• Toxicological Research
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• v.26 no.1
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• pp.61-66
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• 2010

Retinoids have many beneficial effects on dermatological applications. But, retinoids cause skin irritation. In this study, the safety of retinoids was clarified via both primary skin irritation test in rabbits and sensitization study using an integrated model for the differentiation of chemical-induced allergic and irritant skin reaction (IMDS), an alternative method to sensitization test. The effects of retinoids on the change of ultraviolet A (UVA)-induced matrix metalloproteinase-1 (MMP-1) in human skin fibroblasts and the modulation of type-1 pN collagen synthesis in hairless mice were examined to clarify the anti-wrinkle effects. Alltrans retinol (t-ROL) and its derivative, all-trans retinoic acid (t-RA), showed mild skin irritation but did not induce the sensitization. t-ROL and t-RA exerted anti-wrinkle effects by inhibiting the UVA-induced MMP-1 in human skin fibroblasts and increasing the type-1 pN collagen synthesis in hairless mice. These findings suggest that retinoids do not induce the allergy, and show anti-wrinkle effects by decreasing MMP-1 activation and increasing collagen synthesis.

• Current Research on Agriculture and Life Sciences
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• v.32 no.3
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• pp.145-148
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• 2014

To determine whether S-(-)-10,11-dihydroxyfarnesic acid methyl ester (DHFAME) produced by Beauveria bassiana CS1029 potentially causes acute skin irritation as a cosmetic ingredient, a skin toxicity test was conducted as recommended for compliance with Korea Food and Drug Administration regulations. New Zealand White rabbits were treated with 100 mg/dose of DHFAME according to standard guidelines. No significant skin lesions or inflammation was observed in the DHFAME-treated group. Furthermore, DHFAME did not appear to cause skin irritation, as assessed by clinical observation of the rabbits. Thus, when taken together, the present results suggest that DHFAME is a promising potential cosmetic ingredient that does not irritate the skin.

• Toxicological Research
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• v.34 no.4
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• pp.355-361
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• 2018

Methylisothiazolinone (MIT) has been used in combination with methylchloroisothiazolinone (CMIT) for cosmetic products such as shampoo, body lotion, and skin care products. The mixture of CMIT/MIT has been found to cause allergic contact dermatitis and is thus no longer permitted for use as a preservative in leave-on cosmetics. However, MIT itself was approved as a stand-alone preservative at a maximum concentration of 100 ppm as the toxicity was derived from CMIT rather than MIT. However, in many countries, allergic skin irritation caused by MIT remains a social concern. In this study, skin irritation was assessed for the presence of MIT, propylene glycol, and their mixture using a 3D human skin model $EpiDerm^{TM}$. Although non-diluted MIT causes serious skin toxicity, skin irritation was not observed at a concentration of 100 ppm, the maximum permissible level for cosmetics and personal care products according to European regulations. Propylene glycol, the most widely used vehicle for MIT, did not cause skin irritation in the 3D skin model. The results are expected to provide information for regulatory policies and guidelines on the use of biocides in consumer products.

• Korean Journal of Pharmacognosy
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• v.48 no.3
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• pp.202-207
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• 2017

The purpose of this study was to investigate the skin irritation of bee venom (melittin) in human. Skin irritation test was performed at 0.05% bee venom by 48 h single patch test in 30 healthy volunteers with no skin disease and skin sensitization test was performed by local lymph node assay in animal. In single patch test, 28 human subjects showed no reaction and 2 subjects showed 1+ or 3+ grade skin reaction. In a skin sensitization test of bee venom conducted using mice. no erythema was observed on the dorsal side of mice up to 8 days after application of bee venom on the skin. The results of the average stimulation index by ATP values showed that there was no irritation to the mice skin at 0.005% and 0.01% of bee venom. Therefore, bee venom is not likely to induce a significant skin irritation under 0.05% concentration.

• YAKHAK HOEJI
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• v.40 no.2
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• pp.155-162
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• 1996

Hyperkeratinization is a dermatologic disorder, which is due to the increase of corneocyte cohesion force. Glycolic acid, an alpha hydroxy acid(AHA), has been used to breakdown the hyperkeratinization processes. However, it has a problem of skin irritation when applied topically, due to the strong acidity especially in high concentration. A molecular optimization of glycolic acid has been tried to reduce the skin irritation by the way of prodrug formation. Ethyl glycolate was synthesized by the esterification of glycolic acid with ethanol in acidic conditions in the presence of sulfuric acid, and examined under the spectroscopic trials, such as UV, IR, $^1H$-NMR, and GC-MS. The physicochemical and biopharmaceutical properties of the prodrug were also evaluated. Through the toxicological tests of both skin irritation and eye mucous irritation, it has been proved that ethyl glycolate was less irritant than glycolic acid, since the pH value of synthetic prodrug was higher than that of glycolic acid. In the penetration test through nude mouse skin by diffusion cell, ethyl glycolate was continuously hydrolyzed to glycolic acid, which was assayed form the receptor compartment. It was obtained that the penetrated amount of ethyl glycolate was five times higher than that of glycolic acid. These results suggest that ethyl glycolate might be a successful prodrug of glycolic acid to reduce the skin irritation and to increase the skin penetration as well.

• Journal of Pharmacopuncture
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• v.25 no.1
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• pp.46-51
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• 2022

Objectives: This study was performed to evaluate the skin irritation toxicity of processed sulfur. Methods: All experiments were conducted at Medvill (Korea), an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP) regulations. In order to investigate skin irritation toxicity of processed sulfur, we divided the back of six rabbits into two control sites and two test sites. One of each of the two control and test sites was then designated abraded sites and intact sites. In test sites, 0.5 g of processed sulfur was applied to the back of the rabbit for 24 hours, and in control sites, 0.5 g of sterile distilled water was applied in the same way. We observed and evaluated mortality, weight, general symptoms, and skin irritation toxicity. This study was conducted with the approval of the Animal Ethics Committee (Approval number: IAC2020-1549). Results: In all experiments, no dead animals were observed. In all cases, skin coloration was observed at 24 hours after processed sulfur administration. This coloration lasted up to 48 hours and is believed to be the effect of the administration of test substances. Weight measurement indicated that weight was lost 72 hours after administration in three cases, but this is considered an accidental weight change. Normal weight gain was observed in the remaining subjects. In all animals, no skin irritation toxicity was observed, and the primary irritation index (P.I.I) was calculated as 0.0 according to Draize's evaluation method. Conclusion: The above findings suggest that it is relatively safe to apply a processed sulfur to the skin. Further research on this topic is needed to provide more specific evidence.

• Toxicological Research
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• v.13 no.1_2
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• pp.161-165
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• 1997

This study was conducted to investigate the skin irritation by transdermal administration of the three dyes. These dyes were originated from onion by using extraction method. By the order of extraction from onion, A-dye was obtained from onion by using water at 90-100$\circ$C. B-dye was extracted from A-dye with ethylacetate. After ethylacetate extraction from A-dye, the lower layer named as C-dye. Twenty-four New Zealand white rabbits were divided into three groups. The each groups was consisted of two subgroups according to high dose (extracted dyes) and low dose (the 100-fold dilutions of A-, Band C-dye). In primary skin irritation test of male New Zealand White rabbits, body temperature and weights were not significantly changed and blood cells were positioned in normal blood cell ranges of health rabbits. Primary irritation index was "0" in the test and control sites of all animals used in this study. By the results obtained in the present test, all dyes were evaluated as a non-irritant on the basis of the criteria of Draize.of Draize.

• Toxicological Research
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• v.9 no.1
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• pp.69-72
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• 1993

LBD-005, a newly developed recombinant granulocyte-macrophage colony stimulating factor, was tested for primary skin irritation in male New Zealand White rabbits. In the primary skin irritation test, LBD-005 was applied to intact and abraded skins for 24 hours. Primary irritation index was "0" in test and control sites of all animals' thus LBD-005 was evaluated as a non-irritatant on the basis of the criteria of Draize et al. (1994).l. (1994).

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.233-237
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• 2016

Deep sea water (DSW) contains many inorganic materials and minerals, which are extracted for use in diverse fields. However, before application, safety tests should be performed. In the present study, two DSW-extracted minerals were analyzed: calcium (Ca) and magnesium (Mg). Eye and skin irritation tests of DSW-extracted Ca and Mg were performed according to the guidelines of the Ministry of Food and Drug Safety of Korea. These two types of mineral extracts caused no symptoms of eye and skin irritation when compared to the control. These results suggest that DSW-extracted minerals caused no irritation in the eyes and on the skin, and could be safely applied to these areas.

• Toxicological Research
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• v.33 no.3
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• pp.191-203
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• 2017

Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornealike epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility.