A sustainable and innovative method to determine parabens in body creams for exposure and risk assessment.

Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) are among the most widely used preservatives in cosmetics, drugs, and foods. These compounds have been associated with toxic effects due to the overuse of products with parabens in their formulation. The toxicity of parabens may be correlated to endocrine disruption, owing to their ability to mimic the actions of estradiol. In this paper, a simple, sustainable, robust, and innovative dispersive liquid-liquid microextraction (DLLME) technique was developed and employed to extract these xenobiotics from body cream samples, aiming to calculate the margin of safety (MoS) to assess the risk of exposure. The validated method presented suitable linearity (r > 0.99), lower limits of detection (ranging from 0.01 to 0.04 % w/w), and satisfactory precision and accuracy (ranging from 4.33 to 10.47, and from -14.25 to 13.85, respectively). Seven of the ten analysed samples presented paraben contents within the acceptable concentration according to European legislation. The MoS value obtained for PrP (37.58) suggested its reduced safety, indicating that PrP may significantly contribute to systemic exposure resulting from the use of personal care products.

Analysis of preservatives and fragrances in topical medical devices: The need for more stringent regulation.

INTRODUCTION: Medical devices (MDs) have a long history of use, and come with regulatory frameworks to ensure user safety. Although topically applied MDs in the form of gels and creams might be used on damaged skin, their composition is often similar to that of cosmetic products applicable to intact skin, especially in terms of preservatives and fragrances. However, unlike cosmetics, these products are not subject to compound-specific restrictions when used in MDs. OBJECTIVE: This study aimed to identify and quantify preservatives and fragrances in topically applied MDs and assess their safety towards the Cosmetic Regulation (EC) 1223/2009. METHOD: Sixty-nine MDs available on the EU market were subjected to previously validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods to identify and quantify occurring preservatives and fragrances. RESULTS: Findings revealed that 32% of the examined MDs did not provide comprehensive ingredient lists, leaving users uninformed about potential risks associated with product use. Furthermore, 30% of these MDs would not meet safety standards for cosmetic products and, most significantly, 13% of the analysed samples contained ingredients that are prohibited in leave-on cosmetics. CONCLUSION: Results highlight the pressing demand for more stringent requirements regarding the labelling and composition of MDs to enhance patient safety. Improved regulation and transparency can mitigate potential risks associated with the use of topically applied MDs.

A rapid and environmentally friendly method for determination of parabens preservatives in flavors by supercritical fluid chromatography-tandem mass spectrometry.

A rapid method for determination of parabens preservatives (methyl paraben, ethyl paraben, isopropyl paraben, propyl paraben, isobutyl paraben, and butyl paraben) in flavors was established by using supercritical fluid chromatography-tandem mass spectrometry combined with dispersive solid-phase extraction. After adding methanol and primary secondary amine to the sample simultaneously, high extraction efficiency and good sample cleanup could be obtained by simple shaking. Parabens were well separated on a Chiralpak IG-3 column in 6 min by gradient elution. Recoveries from spiked blank samples at 0.5, 1.0, and 5.0 mg/kg were determined to be 88.3-106.6%with relative standard deviations less than 8.0%. All analytes achieved good linear relation (r ≥ 0.999 2). The limits of detection for all analytes ranged from 0.03 to 0.09 mg/kg and the limits of quantification from 0.11 to 0.31 mg/kg, respectively. A total of 20 actual samples were successfully analyzed by taking the proposed method. Being simple, rapid, green, and reliable, this method can be taken for the determination of parabens preservatives in flavors.

Preservatives in non-cosmetic products: Increasing human exposure requires action for protection of health.

The widespread use of skin sensitizing preservatives is well-known. Contact allergy to preservatives is often caused by their presence in cosmetic products. Preservative use in non-cosmetic products is less well-known. We have reviewed European Union (EU) legislations on classification and labelling, biocides and cosmetics, concerning conditions for use of the most used sensitizing preservatives (including formaldehyde-releasing substances, isothiazolinones and parabens). We have analysed temporal trends in their use in non-cosmetic products (tonnes, number of products, concentrations), based on annual reports to the Swedish Products Register 1995-2018; and we discuss implications for stakeholders. Major changes over time are that the use of most of the preservatives has increased by tonnes and/or by number of products, and that several use concentrations have declined following harmonized classification as a skin sensitizer with low concentration limits for this classification. We conclude that the massive increase in use of preservatives is alarming, and that urgent action is needed for protection of health. Their use in non-cosmetic products is broad, increasing and often undisclosed. In the EU, legislations concerning chemicals can provide relevant restrictions to reduce their use and associated health risks, monitored by efficient surveillance. Prevention would be benefited by better coordination between legislations.

Ultraviolet filter, fragrance and preservative allergens in New Zealand sunscreens.

BACKGROUND/OBJECTIVES: Allergic contact dermatitis, photoallergic contact dermatitis and irritant reactions to sunscreens are common reasons for dermatology consultation. Patch testing for contact allergy relies on up-to-date knowledge of allergen exposures. The aim of this study was to investigate contact allergens and photoallergens in sunscreens commercially sold on the shelves of supermarkets and pharmacies in New Zealand. METHODS: A comprehensive market data review of suppliers' websites was performed from March to August 2019 to obtain a list of the commonly sold sunscreens in our region. Ingredients were collated and analysed according to International Nomenclature of Cosmetic Ingredients (INCI) names. Ultraviolet (UV) filters, preservatives and fragrances were included for analysis. Place of sale and cost of sunscreens were also recorded. RESULTS: Ninety-five sunscreens were analysed: 36% sold in supermarkets, 43% in pharmacies and the remainder available in both. The most frequent UV filters were butyl methoxydibenzoylmethane (contained in 70% of products) followed by octocrylene (63%) and homosalate (50%). The common photoallergen benzophenone 3 was found in 19% of products. Phenoxyethanol was the most common preservative (68%) followed by disodium EDTA (30%) and propylparaben (26%). Two sunscreens contained methylisothiazolinone. Sixty-one per cent contained at least one fragrance, the most frequent being limonene (17%) and linalool (13%). There was an average of 1.1 New Zealand baseline series allergens per product (range 0 to 6, standard deviation 1.27). CONCLUSION: Common allergens including those with high sensitising potential were frequently found in New Zealand sunscreen. Knowledge of ingredients used by manufacturers is useful in dermatological assessment of skin contact reactions.

Determination of Intact Parabens in the Human Plasma of Cancer and Non-Cancer Patients Using a Validated Fabric Phase Sorptive Extraction Reversed-Phase Liquid Chromatography Method with UV Detection.

Parabens have been widely employed as preservatives since the 1920s for extending the shelf life of foodstuffs, medicines, and daily care products. Given the fact that there are some legitimate concerns related to their potential multiple endocrine-disrupting properties, the development of novel bioanalytical methods for their biomonitoring is crucial. In this study, a fabric phase sorptive extraction reversed-phase liquid chromatography method coupled with UV detection (FPSE-HPLC-UV) was developed and validated for the quantitation of seven parabens in human plasma samples. Chromatographic separation of the seven parabens and p-hydroxybenzoic acid was achieved on a semi-micro Spherisorb ODS1 analytical column under isocratic elution using a mobile phase containing 0.1% (v/v) formic acid and 66% 49 mM ammonium formate aqueous solution in acetonitrile at flow rate 0.25 mL min-1 with a 24-min run time for each sample. The method was linear at a concentration range of 20 to 500 ng mL-1 for the seven parabens under study in human plasma samples. The efficiency of the method was proven with the analysis of 20 human plasma samples collected from women subjected to breast cancer surgery and to reconstructive and aesthetic breast surgery. The highest quantitation rates in human plasma samples from cancerous cases were found for methylparaben and isobutylparaben with average plasma concentrations at 77 and 112.5 ng mL-1. The high concentration levels detected agree with previous findings for some of the parabens and emphasize the need for further epidemiological research on the possible health effects of the use of these compounds.

Paraben concentrations in human fingernail and its association with personal care product use.

Parabens are used as antimicrobial preservatives in a range of consumer products. However, very limited information is available about the association between use of personal care products and paraben burden in human tissues. Accumulation of parabens in some non-destructive biomarkers (such as human fingernail) is essential for paraben biomonitoring. In this study, 50 human fingernail samples were collected from Nanjing, China. A subset of participants (n = 32) also provided their face cream samples (as the representative of personal care products). Six parabens, including methyl- (MeP), ethyl- (EtP), propyl- (PrP), butyl- (BuP), heptyl- (HeP), and benzyl-parabens (BzP), together with their major metabolites were measured in the fingernail and face cream samples. Total concentrations of parabens and their major metabolites were 39.9-27400 ng/g in fingernails. MeP, PrP and EtP were the three dominant parabens in fingernails with median values of 3140, 1290, and 127 ng/g, respectively. Significantly higher levels in female fingernails than those in male fingernails were observed for MeP, PrP, EtP, BuP, and the MeP metabolite (methyl protocatechuate, OH-MeP) (p < 0.05). Adult fingernails contained greater concentrations of MeP and PrP than juvenile fingernails (p < 0.05). Positive correlations were observed for EtP (R = 0.36, p < 0.05) and BuP (R = 0.48, p = 0.008) concentrations between the fingernail and face cream samples. Our work is a preliminary study trying to explore the quantitative relationship between paraben concentrations in human body and use of personal care products. The result here provides a direct evidence that use of personal care products is one of the major sources for human exposure to parabens.

[Neonates exposure to parabens through medicines administered to inpatients]. / Exposition des nouveau-nés aux parabènes via les médicaments administrés durant leur hospitalisation.

OBJECTIVES: The objective of this study was to quantify parabens intake due to drug administration in neonates during hospitalization following their birth. METHOD: A monocentric prospective study was performed into a neonatalogy unit to collect all drug prescriptions. An exhaustive list of parabens containing medicines commercialized in France was completed from Theriaque® database. This list was combined with drug prescription to establish an exposure profile to parabens. For each paraben containing medicines, a HPLC-UV assay was performed to determine the average daily intake of paraben received by hospitalized neonates. RESULTS: More than 300 medicines commercialized in France contain at least one paraben. A combination of methylparaben and propylparaben was found in most cases. All hospitalized neonates (n=22) were exposed at least once to methylparaben and propylparaben through medicines while 50 % were exposed to ethylparaben. The average daily intake was higher in term newborns (572,0±249,0 versus 414,6±294,1µg/kg/j for methylparaben) but frequency was higher in prematures (65,0 versus 78,6% for methylparaben) as well as cumutives doses (1421,5±758,8 versus 8618,7±7922,3). These doses are lower than toxicological reference values but these latter do not take into account endocrine disrupting effects of these compounds. CONCLUSIONS: These results highlight medicines as a high source of exposure to parabens in hospitalized neonates. It should encourage pharmaceutical companies and health professionnal to prioritize therapeutic cares without parabens.

Migration regularity of six preservatives from wooden children's products to saliva and sweat based on microstructure-related migration models.

Wood preservatives in wooden children's products (WCPs) may migrate into children's body through oral and dermal exposure, resulting in a potential health risk. In this paper, a systematic investigation on the migration regularity of lindane and five chlorophenols preservatives from WCPs to saliva and sweat was introduced. Migration models were established based on the abundant migration data among different time periods (2 min-96 h). Wood exhibited complex porosity for various species, resulting in the deviation of the migration of preservatives from different samples. By introducing a correction coefficient (f) calculated based on the sample microstructure (specific surface area and pore distribution), the predicted values of correcting migration model matched better with the experimental data. Migration data indicated that exposure risks should be noticed when children were in contact with WCPs because a considerable quantity of preservatives migrated into the body in a short time. This work is expected to play a role in the formulation of chemical limit standards to promote the safety of WCPs, and may serve ideas as basis for the migration research of chemicals in wooden products.

GDME-based methodology for the determination of free formaldehyde in cosmetics and hygiene products containing formaldehyde releasers.

Formaldehyde is often applied in the industrial production of different products, such as textiles, insulation materials, or cosmetics, due to its preservative and disinfectant properties. However, formaldehyde is classified by the International Agency for Research on Cancer as carcinogenic, and there are numerous studies about the pernicious health effects that frequent exposure to formaldehyde can pose to human health. In the cosmetic industry, compounds called formaldehyde releasers are added during production, with the intent of releasing small amounts of formaldehyde over time. Although there are many methods available for the determination of formaldehyde, they are usually not suitable for the determination of free formaldehyde in cosmetics with formaldehyde releasers in their composition, as they can promote the accelerated release of formaldehyde. In this work, the gas-diffusion microextraction (GDME) technique was used for the extraction of formaldehyde from cosmetic and personal hygiene products. Acetylacetone was used as the derivatization reagent which was later used for the spectrophotometric determination of formaldehyde. The developed methodology exhibits limits of detection (1.98 mg kg-1) and quantification (6.60 mg kg-1) perfectly adequate for the determination of formaldehyde in these samples. Formaldehyde values between 6.9 ± 0.3 and 365 ± 15 mg kg-1 were found in samples containing the formaldehyde releasers DMDM hydantoin, Diazolidinyl urea, and Bronopol. Furthermore, mass spectrometry studies were performed in order to unbiasedly ensure the presence of formaldehyde in every extract. GDME proved to be an economical, simple, and robust alternative for the extraction of free formaldehyde in personal hygiene and cosmetic samples. Graphical abstract ᅟ.

Miniaturized matrix solid-phase dispersion coupled with supramolecular solvent-based microextraction for the determination of paraben preservatives in cream samples.

An analytical method is presented for the determination of paraben preservatives in semisolid cream samples by matrix solid-phase dispersion combined with supramolecular solvent-based microextraction. Due to the oily and sticky nature of the sample matrix, parabens were first extracted from the samples by matrix solid-phase dispersion using silica as sorbent material with a clean-up performed with tetrahydrofuran in the elution step. The eluate (500 µL), 1-decanol (120 µL), and water (4.4 mL) were then mixed in a polyethylene pipette to form supramolecular solvent. Finally, the analytes in the supramolecular solvent were separated and determined by liquid chromatography with ultraviolet detection. Under optimal extraction conditions, the extraction recoveries of the studied compounds were obtained in the range of 63-83%. The limits of detection for the analytes were between 0.03 and 0.04 µg/g. The precision of the method varied between 4.0-6.7 (intraday) and 6.2-7.9% (interday). Finally, the optimized procedure was applied to the determination of the target preservatives in a variety of cream samples (diaper rash, skin allergy, face and hand moisturizing) with satisfactory recoveries (86-102%).

The Risk of Microbial Contamination in Multiple-Dose Preservative-Free Ophthalmic Preparations.

Multiple-dose ophthalmic preparations that do not contain preservatives carry high risks of microbial contamination. However, there are various types of hospital preparations, with different physicochemical properties. In the present study, we evaluated the association between physicochemical properties and microbial contamination in ophthalmic preparations. The investigated hospital preparations included ophthalmic preparations of physiological saline, 0.2% fluconazole, 0.5% vancomycin hydrochloride, and 2% cyclosporine. We investigated the microbial dynamics of each ophthalmic preparation and microbial contamination in ophthalmic preparations used by patients. Remarkable growth of Pseudomonas aeruginosa, Burkholderia cepacia, and Serratia marcescens was observed in ophthalmic preparations of physiological saline and 0.2% fluconazole. All tested microorganisms displayed decreased counts after inoculation in 0.5% vancomycin hydrochloride. In 2% cyclosporine, all investigated microorganisms were below the limit of detection after inoculation for 6 h. The microbial contamination rates of ophthalmic preparations used by patients were 16.7% (3/18 samples) for 0.5% vancomycin hydrochloride and 0% (0/30 samples) for 2% cyclosporine. All detected contaminants in 0.5% vancomycin hydrochloride were Candida spp., one of which was present at a level of 1×104 colony-forming units/mL. The storage method for in-use ophthalmic preparations should be considered on the basis of their physicochemical properties.

Occurrence and concentrations of isothiazolinones in detergents and cosmetics in Switzerland.

BACKGROUND: In recent years, the frequency of contact allergy to isothiazolinones has increased alarmingly in Europe, but only limited data are available on concentrations of isothiazolinones in consumer products. OBJECTIVES: To examine the current frequency of isothiazolinones [methylisothiazolinone (MI), methylchloroisothiazolinone (MCI), benzisothiazolinone (BIT), and octylisothiazolinone (OIT)] in a wide array of detergents and cosmetics relevant for the Swiss population. METHODS: By means of a market survey, the occurrence of isothiazolinones was investigated in 1948 consumer products. Of these, 88 products were analysed by liquid chromatography-high-resolution mass spectrometry after ultrasonic extraction. RESULTS: Only 7.6% of all cosmetics contained isothiazolinones, but the prevalence in detergents was much higher (42.9%). The measured concentration ranges in detergents were 4.3­10, 3.5­279, 3.8­186 and 7.9 ppm (one product only) for MCI, MI, BIT, and OIT, respectively [corrected]. For cosmetics, these were 1.3-133 and 4.8 ppm (one product only) for MI and MCI, respectively. CONCLUSIONS: Our study has shown that high concentrations of isothiazolinones (including MI) can be found in a large variety of products, in particular in detergents. Therefore, the safe use of these preservatives should be re-evaluated by including detergents in the exposure assessment.

Thinned stone fruits are a source of polyphenols and antioxidant compounds.

BACKGROUND: Thinned fruits are agricultural by-products that contain large quantities of interesting compounds due to their early maturity stage. In this work, the phenolic profile and the antioxidant activity of six thinned stone fruits (apricot, cherry, flat peach, peach, plum and nectarine) have been investigated, focussing on proanthocyanidins. RESULTS: Thinned nectarine had the highest content of total phenols [67.43 mg gallic acid equivalents (GAE) g-1 dry weight (DW)] and total flavonoids (56.97 mg CE g-1 DW) as well as the highest antioxidant activity measured by DPPH scavenging (133.30 mg [Trolox equivalents (TE) g-1 DW] and FRAP assay (30.42 mg TE g-1 DW). Proanthocyanidins were very abundant in these by-products, and the main phenolic group quantified in cherry (10.54 mg g-1 DW), flat peach (33.47 mg g-1 DW) and nectarine (59.89 mg g-1 DW), while hydroxycinnamic acids predominate in apricot, peach and plum (6.67, 22.04 and 23.75 mg g-1 DW, respectively). The low, mean degree of polymerisation of proanthocyanidins suggests that their bioavailability could be very high. CONCLUSIONS: This study shows that thinned stone fruit extracts might be used as antioxidants in foods or as a source of compounds with health-related benefits that can be used in the pharmaceutical, cosmetic and food industries. © 2016 Society of Chemical Industry.

Preservatives in Personal Hygiene and Cosmetic Products, Topical Medications, and Household Cleaners in Spain. / Conservantes en productos de higiene y cosméticos, medicamentos tópicos y productos de limpieza doméstica en España.

INTRODUCTION: Preservatives are added to cosmetic, household cleaning, and other industrial products to prevent the growth of microorganisms. Unfortunately, exposure to these substances can cause sensitization. MATERIAL AND METHODS: Between January and June 2015, we analyzed the ingredients of 2300 products commercially available in Spain to identify the frequency of a wide variety of preservatives in different product categories. We analyzed 1093 skin care and cosmetic products sold exclusively in pharmacies (dermocosmetics), 458 household cleaning and personal hygiene and cosmetic products sold in supermarkets, 636 topical medications, and 113 cosmetic products sold in a herbal shop. RESULTS: Phenoxyethanol, citric acid, sodium benzoate, and potassium sorbate were very common in all the cosmetic product categories. Parabens were present in 16.1% of dermocosmetic products, 14.45% of cosmetic products available in supermarkets, 0.88% of cosmetic products available in the herbal shop, 5.18% of topical medications, and in none of the cleaning products. Isothiazolinones were identified in 2.56% of dermocosmetic products, 18% of cosmetic products in supermarkets, 7.9% of cosmetic products in the herbal shop, 63.63% of household cleaners, and in none of the topical medications. Formaldehyde releasers were detected in 5.76% of dermocosmetic products, 6.42% of cosmetic products sold in supermarkets, 7.96% of cosmetic products sold in the herbal shop, 3.93% of topical medications, and 16.74% of household cleaners. CONCLUSIONS: Evaluation of the presence of preservatives in everyday products allows us to indirectly estimate exposure levels to each one. Measures restricting the use of the most problematic preservatives need to be strengthened.

Ultrasound-assisted temperature-controlled ionic liquid emulsification microextraction coupled with capillary electrophoresis for the determination of parabens in personal care products.

We developed a CE and ultrasound-assisted temperature-controlled ionic liquid emulsification microextraction method for the determination of four parabens (methyl paraben, ethyl paraben, propyl paraben, and butyl paraben) in personal care products including mouthwash and toning lotion. In the proposed extraction procedure, ionic liquid (IL, 1-octyl-3-methylimidazolium hexafluorophosphate) was used as extraction solvent, moreover, no disperser solvent was needed. Parameters affecting the extraction efficiency including volume of IL, heating temperature, ultrasonic time, extraction time, sample pH, ionic strength, and centrifugation time were optimized. Under the optimized conditions, the method was found to be linear over the range of 3-500 ng/mL with coefficient of determination (R(2) ) in the range of 0.9990-0.9998. The LODs and LOQs for the four parabens were 0.45-0.72 ng/mL and 1.50-2.40 ng/mL, respectively. Intraday and interday precisions (RSDs, n = 5) were in the range of 5.4-6.8% and 7.0-8.7%, respectively. The recoveries of parabens at different spiked levels ranged from 71.9 to 119.2% with RSDs less than 9.5%.

Skincare products containing low concentrations of formaldehyde detected by the chromotropic acid method cannot be safely used in formaldehyde-allergic patients.

BACKGROUND: Formaldehyde is a well-known contact sensitizer. Formaldehyde releasers are widely used preservatives in skincare products. It has been found that formaldehyde at concentrations allowed by the European Cosmetics Directive can cause allergic contact dermatitis. However, we still lack information on whether formaldehyde at low concentrations affects dermatitis in formaldehyde-allergic individuals. OBJECTIVES: To study the effects of low concentrations of formaldehyde on irritant contact dermatitis in formaldehyde-allergic individuals. METHODS: Fifteen formaldehyde-allergic individuals and a control group of 12 individuals without contact allergy to formaldehyde and formaldehyde releasers were included in the study. The individuals performed the repeated open application test (ROAT) during 4 weeks with four different moisturizers releasing formaldehyde in concentrations that had been determined as > 40, 20-40, 2·5-10 and 0 p.p.m. by the chromotropic acid (CA) spot test. Dimethyloldimethylhydantoin was used as a formaldehyde releaser in the moisturizers. The ROAT was performed on areas of experimentally induced sodium lauryl sulfate dermatitis. The study was double blind, controlled and randomized. RESULTS: Nine of the 15 formaldehyde-allergic individuals had reappearance or worsening of dermatitis on the areas that were treated with moisturizers containing formaldehyde. No such reactions were observed in the control group (P < 0·001) or for the moisturizers without formaldehyde in the formaldehyde-allergic individuals (P < 0·001). CONCLUSIONS: Our results demonstrate that the low concentrations of formaldehyde often found in skincare products by the CA method are sufficient to worsen an existing dermatitis in formaldehyde-allergic individuals.

Ultrasound-assisted hydrolysis of conjugated parabens in human urine and their determination by UPLC-MS/MS and UPLC-HRMS.

Parabens are preservatives widely used in personal care products, pharmaceutical formulations as well as in food, and they are considered endocrine disruptors. For application in biomonitoring studies we developed a method for the determination of eight parabens from human urine. Sample preparation was enhanced and simplified by the combination of ultrasound-assisted enzymatic hydrolysis of conjugates (glucuronide and sulfate) followed by an extraction-free cleanup step. Quantification, using deuterated parabens as internal standards, was performed by ultrahigh-performance liquid chromatography coupled to either triple-quadrupole (UPLC-QqQ) or time-of-flight (UPLC-QqTOF) mass spectrometry. Full chromatographic separation of three butyl paraben isomers was achieved. Limits of quantification for both mass analyzers ranged from 0.1 to 0.5 µg/L for methyl, ethyl, n-/isopropyl, n-/isobutyl, and benzyl paraben in 200 µL of urine sample. The method was tested for applicability and showed high precision (intra- and interday 0.9-14.5%) as well as high accuracy (relative recovery 95-132%). A total of 39 urine samples were analyzed by both mass analyzers. The results agreed well, with a trend to higher deviation at low concentrations (less than 10 µg/L). Methyl, ethyl, and n-propyl paraben were detected most frequently (in more than 87% of the samples) with median concentrations ranging from 0.8 to 16.6 µg/L. Female urine showed higher median concentrations for all parabens, which may indicate higher exposure due to lifestyle. This method permits accurate and high-throughput analysis of parabens for epidemiological studies. Further, the UPLC-QqTOF approach provides additional information on human exposure to other compounds by post-acquisition analysis.

Vortex-assisted emulsification semimicroextraction for the analytical control of restricted ingredients in cosmetic products: determination of bronopol by liquid chromatography.

Vortex-assisted emulsification semimicroextraction is proposed as a one-step solution-extraction procedure for sample preparation in cosmetic products. The procedure allows rapid preparation based on dispersion of the sample in a mixture of 1 mL of n-hexane and 0.5 mL of ethanol, followed by the addition of 0.5 mL of water and centrifugation to obtain two separated phases. This procedure provides good sample clean-up with minimum dilution and is very useful for the determination of ingredients with restricted concentrations, such as bronopol. The procedure was applied to the determination of bronopol by liquid chromatography with UV detection. The best chromatographic separation was obtained by using a C18 column set at 40 °C and performing a stepwise elution with a mixture of ethanol/aqueous 1 % acetic acid solution as mobile phase pumped at 0.5 mL min(-1). The detection wavelength was set at 250 nm and the total run time required was 12 min. The method was successfully applied to 18 commercial cosmetic samples including creams, shampoos, and bath gels. Good recoveries and repeatability were obtained, with a limit of detection of 0.9 µg mL(-1), which makes the method suitable for the analytical control of cosmetic products. Moreover, it could be considered environmentally friendly, because water, ethanol, and only a low volume of n-hexane are used as solvents.

Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage.

Parabens are used as preservatives in personal care and consumer products, food and pharmaceuticals. Their use is controversial because of possible endocrine disrupting properties. In this study, we investigated metabolism and urinary excretion of methyl paraben (MeP), iso-butyl paraben (iso-BuP) and n-butyl paraben (n-BuP) after oral dosage of deuterium-labeled analogs (10 mg). Each volunteer received one dosage per investigated paraben separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h. In addition to the parent parabens (free and conjugated) which are already used as biomarkers of internal exposure and the known but non-specific metabolites, p-hydroxybenzoic acid (PHBA) and p-hydroxyhippuric acid (PHHA), we identified new, oxidized metabolites with hydroxy groups on the alkyl side chain (3OH-n-BuP and 2OH-iso-BuP) and species with oxidative modifications on the aromatic ring. MeP represented 17.4 % of the dose excreted in urine, while iso-BuP represented only 6.8 % and n-BuP 5.6 %. Additionally, for iso-BuP, about 16 % was excreted as 2OH-iso-BuP and for n-BuP about 6 % as 3OH-n-BuP. Less than 1 % was excreted as ring-hydroxylated metabolites. In all cases, PHHA was identified as the major but non-specific metabolite (57.2-63.8 %). PHBA represented 3.0-7.2 %. For all parabens, the majority of the oral dose captured by the above metabolites was excreted in the first 24 h (80.5-85.3 %). Complementary to the parent parabens excreted in urine, alkyl-chain-oxidized metabolites of the butyl parabens are introduced as valuable and contamination-free biomarkers of exposure.