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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 < 0.05). Importantly, ascorbic acid had no significant effect on the OD values of TP or TN chemicals regardless of chemical reactivity. These findings suggest that supplementation of ascorbic acid in alternative ocular irritation tests may help improve the detection of TN for those commonly misclassified reactive chemicals.

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 < 0.0001). Mean molluscum lesion counts decreased 76% for VP-102 and 0.3% for vehicle at day 84 (p < 0.0001). The most common AEs in the VP-102 group were application site blistering, pruritus, pain, and erythema, which were generally mild or moderate in severity.ConclusionsPooled analyses showed a significantly higher percentage of participants with complete molluscum lesion clearance and larger reductions in lesion counts with VP-102 than with vehicle. AEs were anticipated because of the pharmacodynamic properties of cantharidin.Trial registrationClinicalTrials.gov identifiers: NCT03377790 (first posted 19 December 2017) and NCT03377803 (first posted 19 December 2017). Video abstract: Pooled Results of Two Randomized Phase III Trials Evaluating VP 102, a Drug Devic

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, a, Funding Agency:University of Leuven Research Council JUMO/16/056 GOA/14/011

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.

BACKGROUND: In laboratory animal work, allergens are classically considered to play a prominent role in generation of respiratory and skin symptoms. However, recent development may have changed working conditions and require an updating of preventive measures. OBJECTIVE: In workers exposed to a range of animals besides laboratory mice and rats the relative role of endotoxin, irritants, and allergens in symptom generation was assessed for updating preventative measures and health surveillance. METHODS: Eligible workers were recruited from university units in which exposure to rats and/or mice, occurrence of respiratory and/or skin symptoms, and/or a history of animal bites had been reported. Exposure to endotoxin and rat and mouse allergen was assessed (71 half-day personal samples). 'Symptomatic' was defined by work-related ocular, nasal, respiratory, or skin symptoms. A concentration of specific IgE against rat or mouse (e87 and e88) ≥0.35 kU/l defined sensitization. Sensitivity analyses examined the effect of alternative exposure indicators and definitions of 'sensitized' and 'symptomatic'. RESULTS: From 302 eligible workers, 177 participated. There were 121 and 41 workers in the asymptomatic and non-sensitized and symptomatic but non-sensitized group, respectively. Eight subjects were symptomatic and sensitized. Six sensitized subjects were asymptomatic. One participant could not be assigned to a subgroup. Airborne endotoxin and allergen concentrations were mostly below 20 EU m-3 or the detection limit, respectively. Clinical history showed that irritants and sensitizers other than mouse/rat allergen or endotoxin were a major cause of symptoms. Results were sensitive to the selected exposure indicator and the definition of 'symptomatic'. CONCLUSIONS: Health surveillance programs need to be adapted to include a larger range of allergens and pay more attention to irritants.

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.

BACKGROUND: Hand eczema (HE) is a multifactorial disease, comprising different aetiological conditions and different morphologies. There are two aetiologically distinct groups of HE recognised: exogenous, such as contact dermatitis (allergic and/or irritant HE) and endogenous, such as the classic hyperkeratotic HE. Differences in the skin barrier properties of these two conditions could theoretically be expected.AIM: To examine whether differences exist in the lipid profile and the susceptibility of the stratum corneum (SC) in patients with allergic/irritant HE and those with hyperkeratotic HE.METHODS: Using cyanoacrylate, SC samples were taken from 23 patients with allergic/irritant HE and 15 with hyperkeratotic HE for lipid analysis by high-performance thin-layer chromatography (HPTLC). Samples were also taken from adjacent, unaffected skin. Severity of HE was assessed by the Hand Eczema Severity Index (HECSI), and skin barrier susceptibility was assessed by measuring transepidermal water loss (TEWL) after a 24-hour patch test with sodium lauryl sulfate (SLS).RESULTS: No statistically significant difference was found between groups for the lipid analysis or for skin susceptibility to SLS. We found a significantly higher HECSI score for hyperkeratotic HE compared with irritant or allergic HE (P = 0.02).CONCLUSIONS: There appears to be no difference in skin barrier between allergic/irritant HE (exogenous eczema) and hyperkeratotic HE (endogenous eczema) with regard to SC lipids or susceptibility to SLS.

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 sp

Chronic inflammation of the upper airways is common and can arbitrarily be divided into rhinitis and rhinosinusitis. Infection and allergy represent two well-characterized and most frequently diagnosed etiologies of upper airway inflammation. Persistent upper airway inflammation caused by agents inhaled in the work environment represents a diagnostic challenge in clinical practice, and its pathophysiology has been little studied. Occupational rhinitis is a recognized medical condition with diagnostic and therapeutic guidelines. In contrast, only limited evidence is available about the relationship between work exposures and rhinosinusitis. This review aims at providing a comprehensive overview of the available literature on occupational upper airway disease with a focus on pathophysiological mechanisms and with an emphasis on the current unmet needs in work-related upper airway disease.

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 sp

BACKGROUND: On skin contact, nickel accumulates in the stratum corneum, where it is probably bound to proteins and amino acids. One probable contributor is filaggrin, which binds nickel avidly. Filaggrin gene (FLG) null mutations lead to a complete lack of filaggrin production from the affected allele, and have been associated with an increased risk of nickel contact sensitization in German and Danish adults.OBJECTIVES: To investigate whether the experimental nickel elicitation threshold level differed between heterozygous FLG mutation and non-mutation carriers.METHOD: Thirteen nickel-sensitized female patients, seven heterozygous mutation carriers and six non-mutation carriers (genotyped for R501X, 2282del4, or R2447X), were patch tested and performed a repeated open application test (ROAT) with a nickel sulfate dilution series. Logistic threshold dose-response analyses were used to test for differences between the two groups.RESULTS: No difference was found in the dose-response relationship between FLG mutation and non-mutation carriers.CONCLUSIONS: On the basis of this small patient study, it appears that the elicitation threshold level for nickel is independent of FLG null mutation single-allele carrier status.

BACKGROUND: On skin contact, nickel accumulates in the stratum corneum, where it is probably bound to proteins and amino acids. One probable contributor is filaggrin, which binds nickel avidly. Filaggrin gene (FLG) null mutations lead to a complete lack of filaggrin production from the affected allele, and have been associated with an increased risk of nickel contact sensitization in German and Danish adults.OBJECTIVES: To investigate whether the experimental nickel elicitation threshold level differed between heterozygous FLG mutation and non-mutation carriers.METHOD: Thirteen nickel-sensitized female patients, seven heterozygous mutation carriers and six non-mutation carriers (genotyped for R501X, 2282del4, or R2447X), were patch tested and performed a repeated open application test (ROAT) with a nickel sulfate dilution series. Logistic threshold dose-response analyses were used to test for differences between the two groups.RESULTS: No difference was found in the dose-response relationship between FLG mutation and non-mutation carriers.CONCLUSIONS: On the basis of this small patient study, it appears that the elicitation threshold level for nickel is independent of FLG null mutation single-allele carrier status.

BACKGROUND: Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis. METHODS: The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970-2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated. RESULTS: The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). CONCLUSIONS: Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment.

BACKGROUND: Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis. METHODS: The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970-2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated. RESULTS: The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). CONCLUSIONS: Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment.

BACKGROUND: Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis. METHODS: The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970-2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated. RESULTS: The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). CONCLUSIONS: Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment.

BACKGROUND: Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis. METHODS: The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970-2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated. RESULTS: The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). CONCLUSIONS: Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment.

BACKGROUND: Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis. METHODS: The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970-2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated. RESULTS: The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). CONCLUSIONS: Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment.

Purpose: This case-control study was undertaken to elucidate the controversy concerning whether low-level, long-term exposure to non-sensitising air pollution at workplaces may cause asthma. Methods: A case-control study of 192 adult-onset asthma cases aged 20-65 years and 323 controls was conducted in the southeast of Sweden. Cases were identified from computerised registers from the region, diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents were randomised from the population register of the region. Exposure was monitored by a 16-page questionnaire. Special attention was devoted to identifying and in the final analyses excluding subjects exposed to sensitising agents. Results: Three years or more of occupational exposure to air pollution from dust, smoke, fumes or vapours before the year of diagnosis by analyses adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2) in men, while in women, no risk was seen. In a multiple logistic regression analysis in men without allergy in childhood, a significant risk was seen (OR = 2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were excluded. In women, no excess risk was observed from occupational air pollution. Conclusion: The results of this study support an association between occupational exposure to low level non-sensitising air pollution and adult-onset asthma in men., Funding Agencies|Swedish Cancer and Allergy Foundation||Forss (Medical Research Council of Southeast Sweden)|2002-413

Purpose: This case-control study was undertaken to elucidate the controversy concerning whether low-level, long-term exposure to non-sensitising air pollution at workplaces may cause asthma. Methods: A case-control study of 192 adult-onset asthma cases aged 20-65 years and 323 controls was conducted in the southeast of Sweden. Cases were identified from computerised registers from the region, diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents were randomised from the population register of the region. Exposure was monitored by a 16-page questionnaire. Special attention was devoted to identifying and in the final analyses excluding subjects exposed to sensitising agents. Results: Three years or more of occupational exposure to air pollution from dust, smoke, fumes or vapours before the year of diagnosis by analyses adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2) in men, while in women, no risk was seen. In a multiple logistic regression analysis in men without allergy in childhood, a significant risk was seen (OR = 2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were excluded. In women, no excess risk was observed from occupational air pollution. Conclusion: The results of this study support an association between occupational exposure to low level non-sensitising air pollution and adult-onset asthma in men., Funding Agencies|Swedish Cancer and Allergy Foundation||Forss (Medical Research Council of Southeast Sweden)|2002-413

The workplace can trigger or induce asthma and cause the onset of different types of work-related asthma (WRA). Based on current knowledge of clinical features, pathophysiologic mechanisms, and evidence supporting a causal relationship, the following conditions should be distinguished in the spectrum of WRA: (1) immunologic occupational asthma (OA), (2) nonimmunologic OA, (3) work-exacerbated asthma, and (4) variant syndromes, including eosinophilic bronchitis, potroom asthma, and asthmalike disorders caused by organic dusts. The rationale, issues, and controversies relating to this approach are critically reviewed to stimulate the development of a consensus on operational definitions of the various phenotypes of WRA.

Purpose: This case-control study was undertaken to elucidate the controversy concerning whether low-level, long-term exposure to non-sensitising air pollution at workplaces may cause asthma. Methods: A case-control study of 192 adult-onset asthma cases aged 20-65 years and 323 controls was conducted in the southeast of Sweden. Cases were identified from computerised registers from the region, diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents were randomised from the population register of the region. Exposure was monitored by a 16-page questionnaire. Special attention was devoted to identifying and in the final analyses excluding subjects exposed to sensitising agents. Results: Three years or more of occupational exposure to air pollution from dust, smoke, fumes or vapours before the year of diagnosis by analyses adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2) in men, while in women, no risk was seen. In a multiple logistic regression analysis in men without allergy in childhood, a significant risk was seen (OR = 2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were excluded. In women, no excess risk was observed from occupational air pollution. Conclusion: The results of this study support an association between occupational exposure to low level non-sensitising air pollution and adult-onset asthma in men., Funding Agencies|Swedish Cancer and Allergy Foundation||Forss (Medical Research Council of Southeast Sweden)|2002-413

Purpose: This case-control study was undertaken to elucidate the controversy concerning whether low-level, long-term exposure to non-sensitising air pollution at workplaces may cause asthma. Methods: A case-control study of 192 adult-onset asthma cases aged 20-65 years and 323 controls was conducted in the southeast of Sweden. Cases were identified from computerised registers from the region, diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents were randomised from the population register of the region. Exposure was monitored by a 16-page questionnaire. Special attention was devoted to identifying and in the final analyses excluding subjects exposed to sensitising agents. Results: Three years or more of occupational exposure to air pollution from dust, smoke, fumes or vapours before the year of diagnosis by analyses adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2) in men, while in women, no risk was seen. In a multiple logistic regression analysis in men without allergy in childhood, a significant risk was seen (OR = 2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were excluded. In women, no excess risk was observed from occupational air pollution. Conclusion: The results of this study support an association between occupational exposure to low level non-sensitising air pollution and adult-onset asthma in men., Funding Agencies|Swedish Cancer and Allergy Foundation||Forss (Medical Research Council of Southeast Sweden)|2002-413

Purpose: This case-control study was undertaken to elucidate the controversy concerning whether low-level, long-term exposure to non-sensitising air pollution at workplaces may cause asthma. Methods: A case-control study of 192 adult-onset asthma cases aged 20-65 years and 323 controls was conducted in the southeast of Sweden. Cases were identified from computerised registers from the region, diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents were randomised from the population register of the region. Exposure was monitored by a 16-page questionnaire. Special attention was devoted to identifying and in the final analyses excluding subjects exposed to sensitising agents. Results: Three years or more of occupational exposure to air pollution from dust, smoke, fumes or vapours before the year of diagnosis by analyses adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2) in men, while in women, no risk was seen. In a multiple logistic regression analysis in men without allergy in childhood, a significant risk was seen (OR = 2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were excluded. In women, no excess risk was observed from occupational air pollution. Conclusion: The results of this study support an association between occupational exposure to low level non-sensitising air pollution and adult-onset asthma in men., Funding Agencies|Swedish Cancer and Allergy Foundation||Forss (Medical Research Council of Southeast Sweden)|2002-413

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.

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.

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.

Allergic asthma has increased worldwide in the industrialized countries. This review evaluates whether the major groups of indoor chemical exposures possess allergy-promoting (adjuvant) effects; formaldehyde was excluded, because of the size of the literature. Volatile organic compounds (VOCs) are used as an example of gases and vapors. The precipitation of asthmatic symptoms by VOC exposures is probably because of VOC levels considerably above typical indoor levels, or VOCs may be a surrogate for exposure to allergens, combustion products or dampness. Indoor particles possessed adjuvant effects in animal studies and allergy-promoting effects in humans. Quaternary ammonium compounds may possess adjuvant effects in animal studies and promoted sensitization in humans in occupational settings. The use of cleaning agents, anionic and non-ionic surfactants are not considered to possess an important adjuvant effect in the general population. Regarding phthalate exposures, results from animal and epidemiological studies were found to be discordant. There is little evidence that the indoor chemicals evaluated possess important adjuvant effects. If buildings are kept clean, dry and free of combustion products, the important question may be would it be profitable to look for lifestyle factors and non-chemical indoor exposures in order to abate airway allergy? PRACTICAL IMPLICATIONS: Indoor chemicals (pollutants) have been accused to promote development of airway allergy by adjuvant effects. In this review, we evaluated the scientific literature and found little support for the supposition that indoor chemicals possess important adjuvant effects. This rises the question: would it be profitable for abatement of airway allergy to look for non-chemical indoor exposures, including lifestyle factors, and exposures to allergens, microorganisms, including vira, and their interactions?

Allergic asthma has increased worldwide in the industrialized countries. This review evaluates whether the major groups of indoor chemical exposures possess allergy-promoting (adjuvant) effects; formaldehyde was excluded, because of the size of the literature. Volatile organic compounds (VOCs) are used as an example of gases and vapors. The precipitation of asthmatic symptoms by VOC exposures is probably because of VOC levels considerably above typical indoor levels, or VOCs may be a surrogate for exposure to allergens, combustion products or dampness. Indoor particles possessed adjuvant effects in animal studies and allergy-promoting effects in humans. Quaternary ammonium compounds may possess adjuvant effects in animal studies and promoted sensitization in humans in occupational settings. The use of cleaning agents, anionic and non-ionic surfactants are not considered to possess an important adjuvant effect in the general population. Regarding phthalate exposures, results from animal and epidemiological studies were found to be discordant. There is little evidence that the indoor chemicals evaluated possess important adjuvant effects. If buildings are kept clean, dry and free of combustion products, the important question may be would it be profitable to look for lifestyle factors and non-chemical indoor exposures in order to abate airway allergy? PRACTICAL IMPLICATIONS: Indoor chemicals (pollutants) have been accused to promote development of airway allergy by adjuvant effects. In this review, we evaluated the scientific literature and found little support for the supposition that indoor chemicals possess important adjuvant effects. This rises the question: would it be profitable for abatement of airway allergy to look for non-chemical indoor exposures, including lifestyle factors, and exposures to allergens, microorganisms, including vira, and their interactions?

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.

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.

The knowledge how detergents with different chemical properties influence epidermal keratinocytes is sparse. In the present study, the effects of five detergents were examined with respect to cell-toxicity and mRNA expression of key-enzymes in barrier lipid production and keratinocyte differentiation markers. First, the LD(50) for each detergent were determined. Secondly, keratinocytes were exposed to sub-toxic concentrations and the mRNA expression was analysed by real-time PCR after 24 h exposure to the detergents. SLS and CAPB induced a concentration-dependent increase in the expression of enzymes producing cholesterol and ceramides, while transcripts of enzymes producing fatty acids were unaffected. SLES and cocoglucoside increased the expression of certain enzymes involved in cholesterol and fatty acid synthesis while sodium cocoamphoacetate (SCAA) stimulated expression of transcripts involved in fatty acid synthesis. The expression of differentiation markers were increased by SLS, SLES and CAPB, while SCAA and cocoglucoside exhibited no effect. The present findings show that detergents have variable effects on lipid synthesis and keratinocyte differentiation, which could partly explain their barrier destruction potential in vivo.

[Occupational Dermatitis: Irritation or Allergy?] Occupational dermatitis is a very frequent subject of consultation, as much in general practice as in dermatology. The most frequently found pathologies are linked to environmental factors. In these cases, irritant dermatitis and allergic contact dermatitis represent the majority of the cutaneous problems. Rigorous history taking associated with an attentive examination and a few investigations, essentially consisting of skin testing, form an incontestable tripod. The therapeutic approach, as much preventative as curative, can only be envisaged after having made a precise diagnosis, of which the conclusions should be pertinent and adapted to each patient presenting in consultation. In occupational disease, the distinction between irritant dermatitis and allergic contact dermatitis is primordial.

Studies on the irritative effects of acetone vapor in humans and experimental animals have revealed large differences in the lowest acetone concentration found to be irritative to the respiratory tract and eyes. This has brought on much confusion in the process of setting occupational exposure limits for acetone. A literature survey was carried out focusing on the differences in results between studies using subjective (neuro)behavioral methods (questionnaires) and studies using objective measurements to detect odor and irritation thresholds. A critical review of published studies revealed that the odor detection threshold of acetone ranges from about 20 to about 400 ppm. Loss of sensitivity due to adaptation and/or habituation to acetone odor may occur, as was shown in studies comparing workers previously exposed to acetone with previously unexposed subjects. It further appeared that the sensory irritation threshold of acetone lies between 10,000 and 40,000 ppm. Thus, the threshold for sensory irritation is much higher than the odor detection limit, a conclusion that is supported by observations in anosmics, showing a ten times higher irritation threshold level than the odor threshold found in normosmics. The two-times higher sensory irritation threshold observed in acetone-exposed workers compared with previously nonexposed controls can apart from adaptation be ascribed to habituation. An evaluation of studies on subjectively reported irritation at acetone concentrations < 1000 ppm shows that perception of odor intensity, information bias, and exposure history (i.e., habituation) are confounding factors in the reporting of irritation thresholds and health symptoms. In conclusion, subjective measures alone are inappropriate for establishing sensory irritation effects and sensory irritation threshold levels of odorants such as acetone. Clearly, the sensory irritation threshold of acetone should be based on objective measurements.

Environmental agents, when applied in combination or sequentially, can induce a wide variety of adverse health effects in humans. To determine the effects of sequential allergen challenge and acid exposure on human bronchial epithelial cell function, we subjected normal, nonallergic control and ragweed-allergic individuals to bronchoscopic segmental ragweed challenge in vivo. We harvested bronchial epithelial cells by brush biopsy both before challenge and 24 hr after challenge and exposed cells to an acid stress in vitro (pH 5 for 3 hr), followed by a 1-hr recovery period at normal pH. In normal, nonallergic subjects, segmental allergen challenge produced no effects on ciliary activity; pH 5 exposure produced reduced ciliary activity (a decrease in the percent of the initially active area), with significant recovery after cells were returned to a normal pH. Ciliary activity from allergic subjects was also inhibited by pH 5 exposure; however, activity was not recovered when cells were placed in medium of normal pH. Ciliary activity in allergics who developed a stress response postantigen challenge, as determined by an induction of the 27 kDa stress (heat shock) protein, displayed no ciliary dysfunction when exposed to a pH 5 stress. In this case, a stress sufficient to provoke a heat shock (stress) protein (HSP) response (but not one that produced more severe lung injury and did not provoke an HSP response) protected cells from a subsequent acid stress. Because of our observations and recent findings reported in the literature, we suggest that in order to define the wide variety of health effects of environmental agents, control as well as at-risk populations should be studied and the ability to define potentially beneficial as well as detrimental effects should be built into the experimental design. Inclusion of different and novel end points also should be considered.

The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T(1) relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositions, which ranged from water-continuous to oil-continuous aggregates over possible bicontinuous structures, with excellent solubility properties for both lipophilic and hydrophilic compounds. The microemulsions increased transdermal flux of lidocaine up to four times compared to a conventional oil-in-water emulsion, and that of prilocaine hydrochloride almost 10 times compared to a hydrogel. A correlation between self-diffusion of the drugs in the vehicles and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating a low skin irritancy.

The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T(1) relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositions, which ranged from water-continuous to oil-continuous aggregates over possible bicontinuous structures, with excellent solubility properties for both lipophilic and hydrophilic compounds. The microemulsions increased transdermal flux of lidocaine up to four times compared to a conventional oil-in-water emulsion, and that of prilocaine hydrochloride almost 10 times compared to a hydrogel. A correlation between self-diffusion of the drugs in the vehicles and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating a low skin irritancy.

By determining the intracellular elemental content, information can be obtained on the physiological status of cells. The cellular content of sodium, magnesium, phosphorus, sulfur, chloride, potassium and calcium can be indicative for proliferation, cell membrane damage or cell death. X-ray microanalysis is a method for measuring the intracellular elemental content. In the present study this technique has been used for in vivo and in vitro studies of human epidermal keratinocytes under different physiological conditions. Focus has been on irritant reactions, proliferation/hyperplasia and on methodological aspects. As a part of this, studies on the effects of local anaesthesia on normal skin and the effects of calcipotriol on psoriatic skin were included Irritant reactions were induced with sodium lauryl sulfate and non-anoic acid. In studies on skin invivo, X-ray microanalysis was combined with reverse transcriptase-polymerase chain reaction to determine the cytokine profile and with analysis with the monoclonal antibody Ki67 to determine the proliferation following application of the two irritants. By studying keratinocytes in cell cultures, it is possible to eliminate the influence from other cells in the skin and to perform more controlled studies. In the last part of the study the influence of methodological factors, cell type and exposure to sodium lauryl sulfate on the cellular elemental content were evaluated in cultured keratinocytes. Following application of the irritants to the skin it was possible to identify an early response at 6-24 hours with elemental changes compatible with a cell membrane damage followed by a proliferation with a maximum at 24-48 hours later. It was also possible to detect a difference in the response between the two applied irritants. The elemental changes found in the proliferative phase were similar to those found in psoriatic skin. Calcipotriol has an anti-proliferative effect and this was also reflected in the elemental content

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.

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.

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.

Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR and/or ACE. Exposure concentrations of the mixtures were chosen in such a way that summation of the effects of each chemical would be expected not to exceed 80% reduction of the breathing frequency. FRM, ACR and ACE appeared to act as sensory irritants as defined by Alarie (1966, 1973). With FRM and ACR desensitization occurred, whereas with ACE the breathing frequency gradually decreased with increasing exposure time (up to 30 min). For mixtures, the observed DBF was more pronounced than the DBF for each compound separately, but was less than the sum of the DBFs for the single compounds. A model for three compounds competing for the same receptor was applied to predict the DBF of mixtures of FRM, ACE and ACR. The results also showed that with mixtures no desensitization occurred; in fact, the breathing frequency further decreased in the last 15 min of exposure. These observations were similar to those found for ACE alone, and might have been caused by effects on the upper respiratory tract. The results of the present study allow the conclusion that sensory irritation in rats exposed to mixtures of irritant aldehydes is more pronounced than that caused by each of the aldehydes separately, and that the DBF as a result of exposure to a mixture could well be predicted using a model for competitive agonism, thus providing evidence that the combined effect of these aldehydes is basically a result of competition for a common receptor (trigeminal nerve).

In a series of previous experiments, we showed that the inflammatory response associated with skin barrier function damage induced by sodium laurylsulfate (SLS) was correlated with the concentration of SLS and with the duration of application under occlusion of the surfactant. In this experiment, we measured accumulation of unbound water that occurred when occlusive contact was maintained during a short period of time between the skin and the probe head of an electrometric device. Accumulation of unbound water was expressed as area under the curve (sum of increments of skin capacitance during a 45-second period of time; AUCC). For comparative purposes, we also measured transepidermal water loss (TEWL). Both skin function parameters were established for each individual skin site before and 24 h after removal of SLS patches (10, 5, 1 and 0% control solution under occlusion for 48 h). After SLS insult, AUCC and TEWL were increased, and changes were related to SLS concentration (p less than 0.0002). There was a linear correlation between AUCC and log TEWL (p less than 0.0002). On normal skin before application of SLS both parameters were also correlated (p less than 0.04). The regression line between AUCC and log TEWL of normal skin differed however from that observed on SLS-pretreated sites. This indicates that electrometric data are able to simultaneously characterize changes in skin hydration, a rather static parameter, and changes in the amount of unbound water accumulation (AUCC), a dynamic parameter which proved to reflect TEWL.

Riot control agents (tear gases) cause intense eye irritation and reflex squeezing of the eyes. The intraocular pressure under these circumstances is unknown, but animal and human studies of ocular irritation and forces acting upon the eye indicate a transient increase in intraocular pressure which is not necessarily detrimental to vision.

The acute dermal toxicity of DIGL-RP Solid Propellant was evaluated in six male and six female New Zealand White rabbits. Moistened ground DIGL-RP (2 g/kg) was applied topically to the clipped dorsal skin surface under a semi- occlusive wrap for 24 hours. No signs of dermal irritation, or systemic toxicity, or death were obtained that could be attributed to DIGL-RP. These data indicate that DIGL-RP Solid Propellant does not produce systemic toxicity when administered by 24-hour topical application at a limit dose of 2 g/kg. (kt)

Individual and environmental risk factors in hand eczema have been investigated in a prospective cohort study of 2452 newly employed hospital workers with a follow-up time of 20 months. Current hand eczema was analyzed in 142 wet hospital workers from this cohort with respect to the etiologic importance of irritants, allergens and contact urticants. The density of the microflora and the effect on the microflora of topical treatment with a potent corticosteroid were studied in 20 patients with hand eczema. ’Wet’ hospital work was found to increase the odds of developing hand eczema only twice compared to 'dry' office work. Nursing children under four years old and the lack of a dish-washing machine significantly increased the risk of contracting hand eczema. Unfavourable combinations of these domestic factors increased the risk as much as wet work. A history of atopic dermatitis approximately tripled the odds both in wet as well as in dry work. Histories of earlier hand eczema (HHE), metal dermatitis (HMD) and of atopy were analyzed as risk factors for hand eczema in 1857 women in wet work. HHE increased the odds by a factor of 12.9 and created a subdivision of the population into high risk individuals and normal risk individuals. HHE was found in half of the subjects with atopic dermatitis, in one quarter of the subjects with atopic mucosal symptoms and in one fifth of the non-atopics. A HMD increased the odds by a factor of 1.8. This increase was seen as a high risk level in subjects with HHE and as a normal risk level in subjects with no HHE. A history of atopic disease as a complement to information about HHE and HMD increased the odds by another 1.3 times. The predicted probability of developing hand eczema ranged from 91 % in subjects with a combination of HHE, HMD and atopy to 24% in subjects with none of these risk factors. Subjects with AD were found to suffer a more severe form of hand eczema with significantly higher figures for medical consultation, sick, Härtill 4 uppsatser, digitalisering@umu

Individual and environmental risk factors in hand eczema have been investigated in a prospective cohort study of 2452 newly employed hospital workers with a follow-up time of 20 months. Current hand eczema was analyzed in 142 wet hospital workers from this cohort with respect to the etiologic importance of irritants, allergens and contact urticants. The density of the microflora and the effect on the microflora of topical treatment with a potent corticosteroid were studied in 20 patients with hand eczema. ’Wet’ hospital work was found to increase the odds of developing hand eczema only twice compared to 'dry' office work. Nursing children under four years old and the lack of a dish-washing machine significantly increased the risk of contracting hand eczema. Unfavourable combinations of these domestic factors increased the risk as much as wet work. A history of atopic dermatitis approximately tripled the odds both in wet as well as in dry work. Histories of earlier hand eczema (HHE), metal dermatitis (HMD) and of atopy were analyzed as risk factors for hand eczema in 1857 women in wet work. HHE increased the odds by a factor of 12.9 and created a subdivision of the population into high risk individuals and normal risk individuals. HHE was found in half of the subjects with atopic dermatitis, in one quarter of the subjects with atopic mucosal symptoms and in one fifth of the non-atopics. A HMD increased the odds by a factor of 1.8. This increase was seen as a high risk level in subjects with HHE and as a normal risk level in subjects with no HHE. A history of atopic disease as a complement to information about HHE and HMD increased the odds by another 1.3 times. The predicted probability of developing hand eczema ranged from 91 % in subjects with a combination of HHE, HMD and atopy to 24% in subjects with none of these risk factors. Subjects with AD were found to suffer a more severe form of hand eczema with significantly higher figures for medical consultation, sick, Härtill 4 uppsatser, digitalisering@umu

Dieffenbachia may well be the most toxic genus in the Araceae. Calcium oxalate crystals, a protein and a nitrogen-free compound have been implicated in the toxicity, but the available evidence is unclear. The plants have also been used as food, medicine, stimulants, and to inflict punishment. © 1982.