Preservatives and ocular surface disease: A review.

Ocular surface disease (OSD) is a complex condition that can cause a range of symptoms (e.g, dryness, irritation, and pain) and can significantly impact the quality of life of affected individuals. Iatrogenic OSD, a common finding in patients with glaucoma who receive chronic therapy with topical ocular antihypertensive drugs containing preservatives such as benzalkonium chloride (BAK), has been linked to damage to the ocular surface barrier, corneal epithelial cells, nerves, conjunctival goblet cells, and trabecular meshwork. Chronic BAK exposure activates inflammatory pathways and worsens symptoms, compromising the success of subsequent filtration surgery in an exposure-dependent manner. In eyes being treated for glaucoma, symptomatic treatment of OSD may provide some relief, but addressing the root cause of the OSD often necessitates reducing or, ideally, eliminating BAK toxicity. Strategies to decrease BAK exposure in patients with glaucoma encompass the use of preservative-free formulations or drugs with alternative and less toxic preservatives such as SofZia®, Polyquad, potassium sorbate, or Purite®. Though the benefits of these alternative preservatives are largely unproven, they might be considered when financial constraints prevent the use of preservative-free versions. For patients receiving multiple topical preserved drugs, the best practice is to switch to nonpreserved equivalents wherever feasible, regardless of OSD severity. Furthermore, nonpharmacological approaches, including laser or incisional procedures, should be considered. This review explores the effects of BAK on the ocular surface and reviews strategies for minimizing or eliminating BAK exposure in patients with glaucoma in order to significantly improve their quality of life and prevent complications associated with chronic exposure to BAK.

Preparation of self-preserving personal care cosmetic products using multifunctional ingredients and other cosmetic ingredients.

The development of self-preserving personal care cosmetics represents a significant advancement in the cosmetics industry, offering safer and more natural alternatives to consumers. This study focused on the preparation of such formulations using multifunctional ingredients along with other cosmetic components. Five unique multifunctional ingredients (MFIs) were identified based on their antimicrobial properties: sodium coco PG-dimonium chloride phosphate, ricinoleic acid, palmitoleic acid, raspberry ketone, and sorbitan caprylate. Through meticulous experimentation, 150 combinations of MFIs were prepared and tested to understand their synergistic actions. From these trials, three synergistic antimicrobial compositions were determined: sodium coco PG-dimonium chloride phosphate: ricinoleic acid: raspberry ketone in the ratios 1:6.3:6.3 and 1:6.3:15.7. Sodium coco PG-dimonium chloride phosphate: palmitoleic acid: sorbitan caprylate at a ratio of 1:12.5:37.5. These synergistic compositions exhibited enhanced antimicrobial efficacy compared with their individual components, as evidenced by their lower Minimum Inhibitory Concentration values. Incorporating these formulations into three distinct personal care cosmetic products, including a color protection shampoo, body wash shower gel, and skin-lightening cream, the study further validated their effectiveness. A Preservation Challenge Test study revealed that all three antimicrobial compositions successfully preserved the cosmetic formulations for up to 28 days. This method of product preservation not only ensures consumer safety and stability but also reduces the need for potentially conventional preservatives. In conclusion, the appropriate use of multifunctional ingredients in combination with meticulous formulation techniques has led to the successful development of self-preserving personal care cosmetics. These formulations offer a promising avenue for the cosmetic industry, catering to the rising demand for natural, effective, and consumer-friendly cosmetic products.

Review on the extension of shelf life for fruits and vegetables using natural preservatives.

Fruits and vegetables are important for the nutrition and health of individuals. They are highly perishable in nature because of their susceptibility to microbial growth. Foodborne pathogens create a significant problem for consumers, food businesses, and food safety. Postharvest factors, including transportation, environment, and preservation techniques, cause a reduction in product quality. The present world is using synthetic preservatives, which have negative impacts on consumer health. Food safety and demand for healthy foods among consumers, the scientific community, and the food industry resulted in the exploitation of natural preservatives, which play an important role in their effectiveness, prolonged shelf life, and safety. Natural preservatives include plants, animals, and microbiological sources with polymers to extend shelf life, improve quality, and enhance food safety. This review specifically focuses on mechanism of action of natural preservatives, spoilage of fruit and vegetables, the importance of edible film and coating on fruits and vegetables.

Small Molecule Topical Ophthalmic Formulation Development-Data Driven Trends & Perspectives from Commercially Available Products in the US.

Topical ophthalmic drug product development is a niche research domain as the drug formulations need to be designed to perform in the unique ocular physiological conditions. The most common array of small molecule drug formulations intended for topical ophthalmic administration include solutions, suspensions, emulsions, gels, and ointments. The formulation components such as excipients and container closure are unique to serve the needs of topical ophthalmic delivery compared to other parenteral products. The selection of appropriate formulation platform, excipients, and container closure for delivery of drugs by topical ophthalmic route is influenced by a combination of factors like physicochemical properties of the drug molecule, intended dose, pharmacological indication as well as the market trends influenced by the patient population. In this review, data from literature and packaging inserts of 118 reference listed topical ophthalmic medications marketed in the US are collected and analyzed to identify trends that would serve as a guidance for topical ophthalmic formulation development for small molecule drugs. Specifically, the topics reviewed include current landscape of the available small molecule topical ophthalmic drug products in the US, physicochemical properties of the active pharmaceutical ingredients (APIs), formulation platforms, excipients, and container closure systems.

Microbial Contamination of Food: Probiotics and Postbiotics as Potential Biopreservatives.

Microbial contamination of food and alimentary toxoinfection/intoxication in humans are commonly caused by bacteria such as Salmonella spp., Escherichia coli, Yersinia spp., Campylobacter spp., Listeria monocytogenes, and fungi (Aspergillus, Fusarium). The addition of probiotic cultures (bacterial strains Lactobacillus and Bifidobacterium and the yeast Saccharomyces cerevisiae var. boulardii) to food contributes primarily to food enrichment and obtaining a functional product, but also to food preservation. Reducing the number of viable pathogenic microorganisms and eliminating or neutralizing their toxins in food is achieved by probiotic-produced antimicrobial substances such as organic acids (lactic acid, acetic acid, propionic acid, phenylacetic acid, and phenyllactic acid), fatty acids (linoleic acid, butyric acid, caproic acid, and caprylic acid), aromatic compounds (diacetyl, acetaldehyde, reuterin), hydrogen peroxide, cyclic dipeptides, bacteriocins, and salivabactin. This review summarizes the basic facts on microbial contamination and preservation of food and the potential of different probiotic strains and their metabolites (postbiotics), including the mechanisms of their antimicrobial action against various foodborne pathogens. Literature data on this topic over the last three decades was searched in the PubMed, Scopus, and Google Scholar databases, systematically presented, and critically discussed, with particular attention to the advantages and disadvantages of using probiotics and postbiotics as food biopreservatives.

Insight into the Probiogenomic Potential of Enterococcus faecium BGPAS1-3 and Application of a Potent Thermostable Bacteriocin.

This study aimed to investigate the probiogenomic features of artisanal bacteriocin-producing Enterococcus faecium BGPAS1-3 and the use of the improved pMALc5HisEk expression vector for overexpressing class II bacteriocins and the application of purified bacteriocin 31 in a milk model as a preservative against L. monocytogenes. The BGPAS1-3 strain was isolated from traditional fresh soft cheese manufactured in households on a small scale in rural locations surrounding Pale Mountain City in Bosnia and Herzegovina. The whole-genome sequencing approach and bioinformatics analyses revealed that the strain BGPAS1-3 was non-pathogenic to humans. The presence of bacteriocin operons suggested the ability of the isolate to suppress the growth of pathogens. Coding regions for three maturated bacteriocins (bacteriocin 31, bacteriocin 32, and enterocin P) produced by BGPAS1-3 were amplified and expressed in Escherichia coli ER2523 using the pMALc5HisEk system. All three bacteriocins were successfully overexpressed and purified after enterokinase cleavage but showed different antimicrobial activity. Bacteriocin 31 showed significantly stronger antimicrobial activity compared with bacteriocin 32. It was the only one that proved to be suitable for use as a food preservative against L. monocytogenes in a milk model.

Deciphering trends in replacing preservatives in cosmetics intended for infants and sensitive population.

The present study aims to investigate the current trends in replacing conventional preservatives with multifunctional ingredients with antimicrobial properties for preservation of cosmetics for infants or sensitive population, to decrease their potential for contact dermatitis. We first reviewed the labels of cosmetics purchased from the Chinese market for conventional preservatives and multifunctional ingredients with antimicrobial properties, of which the actual contents were further quantified by chromatographic methods. We identified 7 traditional preservatives (phenoxyethanol, benzoic acid (salts), methylparaben, benzyl alcohol, sorbic acid (salts), propylparaben, and methylisothiazolinone), and 11 alternative ingredients with antimicrobial activities (ethylhexylglycerin, butylene glycol, caprylyl glycol, propylene glycol, 1,2-hexanediol, p-anisic acid, hydroxyacetophenone, pentylene glycol, decylene glycol, caprylhydroxamic acid, and aminomethyl propanol) in descending order of prevalence. The contents of all identified preservatives and ingredients were either below regulatory limits or in the range that is generally regarded to be safe. Further challenge with microorganisms indicated irrespective of the composition of preservation systems, product preservation could be compromised under test conditions. We conclude that multifunctional ingredients with antimicrobial properties in cosmetics have the potential to completely replace or significantly reduce the use of traditional preservatives while retaining comparative preservative efficacy. Future attentions may need to be shifted to the safety of those multifunctional ingredients with antimicrobial properties.

Adaptation and Validation of a Modified Broth Microdilution Method for Screening the Anti-Yeast Activity of Plant Phenolics in Apple and Orange Juice Models.

Yeasts are the usual contaminants in fruit juices and other beverages, responsible for the decrease in the quality and shelf-life of such products. Preservatives are principally added to these beverages to enhance their shelf-life. With the increasing consumer concern towards chemical food additives, plant-derived antimicrobials have attracted the attention of researchers as efficient and safer anti-yeast agents. However, the methods currently used for determining their anti-yeast activity are time- and material-consuming. In this study, the anti-yeast effect of plant phenolic compounds in apple and orange juice food models using microtiter plates has been evaluated in order to validate the modified broth microdilution method for screening the antimicrobial activity of juice preservative agents. Among the twelve compounds tested, four showed a significant in vitro growth-inhibitory effect against all tested yeasts (Saccharomyces cerevisiae, Zygosaccharomyces bailii, and Zygosaccharomyces rouxii) in both orange and apple juices. The best results were obtained for pterostilbene in both juices with minimum inhibitory concentrations (MICs) ranging from 32 to 128 µg/mL. Other compounds, namely oxyresveratrol, piceatannol, and ferulic acid, exhibited moderate inhibitory effects with MICs of 256-512 µg/mL. Furthermore, the results indicated that differences in the chemical structures of the compounds tested significantly affected the level of yeast inhibition, whereas stilbenes with methoxy and hydroxy groups produced the strongest effect. Furthermore, the innovative assay developed in this study can be used for screening the anti-yeast activity of juice preservative agents because it saves preparatory and analysis time, laboratory supplies, and manpower in comparison to the methods commonly used.

Effect of West Indian Bay Leaf (Pimenta racemosa) and Turmeric (Curcuma longa) Essential Oils on Preserving Raw Chicken Breasts.

Research background: While the use of chemical preservatives in meat may appear to be tremendously advantageous, they have long been purported to increase the risk of incidence of certain types of cancers. Consequently, many people have opted for minimally processed alternatives. This consumer shift has placed substantial pressure on the food industry to implement more natural alternatives to these synthetic preservatives in the meat industry. Research on plant extracts as potential agents for food additives is increasing. The bioactive components present in West Indian bay leaf and turmeric essential oils have a promising potential for use as novel, green preservatives in the meat industry. Experimental approach: Raw chicken breast samples (28 g) were each treated with different volumes (0.5, 1 and 1.5 mL) of the essential oil of West Indian bay leaf or turmeric or their mixture (1:1 to make up a final volume of 0.5, 1 and 1.5 mL). Physicochemical, microbiological and sensory evaluations were performed on the fresh and treated samples stored for 14 days at 4 °C. Results and conclusions: The West Indian bay leaf oil had a higher extraction yield and total phenolic content, while the turmeric oil had a higher total flavonoid content. The most effective treatments, compared to the control, significantly (p<0.05) minimized the pH increase by 13.9 % (1.5 mL bay leaf oil), reduced texture loss by 44.8 % (1.5 mL oil mixture) and reduced protein loss by 98.9 % (1 mL bay leaf oil). Most treated samples had reduced microbial loads, with the turmeric oil showing the highest efficacy against lactic acid bacteria, yeasts and moulds. Treated samples had significantly higher (p<0.05) sensory scores than the control on the final day of storage, with the 1.5 mL oil mixture proving to be the most effective, as the storage life of the chicken breast sample was extended by 6 days. Novelty and scientific contribution: This study has shown for the first time that the essential oil from turmeric and West Indian bay leaf can extend the shelf life of raw chicken breast and highlights the potential of the oil as natural preservative agents in lieu of synthetic alternatives.

Preservatives for postmortem brain tissue in biomechanical testing: A pilot study.

Postmortem human subject (PMHS) studies are essential to brain injury research in motor vehicle safety. However, postmortem deterioration reduces the similarity between postmortem test results and in vivo response in material testing of brain tissue and in biomechanical testing of the whole head. This pilot study explores the effect of potential preservatives on brain tissue breakdown to identify promising preservatives that warrant further investigation. To identify preservatives with potential to slow postmortem degradation, samples from an initial PMHS were refrigerated at 10°C to qualitatively compare tissue breakdown from 58 to 152 h postmortem after storage in candidate solutions. On brain tissue samples from a second PMHS, compressive stiffness was measured on six samples immediately after harvest for comparison to the stiffness of 23 samples that were stored at 10°C in candidate solutions for 24 h after harvest. The candidate solutions were artificial cerebrospinal fluid (ACSF) without preservatives; ACSF with a combination of antibiotics and antifungal agents; ACSF with added sodium bicarbonate; and ACSF with both the antibiotic/antifungal combination and sodium bicarbonate. Results were analyzed using multiple linear regression of specimen stiffness on harvest lobe and storage solution to investigate potential differences in tissue stiffness. Qualitative evaluation suggested that samples stored in a solution that contained both the antibiotic/antifungal combination and sodium bicarbonate exhibited less evidence of tissue breakdown than the samples stored without preservatives or with only one of those preservatives. In compression testing, samples tested immediately after harvest were significantly stiffer than samples tested after 24 h of storage at 10°C in ACSF (difference: -0.27 N/mm, 95% confidence interval (CI): -0.50, -0.05) or ACSF with antibiotics/antifungal agents (difference: -0.32 N/mm, 95% CI: -0.59, -0.04), controlling for harvest lobe. In contrast, the stiffness of samples tested after storage in either solution containing sodium bicarbonate was not significantly different from the stiffness of samples tested at harvest. There was no significant overall difference in the mean tissue stiffness between samples from the frontal and parietal lobes, controlling for storage solution. Given the importance of PMHS studies to brain injury research, any strategy that shows promise for helping to maintain in vivo brain material properties has the potential to improve understanding of brain injury mechanisms and tolerance to head injury and warrants further investigation. These pilot study results suggest that sodium bicarbonate has the potential to reduce the deterioration of brain tissue in biomechanical testing. The results motivate further evaluation of sodium bicarbonate as a preservative for biomechanical testing using additional test subjects, more comprehensive material testing, and evaluation under a broader set of test conditions including in whole-head testing. The effect of antibiotics and antifungal agents on brain tissue stiffness was minimal but may have been limited by the cold storage conditions in this study. Further exploration of the potential for microbial agents to preserve tissue postmortem would benefit from evaluation of the effects of storage temperature.

Enhancing Bioactivity through the Transfer of the 2-(Hydroxymethoxy)Vinyl Moiety: Application in the Modification of Tyrosol and Hinokitiol.

Utilizing Density Functional Theory (DFT) calculations at the B3LYP/QZVP level and incorporating the Conductor-like Polarizable Continuum Model (C-PCM) for solvation, the thermodynamic and chemical activity properties of 21-(hydroxymethoxy)henicosadecaenal, identified in cultured freshwater pearls from the mollusk Hyriopsis cumingii, have been elucidated. The study demonstrates that this compound releases formaldehyde, a potent antimicrobial agent, through dehydrogenation and deprotonation processes in both hydrophilic and lipophilic environments. Moreover, this polyenal exhibits strong anti-reductant properties, effectively scavenging free radicals. These critical properties classify the pearl-derived ingredient as a natural multi-functional compound, serving as a coloring, antiradical, and antimicrobial agent. The 2-(hydroxymethoxy)vinyl (HMV) moiety responsible for the formaldehyde release can be transferred to other compounds, thereby enhancing their biological activity. For instance, tyrosol (4-(2-hydroxyethyl)phenol) can be modified by substituting the less active 2-hydroxyethyl group with the active HMV one, and hinokitiol (4-isopropylotropolone) can be functionalized by attaching this moiety to the tropolone ring. A new type of meso-carrier, structurally modeled on pearls, with active substances loaded both in the layers and the mineral part, has been proposed.

Enhanced ε-Poly-L-Lysine Production in Streptomyces albulus through Multi-Omics-Guided Metabolic Engineering.

Safe and eco-friendly preservatives are crucial to preventing food spoilage and illnesses, as foodborne diseases caused by pathogens result in approximately 600 million cases of illness and 420,000 deaths annually. ε-Poly-L-lysine (ε-PL) is a novel food preservative widely used in many countries. However, its commercial application has been hindered by high costs and low production. In this study, ε-PL's biosynthetic capacity was enhanced in Streptomyces albulus WG608 through metabolic engineering guided by multi-omics techniques. Based on transcriptome and metabolome data, differentially expressed genes (fold change >2 or <0.5; p < 0.05) and differentially expressed metabolites (fold change >1.2 or <0.8) were separately subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The integrative analysis of transcriptome, metabolome, and overexpression revealed the essential roles of isocitrate lyase, succinate dehydrogenase, flavoprotein subunit, diaminopimelate dehydrogenase, polyphosphate kinase, and polyP:AMP phosphotransferase in ε-PL biosynthesis. Subsequently, a strain with enhanced ATP supply, L-lysine supply, and ε-PL synthetase expression was constructed to improve its production. Finally, the resulting strain, S. albulus WME10, achieved an ε-PL production rate of 77.16 g/L in a 5 L bioreactor, which is the highest reported ε-PL production to date. These results suggest that the integrative analysis of the transcriptome and metabolome can facilitate the identification of key pathways and genetic elements affecting ε-PL synthesis, guiding further metabolic engineering and thus significantly enhancing ε-PL production. The method presented in this study could be applicable to other valuable natural antibacterial agents.

Microencapsulation to Harness the Antimicrobial Potential of Essential Oils and Their Applicability in Dairy Products: A Comprehensive Review of the Literature.

This literature review explores cutting-edge microencapsulation techniques designed to enhance the antimicrobial efficacy of essential oils in dairy products. As consumer demand for natural preservatives rises, understanding the latest advancements in microencapsulation becomes crucial for improving the shelf life and safety of these products. The bibliometric analysis utilized in this review highlighted a large number of documents published on this topic in relation to the following keywords: essential oils, AND antimicrobials, AND dairy products, OR microencapsulation. The documents published in the last 11 years, between 2013 and 2023, showed a diversity of authors and countries researching this topic and the keywords commonly used. However, in the literature consulted, no study was identified that was based on bibliometric analysis and that critically evaluated the microencapsulation of essential oils and their antimicrobial potential in dairy products. This review synthesizes findings from diverse studies, shedding light on the various encapsulation methods employed and their impact on preserving the quality of dairy goods. Additionally, it discusses the potential applications and challenges associated with implementation in the dairy industry. This comprehensive analysis aims to provide valuable insights for researchers, food scientists, and industry professionals seeking to optimize the use of essential oils with antimicrobial properties in dairy formulations.

Survival of Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes in Ready-to-Eat "Guacamole": Role of Added Antimicrobials.

Ensuring the microbiological safety of food products is majorly important to regulatory agencies, producers, and consumers. This study aimed to examine the effects of three different antimicrobial agents, including chitosan (CH), mastic oil (M), and citric acid (CA), individually or as a combination, against Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes (artificially inoculated) in Guacamole, a ready-to-eat (RTE) avocado-based salad. The Guacamole samples included untreated samples, designated as CNL, and samples treated as follows: CA 0.15% and CA 0.30% with citric acid added at 0.15% and 0.30% v/w; CH 0.5% and CH 1% with chitosan at 0.5 and 1% v/w; M 0.2% and M 0.4% with mastic essential oil (EO) at 0.2% and 0.4% v/w; CACH with CA 0.30% and CH 1% v/w; CAM with CA 0.30% and M 0.4% v/w; CHM with CH 1% and M 0.4% v/w; and CACHM with CA 0.30%, CH 1%, and M 0.4% v/w. Microbiological evaluation, monitoring of the pH values, and proximate analyses (moisture, fat, protein, ash, and water activity) were performed at different time intervals (days 0, 1, 3, 5, and 7) at two storage temperatures (4 and 10 °C). Antimicrobial treatments, particularly CH 1% and CACHM, effectively (p < 0.05) reduced Salmonella spp. and E. coli O157:H7 populations at 4 °C, while CACHM showed the most efficacy against L. monocytogenes. However, at 10 °C, antimicrobials had limited impact, and the bacterial counts exhibited an increasing trend during storage. The pH values in the avocado-based salad samples showed, in general, higher decreases at 10 compared to 4 °C, with the CHM combination showing the highest antimicrobial effect.

Allergic Conjunctivitis Management: Update on Ophthalmic Solutions.

PURPOSE OF REVIEW: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. RECENT FINDINGS: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.

Effects of storage and processing on the residual distribution and behavior of five preservatives and their metabolites in pomegranate.

Pomegranate are often treated with preservatives during storage. This study investigated the effects of storage and food processing on the residual behavior of the five commonly used preservatives (prochloraz, thiophanate-methyl, pyrimethanil, imazalil, and difenoconazole) and their metabolites in pomegranate and its products. The LOQs for all target compounds were 0.001 mg kg-1. The residue levels of five preservatives in the calyx was highest, followed by the peel, stalk, septum, umbilicus, and seed. For the migration ability, the five preservatives from pomegranate peel to seed was negatively correlated with their octanol/water partition coefficients. The processing factors of each procedures of juice, wine, vinegar, and pectin processing were <1. Nevertheless, the PF values in drying peel during the overall process ranged from 1.26 to 4.09. Hence, it is worth noting that consumption of pomegranate essential oil and drying peel may pose a potential risk to the health of consumers.

Preservative contact allergy in occupational dermatitis: a machine learning analysis.

Occupational dermatoses impose a significant socioeconomic burden. Allergic contact dermatitis related to occupation is prevalent among healthcare workers, cleaning service personnel, individuals in the beauty industry and industrial workers. Among risk factors, the exposure to preservatives is frequent, since they are extensively added in products for occupational use. The goal of this study is to investigate the contact allergy patterns in order to understand the linkage among hypersensitivity to preservatives, occupational profiles, patients' clinical and demographic characteristics. Patch test results were collected from monosensitized patients to Formaldehyde 2%, KATHON 0.02%, thimerosal 0.1%, and MDBGN 0.5%; information was also collected for an extended MOAHLFA (Male-Occupational-Atopic-Hand-Leg-Face-Age) index. To assess the relationship between allergen group and occupational-related ACD, the chi-square test for independence was utilized. To uncover underlying relationships in the data, multiple correspondence analysis (MCA) and categorical principal components analysis (CATPCA), which are machine learning approaches, were applied. Significant relationships were found between allergen group and: occupation class, atopy, hand, leg, facial, trunk, neck, head dermatitis, clinical characteristics, ICDRG 48 h and ICDRG 72 h clinical evaluation. MCA and CATPCA findings revealed a link among allergen group, occupation class, patients' demographic and clinical characteristics, the MOAHLFA index, and the ICDRG scores. Significant relationships were identified between the allergen group and various manifestations of dermatitis. The utilization of machine learning techniques facilitated the discernment of meaningful patterns in the data.

A Combined LC-MS and Immunoassay Approach to Characterize Preservative-Induced Destabilization of Human Papillomavirus Virus-like Particles Adsorbed to an Aluminum-Salt Adjuvant.

During the multi-dose formulation development of recombinant vaccine candidates, protein antigens can be destabilized by antimicrobial preservatives (APs). The degradation mechanisms are often poorly understood since available analytical tools are limited due to low protein concentrations and the presence of adjuvants. In this work, we evaluate different analytical approaches to monitor the structural integrity of HPV16 VLPs adsorbed to Alhydrogel™ (AH) in the presence and absence of APs (i.e., destabilizing m-cresol, MC, or non-destabilizing chlorobutanol, CB) under accelerated conditions (pH 7.4, 50 °C). First, in vitro potency losses displayed only modest correlations with the results from two commonly used methods of protein analysis (SDS-PAGE, DSC). Next, results from two alternative analytical approaches provided a better understanding of physicochemical events occurring under these same conditions: (1) competitive ELISA immunoassays with a panel of mAbs against conformational and linear epitopes on HPV16 VLPs and (2) LC-MS peptide mapping to evaluate the accessibility/redox state of the 12 cysteine residues within each L1 protein comprising the HPV16 VLP (i.e., with 360 L1 proteins per VLP, there are 4320 Cys residues per VLP). These methods expand the limited analytical toolset currently available to characterize AH-adsorbed antigens and provide additional insights into the molecular mechanism(s) of AP-induced destabilization of vaccine antigens.

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges.

Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates.

Acute toxicity of petroleum asphalt seal coat leachates to Ceriodaphnia dubia is linked to polymer preservatives.

Low-VOC waterborne asphalt-emulsion (AE) seal coat is considered more sustainable than solvent-based coal-tar emulsion seal coat because asphalt emulsions contain negligible amounts of carcinogenic PAHs and release fewer harmful volatile organic compounds. Yet, many low-VOC coatings leach water-soluble substances under outdoor conditions. To investigate the chemical composition of seal coat leachates, three AE formulations were cured under natural weathering conditions and exposed to simulated runoff over a 10-day field trial. Runoff was collected and concentrated using ion-exchange solid-phase extraction (SPE) and analyzed using gas chromatography/mass spectrometry (GC-MS). Leached compounds included hydrocarbons, esters, amines, siloxanes, plasticizers, biocides, polyethylene glycol (PEG) ethers, urethanes, and toluene diisocyanate (TDI). Glycol ethers comprised 29-97 % of the measured leachate mass. Two seal coat formulations contained isothiazolinone biocides, methylchloro- and methylisothiazolinone (CMIT/MIT; 0.5 mg/L in runoff), while a third seal coat formulation continuously leached TDI, a reactive polyurethane (PU) precursor (0.7 mg/L in runoff). Biocide-containing leachates showed acute toxicity to the freshwater water flea, Ceriodaphnia dubia after 48 h, while TDI-containing leachate showed no acute toxicity, suggesting that leachate toxicity was due to in-can polymer preservatives. As biocides are implicated in impaired reproductive signaling, these results support the use of alkaline pH to avoid biofouling and reinforce the goal of reducing and/or avoiding the use of biocides altogether, especially for environmentally friendly products.