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Background: We describe a novel alcohol-free preservative composed of glucose, mannitol, disodium hydrogen orthophosphate, thymol, and distilled water (glucose-mannitol-disodium dihydrogen orhtophosphate-thymol [GMDT] preservative) in appropriate proportion as an alternative to alcohol prefixation (APF) of body fluids., Objectives: To assess the cytomorphologic preservation and staining quality of serous body fluid smears generated by GMDT preservative and compare it with smears processed by standard 50% APF., Methodology: The study comprised 151 effusion samples. Each sample was equally divided into four tubes. Equal volumes of APF and GMDT preservatives were added to the first two tubes and left at room temperature for 24 h. Similarly, the corresponding preservatives were added to the third and fourth tubes and stored for 48 h. Two smears were prepared from the centrifuged sediments of each tube (all four tubes) and stained with May-Grünwald Giemsa and Papanicolaou (Pap) stains. Using a three-tiered scoring system, the smear examination was blinded to assess the extent of cellular preservation and the staining quality by two cytotechnologists and two cytopathologists. Statistical analysis was performed by STATA 16.0., Results: Samples processed with the GMDT preservative at 24 h showed better cytoplasmic preservation and smear background, while nuclear features and staining quality showed no difference between the two preservatives. Mild cytoplasmic and nuclear degenerative changes were noted with the GMDT at 48 h, while all four parameters remained similar with APF at 24 and 48 h., Conclusions: The newly developed alcohol-free, GMDT preservative, could be a feasible and cost-effective alternative to 50% APF, preferably when samples are processed within 24 h., (© 2024 Wiley Periodicals LLC.)

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation., Competing Interests: Declaration of competing interest No., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Parabens are globally employed as important preservatives in pharmaceutical, food, and personal care products. Nonetheless, improper disposal of commercial products comprising parabens can potentially contaminate various environmental components, including the soil and water. Residues of parabens have been detected in surface water, ground water, packaged food materials, and other consumer items. Long-term exposure to parabens through numerous consumer products and contaminated water can harm human health. Paraben can modulate the hormonal and immune orchestra of the body. Recent findings have correlated paraben use with hypersensitivity, obesity, and infertility. Notably, parabens have also been detected in the samples of breast cancer patients, suggesting a potential cross-talk between parabens and carcinogenesis. Therefore, the present article aims to dissect the significance of parabens as a preservative in several consumer products and their impact of chronic exposure to human health. This review encompasses various facets of paraben, including its sources, mechanism of action at the molecular level, and sheds light on its toxicological implications on human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Parabens are commonly used preservatives in cosmetics, food, and pharmaceutical products. The objective of this study was to examine the effect of nine parabens on human and rat 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) in human placental and rat ovarian cytosols, as well as on estradiol synthesis in BeWo cells. The results showed that the IC 50 values for these compounds varied from methylparaben with the weakest inhibition (106.42 μM) to hexylparaben with the strongest inhibition (2.05 μM) on human 17β-HSD1. Mode action analysis revealed that these compounds acted as mixed inhibitors. For rats, the IC 50 values ranged from the weakest inhibition for methylparaben (no inhibition at 100 μM) to the most potent inhibition for hexylparaben (0.87 μM), and they functioned as mixed inhibitors. Docking analysis indicated that parabens bind to the region bridging the NADPH and steroid binding sites of human 17β-HSD1 and the NADPH binding site of rat 17β-HSD1. Bivariate correlation analysis demonstrated negative correlations between LogP, molecular weight, heavy atoms, and apolar desolvation energy, and the IC 50 values of these compounds. In conclusion, this study identified the inhibitory effects of parabens and their binding mechanisms on human and rat 17β-HSD1, as well as their impact on hormone synthesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome., Method: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones., Results: The eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers., Conclusions: 1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening., (Copyright © 2024 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10 mg/mL eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome., Method: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5±3 °C), at room temperature (25±2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones., Results: The eye drops stored at 5 °C were the most stable; in the 1 mg/mL eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/mL eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/mL, presented a white precipitate from day 14 and 28, respectively. Non-refrigerated 1 mg/mL eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers., Conclusions: 1 mg/mL MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/mL eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening., Competing Interests: Declaration of competing interest None of the co-authors had any conflicts of interest to declare., (Copyright © 2024 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: Parabens are a group of substances commonly employed as antimicrobial preservatives. The effect of parabens on the development of neurotoxicity in children is still controversial. This study aimed to explore the associations between parabens exposure and children's neurodevelopmental performance, emphasizing potential sex differences and the combined effects of parabens., Methods: We used the long-term follow-up study of Taiwanese generation, Taiwan Birth Panel Study II (TBPS II). We recruited the group of children at 6-8 years old. And, we measured parabens in children urine, including methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP). Children's attention-related performance was evaluated using the Conners Kiddie Continuous Performance Test 2nd Edition (K-CPT 2). The study employed both linear regression and mixture analysis quantile g-computation (QGC) methods to discern associations. A stratified analysis by sex and QGC was implemented to delve deeper into the cumulative effects of parabens., Results: A total of 446 subjects completed both the parabens analysis and the K-CPT 2 survey. The overall association between parabens and neurodevelopmental performance was not pronounced, but discernible sex differences emerged. In the single pollutant analysis, elevated PP concentrations were associated with higher K-CPT 2 scores particularly in detectability (d') (β = 0.92 [95 % CI = 0.15 to 1.69]) and commissions (β = 0.95 [95 % CI = 0.12 to 1.78]), among girls. Further, in the mixture analysis, a significant association between PP and detectability (d') was observed in girls (β = 1.68 [95 % CI = 0.11 to 3.26])., Conclusions: This study identified sex-specific associations between parabens and attention performance. Consistent outcomes across single and mixture analysis methods. Further research is crucial to clarify these causal associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Contact sensitivity is a latent state that lasts a lifetime with a clinically manifesting response in the form of allergic contact dermatitis that often has an unfavorable prognosis. In contact urticaria syndrome, can cause anaphylactic reactions. Exposure to irritants or sensitizing factors represents a major risk. Age and gender are not risk factors for contact sensitivity in themselves. A recent meta-analysis has shown that the prevalence of contact sensitivity in the general population is 20.1% and that 4 allergens from cosmetic products are among the top 6 allergens that cause contact sensitivity in the general population. Cosmetics products are responsible for more than half of all allergic contact dermatitis which mainly affects adults of middle and older age, who generally do not have atopy and whose occupations have low academic requirements. It is possible for a cosmetic allergy to develop even after years of using a cosmetic product without previous problems. Beauty products to watch for. Just because a label says that something is “dermatologist tested”, that is no guarantee that the product will be kind to your skin. There are no rules about these terms and criteria how to use them on a label. Ingredients that may cause allergy. Preservatives and fragrances are the most frequently detected allergens in those with an allergy to a cosmetic product. The future of allergen labeling. Allergens identified by the Scientific Committee on Consumer Safety need to be present on a label. Every cosmetic product placed on the European Union market must have a compliant product information and an International Fragrance Association certificate if contains fragrances. Conclusion. Because so-called “hypoallergenic” products are not necessarily less sensitizing, allergy departments should distribute lists of cosmetic products not containing the respective allergen(s) that consumers can use as safe alternatives. [ABSTRACT FROM AUTHOR]

Cosmetic products are chemical substances or mixtures used on the skin, hair, nails, teeth, and the mucous membranes of the oral cavity, whose use is intended to clean, protect, correct body odor, perfume, keep in good condition, or change appearance. The analysis of cosmetic ingredients is often challenging because of their huge complexity and their adulteration. Among various analytical tools, mass spectrometry (MS) has been largely used for compound detection, ingredient screening, quality control, detection of product authenticity, and health risk evaluation. This work is focused on the MS applications in detecting and quantification of some common cosmetic ingredients, i.e., preservatives, dyes, heavy metals, allergens, and bioconjugates in various matrices (leave-on or rinse-off cosmetic products). As a global view, MS-based analysis of bioconjugates is a narrow field, and LC- and GC/GC×GC-MS are widely used for the investigation of preservatives, dyes, and fragrances, while inductively coupled plasma (ICP)-MS is ideal for comprehensive analysis of heavy metals. Ambient ionization approaches and advanced separation methods (i.e., convergence chromatography (UPC 2 )) coupled to MS have been proven to be an excellent choice for the analysis of scented allergens. At the same time, the current paper explores the challenges of MS-based analysis for cosmetic safety studies.

Purpose: This study aims to assess the association between switching patterns and adherence/persistence in Danish patients over the age of 65, who started their first-ever glaucoma treatment with latanoprost eye drops., Methods: Patients were assigned to three different cohorts: (1) switchers, (2) non-switchers, and (3) preservative-free latanoprost (Monoprost®) users. Patients were followed for 1 year until the end of data coverage or censoring. Study covariates were used to compute the propensity score. In the adjusted analysis, the propensity score was added to the model as an independent variable. The Cox regression model was used to calculate the hazard ratio (HR) of discontinuation for the three cohorts (the non-switchers cohort was the reference level) in both adjusted and unadjusted analyses., Results: Non-switchers had a statistically significant lower adherence (proportion of days covered, PDC 92%) than switchers (PDC 96%; p < 0.001) and users of Monoprost® (PDC 99%; p < 0.001). Switchers had a 53% lower risk of treatment discontinuation compared to the reference group within 1 year after the first redemption of latanoprost in both unadjusted (HR 0.47; 95% Confidence interval, 95% CI: 0.41-0.53; p < 0.001) and adjusted (HR 0.47; 95% CI: 0.42-0.53; p < 0.001) analyses. In comparison to the non-switchers, Monoprost® users had a 78% lower risk for the above result in both unadjusted (HR 0.22; 95% CI: 0.17-0.28; p < 0.001) and adjusted (HR 0.22; 95% CI: 0.17-0.29; p < 0.001) analyses., Conclusion: This study found increased adherence and persistence in latanoprost users among those who redeemed preservative-free latanoprost (Monoprost®) and among those who switched between different latanoprost formulations., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Parabens (p-hydroxybenzoic acid esters) commonly used preservatives (in cosmetics, pharmaceuticals, and foods) can pose potential effects on environmental health. In this study, seven parabens were quantified in marine fish samples using an ultra-high performance liquid chromatography triple quadrupole mass spectrometer (UHPLC-MS/MS) system. Parabens in the fish samples were extracted and purified by a rapid, simple, and effective procedure comprising sample homogenization with solvent, solid-phase extraction clean-up, and solvent evaporation. Results demonstrated that the recoveries of seven compounds (with relative standard deviation < 15%) were 88-103% in matrix-spike samples and 86-105% in surrogate standards. The method detection limits and method quantification limits of seven parabens were 0.015-0.030 and 0.045-0.090 ng/g-ww (wet weight), respectively. The optimized method was applied to measure the concentration of parabens in the 37 marine fish samples collected from Vietnam coastal waters. The concentration ranges of seven parabens found in round scad and greater lizardfish samples were 6.82-25.3 ng/g ww and 6.21-17.2 ng/g-ww, respectively. Among parabens, methylparaben accounted for the highest contribution in both fish species (43.2 and 44.9%, respectively). Based on the measured concentrations of parabens in marine fish samples, the estimated daily intake was calculated for children and adults with the corresponding values of 0.0477 µg/kg/day and 0.0119 µg/kg/day, respectively. However, the presence of parabens in Vietnamese marine fish may not pose a significant risk to human health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Parabens are compounds widely utilized in the industry as preservative additives to personal care products, cosmetics and food. They pollute the environment and penetrate to the living organisms through the digestive tract, respiratory system and skin. Till now the knowledge about exposure of terrestrial wild mammals to parabens is extremely scarce. Therefore, this study for the first time assessed the concentration levels of five parabens commonly used in industry (methylparaben-MeP, ethylparaben-EtP propylparaben-PrP, benzylparaben -BeP and butylparaben-BuP). Substances have been analyzed in hair samples collected from wild boars using liquid chromatography-mass spectrometry (LC-MS) method. The hair is a matrix, which allows to study long-term exposure of organisms to parabens. During this study MeP was noted in 96.3% of samples with mean 88.3±72.9 pg/mg, PrP in 87.0% of samples with mean 8.5±3.3 pg/mg, BeP in 44.4% of samples with mean 17.2±12.3 pg/mg and EtP in 11.1% of samples with mean 17.2±4.8 pg/mg. In turn BuP was noted only in 3.7% of samples with concentration levels below limit of quantification (2.6 pg/mg). Statistically significant intragender differences in parabens levels have not been noted. Only BeP concentration levels depended on industrialization and density of human population of area, where the animals lived. This study indicates that wild boars are exposed to parabens, especially to MeP and PrP, and analysis of the hair seems to be a useful tool of biomonitoring of parabens in wild mammals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gonkowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Parabens are preservatives found in cosmetics, processed foods, and medications. The harmful repercussions on the central nervous system by one of the most common parabens, propylparaben (PrP), are yet unknown, especially during development. In this study, the neurodevelopmental effects of PrP and long-term neurotoxicity were investigated in the zebrafish model, using an integrated approach. Zebrafish embryos were exposed to two different concentrations of PrP (10 and 1000 μg/L), then larvae were examined for their behavioral phenotypes (open-field behavior, startle response, and circadian rhythmicity) and relevant brain markers (cyp19a1b, pax6a, shank3a, and gad1b). Long-term behavioral and cognitive impacts on sociability, cerebral functional asymmetry and thigmotaxis were also examined on juveniles at 30 dpf and 60 dpf. Moreover, proteomics and gene expression analysis were assessed in brains of 60 dpf zebrafish. Interestingly, thigmotaxis was decreased by the high dose in larvae and increased by the low dose in juveniles. The expression of shank3a and gad1b genes was repressed by both PrP concentrations pointing to possible effects of PrP on neurodevelopment and synaptogenesis. Proteomics analysis evidenced alterations related to brain development and lipid metabolism. Overall, the results demonstrated that early-life exposure to PrP promotes developmental and persistent neurobehavioral alterations in the zebrafish model, affecting genes and protein levels possibly associated with brain diseases., Competing Interests: Declaration of competing interest The authors affirm that they have no known financial or interpersonal conflicts that would have appeared to have an impact on the research presented in this study., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Benzalkonium chloride (BZK), alkyldimethylbenzlamonium chloride, is a cationic surfactant that is used as an antiseptic. BZK is classified as a quaternary ammonium compound composed of molecules of several alkyl chains of differing lengths, that dictate its effectiveness towards different microbes. As a result, BZK has become one of the most used preservatives in antibacterial solutions. Despite its widespread use, it is not clear whether BZK penetrates human skin. To answer this question, BZK treated skin was analyzed using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry imaging. Solutions containing BZK and differing excipients, including citric acid, caprylyl glycol, and vitamin E, were applied ex vivo to excised human skin using Franz diffusion cells. Treated skin was embedded in gelatin and sectioned prior to MALDI-TOF imaging. BZK penetrates through the epidermis and into the dermis, and the penetration depth was significantly altered by pH and additives in tested solutions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Morse et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Thiomersal (TM) is an excellent preservative that is used in a wide variety of products, like pharmaceuticals, cosmetics, and vaccines, etc. Its usage has been in decline because of safety concerns. Since vaccine production is on the rise, its use may increase further in low-income and developing countries, as a cost-effective vaccine preservative. Further, Thiomersal is still being used as an essential component in various pharmaceutical preparations. In this light, the present study addresses its mechanism of toxicity in zebrafish and unveils a novel strategy for lessening its negative effects by conjugating cysteine to it, while retaining its antibacterial efficacy. We show that the mitochondrial membrane potential is destabilised by TM, leading to the induction of apoptosis. Interestingly, TM-cysteine conjugate (at a ratio of 1:1) showed no toxicity in zebrafish, whereas TM alone was highly toxic. Importantly, assaying for the bactericidal activity, tested using Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA), revealed that the conjugate retains the antibacterial activity, demonstrating that the TM-cysteine conjugate is a safer alternative to TM as a vaccine preservative, and in all the other products that still use TM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Plant-based antimicrobial substances have emerged as promising alternatives to conventional antibiotics and preservatives. Although many review studies have been done in this field, many of these reviews solely focus on specific compounds from particular perspectives. This paper aims to provide a comprehensive review on the various types of plant-based antimicrobial substances, the extraction and purification processes, as well as the application and safety issues. Combining different natural plant-derived substances shows promise in enhancing antimicrobial activities. Moreover, despite the existence of various methods (e.g., microwave-assisted extraction, supercritical fluid extraction) to extract and purify antimicrobial substances, isolating pure compounds remains a laborious process. Sustainability issues should also be considered when developing extraction methods. Additionally, the extraction process generates a significant amount of plant waste, necessitating proper utilization to ensure economic viability. Lastly, not all plant-derived substances are safe, and further research is needed to investigate their toxicity before widespread application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Natural preservatives are causing a rethinking of current preservation means. As a sweetener resource, exploitation of Stevia rebaudiana leaves (SRLs) is still restricted due to human conventional cognition. Herein, Lactobacillus plantarum fermented SRLs containing diverse free secondary metabolites derived from microbial deglycosylation and bioenzymatic decomposition were investigated. The apparent resistance to typical foodborne bacteria (Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomoas aeruginosa, Bacillus amyloliquefaciens) by fermented SRLs and their extracts were validated. The metabolite diversity and in-depth organic solvent extraction gave the possibilities for better antimicrobial actions, anti-HepG2/SGC-7901 cells in vitro in contrast with aqueous extract of unfermented SRLs. Crucially, compound identification and attribution revealed that fermentation products may be maximally contributing to antimicrobial and antitumor mechanisms rather than intrinsic plant and/or microbial components. Additionally, pork sausage models with 15 g/kg ethyl acetate extract as a preservative candidate presented preferred storage characteristics (21 days and 37 °C) compared to those without ethyl acetate extract, e.g. the minimal total plate count (3.86 ± 0.27 log CFU/g), peroxsignide value (8.02 ± 0.92 meq/kg), and acid value (2.01 ± 0.04 (KOH)/(mg/g))., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Many pet owners make food choices for their pets that are similar to those they make for themselves, and food characteristics such as the presence of preservatives can influence this decision. The Theory of Planned Behavior (TPB) is a tool used to predict intentions and behavior and can be an important indicator for the pet food industry. The aim of this study was to investigate pet owner behavior regarding food with or without preservatives, based on the behavior prediction of TPB. A questionnaire was distributed with questions related to direct (attitude, subjective norms, and perceived behavioral control) and indirect (behavioral beliefs, normative beliefs, and intentions) measures for the analysis of TPB. For the statistical analysis the structural equation modeling (SEM) was used. The correlation between owner behavior and the behavior imposed on their dog's diet was evaluated by paired T test or paired Wilcoxon test according to variables' adherence or not to normality, respectively. A total of 1,021 answers were evaluated after the inclusion and exclusion criteria were applied. The results indicated that TPB was effective in predicting the intentions (r2 = 0.58 for dogs and r2 = 0.59 for owners) and behavior (r2 = 0.58 for dogs and r2 = 0.57 for owners) regarding the intake of diets without preservatives. It was observed that owners are more concerned with the diet of their dogs than their own and they believe that the intake of preservatives can be prejudicial to the health of their dogs (p<0.001). However, owners trust more in pet food manufacturers than human food manufacturers (p<0.001). Therefore, it can be concluded that TPB can be an important tool to understand consumer behavior towards their dog food, and that the industry should intensify its approach on safety of preservatives in pet food, since many owners still believe they can be prejudicial to dogs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pedrinelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Most preservatives are irritating and can easily induce skin sensitivities. Therefore, both domestic and international regulations impose clear restrictions on the use of preservatives in cosmetics. Herein, gas chromatography-tandem mass spectrometry (GC-MS/MS) was employed to simultaneously analyze the levels of 15 preservative allergens in cosmetics. Further, a precise identification approach based on a two-column retention index and mass spectrometry matching degree was developed. Cosmetic samples were extracted via acetonitrile vortex ultrasound extraction and then dehydrated with anhydrous MgSO 4 . The preservative allergens were separated on two columns, namely, DB-5MS and DB-WAX. Targets were identified using electron impact ionization (EI) source and the multiple reaction monitoring (MRM) mode and characterized using a retention index calibrated by a series of n -alkane standards. Following two tests, the LODs for the 15 preservative allergens on the DB-5MS column were in the range of 0.02-0.2 mg/kg, while those for 12 preservative allergens on the DB-WAX column were in the range of 0.01-20 mg/kg. The preservative allergens on the DB-5MS and DB-WAX columns demonstrated strong correlations, with all correlation coefficients exceeding 0.99. The recoveries for the 15 preservative allergens were in the range of 70.1%-129.8% at low, medium, and high levels, and the relative standard deviations (RSDs) were all below 15% ( n =6) when using water, lotion, facial mask, and cream as the representative matrix. Next, 80 batches of genuine samples were tested using the established method. Isopropyl 4-hydroxybenzoate, a prohibited preservative, was detected in two sample batches using the DB-5MS and DB-WAX columns. Additionally, 11 and 10 restricted preservative allergens were identified on the DB-5MS and DB-WAX columns, respectively. The test results indicate that the double-column system approach offers excellent accuracy, effectively preventing false-positive and false-negative results, and can detect the 15 preservative allergens in cosmetics. The use of the retention index for the qualitative detection of these preservative allergens offers valuable options for non-targeted screening and meeting regulatory criteria.

Patch tests are often used in safety evaluations to identify the substance causing skin irritation, but the same substance can sometimes give positive or negative results depending on the test conditions. Here, we investigated differences in the skin penetration of two test compounds under different application conditions. We studied the effects of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant polysorbate 80 (PS) on skin penetration of the preservatives methylisothiazolinone (MT) and methylchloroisothiazolinone (MCT), which are used in cosmetics such as shampoos. The skin permeation of MT was enhanced by SDS but was unchanged by PS. Skin impedance decreased in the presence of SDS whereas PS had the same effect as the control aqueous solution, suggesting that SDS reduction of the barrier function of skin affects the permeation of MT, a hydrophilic drug. Application of a mixture of MCT and MT in the presence of SDS did not affect the skin permeation of MCT whereas the permeation of MT was enhanced by SDS, indicating that the skin permeation of MCT is less affected by SDS than is MT. Thus, attention should be paid to the possible effect of co-solutes, especially hydrophilic drugs.

Sodium disulfite, also known as sodium metabisulfite or sodium pyrosulfite, is an inorganic compound, which may cause allergic contact dermatitis. Sulfites act as antioxidants and preservatives; common sources include food/beverages, pharmaceuticals, and personal care products. Importantly, sulfites are not included in most screening patch test series and thus may be missed as a relevant contact allergen. The American Contact Dermatitis Society chose sulfites as the Allergen of the Year for 2024 to raise awareness about this significant allergen.

Multidose formulations have patient-centric advantages over single-dose formats. A major challenge in developing multidose formulations is the prevention of microbial growth that can potentially be introduced during multiple drawings. The incorporation of antimicrobial preservatives (APs) is a common approach to inhibit this microbial growth. Selection of the right preservative while maintaining drug product stability is often challenging. We explored the effects of three APs, 1.1 % (w/v) benzyl alcohol, 0.62 % (w/v) phenol, and 0.42 % (w/v) m-cresol, on a model immunoglobulin G1 monoclonal antibody, termed the "NIST mAb." As measured by hydrogen exchange-mass spectrometry (HX-MS) and differential scanning calorimetry, conformational stability was decreased in the presence of APs. Specifically, flexibility (faster HX) was significantly increased in the C H 2 domain (HC 238-255) across all APs. The addition of phenol caused the greatest conformational destabilization, followed by m-cresol and benzyl alcohol. Storage stability studies conducted by subvisible particle (SVP) analysis at 40 °C over 4 weeks further revealed an increase in SVPs in the presence of phenol and m-cresol but not in the presence of benzyl alcohol. However, as monitored by size exclusion chromatography, there was neither a significant change in the monomeric content nor an accumulation of soluble aggregate in the presence of APs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Madeleine C. Jolliffe reports financial support was provided by AstraZeneca PLC. Isabelle Trayton reports financial support was provided by AstraZeneca PLC. Ramesh Kumar Shanmugam reports financial support was provided by AstraZeneca PLC. Nicholas J. Darton reports financial support was provided by AstraZeneca PLC. David Weis reports financial support was provided by Bristol Myers Squibb]., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Formaldehyde has been classified as carcinogenic to humans by International Agency for Research on Cancer and found in personal care (PC) products containing formaldehyde-donor (FD) preservatives. However, the cancer risk associated with the use of FD-containing PC products has not been well established. Our study provides the quantitative cancer risk assessment of formaldehyde in FD-containing PC products. The carbon-13 nuclear magnetic resonance ( 13 C-NMR) spectroscopy was used in this risk assessment to provide reliable exposure information to formaldehyde in PC products and aqueous solutions containing sodium hydroxymethylglycinate. The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMDs) for 10% effect. For hemolymphoreticular neoplasias in male rats, a BMD of 28.03 mg/kg/day and a BMD lower confidence limit (BMDL) of 2.52 mg/kg/day were calculated from available long-term animal experiments. The worst-case consumer exposure to formaldehyde from FD-containing PC products was 0.007 μg/kg/day. Comparing the consumer exposure with BMDL, the resulting MOE was 360,000 for the worst-case scenario. The consumer exposure to formaldehyde (0.007 μg/kg/day) from using FD-containing PC products represents less than 1.0 × 10 -6 % of background level endogenous formaldehyde (878-1310 mg/kg/day). The cancer risk from formaldehyde to consumers using FD-containing PC products is negligible., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study compared the effect of preservative-containing (PC) and preservative-free (PF) prostaglandin analogue (PGA) formulations on the ocular surface, especially on the meibomian gland (MG) in patients with open-angle glaucoma (OAG). This is a retrospective study of treatment-naïve patients with OAG (n=80) and healthy controls (n=40). OAG patients were randomized into groups using either PC-PGA or PF-PGA for 12 months. All participants underwent ocular surface and MG examinations including their meibum score, meiboscore, and lid margin abnormality score (LAS). Eighty OAG patients were randomized into two groups (n=42 in PC, n=38 in PF). All PGA and control groups showed similar ocular surface and MG parameters at the baseline. Both PC- and PF-PGA groups showed increased meibum scores, meiboscores, and LASs at 12 months compared to the baseline (all p<0.05). At the 12-months visit, PC-PGA group showed severe OSDI, shorter TBUT, greater OSS, and worse MG parameters than those of the other two groups (all p<0.05). In addition, PF-PGA group showed worse meiboscores, meibum scores, and severe OSS scores than those of the control group (all p<0.05). Both PC and PF formulations can cause damage to the MG in patients using PGA. However, PC formulations induced more ocular discomfort, poorer ocular surface, and more severe MG loss compared to PF formulations. Therefore, it would be advisable to use PF formulations in patients with a preexisting or concomitant ocular surface disease or MGD. [ABSTRACT FROM AUTHOR]

Background and Objective: All latanoprost formulations currently available for the treatment of glaucoma or ocular hypertension contain the same concentration of latanoprost (0.005%) but differ in excipients, which may affect corneal drug permeability or stability. This study aimed at comparing corneal penetration of three marketed latanoprost solutions with different excipient formulations in in vitro and in vivo drug permeability studies., Methods: Three latanoprost formulations were tested under good laboratory practice conditions: a formulation containing benzalkonium chloride (BAK) but no surfactant (Preserved latanoprost); the same formulation except preservative-free (PF) without BAK or surfactant (SF) (PF SF latanoprost); and a different formulation without BAK but containing a non-ionic surfactant (MGHS 40 at 5%) combined with thickening agents (Carbomer 974P, Macrogol 4000) (PF latanoprost). Corneal permeation of latanoprost acid (LAT) was first determined in vitro using a reconstructed human corneal epithelium tissue. Then, in vivo pharmacokinetic studies were performed on pigmented rabbits, for which LAT concentration was measured in the aqueous humour (AH) and iris-ciliary body (ICB)., Results: In vitro, the cumulative transport of LAT was linear between 1 h and 4 h for preserved latanoprost and PF SF latanoprost, and LAT concentrations matched exactly at each timepoint. By contrast, the permeation of PF latanoprost was linear between 2 h and 12 h and was significantly lower than that of preserved latanoprost and PF SF latanoprost at 4 and 8 h (p < 0.001). In rabbits, the concentrations of LAT in AH and ICB were not statistically different between preserved latanoprost and PF SF latanoprost at each timepoint, except at 1 h in ICB (p = 0.005). By comparison, the LAT concentration of PF latanoprost was statistically (p < 0.05) lower than that of preserved latanoprost and PF SF latanoprost in AH and ICB from 0.5 to 3 h., Conclusion: BAK did not influence the corneal penetration of latanoprost in in vitro and in vivo studies. The formulation containing a non-ionic surfactant resulted in lower and slower ocular penetration compared with preserved or PF SF formulations. This raises questions about the relevance of BAK and some surfactants in enhancing corneal penetration of ocular formulations., (© 2023. The Author(s).)

Purpose: The systemic and ocular pharmacokinetics (PK), and ocular toxicity of benzalkonium chloride (BAK)-free TearClear latanoprost ophthalmic solution, 0.005% formulation (TC-002) were evaluated. TC-002 is designed to selectively capture BAK at the time of drug administration; therefore, the dose delivered to the eye contains no quantifiable level of preservative. Methods: The systemic and ocular PK of TC-002 were compared to a BAK containing reference listed drug (RLD, Xalatan™) over a 24-h period, after a single topical ocular dose to 1 eye of male Dutch Belted (DB) rabbits ( n  = 3/timepoint). Latanoprost acid concentrations were measured in plasma and ocular tissues. The ocular toxicity was evaluated in a separate study and included toxicokinetic evaluation of TC-002 after once daily topical ocular dosing into each eye of DB rabbits ( n  = 8/group) for at least 28 days. Toxicity endpoints included ophthalmic and clinical evaluations, necropsy, and microscopic evaluation of ocular tissues. Results: Average ratios of C max values for TC-002/RLD ranged from 0.6 to 1.6, and C max and area under the concentration-time curve of last observed concentration (AUC last ) exposures to latanoprost acid were similar (<2-fold) between the 2 treatments. In the 28-day study, the T max was achieved in both groups in <0.5 h. There were no abnormal ocular findings. Conclusions: TC-002 with no quantifiable preservative or BAK-containing RLD exhibited similar ocular and systemic PK profiles. TC-002 was well tolerated and comparable to RLD. TC-002 retains the safety and PK characteristics of RLD without the added concern of long-term exposure of the eye to preservatives.

The progressive use of food additives in "ultra-processed" food has increased attention to them. Propyl gallate (PG) is an essential synthetic preservative that commonly used in food, cosmetics, and pharmacies as an antioxidant. This study aimed to outline the existing evidence on the toxicological studies of PG including its physicochemical properties, metabolism, and pharmacokinetics effects. The methods include updated searches for the relevant databases. The EFSA has evaluated the use of PG in food industry. It establishes an acceptable daily intake (ADI) of 0.5 mg/kg bw per day. Based on exposure assessment, it can be concluded that at the current level of use, PG is not of safety concern., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

New approaches to reducing synthetic preservatives in the preservation of foods draw the attention of plant-derived bioactive compounds, especially for application in foods highly susceptible to spoilage, such as fish products. The review presents relevant data from procurement, application, and methodological research trends to investigate the potential effects of plant-derived bioactive compounds on shelf life extension in fish products. The systematization of data allowed observation that the different methods of extraction and application of bioactive plant compounds result in different effects, such as the reduction of lipid oxidation, antimicrobial effects, and maintenance of sensory characteristics, benefiting the extension of shelf life. In general, plant-derived bioactive compounds are an alternative for the preservation of fish products; however, approaches to the composition of the compounds can contribute to the optimization and efficiency of the process from a technical point of view and industrial viability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To develop new shrimp preservative agents with dual functions of anti-browning and antibacterial, thirteen hydroxypyranone-thiosemicarbazone derivatives were prepared according to molecular hybridization. Thereinto, compound 7j (IC 50  = 1.99 ± 0.19 μM) shown the strongest anti-tyrosinase activity and was about twenty-three folds stronger than kojic acid (45.73 ± 4.03 μM). The anti-tyrosinase mechanism of 7j was illustrated through enzyme kinetic, copper ion chelating ability, fluorescence quenching, ultraviolet spectrum, AFM analysis, and molecular docking study. On the other hand, antibacterial assay and time-kill kinetics analysis confirmed that 7j also had good antibacterial activity against V. parahaemolyticus (MIC = 0.13 mM). PI uptake test, SDS-PAGE, and fluorescence spectrometry analysis proved that 7j can affect the bacterial cell membrane. Finally, the shrimp preservation and safety study indicated that 7j has dual effects of inhibiting bacterial growth and preventing enzyme browning, and can be applied to the preservation of fresh shrimp., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Due to their ubiquitous use, isothiazolinones caused allergic contact dermatitis epidemics and their use was restricted by legal regulations., Objectives: We aimed to evaluate demographic data, clinical findings, and patch test features of patients with methylisothiazolinone (MI) and/or methylchloroisothiazolinone(MCI) sensitivity in our study., Methods: This study is a bidirectional and cross-sectional study, between July 2020 and September 2021. A total of 616 patients, including prospective and retrospective populations, demographic data, clinical findings, and patch test results were reviewed. Patients' demographics, patch test results, allergen sources, presence of occupational contact, and the characteristics of dermatitis attacks were recorded., Results: A total of 50 patients with MI and MCI/MI sensitivity, 36 male (72%) and 14 female (28%), were included in our study. The overall prevalence of MI and MCI/MI between 2014 and 2021 was 8.4% (52/616) with two peak levels in 2015(21%) and 2021 (20%). A statistically significant relationship was found between shampoo use and facial involvement ( p  = 0.031), shower gel use and arm involvement ( p  = 0.027), wet wipe use and hand involvement ( p  = 0.049), detergent use and the pulps ( p  = 0.026) and the lateral aspects of fingers involvement ( p  = 0.048), water-based dye use and periungual involvement ( p  = 0.047)., Conclusion: Although legal regulations related to MI and MCI/MI cause a decrease in the frequency of their sensitivities were still common causes of allergic contact dermatitis.