Strong Irritants Research Articles

Dermal toxicity studies of 1,2-benzisothiazolin-3-one (CAS number: 2634-33-5) in Sprague-Dawley rats

Biocides are used as preservatives in various household products, and 1,2-benzisothiazolin-3-one (BIT) is one of the popular chemicals. Therefore, BIT is highly likely to be exposed to human skin, necessitating dermal toxicity evaluation. In this study, we aimed to investigate dermal toxicity, eyes and skin irritation, and skin sensitization of BIT. All studies were conducted according to the Organisation for Economic Co-operation and Development testing guidelines. In acute dermal toxicity using rats, no treatment-related responses were observed at the highest dose (2000 mg/kg). A 28-day repeated dermal toxicity study at 1, 4, and 12 mg/kg/day showed transient local skin irritation lesions, including erythema, exfoliation, and crust formation. Based on no systemic effects, the no observed adverse effect level (NOAEL) of BIT of the 28-day repeated dermal toxicity study was determined to be 12 mg/kg/day. Eye and skin irritation tests showed that BIT is a strong irritant and corrosive to the eyes and a mild irritant to the skin. However, BIT showed no skin sensitization reactions in a local lymph node assay. These dermal toxicity studies can provide valuable information for the risk assessment of BIT.

Enhanced stability and reduced irritation of 4-n-butylresorcinol via nanoemulsion formulation: Implications for skin pigmentation treatment

4-n-butylresorcinol (4-nBR) is a valuable ingredient to lighten skin and reduce pigmentation, contributing to an even skin tone and a more youthful appearance. However, its poor solubility, low stability, and strong irritation to the skin limit its application. In this study, 4-nBR was prepared into 4-n-butylresorcinol nanoemulsion (4-nBR-NE) for the first time, enhancing the solubility and stability of 4-nBR while greatly reducing its skin irritation. The relationship between the viscosity of nanoemulsion and the formulation process, as well as the impact of surfactant ratio on the formability of 4-nBR-NE were further studied. This led to the successful development of a nanoemulsion with adjustable viscosity (AV-NE) and with a low surfactant content. The particle size of 4-nBR-NE was 13.34 ± 0.16 nm with a PDI of 0.0853 ± 0.0191, indicating a uniform particle size distribution. The encapsulation rate of 4-nBR-NE was determined to be 80.05 ± 0.75 % via UV–Vis spectrophotometry. In addition, 4-nBR-NE demonstrated excellent stability over several months, with negligible changes in particle size. Cellular and transdermal evaluations confirmed that the preparation of 4-nBR-NE effectively reduced the original irritation cause by 4-nBR on cells and skin. Then, 4-nBR-NE was incorporated into an essence. This advancement enhances the applicability of 4-nBR in treating pigmentation disorders such as melasma and freckles, thereby increasing its applicability in pharmaceutical and cosmetic industries.

A case of acute inhalation dinitrogen tetroxide poisoning

Dinitrogen tetroxide is often used as an oxidant in rocket propellant and has strong irritant and corrosive properties. This paper analyzes the clinical data of a patient with dinitrogen tetroxide poisoning admitted in the 63710 Army Hospital of Chinese People's Liberation Army, so as to further explore the poisoning mechanism, clinical characteristics and key points of acute inhaled dinitrogen tetroxide poisoning.

Symptomatic treatment of mosquito bites with a thermo-therapeutic medical device: a prospective, intraindividual compared, placebo-controlled, randomized clinical trial

Objective: Agonizing itching (pruritus), heat, and burning are common symptoms of mosquito bites. In this study, we present a thermo-therapeutic medical device for the symptomatic treatment of mosquito bites. Current research suggests the potential of a thermal (heat) stimulus for pruriceptor counter-stimulation and reduced histamine-signaling to relieve the symptoms of mosquito bites. The purpose of this clinical investigation was to investigate the efficacy and safety of the thermo-therapeutic medical device (class II) in the symptomatic treatment of mosquito bites in an intraindividual comparison to a placebo device (PD) examined under standardized conditions. This was achieved by assessing pruritus and wheal size over time after induction of a mosquito bite on the volar forearm. Methods: The itching was rated on a Visual Analog Scale ranging from 0 mm (no itching) to 100 mm (worst imaginable itching). The wheal size was measured in approximation to the area of an eclipse before and ~30 minutes after the treatment with the investigational device. Local tolerability was assessed by the investigator according to a score ranging from 0 (no irritation) to 4 (very strong irritation) and the subjects stated if the itching sensation was completely gone after treatment (yes/no question). Results: The mean area under the curve of the difference to baseline for the treatment with the medical device was statistically significantly bigger than for the treatment with the PD (1311.71 vs 914.61, respectively; P = 0.0127). Conclusions: Treatment of a mosquito bite with a thermo-therapeutic medical device significantly reduced pruritus and led to a faster reduction of the itching sensation as compared with PD. A significant itch reduction started immediately (1 min) after treatment with the medical device (post hoc analysis). The treatment with the medical device was well tolerated by all subjects and no adverse events related to the medical device occurred.

Behavioral responses and life history traits of Taiwanese and Indonesian populations of Aedes aegypti surviving deltamethrin–clothianidin treatment

BackgroundIndoor residual spraying (IRS) capitalizes on the natural behavior of mosquitoes because Aedes aegypti commonly seeks indoor resting sites after a blood meal. This behavior allows mosquitoes to be exposed to insecticide-treated surfaces and subsequently killed. Combinations of deltamethrin and clothianidin with different modes of action have shown promise in IRS, effectively targeting both susceptible and pyrethroid-resistant malaria vectors. However, the effects of this approach on Aedes mosquitoes remain unclear. The present study tested the effects of deltamethrin–clothianidin mixture treatment on behavioral responses and life history traits of Taiwanese and Indonesian populations of Ae. aegypti.MethodsWe adopted an excito-repellent approach to explore the behavioral responses of pyrethroid-resistant Ae. aegypti populations from Indonesia and Taiwan to a deltamethrin–clothianidin mixture used in contact irritancy and non-contact repellency treatments. We further evaluated the life history traits of surviving mosquitoes (i.e., delayed mortality after 7-day post-treatment, longevity, fecundity, and egg hatching) and investigated the potential transgenerational hormetic effects of insecticide exposure (i.e., development rate and survival of immatures and adult mosquitos).ResultsAll tested field populations of Ae. aegypti displayed strong contact irritancy responses; the percentage of escape upon insecticide exposure ranged from 38.8% to 84.7%. However, repellent effects were limited, with the escape percentage ranging from 4.3% to 48.9%. We did not observe immediate knockdown or mortality after 24 h, and less than 15% of the mosquitoes exhibited delayed mortality after a 7-day exposure period. However, the carryover effects of insecticide exposure on the survival of immature mosquitoes resulted in approximately 25% higher immature mortality than that in the control. By contrast, we further documented stimulated survivor reproduction and accelerated transgenerational immature development resulting from the sublethal effects of the insecticide mixture. In particular, the number of eggs laid by treated (both treatments) female mosquitoes increased by at least 60% compared with that of eggs laid by control female mosquitoes.ConclusionsIRS with deltamethrin–clothianidin effectively deters Aedes mosquitoes from entering residential areas and thereby reduces mosquito bites. However, the application rate (deltamethrin: 25 mg/m2; clothianidin: 200 mg/m2) may be insufficient to effectively kill Aedes mosquitoes. Insecticide response appears to vary across mosquito species; their behavioral and physiological responses to sublethal doses have crucial implications for mosquito control programs.Graphical

Multifunctional gelatin nanoparticle stabilized-Pickering emulsion hydrogel based on dextran and amikacin with controlled drug release and enhanced antibacterial capability for promoting infected wound healing

Plant essential oils possess broad-spectral antimicrobial property, but the applications are impeded by their insolubility in water, extreme volatility, and strong irritation. Nanoparticle-stabilized emulsion (Pickering emulsion) gels are colloidal systems with ability to accommodate two immiscible phases in one system. The thick adsorption nanoparticle layers and the cross-linked networks in continuous phase could provide protective barriers for antibacterial oil and achieve on-demand controlled release. An emulsion hydrogel templated from gelatin nanoparticle-stabilized emulsion is one-pot constructed by conducting a tunable cross-linking process between oxidized dextran (Odex) and amikacin in the continuous phase and concomitantly trapping tea tree essential oil (TO) droplets in the three-dimensional network. The resulted emulsion hydrogel presents tunable gelation time, adequate mechanical strength, fascinating injectability, and self-healing capability. It is pH-responsiveness and presents controlled release of amikacin and TO, exhibiting a long-term bacteriostasis of 144 h. The emulsion hydrogel facilitates the outstanding wound healing efficiency in 14 days (95.2 ± 0.8 % of wound closure), accompanied with enhanced collagen deposition and angiogenic activities. The incorporation of TO into emulsion hydrogel system reduced its irritation and improved its biosafety, showing potential application in bacteria inhibition even as implants in vivo.

Alocasia odora poisoning due to calcium oxalate needle crystals in Japan.

Objective: To elucidate the actual circumstances of damage caused by Japanese Alocasia (A) odora. Materials and Methods: We investigated cases in Japan from our own hospital in the eastern part of Shizuoka Prefecture as well as published reports. Results: A. dorais found in western Japan, and plants of the Alocasia genus are cultivated often. A. odora is frequently associated with food poisoning because its aboveground parts resemble those of Satoimo (Colocasia esculenta). Moreover, A. odora contains insoluble calcium oxalate crystals, which cause poisoning symptoms, such as oral pain, nausea, vomiting, and laryngeal edema, resulting in near asphyxia, diarrhea following shock, and skin dermatitis. Calcium oxalate crystals are abundant in Araceae family plants, and cases of health damage owing to the accidental ingestion of Araceae plants have been reported worldwide. Conclusion: Due to the strong irritation felt in the mouth upon contact with the plant, it is advisable to immediately spit out the plant and rinse the mouth. In addition to drug administration, ensuring a secure airway may be necessary if there is a risk of asphyxiation.

HET-CAM test in evaluation of irritating action of adhesives used in shoe making industry

The global tendency of the contemporary scientific studies is using alternative biologic models as substitutes of experimental animals. HET-CAM (The Hen's Egg Test on the Chorioallantoie Membrane Assay) is an alternative to in vivo tests involving experimental animals. This test is actively used in different biomedical studies. The aim of our work was to study the irritating potential of adhesives used in shoe making industry in experimental setting using the alternative HET-CAM method. Polyurethane, polychloroprene, rubber and styrene-butadiene adhesives that are widely used in shoe-making industry were studied . HET-CAM test was used for the evaluation of the irritating action of the aforementioned adhesives. All adhesives were applied directly onto the chorioallantoic membrane of chick embryos with reactions and changes (hemorrhages, vascular lysis and coagulation) observed and registered in 30, 120 and 300 seconds after the application of the adhesive. Irritating potential of the adhesives was evaluated according to a calculated irritating index. The most pronounced signs of irritating action were caused by polyurethane adhesives, namely hemorrhages and coagulation (30 sec) – two-component adhesive and hemor­rhages (30 sec) and coagulation (120-300 sec) – one-component adhesive. Vascular reactions from application of sty­rene-butadiene adhesives manifested predominantly with lysis and hemorrhages (30 sec), in some samples these reactions were observed at a later time-point (120-300 sec). Irritating action of rubber adhesives manifested mostly with hemor­rhages (30 sec), additionally one observation showed some lysis (120 sec). Polychloroprene adhesive caused hemorrhages (30-120 sec) and also lysis (30 sec) in one of the samples. According to the irritating index, polyurethane (one- and two-component) and styrene-butadiene adhesives were estimated to be strong irritants, while rubber and poly­chloroprene ones of moderate irritating action. НЕТ-САМ test can be used as a component in the evaluation of evidence of irritating action of shoe adhesives.

Irradiation of human oral mucosa by 233 nm far UV-C LEDs for the safe inactivation of nosocomial pathogens

The inactivation of multi resistant pathogens is an important clinical need. One approach is UV-C irradiation, which was previously not possible in vivo due to cytotoxicity. Recently, far UV-C irradiation at λ < 240 nm was successfully used on skin with negligible damage. A potential application site is the nasal vestibule, where MRSA accumulates and cannot be treated using antiseptics. We irradiated 3D mucosa models and excised human mucosa with 222 and 233 nm far UV-C in comparison to 254 nm and broadband UV-B. Eradication efficiency was evaluated by counting colony forming units; irritation potential was evaluated by hen’s egg-chorioallantoic membrane assay and trans epithelial electrical resistance; cell viability was assessed by MTT. DNA damage and cell protective mechanisms were evaluated immunohistopathologically. On mucosa models, MRSA reduced by ≈ 5 log10 for 60 mJ/cm2 irradiation at 233 nm. A slightly increased cell viability was observed after 24 h. Lower doses showed lower irritation potential than the positive controls or commercial mouthwash, while 80 mJ/cm2 had strong irritation potential. DNA damage occurred only superficially and decreased after 24 h. On excised human mucosa, < 10% of keratinocytes were affected after 150 mJ/cm2 222 nm or 60 mJ/cm2 233 nm.

Modelling and Evaluation of Noise Dispersion from Wind Turbine Operations

Abstract All over the world, the need for energy is increasing, and the methods of obtaining it are harmful to the environment. Traditional energy resources are rapidly depleting. During the extraction and burning of fossil fuels, many different pollutants enter the environment. One of the renewable forms of energy is wind energy. Wind energy is mainly used to generate electricity in wind farms. Wind turbines are a unique source of noise because they are installed at a high height above the ground, and the noise emitted is fluctuating and manifests itself in a wide frequency range. Noise from wind turbines as low as 32 dB(A) is a strong nervous system irritant for some people, while noise of 40 dB(A) and above causes severe discomfort for many people [1]. Detailed noise modeling was carried out in the considered area, assessing how noise affects individual dwellings, noise in the living environment of residential buildings were modeled. The noise level without background noise sources of the nearest residential environment was determined by modeling at 31.9 dB(A) during the night, while the limit value for the protection of human health according to HN 33:2011 is 45 dB(A).

Volatile Organic Compound Emissions from Indoor Fragrance Diffusers

People today spend most of their time indoors; many use fragrances in closed restrooms and bathrooms at home and in public spaces for masking odors. However, volatile organic compounds (VOCs) that are emitted from indoor fragrances have been reported in recent years to pose a risk to health. In this work, microneedle trap samplers (NTSs) were fabricated, packed with sulfonated divinylbenzene (SDVB) adsorbents, and used in passive mode to extract the VOCs that were emitted by bamboo diffusers in fragrance bottles in bathrooms. Instrumental analysis revealed that the main VOCs that were emitted from chemically synthesized fragrances were ethanol (19.2–40.5 ppb), propylene glycol (273.4–527.9 ppb), and 3-ethylbenzaldehyde (3.8–12.4 ppb). Lower indoor air change rates were associated with significantly higher emitted concentrations of VOCs. 3-Ethylbenzaldehyde is a strong respiratory irritant, and outdoor pollutants such as toluene, which escapes from paints, have a negative impact on indoor air quality.

A matrine-based supramolecular ionic salt that enhances the water solubility, transdermal delivery, and bioactivity of salicylic acid

Salicylic acid (H[Sal]) is an attractive bionic acid that is widely used in cosmetics and drugs for the treatment of skin diseases, owing to its excellent anti-acne, anti-inflammatory, antibacterial, oil-control, stratum-corneum-conditioning, and anti-photoaging abilities. However, H[Sal] is a relatively strong irritant and cannot be used on sensitive skin, and its poor water solubility limits the amounts that can be included in formulas, resulting in poor transdermal efficiency and bioavailability. In this study, we develop matrinium salicylate ([Mat][Sal]), a supramolecular ionic salt that is less cytotoxic and irritates the skin less than H[Sal], while exhibiting enhanced water-solubility, transdermal-delivery, and bioactivity properties. The anticancer, antioxidant, anti-inflammatory, and antibacterial properties of [Mat][Sal] are found to be superior or comparable to those of H[Sal]. The molecular structure of [Mat][Sal] is thoroughly investigated, including through single-crystal structure refinement, to gain an in-depth understanding of its properties. Moreover, in-vitro skin penetration experiments show that forming a salt with matrine increase the transdermal efficiency of H[Sal] while not damaging the skin barrier. The transdermal mechanisms of H[Sal] and [Mat][Sal] are studied both experimentally and using molecular dynamics simulations, which show that, compared to H[Sal], [Mat][Sal] reacts more strongly with the skin, and [Sal]− diffuses more rapidly in the skin owing to its higher water solubility and the ion-pair effect. Furthermore, [Mat][Sal] exhibits satisfactory anti-acne capabilities in a clinical-efficacy trial, highlighting its great potential for use in biomedical and cosmetics applications.

Assessment of antibacterial properties and skin irritation potential of anodized aluminum impregnated with various quaternary ammonium

The importance of the inert environment in the transmission of pathogens has been reassessed in recent years. To reduce cross-contamination, new biocidal materials used in high touch surfaces (e.g., stair railings, door handles) have been developed. However, their impact on skin remains poorly described. The present study aimed to evaluate the antibacterial properties and the risk of skin irritation of two materials based on hard-anodized aluminum (AA) impregnated with quaternary ammonium compound solutions (QAC#1 or QAC#2). The QAC#1 or QAC#2 solutions vary in composition, QAC#2 being free of dioctyl dimethyl ammonium chloride (Dio-DAC) and octyl decyl dimethyl ammonium chloride (ODDAC). Unlike AA used as a control, both AA-QAC#1 and AA-QAC#2 had excellent and rapid antibacterial efficacy, killing 99.9 % of Staphylococcus aureus and Escherichia coli bacteria, in 15 s and 1 min, respectively. The impregnation solutions (QAC#1 and QAC#2) did not show any skin sensitizing effect on transformed human keratinocytes. Nevertheless, these solutions as well as the materials (AA-QAC#1, AA-QAC#2), and the liquid extracts derived from them, induced a very rapid cytotoxicity on L929 murine fibroblasts (>70 % after 1 h of contact) as shown by LDH, MTS and neutral red assays. This cytotoxicity can be explained by the fast QACs release occurring when AA-QAC#1 and AA-QAC#2 were immersed in aqueous medium. To overcome the limitation of assays based on liquid condition, an in vitro skin irritation assay on reconstructed human epidermis (RHE) was developed. The effect of the materials upon their direct contact with the epidermis grown at the liquid-air interface was determined by evaluating tissue viability and quantifying interleukin-1 alpha (IL-1α) which is released in skin during injury or infection. AA-QAC#1 induced a significant decrease in RHE viability, close to OECD and ISO 10993-10 acceptability thresholds and enhanced the pro-inflammatory IL-1α secretion compared with AA-QAC#2. Finally, these results were corroborated by in vivo assays on mice using erythema and edema visual scores, histological observations, and epidermal thickness measurement. AA had no effect on the skin, while a stronger irritation was induced by AA-QAC#1 compared with AA-QAC#2. Hence, these materials were classified as moderate and slight irritants, respectively. In summary, this study revealed that AA-QAC#2 without Dio-DAC and ODDAC could be a great candidate for high touch surface applications, showing an extremely effective and rapid bactericidal activity, without inducing adverse effects for skin tissue.

Sinapis Semen: A review on phytochemistry, pharmacology, toxicity, analytical methods and pharmacokinetics.

Sinapis Semen (SS), the dried mature seed of Sinapis alba L. and Brassica juncea (L.) Czern. et Coss., is one of the traditional Chinese medicinal materials with a wide range of pharmacological effects being used for asthma, cough and many other ailments. SS is also widely used in food agriculture, medicine and other industries in North America and South Asia. More recently, the research on SS has gradually intensified and increased. However, there is no systematic review of SS. In this review, through literature exploration and analysis, the research advance on phytochemistry, pharmacology, toxicity, analytical methods and pharmacokinetics of SS was aggregated initially. Total 144 compounds have been isolated and identified from SS. Among them, glucosinolates and their hydrolysates and volatile oils are the main active ingredients and important chemical classification markers. SS has a wide range of pharmacological effects, especially in cough suppressing, asthma calming, anti-inflammatory, neuroprotective, cardiovascular protective, inhibiting androgenic effects, anti-tumor, and skin permeation promoting effects. Sinapine and sinapic acid are the main active ingredients of SS for its medicinal effects. However, SS has a strong skin irritation, presumably related to the time of application, the method of processing, and original medicinal plants. This review will provide useful data for the follow-up research and safe and reasonable clinical application of SS.

Hierarchical Superstructure of Plant Polyphenol and Arginine Surfactant for Long-Lasting and Target-Selective Antimicrobial Application.

Antimicrobial agents are massively used to disinfect the pathogen contaminated surfaces since the CoronaVirusDisease2019(COVID-19) outbreak. However, their defects of poor durability, strong irritation, and high environmental accumulation are exposed. Herein, a convenient strategy is developed to fabricate long-lasting and target-selective antimicrobial agent with the special hierarchical structure through bottom-up assembly of natural gallic acid with arginine surfactant. The assembly starts from rodlike micelles, further stacking into hexagonal columns and finally interpenetrating into spherical assemblies, which avoid explosive release of antimicrobial units. The assemblies show anti-water washing and high adhesion on various surfaces; and thus, possess highly efficient and broad-spectrum antimicrobial activities even after using up to eleven cycles. Both in vitro and in vivo experiments prove that the assemblies are highly selective in killing pathogens without generating toxicity. The excellent antimicrobial virtues well satisfy the increasing anti-infection demands and the hierarchical assembly exhibits great potential as a clinical candidate.

Variation of Tolerance to Isothiazolinones Among Daphnia pulex Clones.

Isothiazolinones are a family of broad-spectrum biocides widely used in industry and consumer products. Chloro- and methyl-isothiazolinones (CMIT and MIT) are documented as strong irritants, yet they are still used in a wide variety of applications, including cosmetics, cleansers, hygienic products, and various industrial applications. The subsequent substantial release of these molecules from urban sources into freshwater environments, and their potential impacts on aquatic species, have nevertheless received little attention so far, with few studies reporting on the toxicity of either CMIT or MIT to nontarget organisms. The present study addresses this current knowledge gap by evaluating the acute toxicity to Daphnia pulex (Cladocera) of CMIT/MIT (3:1) and MIT, the two formulations most commonly used by manufacturers. In addition, genetic diversity is known to be a major component of variability in phenotypic responses, although it is largely overlooked in typical toxicity tests. Thus the potential range of responses inherent to genetic diversity is rarely considered. Therefore, to account for intraspecific variations in sensitivity, our design involved eight clonal lines of D. pulex stemming from distinct natural populations or commercial strains. Clones exhibited strong variation in their responses, with median lethal concentration (LC50) values ranging from 0.10 to 1.84 mg/L for the mixture CMIT/MIT, and from 0.68 to 2.84 mg/L for MIT alone. These intraspecific ranges of LC50 values challenge the use of single clones of daphnids in standard ecotoxicological tests and the predictions based on their results. The present study brings new evidence that assessing ecological risk of chemicals while ignoring genotype diversity is neither ecologically relevant, nor a representative evaluation of the diversity of potential adverse outcomes. Environ Toxicol Chem 2023;42:805-814. © 2023 SETAC.

Pinellia ternata lectin induces inflammation through TLR4 receptor and mediates PI3K/Akt/mTOR axis to regulate NF-κB signaling pathway

Pinellia ternata, a widely used traditional Chinese medicine, contains a strong mucosal irritant that is connected with Pinellia ternata lectin (PTL) in its tubers. The purpose of this study was to explore the mechanisms by which PTL induces inflammation. We found that in RAW264.7 cells, PTL activated the PI3K/Akt/mTOR and NF-κB pathways, which resulted in the release of proinflammatory cytokines. Flow cytometry and laser confocal microscopy analysis showed that FITC-labeled PTL bound to the macrophages’ surface. Based on kinetic analyses and protein-protein docking simulations, PTL was shown to bind toll-like receptor 4 (TLR4).it was demonstrated that PTL binds highly to Toll-like receptor 4 (TLR4). TLR4 knock-down or knockout resulted in a decrease in both cytokine release and PI3K/Akt/mTOR and NF-κB pathway activation in PTL-stimulated macrophages or mice. RNA-seq analysis showed that genes involved in the PI3K/Akt/mTOR signaling pathway were strongly upregulated in response to PTL stimulation, confirming that the PI3K/Akt/mTOR pathway is linked to the inflammatory effect of PTL in RAW264.7 cells. These findings reveal that PTL can mediate inflammation through TLR4 and activating the PI3K/Akt/mTOR to regulate NF-κB signaling pathways.

Fermented Cosmetics and Metabolites of Skin Microbiota—A New Approach to Skin Health

The skin covers our entire body and is said to be the “largest organ of the human body”. It has many health-maintaining functions, such as protecting the body from ultraviolet rays and dryness and maintaining body temperature through energy metabolism. However, the number of patients suffering from skin diseases, including atopic dermatitis, is increasing due to strong irritation of the skin caused by detergents that are spread by the development of the chemical industry. The skin is inhabited by about 102–107 cells/cm2 and 1000 species of commensal bacteria, fungi, viruses, and other microorganisms. In particular, metabolites such as fatty acids and glycerol released by indigenous skin bacteria have been reported to have functional properties for the health of the skin. Therefore, skin-domesticating bacteria and the metabolites derived from those bacteria are used in many skincare product ingredients and function as probiotic cosmetics. Japanese traditional fermented stuff, used as foods in Japan for over 1300 years, are now being applied as fermented cosmetics. Fermented cosmetics are expected to have multifaceted health functionality and continue to grow as products in the natural skincare product market. In this review, we consider approaches to skin health using fermented cosmetics and modulation of skin microflora metabolites.

New Method to Biomonitor Workers Exposed to 1,6-Hexamethylene Diisocyanate.

Isocyanates such as 1,6-hexamethylene diisocyanate (HDI), 4,4'-methylenediphenyl diisocyanate, and toluene diisocyanate are highly reactive compounds that have a variety of commercial applications, including manufacturing polyurethane foam, elastomers, paints, adhesives, coatings, insecticides, and many other products. Their primary route of occupational exposure is through inhalation. Due to their high chemical reactivity, they are toxic and have adverse effects at the cellular and subcellular levels, leading to irritative and immunological reactions associated with lung disease. High concentrations of isocyanates are strong respiratory irritants. Bronchial sensitization and asthma are among the major adverse clinical reactions associated with low-level chronic exposure to isocyanates. Albumin adducts have been linked to the mechanism of occupational asthma caused by isocyanates. Isocyanates react in vivo with albumin, which is recognized by the immune system. Albumin adducts of isocyanates trigger immune responses and are probably the antigenic basis for isocyanate asthma. Sensitization to isocyanates is the main pathway for adverse health effects. Therefore, markers for the biologically effective dose such as albumin adducts of HDI are needed. A new isocyanate adduct of HDI with lysine─Nε-[(6-amino-hexyl-amino)carbonyl]-lysine (HDI-Lys)─was synthesized and characterized by 1H-NMR, 13C-NMR, and mass spectrometry (MS). Appropriate internal standards─HDI-Lys-4,4'-5,5'-d4 (HDI-d4-Lys) and Nε-[(7-amino-heptyl-amino)carbonyl]-lysine (Hep-Lys)─were synthesized to establish a LC-MS/MS method for the analysis of HDI adducts in in vitro modified albumin and in workers. The presence of HDI-Lys was found after pronase digestion of albumin and confirmed by two independent chromatographic approaches: with a C8 reversed-phase column and with a hydrophilic interaction liquid chromatography column. Quantification was performed with positive electrospray ionization (ESI)-MS. The adduct peak found in vivo was confirmed with the less sensitive negative ESI-MS. In summary, these are new compounds and methods to determine isocyanate-specific adducts with albumin in workers exposed to HDI.

Intelligent-Responsive Enrofloxacin-Loaded Chitosan Oligosaccharide–Sodium Alginate Composite Core-Shell Nanogels for On-Demand Release in the Intestine

Simple SummaryNovel pharmaceutical formulations are attracting interest in their potential to overcome the poor palatability and strong gastric irritation of enrofloxacin. To overcome the difficulty of treating intestinal Escherichia coli infections, an oral intelligent-responsive chitosan-oligosaccharide (COS)–sodium alginate (SA) composite core-shell nanogel loaded with enrofloxacin was designed and systematically evaluated. Scanning electron microscopy images revealed that enrofloxacin nanogels were incorporated into the nano-sized cross-linked networks. The physical state and molecular interaction among the components of the nanogel and the enrofloxacin were evaluated by Fourier transform infrared spectroscopy. Furthermore, their biocompatible structure, high drug loading efficacy, ideal stability, “on-demand” release at the target site, and antibacterial activity were confirmed. Thus, the present study may serve as a fruitful platform to explore nanogel to resolve the challenge of enrofloxacin formulation development and the fight against intestinal bacterial infections.Enrofloxacin has a poor palatability and causes strong gastric irritation; the oral formulation of enrofloxacin is unavailable, which limits the treatment of Escherichia coli (E. coli) infections via oral administration. To overcome the difficulty in treating intestinal E. coli infections, an oral intelligent-responsive chitosan-oligosaccharide (COS)–sodium alginate (SA) composite core-shell nanogel loaded with enrofloxacin was explored. The formulation screening, characteristics, pH-responsive performance in gastric juice and the intestinal tract, antibacterial effects, therapeutic effects, and biosafety level of the enrofloxacin composite nanogels were investigated. The optimized concentrations of COS, SA, CaCl2, and enrofloxacin were 8, 8, 0.2, and 5 mg/mL, respectively. The encapsulation efficiency, size, loading capacity, zeta potential, and polydispersity index of the optimized formulation were 72.4 ± 0.8%, 143.5 ± 2.6 nm, 26.6 ± 0.5%, −37.5 ± 1.5 mV, and 0.12 ± 0.07, respectively. Scanning electron microscopy images revealed that enrofloxacin-loaded nanogels were incorporated into the nano-sized cross-linked networks. Fourier transform infrared spectroscopy showed that the nanogels were prepared by the electrostatic interaction of the differently charged groups (positive amino groups (-NH3+) of COS and the negative phenolic hydroxyl groups (-COO−) of SA). In vitro, pH-responsive release performances revealed effective pH-responsive performances, which can help facilitate targeted “on-demand” release at the target site and ensure that the enrofloxacin has an ideal stability in the stomach and a responsive release in the intestinal tract. The antibacterial activity study demonstrated that more effective bactericidal activity against E. coli could have a better treatment effect than the enrofloxacin solution. Furthermore, the enrofloxacin composite nanogels had great biocompatibility. Thus, the enrofloxacin composite core-shell nanogels might be an oral intelligent-responsive preparation to overcome the difficulty in treating intestinal bacterial infections.