Search

Objective: The aim of the study is to assess the long-term physical condition, health-related quality of life, employment, and work ability of irritant-induced asthma (IIA) patients. Methods: Forty-three IlA patients completed a follow-up questionnaire a median of eight (interquartile range 4-11 ) years after asthma diag- nosis. We compared their results with those of 43 low-molecular-weight (LMW) sensitizer-induced occupational astlima (OA) patients and those of 206 adult- onset asthmatics in the general population. Results: Of the I IA patients, 40% re- ported depressive symptoms. Of the <65-year-olds. 56% were employed of whom 39% assessed their work ability as limited. IIA patients had more difficulty climbing several flights of stairs than LMW-induced OA patients (70% vs 47%, OR= 4.8395% CI: 1.51-15.47).Most ofthe IIA patients' outcomes were inferior to those ofthe adult-onset asthmatics in the general population. Conclusions: HA prognosis appeared poor but resembled that of LMW-induced OA [ABSTRACT FROM AUTHOR]

Proliferative fibrous lesions of the oral mucosa and gingiva, known as fibromas, can lead to both functional and esthetic concerns. Although the size of an intraoral fibroma might vary from millimeters to a few centimeters, it is usually well defined. An irritation or traumatic fibroma is a benign, exophytic reactive oral lesion that occurs following trauma. Although it is rare, recurrences might occur if the same area experiences repeated trauma. These iatrogenic factors, that involve restorations and their overhanging margins, foreign materials and calculi, may result in trauma. Usually, it is characterized by gradual, painless expansion that develops up over several months or years. In this case report, the lower back tooth region showed signs of growth. The diode laser was used to completely remove the lesion. This example shows the need of a correct diagnosis, the importance of a biopsy, and a thorough histologic examination in the treatment of these lesions. [ABSTRACT FROM AUTHOR]

Recently, we showed that the addition of physiological concentrations of ascorbic acid, a tear antioxidant, to the OptiSafe™ macromolecular eye irritation test reduced the false-positive (FP) rate for chemicals that had reactive chemistries, leading to the formation of reactive oxygen species (ROS) and molecular crosslinking. The purpose of the current study was to 1) increase the number of chemicals tested to comprehensibly determine whether the antioxidant-associated reduction in OD is specific to FP chemicals associated with ROS chemistries and 2) determine whether the addition of antioxidants interferes with the detection of true positive (TP) and true negative (TN) ocular irritants. We report that when ascorbic acid is added to the test reagents, retesting of FP chemicals with reactive chemistries show significantly reduced OD values (P

BackgroundCompounded cantharidin has been used for decades to treat molluscum contagiosum but lacks rigorous clinical evidence to support its safety and efficacy. VP-102 is a shelf-stable drug-device combination product that contains topical cantharidin (0.7% weight/volume [w/v]) and is being evaluated for the treatment of molluscum.ObjectivesOur objective was to present pooled safety and efficacy analyses of VP-102 in the treatment of molluscum compared with vehicle.MethodsParticipants aged ≥ 2 years were randomized 3:2 to topical administration of VP-102 or vehicle in two randomized, double-blind, vehicle-controlled phase III trials. Study drug was applied to all baseline and new lesions once every 21 days until clear or for a maximum of four applications. Assessors blinded to treatment counted all lesions at each study visit. All adverse events (AEs) were documented. Data were pooled for analyses.ResultsIn total, 310 participants received VP-102 and 218 received vehicle. Mean age was 7.5 years (range 2-60) for VP-102 and 6.8 (2-54) for vehicle. Complete clearance of all molluscum lesions at day 84 occurred in 50% of VP-102 participants and 15.6% of vehicle recipients (p

Educating pediatric eczema patients and caregivers on appropriate product selection and avoidance of common irritants or allergens is a crucial aspect of eczema management. This study surveyed 80 pediatric caregivers in an academic pediatric dermatology clinic to assess influential factors in caregivers' selection of pediatric eczema‐care products and identify ways to improve patient counseling on appropriate product selection and avoidance of common irritants or allergens. Caregivers frequently reported positive perceptions of commonly recommended ingredients for eczema but had inconsistent perceptions of fragrant plant oils and extracts, regardless of previous counseling on fragrance avoidance. These findings demonstrate uncertainty and misperceptions perpetuated by product labeling and a need for improved counseling strategies for avoiding fragrance and excessive product costs. [ABSTRACT FROM AUTHOR]

Background: A modulating effect of aluminium regarding type IV reactions might exist but has not been further investigated. Objectives: The aim of this study was to investigate the effect on patch test reactions when adding aluminium chloride hexahydrate (Al‐Cl) to common test preparations. Materials and methods: Al‐Cl in different concentrations was added to nickel sulphate 15.0% aqua (Ni), methylisothiazolinone 0.2% aqua (MI) and fragrance mix I 10.0% aqua/ethanol (FM I). The Ni preparations were tested in 120 consecutive patients. MI and FM I were tested in participants known to have contact allergy to the respective allergen. McNemar's test was used to decide which Ni preparation had the highest sensitivity. Wilcoxon signed‐rank test was used to calculate pairwise comparison in summarized test score for the preparations with MI and FM I. Results: Adding Al‐Cl 20.0%/30.0% to Ni identified twice as many patients with contact allergy to nickel compared to Ni without Al‐Cl. Adding Al‐Cl 20.0%/10.0% to MI, decreased the patch test reactivity compared to MI without Al‐Cl. No differences in patch reactivity were noticed when adding Al‐Cl to FM I. Conclusion: Al‐Cl 20.0% or 30.0% seems to enhance the patch test reactivity to Ni 15.0% aqua. [ABSTRACT FROM AUTHOR]

Introduction: Oral pyogenic granulomas (PGs) presenting in association with dental implants are uncommon occurrences. While tooth‐associated PGs are well‐documented in the literature, there are only seven case reports with biopsy‐confirmed diagnoses of PG related to dental implants. This case report details the treatment of an intraoral PG related to dental implants that had been osseointegrated and asymptomatic for 10 years. Case Presentation: A 39‐year‐old female presented with a hyperplastic erythematous mass that encompassed the dental implants in the position of the maxillary central incisors. Surgical exploration of the site revealed nonintegrated, particulate bone material distributed throughout the peri‐implant tissues approximating the granuloma. Treatment involved surgical excision of the lesion, elimination of all nonintegrated bone material, and implant surface debridement. Laser therapy was later used to manage a recurrence. Histology of the biopsied tissue confirmed the diagnosis of PG and described the presence of multiple exogenous, refractile, particulate materials in the specimen. Conclusion: The combination of surgical excision, implant debridement, and conservative laser therapy resulted in the elimination of a dental implant‐related PG and successful soft tissue management. The localized presence of nonintegrated particulate bone material surrounding the granuloma appears to have functioned as a chronic irritant to the peri‐implant soft tissues over time and is likely, along with oral bacteria, the primary etiological agents. Key points: Why is this case new information? There is a paucity of reports describing the management of dental implant‐related pyogenic granulomas especially in the esthetic region. The present case demonstrates that particulate bone materials used in guided bone regeneration have the capacity to behave as a low‐grade irritant to the gingival tissues. It also demonstrates the successful elimination of the tissues and management of the peri‐implant soft tissues for an esthetic result. What are the keys to successful management of this case? The key to successful management of this case was adequate removal of the exogenous irritant, proper implant surface debridement, and decontamination and adequate gingivoplasty to remove all residual hyperplastic granulomatous tissues. Additionally, patient education and appropriate oral hygiene instructions were important to proper healing and maintenance of the area. What are the primary limitations to success in this case? The ambiguity of the clinical boundaries of PGs makes it challenging to guarantee complete excision beyond the base of the lesion, leading to recurrence. [ABSTRACT FROM AUTHOR]

Inhalation of noxious irritants activates nociceptive sensory afferent nerves innervating the airways, inducing reflex regulation of autonomic networks and the modulation of respiratory drive and cardiovascular (CV) parameters such as heart rate and blood pressure. In healthy mammals, irritant-evoked pulmonary-cardiac reflexes cause parasympathetic-mediated bradycardia. However, in spontaneously hypertensive (SH) rats, irritant inhalation also increases sympathetic drive to the heart. This remodeled pulmonary-cardiac reflex may contribute to cardiovascular risk caused by inhalation of air pollutants/irritants in susceptible individuals with cardiovascular disease (CVD). Previous studies have shown that the cooling mimic L-menthol, an agonist for the cold-sensitive transient receptor potential melastatin 8 (TRPM8), can alleviate nasal inflammatory symptoms and respiratory reflexes evoked by irritants. Here, we investigated the impact of inhalation of TRPM8 agonists L-menthol and WS-12 on pulmonary-cardiac reflexes evoked by inhalation of the irritant allyl isothiocyanate (AITC) using radiotelemetry. L-Menthol, but not its inactive analog d-menthol, significantly reduced the AITC-evoked reflex tachycardia and premature ventricular contractions (PVCs) in SH rats but had no effect on the AITC-evoked bradycardia in either SH or normotensive Wistar–Kyoto (WKY) rats. WS-12 reduced AITC-evoked tachycardia and PVCs in SH rats, but this more potent TRPM8 agonist also reduced AITC-evoked bradycardia. L-Menthol had no effect on heart rate when given alone, whereas WS-12 evoked a minor bradycardia in WKY rats. We conclude that stimulation of TRPM8-expressing afferents within the airways reduces irritant-evoked pulmonary-cardiac reflexes, especially the aberrant reflex tachyarrhythmia in SH rats. Airway menthol treatment may be an effective therapy for reducing pollution-associated CV exacerbations. [ABSTRACT FROM AUTHOR]

Chemical weapons are a diverse range of substances that can be used to cause intentional death or harm through their toxic properties. They include nerve agents, vesicants, lung-damaging agents, cyanide, biological toxins, and riot control agents, as well as emerging threats such as the highly potent opioid carfentanil. Although infrequent, chemical weapons casualties can and have presented to civilian hospitals as the result of terrorist attacks, assassination attempts, and accidental exposure. Recognition of the potential chemical casualty is required to initiate specific treatment and appropriate personal protective measures. However, this is made challenging by a low index of suspicion, unclear history of exposure, limitations of field-testing equipment, and variable presentations that may be confounded by psychological symptoms, physical injuries, hyperthermia from personal protective equipment (PPE), and the side effects of antidotes. This article gives a brief overview of how to identify and manage chemical incidents, the toxicology, symptomatology, and treatment of a selected number of chemical agents. Further detail can be found in the listed references. [ABSTRACT FROM AUTHOR]

While exposure to irritant and sprayed cleaning products at home is known to have a harmful role in asthma, the potential health effect of other categories or forms has not been investigated. We studied the associations of household use of cleaning products, including green, homemade products, and disinfecting wipes, with asthma based on data from the large French population‐based CONSTANCES cohort. Participants completed standardized questionnaires on respiratory health and household use of cleaning products. Cross‐sectional associations of cleaning products with current asthma, adjusted for gender, age, smoking status, BMI, and educational level, were evaluated by logistic regressions. Analyses were conducted in 41 570 participants (mean age: 47 years, 56% women, weekly use of the six specific products/forms studied varied from 11% to 37%). Weekly use of irritants (OR = 1.23 [1.13–1.35]), scented (OR = 1.15 [1.06–1.26]), green (OR = 1.09 [1.00–1.20]), and homemade products (OR = 1.19 [1.06–1.34]), as well as sprays (OR = 1.18 [1.08–1.29]), disinfecting wipes (OR = 1.21 [1.09–1.34]) were significantly associated with asthma, with significant trends according to the frequency of use. When they were not co‐used with irritants/sprays, associations were reduced and persisted only for disinfecting wipes. Weekly use of disinfecting wipes at home was associated with current asthma, but fewer risks were observed for the use of green and homemade products. [ABSTRACT FROM AUTHOR]

Electronic Nicotine Delivery Systems (ENDS) aerosol exposures can induce endothelial dysfunction (ED) in healthy young humans and animals. Thermal degradation of ENDS solvents, propylene glycol and vegetable glycerin (PG: VG), generates abundant formaldehyde (FA) and other carbonyls. Because FA can activate the transient receptor potential ankyrin-1 (TRPA1) sensor, we hypothesized that FA in ENDS aerosols provokes TRPA1-mediated changes that include ED and 'respiratory braking' - biomarkers of harm. To test this, wild-type (WT) and TRPA1-null mice were exposed by inhalation to either filtered air, PG: VG-derived aerosol, or formaldehyde (FA, 5 ppm). Short-term exposures to PG: VG and FA induced ED in female WT but not in female TRPA1-null mice. Moreover, acute exposures to PG: VG and FA stimulated respiratory braking in WT but not in TRPA1-null female mice. Urinary metabolites of FA (ie, N  -1,3-thiazolidine-4-carboxylic acid, TCA; N  -1,3-thiazolidine-4-carbonyl glycine, TCG) and monoamines were measured by LC-MS/MS. PG: VG and FA exposures significantly increased urinary excretion of both TCA and TCG in both WT and TRPA1-null mice. To confirm that inhaled FA directly contributed to urinary TCA, mice were exposed to isotopic 13C-FA gas (1 ppm, 6 h).13C-FA exposure significantly increased the urine level of 13C-TCA in the early collection (0-3 h) supporting a direct relationship between inhaled FA and TCA. Collectively, these data suggest that ENDS use may increase CVD risk dependent on FA, TRPA1, and catecholamines, yet independently of either nicotine or flavorants. This study supports that levels of FA in ENDS-derived aerosols should be lowered to mitigate CVD risk in people who use ENDS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Le syndrome de dysfonction réactive des bronches (RADS) ou syndrome de Brooks est une entité indépendante de l'asthme non immunologique définie par des critères diagnostiques bien précis. L'émergence des produits chimiques irritants dans l'environnement du travail a des répercussions sur l'appareil respiratoire et des conséquences sur la vie professionnelle. Dresser le profil socio-démographique, professionnel, clinique et paraclinique des patients présentant un RADS. Enquête descriptive rétrospective qui a porté sur les dossiers des sujets présentant un RADS et ayant consulté au service de médecine du travail de Sousse, en vue d'une déclaration en accident de travail ou dans le cadre d'une enquête étiologique de leur syndrome, sur une période de 10 ans. Nous rapportons les cas de 15 patientes. L'âge moyen était de 43,13 ± 8 ans. Les 2 principaux secteurs d'activité concernés étaient celui de la santé et du nettoyage. Les agents chimiques responsables du RADS étaient les détergents, les solvants (peinture et colle), les pesticides, les désinfectants (formaldéhyde) et les acides forts. Les symptômes ce sont améliorés au bout de 3 mois chez 6 patientes. La symptomatologie se répétait à chaque réexposition à un produit irritant chez 13 patientes. Les explorations fonctionnelles respiratoires ont montré dans la majorité des cas un trouble ventilatoire obstructif réversible. Quatre patientes n'avaient pas nécessité un traitement de fond. Six patientes ont bénéficié d'une déclaration en accident de travail. Il est très important à la fois de reconnaître et de signaler les accidents d'inhalation sur les lieux de travail pour pouvoir identifier l'agent en cause ainsi que les travailleurs concernés pour leur permettre, le cas échéant, un changement de poste ainsi qu'une mise en œuvre de moyens préventifs adéquats. Reactive airways dysfunction syndrome or Brook's syndrome is a distinct entity of non-immunologic asthma with specific diagnostic criteria. The emergence of chemical irritants at workplace had short-, medium- and long-term repercussions on the respiratory system and negatives consequences on occupational life. To describe the socio-demographic, professional, clinical and paraclinical profile of patients with Brooks syndrome. We carried out a descriptive epidemiological study from January 2010 to December 2019 at the Department of Occupational Medicine in Farhat Hached Teaching Hospital-Tunisia including patients diagnosed with Brooks syndrome. A total of 15 patients was enrolled in the study with a mean age of 43.13 ± 8 years. The average job tenure was 17.27 ± 9 years. Healthcare sector and Textile and clothing industry were the most represented sectors. Agents incriminated in RADS were, detergents (dominated by chlorine found in bleach), solvents (paint and glue), pesticides, disinfectants (formaldehyde), strong acids. A major improvement in RADS symptoms within 3 months was noticed in 6 patients. A recurrence of symptoms after every exposure to irritant agent was notified in 13 patients. In most cases, spirometry showed an obstructive reversible syndrome. The non-specific methacholine bronchial provocation test was applied to only 2 patients. Only 4 patients needed to receive long-term treatment. Six cases of RADS were recorded as a work-related accident. It is necessary to highlight the importance of early detection of inhalation injuries and identification of agents in cause in order to establish adequate preventives measures at workplace. [ABSTRACT FROM AUTHOR]

Contact dermatitis is one of the most common occupational diseases, with serious impact on quality of life, lost days at work and a condition that may be chronically relapsing. Regular prophylactic skin cream application is widely acknowledged to be an effective prevention strategy against occupational contact dermatitis; however, compliance rates remain low. To present a simple programme for skin cream application in the workplace with focus on implementation to drive down the rate of occupational irritant contact dermatitis, an expert panel of eight international dermatologists combined personal experience with extensive literature review. The recommendations are based on clinical experience as supported by evidence-based data from interventional studies. The authors identified three moments for skin cream application in the work place: (i) before starting a work period; (ii) after washing hands; and (iii) after work. Affecting behaviour change requires systematic communications, monitoring and reporting, which is proposed through Kotter's principles of organizational change management. Measurement tools are provided in the appendix. Interventional data based on application of this proposal is required to demonstrate its effectiveness.

Intestinal M (microfold) cells are specialized epithelial cells overlying lymphoid tissues in the small intestine. Unlike common enterocytes, M cells lack an organized apical brush border, and are able to transcytose microparticles across the mucosal barrier to underlying antigen-presenting cells. We found that in both the dextran sodium sulfate and Citrobacter rodentium models of colitis, significantly increased numbers of Peyer's patch (PP) phenotype M cells were induced at the peak of inflammation in colonic epithelium, often accompanied by loosely organized lamina propria infiltrates. PP type M cells are thought to be dependent on cytokines, including tumor necrosis factor (TNF)-α and receptor activator of nuclear factor kappa-B ligand; these cytokines were also found to be induced in the inflamed tissues. The induction of M cells was abrogated by anti-TNF-α blockade, suggesting that anti-TNF-α therapies may have similar effects in clinical settings, although the functional consequences are not clear. Our results suggest that inflammatory cytokine-induced PP type M cells may be a useful correlate of chronic intestinal inflammation.

Ethnopharmacological Relevance: Polygala tenuifilia Willd (Polygalaceae), a traditional Chinese medicine, has been used for a long time to treat various illnesses with serious adverse reactions. Glycyrrhizae radix et rhizoma processing is generally used to reduce the adverse reactions., Aim of the Study: The aim of this study was to validate the irritation caused by raw Polygalaceae (RPA), to investigate whether processed Polygalaceae (PGA) was less irritating, and to screen and validate irritant properties of virgaureagenin G (polygala acid, PA), 3,6'-disinapoylsucrose (DSS), Tenuifolia (TEN) and polygalaxanthone III (POL), which had pharmacologically active in Polygalaceae. Zebrafish model, Draize test and High-Performance Liquid Chromatography (HPLC) were utilized to achieve the aim., Materials and Methods: Scanning Electron Microscopy (SEM) and optical microscope were used to determine the presence of calcium oxalate needle crystal in RPA and PGA. Zebrafish egg spinning changes and zebrafish embryo behavior were used for irritation validation, irritation comparison and irritant screening. For additional evidence, the Draize test, HE staining of rabbit eyes and ELISA kit were used. Finally, changes in the composition of RPA and PGA were investigated using HPLC., Results: SEM and optical microscopy revealed no calcium oxalate needle crystals in Polygalaceae. RPA, PGA, PA and DSS were able to accelerate the spinning of zebrafish eggs and the movement of embryos, while TEN and POL were not. RPA, PGA, DSS and PA may cause rabbit eyes to become hyperemic and swollen, resulting in damage to the iris, cornea and conjunctiva and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Comparatively, the effects caused by PGA were less severe than those caused by RPA. In addition, compared to RPA, PGA had lower levels of DSS and PA., Conclusions: RPA, PGA, DSS, and PA were irritating. However, processing and curing could reduce the irritation by reducing the levels of DSS and PA. DSS and PA could be two potential irritants of Polygalaceae., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Distinguishing between allergic and nonallergic forms of Contact Dermatitis (CD) is challenging and requires investigations based on patch-testing. Early detection of allergy biomarkers in active CD lesions could refine and simplify the management of CD patients., Objective: To characterize the molecular signatures of active CD lesions., Methods: We studied the expression of 12 allergy biomarkers by qRT-PCR in active lesions of 38 CD patients. Allergic CD (ACD) was diagnosed based on patch test (PT) results and exposure assessment. Molecular signatures of active lesions, as well as positive PT reactions, were compared with those of reference chemical allergens and irritants., Results: Nineteen of the 38 CD patients reacted positively upon patch-testing and exposure assessment confirmed ACD diagnosis for 17 of them. Gene profiling of active CD lesions revealed 2 distinct molecular patterns: patients harboring signatures similar to reference allergens (n = 23) or irritants (n = 15). Among the 23 patients with an "allergy signature," we found the 17 patients with confirmed ACD, while no culprit allergen was identified for the 6 other patients. Interestingly, the 15 patients without biomarker induction had negative PT, suggesting that they developed nonallergic CD reactions., Conclusion: Molecular signatures from active skin lesions may help to stratify CD patients and predict those suffering from ACD., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To study the stability of physicochemical properties and sterilizing effect about two commercially available hypochlorous acid (HClO) products under simulated clinical conditions, and to evaluate the compatibility of HClO on soft and hard tissues and cells in oral cavity., Methods: Samples of HClO solution with different production processes were prepared, to detect the changes of physicochemical indexes of each sample over time under simulated clinical conditions (shielded from light at 20-25 ℃, open the cover for 5 minutes every day), including free available chlorine, oxidation-reduction potential and pH. Through suspension quantitative germicidal test, the antibiosis-concentration curve of HClO solution was made, so as to calibrate the change of antibacterial ability of disinfectant with the decrease of available chlorine content during storage. Pulp, tongue and dentine were immersed in PBS, 100 ppm HClO, 200 ppm HClO and 3% NaClO. The influence on soft and hard tissues was evaluated by weighing method and microhardness test. The toxic effects of HClO, NaClO and their 10-fold diluent on human gingival fibroblasts were determined by CCK-8 cytotoxicity assay. GraphPad PRIS 8.0 software was used to analyze the data., Results: Under simulated conditions, the free available chlorine (FAC) of HClO solution decayed with time, and the attenuation degree was less than 20 ppm within 1 month. The bactericidal effect of each HClO sample was still higher than 5log after concentration decay. There was no obvious dissolution and destruction to soft and hard tissues for HClO(P＞0.05). The cell viability of HClO to human gingival fibroblast cells (HGFC) was greater than 80%, which was much higher than 3% NaClO (P＜0.001)., Conclusions: The bactericidal effect and stability of HClO solution can meet clinical needs, which has low cytotoxicity and good histocompatibility. It is expected to become a safe and efficient disinfection product in the field of living pulp preservation and dental pulp regeneration.

Background: The use of household disinfectants and cleaning products (HDCPs) may negatively impact asthma control, but studies remain scarce. Moreover, no study considered green products or wipes, increasingly used during home cleaning., Objective: To assess the associations between the use of HDCPs, including disinfecting wipes and green products, and asthma control based on data from the French Web-based NutriNet-Santé cohort., Methods: Using a standardized questionnaire (2018), we assessed asthma control (never asthma: reference; controlled: Asthma Control Test ≥ 20; uncontrolled: Asthma Control Test < 20) and the use of HDCPs, including 2 types of products (irritants and green products) and 2 application modes (sprays and disinfecting wipes). Cross-sectional associations of the frequency of weekly use of HDCPs at home with asthma control, adjusted for sex, age, smoking status, body mass index, and educational level were assessed by multinomial logistic regressions., Results: Analyses were performed on 37,043 adults (mean age 47 y; 75% women; 62% with a weekly use of at least 1 HDCP). Strong associations were observed between weekly use of HDCPs and uncontrolled asthma. In particular, an almost daily use (4-7 d/wk) of irritants (odds ratio [OR] 2.81; 95% confidence interval [95% CI] 1.97-4.00) and green products (OR 2.40; 95% CI 1.70-3.39) as well as sprays (OR 2.69; 95% CI 1.97-3.68) and disinfecting wipes (OR 3.51; 95% CI 2.31-5.33) was associated with uncontrolled asthma. When not co-used with irritants and sprays, associations remained statistically significant for both disinfecting wipes and green products., Conclusions: Weekly use of HDCPs, including green products or wipes, was associated with uncontrolled asthma and should be considered by health practitioners in order to improve asthma control., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Studying associations between genes and asthma endotypes and interactions with environment could help to identify new susceptibility genes. We used a previously identified asthma endotype characterized by adult-onset asthma, poor lung function, and high level of Fluorescent oxidation products, a marker of damages due to oxidative stress. This endotype was associated with high occupational exposure to irritants. We aimed to investigate the associations between genes related to oxidative stress and this endotype, and if the associations differed according to irritants exposure. We conducted association analyses between the asthma endotype and genetic variants (4715 SNPs) located in 422 genes involved in the "response to oxidative stress" in adults from the Epidemiological study on the Genetic and Environment of Asthma. Analyses using logistic regression were conducted first in all participants, and then separately among high vs. non-exposed participants to assess whether association differs according to irritants exposure. An association was found between the SNP rs1419958 located in PID1 gene and the endotype (P = 2.2E-05), reaching significance level after correction for multiple testing. This association was even more significant in non-exposed participants (P = 1.06E-06) while there was no association in participants with high exposure to occupational irritants. This study showed a significant association between an asthma endotype and PID1 , a promising candidate gene, the association being different according to the exposure to irritants. These results highlight the interest of studying asthma endotypes in association with genes from candidate pathways and their link with occupational irritants to decipher asthma etiology. [Display omitted] • PID1 gene involved in oxidative stress associated with a distinct asthma endotype. • Association found in unexposed participants but not in those exposed to irritants. [ABSTRACT FROM AUTHOR]

Background: People are exposed to mixtures containing allergens and irritants often causing contact dermatitis. Therefore, regulatory authorities require systematic information on the effects of mixtures on the sensitization threshold. In this study a moderate (cinnamal) and a weak (ethylene glycol dimethacrylate) allergen were combined with irritants covering different mechanisms of action (sodium dodecyl sulfate, salicylic acid, and α‐pinene). For a systematic approach, the single substances were initially tested using the KeratinoSens assay. Thereafter, each allergen was combined with noncytotoxic concentrations of the irritants. Method: The KeratinoSens assay was applied for the single substances according to OECD (Organisation for Economic Co‐operation and Development) Test Guideline 442D. Based on these results, three noncytotoxic concentrations of the irritants were selected and applied simultaneously with 12 concentrations of the allergens to the KeratinoSens cells. Sensitization threshold and cytotoxicity were measured and compared with the individual testing. Results: The combinations of allergens and irritants differed from the effects of the single substances and lowered the sensitization threshold. The quantitative approach allowed a clear description of the changes which varied by factors between 1.1 and 10.3. Conclusions: Overall, the allergen was the prominent compound in the mixture and its nature appeared to determine the degree of the response. [ABSTRACT FROM AUTHOR]

After more than a decade of electronic cigarette (E-cig) use in the United States, uncertainty persists regarding E-cig use and long-term cardiopulmonary disease risk. As all E-cigs use propylene glycol and vegetable glycerin (PG-VG) and generate abundant saturated aldehydes, mice were exposed by inhalation to PG-VG–derived aerosol, formaldehyde (FA), acetaldehyde (AA), or filtered air. Biomarkers of exposure and cardiopulmonary injury were monitored by mass spectrometry (urine metabolites), radiotelemetry (respiratory reflexes), isometric myography (aorta), and flow cytometry (blood markers). Acute PG-VG exposure significantly affected multiple biomarkers including pulmonary reflex (decreased respiratory rate, −50%), endothelium-dependent relaxation (−61.8 ± 4.2%), decreased WBC (−47 ± 7%), and, increased RBC (+6 ± 1%) and hemoglobin (+4 ± 1%) versus air control group. Notably, FA exposure recapitulated the prominent effects of PG-VG aerosol on pulmonary irritant reflex and endothelial dysfunction, whereas AA exposure did not. To attempt to link PG-VG exposure with FA or AA exposure, urinary formate and acetate levels were measured by GC-MS. Although neither FA nor AA exposure altered excretion of their primary metabolite, formate or acetate, respectively, compared with air-exposed controls, PG-VG aerosol exposure significantly increased post-exposure urinary acetate but not formate. These data suggest that E-cig use may increase cardiopulmonary disease risk independent of the presence of nicotine and/or flavorings. This study indicates that FA levels in tobacco product-derived aerosols should be regulated to levels that do not induce biomarkers of cardiopulmonary harm. There remains a need for reliable biomarkers of exposure to inhaled FA and AA.NEW & NOTEWORTHY Use of electronic cigarettes (E-cig) induces endothelial dysfunction (ED) in healthy humans, yet the specific constituents in E-cig aerosols that contribute to ED are unknown. Our study implicates formaldehyde that is formed in heating of E-cig solvents (propylene glycol, PG; vegetable glycerin, VG). Exposure to formaldehyde or PG-VG–derived aerosol alone stimulated ED in female mice. As ED was independent of nicotine and flavorants, these data reflect a “universal flaw” of E-cigs that use PG-VG. [ABSTRACT FROM AUTHOR]

Abstract The use of household cleaners during non‐commercial cleaning applications is a very common task, and the chemical makeup of the cleaning solutions vary as much as their applications do. Although most users of these products follow the written safety directions and are generally careful with their use, it is not uncommon for users to suffer toxicologic effects of these cleaners without proper protective equipment. In this case report, we describe an unusual chemical burn pattern to the hand of a young female patient after prolonged exposure to a xylene‐containing product without proper chemical‐resistant gloves. Fortunately, with prompt recognition, and urgent referral for burn treatment, the patient underwent a successful debridement of the burn and suffered minimal functional impairment.

BackgroundPepper spray is a common lacrimator used by law enforcement and the public to subdue individuals and for self-defense. The risk factors for severe injury due to pepper spray exposure are not well documented and there is a lack of guidelines to identify patients that require transport and medical evaluation in an emergency department.ObjectiveThe aim of this study was to determine the prevalence of and circumstances associated with symptoms suggestive of tissue injury beyond transient irritation in persons exposed to pepper spray.MethodsWe reviewed all human exposures to pepper spray reported to a poison control system between 2002 and 2011. Cases were differentiated into 2 outcome groups: minor or self-limiting symptoms versus those with more severe symptoms suggestive of tissue injury that warranted a medical evaluation. A comparison of the variables between the outcome groups was performed using odds ratios (ORs), 95% confidence intervals (CIs), and associated P values.ResultsA total of 4,544 cases were identified and 3,671 met the inclusion criteria. Of these, 249 cases (6.8%) were found to have more severe symptoms that warranted a medical evaluation. There were no reported deaths. The cases with more severe symptoms most commonly involved the ocular (53.8%), respiratory (31.7%), and dermal (17.7%) organ systems. Factors with largest independent associations with more severe outcomes were use for law enforcement training (OR, 7.39; 95% CI, 2.98-18.28), direct intentional exposure for purposeful use to incapacitate (OR, 3.02; 95% CI, 1.80-5.06), and for law enforcement on individual target suspects or crowd control (OR, 2.45; 95% CI, 1.42-4.23).ConclusionsThere was a low 1 in 15 potential risk for more severe adverse health effects in persons exposed to pepper spray that warranted a medical evaluation. The risk was highest when used for training of law enforcement personnel and involved severe ocular symptoms. This suggests that routine use of pepper spray for training of law enforcement or military personnel be reconsidered. Protective goggles may be an option when direct spraying into the face of trainees. Transport for medical evaluation should be considered for exposed persons that manifest persistent ocular or respiratory symptoms.

Introduction: The aim of the study was to assess the effect of nasal mucosa irritants on the occurrence of chronic rhinosinusitis without/and with nasal polyps. Material and methods: The study involved 100 adult participants, including 39 women and 61 men, aged 21-68, diagnosed and treated at the Department of Otolaryngology, ENT Oncology, Audiology and Phoniatrics at the University Clinical Hospital WAM in Łódź. Based on the otorhinolaryngological and imaging (CT) tests they were divided into two groups: I - 50 patients, including 23 women and 27 men, aged 21-64 - with chronic rhinosinusitis without nasal polyps, II - 50 patients, including 16 women and 34 men, aged 22-68 - with chronic rhinosinusitis with nasal polyps. The control group consisted of 50 people (group III), including 25 women and 25 men, aged 18-30, students of the Faculty of Military Medicine at the Medical University of Lodz. All respondents completed a prepared questionnaire consisting of 17 questions addressed in the form of an anonymous interview among patients treated in the Department of Otolaryngology, ENT Oncology, Audiology and Phoniatrics. Results: The conducted surveys indicate the impact of the following factors in pathogenesis of chronic rhinosinusitis without/with nasal polyps: exogenous factors (viruses, bacteria, fungi, drugs, injuries, toxic substances, environmental pollution), general endogenous factors (allergy, hypersensitivity to acetylsalicylic acid and its derivatives, hormonal disorders, supraesophageal reflux disease, granulation disease, immunity disorders, local endogenous factors. Conclusions: In the examined material, patients with chronic rhinosinusitis without/and nasal polyps in most cases are in the age range 51-60 years and over 60 years, they most often live in large cities over 250 thousand inhabitants, suffer from allergic rhinorhinitis in 38.0% in group I and 36.0% in group II, rapid temperature changes and dry air have a negative impact on comfort of breathing. The conducted surveys confirm that the cause of chronic rhinosinusitis with polyps is multifactorial, but a significant factor affecting typical tissue remodeling in this disease is long-term breathing of polluted atmospheric air. [ABSTRACT FROM AUTHOR]

An adverse role of frequent domestic use of cleaning agents, especially in spray form, on asthma has been reported. However, sparse studies have investigated respiratory health effects of chronic domestic exposure to irritant cleaning agents. This study aims to investigate associations between weekly use of irritant domestic cleaning products and current allergic and non-allergic asthma in a large cohort of elderly women.We used data from the Asthma-E3N nested case-control study on asthma (n = 19,404 women, response rate: 91%, 2011), in which participants completed standardized questionnaires on asthma and on the use of domestic cleaning products including irritants (bleach, ammonia, solvents and acids). Allergic multimorbidity in asthma was assessed from allergic-related medications recorded in drug refunds database. The association between use of irritants and current asthma was estimated by logistic regression (current vs. never asthma) and multinomial logistic regression (never asthma, non-allergic asthma, allergic asthma) adjusted on age, smoking status and body mass index (BMI).In the 12,758 women included in the analysis (mean age: 70 years, current smokers: 4%, BMI ≥ 25 kg/m2: 32%, low education: 11%, current asthma: 23%), 47% reported weekly use of at least one irritant cleaning product at home. Weekly use of irritant products was associated with a higher risk of current asthma (adjusted Odds-Ratio: 1.17, 1.07–1.27). A statistically significant dose–response association was reported (p trend

Air pollution plays an important role in the mortality and morbidity of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Particulate matter (PM) is a significant fraction of air pollutants, and studies have demonstrated that it can cause airway inflammation and injury. The airway epithelium forms the first barrier of defense against inhaled toxicants, such as PM. Airway epithelial cells clear airways from inhaled irritants and orchestrate the inflammatory response of airways to these irritants by secreting various lipid mediators, growth factors, chemokines, and cytokines. Studies suggest that PM plays an important role in the pathogenesis of chronic airway diseases by impairing mucociliary function, deteriorating epithelial barrier integrity, and inducing the production of inflammatory mediators while modulating the proliferation and death of airway epithelial cells. Furthermore, PM can modulate epithelial plasticity and airway remodeling, which play central roles in asthma and COPD. This review focuses on the effects of PM on airway injury and epithelial plasticity, and the underlying mechanisms involving mucociliary activity, epithelial barrier function, airway inflammation, epithelial-mesenchymal transition, mesenchymal-epithelial transition, and airway remodeling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kayalar, Rajabi, Konyalilar, Mortazavi, Aksoy, Wang and Bayram.)

Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades, chemical warfare use has surged in the Middle East and Eastern Europe, with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities is a major concern as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms of CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction and rescue with mechanical ventilation to improve gas exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis, which require long-term clinical care. SIGNIFICANCE STATEMENT: Inhaled chemical threats are of growing concern in both civilian and military settings, and there is an increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development as well as challenges in developing countermeasures applicable for administration in mass casualty situations., (U.S. Government work not protected by U.S. copyright.)

Vesicants such as arsenicals and mustards produce highly painful cutaneous inflammatory and blistering responses, hence developed as chemical weapons during World War I/II. Here, using lewisite and sulfur mustard surrogates, namely phenylarsine oxide (PAO) and 2-chloroethyl ethyl sulfide (CEES), respectively, we defined a common underlying mechanism of toxic action by these two distinct classes of vesicants. Murine skin exposure to these chemicals causes tissue destruction characterized by increase in skin bifold thickness, Draize score, infiltration of inflammatory cells, and apoptosis of epidermal and dermal cells. RNA sequencing analysis identified ∼346 inflammatory genes that were commonly altered by both PAO and CEES, along with the identification of cytokine signaling activation as the top canonical pathway. Activation of several proinflammatory genes and pathways is associated with phosphorylation-dependent activation of heat shock protein 90 α (p-HSP90 α ). Topical treatment with known HSP90 inhibitors SNX-5422 and IPI-504 post PAO or CEES skin challenge significantly attenuated skin damage including reduction in overall skin injury and clinical scores. In addition, highly upregulated inflammatory genes Saa3, Cxcl1, Ccl7, IL-6, Nlrp3, Csf3, Chil3 , etc. by both PAO and CEES were significantly diminished by treatment with HSP90 inhibitors. These drugs not only reduced PAO- or CEES-induced p-HSP90 α expression but also its client proteins NLRP3 and pP38 and the expression of their target inflammatory genes. Our data confirm a critical role of HSP90 as a shared underlying molecular target of toxicity by these two distinct vesicants and provide an effective and novel medical countermeasure to suppress vesicant-induced skin injury. SIGNIFICANCE STATEMENT: Development of effective and novel mechanism-based antidotes that can simultaneously block cutaneous toxic manifestations of distinct vesicants is important and urgently needed. Due to difficulties in determining the exact nature of onsite chemical exposure, a potent drug that can suppress widespread cutaneous damage may find great utility. Thus, this study identified HSP90 as a common molecular regulator of cutaneous inflammation and injury by two distinct warfare vesicants, arsenicals and mustards, and HSP90 inhibitors afford significant protection against skin damage., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

A composite silicone skin adhesive material was designed to improve its water vapor permeability to offer advantages to wearer comfort compared to existing skin adhesive dressings available (including perforated silicone and hydrocolloid products). The chemical and mechanical properties of this novel dressing were analyzed to show that it has a high creep compliance, offering anisotropic elasticity that is likely to place less stress on the skin. A participant study was carried out in which 31 participants wore a novel silicone skin adhesive (Sil2) and a hydrocolloid competitor and were monitored for physiological response to the dressings. Trans-epidermal water loss (TEWL) was measured pre- and postwear to determine impairment of skin barrier function. Sil2 exhibited a higher vapor permeability than the hydrocolloid dressings during wear. Peel strength measurements and dye counter staining of the removed dressings showed that the hydrocolloid had a higher adhesion to the participants' skin, resulting in a greater removal of proteins from the stratum corneum and a higher pain rating from participants on removal. Once the dressings were removed, TEWL of the participants skin beneath the Sil2 was close to normal in comparison to the hydrocolloid dressings that showed an increase in skin TEWL, indicating that the skin had been highly occluded. Analysis of the skin immediately after removal showed a higher incidence of erythema following application of hydrocolloid dressings (>60%) compared to Sil2, (<30%). In summary, this modified silicone formulation demonstrates superior skin protection properties compared to hydrocolloid dressings and is more suitable for use as a skin adhesive.

Multiple in vitro eye irritation methods have been developed and adopted as OECD health effects test guidelines. However, for predicting the ocular irritation/damage potential of agrochemical formulations there is an applicability domain knowledge gap for most of the methods. To overcome this gap, a retrospective evaluation of 192 agrochemical formulations with in vivo (OECD TG 405) and in vitro (OECD TG 437, 438, and/or 492) data was conducted to determine if the in vitro methods could accurately assign United Nations Globally Harmonized System for Classification and Labelling of Chemicals (GHS) eye irritation hazard classifications. In addition, for each formulation the eye irritation classification was derived from the classification of the contained hazardous ingredients and their respective concentration in the product using the GHS concentration threshold (CT) approach. The results herein suggest that the three in vitro methods and the GHS CT approach were highly predictive of formulations that would not require GHS classification for eye irritation. Given most agrochemical formulations fall into this category, methods that accurately identify non-classified agrochemical formulations could significantly reduce the use of animals for this endpoint., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The airway epithelium is continuously exposed to environmental irritants, which can cause adverse effects such as irritant-induced asthma (IIA). Mast cells are located near airway epithelia and are able to respond to a variety of stimuli. We aimed to investigate whether mast cells influence the response of the epithelium upon irritant exposure. Two cell lines and three different seeding conditions, that is, bronchial epithelial cells (16HBE) only, 16HBE with mast cells (HMC-1's) basolaterally, and 16HBE with HMC-1's apically, were established. Upon exposure to the environmental irritants, graphene (G), graphene oxide (GO), diesel exhaust particles (DEPs) or hypochlorite (ClO−), transepithelial electrical resistance (TEER) and paracellular flux of fluorescent-labeled dextrans were determined, along with the release of mediators. Identical experiments were conducted with the Ca2+ ionophore ionomycin. Exposure to G and GO induced a significant and permanent decrease of approximately 70% in TEER after 3 h of exposure, whereas DEP and ClO− exposure resulted in a transient decrease of approximately 20% in TEER. This response pattern was similar in all the different seeding conditions. After 24 h of exposure, fluorescein isothiocyanate–dextran transport was 10-fold greater for G and 5-fold greater for GO in each of the tested seeding conditions, while DEP and ClO− induced no change compared to the control. Upon exposure to the irritants, 16HBE did not release thymic stromal lymphopoietin, interleukin 33 (IL-33), or IL-1α, and HMC-1 cells did not release histamine, IL-6, or IL-8. Epithelial barrier integrity upon treatment with ionomycin was not affected by the presence of HMC-1 cells. A limited amount of IL-6 and IL-8 was released by ionomycin-exposed HMC-1 cells. To conclude, we found that the studied environmental irritants do not directly or indirectly activate HMC-1 cells. These mast cells did not influence the epithelial barrier function upon environmental exposure, and thus currently do not provide additional information for the underlying mechanism of IIA. [ABSTRACT FROM AUTHOR]

Hamster cheek pouches were exposed to 2-chloroethyl ethyl sulfide [CEES, half-mustard gas (HMG)] at a concentration of 0.4, 2.0, or 5.0 mg/ml for 1 or 5 min. Twenty-four hours post-HMG exposure, tissue damage was assessed by both stereomicrography and optical coherence tomography (OCT). Damage that was not visible on gross visual examination was apparent in the OCT images. Tissue changes were found to be dependent on both HMG concentration and exposure time. The submucosal and muscle layers of the cheek pouch tissue showed the greatest amount of structural alteration. Routine light microscope histology was performed to confirm the OCT observations.

In a series of experiments, we looked at a "cutoff" effect for the detection of eye irritation from neat vapors of homologous n-alkylbenzenes and 2-ketones. Stimuli comprised pentyl, hexyl, and heptyl benzene, 2-dodecanone, and 2-tridecanone, presented to each eye at 4 and 8 l/min for 6 sec, using a three-alternative forced-choice procedure against blanks. Detection probability corrected for chance (i.e., detectability) decreased with carbon chain length such that heptyl benzene and 2-tridecanone were virtually undetectable, irrespective of flow rate to the eye. Heating both stimuli sources to 37 degrees C (body temperature) from 23 degrees C (room temperature) increased vapor concentration by 5.0 and 6.9 times, respectively, for heptyl benzene and 2-tridecanone. Still, both chemicals failed to show increased detection for 13 of the 21 participants. In addition, plots of experimentally measured and calculated eye irritation thresholds as a function of carbon chain length for each series indicated that, based on the trend, the concentration of the two cutoff homologs at 37 degrees C should have been high enough to allow detection. Taken together, the results suggest that these cutoffs rest on limitations related to the dimension of the molecules rather than on limitations related to their vapor concentration. For example, the stimulus molecule could exceed the size that allows it to fit into the receptor pocket of a receptive protein. Plots of calculated molecular dimensions across homologous alkylbenzenes, from ethyl to dodecylbenzene, and across 2-ketones, from 2-octanone to 2-octadecanone, provided additional support to the above conclusion.

Background: Previous epidemiological studies have shown inconsistent results regarding the relation between the risk of asthma in offspring and parental occupational exposure. Therefore, we conducted a comprehensive and systematic collection of currently available epidemiological data to quantify the correlation between the 2., Methods: Related studies published before March 2023 were identified through searches of the Cochrane Library, Embase, PubMed, and Web of Science databases. The quality of included studies was assessed using the Newcastle-Ottawa Scale, while pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed using fixed-effect or random-effects models., Results: This systematic review included 10 cohort studies, with a total of 89,571 parent-child pairs included in the quantitative analysis. The results exhibited a substantial association between parental occupational exposure to allergens (OR = 1.11; 95% CI: 1.00, 1.23; P = .051) and irritants (OR = 1.19; 95% CI: 1.07, 1.32; P = .001) and an increased risk of asthma in offspring. This association was also observed in the analysis of wheezing (OR = 1.22; 95% CI: 1.11, 1.35; P < .001 and OR = 1.19; 95% CI: 1.08, 1.32; P = .001). Subgroup analysis demonstrated that maternal occupational exposure to allergens (OR = 1.07; 95% CI: 1.02, 1.12; P = .008) and irritants (OR = 1.13; 95% CI: 1.05, 1.21; P = .001) significantly increased the risk of childhood asthma. Furthermore, parental postnatal occupational exposure to allergens (OR = 1.26; 95% CI: 1.10, 1.46; P = .001) and irritants (OR = 1.26; 95% CI: 1.06, 1.49; P = .009) had a more pronounced impact on childhood asthma. Higher levels of exposure (OR = 1.26; 95% CI: 1.10, 1.46; P = .001 and OR = 1.30; 95% CI: 1.16, 1.47; P < .001) were recognized as significant risk factors for childhood asthma., Conclusion: Parental occupational exposure to allergens and irritants increases the risk of asthma and wheezing in offspring, with maternal exposure, postnatal exposure, and high-dose exposure being the primary risk factors for childhood asthma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Homemade topical preparations are becoming increasingly popular due to the widespread belief that herbal and natural products are a safer and better option in the treatment of various conditions. However, homemade topical preparations can precipitate allergic and irritant reactions, depending on the herbal composition of the preparation. Hypersensitivity reactions to such preparations range from contact allergic dermatitis, contact irritant dermatitis, contact urticaria, toxic reaction, photosensitivity, and phototoxic reaction. In Europe, and especially in the Mediterranean area, medicinal herbs from the Compositae family and aromatic Mediterranean herbs are most frequently used in the formulation of topical preparations. Although plants are regarded as strong sensitizers, the number of reported cases of hypersensitivity reactions is relatively small. The problems are limitations in diagnostics due to the lack of necessary patch test substances and the danger of active sensitization during testing. Caution is required in patients prone to allergies and those with existing dermatoses, who should be advised to use registered preparations. The first step in management is cessation of exposure, followed by implementation of topical corticosteroids. Systemic corticosteroid therapy is reserved for more severe cases.

The FDA Modernization Act 2.0 has brought nonclinical drug evaluation into a new era. In vitro models are widely used and play an important role in modern drug development and evaluation, including early candidate drug screening and preclinical drug efficacy and toxicity assessment. Driven by regulatory steering and facilitated by well-defined physiology, novel in vitro skin models are emerging rapidly, becoming the most advanced area in alternative testing research. The revolutionary technologies bring us many in vitro skin models, either laboratory-developed or commercially available, which were all built to emulate the structure of the natural skin to recapitulate the skin's physiological function and particular skin pathology. During the model development, how to achieve balance among complexity, accessibility, capability, and cost-effectiveness remains the core challenge for researchers. This review attempts to introduce the existing in vitro skin models, align them on different dimensions, such as structural complexity, functional maturity, and screening throughput, and provide an update on their current application in various scenarios within the scope of chemical testing and drug development, including testing in genotoxicity, phototoxicity, skin sensitization, corrosion/irritation. Overall, the review will summarize a general strategy for in vitro skin model to enhance future model invention, application, and translation in drug development and evaluation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Phenylarsine oxide (PAO), an analog of lewisite, is a highly toxic trivalent arsenical and a potential chemical warfare agent. PAO-induced toxicity has been studied in lung, liver, and skin tissues. Nevertheless, very few studies have been published to comprehend the impact of PAO-induced toxicity on ocular tissues, even though eyes are uniquely vulnerable to injury by vesicants. Notably, arsenical vesicants such as lewisite have been shown to cause edema of eyelids, inflammation, massive corneal necrosis, and blindness. Accordingly, human corneal epithelial cells were used to study the effects of PAO exposure. PAO (100 and 200 nM) induced significant oxidative stress in corneal epithelial cells. Simultaneous treatment with N-acetyl-l-cysteine (NAC), an FDA-approved antioxidant, reversed the PAO-induced toxicity in human corneal epithelial cells. Furthermore, oxidative stress induction by PAO was accompanied by unfolded protein response (UPR) signaling activation and ferroptotic cell death. Further, to validate the findings of our in vitro studies, we optimized injury biomarkers and developed an ex vivo rabbit corneal culture model of PAO exposure. Investigations using PAO in ex vivo rabbit corneas revealed similar results. PAO (5 or 10 μg) for 3, 5, and 10 min caused moderate to extensive corneal epithelial layer degradation and reduced the epithelial layer thickness in a concentration- and time-dependent manner. Similar to human corneal cells, injuries by PAO in ex vivo cultured rabbit corneas were also associated with elevated oxidative stress, UPR signaling, and ferroptosis induction. NAC mitigated PAO-induced corneal injuries in rabbit ex vivo cornea culture as well. The reversal of PAO toxicity upon NAC treatment observed in our studies could be attributed to its antioxidant properties. These findings suggest that PAO exposure can cause significant corneal injury and highlight the need for further mechanistic studies to better understand the pathobiology of different arsenical vesicants, including PAO and lewisite., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Smoke inhalation injury (SII) is a major morbidity and cause of mortality in patients with burns. Damage caused by inhalation of thermal or chemical irritants, including toxic fumes and chemicals, leads to respiratory cilia and epithelial cell injuries, which turn to severe bronchospasm and alveolar damage and results in acute respiratory distress syndrome. Respiratory management plays a vital role in the treatment of SII. In this review, we provide an overview of SII with emphasis on respiratory management, including aerosol therapy, bronchial hygiene therapy, advanced ventilation modes, and heated humidified high-flow nasal cannula. In summary, the information may be helpful for further improvements in outcomes. [ABSTRACT FROM AUTHOR]

Background: Little is known regarding the characteristics of patients with negative patch test (NPT) results.Objective: To characterize patients with NPT results.Methods: Retrospective cross-sectional analysis of 34,822 patch tested patients. NPT results were defined as negative or irritant final interpretations of all North American Contact Dermatitis Group screening allergens and no relevant allergens on supplemental series.Results: Almost one-third of patients (n = 10,888 [31.3%]) had NPT results. Patients with NPT results were significantly more likely to be male (P < .0001), be age 40 years or younger (P = .0054), be nonwhite (P = .0005), and have dermatitis primarily having a scattered generalized distribution (P = .0007) or primarily located on the lips (P = .0214) or eyelids (P = .0364). However, the absolute differences in age, race, and site were small and may not be clinically meaningful. Patients with NPT results were significantly less likely to have occupationally related skin disease (P < .0001). Overall, 8.3% of patients with NPT results had occupationally related skin disease, with precision production worker/machine operator (28.5%), health care worker (17.0%), and mechanic/repairer (7.5%) being the most commonly related occupations. In all, 22.9% of patients with NPT results had relevant irritants and 41.6% of irritants were occupationally related; cosmetics/health care products and soaps were common sources for both occupationally related and non-occupationally related irritants.Limitations: Retrospective cross-sectional study of tertiary referral population.Conclusions: Patients with NPT results have distinct characteristics. [ABSTRACT FROM AUTHOR]

Irritant contact dermatitis (ICD), the most common occupational cutaneous illness, is an acute inflammatory response caused by topical irritant exposure. Multiple factors are associated with the manifestation and severity of ICD and contribute to the lack of effective prophylactic and treatment strategies. To determine the pathomechanism of ICD caused by the irritants, benzalkonium chloride (BKC) and JP-8 jet fuel, 2 mouse strains, C57BL/6 and Balb/c, were assessed due to their differential immune predispositions. Dermatitis lesions were obtained for histological examination, cytokine protein expression analysis, and determination of immune cell infiltration via flow cytometric analysis. Following acute (3-day) BKC exposure C57BL/6 skin displayed increased neutrophils and expression of 19 distinct cytokines, but fewer dendritic cells and lower expression of IL-1α and IL-9 as compared with Balb/c skin. Following prolonged (7-day) exposure to BKC, inflammatory cell populations trended similar to 3-day exposure; however, only 6 distinct cytokines were higher in C57BL/6, whereas Balb/c displayed higher expression of IL-27, 28, and 31. Following acute JP-8 exposure, C57BL/6 skin displayed higher levels of γδ T cell infiltration, G and M-CSF expression, but lower populations of neutrophils, monocytes, and dendritic cells compared with Balb/c skin. As with BKC, skin inflammatory cell populations following 7-day JP-8 exposure trended similar to 3-day exposure. However, C57BL/6 skin displayed higher levels of IL-6 and LIF, whereas Balb/c showed increased IL-1β, IL-27, G-CSF, TNFα, and 7 additional chemokines. These findings further define the pathology of ICD, partially explain individual variation of ICD, and offer insight into biomarkers for risk assessment. [ABSTRACT FROM AUTHOR]

Chemical agents that can potentially cause skin irritation are typically tested in animal models or in vitro assays of cell viability or cytokine expression. However, these methods do not always provide translatable results and are not sufficiently sensitive for subtoxicity detection. Here, we introduce the mechanical properties of keratinocytes as novel endpoints for the safety assessment of chemical agents at the subtoxicity level. Human primary keratinocytes were treated with various concentrations of sodium lauryl sulfate (SLS) and their biological properties (proliferation, membrane integrity, inflammatory response, and morphology) were observed. Their biomechanical and geometrical parameters (stiffness and surface roughness) were also investigated by atomic force microscopy. Keratinocyte morphophysiological changes and inflammatory responses were significant at ≥25 μM SLS. The keratinocytes became less stiff due to changes in the distribution of F‐actin filaments and α‐tubulin; these changes were significant even at lower doses of SLS (≤10 μM). The morphophysiological changes of keratinocytes were clearly seen at a relatively high dose of SLS, while the mechanical properties of keratinocytes responded linearly to SLS at lower doses. Therefore, changes in mechanical properties can be used as new endpoints for in vitro toxicity testing with keratinocytes. Morphophysiological changes of keratinocytes were clearly seen at a relatively high concentration of SLS (≥25 μM), while their mechanical properties responded linearly to SLS at lower concentrations (≤10 μM). Mechanical properties were more sensitive to SLS. [ABSTRACT FROM AUTHOR]

Traditional protective measures to keep wildlife away from areas include exclusion by use of netting, hazing, and chemical repellents. The primary problem with most hazing systems is that wildlife quickly habituate to the devices if their use falls into a predictable pattern. Repellent substances cause wildlife species to avoid otherwise attractive or palatable resources by creating a disincentive to visit a specific area or consume a particular resource. Chemical repellents, both lethal and non-lethal, are typically used for agricultural and horticultural purposes, but in addition may provide a strategy to deter wildlife in other contexts. Aerosol delivery of chemical repellents might work to effectively target birds in the air prior to landing in a hazardous area (i.e., a toxic waste water impoundment). In theory, aerosol delivery of a known avian irritant could be used as an ancillary tool in bird hazing systems, to complement more traditional auditory and visual scare tactics.

Repellents include chemical substances, visual displays, and sonic and ultrasonic deterrent systems. The use of electric shock also can be considered as a repellent category. Each of these categories is discussed, together with their respective utilities, constraints on their usefulness, and possibilities for future development. Economic considerations that may impede or expedite the development of new strategies are presented. Repellent effectiveness depends upon a complex of variables, including the palatability of protected and alternative foods, weather conditions, and the number of animals causing problems. Invariably, repellents are most useful when used as components of integrated pest management strategies.

Proctitis is an inflammatory change of rectal mucosa induced by various agents or stimulus. Among many etiologies, it may be caused by medical treatments such as radiation or antibiotics. Proctitis usually presents with rectal ulcer but abscess formation is uncommon. Therapy using Ssukjwahun exerts its effect by directly applying the smoke around genital area and anus with various medicinal brewed herbs, especially worm-wood. Secondary metabolite of this plant, monoterpene, is known to facilitate circulation, exert anti-inflammatory effect, and help control pain. Herein, we report an unusual case of infectious proctitis presenting with rectal ulcer and abscess formation after perianal application of warm steam made by Artemisia asiatica smoke for treatment of dysmenorrhea. (Korean J Gastroenterol 2016;67:212-215)

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, associated with impaired skin barrier function and an atopic background. Various complicating factors, such as irritants, aeroallergens, food, microbial organisms, contact allergens, sweat, and scratching can induce the development of AD symptoms. Irritants, including soap/shampoo and clothes, can cause itching and eczematous lesions. In addition, young children with AD tend to become sensitized to eggs, milk, or peanuts, while older children and adults more often become sensitized to environmental allergens, such as house dust mites (HDM), animal dander, or pollen. Serum-specific IgE levels and skin prick test reactions to food tend to show high negative predictive values and low specificity and positive predictive values for diagnosing food allergy. On the other hand, AD adult patients tend to have severe skin symptoms and exhibit high HDM-specific IgE levels. Microbial organisms, e.g., Staphylococcus aureus and Malassezia furfur, might contribute to the pathogenetic mechanisms of AD. While sweat plays a major role in maintaining skin homeostasis, it can become an aggravating factor in patients with AD. Furthermore, scratching often exacerbates eczematous lesions. Several patient-specific complicating factors are seen in most cases. The identification and management of complicating factors are important for controlling AD.