. Ovariectomized CF-1 and CD-1 mice were administered butylparaben in doses ranging from 0.735 to 35 mg per animal for three consecutive days. Mice were sacrificed on the fourth day, and uterine mass was recorded. There was no effect of butylparaben on uterine wet or dry mass at any dose in either strain. In contrast, administration of 17beta-estradiol consistently increased uterine mass in both strains. These data indicate that the estrogen-sensitive period of implantation is not vulnerable to paraben exposure, and that the in vivo estrogenicity of parabens may not be as potent as previously reported.

  7. Antibacterial Effects of Cinnamon: From Farm to Food, Cosmetic and Pharmaceutical Industries

    PubMed Central

    Nabavi, Seyed Fazel; Di Lorenzo, Arianna; Izadi, Morteza; Sobarzo-Sánchez, Eduardo; Daglia, Maria; Nabavi, Seyed Mohammad

    2015-01-01

    Herbs and spices have been used since ancient times, because of their antimicrobial properties increasing the safety and shelf life of food products by acting against foodborne pathogens and spoilage bacteria. Plants have historically been used in traditional medicine as sources of natural antimicrobial substances for the treatment of infectious disease. Therefore, much attention has been paid to medicinal plants as a source of alternative antimicrobial strategies. Moreover, due to the growing demand for preservative-free cosmetics, herbal extracts with antimicrobial activity have recently been used in the cosmetic industry to reduce the risk of allergies connected to the presence of methylparabens. Some species belonging to the genus Cinnamomum, commonly used as spices, contain many antibacterial compounds. This paper reviews the literature published over the last five years regarding the antibacterial effects of cinnamon. In addition, a brief summary of the history, traditional uses, phytochemical constituents, and clinical impact of cinnamon is provided. PMID:26378575

  8. Antibacterial Effects of Cinnamon: From Farm to Food, Cosmetic and Pharmaceutical Industries.

    PubMed

    Nabavi, Seyed Fazel; Di Lorenzo, Arianna; Izadi, Morteza; Sobarzo-Sánchez, Eduardo; Daglia, Maria; Nabavi, Seyed Mohammad

    2015-09-11

    Herbs and spices have been used since ancient times, because of their antimicrobial properties increasing the safety and shelf life of food products by acting against foodborne pathogens and spoilage bacteria. Plants have historically been used in traditional medicine as sources of natural antimicrobial substances for the treatment of infectious disease. Therefore, much attention has been paid to medicinal plants as a source of alternative antimicrobial strategies. Moreover, due to the growing demand for preservative-free cosmetics, herbal extracts with antimicrobial activity have recently been used in the cosmetic industry to reduce the risk of allergies connected to the presence of methylparabens. Some species belonging to the genus Cinnamomum, commonly used as spices, contain many antibacterial compounds. This paper reviews the literature published over the last five years regarding the antibacterial effects of cinnamon. In addition, a brief summary of the history, traditional uses, phytochemical constituents, and clinical impact of cinnamon is provided.

  9. The industrial potential of herbs and spices - a mini review.

    PubMed

    Leja, Katarzyna B; Czaczyk, Katarzyna

    2016-01-01

    Herbs and spices have been used for food and medicinal purposes for centuries - the first recorded evidence of their use dates back to 1500BC and the Ebers Papyrus, which mentioned spices such as anise, mustard, saffron, cinnamon, and cassia. Now, in the 21st century, a variety of secondary compounds produced by plants are used in many fields of industry, such as food production (to improve taste, to provide vitamins and macro- and microelements, and also to inhibit food spoilage caused by foodborne bacteria), in medicine (in the treatment of various diseases; in chemoprevention and cancer therapy; as a source of natural antimicrobials for the treatment of infectious disease), and in pharmacology and cosmetology (in dietary supplements, and as a result of the demand for preservative-free cosmetics, to reduce the risk of methylparaben allergies). The aim of this review is to present the major active compounds in herbs and spices and explore their potential applications in industry.

  10. Determination of selected parabens, benzophenones, triclosan and triclocarban in agricultural soils after and before treatment with compost from sewage sludge: A lixiviation study.

    PubMed

    Camino-Sánchez, F J; Zafra-Gómez, A; Dorival-García, N; Juárez-Jiménez, B; Vílchez, J L

    2016-04-01

    An accurate and sensitive method for the determination of selected EDCs in soil and compost from wastewater treatment plants is developed and validated. Five parabens, six benzophenone-UV filters and the antibacterials triclosan and triclocarban were selected as target analytes. The parameters for ultrasound-assisted extraction were thoroughly optimized. After extraction, the analytes were detected and quantified using ultra-high performance liquid chromatography tandem mass spectrometry. Ethylparaben (ring-(13)C6 labelled) and deuterated benzophenone (BP-d10) were used as internal standards. The method was validated using matrix-matched calibration and recovery assays with spiked samples. The limits of detection ranged from 0.03 to 0.40 ng g(-1) and the limits of quantification from 0.1 to 1.0 ng g(-1), while precision in terms of relative standard deviation was between 9% and 21%. Recovery rates ranged from 83% to 107%. The validated method was applied for the study of the behavior of the selected compounds in agricultural soils treated and un-treated with compost from WWTP. A lixiviation study was developed in both agricultural soil and treated soil and first order kinetic models of their disappearance at different depths are proposed. The application of organic composts in the soil leads to an increase of the disappearance rate of the studied compounds. The lixiviation study also shows the risk of pollution of groundwater aquifers after disposal or waste of these EDCs in agricultural soils is not high.

  11. UHPLC-MS/MS method for the determination of bisphenol A and its chlorinated derivatives, bisphenol S, parabens, and benzophenones in human urine samples.

    PubMed

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

    2014-06-01

    In the present work, a new method based on a sample treatment by dispersive liquid-liquid microextraction (DLLME) for the extraction of six bisphenols (bisphenol A, bisphenol S, and monochloro-, dichloro-, trichloro-, and tetrachlorobisphenol A), four parabens (methyl-, ethyl-, propyl-, and butylparaben), and six benzophenones (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8, and 4-hydroxybenzophenone) in human urine samples, followed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is validated. 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, benzophenone-d10, and bisphenol A-d16 were used as surrogates. Limits of quantification ranging from 0.1 to 0.6 ng mL(-1) and interday variabilities (evaluated as relative standard deviations) from 2.0 to 13.8% were obtained. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 94 to 106%. A good linearity, for concentrations up to 300 ng mL(-1) for parabens and 40 ng mL(-1) for benzophenones and bisphenols, was also obtained. The method was satisfactorily applied for the determination of target compounds in human urine samples from 20 randomly selected individuals.

  12. Ultra-performance liquid chromatography MS/MS method for the determination of parabens in compost from sewage sludge: comparison of the efficiency of two extraction techniques.

    PubMed

    Benítez-Villalba, Julio César; Zafra-Gómez, Alberto; Dorival-García, Noemí; Camino-Sánchez, Francisco Javier; Cantarero, Samuel; Vílchez, José Luis

    2013-08-01

    The efficiency of two extraction techniques--ultrasound-assisted extraction and pressurized liquid extraction--are compared and evaluated in the determination of parabens in compost samples. The extraction parameters for each technique were accurately optimized. The selected compounds were detected and quantified using ultra-performance LC MS/MS, operating in negative ESI and in SRM mode. The analytes were separated in less than 5 min. Ethylparaben (ring-(13)C6 labeled) was used as an internal standard. Two selective, sensitive, and accurate analytical methods were developed and validated. The LODs of the methods ranged from 3 to 7 ng/g and the LOQs from 10 to 23 ng/g, while inter- and intraday variability was under 6% in all cases. The methods were validated separately by using matrix-matched calibration and recovery assays with spiked samples. Recovery rates ranged from 94.0 to 105.0%. Compost samples were taken from different composting plants. Although the statistical comparison demonstrated no statistically significant differences between the two extraction techniques, the method based on pressurized liquid extraction was more sensitive than the ultrasound extraction based method.

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

    PubMed

    Terasaki, Masanori; Makino, Masakazu; Tatarazako, Norihisa

    2009-04-01

    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.

  14. Transesterification of a series of 12 parabens by liver and small-intestinal microsomes of rats and humans.

    PubMed

    Fujino, Chieri; Watanabe, Yoko; Uramaru, Naoto; Kitamura, Shigeyuki

    2014-02-01

    Hydrolytic transformation of parabens (4-hydroxybenzoic acid esters; used as antibacterial agents) to 4-hydroxybenzoic acid and alcohols by tissue microsomes is well-known both in vitro and in vivo. Here, we investigated transesterification reactions of parabens catalyzed by rat and human microsomes, using a series of 12 parabens with C1-C12 alcohol side chains. Transesterification of parabens by rat liver and small-intestinal microsomes occurred in the presence of alcohols in the microsomal incubation mixture. Among the 12 parabens, propylparaben was most effectively transesterified by rat liver microsomes with methanol or ethanol, followed by butylparaben. Relatively low activity was observed with longer-side-chain parabens. In contrast, small-intestinal microsomes exhibited higher activity towards moderately long side-chain parabens, and showed the highest activity toward octylparaben. When parabens were incubated with liver or small-intestinal microsomes in the presence of C1-C12 alcohols, ethanol and decanol were most effectively transferred to parabens by rat liver microsomes and small-intestinal microsomes, respectively. Human liver and small-intestinal microsomes also exhibited significant transesterification activities with different substrate specificities, like rat microsomes. Carboxylesterase isoforms, CES1b and CES1c, and CES2, exhibited significant transesterification activity toward parabens, and showed similar substrate specificity to human liver and small-intestinal microsomes, respectively.

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

    PubMed

    Radovan, Ciprian; Cinghită, Dan; Manea, Florica; Mincea, Manuela; Cofan, Codruta; Ostafe, Vasile

    2008-07-25

    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.

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

    PubMed Central

    Radovan, Ciprian; Cinghiță, Dan; Manea, Florica; Mincea, Manuela; Cofan, Codruța; Ostafe, Vasile

    2008-01-01

    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. PMID:27879939

  17. Multi-class method for biomonitoring of hair samples using gas chromatography-mass spectrometry.

    PubMed

    Martín, Julia; Möder, Monika; Gaudl, Alexander; Alonso, Esteban; Reemtsma, Thorsten

    2015-11-01

    Currently, non-invasive biomonitoring of human exposure to organic pollutants bases upon the analysis mainly of urine and human breast milk. While mostly persistent organic pollutants are the center of interest, the aim of our study was to develop a method for the determination of different chemical classes of emerging pollutants (organophosphorus flame retardants, plastic additives such as phthalates, bisphenol A, insecticides, antimicrobials, preservatives and musk fragrances) in hair by gas chromatography-mass spectrometry. The preferred sample preparation included hydrolysis of the hair with trifluoroacetic acid in methanol followed by a liquid-liquid extraction using hexane/ethyl acetate. The validated method is characterized by recoveries higher than 77 % for most analytes, relative standard deviations below 16 % and limits of detection between 2 pg mg(-1) (HHCB) and 292 pg mg(-1) (propylparaben) using 50 mg of dry hair. After respective blank corrections, bis-(2-ethylhexyl)phthalate (DEHP) and the musk fragrance HHCB were the predominant compounds determined in all hair samples at concentrations between 32 and 59 ng mg(-1) and 0.8-13 ng mg(-1), respectively. The bactericide triclosan and the insect repellent N,N-diethyl-3-methylbenzamide (DEET) were detected in selected hair samples at 2 and 0.8 ng mg(-1), respectively.

  18. Effect-directed identification of endocrine disruptors in plastic baby teethers.

    PubMed

    Berger, Elisabeth; Potouridis, Theodoros; Haeger, Astrid; Püttmann, Wilhelm; Wagner, Martin

    2015-11-01

    Concerns have been raised regarding the human health effects of endocrine disrupting chemicals (EDCs), many of which are associated with and leaching from plastics. As infants are particularly vulnerable to EDCs, we have investigated whether plastic teethers for babies represent a relevant source of exposure. Applying effect-directed analysis, we use bioassays to screen teethers, toys used to soothe a baby's teething ache, for endocrine activity and chemical analysis to identify the causative compounds. We detected significant endocrine activity in two of 10 plastic teethers. Those samples leached estrogenic and/or antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast Antiandrogen Screen. After sample fractionation, gas chromatography-mass spectrometry non-target screening revealed that methyl-, ethyl- and propylparaben were responsible for the observed estrogenic and antiandrogenic activity in one product. The second product is likely to contain at least six different antiandrogenic compounds that remain so far unidentified. This study demonstrates that plastic teethers can be a source of infant exposure to well-established and unknown EDCs. Because of their limited value to the product, but potential toxicity, manufacturers should critically revisit the use of parabens in plastic teethers and further toys. Moreover, plastic teethers might leach EDCs that escape routine analysis and, thus, toxicological evaluation. The resulting uncertainty in product safety poses a problem to consumers, producers and regulators that remain to be resolved.

  19. Occurrence and fate of endocrine disrupting chemicals in ASP based sewage treatment plant in Hardwar.

    PubMed

    Saini, Gita; Pant, Shalini; Alam, Tanveer; Kazmi, A A

    The occurrence of emerging contaminants such as endocrine disrupting chemicals (EDCs) in our water resources is of prime concern. With this context, fate and seasonal variation of six EDCs (testosterone, T; progesterone, P; diethyl phthalate, DEP; dibutyl phthalate, DBP; propyl-paraben, PP and butyl-paraben, BP) were assessed throughout the year, i.e. in rainy, winter, spring and summer seasons in the raw, treated wastewater and activated sludge in an activated sludge process (ASP) based sewage treatment plant (STP) located in Haridwar, India. Qualitative and quantitative measurements were performed by gas chromatography-mass spectrometry (GC-MS) analysis. Results indicate that in summer, the examined STP could effectively remove 82.9% of T, 86.4% of P, 95.5% of DEP, 92.4% of DBP, 91.5% of PP, and 89.9% of BP from the wastewater. Among the EDCs considered, higher removal efficiencies were achieved for phthalates in the summer season. GC-MS analysis showed that a small fraction of EDCs was sorbed on the solid fraction of activated sludge. Scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transformation infrared spectroscopy analysis were also performed to investigate the occurrence of EDCs in biomass samples. Results of this study also demonstrated that removal efficiency, assessed in terms of physicochemical and microbiological parameters, was maximum in summer and reached minimum in rainy season.

  20. A Novel Two-Step Liquid-Liquid Extraction Procedure Combined with Stationary Phase Immobilized Human Serum Albumin for the Chiral Separation of Cetirizine Enantiomers along with M and P Parabens.

    PubMed

    Chmielewska, Aleksandra; Konieczna, Lucyna; Bączek, Tomasz

    2016-12-07

    The research into the separation of drug enantiomers is closely related to the safety and efficiency of the drugs. The aim of this study was to develop a simple and validated HPLC method to analyze cetirizine enantiomers. In the case of liquid dosage forms, besides the active substance in large amounts there are usually also inactive ingredients such as methyl- and propylparaben. Unfortunately, these compounds can interfere with the analyte, inter alia during chiral separation of the analyte enantiomers. The proposed innovative two-step liquid-liquid extraction procedure allowed for the determination of cetirizine enantiomers (along with M and P parabens) also in liquid dosage forms. The main focus of this study was the chromatographic activity of cetirizine dihydrochloride on the proteinate-based chiral stationary phase. The chromatographic separation of cetirizine enantiomers was performed on an immobilized human serum albumin (HSA) column for the first time. Measurements were performed at a wavelength of 227 nm. Under optimal conditions, baseline separation of two enantiomers was obtained with 1.43 enantioseparation factor (α) and 1.82 resolution (Rs). Finally, the proposed method was successfully applied to the selected pharmaceutical formulations.

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

    PubMed

    Sonnenburg, Anna; Schreiner, Maximilian; Stahlmann, Ralf

    2015-12-01

    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.

  2. New method for the determination of parabens and bisphenol A in human milk samples using ultrasound-assisted extraction and clean-up with dispersive sorbents prior to UHPLC-MS/MS analysis.

    PubMed

    Rodríguez-Gómez, R; Dorival-García, N; Zafra-Gómez, A; Camino-Sánchez, F J; Ballesteros, O; Navalón, A

    2015-06-15

    A sensitive and accurate analytical method for the determination of methyl-, ethyl-, propyl- and butylparaben and bisphenol A in human milk samples has been developed and validated. The combination of ultrasound-assisted extraction (UAE) and a simplified and rapid clean-up technique that uses sorbent materials has been successfully applied for the preparation of samples prior to ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The analytes were extracted from freeze-dried human milk samples using acetonitrile and ultrasonic radiation (three 15-min cycles at 70% amplitude), and further cleaned-up with C18 sorbents. The most influential parameters affecting the UAE method and the clean-up steps were optimized using design of experiments. Negative electrospray ionization (ESI) in the selected reaction monitoring (SRM) mode was used for MS detection. The use of two reactions for each compound allowed simultaneous quantification and identification in one run. The analytes were separated in less than 10min. Deuterium-labeled ethylparaben-d5 (EPB-d5) and deuterium-labeled bisphenol A-d16 (BPA-d16) were used as surrogates. The limits of quantification ranged from 0.4 to 0.7ngmL(-1), while inter- and intra-day variability was under 11.1% in all cases. In the absence of certified reference materials, recovery assays with spiked samples using matrix-matched calibration were used to validate the method. Recovery rates ranged from 93.8% to 112.2%. The proposed method was satisfactorily applied for the determination of four selected parabens and bisphenol A in human milk samples obtained from nursing mothers living in the province of Granada (Spain).

  3. Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.

    PubMed

    Cai, Zheng; Song, Xiangrong; Sun, Feng; Yang, Zhaoxiang; Hou, Shixiang; Liu, Zhongqiu

    2011-12-01

    Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

  4. Urinary concentrations of parabens in Chinese young adults: implications for human exposure.

    PubMed

    Ma, Wan-Li; Wang, Lei; Guo, Ying; Liu, Li-Yan; Qi, Hong; Zhu, Ning-Zheng; Gao, Chong-Jing; Li, Yi-Fan; Kannan, Kurunthachalam

    2013-10-01

    Parabens are widely used as preservatives in foods, cosmetics, and pharmaceuticals. However, recent studies have indicated that high and systemic exposure to parabens can be harmful to human health. Although a few studies have reported urinary paraben levels in western countries, studies on paraben exposure in the Chinese population are limited. China is currently a major producer of parabens in the world. In this study, 109 urine samples collected from Chinese young adults (approximately 20 years old) were analyzed for five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens) by high-performance liquid chromatography-tandem mass spectrometry. Methyl-, propyl-, and ethyl-parabens were the three major paraben analogues found in all (100%) samples. The concentration of the sum of the five parabens ranged from 0.82 to 728 ng/mL with a geometric mean value of 17.4 ng/mL. Urinary concentration of parabens was 2-fold greater in females than in males. Based on the measured urinary concentrations, daily intake of parabens by the Chinese young adults was estimated and compared with those reported for United States adults. The estimated daily intakes (EDIurine) of parabens were 18.4 and 40.8 μg/kg bw/day for Chinese males and females, respectively, values that were lower than those reported for United States adults (74.7 μg/kg bw/day). Based on the reported concentrations of parabens in foods from China and the United States, the contribution of dietary intake to EDIurine was estimated to be 5.5, 2.6, and 0.42% for Chinese males, Chinese females, and United States adults, respectively, which indicates the significance of nondietary sources of parabens to human exposures.

  5. A new treatment by dispersive liquid-liquid microextraction for the determination of parabens in human serum samples.

    PubMed

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

    2013-09-01

    Alkyl esters of p-hydroxybenzoic acid (parabens) are a family of compounds that have been in use since the 1920s as preservatives in cosmetic formulations, with one of the lowest rates of skin problems reported in dermatological patients. However, in the last few years, many scientific publications have demonstrated that parabens are weak endocrine disruptors, meaning that they can interfere with the function of endogenous hormones, increasing the risk of breast cancer. In the present work, a new sample treatment method is introduced based on dispersive liquid-liquid microextraction for the extraction of the most commonly used parabens (methyl-, ethyl-, propyl-, and butylparaben) from human serum samples followed by separation and quantification using ultrahigh performance liquid chromatography-tandem mass spectrometry. The method involves an enzymatic treatment to quantify the total content of parabens. The extraction parameters (solvent and disperser solvent, extractant and dispersant volume, pH of the sample, salt addition, and extraction time) were accurately optimized using multivariate optimization strategies. Ethylparaben ring (13)C6-labeled was used as surrogate. Limits of quantification ranging from 0.2 to 0.7 ng mL(-1) and an interday variability (evaluated as relative standard deviations) from 3.8 to 11.9 % were obtained. The method was validated using matrix-matched calibration standard and a spike recovery assay. Recovery rates for spiked samples ranged from 96 to 106 %, and a good linearity up to concentrations of 100 ng mL(-1) was obtained. The method was satisfactorily applied for the determination of target compounds in human serum samples.

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

    PubMed

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

    2014-12-05

    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.

  7. Alkyl protocatechuates as novel urinary biomarkers of exposure to p-hydroxybenzoic acid esters (parabens).

    PubMed

    Wang, Lei; Kannan, Kurunthachalam

    2013-09-01

    Human exposure to p-hydroxybenzoic acid esters (parabens) is a concern, owing to adverse health effects of these compounds. Parabens are metabolized and eliminated from the human bodies within a few hours of exposure. In this study, for the first time, methyl- and ethyl-protocatechuates (OH-MeP and OH-EtP) and their parent compounds, methyl- (MeP) and ethyl-parabens (EtP), were determined in urine samples collected from U.S. children and adults. Alkyl protocatechuates were found in almost all urine samples, with median concentrations of 11.8 (OH-MeP) and 2.90ng/mL (OH-EtP) in adults, and 5.43 (OH-MeP) and 0.85ng/mL (OH-EtP) in children. In adults, the concentrations of urinary OH-MeP and OH-EtP were higher than the corresponding concentrations of MeP and EtP. Significant correlation between OH-MeP/OH-EtP and MeP/EtP was observed. This is the first report to document hydroxylation of parabens in humans, and to propose hydroxylated metabolites (i.e., alkyl protocatechuates) as alternative biomarkers of exposure to parabens in human biomonitoring studies. The rates of transformation of parabens between children and adults appeared to be different, as evidenced from the slopes of regression between alkyl protocatechuates and parabens. In addition to alkyl protocatechuates, hydroxybenzoic acid (4-HB) and 3,4-dihydroxybenzoic acid (3,4-DHB) were found at considerable levels in the urine samples. The occurrence of a significant proportion of alkyl protocatechuates and 3,4-DHB suggests the need for inclusion of these derivatives in accurate estimation of human exposure to parabens and in epidemiological studies that associate paraben exposure to health outcomes in populations.

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

    PubMed

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

    2014-01-01

    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.

  9. A new method for rapid determination of indole-3-carbinol and its condensation products in nutraceuticals using core-shell column chromatography method.

    PubMed

    Fibigr, Jakub; Šatínský, Dalibor; Havlíková, Lucie; Solich, Petr

    2016-02-20

    Indole-3-carbinol is a natural glucosinolate known for prevention of human breast, prostate and other types of cancer and it started to be used in commercial preparations, as food supplements. However no analytical method has been proposed for quality control of nutraceuticals with this substance yet. In this paper a new high-performance liquid chromatography (HPLC) method using core-shell column for separation of indole-3-carbinol and its condensation/degradation products was developed and used for the quantitative determination of indole-3-carbinol in nutraceuticals. Separation of indole-3-carbinol, its condensation/degradation products and internal standard ethylparaben was performed on the core-shell column Kinetex 5μ XB-C18 100A (100×4.6mm), particle size 5.0μm, with mobile phase acetonitrile/water according to the gradient program at a flow rate of 1.25mLmin(-1) and at temperature 50°C. The detection wavelength was set at 270nm. Under the optimal chromatographic conditions good linearity of determination was achieved. Available commercial samples of nutraceuticals were extracted with 100% methanol using ultrasound bath. A 5-μL sample volume of the supernatant was directly injected into the HPLC system. The developed method provided rapid and accurate tool for quality control of nutraceuticals based on cruciferous vegetable extracts with indole-3-carbinol content. The presented study showed that the declared content of indole-3-carbinol significantly varied in the different nutraceuticals available on the market. Two analyzed preparations showed the presence of condensation/degradation products of indole-3-carbinol which were not officially declared by the manufacturer. Moreover, further two analyzed nutraceutical preparations showed absolutely no content of declared amount of indole-3-carbinol.

  10. Concentrations of parabens in human breast tumours.

    PubMed

    Darbre, P D; Aljarrah, A; Miller, W R; Coldham, N G; Sauer, M J; Pope, G S

    2004-01-01

    Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng x g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng x g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues.

  11. p-Hydroxybenzoate esters metabolism in MCF7 breast cancer cells.

    PubMed

    Dagher, Zeina; Borgie, Mireille; Magdalou, Jacques; Chahine, Ramez; Greige-Gerges, Hélène

    2012-11-01

    Parabens are among the most frequently used preservatives to inhibit microbial growth and extend the shelf life of a range of consumer products. The objective of the present study was to gain insight into the metabolism of parabens in breast cancer cells (MCF7) since they have demonstrated estrogenic activity towards these cells and have been detected in breast cancer tissues. The toxicity of parabens to MCF7 cells was determined using MTT assays. Hydrolysis of methyl-, butyl and benzyl-paraben to p-hydroxybenzoic acid was analyzed in cultured MCF7 cells and in cellular homogenates. Glucuronidation and sulfoconjugation were studied in MCF7 homogenates, and parabens were analyzed by HPLC. Methyl-paraben was shown to be far less toxic than butyl and benzyl-paraben. Parabens were completely stable in MCF7 homogenates whereas p-nitrophenyl acetate, a substrate type, underwent hydrolysis. MCF7 cell homogenates did not express glucuronidation and sulfoconjugation activities toward parabens. The higher stability of parabens may explain their accumulation in breast cancer tissue as previously reported in the literature.

  12. Preliminary assessment on the bioaccessibility of contaminants of emerging concern in raw and cooked seafood.

    PubMed

    Alves, Ricardo N; Maulvault, Ana L; Barbosa, Vera L; Cunha, Sara; Kwadijk, Christiaan J A F; Álvarez-Muñoz, Diana; Rodríguez-Mozaz, Sara; Aznar-Alemany, Òscar; Eljarrat, Ethel; Barceló, Damià; Fernandez-Tejedor, Margarita; Tediosi, Alice; Marques, António

    2017-02-13

    A preliminary assessment of the bioaccessibility of contaminants of emerging concern (CeCs), including perfluorinated compounds (PFCs; i.e. PFOS and PFUnA), brominated flame retardants (BFRs; i.e. BDE47, BDE100, α-HBCD) and pharmaceuticals and personal care products (PPCPs; i.e. venlafaxine, methylparaben and UV-filter OC) was performed in seafood species available in the European markets. Additionally, the effect of steaming on CeCs bioaccessibility was also investigated for the first time. Overall, steaming affected differentially contaminants' concentrations, for instance, decreasing PFOS levels in flounder, but increasing both BDE47 and BDE100. CeCs bioaccessibility varied according to seafood species and contaminant group, i.e. in general, lower bioaccessibility values were obtained for PBDEs (<70%, except for mackerel), while PFCs and PPCPs revealed higher bioaccessibility percentages (between 71 and 95%). The lowest bioaccessibility value was obtained for α-HBCD (mussel; 14%), whereas the highest percentage was observed in venlafaxine (mullet; 95%). Our preliminary study reports also, for the first time, the effects of steaming on CeCs bioaccessibility. In most cases, bioaccessibility was not affected by cooking, however, a decrease was observed in PBDEs and venlafaxine bioaccessibility in steamed mussels and mullet, respectively, thus lowering the potential health risks associated with seafood consumption.

  13. Sustained prediction ability of net analyte preprocessing methods using reduced calibration sets. Theoretical and experimental study involving the spectrophotometric analysis of multicomponent mixtures.

    PubMed

    Goicoechea, H C; Olivieri, A C

    2001-07-01

    A newly developed multivariate method involving net analyte preprocessing (NAP) was tested using central composite calibration designs of progressively decreasing size regarding the multivariate simultaneous spectrophotometric determination of three active components (phenylephrine, diphenhydramine and naphazoline) and one excipient (methylparaben) in nasal solutions. Its performance was evaluated and compared with that of partial least-squares (PLS-1). Minimisation of the calibration predicted error sum of squares (PRESS) as a function of a moving spectral window helped to select appropriate working spectral ranges for both methods. The comparison of NAP and PLS results was carried out using two tests: (1) the elliptical joint confidence region for the slope and intercept of a predicted versus actual concentrations plot for a large validation set of samples and (2) the D-optimality criterion concerning the information content of the calibration data matrix. Extensive simulations and experimental validation showed that, unlike PLS, the NAP method is able to furnish highly satisfactory results when the calibration set is reduced from a full four-component central composite to a fractional central composite, as expected from the modelling requirements of net analyte based methods.

  14. Liquid Chromatography-Electrospray Ionization Mass Spectrometry Analysis of Limonoids and Flavonoids in Seeds of Grapefruits, Other Citrus Species, and Dietary Supplements.

    PubMed

    Avula, Bharathi; Sagi, Satyanarayanaraju; Wang, Yan-Hong; Wang, Mei; Gafner, Stefan; Manthey, John A; Khan, Ikhlas A

    2016-07-01

    A selective UHPLC-DAD-QToF-MS method was developed to screen grapefruit seeds, and the seeds of other Citrus species for limonoid aglycones, acids, glucosides, and flavonoids. These classes of compounds were identified in positive and negative ion modes over a mass-to-charge range from 100-1500. Accurate mass values, elution times, and fragmentation patterns obtained by QToF-mass spectrometry were used to identify or tentatively characterize the compounds detected in the sample of this study. Limonin was the major limonoid in most of the seeds of Citrus species, followed by nomilin. This analytical method was successfully applied for the analysis of commercial extracts and dietary supplements claiming to contain grapefruit seed extract, or extracts made from the seed and other fruit parts such as the peel or pulp. Many commercial products contained large numbers of flavonoids, indicating the use of peel, pulp, or seed coat. This method also permitted detection of synthetic preservatives such as benzethonium chloride, methylparaben, and triclosan in commercial grapefruit seed extract products. Out of the 17 commercial products analyzed, two contained the synthetic antimicrobial agent benzethonium chloride.

  15. Quantitation of buclizine hydrochloride in pharmaceutical formulations and human serum by RP-HPLC.

    PubMed

    Arayne, M Saeed; Sultana, Najma; Siddiqui, Farhan Ahmed

    2006-10-01

    An isocratic reversed phase high-performance liquid chromatographic (HPLC) method with ultraviolet detection at 230 nm has been developed for the determination of buclizine hydrochloride in human serum and dosage formulation. Methylparaben was successfully used as an internal standard. Good chromatographic separation between buclizine and internal standard peaks was achieved by using a stainless steel analytical column Nucleosil, C18 (10 microm, 25 cm x 0.46 cm). The system was operated at room temperature using a mobile phase consisting of acetonitrile-water (1:1) (pH 2.6) with phosphoric acid 85% at a flow rate of 2 ml/min. The calibration curve for buclizine hydrochloride in human serum was linear over the tested concentration range of 10, 3, 1.5, 0.5, 0.15, 0.05, and 0.025 microg/ml with a correlation coefficient of 0.9999. The intra- and inter-run precision and accuracy results were 98.07 to 100.34. The proposed method was validated for selectivity, linearity, accuracy, and precision. The method was found to be suitable for the quality control of buclizine hydrochloride in bulk drug as well as in human serum.

  16. Determination of personal care products -benzophenones and parabens- in human menstrual blood.

    PubMed

    Jiménez-Díaz, I; Iribarne-Durán, L M; Ocón, O; Salamanca, E; Fernández, M F; Olea, N; Barranco, E

    2016-11-01

    Benzophenones and parabens are synthetic chemicals used in many personal care products, foods and pharmaceuticals. Benzophenones are used to protect the skin and materials from the adverse effects of UV-radiation, and parabens are used as preservatives. Despite their widespread occurrence and proven endocrine disrupting activity, relatively little is known about human exposure to these compounds. In the present work, an analytical method based on sample treatment using dispersive liquid-liquid microextraction (DLLME) for the extraction of six benzophenones (benzophenone-1, -2, -3, -6, -8 and 4-hydroxybenzophenone) and four parabens (methyl-, ethyl-, propyl- and butyl- paraben) from human menstrual blood samples, followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is proposed and validated. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. The limits of detection ranged from 0.1 to 0.3ngmL(-1), with recoveries of 93.8% to 108.9%, and precision (evaluated as relative standard deviation) lower than 14% for all selected compounds. This method was successfully applied for the determination of the target compounds in 25 samples of human menstrual blood. Methylparaben and benzophenone-3 were the most frequently detected compounds (96%).

  17. Changes in the Metabolome in Response to Low-Dose Exposure to Environmental Chemicals Used in Personal Care Products during Different Windows of Susceptibility

    PubMed Central

    Chen, Jia; Belpoggi, Fiorella; Manservisi, Fabiana; Sánchez-Guijo, Alberto; Wudy, Stefan A.; Teitelbaum, Susan L.

    2016-01-01

    The consequences of ubiquitous exposure to environmental chemicals remain poorly defined. Non-targeted metabolomic profiling is an emerging method to identify biomarkers of the physiological response to such exposures. We investigated the effect of three commonly used ingredients in personal care products, diethyl phthalate (DEP), methylparaben (MPB) and triclosan (TCS), on the blood metabolome of female Sprague-Dawley rats. Animals were treated with low levels of these chemicals comparable to human exposures during prepubertal and pubertal windows as well as chronically from birth to adulthood. Non-targeted metabolomic profiling revealed that most of the variation in the metabolites was associated with developmental stage. The low-dose exposure to DEP, MPB and TCS had a relatively small, but detectable impact on the metabolome. Multiple metabolites that were affected by chemical exposure belonged to the same biochemical pathways including phenol sulfonation and metabolism of pyruvate, lyso-plasmalogens, unsaturated fatty acids and serotonin. Changes in phenol sulfonation and pyruvate metabolism were most pronounced in rats exposed to DEP during the prepubertal period. Our metabolomics analysis demonstrates that human level exposure to personal care product ingredients has detectable effects on the rat metabolome. We highlight specific pathways such as sulfonation that warrant further study. PMID:27467775

  18. Occurrence, fate and risk assessment of parabens and their chlorinated derivatives in an advanced wastewater treatment plant.

    PubMed

    Li, Wenhui; Shi, Yali; Gao, Lihong; Liu, Jiemin; Cai, Yaqi

    2015-12-30

    In the present study, parabens, p-hydroxybenzoic acid (PHBA) and chlorinated derivatives, were simultaneously determined in wastewater and sludge samples along the whole process in an advanced wastewater treatment plant (WWTP). Nine target compounds were detected in this WWTP, and methylparaben and PHBA were the dominant compounds in these samples. It is noteworthy that octylparaben with longer chain was firstly detected in this work. Mass balance results showed that 91.8% of the initial parabens mass loading was lost mainly due to degradation, while the contribution of sorption and output of primary and excess sludge was much less (7.5%), indicating that biodegradation played a significant role in the removal of parabens during the conventional treatment process. Specifically, parabens were mainly degraded in the anaerobic tank, and PHBA could be effectively removed at high rates after the advanced treatment. However, both biodegradation and adsorption accounted for minor contribution to the removal of chlorinated parabens during conventional treatment process, and they were only scantly removed by conventional treatment (33.9-40.7%) and partially removed by advanced treatment (59.2-82.8%). Risk assessment indicated that parabens and their chlorinated derivatives in second and tertiary effluent are not likely to produce biological effects on aquatic ecosystems.

  19. Removal of parabens and their chlorinated by-products by periphyton: influence of light and temperature.

    PubMed

    Song, Chaofeng; Hu, Hongjuan; Ao, Hongyi; Wu, Yonghong; Wu, Chenxi

    2017-02-01

    The extensive use of parabens as preservatives in food and pharmaceuticals and personal care products results in frequent detection of their residuals in aquatic environment. In this work, the adsorption and removal of four parabens (methyl-, ethyl-, propyl-, and butyl-paraben) and two chlorinated methyl-parabens (CMPs) by periphyton were studied. Characteristics of the periphyton were identified to explore the possible relationship between paraben removal and periphyton properties. Results showed that linear adsorption coefficients (K d) vary from 554.4 to 808.6 L kg(-1) for the adsorption parabens and CMPs to autoclaved periphyton. The adsorption strength is positively related to the hydrophobicity of these compounds. Removal of parabens from water by periphyton was efficient with half-life (t 1/2) values estimated using first-order kinetic model ranging from 0.49 to 3.29 days, but CMPs were more persistent with t 1/2 ranging from 1.15 to 25.57 days, and t 1/2 increased with the chlorination degree. Higher incubation temperature accelerated the removal of all tested compounds, while a better removal of CMPs was observed in dark condition. Analysis of periphyton properties suggests that bacteria played a more important role in the removal of CMPs, but no specific relationship between periphyton properties and paraben removal ability can be established.

  20. Overcoming the nail barrier: A systematic investigation of ungual chemical penetration enhancement.

    PubMed

    Brown, M B; Khengar, R H; Turner, R B; Forbes, B; Traynor, M J; Evans, C R G; Jones, S A

    2009-03-31

    This study investigated the in vitro nail permeability of penetrants of varying lipophilicity-caffeine (CF, logP -0.07), methylparaben (MP, logP 1.96) and terbinafine (TBF, logP 3.3) and the effect of 2 novel penetration enhancers (PEs), thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) on their permeation. Studies were conducted using full thickness human nail clippings and ChubTur((R)) diffusion cells and penetrants were applied as saturated solutions. The rank order of steady-state penetrant flux through nails without PE application (MP>CF>TBF) suggested a greater sensitivity to penetrant molecular weight rather than logP. TA increased the flux of CF and MP approximately 4- and approximately 2-fold, respectively, whilst urea H(2)O(2) proved ineffective at enhancing permeability. The sequential application of TA followed by urea H(2)O(2) increased TBF and CF flux ( approximately 19- and approximately 4-fold, respectively) but reversing the application order of the PEs was only mildly effective at increasing just MP flux ( approximately 2-fold). Both nail PEs are likely to function via disruption of keratin disulphide bonds and the associated formation of pores that provide more 'open' drug transport channels. Effects of the PEs were penetrant specific, but the use of a reducing agent (TA) followed by an oxidising agent (urea H(2)O(2)) dramatically improved human nail penetration.

  1. [Preservation and stability of corn tortillas at room temperature].

    PubMed

    Higuera-Ciapara, I; Nieblas, J M

    1995-06-01

    Three treatments with chemical preservative (sodium propionate, potassium sorbate-methylparaben and hydrogen peroxidemethyl paraben) were tested to delay microbial spoilage and extend shelf-life of corn tortillas at room temperature (25 degrees C). The treatment with the best results was selected for further studies using two types of packaging: Paper and high density polyethylene. Quality of corn tortillas during storage was assessed by measuring water content, microbial analysis (Total Plate Count, molds and yeast) and throguh sensory evaluation. Results were analyzed by covariance analysis and slope contrast between packaging materials at p<0.05. Spoilage of tortilla without preservative occurred within 24 hours due to a large number of gram negative bacteria, molds and yeasts, which were responsible for offensive odors. Only the combination of hydrogen peroxide-methyl paraben had a significant effect on retarding bacterial yeast spoilage. In addition, hydrogen peroxide residues could not [correction of no] be chemically detected after 2 days of storage. Results from this study show that tortilla can be kept for up to six days at room temperature with acceptable sensory properties with proper preservative treatment and packaging.

  2. Synthesis and analysis of nanostructured composite particles from gas-saturated solutions

    NASA Astrophysics Data System (ADS)

    Gil'mutdinov, I. I.; Gil'mutdinov, I. M.; Kuznetsova, I. V.; Sabirzyanov, A. N.

    2015-05-01

    Ibuprofen/polyethylene glycol 4000 and methylparaben/polyethylene glycol 4000 nanostructured composite particles are synthesized from gas-saturated solutions (PGSS, particles from gas saturated solution). The dependences of the mean size of composite particles on pressure, temperature, and the expansion channel diameter are revealed. The studies are conducted in the pressure range of 10 to 30 MPa, at temperatures ranging from 40 to 80°C, and for expansion channel diameters in the range of 200 to 500 μm. The physicochemical properties of the composite particles are investigated using a differential scanning calorimeter and phase analysis is performed by means of X-ray diffraction. The composition of composite particles is determined via mass spectrometric analysis. Chromatography-tandem mass spectrometry with electronic ionization is used for the quantitative analysis of ibuprofen, while mass spectrometry of matrix-assisted laser desorption/ionization (MALDI) is used in the analysis of polyethylene glycol 4000. The dependence of the concentration of components in composite particles on pressure is obtained.

  3. Optimization of a Modified QuEChERS Method for Multiresidue Analysis of Pharmaceuticals and Personal Care Products in Sewage and Surface Water by LC-MS/MS.

    PubMed

    Kachhawaha, Akanksha S; Nagarnaik, Pranav M; Jadhav, Manjusha; Labhasetwar, Anjali Pudale Pawan K; Banerjee, Kaushik

    2017-03-16

    A quick, sensitive multiresidue method was developed for the analysis of 19 multiclass pharmaceuticals and personal care products (PPCPs) in surface water and sewage water. The proposed modified QuEChERS method involved the extraction of water samples (10 mL) with acetonitrile (10 mL) after the addition of 1% acetic acid, 4 g magnesium sulfate, and 0.2 g ammonium acetate, and was validated in distilled water, surface water, and sewage water with respect to linearity, LOD and LOQ, precision, and accuracy. The LOD and LOQ varied within the ranges of 0.001-0.167 and 0.002-0.25 ng/mL, respectively. Recoveries of the target compounds ranged from 73 to 125%, with precision RSD values <27%. The method provided a precise estimation of PPCPs in field samples, and acetaminophen, atenolol, metformin, sulfamethoxazole, carbamazepine, methylparaben, and triclosan were detected in concentrations ranging from 0.10 to 1.40 and 0.10 to 3.4 ng/mL in surface water and sewage water, respectively. This is an innovative application of the QuEChERS approach for estimation of PPCPs from aqueous matrixes. The method provides significantly higher output (preparation of 25-30 samples a day) compared to conventionalSPE-based methods (<10 samples a day).

  4. Induction of Pseudomonas syringae pv. tomato DC3000 MexAB-OprM multidrug efflux pump by flavonoids is mediated by the repressor PmeR.

    PubMed

    Vargas, Paola; Felipe, Antonia; Michán, Carmen; Gallegos, María-Trinidad

    2011-10-01

    In this study, we have analyzed the expression of the Pseudomonas syringae pv. tomato DC3000 mexAB-oprM efflux pump operon and of the regulatory gene pmeR, and we have investigated the role of the PmeR protein on transcription from both promoters. We demonstrate that mexAB-oprM and pmeR are expressed in vivo at a relatively high and moderate basal level, respectively, which, in both cases, increases in the presence of different flavonoids and other compounds, such as butyl and methylparaben. We show that PmeR is the local repressor of the mexAB-oprM promoter and is able to regulate its own expression. The mechanism for this regulation includes binding to a pseudopalindromic operator site which overlaps both mexAB-oprM and pmeR promoters. We have also proven that flavonoids are able to interact with PmeR and induce a conformational change that interferes with the DNA binding ability of PmeR, thereby modulating mexAB-oprM and pmeR expression. Finally, we demonstrate by in vivo experiments that the PmeR/MexAB-OprM system contributes to the colonization of tomato plants. These results provide new insight into a transcriptional regulator and a transport system that play essential roles in the ability of P. syringae pv. tomato DC3000 to resist the action of flavonoids produced by the host.

  5. Seasonal fate and gas/particle partitioning of semi-volatile organic compounds in indoor and outdoor air

    NASA Astrophysics Data System (ADS)

    Moreau-Guigon, Elodie; Alliot, Fabrice; Gaspéri, Johnny; Blanchard, Martine; Teil, Marie-Jeanne; Mandin, Corinne; Chevreuil, Marc

    2016-12-01

    Fifty-eight semi-volatile organic compounds (SVOCs) were investigated simultaneously in three indoor (apartment, nursery and office building) and one outdoor environment in the centre of Paris (France). All of these compounds except tetrabromobisphenol A were quantified in the gaseous and particulate phases in all three environments, and at a frequency of 100% for the predominant compounds of each SVOC class. Phthalic acid esters (PAEs) were the most abundant group (di-iso-butyl phthalate: 29-661 ng m-3, diethyl phthalate: 15-542 ng m-3), followed by 4-nonylphenol (1.4-81 ng m-3), parabens (methylparaben: 0.03-2.5 ng m-3), hexachlorobenzene (HCB) (0.002-0.26 ng m-3) and pentachlorobenzene (PeCB) (0.001-0.23 ng m-3). Polycyclic aromatic hydrocarbons (as ∑8PAHs) ranged from 0.17 to 5.40 ng m-3, polychlorinated biphenyls (as ∑7PCBi) from 0.06 to 4.70 ng.m3 and polybromodiphenyl ethers (as ∑8PBDEs) from 0.002 to 0.40 ng m-3. For most pollutants, significantly higher concentrations were observed in the nursery compared to the apartment and office. Overall, the indoor air concentrations were up to ten times higher than outdoor air concentrations. Seasonal variations were observed for PAEs, PCBs and PAHs. SVOCs were predominantly identified in the gaseous phase (>90%), except for some high-molecular-weight PAEs, PAHs and PCBs.

  6. Antimicrobial activity of bone cements embedded with organic nanoparticles.

    PubMed

    Perni, Stefano; Thenault, Victorien; Abdo, Pauline; Margulis, Katrin; Magdassi, Shlomo; Prokopovich, Polina

    2015-01-01

    Infections after orthopedic surgery are a very unwelcome outcome; despite the widespread use of antibiotics, their incidence can be as high as 10%. This risk is likely to increase as antibiotics are gradually losing efficacy as a result of bacterial resistance; therefore, novel antimicrobial approaches are required. Parabens are a class of compounds whose antimicrobial activity is employed in many cosmetic and pharmaceutical products. We developed propylparaben nanoparticles that are hydrophilic, thus expanding the applicability of parabens to aqueous systems. In this paper we assess the possibility of employing paraben nanoparticles as antimicrobial compound in bone cements. The nanoparticles were embedded in various types of bone cement (poly(methyl methacrylate) [PMMA], hydroxyapatite, and brushite) and the antimicrobial activity was determined against common causes of postorthopedic surgery infections such as: Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, and Acinetobacter baumannii. Nanoparticles at concentrations as low as 1% w/w in brushite bone cement were capable of preventing pathogens growth, 5% w/w was needed for hydroxyapatite bone cement, while 7% w/w was required for PMMA bone cement. No detrimental effect was determined by the addition of paraben nanoparticles on bone cement compression strength and cytocompatibility. Our results demonstrate that paraben nanoparticles can be encapsulated in bone cement, providing concentration-dependent antimicrobial activity; furthermore, lower concentrations are needed in calcium phosphate (brushite and hydroxyapatite) than in acrylic (PMMA) bone cements. These nanoparticles are effective against a wide spectrum of bacteria, including those already resistant to the antibiotics routinely employed in orthopedic applications, such as gentamicin.

  7. Antimicrobial activity of bone cements embedded with organic nanoparticles

    PubMed Central

    Perni, Stefano; Thenault, Victorien; Abdo, Pauline; Margulis, Katrin; Magdassi, Shlomo; Prokopovich, Polina

    2015-01-01

    Infections after orthopedic surgery are a very unwelcome outcome; despite the widespread use of antibiotics, their incidence can be as high as 10%. This risk is likely to increase as antibiotics are gradually losing efficacy as a result of bacterial resistance; therefore, novel antimicrobial approaches are required. Parabens are a class of compounds whose antimicrobial activity is employed in many cosmetic and pharmaceutical products. We developed propylparaben nanoparticles that are hydrophilic, thus expanding the applicability of parabens to aqueous systems. In this paper we assess the possibility of employing paraben nanoparticles as antimicrobial compound in bone cements. The nanoparticles were embedded in various types of bone cement (poly(methyl methacrylate) [PMMA], hydroxyapatite, and brushite) and the antimicrobial activity was determined against common causes of postorthopedic surgery infections such as: Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, and Acinetobacter baumannii. Nanoparticles at concentrations as low as 1% w/w in brushite bone cement were capable of preventing pathogens growth, 5% w/w was needed for hydroxyapatite bone cement, while 7% w/w was required for PMMA bone cement. No detrimental effect was determined by the addition of paraben nanoparticles on bone cement compression strength and cytocompatibility. Our results demonstrate that paraben nanoparticles can be encapsulated in bone cement, providing concentration-dependent antimicrobial activity; furthermore, lower concentrations are needed in calcium phosphate (brushite and hydroxyapatite) than in acrylic (PMMA) bone cements. These nanoparticles are effective against a wide spectrum of bacteria, including those already resistant to the antibiotics routinely employed in orthopedic applications, such as gentamicin. PMID:26487803

  8. Occurrence of and dietary exposure to parabens in foodstuffs from the United States.

    PubMed

    Liao, Chunyang; Liu, Fang; Kannan, Kurunthachalam

    2013-04-16

    Parabens are esters of p-hydroxybenzoic acid and are widely used as preservatives in cosmetics, pharmaceuticals, foodstuffs, including beverages. Information on the occurrence of parabens in foodstuffs and dietary exposure of humans to these chemicals is not available. In this study, food samples (n = 267) collected from Albany, New York, United States, were grouped into eight categories, namely, beverages, dairy products, fats and oils, fish and shellfish, grains, meat, fruits, and vegetables, and analyzed for five parabens by high-performance liquid chromatography-tandem mass spectrometry. The majority (>90%) of food samples contained measurable concentrations of parabens, and the total concentrations (Σparabens; sum of five parabens) ranged from below the limit of quantitation to 409 ng/g fresh weight (mean: 9.67 ng/g; median: 0.92 ng/g). Methyl-, ethyl-, and propyl-parabens were the predominant compounds, accounting for ∼90% of the total concentrations. Butyl- and benzyl-parabens were less frequently detected. There were no significant differences in paraben concentrations among the eight food categories, including the canned foods. On the basis of the concentrations measured and per capita daily ingestion rates of foods, we estimated the daily intake (EDI; ng/kg of body weight (bw)/day)) of parabens through food ingestion. The EDI values of total parabens (calculated from the mean concentrations measured and the mean daily ingestion rates of food items) were 940, 879, 470, 273, and 307 ng/kg bw/day for infants, toddlers, children, teenagers, and adults, respectively. To our knowledge, this is the first study to report the occurrence of parabens in foodstuffs.

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

    PubMed

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

    2014-05-01

    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).

  10. Disruption of 3D MCF-12A Breast Cell Cultures by Estrogens – An In Vitro Model for ER-Mediated Changes Indicative of Hormonal Carcinogenesis

    PubMed Central

    Marchese, Stephanie; Silva, Elisabete

    2012-01-01

    Introduction Estrogens regulate the proliferation of normal and neoplastic breast epithelium. Although the intracellular mechanisms of estrogens in the breast are largely understood, little is known about how they induce changes in the structure of the mammary epithelium, which are characteristic of breast cancer. In vitro three dimensional (3D) cultures of immortalised breast epithelial cells recapitulate features of the breast epithelium in vivo, including formation of growth arrested acini with hollow lumen and basement membrane. This model can also reproduce features of malignant transformation and breast cancer, such as increased cellular proliferation and filling of the lumen. However, a system where a connection between estrogen receptor (ER) activation and disruption of acini formation can be studied to elucidate the role of estrogens is still missing. Methods/Principal Findings We describe an in vitro 3D model for breast glandular structure development, using breast epithelial MCF-12A cells cultured in a reconstituted basement membrane matrix. These cells are estrogen receptor (ER)α, ERβ and G-protein coupled estrogen receptor 1 (GPER) competent, allowing the investigation of the effects of estrogens on mammary gland formation and disruption. Under normal conditions, MCF-12A cells formed organised acini, with deposition of basement membrane and hollow lumen. However, treatment with 17β-estradiol, and the exogenous estrogens bisphenol A and propylparaben resulted in deformed acini and filling of the acinar lumen. When these chemicals were combined with ER and GPER inhibitors (ICI 182,780 and G-15, respectively), the deformed acini recovered normal features, such as a spheroid shape, proliferative arrest and luminal clearing, suggesting a role for the ER and GPER in the estrogenic disruption of acinar formation. Conclusion This new model offers the opportunity to better understand the role of the ER and GPER in the morphogenesis of breast glandular

  11. Nutrients versus emerging contaminants-Or a dynamic match between subsidy and stress effects on stream biofilms.

    PubMed

    Aristi, I; Casellas, M; Elosegi, A; Insa, S; Petrovic, M; Sabater, S; Acuña, V

    2016-05-01

    Freshwater ecosystems are threatened by multiple anthropogenic stressors, which might be differentiated into two types: those that reduce biological activity at all concentrations (toxic contaminants), and those that subsidize biological activity at low concentrations and reduce it at high concentrations (assimilable contaminants). When occurring in mixtures, these contaminants can have either antagonistic, neutral or synergistic effects; but little is known on their joint effects. We assessed the interaction effects of a mixture of assimilable and toxic contaminants on stream biofilms in a manipulative experiment using artificial streams, and following a factorial design with three nutrient levels (low, medium or high) and either presence or absence of a mixture of emerging contaminants (ciprofloxacin, erythromycin, diclofenac, methylparaben, and sulfamethoxazole). We measured biofilm biomass, basal fluorescence, gross primary production and community respiration. Our initial hypotheses were that biofilm biomass and activity would: increase with medium nutrient concentrations (subsidy effect), but decrease with high nutrient concentrations (stress effect) (i); decrease with emerging contaminants, with the minimum decrease at medium nutrient concentrations (antagonistic interaction between nutrients subsidy and stress by emerging contaminants) and the maximum decrease at high nutrient concentrations (synergistic interaction between nutrients and emerging contaminants stress) (ii). All the measured variables responded linearly to the available nutrients, with no toxic effect at high nutrient concentrations. Emerging contaminants only caused weak toxic effects in some of the measured variables, and only after 3-4 weeks of exposure. Therefore, only antagonistic interactions were observed between nutrients and emerging contaminants, as medium and high nutrient concentrations partly compensated the harmful effects of emerging contaminants during the first weeks of the

  12. Parabens can enable hallmarks and characteristics of cancer in human breast epithelial cells: a review of the literature with reference to new exposure data and regulatory status.

    PubMed

    Darbre, Philippa D; Harvey, Philip W

    2014-09-01

    A framework for understanding the complexity of cancer development was established by Hanahan and Weinberg in their definition of the hallmarks of cancer. In this review, we consider the evidence that parabens can enable development in human breast epithelial cells of four of six of the basic hallmarks, one of two of the emerging hallmarks and one of two of the enabling characteristics. In Hallmark 1, parabens have been measured as present in 99% of human breast tissue samples, possess oestrogenic activity and can stimulate sustained proliferation of human breast cancer cells at concentrations measurable in the breast. In Hallmark 2, parabens can inhibit the suppression of breast cancer cell growth by hydroxytamoxifen, and through binding to the oestrogen-related receptor gamma may prevent its deactivation by growth inhibitors. In Hallmark 3, in the 10 nm-1 μm range, parabens give a dose-dependent evasion of apoptosis in high-risk donor breast epithelial cells. In Hallmark 4, long-term exposure (>20 weeks) to parabens leads to increased migratory and invasive activity in human breast cancer cells, properties that are linked to the metastatic process. As an emerging hallmark methylparaben has been shown in human breast epithelial cells to increase mTOR, a key regulator of energy metabolism. As an enabling characteristic parabens can cause DNA damage at high concentrations in the short term but more work is needed to investigate long-term, low-dose mixtures. The ability of parabens to enable multiple cancer hallmarks in human breast epithelial cells provides grounds for regulatory review of the implications of the presence of parabens in human breast tissue.

  13. Fast and sensitive method to determine parabens by capillary electrophoresis using automatic reverse electrode polarity stacking mode: application to hair samples.

    PubMed

    Sako, Alysson V F; Dolzan, Maressa D; Micke, Gustavo Amadeu

    2015-09-01

    This paper describes a fast and sensitive method for the determination of methyl, ethyl, propyl, and butylparaben in hair samples by capillary electrophoresis using automatic reverse electrode polarity stacking mode. In the proposed method, solutions are injected using the flush command of the analysis software (940 mbar) and the polarity switching is carried out automatically immediately after the sample injection. The advantages compared with conventional stacking methods are the increased analytical frequency, repeatability, and inter-day precision. All analyses were performed in a fused silica capillary (50 cm, 41.5 cm in effective length, 50 μm i.d.), and the background electrolyte was composed of 20 mmol L(-1) sodium tetraborate in 10 % of methanol, pH 9.3. For the reverse polarity, -25 kV/35 s was applied followed by application of +30 kV for the electrophoretic run. Temperature was set at 20 °C, and all analytes were monitored at 297 nm. The method showed acceptable linearity (r (2) > 0.997) in the studied range of 0.1-5.0 mg L(-1), limits of detection below 0.017 mg L(-1), and inter-day, intra-day, and instrumental precision better than 6.2, 3.6, and 4.6 %, respectively. Considering parabens is widely used as a preservative in many products and the reported possibility of damage to the hair and also to human health caused by these compounds, the proposed method was applied to evaluate the adsorption of parabens in hair samples. The results indicate that there is a greater adsorption of methylparaben compared to the other parabens tested and also dyed hairs had a greater adsorption capacity for parabens than natural hairs.

  14. Assumed non-persistent environmental chemicals in human adipose tissue; matrix stability and correlation with levels measured in urine and serum.

    PubMed

    Artacho-Cordón, F; Arrebola, J P; Nielsen, O; Hernández, P; Skakkebaek, N E; Fernández, M F; Andersson, A M; Olea, N; Frederiksen, H

    2017-03-22

    The aim of this study was to (1) optimize a method for the measurement of parabens and phenols in adipose tissue, (2) evaluate the stability of chemical residues in adipose tissue samples, and (3) study correlations of these compounds in urine, serum, and adipose tissue. Samples were obtained from adults undergoing trauma surgery. Nine phenols and seven parabens were determined by isotope diluted TurboFlow-LC-MS/MS. The analytical method showed good accuracy and precision. Limits of detection (LOD) for parabens and phenols ranged from 0.05 to 1.83ng/g tissue. Good recovery rates were found, even when biological samples remained defrosted up to 24h. Benzophenone-3 (BP-3; range of values: methylparaben (MeP; 70% of adipose tissue samples, while bisphenol-A (BPA; 40% of adipose tissue samples. In general, levels were similar between adipose tissue and serum, while a correlation between adipose tissue and urine was only found for BP-3. In conclusion, adipose tissue samples in this study were found to contain environmental chemicals considered to be non-persistent, whose levels were weakly or not at all correlated with the urine burden. Therefore, adipose tissue may potentially provide additional information to that obtained from other biological matrices. Further investigations are warranted to explore whether adipose tissue might be a suitable matrix for assessment of the consequences for human health of mid/long-term exposure to these chemicals.

  15. Activation of the mTOR pathway by low levels of xenoestrogens in breast epithelial cells from high-risk women

    PubMed Central

    Goodson, William H.; Luciani, Maria Gloria; Sayeed, S. Aejaz; Jaffee, Ian M.; Moore, Dan H.

    2011-01-01

    Breast cancer is an estrogen-driven disease. Consequently, hormone replacement therapy correlates with disease incidence. However, increasing male breast cancer rates over the past three decades implicate additional sources of estrogenic exposure including wide spread estrogen-mimicking chemicals or xenoestrogens (XEs), such as bisphenol-A (BPA). By exposing renewable, human, high-risk donor breast epithelial cells (HRBECs) to BPA at concentrations that are detectable in human blood, placenta and milk, we previously identified gene expression profile changes associated with activation of mammalian target of rapamycin (mTOR) pathway genesets likely to trigger prosurvival changes in human breast cells. We now provide functional validation of mTOR activation using pairwise comparisons of 16 independent HRBEC samples with and without BPA exposure. We demonstrate induction of key genes and proteins in the PI3K-mTOR pathway—AKT1, RPS6 and 4EBP1 and a concurrent reduction in the tumor suppressor, phosphatase and tensin homolog gene protein. Altered regulation of mTOR pathway proteins in BPA-treated HRBECs led to marked resistance to rapamycin, the defining mTOR inhibitor. Moreover, HRBECs pretreated with BPA, or the XE, methylparaben (MP), surmounted antiestrogenic effects of tamoxifen showing dose-dependent apoptosis evasion and induction of cell cycling. Overall, XEs, when tested in benign breast cells from multiple human subjects, consistently initiated specific functional changes of the kind that are attributed to malignant onset in breast tissue. Our observations demonstrate the feasibility of studying renewable human samples as surrogates and reinforce the concern that BPA and MP, at low concentrations detected in humans, can have adverse health consequences. PMID:21890461

  16. Phototoxicity and chronic toxicity of methyl paraben and 1,2-hexanediol in Daphnia magna.

    PubMed

    Lee, Jiyun; Park, Nayeon; Kho, Younglim; Lee, Kiyoung; Ji, Kyunghee

    2017-01-01

    Parabens are used as antimicrobial preservatives in consumer products. Exposure to methylparaben (MP) has been associated with adverse health outcomes, therefore, an alternative compound, 1,2-hexanediol (1,2-H), has been applied for cosmetics. In the present study, the phototoxicity of MP and 1,2-H, as well as the toxic effect caused by chronic exposure, were investigated using Daphnia magna. The 48 h acute toxicity tests with D. magna were conducted under indoor or ultraviolet (UV) light irradiation conditions, i.e., exposure to 4 h/d sunlight. Changes in the transcription of genes related to oxidative stress were determined in D. magna juveniles, to investigate the underlying mechanism of phototoxicity. The 21 d chronic toxicity tests of MP and 1,2-H were performed under indoor light irradiation. Exposure to MP under environmental level of UV light was more detrimental to D. magna. Transcripts of catalase and glutathione-S-transferase genes in D. magna was significantly increased by co-exposure to MP and UV light. After 21 d of chronic exposure to MP and 1,2-H, the reproduction no-observed effect concentrations for D. magna were 1 and >10 mg/L, respectively. The present study showed that exposure to UV could magnify the toxicity of MP on daphnids. Although acute and chronic toxicities of 1,2-H were generally lower than those of MP, its effects on other aquatic organisms should not be ignored. Further studies are needed to identify other mechanisms of MP phototoxicity.

  17. Establishing the importance of oil-membrane interactions on the transmembrane diffusion of physicochemically diverse compounds.

    PubMed

    Najib, Omaima N; Martin, Gary P; Kirton, Stewart B; Sallam, Al-Sayed; Murnane, Darragh

    2016-06-15

    The diffusion process through a non-porous barrier membrane depends on the properties of the drug, vehicle and membrane. The aim of the current study was to investigate whether a series of oily vehicles might have the potential to interact to varying degrees with synthetic membranes and to determine whether any such interaction might affect the permeation of co-formulated permeants: methylparaben (MP); butylparaben (BP) or caffeine (CF). The oils (isopropyl myristate (IPM), isohexadecane (IHD), hexadecane (HD), oleic acid (OA) and liquid paraffin (LP)) and membranes (silicone, high density polyethylene and polyurethane) employed in the study were selected such that they displayed a range of different structural, and physicochemical properties. Diffusion studies showed that many of the vehicles were not inert and did interact with the membranes resulting in a modification of the permeants' flux when corrected for membrane thickness (e.g. normalized flux of MP increased from 1.25±0.13μgcm(-1)h(-1) in LP to 17.94±0.25μgcm(-1)h(-1)in IPM). The oils were sorbed differently to membranes (range of weight gain: 2.2±0.2% for polyurethane with LP to 105.6±1.1% for silicone with IHD). Membrane interaction was apparently dependent upon the physicochemical properties including; size, shape, flexibility and the Hansen solubility parameter values of both the membranes and oils. Sorbed oils resulted in modified permeant diffusion through the membranes. No simple correlation was found to exist between the Hansen solubility parameters of the oils or swelling of the membrane and the normalized fluxes of the three compounds investigated. More sophisticated modelling would appear to be required to delineate and quantify the key molecular parameters of membrane, permeant and vehicle compatibility and their interactions of relevance to membrane permeation.

  18. Stability indicating LC method for simultaneous determination of irbesartan and hydrochlorothiazide in pharmaceutical preparations.

    PubMed

    Rane, V P; Patil, K R; Sangshetti, J N; Yeole, R D; Shinde, D B

    2010-08-01

    A simple and precise stability-indicating liquid chromatography method is developed and validated for the quantitative simultaneous estimation of irbesartan (IRB) and hydrochlorothiazide (HCTZ) in combined pharmaceutical dosage form. A chromatographic separation of the two drugs was achieved with an Ace5 C(18) 25-cm analytical column using buffer-acetonitrile (70:30 v/v). The buffer used in mobile phase contains 50 mM ammonium acetate pH adjusted 5.5 with acetic acid. The instrumental settings are flow rate of 1.5 mL/min, column temperature at 30 degrees C, and detector wavelength of 235 nm using a photodiode array detector. IRB, HCTZ, and their combination drug products were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Peak homogeneity data of IRB and HCTZ is obtained using photodiode array detector. In the stressed sample chromatograms, it demonstrated the specificity of the assay method for their estimation in presence of degradation products. The described method shows excellent linearity over a range of 10-200 microg/mL for IRB and 5-100 microg/mL for HCTZ. Methylparaben was used as internal standard. The correlation coefficient for IRB and HCTZ are 0.998 and 0.999. The mean recovery values for IRB and HCTZ ranged from 100.45% to 101.25%. The limit of detection for IRB and HCTZ were 0.019 and 0.023 microg/mL, respectively, and the limit of quantification were 0.053 and 0.070 microg/mL, respectively. The proposed method was suitable for quantitative determination and stability study of IRB and HCTZ in pharmaceutical preparations and also can be used in the quality control of bulk manufacturing and pharmaceutical dosage forms.

  19. 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.

    PubMed

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

    2015-07-01

    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 μgL(-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 μgL(-1) (depending on the paraben), average relative recoveries (RR, in %) of 80.3% at the low spiked level (7 μgL(-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 μgg(-1) for EPB in the healing cream analyzed to 1.12 ± 0.07 mgg(-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

  20. A novel method to generate monocyte-derived dendritic cells during coculture with HaCaT facilitates detection of weak contact allergens in cosmetics.

    PubMed

    Frombach, Janna; Sonnenburg, Anna; Krapohl, Björn-Dirk; Zuberbier, Torsten; Stahlmann, Ralf; Schreiner, Maximilian

    2017-01-01

    The in vitro sensitization assay LCSA (Loose-fit Coculture-based Sensitization Assay) has proved reliable for the detection of contact sensitizers in the past. However, the coculture of human monocyte-derived dendritic cells (DCs) with primary human keratinocytes (KCs) in serum-free medium is relatively complex compared to other sensitization assays which use continuous cell lines. To facilitate high-throughput screening of chemicals, we replaced KCs with the HaCaT cell line under various culture conditions. Coculture of HaCaT with peripheral blood mononuclear cells in serum-supplemented medium leads to generation of CD1a(+)/CD1c(+) DCs after addition of GM-CSF, IL-4, and TGF-β1 (as opposed to CD1a(-)/CD1c(-) DCs which arise in the "classic" LCSA coculture). These cells resemble monocyte-derived DCs generated in monoculture, but, unlike those, they show a marked upregulation CD86 after treatment with contact allergens. All of the nine sensitizers in this study were correctly identified by CD1a(+)/CD1c(+) DCs in coculture with HaCaT. Among the substances were weak contact allergens such as propylparaben (which is false negative in the local lymph node assay in mice) and resorcinol (which was not detected by CD1a(-)/CD1c(-) DCs in the "classic" LCSA). The level of CD86 upregulation on CD1a(+)/CD1c(+) DCs was higher for most allergens compared to CD1a(-)/CD1c(-) DCs, thus improving the assay's discriminatory power. Three out of four non-sensitizers were also correctly assessed by the coculture assay. A false-positive reaction to caprylic (octanoic) acid confirms earlier results that some fatty acids are able to induce CD86 on DC in vitro. In conclusion, change of the LCSA protocol led to reduction of time and cost while even increasing the assay's sensitivity and discriminatory power.

  1. Ecological risks of home and personal care products in the riverine environment of a rural region in South China without domestic wastewater treatment facilities.

    PubMed

    Zhang, Nai-Sheng; Liu, You-sheng; Van den Brink, Paul J; Price, Oliver R; Ying, Guang-Guo

    2015-12-01

    Home and personal care products (HPCPs) including biocides, benzotriazoles (BTs) and ultraviolet (UV) filters are widely used in our daily life. After use, they are discharged with domestic wastewater into the receiving environment. This study investigated the occurrence of 29 representative HPCPs, including biocides, BTs and UV filters, in the riverine environment of a rural region of South China where no wastewater treatment plants were present, and assessed their potential ecological risks to aquatic organisms. The results showed the detection of 11 biocides and 4 BTs in surface water, and 9 biocides, 3 BTs and 4 UV filters in sediment. In surface water, methylparaben (MeP), triclocarban (TCC), and triclosan (TCS) were detected at all sites with median concentrations of 9.23 ng/L, 2.64 ng/L and 5.39 ng/L, respectively. However, the highest median concentrations were found for clotrimazole (CLOT), 5-methyl-1H-benzotriazole (MBT) and carbendazim (CARB) at 55.6 ng/L, 33.7 ng/L and 13.8 ng/L, respectively. In sediment, TCC, TCS, and UV-326 were detected with their maximum concentrations up to 353 ng/g, 155 ng/g, and 133 ng/g, respectively. The concentrations for those detected HPCPs in surface water and sediment were generally lower in the upper reach (rural area) of Sha River than in the lower reach of Sha River with close proximity to Dongjiang River (Pt-test<0.05), indicating other input sources of HPCPs in the lower reach. Biocides showed significantly higher levels in surface water in the wet season than in the dry and intermediate seasons. Preliminary risk assessment demonstrated that the majority of HPCPs monitored represented low risk in surface waters. There are potentially greater risks to aquatic organisms from the use of TCS and TCC in the wet season than in dry and intermediate seasons in surface waters. This preliminary assessment also indicates potential concerns associated with TCC, TCS, DEET, CARB, and CLOT in sediments, although additional data