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.

[Determination of seven paraben preservatives in aquatic seasoning using solid-phase extraction coupled with high performance liquid chromatography].

Seven parabens are widely used in soy sauce, vinegar, jam, oyster sauce, stuffing, and other foods. The long-term intake of large amounts of parabens and similar substances may be harmful to the human body. Therefore, the addition of paraben preservatives to food should be strictly controlled. The current detection method is applicable to single target compound and several food categories, and the experimental pretreatment method involves extraction with anhydrous ethyl ether, which is a toxic reagent. Moreover, interferences in the analysis of parabens via gas chromatography limit the versatility and accuracy of the detection method. Herein, a novel method based on solid-phase extraction (SPE) coupled with high performance liquid chromatography (HPLC) was developed for the determination of seven paraben preservatives (methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate, and heptyl p-hydroxybenzoate) in oyster sauce, shrimp sauce, and fish sauce. Compared with the conventional method, the proposed work enables the determination of more compounds, thereby expanding its scope of application to different food types. This strategy also optimizes the pretreatment method and device parameters. The samples were extracted with methanol and 20% methanol aqueous solution by ultrasonication, respectively, and then centrifuged. The experimental pretreatment method was enriched, and sample clean-up was conducted using a MAX SPE column. The seven parabens were separated using a Chromcore 120 C18 column (150 mm×4.6 mm, 3.0 µm). Gradient elution was performed with acetonitrile-5 mmol/L ammonium acetate aqueous solution as the mobile phase (initial mobile phase volume ratio, 30∶70). The flow rate was 0.7 mL/min, and the column temperature was 35 ℃. A diode array detector with a detection wavelength of 254 nm was also used. The seven paraben preservatives showed good linearity in the range of 0.5-50.0 mg/L, with correlation coefficients greater than 0.9999. The limits of detection (LODs) and quantification (LOQs) for the seven paraben preservatives were 0.2-0.4 mg/kg and 0.5-1.3 mg/kg, respectively. A spiked recovery test was conducted using oyster sauce, shrimp sauce, and fish sauce at three spiked levels of 2, 40, and 200 mg/kg. Good recoveries for the seven paraben preservatives were obtained and the recoveries of the analytes in oyster sauce, shrimp sauce, and fish sauce were 91.0%-102%, 95.5%-106%, and 95.0%-105%, respectively, with relative standard deviations of ≤6.97%. Compared with the liquid-liquid extraction method, the proposed method demonstrated better purification effects. The recoveries of the seven paraben preservatives extracted using this method were also much higher than those obtained from liquid-liquid extraction. We determined the contents of these preservatives in 135 food products using the method established in this study and detected methyl p-hydroxybenzoate and ethyl p-hydroxybenzoate in soy sauce, vinegar, and pickles. Thus, the established method can be used for the effective determination of seven parabens in aquatic seasoning such as oyster sauce, shrimp sauce, and fish sauce.

Rapid Determination of Preservatives in Cosmetics Using a Core-Shell Column.

Preservatives are frequently added to cosmetics to maintain product quality. Our laboratory quantifies 11 preservatives in cosmetics each year for regulatory purposes. In laboratories, many manufactures also analyze the preservatives in their products for quality control. To analyze many cosmetic samples, a rapid analysis method is required for efficiency. In this study, we developed a rapid method for the simultaneous determination of 11 regulated preservatives in cosmetics using a core-shell column by high-performance liquid chromatography. In this method, the 11 preservatives were separated within 17 min, which was approximately half the time reported in the previous study. The peak resolution for each preservative was >2.6, the correlation coefficients of the calibration curves were >0.9988, the percent recoveries were 92.0-111.9% and the relative standard deviations were <3.5% (n = 3). The relative standard deviations among 6 researchers were <4.7%. Thus, it is an effective rapid determination method for the analysis of preservatives in cosmetics.

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.

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.

Ultrasound-assisted cloud point microextraction of certain preservatives in real samples and determination by HPLC.

Ultrasound-assisted cloud point microextraction (UA-CPME) was performed for certain preservatives (p-hydroxy benzoic acid and its alkyl esters, methyl, ethyl, propyl and butyl parabens). Then, an HPLC method was developed for their simultaneous determination in pharmaceutical and cosmetic samples. The chromatograms of these substances were recorded on a C18 column using a gradient elution technique with various solvent systems at different flow rates and at 254 nm wavelength using a diode-array detector (DAD). The analysis conditions found by the classical method were optimized using the Box-Behnken design (BBD). In the design, the effect of each factor was examined with 3 and 4 factors for UA-CPME and HPLC analyses, respectively. The brij 58 concentration (BC), Na2SO4 amount (SA) and extraction time (ET) for UA-CPME, and the mobile phase 1 (MP1) ratio, mobile phase 2 (MP2) ratio, flow rate (FR) and column temperature parameters for HPLC analysis were obtained for the investigated levels. The factors affecting the resolution were determined by applying regression analysis to the experimental results. The analysis of variance (ANOVA) test was applied to ensure result reliability. The ANOVA test was used to determine the reliability of the results. A model was created with the obtained data. The developed method was validated by examining linearity, reproducibility, accuracy, limit of quantification and limit of the detection. Methyl paraben (with 0.148% RSD value and 0.060% relative error), and propyl paraben (with 0.149% RSD value and 0.120% relative error) were determined in the syrup sample by the developed method. Methyl paraben with recovery values of (98.32-99.42)% and ethyl paraben with recovery values of (99.17-99.41)%, were determined in a hand cream.

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.

Green, rapid and simultaneous determination of 'alternative preservatives' in cosmetic formulations by gas chromatography-mass spectrometry.

Some hydroxylated compounds commonly used in cosmetic formulations including short chain glycols, benzylic alcohols, and organic acids show antimicrobial activity, although they are not considered as preservatives according to the existing European legislation. These 'alternative preservatives' are not exempt of potential side-effects for cosmetics users. The aim of this work is to develop a simple and affordable analytical method useful for the simultaneous and green determination of fourteen compounds used as 'alternative preservatives' in cosmetic samples with different matrices. The proposed method allows a rapid sample preparation by simple dissolution or dispersion of the sample in ethanol using ultrasound-assisted leaching of the analytes from the cosmetic matrix. Gas chromatography coupled to mass spectrometry (GC-MS) is used for the analysis of the samples. Working conditions for the instrumental measure and the quantification of analytes were studied. The method was found to have high sensitivity and good precision (relative standard deviation below 13%) as well as low limits of detection (i.e., 0.01·10-3-2.14·10-3% w/w) and quantification (i.e., 0.04·10-3-7.14·10-3% w/w). The method was successfully applied to five commercial cosmetic samples of different composition. Recovery values near 100% were obtained. Each sample was found to contain at least three of the analytes of the study and their concentrations were determined with low standard deviations. The analytical features of the proposed method and the obtained results agree with the principles of Green Analytical Chemistry and make it a useful tool for controlling these alternative preservatives in the cosmetic industry in order to guarantee quality and safety of the products.

Occurrence of parabens in outdoor environments: Implications for human exposure assessment.

Parabens (PBs) are widely used as preservatives in food, pharmaceuticals and personal care products (PCPs). Due to their potential characteristics, similar to endocrine-disrupting compounds, their safety in our daily products and frequent exposure to human health have become public concerns. Nevertheless, little information is available about the occurrence of PBs in outdoor environments and their implications for human exposure. In this study, seven pairs of gas- and particle-phase air samples and 48 soil samples from Harbin City, China, were collected for the analysis of eight typical PBs (including methyl-paraben, ethyl-paraben, propyl-paraben, isopropyl-paraben, butyl-paraben, isobutyl-paraben, benzyl-paraben, and heptyl-paraben), which have been frequently selected as target compounds in previous studies. Concentrations of ∑8PBs in outdoor air samples were 253-1540 pg/m3 with a median of 555 pg/m3. The results of the gas-particle partitioning indicated that PBs had not reached equilibrium between the gas phase and particle phase. Concentrations of ∑8PBs in the soil samples were

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.

Men's Facial Moisturizers in the Metrosexual Era.

BACKGROUND: Manufacturers are increasingly branding personal care products (PCPs) specifically for men. OBJECTIVE: The aim of the study was to characterize ingredients and claims of facial moisturizers marketed to men. METHODS: Men's facial moisturizers from 7 different online retailers were identified in June-September 2018. Ingredients were grouped and identified per the Ingredient Database of the Personal Care Products Council. Potential allergens were identified using the 2017 American Contact Dermatitis Society (ACDS) Core Allergen Series and 2017-2018 North American Contact Dermatitis Group Screening Series. RESULTS: Sixty-five men's facial moisturizers were identified with a total of 1930 ingredients. On average, there were 12 ACDS Core and 9 North American Contact Dermatitis Group Screening allergens per product. A total of 70.8% of products contained between 6 and 15 ACDS Core allergens. The most notable allergens were fragrances (present in 98.5% of products), propylene glycol/derivatives (32.3%), parabens (29.2%), and alkyl glucosides (26.2%). Interestingly, less than 10% of products contained the most common allergenic preservatives in PCPs: formaldehyde releasers and methylisothiazolinone. CONCLUSIONS: Men's facial moisturizers commonly contain fragrances, emulsifiers, and glucosides but relatively few allergenic preservatives. This may reflect changes in modern PCP preservation. These findings are important for modern dermatologists to be aware, especially in a new era of male skincare.

Plasticisers and preservatives in commercial milk products: A comprehensive study on packages used in the Spanish market.

A comprehensive study on packaging used in commercially available milk products from Spanish markets has been presented. Concentrations of four phthalates, seven parabens and BPA were determined in forty-two milk products. Eleven brands and five types of packaging (metallic aluminium bag, carton, high-density polyethylene, metal pail and polyethylene terephthalate) were included in the study. BPA showed the lowest concentrations (8.3 pg/g f.w.), far below those of phthalates (6431 pg/g f.w.) and parabens (6234 pg/g f.w.). Metallic aluminium bags were the least migrating packaging (considering plasticisers and monomers) followed by HDPE bottles, in the case of phthalates. Parabens showed their highest concentrations for fresh-milk samples. Levels found were far below the specific migration limits established by the EU and the cumulative hazard index was lower than 1, indicating that adverse health effects were not expected. In general, the results found in Spanish samples were lower than those reported in other countries.

Urinary Paraben Concentration and Its Association with Serum Triglyceride Concentration in 2013-2014 NHANES Participants: A Cross-Sectional Study.

Background: Alkyl esters of para-hydroxybenzoic acid, colloquially known as parabens, are types of preservatives found in multiple foodstuffs, pharmaceuticals, and personal care products to which Americans are exposed daily. It is unclear if parabens exhibit endocrine-disrupting properties. Parabens may interact with triglycerides in adipose tissue and impact lipid metabolism. Objective: To evaluate the association between urinary paraben concentrations and serum triglyceride concentrations. Design: A cross-sectional study. Setting. The Mobile Examination Centers affiliated with 2013-2014 NHANES. Participant(s). 827 adults (20 years or older) affiliated with the 2013-2014 NHANES. Intervention(s). None. Main Outcome Measure(s). Triglyceride levels were associated with urinary paraben concentrations (methyl, ethyl, and propyl) using a hierarchical multiple regression, adjusting for ethnicity/race, gender, BMI, and age. Unadjusted results are also reported. Results: The geometric mean of the urinary concentration of methylparaben, ethylparaben, and propylparaben was 57.100, 2.537, and 6.537 ng/ml, respectively. Triglyceride concentrations were inversely associated with methylparaben (ß = -0.092, P=0.07), ethylparaben (ß = -0.066, P=0.045), and propylparaben (ß = -0.076, P=0.025). Being female, non-Hispanic White, and non-Hispanic Black were associated with decreasing triglyceride levels in the presence of methylparaben, ethylparaben, and propylparaben, and age, BMI, and being male were associated with increasing circulating triglycerides. Conclusion: Despite the potential detrimental effects of parabens on triglycerides, our results suggest that urinary excretions of methylparaben, ethylparaben, and propylparaben are associated with lower concentrations of circulating triglycerides in certain populations. Further research is needed to confirm the mechanisms and health impact of this relationship.

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.

Combination of large volume sample stacking with polarity switching and cyclodextrin electrokinetic chromatography (LVSS-PS-CDEKC) for the determination of selected preservatives in pharmaceuticals.

In this study, a large volume sample stacking (LVSS) with polarity switching (PS) and cyclodextrin electrokinetic chromatography (CDEKC) method has been developed for the simultaneous separation and determination of 8 preservatives: methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), isobutylparaben (IBP), sorbic acid (SA), benzoic acid (BA), p-hydroxybenzoic acid (PHBA) in pharmaceuticals. The effects of some typical parameters such as sample volume, applied voltage, composition and pH of the running buffer and organic modifier concentration were examined and optimized. Moreover, the impact of type and concentration of cyclodextrin as electrolyte modifiers was also investigated. The detection limits of analytes for the elaborated LVSS-PS-CDEKC method were found to be in 0.8-5 ng mL-1 range, which were around 500 times lower than normal CDEKC without preconcentration technique. All analytes were completely resolved in less than 11 min in an uncoated fused-silica capillary of 75 µm internal diameter (I.D) x 50 cm length. The electrophoretic separation was performed in a 2 mM α-cyclodextrin and 25 mM tetraborate system (pH = 9.3) with an applied voltage of 25 kV. The established method was validated and confirmed to be applicable for the determination of the preservatives in a quality control of pharmaceuticals.

Maternal paraben exposure triggers childhood overweight development.

Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially in recent years. Here we investigate the effect of prenatal paraben exposure on childhood overweight by combining epidemiological data from a mother-child cohort with experimental approaches. Mothers reporting the use of paraben-containing cosmetic products have elevated urinary paraben concentrations. For butyl paraben (BuP) a positive association is observed to overweight within the first eight years of life with a stronger trend in girls. Consistently, maternal BuP exposure of mice induces a higher food intake and weight gain in female offspring. The effect is accompanied by an epigenetic modification in the neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading to a reduced hypothalamic POMC expression. Here we report that maternal paraben exposure may contribute to childhood overweight development by altered POMC-mediated neuronal appetite regulation.

Screening of Concentration and Antimicrobial Effectiveness of Antimicrobial Preservative in Betastatin Besylate Nasal Spray.

OBJECTIVE: To explore the optimal concentration and antimicrobial effectiveness of antimicrobial preservative in betastatin besylate nasal spray. METHODS: By using Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Aspergillus niger as test strains, the antimicrobial effectiveness of betastatin besylate nasal spray containing different concentrations of antimicrobial preservative (0.02%, 0.0125%, and 0.005% benzalkonium chloride, respectively) was determined by using bacteriostatic effect test (Chinese Pharmacopoeia, 2015 edition). RESULTS: The antimicrobial effectiveness of betastatin besylate nasal spray containing 0.02% and 0.0125% benzalkonium chloride, respectively, complied with the regulations of Chinese Pharmacopoeia (2015 Edition) against five test strains. However, the antimicrobial effectiveness of betastatin besylate nasal spray containing 0.005% benzalkonium chloride against P. aeruginosa did not meet the requirements of Chinese Pharmacopoeia. CONCLUSION: Benzalkonium chloride at a concentration of 0.125% can be used as an added antimicrobial preservative in betastatin besylate nasal spray.

Probabilistic exposure assessment of aggregate rates of dermal exposure of Japanese women and children to parabens in personal care products.

Parabens (p-hydroxybenzoic acids) are commonly used as preservatives in personal care products. Although the rate of exposure to a single product may be small, it is possible for an individual to have marked exposure to parabens through the use of multiple personal care products (aggregate exposure). To assess the risks associated with aggregate exposure to parabens, we estimated the dermal exposure rate distributions of four major parabens (methylparaben, MP; ethylparaben, EP; propylparaben, PP; butylparaben, BP) in various products for women (>20 years old) and children (1-3 years old) by using the probabilistic exposure assessment tool ConsExpo. Integrated exposure rates were then calculated as the sum of exposure rates for individual products. Aggregate exposure rates for women were 1.2 (median) (0.13 [5%ile], 6.9 [95%ile]), 0.43 (0.029, 3.0), 0.35 (0.032, 1.9), and 0.25 (0.027, 1.2) mg kg-bw-1 day-1 for MP, EP, PP, and BP, respectively. Those for children were 0.47 (0.054, 2.2), 0.11 (0.012, 0.60), 0.13 (0.012, 0.78), and 0.13 (0.0065, 0.85) mg kg-bw-1 day-1 for MP, EP, PP, and BP, respectively. Integrated exposure rates for women were several times those for children. In both cases, personal care products that were applied to larger areas of skin and were used more frequently were more likely to be associated with higher exposure rates. According to the results of a risk assessment using a margin of exposure approach, aggregate rates of exposure to PP and BP, but not MP or EP, were high enough to warrant concern about disruption of the reproductive system.