Influence of a detergent on skin response to methyldibromo glutaronitrile in sensitized individuals

The present study was undertaken to evaluate the combined effect of the preservative methyldibromo glutaronitrile (MDBGN) and sodium lauryl sulfate (SLS) on the elicitation response of allergic contact dermatitis. 20 volunteers with contact allergy to MDBGN were patch tested with 5 concentrations (10, 50, 100, 500 and 1000 p.p.m.) of MDBGN alone and in combination with 0.25% SLS on the upper arms for 24 h. Skin reactions were evaluated by clinical scoring, and data were evaluated by logistic dose-response models. Additionally, evaluation of skin reactions was performed by measurement of transepidermal water loss (TEWL) and skin colour. Measurements were obtained at baseline and at D3 and D7. As evaluated by clinical assessment, allergic reactions to MDBGN were elicited at lower concentrations when applied in combination with SLS than when applied alone. The response was augmented by a factor of 6.4. An increased response to combined exposure to SLS and MDBGN as compared with MDBGN alone was confirmed by TEWL and colour measurements. Effects of exposure time and concentration of the detergent are discussed. In conclusion, an augmented response was found after concurrent application of MDBGN and SLS. The response was augmented by a factor of 6.4, with confidence limits of 2.8-14.6 (P < 0.0001). This result is important in relation to the determination of threshold values and the risk assessment of contact allergens in consumer and industrial products, where allergens are often present in combination with surfactants.     

Comparison of human back versus arm skin region for its suitability to test weak irritants

Background/aims: Large-scale comparative screening of der-matological and cosmetic products require non-invasive bioengineering methods which give reproducible results that can be statistically analyzed. To determine the most suitable test region for testing irritating substances, the response of the skin to the weak irritant sodium lauryl sulphate (SLS) was measured on standardized locations on the forearm and back. Furthermore, using 3 bioengineering methods, we aimed to establish the most sensitive method to measure skin response to SLS.
Methods: The baseline measurements of transepidermal water loss (TEWL), cutaneous blood flow (CBF) and skin colour a*-value were performed at 6 standardized locations on the volar forearms and at 12 locations on the back on 2 consecutive days, day 1 and 2, in 9 healthy volunteers. On day 2, 9 out of the 18 sites were exposed to 0.5% SLS by occlusive 24-h patches and the skin response was evaluated on days 3 and 4.
Results: For TEWL, CBF and a*-value, no significant regional variations were found within individuals at any time on the arm locations and on the back locations. However, significant inter-individual variation was found. At the back on day 4, a slightly higher skin response to SLS was found compared to that found on the forearms as measured by TEWL and the a*-value. Of the 3 bioengineering methods used, TEWL was the most sensitive method to detect cutaneous response to the weak irritant used. TEWL measurements on days 1 and 2 performed at the 6 standardized locations on the volar forearms inside and outside a specially constructed air convection protection box, showed no relevant differences in measured TEWL values.
Conclusion: Both the forearms and the back were found to be suitable sites for irritancy testing. Since considerable differences in mean reactivity between subjects have been observed the use of large numbers of subjects in predictive irritant patch testing is required.     

Combined effects of irritants and allergens. Synergistic effects of nickel and sodium lauryl sulfate in nickel- sensitized individuals

Knowledge of the combined effects of irritants and allergens is of interest with respect to accurate risk assessment. The threshold for elicitation of allergic contact dermatitis in previously sensitized individuals may theoretically be markedly influenced by the simultaneous presence of irritants and allergens. Combined exposures have, however, only been studied infrequently. In the present study, the combined effect of an irritant and an allergen was evaluated in a dose-response designed experimental study. 20 nickel-sensitized subjects were exposed to patch testing with varying concentrations of NiCl2 (nickel chloride) and sodium lauryl sulfate (SLS) alone and in combination. Evaluation of skin reactions was performed by colorimetry, measurement of transepidermal water loss and clinical evaluation, and the data were analyzed by logistic dose-response models. A synergistic effect was found of combined exposure to NiCl2 and SLS, as compared to each of the substances applied separately, as evaluated by colorimetry and clinical scoring. This means that the effect produced by the combined exposure was substantially greater than the effect produced by either of the substances alone. A synergistic effect of combined exposure on skin barrier impairment was not found, since the barrier function is significantly influenced by SLS-exposure only and not by NiCl2. Concentration limits are used by industry and government agencies to protect consumers. The present results clearly illustrate that elicitation thresholds and concentration limits may be influenced considerably by combined exposure to allergens and irritants.     

Water protective effect of barrier creams and moisturizing creams: a new in vivo test method

Frequent exposure to water is an important risk factor for the development of irritant hand eczema. Evaluation of cream efficacy in protecting against water is difficult. A new non-irritant, non-invasive method is introduced, based on evaluation of colour intensities when an aqueous solution of crystal violet is applied to the skin, after pretreatment with different creams. By skin reflectance measurement, differences in colour intensity were objectified. Measurements of transepidermal water loss were also performed. 2 barrier creams and a moisturizer were tested on the dorsal and volar aspects of the handy One barrier cream contained silicone the other solid particles. The moisturizer had a high content of lipid. In one experiment, the immediate effect of the cream in protecting against water was evaluated. In a second experiment, the water resistancy of the creams was tested, using a standard water immersion procedure (4X20 min). The barrier cream with particles gave the best immediate protection (dorsal 76% volar 69%). The moisturizer was intermediately protective (dorsal 57% volar 34%) while very link protection was found for the silicone-containing cream (dorsal 16% volar 10%). The water immersion procedure resulted in only minor changes in protection for each cream. When comparing transepidermal water loss in the treated areas with pretreatment values, a reduction was recorded only for the particle-containing barrier cream. The colour method described may be used as a quick and easy test of the protective effect of creams against water.     

Evaluation of a non-invasive human and an in vitro cytotoxicity method as alternatives to the skin irritation test on rabbits

5 substances were investigated for their primary irritant effect by means of different protocols. The cutaneous blood flow values (CBFV) were measured in humans: in a 1st series of experiments 12 h after application of the pure substances for 48 h and in a 2nd series of experiments 1, 24, 48 and 72 h after application of the 10% diluted substances (subclinical concentration) for 3 h. Rabbit skin erythema scores were obtained 1, 24, 48 and 72 h after application of the undiluted substances for 4 h. The uridine uptake inhibition assay on KB cells was included as a cytotoxicity test. Results obtained for both protocols on humans are compared with each other and with the test data obtained on rabbits, and with the cytotoxicity data. Application of the undiluted substances for 48 h on human skin or for only 3 h at a 10% dilution resulted in the same ranking between the substances. The CBFV in the human correlated very well (r = 0.99) with erythema scores obtained on rabbits. A poor correlation was observed between the in vitro and the in vivo results. From this study, it can be concluded that CBFV measurement is a valid method for the detection of erythema at subclinical concentrations.     

Comparison between 2 test models in evaluating the effect of a moisturizer on irritated human skin

The purpose of the present study was to compare 2 experimental models of moisturizer efficacy on the recovery of irritated skin on the hands and the volar forearms. 12 healthy volunteers had their hands immersed in sodium lauryl sulfate (SLS) 10 min 2x daily for 2 days, and at the same time the volunteers had patch tests with SLS (0.125%, 0.25% and 0.5%) applied on their forearms for 24 h. After irritation of the skin, the volunteers had a moisturizer applied on one arm/hand 3x daily for the following 9 days. The other arm/hand served as untreated control. Evaluation was done on days (D) 1, 3, 5, 8 and 12 by transepidermal water loss, electrical capacitance, laser Doppler flowmetry and DermaSpectrometry. Both models were found useful, and the moisturizer was found to accelerate regeneration of the skin barrier function in both the hands (D8, p<0.05) and the volar forearms (0.5% SLS, D5 and D8, p<0.01). When the forearm model is used in the present set-up, a relatively high concentration of SLS (>0.25%) should be used and evaluation measurements are best performed on D5-D8. The forearm model proved reliable and easy to handle and we suggest that this model is used in future studies on moisturizer evaluation.     

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 × during the 1st week and 4 × 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 asses 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.     

Contact vitiligo following a strong patch test reaction to triglycidyl-p-aminophenol in an aircraft industry worker: case report and review of the literature

Epoxy resin systems (ERSs) are a frequent cause of occupational allergic contact dermatitis. A 50-year-old patient developed eczematous skin lesions on the back of his hands, lower arms and eye lids, 2 months after he had started working in aircraft construction. Patch tests showed positive reactions at day 3 to nickel sulfate, epoxy resin based on diglycidyl ether of bisphenol F (DGEBF) and 1,4-butanediol diglycidyl ether (1,4-BDDGE). The chemical triglycidyl-p-aminophenol (TGPAP) applied at 1% and 0.1% induced the strongest (+++ positive) reaction. About 4 months after the patch test with TGPAP, the patient presented with 2 circular depigmented spots in the former TGPAP-patch test areas. Dermatohistopathology confirmed the diagnosis of contact vitiligo.     

Efficacies of a barrier cream and an afterwork emollient cream against cutting fluid dermatitis in metalworkers: a prospective study

We compared the point prevalence of cutting fluid dermatitis and transepidermal water vapour loss (TEWL) changes in groups of new machinists who (a) used a barrier cream; (b) used an afterwork emollient cream; and (c) did not use any cream (controls) over a 6-month period. All machinists handled cutting fluid (neat mineral oil) during their work. There was no significant difference in the prevalence of cutting fluid dermatitis in the 3 groups throughout the study period. The prevalence of cutting fluid dermatitis in all groups increased rapidly during the first 6 weeks and thereafter remained steady throughout the remainder of the study period. The prevalence of cutting fluid dermatitis was slightly lower in machinists using afterwork emollient cream compared to those using barrier cream and controls (not significant). The differences in the mean TEWL changes during the study period among the 3 groups were also not statistically significant. The mean TEWL values in the 3 groups increased rapidly during the first 6 weeks of exposure to cutting fluids and thereafter remained fairly constant throughout the remainder of the study period. Barrier cream and afterwork emollient cream did not appear to have any significant effect against either cutting fluid dermatitis or TEWL changes in machinists exposed to cutting fluid. However, afterwork emollient cream appeared clinically to help reduce the prevalence of cutting fluid irritation.     

Pretreatment of the test area with 1-day occlusion improves the response rate to NiSO4 5% pet. Patch tests in subjects with a positive history of nickel allergy

A group of 58 women, aged 18 to 51 years, with a clinical history of nickel allergy, who exhibited equivocal or negative reactions to nickel sulfate 5% pet, patch tests performed on the skin of the back, were recruited consecutively from the patch test clinic from September 1993 to June 19944. In order to improve the response rate to NiSO₄ 5% pet, patch tests, a testing procedure utilizing pretreatment of the test area by 1-day (24-h) occlusion was introduced. Patients underwent 2 patch tests on adjacent sites of the volar surface of both forearms. 3 of the patch tests were performed with 40 mg nickel sulfate 5% pet., whereas a control test was carried out by occluding with an empty chamber. 2 of the nickel sulfate test sites were pretreated with 1-day occlusion performed with an empty chamber. A visual grading system and echographic measurement were used to quantify the responses 30–40 min after patch test removal. Echographic evaluations were carried out using a 20 MHz B-scanner. Measurement of skin thickness and determination of the hypoechogenic dermal area, both considered to be parameters of inflammation, were used to evaluate the intensity of the allergic reaction. At the 3-day (72-h) evaluation. 19 subjects out of 58 clearly showed positive reactions to nickel sulfate 5% pet, at pre-occluded skin sites. Moreover, values of skin thickness and of 0–30 areas at positive pre-occluded nickel test areas were higher in respect to control test areas, confirming clinical evidence of increased response to NiSO₄, after occlusion.