The MOAHLFA index of irritant sodium lauryl sulfate reactions: first results of a multicentre study on routine sodium lauryl sulfate patch testing

In a multicentre study of the German Contact Dermatitis Research Group, sodium lauryl sulfate (SLS) 0.25% and 0.5% aq. has been added to routine allergen patch tests to assess its properties as a convenient diagnostic indicator of individual susceptibility to irritation at the time of patch testing. Previous studies indicated that irritant SLS reactivity may be related to individual factors such as age and sex. As these factors are, in turn, among the important predictors of contact allergy to many allergens, e.g. summarized in the 'MOAHLFA index', the impact of the MOAHLFA factors on irritant SLS patch test reactivity, and thus a potential for confounding, was assessed in the 5971 participating patients. As a result of 2 logistic regression analyses with an irritant reaction to 0.25% and 0.5% SLS, respectively, as outcome, male sex was identified as a relatively weak but significant risk factor (OR 1.38), while age 40 years or older was an even weaker risk factor (OR 1.22 and 1.15, respectively). Upon detailed analysis, no clear age gradient could, however, be identified. 1-day exposure time almost halved the odds of an irritant SLS reaction. In conclusion, this type of SLS patch test can be regarded as robust, indicating individual irritability relatively independent from the individual factors analysed here.     

Sodium lauryl sulfate irritant patch tests: Degree of inflammation at various times

Irritant reactions were induced on the forearms of 10 normal subjects with 10% aqueous sodium lauryl sulfate under patch test occlusion for 24 h. Test sites were observed at 24, 26, 28, 30, 48, 72 and 96 h and the degree of inflammation recorded. Inflammation was most prominent at 28 h and decreased in intensity over the time course of the study. Inflammation at 48 and 72 h was similar to when patches were removed. This suggests that inflammatory responses in skin for at least certain irritants like sodium lauryl sulfate do slowly decrease in intensity after 48 h. However, the inflammatory response may initially accelerate after patch test removal and remain intense for at least 48 h. Fading of irritant reactions by 48 or 72 h may not reliably distinguish irritant from allergic patch test reactions. This does not refute the usefulness of a delayed (96 h) reading since inflammation from sodium lauryl sulfate had decreased significantly by this time.     

Sodium lauryl sulfate effect on the density of epidermal Langerhans cells.

The effect of different test models for sodium lauryl sulfate (SLS)-induced irritant contact dermatitis on epidermal Langerhans cells (LC) numbers was examined. Finn Chambers, 8 and 12 mm, containing 15 and 34 or 50 μl, respectively. of l% aq. solution of SLS were applied to human forearm skin for 48h as single or repeated application. The results showed a clear difference between the effects with the 2 chamber Sizes. The effect of the 8-mm chambers could result in increased, unchanged or decreased LC numbers, while 12-mm chambers always produced a decrease. These results seem to explain, at least partly, the discrepant results reported from various laboratories.     

Post-application occlusion substantially increases the irritant response of the skin to repeated short-term sodium lauryl sulfate (SLS) exposure

Occlusion often, but not always, enhances percutaneous absorption and thus may facilitate skin irritation. Quantitative data about the impact occlusivity may have on minimal irritant stimuli to which the skin is exposed in daily life, and which may lead to chronic irritant contact dermatitis, are however lacking. Irritant stimuli were administered by repeated application of sodium lauryl sulfate (SLS) in an open application procedure. After the open exposure, the skin was either left open or occluded with plastic. Skin irritancy was assessed by means of visual grading and by transepidermal water loss (TEWL) measurements. Post-exposure occlusive treatment markedly enhanced the irritant response. 5 consecutive daily applications produced more irritation, with or without occlusion, than alternate day application. Occlusion may be a relevant factor in the development of irritant contact dermatitis from certain chemicals.     

The sodium lauryl sulfate model: an overview

Irritant contact dermatitis is a complex entity with several clinical forms (acute, cumulative, etc.) and multiple mechanisms. Sodium lauryl sulfate (SLS), the most widely utilized model for studying acute and cumulative irritation, has proved highly practical and informative for such studies. This article summarizes several decade of investigation, and provides details of dosing, application method (closed versus open), and biologic endpoints (visual grading, transpidermal water loss) that may be utilized in future studies.     

Benzalkonium chloride neutralizes the irritant effect of sodium dodecyl sulfate

When benzalkonium chloride (BKC), a cationic surfactant, is added to sodium dodecyl sulfate (SDS), an anionic surfactant, and used in patch testing, on the basis of their known physicochemical interaction, it is possible to predict that there will be a tendency towards a reduction in the expected irritant response when compared to SDS alone. The aim of this study was to investigate whether BKC could reduce the irritant response to SDS when applied after the SDS exposure. 54 non-atopic adult volunteers were recruited for the study. 20% SDS was applied for 2 h under occlusion. 1% BKC was then applied to the same site. Various controls, including SDS application followed by water for 2 h, were included. The irritant reaction was assessed at 24 h and 48 h. 40 of the 54 subjects had some reaction when SDS was applied for 2 h followed by either benzalkonium chloride or water control under occlusion. In comparison to water control, where BKC was applied after SDS, 20 of the 40 responders had a weaker reaction but only 4 had a stronger response. This study shows that BKC applied to skin exposed to SDS attenuates the resulting irritant reaction.     

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.     

Acute irritant reactivity to sodium lauryl sulfate in atopics and non-atopics

Predictive testing of chemicals to assess their acute skin irritation potential is an important part of the assessment of their toxicological profile. It is possible, where safety and ethical considerations can be met, to do this work in groups of human volunteers. Previously, the relative responsiveness of atopics and non-atopics has been evaluated. The results showed that atopics (defined broadly by high IgE reactivity) were a little more susceptible to skin irritation, but not significantly so. In the present work, the relative reactivity of a skin atopic group versus a non-atopic group was examined in more detail. Sodium lauryl sulfate (SLS) was applied at a range of concentrations and exposure times, such that a fairly constant degree of skin irritation was produced. At various time points, the irritation response was measured by visual assessment, chromametry, laser Doppler flowmetry and transepidermal water loss. Using all of the methods of assessment, the reactions in atopics were similar to or a little less than those seen in non-atopics. The conclusion is that atopics and non-atopics will give similar results in a predictive human test for acute skin irritation. Furthermore, the pattern of response obtained from short duration exposure should be predictive of that following longer durations of (single) exposure.     

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 i. preventable by protective measures The development of screening methods to identify subject with increased susceptibility in irritants is essential in 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/1 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 tests assess different mechanisms of irritation.     

The association between ambient air conditions (temperature and absolute humidity), irritant sodium lauryl sulfate patch test reactions and patch test reactivity to standard allergens

To support the decision as to whether erythematous patch test reactions to allergens are irritant or allergic, sodium lauryl sulfate (SLS, 0.5% in water) has been added to the standard patch tests since July 1996 in the Dortmund Department of Dermatology. Data on 1600 patients patch tested up until June 2001, as well as standardized data on ambient temperature and humidity obtained by the German Meteorological Service, were included in a logistic regression analysis taking age, sex and atopy as potential confounders into account. The pattern of association was heterogeneous: while doubtful reactions to nickel sulfate were significantly associated with dry/cold weather conditions, but not with SLS reactivity, the opposite was observed for lanolin alcohol, benzocaine and Myroxylon pereirae resin (balsam of Peru). Doubtful reactions to other allergens, namely formaldehyde, fragrance mix or p-phenylenediamine, were associated with both factors. For several other allergens of the standard series, no distinct, significant pattern could be discerned. In conclusion, meteorological conditions and SLS reactivity independently contribute information on individual irritability at the time of patch testing, and both should be considered.     

A stronger patch test elicitation reaction to the allergen hydroxycitronellal plus the irritant sodium lauryl sulfate

Household and cleaning products often contain both allergens and irritants. The aim of this double-blinded, randomized, paired study was to determine whether patch testing with an allergen (hydroxycitronellal) combined with an irritant [sodium lauryl sulfate (SLS)] cause a stronger patch test elicitation reaction than patch testing with the allergen (hydroxycitronellal) alone, in patients previously patch tested positive to hydroxycitronellal. A stronger patch test elicitation reaction was defined as at least 1 day of patch test reading showing more positive patch tests (+, ++ or +++) on the forearm patch tested with 6 concentrations of SLS plus hydroxycitronellal than on the forearm tested with 6 concentrations of hydroxycitronellal alone and no day of patch test readings showing more positive tests on the hydroxycitronellal forearm. 15/20 (75%) had at least 1 day of patch test reading with more positive patch tests on the forearm patch tested with SLS plus hydroxycitronellal and no day of patch test readings with more positive patch tests on the forearm tested with hydroxycitronellal (P = 0.0253). Estimation of the blood flow with laser Doppler supported these findings.     

Sodium lauryl sulfate (SLS) induced irritant contact dermatitis: a correlation study between ceramides and in vivo parameters of irritation

Sodium lauryl sulfate (SLS), a surfactant frequently used in the induction of experimental irritant contact dermatitis in animals and in humans, characterstically induces a dose-related increase in TEWL (transepidermal water loss). Ceramides are considered to be important in the regulation of the skin barrier. We therefore examined the relationship between initial ceramide content of stratum corneum and induced changes in skin color (erythema) and barrier function, after SLS application under occlusion (1% and 3% in water) to the forearm of 14 volunteers. Stratum corneum sheets were removed, stratum corneum lipids extracted, and ceramide composition determined from chromatograms (TLC) using densitometry. After determining baseline skin color and TEWL at each area. 2 samples of stratum corneum were obtained from each volunteer. Clinical and instrumental controls of the SLS-induced irritation were performed at 24, 48, 72 and 96 h. Erythema was evaluated by colorimetry; barrier impairment by changes in TEWL. We found inverse correlations between baseline ceramide 61 (weight) and the 24 h erythema score for SLS: between ceramide I and 24 h TEWL, and between ceramide 611 and 72 h TEWL for SLS 3%. Our findings suggest that low levels of these ceramides may determine a proclivity to SLS-induced irritant contact dermatitis.     

Open application assay in investigation of subclinical irritant dermatitis induced by sodium lauryl sulfate (SLS) in man: advantage of squamometry

Background/aims: After a single occlusive application (24 h patch test), SLS can cause irritation, dryness, and tightness. In typical use, clinical surfactant exposure is usually brief, of open application, and cumulative. The open application model becomes relevant when phenomena, such as dryness and subclinical, i.e., non-visible, irritation are induced. Methods: Exaggerated hand wash was performed in a total of 21 healthy individuals. Signs of skin irritation were scored, and skin reactions were measured using various bioengineering techniques. Results: These studies demonstrate that an exaggerated hand wash model permits exploration of sub-clinical irritation. Conclusions: Squamometry proved to be a sensitive, complementary method to detect surfactant-induced, sub-clinical skin alterations.     

Effect of surfactant mixtures on irritant contact dermatitis potential in man: sodium lauroyl glutamate and sodium lauryl sulphate

Our purpose was to ascertain the irritant contact dermatitis potential of sodium lauroyl glutamate (SLG) and to assess its possible anti-irritating potential in a surfactant mixture on human skin, using visual scores and measurement of transepidermal water loss (TEWL). 15 healthy adult volunteers free of skin disease and with no history of atopic dermatitis were treated with sodium lauryl sulphate (SLS) solution (1%, 0.75%, 0,50%, 0.25%), 1% SLG solution, and 1% surfactant mixture solutions, Ml (75/25), M2 (50/50), M3 (25/50) (SLG/SLS). We applied 100μl of solution using a polypropylene chamber for 24 h. Application sites for each solution were randomized to minimize anatomical bias. We measured baseline TEWL before test solution application. After removal of the patches, each site was visually graded and TEWL recorded with an evaporimeter daily for 4 days. The visual scores and TEWL values of 1% SLG solutions were lower than those of the other test solutions, except the vehicle control (deionized water). 1% surfactant mixture solutions showed lower visual scores and TEWL values than 1% SLS solution. Increase of SLG concentration decreased the visual scores and TEWL values. Comparing the visual scores and TEWL values of Ml and 0.25% SLS solution, M2 and 0.50% SLS solution, and M3 and 0.75% SLS solution. Ml, M2, and M3 showed lower values, although not statistically different. These findings suggest that SLG is a mild surfactant and its utilization can decrease irritation potential in SLS and possibly other mixtures. This model may offer a facile system for screening the surfactant and other mixtures for decreased irritancy potential.     

Profile of irritant patch testing with detergents: sodium lauryl sulfate,sodium laureth sulfate and alkyl polyglucoside

The cutaneous reaction to detergents follows distinct kinetic rules: the duration of application and the irritant concentration are of major importance. The aim of this study was to evaluate the differences in kinetics of skin reaction between the standard irritant sodium lauryl sulfate (SLS), and 2 modern detergents: sodium laureth sulfate (SLES) and alkyl polyglucoside (APG). We performed patch testing with SLS and SLES (or APG) at different concentrations (0.125, 0.25, 0.5, 1.0 and 2.0%) and with different exposure times (6, 12 and 24 h). Evaluation was conducted by measurement of transepidermal water loss (TEWL) and laser Doppler flowmetry (LD) 24 h, 7 and 10 days after patch removal. We found a pronounced reaction to SLS, and a far milder one to SLES. Even at the highest concentration the skin reaction to APG was hard to detect. During the regeneration period (day 3-10) SLS showed even at day 10 an increased TEWL at all concentrations tested. The irritation due to SLES was convincingly detectable only up to day 7, whereas the APG-tested skin areas showed no significant reaction even at day 3. These results demonstrate the improvement in reduction of skin irritation achieved by development of novel detergents.     

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.