Cutting oil dermatitis on guinea pig skin

We assessed the effect of repeated application of cutting oil on 9 guinea pigs' skin by visual scoring and skin water vapour loss measurement. The visual scores (severity score) were significantly higher on skin treated with cutting oil (positive control) compared to untreated skin (negative control). The corresponding mean SVL values were also significantly higher. We also assessed the effect of 2 barrier creams on the 9 guinea pigs' skin treated with cutting oil. The visual scores on skin treated with either barrier cream were significantly higher than positive control skin. The corresponding mean SVL values on skin treated with either barrier cream were also higher (not statistically significant). It appeared that the 2 barrier creams did not confer protection against the irritant effect of the cutting oil. On the contrary, barrier creams appeared to exacerbate the irritant effect of cutting oil.     

Efficacy of skin barrier creams

An animal model for the evaluation of skin protective creams against chemical irritants is described. The irritants were applied daily for 2 weeks to shaved back skin of young guinea pigs: sodium tauryl sulphate (5% aq.: 30 min), sodium hydroxide (0,5% aq.; 2 min). and toluene (20'i. eth.; 2 mint. "The harrier cream was applied 2 h prior to and immediately after exposure to the irritant. Control animals were treated with the irritant only. The irritant reaction was scored on a 4–point scale for erythema and quantified with regard to transepidennal water loss (TEWL) by evaporime-try and skin blood flow volume (BFV) by laser Doppler velocimetry. A total of 90 guinea pigs, consisting of" individual panels of 5 to 10 animals, was tested. While one barrier cream (Slokoderm) significantly suppressed the irritation due 10 sodium lauryl sulphate and toluene, the other (Contra-Alkalh failed to do so and even aggravated the response, which was particularly evident with sodium hydroxide. This model may be useful in developing more effective barrier creams.     

Effect of mineral oil and linoleic-acid-containing emulsions on the skin vapour loss of sodium-lauryl-sulphate-induced irritant skin reactions

This study evaluates the influence of mineral oil and linoleic-acid-containing emulsions on the skin vapour loss (SVL) of detergent-induced irritant skin reactions. During a period of 2 weeks, 2 x 45 min applications of a sodium lauryl sulphate solution of low molarity were performed on the forearm of 9 volunteers. In the same period, a standard amount of each emulsion was applied on the induced irritant skin reactions, 3 times each day. The effect of the emulsions on the barrier function of the skin was evaluated by means of SVL measurements. The emulsion based on mineral greases significantly reduced SVL values during both weeks, possibly because of an occlusive effect. The emulsion with 15% of linoleic acid significantly reduced SVL values during the 1st week but not during the 2nd week. The emulsion with 38% of linoleic acid did not reduce SVL values at all.     

Allergic contact dermatitis from di-isodecyl phthatate in a polyvinyl chloride identity band

An animal model for the evaluation of skin protective creams against chemical irritants is described. The irritants were applied daily for 2 weeks to shaved back skin of young guinea pigs: sodium tauryl sulphate (5% aq.: 30 min), sodium hydroxide (0,5% aq.; 2 min). and toluene (20′i. eth.; 2 mint. “The harrier cream was applied 2 h prior to and immediately after exposure to the irritant. Control animals were treated with the irritant only. The irritant reaction was scored on a 4–point scale for erythema and quantified with regard to transepidennal water loss (TEWL) by evaporime-try and skin blood flow volume (BFV) by laser Doppler velocimetry. A total of 90 guinea pigs, consisting of” individual panels of 5 to 10 animals, was tested. While one barrier cream (Slokoderm) significantly suppressed the irritation due 10 sodium lauryl sulphate and toluene, the other (Contra-Alkalh failed to do so and even aggravated the response, which was particularly evident with sodium hydroxide. This model may be useful in developing more effective barrier creams.     

Skin protection against ionized cobalt and sodium lauryl sulphate with barrier creams

853 individuals who are still working or had previously worked in hard metal manufacture were examined and selected for patch tests with materials from their working environment including metal allergens. The majority of the individuals with positive test reactions to cobalt chloride were retested with serial dilutions of cobalt chloride and with the same serial dilutions after preparation of the skin with a layer of barrier or emollient cream used for hand care in this factory. The irritant effect of sodium lauryl sulphate (SLS) was similarly investigated. The barrier and emollient creams did not give any protection against cobalt chloride or sodium lauryl sulphate. In fact they seemed to enhance the penetration of cobalt ions. Their use in protection against metal allergens and cutting fluids is questionable.     

Reverse iontophoresis: monitoring prostaglandin E2 associated with cutaneous inflammation in vivo

Abstract In response to topical application of irritants, increased concentrations of prostaglandin E₂ (PGE₂) are found in human skin exudate and in cultured dermal fibroblasts. In this study, PGE₂ generated in response to transdermal delivery of irritant drug compounds was monitored in hairless guinea pig (HOP) by a non-invasive method, reverse iontophoresis. Reverse iontophoresis is the movement of molecules from the skin under the influence of an applied electric field. Irritant drug compounds were applied with iontophoresis (electrotransport), and reverse iontophoresis of PGE₂ from skin was monitored by radioimmunoassay (RIA) after extraction from the delivery system. Chlorpromazine was used as a model drug irritant. When chlorpromazine and saline were applied over a range of current densities from 0 to 200 μA/cm², visual scores of erythema and edema yielded a correlation with measured skin efflux of PGE₂ (r=0.86). Delivery of chlorpromazine resulted in greater efflux of PGE₂ than delivery of non-irritant saline controls under the same delivery conditions. Five drug compounds, chloroquine, promazine, chlorpromazine, tetracaine, metoclopramide, and saline were applied to hairless guinea pig skin. The 6 agents were similarly rank ordered by visual erythema/edema scores and by PGE₂ efflux, indicating that the quantity of PGE₂ effluxed reflects the intensity of skin irritation. In contrast, vasoconstriction or vasodilation produced by the local delivery of vasoactive agents did not correlate with PGE₂ skin efflux, indicating that this measurement is specific for an inflammatory response. In summary, PGE₂ generated in response to transdermally applied drug irritants can be monitored non-invasively in vivo by reverse iontophoresis.     

Epidermal hyperplasia induced in guinea pig flank skin by intradermal injection of Sudan red.

Studies of dermal-epidermal interactions were conducted with guinea pig flank skin and intradermal injections of the irritant, Sudan IV dye in olive oil. These injections led to epidermal hyperplasia in areas overlying the irritant and the effect was most significant when the irritant was placed in the upper dermis. Basal cell mitotic activity and thymidine uptake reached a peak by 24 h and thereafter dropped rapidly. Maximal epidermal thickness (4.3 times the control) resulting from an increase in cell number occurred within 2-4 days. Despite the very short period of increased cell growth, epidermal thickness returned to control values only after a 24-day period. A similar growth response could not be induced by saline injections. A single topical application of the irritant showed a qualitatively and quantitatively different epidermal response. These experiments indicate that an intradermal irritant can lead to epidermal hyperplasia and a long-lasting epidermal thickening.     

The effect of daily treatment with an olive oil/lanolin emollient on skin integrity in preterm infants: a randomized controlled trial

Abstract:  To date, appropriate skin therapy for premature infants has not been clearly defined. Emollient creams are often used without solid evidence for a benefit to the neonate. The aim of the current study was to investigate the cutaneous effects of two different topical ointment therapies. Between October 2004 and November 2006 we prospectively enrolled 173 infants between 25 and 36 weeks of gestation admitted to a neonatal intensive care unit. Infants were randomly assigned to daily topical treatment with water-in-oil emollient cream (Bepanthen^®), olive oil cream (70% lanoline, 30% olive oil), or to a control group. Each neonate was continuously treated for a maximum of 4 weeks. Skin condition (skin score reflecting degree of dermatitis) in these groups was compared at weeks 1, 2, 3, and 4. Neonates treated with olive oil cream showed statistically less dermatitis than did neonates treated with emollient cream, and both had a better outcome than those in the control group (p < 0.001 in weeks 2–4). Treatment effects persisted throughout the study period and applied to infants of all gestational ages. This study demonstrates that topical skin therapy lowers the risk of dermatitis. Olive oil cream was superior to water-in-oil emollient cream.     

Percutaneous absorption of 3 organic solvents in the guinea pig (III). Effect of barrier creams

The efficacy of 4 barrier preparations presented as cream or foam against percutaneous absorption of organic solvents was investigated in the guinea pig. An ordinary hand cream was also tested. Slight reduction in blood concentration of the solvents was seen when normal skin treated with barrier creams was exposed. Absorption of butanol through stripped skin treated with barrier creams was higher than absorption through skin not so treated. Barrier creams can be considered to give poor skin protection against the organic solvents investigated.     

Antiflammin 1 peptide delivered non-invasively by iontophoresis reduces irritantinduced inflammation in vivo

Abstract The potential of an anti-inflammatory peptide (antiflammin 1) to reduce irritation when delivered transdermally by iontophoresis was examined. A model drug irritant, chlorpromazine, was co-delivered with and without antifiammin 1 by iontophoresis to hairless guinea pigs transdermally. Quantitative skin irritation measurements were obtained by monitoring erythema by skin color reflectance with the Minolta Chromameter. Antifiammin 1 delivered by iontophoresis significantly decreased, but did not eliminate, the erythema associated with co-delivery of an irritating drug compound. Lesion formation was also reduced in the presence of antiflammin 1. In vitro flux across hairless guinea pig skin demonstrated no significant differences in flux of the irritant compound in the presence or absence of antiflammin 1. In vivo generation and efflux of the inflammation mediator Prostaglandin E₂ increased during 24-h application of irritant and was unchanged in the presence of antiflammin 1. This result is discussed with respect to recent evidence that antiflammins may act on the lipo-oxygenase pathway. In summary, antiflammin 1, an antiflammatory peptide, can be delivered transdermally by iontophoresis with retention of its biological activity in vivo.     

Bioengineering measurements of barrier creams efficacy against toluene and NaOH in an in vivo single irritation test

Background/aims: By now, only a few models have been published with the goal of testing barrier creams in vivo in humans. The aim of this study was to evaluate with a single irritation test, barriers creams in humans against a lipophilic and a hydrophilic irritant, toluene and NaOH, respectively.
Methods: Both irritants were applied for 15 min after pretreatment of the skin with barrier creams. Non-invasive bioengineering methods, such as skin colorimetry (a*) and cutaneous blood flow (CBF) measurements were used to assess product protection.
Results: After toluene application on control sites, the irritation appeared quickly (T_max=3 min after patch removal), was significant (+5-6 units for a* and+80% for CBF) and did not return to base value within 1 h. Skin irritation after NaOH application, as measured by a*, was less important (+2 units) and occurred later ( T "max=40 min after patch removal). For this irritant, CBF response was minor and variable. When testing barrier properties of the products, none of them were able to prevent the skin erythema induced by toluene. Against NaOH, one barrier cream as well as petrolatum and a fatty cream protected the skin significantly.
Conclusion: The present study points out the unsatisfactory effectiveness of several commercially available barrier creams claimed to protect against lipophilic or hydrophilic irritants.     

Effects of topical corticosteroid and tacrolimus on ceramides and irritancy to sodium lauryl sulphate in healthy skin

The skin barrier, located in the stratum corneum, is influenced mainly by the lipid and protein composition of this layer. In eczematous diseases impairment of the skin barrier is thought to be of prime importance. Topical anti-inflammatory drugs and emollients are the most widely used eczema treatments. The aim of this study was to examine the effects of topically applied corticosteroid, tacrolimus and emollient on stratum corneum lipids and barrier parameters. Nineteen healthy volunteers participated in the study. Both forearms of the subjects were divided into four areas, which were treated twice daily for one week with betamethasone, tacrolimus, emollient, or left untreated, respectively. After one week each area was challenged with a 24 h sodium lauryl sulphate patch test. The lipids were collected using the cyanoacrylate method and evaluated by high performance thin layer chromatography. For evaluation of the skin barrier, transepidermal water loss, erythema and electrical capacitance were measured. The ceramide/cholesterol ratio was increased in betamethasone- (p?=?0.008) and tacrolimus-treated (p?=?0.025) skin compared with emollient-treated skin. No differences in ceramide subgroups were found between treatment regimes. Pretreatment with betamethasone (p?=?0.01) or with tacrolimus (p?=?0.001) causes a decreased inflammatory response to sodium lauryl sulphate compared with emollient. In conclusion, treatment with betamethasone and tacrolimus has a positive effect on the ceramide/cholesterol ratio and susceptibility to irritant reaction compared with an emollient.     

Rubbing test responses of the skin to man-made mineral fibres of different diameters

The irritant potency of 5 types of insulation wools (2 types of rockwool and 3 types of glass wool) were studied on the basis of their differences in diameter by a standardized rubbing test. Assessment was done by laser Doppler flowmetry (LDF) and erythema scores. Insulation wools show a wide distribution of the diameter around the mean. Of the rockwool material, 30% consisted of small grains, called "shot". The control test site did not change over time; thus, the rubbing procedure itself does not seem to contribute to the skin reactions. All fibre types proved to be irritant to the skin. The irritant reactions did not correspond with the mean diameter, although the fibre type with the smallest diameter was the least irritant and the fibre type with the largest diameter the strongest. The presence of "shot" had a significant effect on the LDF responses. "Shot" and the distribution around the mean diameter may play a role in eliciting the skin irritation by insulation wools.     

The efficiency of humectants as skin moisturizers in the presence of oil

Background/aims: The research on the treatment of “dry skin syndrome” is hampered by the lack of a suitable animal model. Formerly, we developed a validated guinea pig in vivo model in which the dry skin syndrome persists at least for 1 week. We can, therefore, compare the pharmacological effectiveness of known and potential moisturizers for the treatment of dry skin syndrome. Our aim is to study whether the moisturizing efficiency of humectants depends on the solvents in which they are dissolved. Methods: “Dry skin syndrome” was induced on the shaved skin on one side of guinea pigs by daily application of 2% sodium lauryl sulphate in deionized water (SLS) for 3 days. The other shaved side was used as control. After ascertaining skin dryness, that side was treated for 6 days with glycerol or 1,2‐hexanediol in different solvents: water, or medium chain triglycerides (MCT) or mixtures of MCT with isopropyl alcohol in different proportions. Measurement of the in vivo moisturizing effect was carried out by a Corneometer CM 825^®; erythema was measured by a Mexameter MX 16^®. Results: Treatments with glycerol (1M) in water reversed the skin dryness shown by both instruments. When dissolving glycerol in MCT, no moisturizing effect was found, probably because glycerol does not dissolve in the oil. No moisturizing effect was found with different combinations of glycerol in the mixtures of MCT and isopropyl alcohol. No moisturizing effect was found using another polyol moisturizer: 1,2 hexanediol (1M) dissolved in MCT oil. Glycerol or 1,2‐hexanediol abolished the erythema only when they were dissolved in water alone. Conclusion: Polyol moisturizers such as glycerol or 1,2‐hexanediol do not act in the presence of oils against the sodium lauryl sulphate‐induced dry skin in our guinea pig model. Since in an oil‐in‐water (O/W) emulsion, the water evaporates within several minutes, one has to question the ability of moisturizing emulsions to treat dry skin. In such instances, one cannot draw conclusions about the moisturizing efficiency of the preparation merely from the presence of the humectant. One has to study the effect of the finished preparation.     

Irritancy of industrial hand cleansers tested by repeated open application on human skin

The aim of this study was to compare the irritancy potential of 2 industrial hand cleansers with a brand leader of "mild" children's hand cleanser and with an emollient. The products were tested using repeated open application tests (ROATs) on the forearms of 40 subjects. Scoring of signs and symptoms (itching or burning), transepidermal water loss (TEWL) and stratum corneum hydration (Corneometer) evaluated responses. On all assessments, the children's hand cleanser was more irritant than the 2 industrial hand cleansers. The children's hand cleanser and industrial hand cleansers were more irritant than the emollient. The finding that a hand cleanser for children was more irritant than 2 industrial hand cleansers was surprising, and one which might hold serious implications for inducing or exacerbating atopic eczema in children. The combination of visual scoring, TEWL and Corneometer readings on ROATs is a potentially useful way of assessing irritancy strength of soap products on human skin.     

Effect of Emollients Containing Vegetable-Derived Lactobacillus in the Treatment of Atopic Dermatitis Symptoms: Split-Body Clinical Trial

Background

Atopic dermatitis (AD) patients suffer from xerosis. Proper skin care, including the use of emollients, may help improve xerosis and minimize disease exacerbation. Lactobacillus sakei probio 65, isolated from the Korean vegetable-based product kimchi, can decrease interleukin 4 and immunoglobulin E levels and inhibit Staphylococcus aureus. Moreover, it has reportedly shown positive dermatological effects in both animal and clinical studies.

Objective

To compare the effects of an emollient that contains Lactobacillus (treated) with a normal emollient (control) on AD.

Methods

This double-blind, randomized, split-body clinical trial involved 28 patients with AD. The patients applied the Lactobacillus-containing emollient on one side of their body and the control emollient on the other side twice daily for 4 weeks. Trans-epidermal water loss (TEWL) and skin capacitance were evaluated and investigator global assessment and the visual analogue scale (VAS) were administered on weeks 0, 1, 2, and 4.

Results

The treated sides had significantly lower TEWL and VAS values and significantly higher skin capacitance values over time than the control sides.

Conclusion

Topical application of Lactobacillus-containing emollients may improve the skin permeability of patients with AD.     

P09Comparison between mild irritant response in haired and hairless guinea pigs

The hairless guinea pig offers the possibility of performing irritant studies without the use of depilatory agents or clipping. Studies have shown a response to allergens and simple irritants comparable to that of the haired guinea pig. Histoanatomical studies have demonstrated differences in cutaneous structure in the two strains, differences that might influence the response to mild irritants such as topical drug vehicles. The purpose of this study was to compare the usability of hairless (HLGP) and shaved haired guinea pigs (SGP) in tolerability studies of complex topical formulations. The tolerability of 6 selected skin care formulations (SCF), known to cause a differentiated irritative response in HLGP, was studied in 15 male SGP and 15 male HLGP. All animals were treated on a 5 × 5 cm area on each flank twice daily for 4 consecutive days with SCF. The irritant effects of the SCF were quantified clinically and by measurement of transepidermal water loss (TEWL) and colorimetry (a*‐parameter). Both species were able to differentiate between SCF in relation to skin tolerance and although the response pattern was somewhat different in the two species the ranking of the SCF was essentially the same using TEWL and clinical scoring. However, colorimetry was found to be unsuited for the evaluation of cutaneous irritation in the SGP over a period of days as regrowth of fur obfuscated the underlying erythema. In conclusion the HLGP appears to be a more suitable model for tolerability testing of composite formulations.     

Pustular irritant dermatitis due to croton oil. Evaluation of the role played by leukocytes and complement

To elucidate the pathomechanisms of irritant pustular dermatitis and to evaluate the role of leukocytes in pustulation induced by croton oil, we compared the skin responses in leukopenic-and decomplemented guinea pigs with those in control saline-injected animals, to 1% croton oil application. Both decomplemented and control animals responded similarly to croton oil, showing erythema and pustulation at 24 h after topical application; microscopically numerous mononuclear and polymorphonuclear cells infiltrated the skin. Meanwhile, the clinical and histopathological response of leukopenic animals to croton oil was significantly depressed. Time-course study of inflammatory infiltrate in the dermis of controls revealed that mononuclear cells preceded the infiltration of polymorphonuclears. Although leukocytes constitute an important component in croton oil dermatitis, our results suggest that unclarified chemical mediators, other than complement-derived chemotactic factors, play a crucial role as a primary chemoattractant in the production of pustulation at the croton oil-applied site.     

Measurement of skin-fold thickness in the guinea pig

The rabbit has been used for decades for predictive testing of skin irritancy, but in recent years, the guinea pig has been suggested as an alternative, especially for assessment of one of the components of the irritant reaction: edema (fluid accumulation). A method based on skin-fold measurements with Harpenden calipers has been developed and modified. In previous papers, experience with sodium lauryl sulphate, nonanoic acid and industrial solvents was reported. The present results concern the use of cutting fluids, buffered and unbuffered acid and alkaline solutions, formalin and dimethyl sulfoxide. This inexpensive and comparatively unsophisticated method afforded clear dose-response relationships and good discriminating power. The only exception was the acid and alkaline solutions, where no changes in skin-fold thickness were observed despite their documented irritant potential. The appearance of erythema (visual scoring) and the increase in skin-fold thickness, and their relationship, are discussed with some illustrative examples. The method described is now well standardized and is suited for predictive testing of the edema-inducing capacity of chemicals and products.     

Assessment of erythema in irritant contact dermatitis

Assessment of erythema in experimentally-induced irritant contact dermatitis has been performed visually and using the laser Doppler flowmeter (LDF). A close correlation was shown between the 2 methods (r = 0.9079, p less than 0.001), with the LDF producing mean blood flow values which were able to discriminate between the different visual scores. Of the 100 patch tests evaluated, 3 gave poor correlations between their visual and LDF readings, including 2 dithranol reactions and 1 sodium hydroxide response. Patch tests with no visible erythema had blood flow values similar to those of normal untreated skin. Although the LDF was an easy instrument to operate, it was not considered suitable for use in the routine patch test clinic, due mainly to the unacceptable length of time required to measure each patch test.