Parabens Research Articles

Picking Up on Preservatives: New Biomarkers for Gauging Paraben Exposure

As scientists seek to characterize human exposures to chemicals, they need more valid, accurate biomarkers—telltale molecular signatures that indicate a particular exposure has occurred. A team from the CDC has now provided the field with a new biomarker that could help researchers document exposures to a class of antimicrobial preservatives called parabens [EHP 114:1843–1846; Ye et al.]. Parabens are used in shampoos, cosmetics, moisturizers, medications, foods, and beverages. Concerns have arisen about the potential human health risks associated with the widespread use of these weakly estrogenic compounds, including widely publicized speculation that parabens in antiperspirants were linked to breast cancer. Although that theory was later refuted, frequent and common human exposure to parabens means that research attention will continue to focus on these chemicals. Until now, the only biomarker used for human paraben exposure was p-hydroxybenzoic acid in urine. But that metabolite is produced by the hydrolysis of all of the various paraben compounds, so it is nonspecific to individual parabens, which vary widely in estrogenic bioactivity. The CDC team measured the presence of free and conjugated parent parabens in urine to determine their suitability to be biomarkers of human exposures. They analyzed the urinary concentrations of methyl, ethyl, n-propyl, butyl (n- and iso-), and benzyl parabens in 100 human adults with no known industrial exposure to the compounds. The results appear to support the viability of those measures as biomarkers of exposure. Methyl and n-propyl parabens, the parabens most commonly used in cosmetics and foods, were found at the highest median concentrations in almost all the samples—99% contained the former and 96% the latter. The authors say this could result from the widespread use of these compounds; from differences in the absorption, distribution, metabolism, and excretion of the various parabens; or from a combination of both factors. Other parent compounds, such as ethyl and butyl paraben, appeared in more than half of the samples. Regardless of the reason for such high frequencies of detection, the researchers say their results suggest that urinary parabens and their conjugates could be valid biomarkers of exposure to these chemicals. The detection and measurement methodologies used by the CDC scientists could help investigators as they seek to characterize the potential health risks associated with exposure to the individual paraben compounds.

Parabens as urinary biomarkers of exposure in humans.

BackgroundParabens appear frequently as antimicrobial preservatives in cosmetic products, in pharmaceuticals, and in food and beverage processing. In vivo and in vitro studies have revealed weak estrogenic activity of some parabens. Widespread use has raised concerns about the potential human health risks associated with paraben exposure.ObjectivesAssessing human exposure to parabens usually involves measuring in urine the conjugated or free species of parabens or their metabolites. In animals, parabens are mostly hydrolyzed to p-hydroxybenzoic acid and excreted in the urine as conjugates. Still, monitoring urinary concentrations of p-hydroxybenzoic acid is not necessarily the best way to assess exposure to parabens. p-Hydroxybenzoic acid is a nonspecific biomarker, and the varying estrogenic bioactivities of parabens require specific biomarkers. Therefore, we evaluated the use of free and conjugated parent parabens as new biomarkers for human exposure to these compounds.ResultsWe measured the urinary concentrations of methyl, ethyl, n-propyl, butyl (n- and iso-), and benzyl parabens in a demographically diverse group of 100 anonymous adults. We detected methyl and n-propyl parabens at the highest median concentrations (43.9 ng/mL and 9.05 ng/mL, respectively) in nearly all (> 96%) of the samples. We also detected other parabens in more than half of the samples (ethyl, 58%; butyl, 69%). Most important, however, we found that parabens in urine appear predominantly in their conjugated forms.ConclusionsThe results, demonstrating the presence of urinary conjugates of parabens in humans, suggest that such conjugated parabens could be used as exposure biomarkers. Additionally, the fact that conjugates appear to be the main urinary products of parabens may be important for risk assessment.

Quantification of the urinary concentrations of parabens in humans by on-line solid phase extraction-high performance liquid chromatography–isotope dilution tandem mass spectrometry

Parabens (alkyl esters of p-hydroxybenzoic acid) are widely used as antimicrobial preservatives in cosmetic products, pharmaceuticals, and food processing. However, weak estrogenicity of some parabens has been revealed from several studies. Human exposure to parabens may be assessed by measuring the conjugated or free species of these compounds or their metabolites in urine. We have developed a method using on-line solid phase extraction-high performance liquid chromatography–isotope dilution tandem mass spectrometry with peak focusing to measure the urinary concentrations of methyl, ethyl, propyl, n- and iso- butyl, and benzyl parabens. This method has good reproducibility and accuracy with detection limits for all analytes below 0.2 ng/mL in 100 μL of urine, and permits quick and accurate analysis of a large number of samples in epidemiologic studies for assessing the prevalence of human exposure to parabens. Using this method, we detected methyl, ethyl, and propyl parabens, mostly as conjugated species, in 22 urine samples collected from anonymous adults.

Optimisation of a solid-phase microextraction method for the determination of parabens in water samples at the low ng per litre level

A procedure for the determination of five esters of p-hydroxybenzoic acid (parabens) in water samples is presented. Analytes (methyl, ethyl, propyl, butyl and benzyl paraben) are concentrated on a solid-phase microextraction (SPME) fibre, converted on their tert-butyldimethylsilyl derivatives and selectively determined using gas chromatography in combination with tandem mass spectrometry (GC–MS/MS). Influence of different factors on the efficiency of extraction and on-fibre derivatization steps is described in detail. For all species, the highest enrichment factors were achieved using a polyacrylate (PA) fibre exposed directly to stirred water samples, containing 150 mg/ml of sodium chloride, at room temperature. Performance of the further on-fibre derivatization reaction was also maximum at room temperature, considering a short exposition period of the SPME fibre to vapours of the silylation reagent. Under optimised conditions, the proposed method achieved quantification limits from 0.001 to 0.025 ng/ml and it was free of matrix effects; therefore, external calibration can be used as the quantification technique. From our knowledge, this work describes the first application of SPME and gas chromatography to the determination of parabens in water. The analysis of a limited number of real samples revealed the presence of parabens in raw sewage water at concentrations up to 3 ng/ml.

Determination of Parabens in Pharmaceutical Formulations by Solid-Phase Microextraction-Ion Mobility Spectrometry

Solid-phase microextraction (SPME) coupled with ion mobility spectrometry (IMS) was used for the detection and quantitation of 4-hydroxybenzoate preservatives, methylparaben, ethylparaben, propylparaben, and butylparaben, in commercial pharmaceutical products. For the first time, SPME-IMS is described for the simultaneous detection, separation, and quantitation of multiple analytes in complex matrixes. The parabens are extracted from the samples using SPME, and the analytes on the fiber are heated by the IMS desorber unit and vaporized into the drift tube. The four preservatives differing only by a methyl group were separated in less than 18 ms. The analytical procedure was optimized for fiber coating selection, extraction time, sample pH, sample volume, ionic strength, and IMS conditions. Separation characteristics such as resolution, theoretical plates, and drift times of the parabens were also evaluated based on the direct interfacing of SPME to IMS. The conditions were tested using six over-the-counter topical products containing various combinations of preservatives. Analysis of the samples by SPME-IMS using benzyl paraben as an internal standard yields good comparison to an HPLC method, thereby reinforcing the applicability of this technique as a method for routine analysis. Limits of detection were 10 ng/mL for methylparaben and ethylparaben and 5 ng/mL for propylparaben and butylparaben. Good linearity range and reproducibility of less than 8% were obtained.

High-performance Liquid Chromatographic Analysis of Sildenafil Citrate and Methyltestosterone Adulterants in a Herbal Medicine

Sildenafil citrate (Viagra) and methyltestosterone were detected in herbal medicine capsules from mainland China by thin layer chromatography (TLC), ultraviolet spectrometry (UV), gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass-mass spectrometry (LC-MS-MS). The sample was further assayed by high-performance liquid chromatography (HPLC). Separation was conducted on an Inertsil ODS-2 reversed-phase column using gradient: elution with acetonitrile and 0.1 % (v/v) phosphoric acid as the mobile phase. Propyl paraben was used as an internal standard and the monitor wavelength was 254 nm. Calibration curves of standard sildenafil citrate and methyltestosterone were constructed in the range of 80-800 and 20-200μ/m L, respectively. The relative standard deviations of sildenafil citrate and methyltestosterone for intra-day and inter-day analyses were 0.54-3.56 % and 1.62-3.75 %, respectively. The recoveries of the synthetic drugs from herbal medicine ranged from 98.0 to 100.4 %. The sildenafil citrate and methyltestosterone content in herbal medicine was 20.0 and 1.6 mg/cap, respectively.

Epikutantest-Reaktionen auf Paraben-Mixe und ihre Aufschlüsselungen. Studien der Deutschen Kontaktallergie-Gruppe (DKG) und des Informationsverbundes dermatologischer Kliniken (IVDK), 1990 – 2000

Parabens are commonly used preservatives in topical preparations, including cosmetics, in medicines, and in food. They are capable of inducing contact sensitisation, especially in patients with stasis dermatitis. Between 1990 and 1994, a mix containing 5 parabens (benzyl-, butyl-, ethyl-, methyl- and propylparaben, 3% each) was used for diagnostic patch testing. Of 23025 patients tested with this mix, 1.6% had positive test reactions. In break-down testing with single constituents (tested with 3%) mainly benzyl paraben, which was not tested (and not used) due to possible carcinogenic risk any more, and propyl caused positive test reactions (in 10 of 184 and 13 of 616 patients, respectively). The sensitivity of the mix with regard to detecting contact allergy to one (or more) of the constituents was 88% and specifity 96%; however, the positive predictive value (PPV) was only 23%, i.e., about 3/4 false-positive reactions occurred. In a subsequent study of the German Contact Dermatitis Research Group (DKG) 1286 patients were patch tested with the above mentioned mix, which had to be replaced, and 2 mixes (4 x 3% and 4 x 4%) containing the remaining parabens; positive reactions were observed in 2.1%, 1.2% and 1.5%, respectively. The sensitivity of the new mixes was lower (47% and 53%, resp.), however, the PPV (44% and 42%, resp.) was more acceptable. Between 1995 and 2000 altogether 51260 patients were patch tested with the standard series, including the 4 x 4% paraben-mix in the IVDK centres, with 1.5% positive reactions. Break-down testing was performed in 1270 of these. The diagnostic performance of the mix found here (sensitivity: 78%, PPV: 44%) was similar to that in the DKG-study. In conclusion, patch testing with parabens is still difficult, in particular, as several paraben paradoxes hamper the application of a valid gold standard (e.g., a repeated open application test [ROAT] on uninvolved skin) when judging patch test reactions. Despite these limitations in risk assessment, parabens can be regarded as relatively safe, although this benefit is somewhat limited by the necessity to add other - potentially more sensitising - biocides to achieve adequate protection against microbial decay in some products.

Discontinuous electrokinetic chromatography of parabens using different substituted resonances as pseudostationary phases

Discontinuous electrokinetic chromatography of parabens using different substituted resonances as pseudostationary phases

Contact allergy to benzyl alcohol and benzyl paraben

Contact allergy to benzyl alcohol and benzyl paraben

Respiratory smooth muscle relaxing effect of commercial steroid preparations.

The isolated guinea pig trachea was used as an animal model to test the possible direct effect of dexamethasone phosphate injectable solutions on bronchial smooth muscle. the dose-dependent relaxation and the potentiation of both isoproterenol and dibutyryl cyclic 3′,5′-adenosine monophosphate that was found for these glucocorticoid solutions on tracheal smooth muscle was due to the preservatives methyl and propyl paraben that are present in these and most glucocorticoid solutions and was not due to the dexamethasone phosphate. In high doses (> 50 µg per ml), dexamethasone phosphate itself caused contraction of guinea pig trachea. the dexamethasone phosphate itself did not potentiate either isoproterenol or dibutyryl cyclic 3′,5′-adenosine monophosphate. Hence, the mechanism of action of dexamethasone on trachea differs from that of other glucocorticoids on vascular smooth muscle because others have been reported to potentiate catecholamines on vascular smooth muscle. the mechanism of action of the parabe...

Solubility of Alkyl Benzoates II: Effect of Dielectric Constant on the Solubility of Substituted Alkyl Benzoates

The solubility of a homologous series of alkyl parabens, ranging from methyl to butyl together with benzyl paraben and methyl p-methoxybenzoate, were evaluated in solvents consisting of polyethylene glycol and water in various proportions. The relationship between dielectric constant value and mutual solubilizing effect, which was observed upon combining two parabens (benzyl paraben with any one of the parabens in the series), was evaluated. Decreasing the dielectric constant value of the solvent induced solubility of these esters. The dielectric constant, however, was observed to be not the sole factor, and there seems to exist a concentration effect of one paraben on the solubility of the other.

Solubility of Alkyl Benzoates I: Effect of Some Alkyl p-Hydroxybenzoates (Parabens) on the Solubility of Benzyl p-Hydroxybenzoate

The solubility features of a homologous series of alkyl p-hydroxybenzoates (parabens) with alkyl groups, in an ascending order from methyl to n-butyl, were investigated together with benzyl paraben and methyl p-methoxybenzoate. A phenomenon of mutual solubilizing potential was observed to exist when the solubility of a mixture of an alkyl paraben and benzyl paraben in 60% polyethylene glycol 400-water was examined. The analysis was carried out by means of UV spectrophotometry and NMR spectroscopy. The scope of application of these esters for their antimicrobial properties, for which they are primarily employed in pharmaceutical sciences, is envisaged to be augmented by considering factors influencing solubility.

Lidocaine vs parabens as convulsants

Lidocaine vs parabens as convulsants

1234. Parabens pose no real threat

Esters of p-hydroxybenzoic acid, commonly known as parabens are preservatives used in a variety of personal care products, cosmetics, pharmaceutical and food products.This paper presents the results of studies on photochemical degradation of hazardous water contaminants – methyl- (MP), ethyl- (EP), propyl- (PP), butyl- (BuP), benzylparaben (BeP) and p-hydroxybenzoic acid (p-HBA) (individually or in mixture) using ultraviolet C lamps in the presence and absence of hydrogen peroxide. Both systems were very efficient on the degradation of the single parent compounds. Total removal of individual pollutant was achieved after 2 h or 6 min for UVC and UVC/H2O2, respectively. The kinetic constants of hydroxyl radicals reaction and the photolysis quantum yields were obtained for each pollutant. The decomposition of the mixture of the six compounds with the H2O2/UVC system ensures a complete degradation after 30 min with a degree of mineralization of 25%. Whereas only 10% of mineralization was observed after the same time for photolysis. The pseudo-first-order fluence-based rate constants (for UVC and H2O2/UVC) for each paraben in the mixture reaction were calculated for the first time. The analysis using UHPLC/MS/MS technique shows that hydroxylation is the main pathway of the reaction with hydroxyl radicals. In fact, p-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 3,4-dihydroxybenzoic acid were identified as a major transformation products. Moreover the mono, di and tri derivatives of parabens were detected as the main intermediates formed during oxidation. The fluence-based experimental data and cost analysis showed that the H2O2/UVC treatment was effective in mineralizing of the parabens mixture.