Optimal patch application time in the evaluation of skin irritation.

We investigated the optimum application for evaluating skin irritation response by using samples of irritants commonly used as additives in cosmetics and other common household products. We studied 47 volunteers (16 men and 31 women). We selected three types of surfactant, one moisturizer, one anti-infective agent and one oil solution. Using Finn chambers on Scanpor tape, we performed the patch test. A total of 0.015 mL of each sample was applied to the Finn chamber. For liquids, circular filter paper was soaked in 0.015 mL of the sample. Samples were placed on the upper back of participants, and closed for 4, 24 or 48 h. A patch application time of 24 h is sufficient to detect primary skin irritation from irritants in cosmetics and other common household products. In addition, we found that skin irritation reactions were strongest at 24 h after patch removal and that the reaction tended to be weaker at 48 h after patch removal. Patch testing to evaluate irritants should be performed by means of a 24-h patch test with a follow-up reading at 24 h after patch removal. An application time of 24 h places less of a burden on patients than a 48-h patch test.

Safety studies of Pseudo-Ceramide SLE66. Part 2: Metabolism, cytotoxicity and genotoxicity.

A synthetic pseudo-ceramide (SLE66) has been shown to improve dryness/itching of human skin. The objective of this study was to investigate metabolism, genotoxicity and cytotoxicity of SLE66. Pharmacokinetic profile of [14C]-SLE66 was investigated following oral or transdermal administration to Sprague-Dawley rats. The plasma radioactivity following oral administration (1000 mg SLE66/kg) reached maximum (Cmax--39.77 µg eq/ml) at 4 h and then declined with apparent elimination half-life of 23.6 h. Following transdermal application of [14C]-SLE66 (1000 mg/kg) or as prescription formulation (8%; 160 mg/kg) to normal skin-rats, no radioactivity was noted in plasma, while in damaged skin-rats, trace amount of plasma radioactivity was detected for up to 8 h. The radioactivity excreted in urine, feces, and expiratory air collected for up to 24 h accounted for 5.7, 84.8, and 0.6%, respectively. In the cytotoxicity experiments, SLE66 did not cause toxicity in human skin model. In the genotoxicity studies, SLE66 was not mutagenic in Ames assay and chromosomal aberration assay. These results suggest that following oral administration a small amount of SLE66 is absorbed and excreted in urine, while no absorption was noted after transdermal application to normal skin and SLE66 does not cause cytotoxicity or genotoxicity.

Safety studies of pseudo-ceramide SLE66: acute and short-term toxicity.

Topical application of ceramides is reported to improve the structure and texture of the skin. Synthetic pseudo-cermaide, SLE66 has been shown to reduce dryness/scaling/itching of human skin. Although efficacy of topically applied ceramides and their analogs has been investigated to some extent, safety information is scarce. The objective of the present investigation was to evaluate potential adverse effects of SLE66. The oral LD(50) of SLE66 in rats and mice was >5000 mg/kg, while dermal LD(50) in rats was >2000 mg/kg. In animal and human studies, SLE66 did not cause skin irritation or sensitization. SLE66 does not possess phototoxicity or photosensitization potentials. Instillation of SLE66 into rabbit eye elicited transient conjunctival irritation. In 28 day repeat-dose studies, administration of SLE66 via gavage (daily) or by dermal application (five days/week) to Sprague Dawley rats at levels up to 1000 mg/kg/day did not cause mortality or morbidity. Compared to the controls, the clinical condition of the animals, body weights, feed consumption, hematology, clinical chemistry, organ weights, and gross necropsy findings were unaffected by oral or dermal administration of SLE66. The no-observed-adverse-effect level (NOAEL) for systemic toxicity following oral or dermal administration of SLE66 was 1000 mg/kg/day (the highest level tested).

Detergent-induced epidermal barrier dysfunction and its prevention.

Various detergents are used as skin cleansing products. In some cases, skin cleanser removes not only dirt but also valuable skin lipids. Therefore, detergents may disrupt epidermal barrier function despite that using of detergents are required for good skin hygiene. Lipid supplements can reverse detergent-induced dysfunction of the skin barrier. Elevated transepidermal water loss (TEWL) and riboflavin penetration in 5% SLS-treated rat and human skin were reversed by supplementation of monoglyceride (MG), squalene (SQ), cholesterol ester (CE) and pseudo-ceramide (Cer2). MG and Cer2 achieved the best results. MG appears to inhibit elution of intercellular ceramides, since more ceramides remained when the detergent was supplemented with MG. Topical application of Cer2 is not effective for recovery from artificially induced barrier disruption, but supplemented Cer2 into skin cleanser has a beneficial effect for prevention of detergent-induced barrier disruption. In conclusion, the prevention of barrier disruption is most important matter for maintaining skin health and barrier function. Therefore, we think that Cer2-supplemented skin cleanser is useful for conservation of skin barrier function.