Increased fermentable carbohydrate intake alters colonic mucus barrier function through glycation processes and increased mast cell counts.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder for which dietary interventions can be a useful treatment. In recent years, the low-FODMAP approach is gaining traction in this regard. The fermentation of these non-absorbed carbohydrates by the gut microbiota can generate toxic glycating metabolites, such as methylglyoxal. These metabolites can have harmful effects by their role in the generation of advanced glycation end products (AGEs), which activates Receptor for AGEs (AGER). Mast cells can be stimulated by AGEs and play a role in IBS. We have treated mice with lactose or fructo-oligosaccharides (FOS), with or without co-administration of pyridoxamine and investigated the colonic mucus barrier. We have found that an increased intake of lactose and fructo-oligosaccharides induces a dysregulation of the colonic mucus barrier, increasing mucus discharge in empty colon, while increasing variability and decreasing average thickness mucus layer covering the fecal pellet. Changes were correlated with increased mast cell counts, pointing to a role for the crosstalk between these and goblet cells. Additionally, AGE levels in colonic epithelium were increased by treatment with the selected fermentable carbohydrates. Observed effects were prevented by co-treatment with anti-glycation agent pyridoxamine, implicating glycation processes in the negative impact of fermentable carbohydrate ingestion. This study shows that excessive intake of fermentable carbohydrates can cause colonic mucus barrier dysregulation in mice, by a process that involves glycating agents and increased mucosal mast cell counts.

Chronic mechanical trauma/irritation and oral carcinoma: A systematic review showing low evidence to support an association.

BACKGROUND: Chronic trauma of oral mucosa, resulting from repeated and persistent mechanical irritative action of an intraoral injury agent, has repeatedly been reported to be possibly implicated in the development of oral squamous cell carcinoma (OSCC). OBJECTIVES: The present systematic review aimed to assess whether chronic mechanical trauma can be considered a risk factor for OSCC. DATA SOURCES: PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus; EMBASE, Web of Science. STUDY ELIGIBILITY CRITERIA: Cohort studies comparing OSCC incidence among subjects with/without chronic mechanical trauma or case-control or cross-sectional studies comparing chronic mechanical trauma among subjects with/without OSCC. RESULTS: Only one prospective case-control study fulfilled the inclusion criteria, but the quality of the evidence provided is not enough to define trauma as a risk factor for OSCC. The main limitation is the presence of only one case-control study at high risk of bias. In the absence of strong evidence supporting the role of trauma in OSCC, a thorough discussion on trauma and carcinogenesis has been performed. CONCLUSIONS: Available evidence does not support an active role for chronic trauma in oral carcinogenesis, neither as promoter nor as progressor factor. Prospective cohort studies able to better assess trauma in OSCC are needed.

Using the Slug Mucosal Irritation Assay to Investigate the Tolerability of Tablet Excipients on Human Skin in the Context of the Use of a Nipple Shield Delivery System.

PURPOSE: Neonates are particularly challenging to treat. A novel patented drug delivery device containing a rapidly disintegrating tablet held within a modified nipple shield (NSDS) was designed to deliver medication to infants during breastfeeding. However concerns exist around dermatological nipple tolerability with no pharmaceutical safety assessment guidance to study local tissue tolerance of the nipple and the areola. This is the first Slug Mucosal Irritation (SMI) study to evaluate irritancy potential of GRAS excipients commonly used to manufacture rapidly disintegrating immediate release solid oral dosage form METHODS: Zinc sulphate selected as the antidiarrheal model drug that reduces infant mortality, was blended with functional excipients at traditional levels [microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium, magnesium stearate]. Slugs were exposed to blends slurried in human breast milk to assess their stinging, itching or burning potential, using objective values such as mucus production to categorize irritation potency RESULTS: Presently an in vivo assay, previously validated for prediction of ocular and nasal irritation, was used as an alternative to vertebrate models to anticipate the potential maternal dermatological tolerability issues to NSDS tablet components. The excipients did not elicit irritancy. However, mild irritancy was observed when zinc sulphate was present in blends. CONCLUSION: These promising good tolerability results support the continued investigation of these excipients within NSDS rapidly disintegrating tablet formulations. Topical local tolerance effects being almost entirely limited to irritation, the slug assay potentially adds to the existing preformulation toolbox, and may sit in between the in vitro and existing in vivo assays.

[Process of gallnut suppository preparation].

The main objective was to research the process of gallnut suppository preparation with its water extract as the main drug, and evaluate its irritation to rectal mucosa. gallnut extract was obtained by decocting method, and its suppository preparation was obtained by fusion method with semi-synthetic aliphatic esters and rose flower oil as the matrix. Weight difference and in vitro melting time limit of the suppository were assayed and UV-Vis was used to determine the contents of polyphenols, tannin and saccharide. The irritation to colon mucosa was evaluated after successive administration of 14 days to New Zealand white rabbits. Finally, the prescription compositions were determined: semi-synthetic aliphatic esters and rose flower oil with the ratio of 2:1 as the proper matrix, with the drug loading of 54%. The prepared suppository was brown, conical and smooth. The weight difference was (1.43±0.03) g, with an average melting time limit of (17±2) min. The Contents of Polyphenols, tannic and polysaccharide were 332.4, 245.0, 3.3 mg•g-1 respectively in each suppository. The results also showed that the continuous administration had no irritation to rectal mucosa. It can be concluded that the suppository was an acceptable administrate form, whose preparation process was easily controlled, and with no irritation to rectum mucosa.

Safety evaluation of standardized allergen extract of Japanese cedar pollen for sublingual immunotherapy.

Japanese cedar (JC) pollinosis is caused by Japanese cedar pollen (JCP) and most common seasonal allergic disease in Japan. Subcutaneous immunotherapy (SCIT) with allergen extract of JCP (JCP-allergen extract) is well established for JC pollinosis treatment with improvement of symptoms. However, major drawbacks for SCIT are repeated painful injections, frequent hospital visits and anaphylactic risk. Currently, sublingual immunotherapy (SLIT) has received much attention as an advanced alternative application with lower incidence of systemic reactions because the liquid or tablet form of allergen is placed under the tongue. The aim of this study was safety evaluation of standardized JCP-allergen extract currently developed for SLIT in JC pollinosis. JCP-allergen extract showed no potential genotoxicity. No systemic effects were observed in rats administered JCP-allergen extract orally for 26 weeks followed by 4-week recovery period. Mild local reactions such as hyperplasia and increased globule leukocytes resulting from vehicle (glycerin)-induced irritation were observed in stomach. No-observed-adverse-effect level was greater than 10,000 JAU/kg/day for systemic toxicity, equivalent to 300-fold the human dose. No local irritation was found in rabbits oral mucosae by 7-day sublingual administration. These results demonstrate the safe profile of standardized JCP-allergen extract, suggesting it is suitable for SLIT in JC pollinosis.

Formation mechanism, prevention of malignant ascites effusion and reduction of intestinal mucosal irritation of natural microemulsion from Euphorbia lathyris Pulveratum.

Malignant ascites effusion (MAE) is a common complication of advanced malignant tumors with limited treatments. Euphorbia lathyris (EL) has a long history of application in patients with edema and ascites. Herein, we reported for the first time a mode in which EL and EL Pulveratum (PEL) spontaneously formed natural microemulsions (ELM and PELM) without the addition of any carriers and excipients, and found that the protein and phospholipid contained in them encapsulated fatty oil and diterpenoid esters through non-covalent interactions. The denaturation and degradation of protein in PELM resulted in stronger binding of diterpenoid esters to the hydrophobic region of protein, which facilitated the sustained and slow release of diterpenoid esters and improved their bioavailability in vivo, thereby retaining the efficacy of preventing MAE while alleviating the irritation of intestinal mucosa. The mechanism by which PELM retained efficacy might be related to increased feces moisture and urine volume, and decreased expression of AVPR2, cAMP, PKA and AQP3 in MAE mice. And its mechanism of reducing intestinal mucosal irritation was related to decreased cell apoptosis, amelioration of oxidative stress, elevation of mitochondrial membrane potential, and up-regulation of Occludin and Claudin-1 expression in IEC-6 cells. This nano-adjuvant-free natural microemulsions may be a promising therapeutic strategy in the field of phytochemistry for promoting the application of natural and efficient nano-aggregates spontaneously formed by medicinal plants in MAE, and provide a new perspective for advancing the development of the fusion of Chinese herbal medicine and nanomedicine and its clinical translation.

A Retrospective Analysis of the Clinicopathological Profile of Oral Squamous Cell Carcinoma in Tobacco and Non-tobacco Users: Highlighting the Significance of Chronic Mechanical Irritation.

BACKGROUND AND AIM: Oral squamous cell carcinoma (OSCC) is among the leading top three cancers in India. However, recent literature has shown an increase in the rise of oral cancer in younger individuals without any history of tobacco-related habits. Chronic mucosal irritation (CMI) has been noted to have a substantial impact on the development and etiology of OSCC. With the shift in the trend, it is imperative to observe and monitor alterations associated with its etiological factors. The study aims to evaluate the prevalence and clinical characteristics of OSCC patients and the association of these parameters in cases with and without tobacco usage. METHODOLOGY: A retrospective study spanning a period of 10 years was done on histopathologically diagnosed cases of OSCC. Various clinicopathological characteristics were collected from patient records, including demographic features, tobacco-related habits, including tobacco chewing and smoking, clinical presentation, anatomic sites, and histopathological grading based on the inclusion and exclusion criteria. The data were tabulated to Microsoft Excel (Microsoft Corporation, Redmond, WA), and descriptive statistics analysis and chi-square test of significance were applied to the data using IBM SPSS Statistics (version 29.0.2; IBM Corp., Armonk, NY). The study correlated the epidemiologic behavior of OSCC with age, gender, site, and tobacco-related habits. RESULTS: This study included a sample size of 204 (72 females & 132 males). Tobacco-related habit-associated cases were 98 (48.5%) and without tobacco habits were 61 cases (29.6%). Etiology associated with CMI emerged to be a significant tooth-related factor. Out of 72 females, 32 (44.4%) of the females were without habit. OSCC caused by trauma from CMI was analyzed in 40 cases (19.6%) and 22 (55%) were females. The majority of lesions (76 (37.4%) cases) presented on the lateral border of the tongue. Among the OSCC patients with a history of chronic mechanical irritation, 37 (48.7%) cases were observed to be specifically on the lateral border of the tongue. CONCLUSION: These 10-year data will generate awareness about the disease pattern occurring within a community and provide an overview of the prerequisite of considering CMI as an etiological factor for the development of OSCC without the association of tobacco-related habits.

Development of an oral mucosal irritation test using a three-dimensional human buccal oral mucosal model.

The oral mucosa can become irritated by oral care products and lip cosmetics. Therefore, it is important to determine the irritation potential of their ingredients and products during safety evaluations. We developed a method for oral mucosal irritation test using EpiOral, which is a three-dimensional cultured model. Exposure of sodium lauryl sulphate (SLS) to EpiOral showed a dose-dependent decrease in cell viability. Under 120 min exposure conditions, SLS irritation was detected when 60% cell viability was set as a criterion. Evaluation of the irritancy of SLS and four other raw materials used in oral products at three laboratories under the above conditions confirmed good transferability of the test. Focused on the similarity of the oral and eye mucous, 32 chemicals categorised by the UN-GHS eye-irritation classification were evaluated to ensure the reliability of our criteria at these laboratories. The concordance rate between the UN-GHS classification and our test results was 100% for irritants and 60% for non-irritants. The good intra-laboratory reproducibility of our test was confirmed from the evaluation results of negative and positive controls, and the good inter-laboratory reproducibility was confirmed from the results of 32 chemicals. These findings showed that oral mucosal irritation can be evaluated using EpiOral.

Gold Dental Implant-Induced Oral Lichen Planus.

Lichen planus is a chronic inflammatory cutaneous and mucosal disease mostly affecting middle-aged individuals. The etiology of lichen planus is unknown, but current literature suggests that it is an altered immune response characterized by dysregulated T-cell activation and subsequent inflammation which can be associated with conditions like allergic contact dermatitis and hepatitis C. Additionally, heavy metals like lead, tin, arsenic, and bismuth can create inflammatory and allergic reactions that can predispose to the formation of lichen planus. This report examines the case of a 64-year-old female with longstanding oral lichenoid lesions with superimposed Wickham's striae, allergic skin reactions to several medications, and a history of receiving gold-containing dental implants. As a result of her history and subsequent allergy testing, she was found to have a gold allergy. The constant mucosal irritation from her dental implants likely was associated with the development of her oral lesions, which were confirmed to be oral lichen planus. She was recommended to apply triamcinolone 0.1% ointment to her oral lesions and to follow up with her dentist for evaluation of her filings. Further, it was recommended she replaces the dental crowns with compounds lacking gold to decrease the persistent irritation. This case represents the first such instance of gold dental fillings directly having an appreciable role in the development of oral lichen planus.

Nasal Powder Formulations: In-Vitro Characterisation of the Impact of Powders on Nasal Residence Time and Sensory Effects.

Nasal drug delivery is still primarily associated with locally-effective drugs, but next-generation products utilising the benefits of nasal administration-such as easy access to a relatively permeable mucosa, the presence of immunocompetent cells, and a direct route to the brain-are under investigation. Nasal powders offer the potential to improve the drugs' effects by providing higher resistance against the mucociliary clearance, and thus prolonging the contact time of the drug with its target site. However, suitable and easy-to-use in-vitro setups tailored to the characterisation of this effect are missing. In this study, a selection of excipients for powder formulations were used to evaluate the applicability of different methods which investigate the influence on the contact time. The combination of the assessment of rheological properties, dynamic vapour sorption, and adhesiveness on agar-mucin plates was found to be a valuable predictive tool. For the additional assessment of the sensations associated with the close contact of powders and the mucosa, a slug mucosal irritation assay was conducted and adapted to powders. These methods are regarded as being especially useful for comparative screenings in early formulation development.

Short-term association of in-vehicle ultrafine particles and black carbon concentrations with respiratory health in Parisian taxi drivers.

INTRODUCTION: Professional drivers are exposed inside their vehicles to high levels of air pollutants due to the considerable time they spend close to motor vehicle emissions. Little is known about ultrafine particles (UFP) or black carbon (BC) adverse respiratory health effects compared to the regulated pollutants. OBJECTIVES: We aimed to study the short-term associations between UFP and BC concentrations inside vehicles and (1) the onset of mucosal irritation and (2) the acute changes in lung function of Parisian taxi drivers during a working day. METHODS: An epidemiological study was carried out on 50 taxi drivers in Paris. UFP and BC were measured inside their vehicles with DiSCmini® and microAeth®, respectively. On the same day, the frequency and the severity of nose, eye, and throat irritations were self-reported by each participant and a spirometry test was performed before and after the work shift. Multivariate analysis was used to evaluate the associations between in-taxis UFP and BC concentrations and mucosal irritation and lung function, after adjustment for potential confounders. RESULTS: In-taxis UFP concentrations ranged from 17.9 to 37.9 × 103 particles/cm3 and BC concentrations from 2.2 to 3.9 µg/m3, during a mean of 9 ± 2 working hours. Significant dose-response relationships were observed between in-taxis UFP concentrations and both nasal irritation and lung function. The increase of in-taxis UFP (for an interquartile range of 20 × 103 particles/cm3) was associated to an increase in nasal irritation (adjusted OR = 6.27 [95% CI: 1.02 to 38.62]) and to a reduction in forced expiratory flow at 25-75% by -7.44% [95% CI: -12.63 to -2.24], forced expiratory volume in one second by -4.46% [95% CI: -6.99 to -1.93] and forced vital capacity by -3.31% [95% CI: -5.82 to -0.80]. Such associations were not found with BC. Incident throat and eye irritations were not related to in-vehicle particles exposure; however, they were associated with outdoor air quality (estimated by the Atmo index) and in-vehicle humidity, respectively. CONCLUSION: To our knowledge, our study is the first to show a significant association, within a short-period of time, between in and vehicle UFP exposure and acute respiratory effects in professional drivers.

Potential Mucosal Irritation Discrimination of Surface Disinfectants Employed against SARS-CoV-2 by Limacus flavus Slug Mucosal Irritation Assay.

Preventive measures have proven to be the most effective strategy to counteract the spread of the SARS-CoV-2 virus. Among these, disinfection is strongly suggested by international health organizations' official guidelines. As a consequence, the increase of disinfectants handling is going to expose people to the risk of eyes, mouth, nose, and mucous membranes accidental irritation. To assess mucosal irritation, previous studies employed the snail Arion lusitanicus as the mucosal model in Slug Mucosal Irritation (SMI) assay. The obtained results confirmed snails as a suitable experimental model for their anatomical characteristics superimposable to the human mucosae and the different easily observed readouts. Another terrestrial gastropod, Limacus flavus, also known as " Yellow slug ", due to its larger size and greater longevity, has already been proposed as an SMI assay alternative model. In this study, for the first time, in addition to the standard parameters recorded in the SMI test, the production of yellow pigment in response to irritants, unique to the snail L. flavus, was evaluated. Our results showed that this species would be a promising model for mucosal irritation studies. The study conducted testing among all those chemical solutions most commonly recommended against the SARS-CoV-2 virus.

Oral mucosal irritation potential of antimicrobial chemotherapy involving hydrogen peroxide photolysis with high-power laser irradiation for the treatment of periodontitis.

In the present study, we assessed the oral mucosal irritation potential of antimicrobial chemotherapy involving hydrogen peroxide (H2O2) photolysis with a 405-nm laser device at an output power of ≥100 mW in hamsters. Twenty-four cheek pouches from 12 male Syrian hamsters received 7-min treatment with pure water (PW), 3% H2O2, laser irradiation of PW at 100 mW, laser irradiation of 3% H2O2 at 100 mW, laser irradiation of PW at 200 mW, or laser irradiation of 3% H2O2 at 200 mW (n = 4 each). The diameter of the irradiation area was set at 3 mm; accordingly, the calculated irradiances (optical power densities) of the 100- and 200-mW laser lights were approximately 1400 and 2800 mW/cm2, respectively. In addition, 12 cheek pouches from six animals received laser irradiation of 3% H2O2 at 100 mW for 1, 3, or 5 min (n = 4 each). Each treatment was repeated three times at 1-h intervals. Macroscopic and histological changes were evaluated 24 h after the last treatment. In addition, in vitro bactericidal activity of the treatment against periodontal pathogens was evaluated. We found that 405-nm laser irradiation of 3% H2O2 caused moderate to severe oral mucosal irritation when performed at powers of 100 and 200 mW for ≥3 min, while the same treatment performed at 100 mW for 1 min resulted in mild irritation. Moreover, 1-min H2O2 photolysis at 100 mW caused a >4-log decrease in viable bacterial counts. These findings suggest that 1-min H2O2 photolysis, which can effectively kill periodontal pathogens, may be acceptable when a 405-nm laser device is used at 100 mW. However, use of the laser at a lower power would be preferable for the prevention of unnecessary oral mucosal irritation.

Acrylated Eudragit® E PO as a novel polymeric excipient with enhanced mucoadhesive properties for application in nasal drug delivery.

Eudragit® E PO (EPO) is a terpolymer based on N,N-dimethylaminoethyl methacrylate with methylmethacrylate and butylmethacrylate, produced by Evonik Industries AG as a pharmaceutical excipient. In this work, EPO was chemically modified through reaction with acryloyl chloride. The successful modification of EPO was confirmed by FTIR, NMR-spectroscopy, elemental and thermal analysis. The degree of acrylation was determined by permanganatometric titration. The slug mucosal irritation test was used to demonstrate non-irritant nature of EPO and its acrylated derivatives (AEPO). The mucoadhesive properties of EPO and AEPO were evaluated using freshly excised sheep nasal mucosa and it was demonstrated that acrylated polymers facilitated greater retention of sodium fluorescein on mucosal surfaces compared to solution mixture of this dye solution with EPO as well as free dye.

Del COVID leve al síndrome persistente: evaluación integral de la salud oral / From mild COVID to long COVID: comprehensive oral health assessment

Introducción: El COVID-19 ha causado una amplia sintomatología, incluyendo la presente en la cavidad oral. Cada día cobra más importancia un nuevo síndrome relacionado: el COVID persistente. El objetivo de este trabajo es analizar el efecto de la infección por SARS-CoV-2 a nivel oral en sujetos diagnosticados de COVID persistente, en comparación con la infección aguda. Métodos: Se llevó a cabo un estudio de casos y controles con 102 sujetos reclutados entre 2021 y 2022, de los que se obtuvieron 34 variables de salud oral y posibles factores de riesgo. Resultados: El análisis estadístico reveló que los sujetos COVID persistente presentaban significativamente mayor prevalencia de: adenopatías, dolor de ATM, irritación faríngea, xerostomía, obturaciones, ausencias y coronas dentales, mayor valor en índices CAOM y CAOD y mayor número de síntomas odontológicos en total. Además, el estrés apareció como factor de riesgo; aquellos pacientes con COVID persistente que presentaron mayor nivel de estrés (7,73 ± 2,02) también eran los que sufrían, en mayor medida, xerostomía o bruxismo, responsable del dolor de ATM, también más prevalente en este grupo. Conclusiones: El COVID persistente provoca manifestaciones orales relacionadas, algunas de ellas, con el hecho de que la cavidad oral sea vía de entrada del virus, como la irritación mucosa; otras, relacionadas con su posible naturaleza autoinmune, como la xerostomía y, de la misma manera, otras relacionadas con el estrés, reflejado en la presencia de bruxismo. Resulta imprescindible desarrollar protocolos que mejoren tanto el diagnóstico precoz como el manejo de estos pacientes en nuestras clínicas. (AU)

Introduction: COVID-19 has caused a wide range of symptomatology, including that present in the oral cavity. A new related syndrome is gaining importance: Long COVID. The aim of this work is to analyse the effect of SARS-CoV-2 infection at the oral level in subjects diagnosed with Long COVID, compared to acute infection. Methods: A case-control study was conducted with 102 subjects recruited between 2021 and 2022, from whom 34 oral health variables and possible risk factors were obtained. Results: Statistical analysis revealed that Long COVID subjects had significantly higher prevalence of: adenopathies, TMJ pain, pharyngeal irritation, xerostomia, fillings, dental absences and dental crowns, higher CAOM and CAOD index values and higher total dental symptoms. In addition, stress appeared as a risk factor; those patients with Long COVID who presented a higher level of stress (7.73 ± 2.02) were also those who suffered, to a greater extent, from xerostomia or bruxism, responsible for TMJ pain, also more prevalent in this group. Conclusions: Long COVID causes oral manifestations related, some of them, to the fact that the oral cavity is a route of entry of the virus, such as mucosal irritation; others, related to its possible autoimmune nature, such as xerostomia and, in the same way, others related to stress, reflected in the presence of bruxism. It is essential to develop protocols that improve both the early diagnosis and management of these patients in our clinics. (AU)

Maleimide-functionalised PLGA-PEG nanoparticles as mucoadhesive carriers for intravesical drug delivery.

Low permeability of the urinary bladder epithelium, poor retention of the chemotherapeutic agents due to dilution and periodic urine voiding as well as intermittent catheterisations are the major limitations of intravesical drug delivery used in the treatment of bladder cancer. In this work, maleimide-functionalised poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG-Mal) nanoparticles were developed. Their physicochemical characteristics, including morphology, architecture and molecular parameters have been investigated by means of dynamic light scattering, transmission electron microscopy and small-angle neutron scattering techniques. It was established that the size of nanoparticles was dependent on the solvent used in their preparation and molecular weight of PEG, for example, 105 ±â€¯1 nm and 68 ±â€¯1 nm particles were formed from PLGA20K-PEG5K in dimethyl sulfoxide and acetone, respectively. PLGA-PEG-Mal nanoparticles were explored as mucoadhesive formulations for drug delivery to the urinary bladder. The retention of fluorescein-loaded nanoparticles on freshly excised lamb bladder mucosa in vitro was evaluated and assessed using a flow-through fluorescence technique and Wash Out50 (WO50) quantitative method. PLGA-PEG-Mal nanoparticles (NPs) exhibited greater retention on urinary bladder mucosa (WO50 = 15 mL) compared to maleimide-free NPs (WO50 = 5 mL). The assessment of the biocompatibility of PEG-Mal using the slug mucosal irritation test revealed that these materials are non-irritant to mucosal surfaces.

Potential adverse effects of antimicrobial chemotherapy based on ultraviolet-A irradiation of polyphenols against the oral mucosa in hamsters and wounded skin in rats.

Antimicrobial chemotherapy based on ultraviolet-A (UVA) irradiation of polyphenol solution has been proposed as an adjunctive treatment for dental caries. However, the safety of this treatment has not been thoroughly evaluated. Therefore, the aim of the present study was to assess the influence of this treatment on the oral mucosa in hamsters and wounded skin in rats. An oral mucosal irritation test was performed in hamsters. The cheek pouch was everted and treated with UVA irradiation (wavelength: 365 nm) of pure water, 1 mg/mL of caffeic acid, or 1 mg/mL of grape seed extract using a light-emitting diode at an irradiance of 275 mW/cm2. Each treatment was performed for 2 or 5 min and repeated three times. Macroscopic and histological evaluations were performed 24 h after the last treatment. We also examined the effects of the treatment on the healing process of skin wounds in rats. Full-thickness skin wounds created on the back of the rats were treated for 2 min as described above, but only once. The wound area was then assessed daily for 9 days. The results demonstrated that the treatment induced oral mucosal irritation depending on the irradiation time; however, it did not influence the wound healing process. The oral mucosal irritation potential of three treatment sessions performed for 2 and 5 min was minimal and mild to moderate, respectively, according to histological analysis. These findings suggest that the duration of treatment based on UVA irradiation of polyphenols in the oral cavity should be as short as possible, considering the clinical efficacy of the antimicrobial effects and the irritation potential.

CON4EI: Slug Mucosal Irritation (SMI) test method for hazard identification and labelling of serious eye damaging and eye irritating chemicals.

Assessment of ocular irritancy is an international regulatory requirement in the safety evaluation of industrial and consumer products. Although many in vitro ocular irritation assays exist, alone they are incapable of fully categorizing chemicals. The objective of CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for eye irritation assessment that can lead to complete replacement of the in vivo Draize rabbit eye test (OECD TG 405). A set of 80 reference chemicals was tested with seven test methods, one method was the Slug Mucosal Irritation (SMI) test method. The method measures the amount of mucus produced (MP) during a single 1-hour contact with a 1% and 10% dilution of the chemical. Based on the total MP, a classification (Cat 1, Cat 2, or No Cat) is predicted. The SMI test method correctly identified 65.8% of the Cat 1 chemicals with a specificity of 90.5% (low over-prediction rate for in vivo Cat 2 and No Cat chemicals). Mispredictions were predominantly unidirectional towards lower classifications with 26.7% of the liquids and 40% of the solids being underpredicted. In general, the performance was better for liquids than for solids with respectively 76.5% vs 57.1% (Cat 1), 61.5% vs 50% (Cat 2), and 87.5% vs 85.7% (No Cat) being identified correctly.

Assessment of ocular discomfort caused by 5 shampoos using the Slug Mucosal Irritation test.

Assessment of ocular discomfort caused by veterinary care products is less legitimately regulated than that caused by human care products. The Slug Mucosal Irritation (SMI) assay was adapted to evaluate canine hygiene shampoos to predict ocular discomfort. Experiments were performed using four commercial canine shampoos, a baby care product, and two controls (ArtTear® and BAC1%). Groups of 3 slugs were tested with 5% dilution of the 7 test substances. The negative control (ArtTear®) was the best tolerated. The baby care product Mixa bébé as well as Douxo Entretien Démêlant and Phlox Shampooing Entretien were classified to cause mild ocular discomfort. Together with the positive control (BAC 1%), Shampooing Physiologique Virbac and Physiovet Shampooing were considered to cause severe ocular discomfort. Different intensities of ocular discomfort were measured for veterinary care products. The SMI model was considered as a reproducible and adaptable evaluation method for screening veterinary care products causing ocular discomfort.