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At least 19 recordsLinked to original sources

The outcome of asthma related to workplace irritant exposures: a comparison of irritant-induced asthma and irritant aggravation of asthma.

STUDY OBJECTIVES: (1) To characterize workers' compensation claims accepted on the basis of new-onset asthma associated with accidental high respiratory irritant exposure at work; (2) to compare the frequency, characteristics, and outcomes in this group of workers to workers who were compensated for an exacerbation of preexisting asthma associated with accidental high respiratory irritant exposure at work. DESIGN: A retrospective review was performed of 469 asthma claims accepted by the Ontario Workers' Compensation Board (WCB) between 1984 and 1988. Among these, claims attributed to an accidental high respiratory irritant exposure at work were classified into two groups: one group with reported preexisting asthma prior to the exposure (accidental aggravation of asthma [AAA]) and another group with no previous history of asthma (irritant-induced asthma [IIA]). RESULTS: Of the 469 claims, 89 subjects (19%) had symptoms related to accidental high respiratory irritant exposure in the workplace; of these, 68 subjects (76%) had AAA, 12 subjects (13%) had IIA, and 9 subjects (10%) had possible IIA but were excluded from the analysis because of insufficient data. Those with IIA had a longer duration of work-attributed symptoms (mean, 219 +/- 208 days) than the subjects with AAA (mean, 32 +/- 38 days; p < 0.001). Nine subjects (75%) with IIA were no longer in the same work environment, while 47 subjects in the AAA group (71%) were still in the same work environment (p < 0.001). The most common triggering agent for subjects with IIA was an isocyanate spill; for those with AAA, the most common triggering agent was paint. CONCLUSIONS: The WCB-accepted claims related to accidental, high respiratory irritant exposure at work are more commonly assigned to the category of AAA than to IIA. IIA patients in this claimant group had a longer mean duration of work-attributed respiratory symptoms, perhaps due to a need for a larger (and thus less common) irritant exposure to induce asthma in previously normal subjects.

Adult↗

[Irritation test of dexamethasone valerate (DV-17) and other steroid ointments in rabbits. Skin and eye primary irritation tests, and skin cumulative irritation test].

The skin and eye primary irritation tests, and skin cumulative irritation test were performed on male rabbits, which were topically treated with a volume of 1 g/body of 0.06% and 0.12% dexamethasone valerate (DV-17) ointments as a test drug, and 0.1% hydrocortisone butyrate (HB) and 0.12% betamethasone valerate (BMV) ointments as an active control drug in order to evaluate the topical and systemic effects. No skin and eye primary irritations except minimal skin erythema and slight conjunctival redness were seen in above four corticosteroids. Judging from the results such as skin atrophy, inhibition of body weight gains, and decreases of thymus, spleen and adrenal weights, the potency of toxicities among the four corticosteroid ointments appeared to be as follows: 0.12% DV-17, 0.12% BMV greater than 0.1% HB greater than 0.06% DV-17.

Adrenal Cortex Hormones↗

Skin irritant reactivity following experimental cumulative irritant contact dermatitis.

Despite the frequency of irritant contact dermatitis, very little is known about the duration of barrier function impairment following cumulative irritant contact dermatitis. We studied post-irritation irritant reactivity by assessing the response to SLS irritation in previously irritated sites. Cumulative irritant contact dermatitis was induced on the forearms of 15 volunteers aged 18 to 50 years by repeated occluded application of 0.5% SLS 1 h per day over 3 weeks. 3, 6 and 9 weeks later, previously irritated and unirritated control sites were challenged with 2% SLS under occlusion for 23 h. Irritation was assessed by visual scoring, transepidermal water loss (TEWL) as an indicator of epidermal barrier function, and capacitance as a parameter of epidermal water content. While no difference in irritant reactivity between pre-irritated and unirritated sites was observed 3 weeks following irritant contact dermatitis, there was a significant hyporeactivity of previously irritated skin as expressed by clinical scores, TEWL and capacitance at 6 and 9 weeks. Our results indicate that epidermal barrier function remains altered even 9 weeks after cumulative irritant contact dermatitis. With regard to patch testing, post-irritation hyporeactivity might be a cause of false-negative tests on previously irritated sites.

Adolescent↗

The sense of coherence index and the irritable bowel syndrome. A cross-sectional comparison among irritable bowel syndrome patients with and without coexisting fibromyalgia, irritable bowel syndrome non-patients, and controls.

BACKGROUND: Sense of Coherence (SOC) is a global orientation that affects coping with stressors. A strong SOC is associated with better health outcomes. The purpose of this study was to evaluate SOC among patients with irritable bowel syndrome (IBS) and matched controls. METHODS: Seventy-nine IBS patients and 72 matched controls completed questionnaires and were tested for fibromyalgia (FS). The controls were subdivided into healthy controls (n = 49) or IBS non-patients (n = 23), and the patients into IBS only (n = 54) or IBS and FS (n = 25). RESULTS: The mean SOC score was higher for the controls than for the IBS patients (65.7+/-1.2 and 59.6+/-1.1, respectively; P = 0.003). There was no significant difference between the healthy controls and the IBS non-patients. The controls had a higher SOC than patients with IBS only and patients with IBS and FS (P = 0.0004). CONCLUSIONS: An association was found between IBS and SOC. No causality can be inferred from this study. Individuals with low SOC may be more likely to express symptoms in terms of psychologic distress and increased health care utilization because of poor coping skills. Conversely, the presence of IBS may affect SOC negatively. Further longitudinal studies could clarify the potential of SOC as a predictor variable (for example, for treatment results) or an outcome variable.

Adaptation, Psychological↗

Surfactant-induced skin irritation and skin repair: evaluation of a cumulative human irritation model by noninvasive techniques.

BACKGROUND: Although surfactant-induced acute irritant dermatitis has been extensively studied, our understanding about the induction and repair of the clinically more relevant chronic form is limited. OBJECTIVE: Our purpose was to investigate qualitative and quantitative differences in surfactant-induced irritant skin reactions from cumulative exposure to structurally unrelated surfactants and to compare the maximal irritant responses from this model with corresponding reactions noted in a previously reported acute irritation model. METHODS: Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (7.5%) were applied for 20 minutes daily (for 8 consecutive days excluding the weekend) to the volar aspect of the forearm of 11 volunteers. Irritant reactions were repeatedly assessed until complete healing was indicated by visual assessment and by measurements of transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). Maximum irritant responses were compared with corresponding reactions from an acute irritation model. RESULTS: TEWL was increased by SLS and DTAB to the same extent, but erythema was significantly higher in DTAB-treated skin. Skin dryness, as demonstrated by decreased capacitance values and increased scores for scaling and fissuring, was significantly more pronounced than in an acute irritation model for SLS and DTAB, although no difference was detected between the two surfactants. Potassium soap led to a slight increase in TEWL, whereas the remaining features were not significantly changed. CONCLUSION: This chronic irritation model appears to represent the clinical situation of irritant contact dermatitis with pronounced skin dryness more closely than the acute irritation model. The present study confirms that an extended time is needed for complete healing of irritant skin reactions. We also demonstrated that the evaluation of the irritation potential of diverse surfactants depended significantly on the feature evaluated (erythema vs electrical capacitance and TEWL), on the mode of application (acute vs cumulative), and, in the cumulative model, on the point of observation.

Adult↗

Ocular irritation: microscopic changes occurring over time in the rat with surfactants of known irritancy.

The pathology of surfactant-induced ocular irritation, especially in the context of accidental human exposures and animal tests used to assess a surfactant's potential ocular irritation, is not well understood. The purpose of this study was to characterize the microscopic changes in rats at 3 hr and on days 1, 2, 3, 4, 7, 14, and 35 following treatment with anionic, cationic, and nonionic surfactants of differing irritancy. The right eye of each rat was treated by placing 10 microliters of a surfactant directly on the cornea. Untreated left eyes served as the controls. At each time point, eyes and eyelids were macroscopically examined and collected for microscopic examination. Macroscopically, the differing levels of irritation were characterized by differences in incidence and magnitude of scores, reflecting involvement of the cornea, conjunctiva, and iris, as well as by the incidence of neovascularization and time to recovery. Microscopically, differences in the area and depth of injury paralleled the differences seen grossly and the relative irritancy of the various surfactants. All surfactants affected the corneal and conjunctival epithelium. All surfactants, except the slightly irritating anionic surfactant, caused corneal stromal changes, with this involvement being proportional to their overall level of irritation. Corneal endothelial cell effects principally occurred with only the severely irritating cationic surfactant. Over time, responses to surfactants of differing irritancy were qualitatively and quantitatively different, and these differences correlated with the extent of initial injury. Qualitative differences in response included presence of keratocyte regeneration, corneal neovascularization, and conjunctivalization of the corneal epithelium with all of the surfactants except the slight irritant. Quantitative differences in response occurred in the extent of epithelial regeneration, edema, and inflammation for surfactants of slight to severe irritancy, and with neovascularization, keratocyte regeneration, and conjunctivalization for surfactants of mild to severe irritancy. These results suggest that by defining initial area and depth of injury associated with an ocular irritant, it may be possible to predict the subsequent response and final outcome. Such an approach would be applicable to the development of mechanistically based in vitro assays.

Administration, Topical↗

Efficacy of skin barrier creams (IV). The repetitive irritation test (RIT) with a set of 4 standard irritants.

An improved human model for the quantification of skin barrier creams (BCs) is described. In contrast to the previously published procedure, the back, instead of the forearm, and a total of 4 irritants are used. Due to the larger area, 3 BC formulations can be simultaneously compared to the control field, which receives the irritant only, without BC-pretreatment. On 10 human volunteers, the irritants 10% sodium lauryl sulfate (SLS), 1% sodium hydroxide (NaOH), 30% lactic acid (LA) and undiluted toluene (TOL) were applied via large Finn Chambers for 30 min, 5 x during the 1st week and 4 x during the 2nd week. Taktosan Salbe (water-in-oil emulsion) and RAWI Speerschutzcreme (oil-in-water emulsion) were applied 30 min before contact with the irritants. In order to assess reproducibility and interindividual variation, the BC RAWI was tested in duplicate. Irritant cutaneous reactions were quantified by 4 parameters: erythema score, transepidermal water loss, blood flow volume and stratum corneum hydration by measuring capacitance. The results showed marked differences in efficacy. Taktosan significantly suppressed irritation by SLS, NaOH and LA, which was apparent in nearly all parameters. RAWI caused significant inhibition of SLS irritation, and a positive trend against NaOH and LA was observed. Both BCs failed against TOL. The results of duplicate testing with RAWI showed good reproducibility. The dogma that oil-in-water emulsions are primarily effective against lipophilic irritants, and water-in-oil emulsions against hydrophilic irritants, needs to be re-evaluated on the basis of our findings. This model seems to have potential for further studies on BCs and might elucidate the complex interaction of BCs with irritants.

Adult↗

Prediction of ocular irritancy potential from dermal irritation test results.

In a survey of the test files of Haskell Laboratory, it was found that of the materials that had been tested on rabbit skin for primary irritation or corrosivity, 60 were severe irritants or corrosive on the skin and had also been tested for ocular irritancy. Of these 60 materials only 39 were severe eye irritants, while 15 were mild irritants or non-irritants and the remainder were considered to be moderate irritants. Thus, to suggest that materials are eye irritants solely on the basis of their skin-irritation properties may be misleading, even when severe dermal irritants are considered.

Animals↗

Surfactant-induced skin irritation and skin repair. Evaluation of the acute human irritation model by noninvasive techniques.

BACKGROUND: Although the induction of irritant dermatitis by surfactants has been extensively studied in recent years, our understanding of the repair phase of irritant dermatitis is limited. OBJECTIVE: We investigated qualitative and quantitative differences in surfactant-induced irritant skin reactions from short-term exposure to three structurally different surfactants. METHODS: Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (0.5%) were applied for 24 hours to the volar aspect of the forearm of 11 volunteers. Irritant reactions were assessed until complete healing was indicated by visual assessment and by various aspects of skin function, that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). RESULTS: SLS and DTAB induced similar degrees of erythema, whereas SLS induced significantly higher TEWL increase. Although both erythema and TEWL were highest 1 hour after exposure to surfactants, skin dryness was a symptom with delayed onset, justifying the long observation period in this study. Minimum hydration values were measured as late as 7 days after surfactant exposure. Dryness was significantly more pronounced in areas exposed to SLS than in areas exposed to DTAB. Complete repair of the irritant reaction induced by either SLS or DTAB was achieved 17 days after surfactant exposure. Stratum corneum hydration was the last feature to return to baseline values. Potassium soap did not significantly influence any skin function. CONCLUSION: We emphasize the importance of extended periods needed before a patient with irritant contact dermatitis can be reexposed to irritant substances. The evaluation of the irritation potential of diverse surfactants depended significantly on the feature (erythema vs hydration and TEWL) measured.

Adult↗

Studies on eye irritation caused by chemicals in rabbits--II. An in vitro testing method using rat red blood cells for the prediction of eye irritation potential of chemicals.

Rat red blood cells were used as an in vitro method to evaluate the eye irritation potential of chemicals in rabbits. The results using 116 chemicals of various categories including medicines, pesticides, detergents and solvents were analyzed for the prediction of possibility of eye irritation potentials. Eye irritation of chemicals was examined according to Draize method and chemicals were classified into three categories, (1) non or mild irritants, (2) moderate or severe irritants and (3) strong or corrosive irritants, based on the recovery of damages. The in vitro method consisted of two methods detecting the effects of chemicals mainly on protein and lipid in the membrane, which were evaluated by the induction of methemoglobin and hemolysis, respectively. Non- or mild irritants induced neither methemoglobin formation nor hemolysis. Most of moderate or severe irritants induced hemolysis, however, the potentials were low. Strong or corrosive irritants had high potentials for the induction of methemoglobin. The multivariate estimation by the above two in vitro data sets were 77.6% predictive of the in vivo classification.

Animals↗

Irritancy testing in occupational dermatology: comparison between two quick tests and the acute irritation induced by sodium lauryl sulphate.

To reduce the incidence of irritant contact dermatitis, the development of screening methods to identify subjects with increased susceptibility to irritants is essential. In a pilot study on the comparison between two quick, non-invasive irritancy tests (dimethyl sulfoxide (DMSO) and sodium hydroxide (NaOH) with the time-consuming patch testing with sodium lauryl sulphate (SLS), no correlation between the "quick tests" and SLS patch testing was observed. In the present paper the results of irritancy testing in 181 metal worker trainees are presented. Experimental irritant contact dermatitis reactions were induced on the medial third of the volar forearm using SLS 0.5%, applied for 23 h and as "quick tests" DMSO 90% and 95% and a solution of 0.2% mol/l NaOH applied for 5 min. Assessment of skin irritability was made by visual scoring and measurement of transepidermal water loss. Except for a statistically significant relationship between the irritations by DMSO 90% and 95%, correlations between the different techniques were weak or non-existent. This is most probably due to different pathophysiological pathways for the irritant reactions. We therefore propose to use a spectrum of different tests in occupational dermatology for predicting the individual's risk of irritant contact dermatitis.

Adolescent↗

Quantitative assessment of primary skin irritants in vitro in a cytotoxicity model: comparison with in vivo human irritation tests.

BACKGROUND: While great efforts have been made in recent years to develop in vitro methods for assessing skin irritation potential, there are relatively few data that correlate in vitro data with in vivo data. OBJECTIVES: To expand our previously reported investigations on in vitro vs. in vivo correlation of a series of homologous N-alkyl sulphates of different alkyl chain length to include primary skin irritants of different chemical classes. METHODS: Anionic surfactants (three different sodium alkyl sulphonates and sodium lauryl sulphate), cationic surfactants (three alkyl trimethyl ammonium bromides), non-ionic surfactants (polyoxyethylene-20-cetyl ether and Tween 20), benzoic acid, dimethyl sulphoxide and phenol were chosen as model irritants. A spontaneously immortalized human keratinocyte line, HaCaT, was used as an in vitro model to predict the cutaneous irritation. The end-point used to assess toxicity was uptake of the vital dye neutral red (NR) 24 h after dosing. The cytotoxicity data from these assays were compared with the irritant responses (as evaluated by measurement of erythema and transepidermal water loss) obtained after 24-h application of the same compounds (100 microL of 20 mmol L(-1) aqueous solution) to the volar forearm of human volunteers. RESULTS: All tested irritants had cytotoxic effects as demonstrated by a decreased NR uptake, which showed a clear dose-response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC(50)) ranged from 8 micromol L(-1) (hexadecyl trimethyl ammonium bromide) to 328 mmol L(-1) (dimethyl sulphoxide). We found a good overall correlation between in vitro cytotoxicity (NR uptake IC(50) values) and in vivo irritation potential in humans. Only the high molecular weight compounds Tween 20 and polyoxyethylene-20-cethyl ether were problematic, as their irritation potential was overestimated by the in vitro assay. This non-conformity of these high molecular weight (> 1000) compounds was expected, and can be largely attributed to the epidermal permeability barrier. The epidermal barrier, which greatly limits the percutaneous penetration of xenobiotics in vivo, does not exist in cell culture models. CONCLUSIONS: The in vitro cytotoxicity model is a useful screening tool, but data should be interpreted critically and require confirmation by appropriate in vivo studies.

Cell Culture Techniques↗

Utility of MTT assay in three-dimensional cultured human skin model as an alternative for draize skin irritation test: approach using diffusion law of irritant in skin and toxicokinetics-toxicodynamics correlation.

PURPOSE: A cytotoxicity assay using a three-dimensional cultured human skin model, Living Skin Equivalent-high (LSE-high) was evaluated as an alternative to the Draize skin irritation tests using animals. A relation between the cytotoxicity and calculated concentration of an irritant in skin was also evaluated. METHODS: Colorimetric thiazoyl blue (MTT) conversion assay and a surfactant, cetylpyridinium chloride (CPC), were selected as a cytotoxicity assay and a model irritant. The fraction of dead cell number in the MTT assay or the Draize irritation score (in vitro and in vivo irritation data, respectively) was treated as a function of CPC concentration in the viable skin of LSE-high and guinea pig. Separately, in vitro permeations of CPC through the LSE-high or excised guinea pig skin were determined to calculate the average concentration of CPC in the viable skin using the Fickian diffusion theory. The obtained relations between the irritation scores and CPC concentration were evaluated by the Emax model (Hill equation). RESULTS: CPC concentration showing 50% irritation (IC50) was similar for the MTT assay (18.9%) and Draize test (12.3%), and a good relationship (r = 0.981) was observed between the fraction of dead cell number and the Draize score. In contrast, IC50, 1.32%, for the MTT assay in LSE-high was much lower than that using guinea pig skin. We then corrected the results for the MTT assay using a ratio of IC50 in guinea pig skin against LSE-high, resulting in a good relation between both MTT results in guinea pig skin and LSE-high. CONCLUSION: The present results suggest that the MTT assay using LSE-high may be utilized as an alternative for the Draize test in animals for evaluating skin irritation.

Animals↗

Ocular irritation: pathological changes occurring in the rat with surfactants of unknown irritancy.

We believe the development and validation of in vitro alternatives to eliminate the need to use animals in ocular irritation testing must be based on a thorough understanding of the mechanisms of ocular irritation. We have recently undertaken the task of developing such an understanding for a panel of surfactants. The purpose of this study was to expand our current panel of surfactants for which the microscopic changes occurring over time have been characterized. Macroscopic and microscopic findings regarding the ocular irritation of 6 surfactants of relatively unknown irritancy were compared to those of 6 surfactants of known irritancy. The right eye of each rat was treated by placing 10 microliters of a surfactant directly on the cornea. Untreated left eyes served as the controls. At 3 hr and on days 1, 3, and 35, eyes and eyelids were collected for microscopic examination. Collectively, the macroscopic and microscopic findings revealed 3 surfactants to be similar to the mildly irritating surfactants previously studied, and 3 surfactants to be similar to the moderately irritating surfactant previously studied. Information such as this will be important to develop mechanistically based in vitro alternatives to replace the use of animals for ocular irritation testing.

Administration, Topical↗

Is there an irritable bladder in the irritable bowel syndrome?

In this prospective case controlled study 16 premenopausal women with documented irritable bowel syndrome were recruited from the gastroenterology clinic and 16 premenopausal controls without symptoms of irritable bowel syndrome were recruited from the gynaecology clinic. All women answered a standardised bowel and urinary symptom questionnaire and underwent twin channel subtracted cystometry. Women with irritable bowel syndrome also underwent oesophageal balloon distension studies for perception and pain. Oesophageal and bladder sensory thresholds were compared. Urinary frequency and urgency and the urodynamic finding of detrusor instability were significantly more common in women with irritable bowel syndrome (P < 0.05). We were unable to demonstrate a relationship between first sensation of bladder fullness and oesophageal perception or between maximum bladder capacity and oesophageal pain thresholds. These findings suggest that there is an irritable bladder in the irritable bowel syndrome and support the concept that irritable bowel syndrome is part of a generalised disorder of smooth muscle.

Adult↗

The tandem repeated irritation test: a new method to assess prevention of irritant combination damage to the skin.

The effect of a protective cream was tested in a new tandem repeated irritation test with tandem application of 0.5% sodium lauryl sulphate (SLS) and undiluted toluene. The irritants were applied twice daily for 30 min to the ventral forearms of 20 volunteers. Irritant cutaneous reactions were quantified by a visual score, transepidermal water loss, chromametry and skin capacitance. Concurrent application of SLS/toluene induced stronger reactions than those caused by twice daily application of each irritant on its own. A protective effect of the protective cream was obtained against all treatment combinations and was significant for SLS/SLS (p < or = 0.01) and SLS/ toluene (p < or = 0.05). Our results indicate that the tandem repetitive irritation test has great potential in the evaluation of skin care products to prevent irritant contact dermatitis.

Adolescent↗

A psychophysical task to quantify smoking cessation-induced irritability: the reactive irritability scale (RIS).

A psychophysical rating scale using magnitude estimation was developed as a tool to quantify irritability as one index of drug withdrawal. The scale measures reactive irritability by using environmental sounds as probes. Three studies are described in which target and reference stimuli are selected, tested for reliability, and presented to cigarette smokers abstaining from smoking, cigarette smokers who are not abstaining, and nonsmokers. This reactive irritability scale (RIS) was found to have test/re-test reliability and content validity. The RIS significantly differentiated abstaining smokers from nonsmokers and from smokers allowed to smoke, whereas the commonly used self-report measures of irritability failed to distinguish the two groups of smokers. By measuring irritability as a type of reactivity rather than as a static attribute, a different type of irritability is measured than that which is assessed by self-report questionnaires. The RIS should be used in the study of withdrawal from nicotine and other drugs of abuse.

Acoustic Stimulation↗