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At least 37 records · Page 2Linked to original sources
PubMed2004

Intra-individual variation of irritant threshold and relationship to transepidermal water loss measurement of skin irritation.

Irritant susceptibility studies have used either visual assessment or transepidermal water loss (TEWL) to determine subject response. We have developed a visual assessment method which determines subject irritant threshold. We examined the relationship between sodium lauryl sulfate (SLS) irritant threshold and TEWL measurements from normal skin and SLS patch tests. 19 subjects were recruited. The irritant threshold of each subject was measured and TEWL measurements made from the applied SLS patch tests. Individuals with a lower irritant threshold (easily irritated skin) had elevated TEWL levels compared to those with higher thresholds. The irritant threshold test had a low intraindividual variation. This study showed that the 2 methods grouped patients in a similar manner. The variation seen may reflect the different outcomes measured: irritant threshold visually assesses the skin inflammatory response while TEWL measures skin barrier modification.

Adult↗
PubMed2002

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↗
PubMedDate not supplied

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↗
PubMed2006

Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration.

Skin irritants and contact allergens reduce the number of Langerhans cells (LCs). It has been assumed that this reduction is due their migration to the draining lymph node (LN) for initiating immune sensitization in a host. Skin irritation, however, as opposed to contact allergy is not considered to be an immunological disease. Nevertheless, skin irritants are also known for their adjuvant-like effects on contact allergy, resulting in skin hypersensitivity reactions like toxic dermatitis. The human organotypic skin explant culture (hOSEC) model is used to study the characteristics of chemical-induced migration of CD1a(+) LCs out of the epidermis in relation to irritancy or toxicity. We analysed cells emigrating out of hOSEC for CD1a(+) LCs, CD83(+) mature dendritic cells (DCs) and CCR7(+) LN homing cells. After exposure to a toxic concentration of a non-immunogenic irritant, an increase of CD1a(+)CD83(+) LCs was found in the culture medium. A non-toxic concentration of an sensitizer induced an increase of CD1a(+) cells. About 50% of skin emigrating CD1a(+) LCs were CD83(-) (immature) but all were CCR7(+). Skin irritation by both non-allergenic and allergenic compounds induces LC migration and maturation. In contrast, only allergenic compounds induced LC migration with partial maturation at subtoxic concentration. This effectively demonstrates that irritation is physiologically needed stimuli for inducing LC maturation.

Allergens↗
PubMed2006

Anti-irritants I: Dose-response in acute irritation.

The term 'anti-irritant' (AI) was coined in 1965 by Goldemberg to describe a diverse group of topical product ingredients, which were able to reduce the irritation potential of other more irritating ingredients in the same product. 'AIs' are being added to cosmetic formulations in order, allegedly, to benefit tolerability of the products and allow claims such as 'soothing' and 'healing' ingredients. Limited documentation in favour of the efficacy of AIs is published. We studied the dose-related effect of 4 alleged AIs (nifedipine, (-)-alpha-bisabolol, canola oil and glycerol) on experimentally induced acute irritation in healthy volunteers. Each AI was used in 3 concentrations. Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate and 20% nonanoic acid in N-propanol. The irritant reactions were treated twice daily with AI-containing formulations from the time of removal of the patches. Evaluation of skin irritation and efficacy of treatments were performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement and colourimetry. Only glycerol showed dose-response and effects potentially better than no treatment. There was no significant effect and no difference between the three other AIs.

Acute Disease↗
PubMed2006

Anti-irritants II: Efficacy against cumulative irritation.

So-called anti-irritants (AI) are widely used in cosmetic formulations, with the aim of reducing irritation from substances in the formulation. It may also be claimed that they are 'soothing' and 'healing' ingredients. However, the proof for these claims is circumstantial. The dose-response effect of 4 alleged AI (nifedipine, (-)-alpha-bisabolol, canola oil and glycerol) was studied on experimentally induced acute irritation in healthy volunteers, and only glycerol showed dose-related response and effects potentially better than no treatment. The acute irritation model only allowed a small window of opportunity in which to demonstrate efficacy. Therefore, the effect of AI was studied in a cumulative irritation model by inducing irritant dermatitis with 10 min daily exposures for 5+4 days (no irritation on weekend) to 1% sodium lauryl sulfate on the right and 20% nonanoic acid on the left volar forearm. AI ointments were applied twice daily. Clinical scoring was performed daily, evaporimetry (Trans Epidermal Water Loss), hydration and colourimetry were measured at baseline (D0), in the middle and at the end of treatment. The glycerol ointment was the only treatment statistically better than both 'no treatment' and vehicle.

Adult↗
PubMed2005

A shortened psychophysical task to quantify irritability: the Reactive Irritability Scale II (RIS-II).

The Reactive Irritability Scale (RIS) uses magnitude estimation to measure reactive irritability. Respondents rate target sounds in comparison to a neutral reference sound. The RIS proved more sensitive than self-report measures to detect irritability associated with withdrawal from cigarette smoking and with exposure to a stressful environment, but was too long (30 min) for routine use. We report here on a shortened version (13 min)--RIS-II. The RIS-II exhibited robust test-retest reliability and correlated strongly with the original RIS (Study 1). In Study 2, the RIS-II was administered to subjects who experienced psychological stress and then were exposed to progressive relaxation, music, cognitive tasks, or silence; the Progressive Relaxation group was the most irritable. In Study 3, the RIS-II was administered to chronic pain patients. Pain patients found the sounds less irritating than did controls with the exception of the reference sound; repeated presentation of the reference sound increased irritability. These studies indicate that the RIS-II is a reliable instrument that may have utility for the measurement of irritability in laboratory and clinical settings. In addition, these studies indicate that the RIS-II is understandable by individuals of different ages who are from educationally- and culturally-diverse backgrounds and individuals who are healthy as well as individuals suffering from chronic medical conditions who are on multiple medications.

Adolescent↗
PubMed2005

Eye irritation of low-irritant cosmetic formulations: correlation of in vitro results with clinical data and product composition.

Alternative methods to the Draize eye irritation test, such as the hen's egg test-chorioallantoic membrane (HET-CAM) or the bovine corneal opacity and permeability (BCOP) tests, are currently used to evaluate the irritant potential of cosmetic or consumer products. Although, for strong irritants, the results of these tests correlate well with those of the Draize test, they appear to be less suited to identify mild irritants. In order to improve the sensitivity of alternative eye irritation tests, we developed a novel method that uses a human corneal epithelial cell line (CEPI), and the endpoints of cytotoxicity and IL-8 release. Twelve make-up removers were assessed by the HET-CAM, BCOP and CEPI tests, as well as in a clinical in-use test under ophthalmological control after their application to the external eye lid. In addition, we investigated the impact of osmolality and raw material composition on in vitro and clinical results and compared the in vitro results with those of clinical studies. Overall, although HET-CAM results were unrelated to eye discomfort and adverse clinical signs, they correlated mainly with the presence and concentration of surfactants in the test articles. BCOP scores were unrelated to clinical signs, but related mainly to glycol and sodium lactate content and concentration in the test articles. Cytotoxicity in CEPI mainly correlated with presence and concentrations of surfactants, and IL-8 release to clinical signs and/or glycol and sodium lactate concentrations. Overall, IL-8 release appeared to be the most sensitive and reliable endpoint to predict human eye tolerance to mildly irritant products. Although our results suggest that the IL-8 assay appears to be a promising screen for borderline-irritant formulations, further experiments are required to confirm and validate these preliminary results.

Allantois↗
PubMed2006

Irritant contact dermatitis induced by a common household irritant: a noninvasive evaluation of ethnic variability in skin response.

OBJECTIVE: This study was undertaken to investigate the ethnic susceptibility to irritant contact dermatitis induced by a common dishwashing liquid using noninvasive technologies. METHODS: A total of 30 participants (15 Caucasian, 15 African American) were patch tested to graded concentrations of a common household irritant and evaluated using clinical scoring, reflectance confocal microscopy, transepidermal water loss, and fluorescence excitation spectroscopy. RESULTS: At 24 hours, the concentration thresholds for clinically perceptible irritancy were significantly higher for African American compared with Caucasian participants. Reflectance confocal microscopy showed stratum corneum disruption, parakeratosis, and spongiosis; these features were more severe in Caucasian participants (P < or = .002). Mean values for transepidermal water loss were significantly higher in the Caucasian group at comparable clinical scores (P < or = .005). Fluorescence excitation spectroscopy showed a broad excitation band at 300 nm (emission 340 nm) and values in both groups returned to baseline by day 7. LIMITATIONS: This pilot study was limited in scope and larger studies are needed to further evaluate ethnic differences in irritant contact dermatitis and to demonstrate the applicability of our findings for other irritants. CONCLUSION: Clinical evaluation, reflectance confocal microscopy, and transepidermal water loss showed significant differences in the cutaneous irritant response between both groups suggesting a superior barrier function of African American skin. Fluorescence excitation spectroscopy on the other hand demonstrated no differences in the hyperproliferative response after irritant exposure and indicated similar kinetics for the two groups.

Adolescent↗
PubMed2003

Patch testing with the irritant sodium lauryl sulfate (SLS) is useful in interpreting weak reactions to contact allergens as allergic or irritant.

Several contact allergens are tested at concentrations which might cause irritant reactions. In this study we investigated whether the reactivity to a standard irritant is useful in identifying subjects with hyperreactive skin yielding a higher rate of doubtful or irritant reactions. Sodium lauryl sulfate (SLS) 0.5% (aqua) was tested in addition to the standard series routinely for 5 years in the Department of Dermatology, Dortmund. For data analysis, we compared reactions at D3 to the standard series, the vehicle/emulsifier and preservative series and benzoyl peroxide to the reactions obtained with SLS. Proportions were standardized for age and sex. The association between reactivity to a certain allergen and SLS reactivity as a dichotomous outcome, controlled for age and sex as potential confounders, was assessed with logistic regression analysis. Results showed that of the 1600 tested patients, 668 (41.8%) had an irritant reaction to SLS which exceeded 2 + in only 41 patients. Seasonal variation was statistically significant, showing reduced SLS reactivity in summer vs. winter. Patients with irritant reactions to SLS showed significantly more erythematous reactions to the following 10 allergens of the standard series: fragrance mix, cobalt chloride, balsam of Peru (Myroxylon pereirae), lanolin alcohol, 4-phenylenediamine base (PPD), propolis, formaldehyde, N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), benzocaine, and 4-tert-butylphenol-formaldehyde resin. No significant differences regarding strong positive allergic reactions were observed. Concerning other allergens, significantly more erythematous reactions were observed in SLS-reactive patients to benzoyl peroxide, octyl gallate, cocamidopropyl betaine, Amerchol L-101, tert-butylhydroquinone, and triethanolamine. In the SLS-reactive group of patients, the reaction index was negative for 10 allergens of the standard series compared to only 5 in the SLS non-responder group. For the first time, this study, based on a large data pool, revealed a significant association between reactivity to the irritant SLS and erythematous reactions to certain allergens. With SLS as a marker for hyperreactive skin at hand, some of these reactions can now be classified as irritant more confidently, particularly if there is no history of exposure to the allergen.

Allergens↗
PubMed2006

Irritants in combination with a synergistic or additive effect on the skin response: an overview of tandem irritation studies.

Sodium lauryl sulfate (SLS) has often been chosen as a model for irritant contact dermatitis (ICD) to study the effect of irritants in combination (1-14). Recently 'tandem', or sequential, exposures with SLS have been performed to study the mechanism of skin barrier impairment in ICD (1-6, 15). The assessment of reactions have been documented with visual scoring, transepidermal water loss (TEWL), skin colour reflectance measurements, skin blood flow; among which TEWL has been noted as the most sensitive value (16). The matched control groups were treated with either a single exposure to a single irritant or in tandem with the same irritant repeatedly. Synergistic and additive effects have been reported for various tandem pairs of irritants, however, the mechanism for both remains unclear. The results of tandem irritation studies were evaluated to define and investigate the responses produced and deduce a possible mechanism of action. Clinical ramifications, albeit complex, are discussed.

Air Movements↗
PubMed1997

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↗
PubMed2002

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↗
PubMed2004

On the course of the irritant reaction after irritation with sodium lauryl sulphate.

BACKGROUND: The sodium lauryl sulphate (SLS) irritation test is a well-established model for irritant contact dermatitis after the effects of surfactants. AIM OF THE STUDY: The course of changes in corneometric measurements (stratum corneum hydration), in transepidermal water loss (TEWL), in laser Doppler measurements (epidermal perfusion) and in colorimetric measurements (skin redness), after a single SLS irritation, should be studied over time. METHODS: Twenty healthy volunteers were studied. Irritation with 1% SLS solution was applied to the side of one forearm for 24 h under occlusive conditions, while the symmetrical experimental site remained untreated. Measurements were made for 9 days after completion of SLS irritation. RESULTS: Stratum corneum hydration was reduced immediately after irritation, and subsequently a hyper-hydration was observed. The increase in TEWL, laser Doppler measurements and skin redness persisted for 7-9 days. With regard to skin redness, a mild blanching effect was noticeable after 9 days. DISCUSSION: The evidence of very short-term exsiccation of the stratum corneum with persistent barrier damage, as well as reactive hyper-hydration and blanching of the skin, is remarkable. These first findings suggest that exsiccation of the stratum corneum is not caused by a damage to barrier lipids.

Adult↗
PubMedDate not supplied

Additive impairment of the barrier function and irritation by biogenic amines and sodium lauryl sulphate: a controlled in vivo tandem irritation study.

Biogenic amines are potential irritants e.g. in fish-, meat-, milk- and egg-processing professions like cooks, butchers and bakers. The aim of this study was to test the irritative and barrier-disrupting properties of the biogenic amines ammonium hydroxide (AM), dimethylamine (DMA) and trimethylamine (TMA). A repeated sequential irritation of 30 min twice per day was performed over a total of 4 days (tandem repeated irritation test) on the back of 20 healthy volunteers of both sexes with AM, DMA, TMA and sodium lauryl sulphate (SLS). The epidermal barrier function was assessed with a Tewameter TM 210, stratum corneum surface pH was measured with a Skin-pH-Meter 900, inflammation was assessed with a Chromameter CR-300 on the a* axis for redness and a visual score was recorded. All tested biogenic amines (AM, DMA and TMA) induced a barrier disruption and a pH increase paralleled with a 1-day-delayed onset of inflammatory signs. These effects were further enhanced and accelerated by a sequential application of SLS together with the biogenic amines, and inflammation occurred earlier than with the single compounds. Acetic acid (AA) in contrast did only show mild barrier disruption and no significant inflammatory signs. Our system allowed a ranking of the different compounds in their irritative potential in the tandem irritation with SLS: SLS > NaOH > TMA > AA > AM > DMA. The results are suggestive that in the food-processing industry the simultaneous contact with biogenic amines and harmful detergents like SLS should be minimized.

Administration, Cutaneous↗
PubMedDate not supplied

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↗
PubMed2006

Adenosine sensory transduction pathways contribute to activation of the sensory irritation response to inspired irritant vapors.

The molecular mechanisms through which sensory irritants stimulate nasal trigeminal nerves are poorly understood. The current study was aimed at evaluating the potential contribution of purinergic sensory transduction pathways in this process. Aerosols of 4-36 mM adenosine 5'-triphosphate (ATP) and adenosine both acted as sensory irritants. Large dose capsaicin pretreatment to induce degeneration of transient receptor potential vanilloid type-1 (TRPV1)-expressing C fibers greatly reduced, but did not abolish, the sensory irritation response to ATP aerosol and was without effect on the response to adenosine aerosol, indicating that ATP acts largely on capsaicin-sensitive (primarily C fibers) and adenosine acts on capsaicin-insensitive (primarily Adelta fibers) nerves. The response to adenosine was diminished by pretreatment with the broad-based adenosine receptor antagonist theophylline (20 mg/kg) and A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 mg/kg), providing evidence that adenosine stimulates capsaicin-insensitive nerves via the A1 receptor. The sensory irritation responses to 275 ppm styrene and 110 ppm acetic acid vapors were significantly reduced by theophylline pretreatment suggesting a role for adenosine signaling pathways in activation of the sensory irritant response by these vapors. If sensory nerves are activated by mediators that are released from injured airway mucosal cells, then nasal sensory nerve activation may be a reflection of irritant-induced alterations in airway cell integrity.

Adenosine↗
PubMed1995

Assessment of skin irritancy by 2 short tests compared to acute irritation induced by sodium lauryl sulfate.

Irritant contact dermatitis is a very common disease that is preventable by protective measures. The development of screening methods to identify subjects with increased susceptibility to irritants is essential to reduce the incidence of this disorder in the workplace. On the outlook for such methods, 2 quick non-invasive tests for irritability of the skin were compared to reliable, but time-consuming, patch testing with sodium lauryl sulfate (SLS). In 20 healthy volunteers, 0.5% SLS was applied on the medial 1.3 of the forearm for 23 h in order to induce experimental irritant contact dermatitis. On the same part of the forearm, 3 concentrations of dimethylsulfoxide (DMSO) and a solution of 0.2 mol/l NaOH were applied for 5 min. Assessment of skin irritability was made by visual scoring and measurement of transepidermal water loss. No correlation between the "quick tests" and SLS patch testing was found, indicating that these tests assess different mechanisms of irritation.

Acute Disease↗