• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.417-423
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• 2018

Extracellular interleukin 1 alpha (IL-$1{\alpha}$) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-$1{\alpha}$ is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-$1{\alpha}$ and IL-$1{\beta}$ mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-$1{\alpha}$ and IL-$1{\beta}$ in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-$1{\alpha}$ and IL-$1{\beta}$, suggesting potential applications to predict skin irritation.

• Journal of Korean Physical Therapy Science
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• v.9 no.4
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• pp.185-192
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• 2002

Ultrasound has been found useful as a therapeutic modality for the reduction of muscular and tendinous spasm. It has also been utilized for pain and other pathologic conditions through the ability of soundwaves to introduce molecules of chemical substances through the skin by a process. Choice of the transmission medium is very important for effective ultrasound treatment in clinical field. The purpose of this study was to analyze the effects of various ultrasound conduction media in regard to ultrasound conductivity and degree of absorption, evaporation and of skin irritation. The media used in this study were Antiphlamine, Sacch lotion, Stereogel, Trastgel, Antiphlamine S lotion, and Mentholatum lotion that have been used in clinical medicine. The study revealed that Antiphlamine was not compatible with a good ultrasound transmitter. Other media excluding Antiphlamine were compatible with a good ultrasound conductor, but they had some drawback with their nature of higher absorption, evaporation and skin irritation. The medium that was prepared by mixing of Antiphlamine with Gel in 1 to 10 ratio was a good ultrasound transmitter and extents of absorption and evaporation and of skin irritation of it were less than the other media.

• Toxicological Research
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• v.18 no.1
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.

• Journal of Food Hygiene and Safety
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• v.22 no.2
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• pp.110-115
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• 2007

This test was performed to evaluate the skin irritation and sensitization of Creocomplex, disinfectant, Containing 10% 4-chloro-m-cresol, 10% didecyl dimethyl ammonium chloride, and 10% glutaraldehyde. In primary skin irritation test, rabbits were dermally treated with Creocomplex for 24 hrs. The disinfectant did not induce any adverse reactions such as erythema and edema on intact skin sites, but on abraded skin sites, some rabbits showed very slight erythema and edema 24hr after topical application. So, the disinfectant was classified as a practically non-irrifating material based on the score 0.13 of primary irritation index. In the skin sensitization test, guinea pigs were sensitized with intradermal injection of 0.1ml Creocomplex for 24 hr. After 1 week, Creocomplex was treated on the site of injection, and challenged 2 weeks later. Creocomplex did not induce any allergic reactions. Therefore, 10% Creocomplex was graded as a weak material from 0 in both sensitization score· and rate. From results of the present study, it is suggested that 10% Creocomplex does not cause contact irritation and sensitization.

• Journal of Food Hygiene and Safety
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• v.36 no.1
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• pp.17-23
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• 2021

This evaluation tested the skin irritation and sensitization of an acaricide (Wagoojabi II®, WGJB) for the control of poultry red mite, containing 20% Chamaecyparis obtusa oil and 56% Cinnamomum camphora oil. In a primary skin irritation test, rabbits were dermally treated with WGJB for 24 h. The acaricide did not induce any adverse reactions such as erythema and edema on intact skin sites, but on abraded skin sites, some rabbits showed very slight erythema and edema 24 h after topical application. So, the acaricide was classified as a practically mild-irritating material based on a 0.625 primary irritation index score. In the skin sensitization test, guinea pigs were sensitized with intradermal injection of 0.1mL WGJB for 24 h. After 1 week, The WGJB was treated on the site of injection, and challenged 2 weeks later. The WGJB did not induce any allergic reactions. Therefore, the WGJB was graded as a weak material at '0' in both sensitization score and rate. From the results of this study, it is suggested that WGJB does not cause contact irritation and sensitization.

• Toxicological Research
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• v.16 no.1
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• pp.17-25
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• 2000

Chitosan cross-linked collagen-glycosaminoglyan (CCGM) is an artificial skin substitute made to form a sponge like dimensional matrix. It can be used to facilitate reconstruction of dermal tissue when applied on large wounds such as severe burns. In order to study the toxicological effects of CCGM the cytotoxicity, local irritation and skin sensitization test were carried out according to the standards of ISO 10993. In the cytotoxicity test utilizing LDH and MTT test, both the CCGM and its extract had no toxicity of Balb/c 3T3 cells. The local irritatioin test on rabbit skin demonstrated that CCGM did not promote any harmful when directly applied on skin. In addition, it did not elicit any allergic reaction in the guinea pig maximization test. Based on these results, it is suggested that CCGM is a material without cytotoxicity, local irritation and allergenicity.

• Molecular & Cellular Toxicology
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• v.3 no.1
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• pp.68-75
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• 2007

[ $\alpha$ ]-Terpinene has been known as a repellent against the mosquito Culex pipiens pallens Coquillett based on a human forearm bioassay. $\alpha$-Terpinene showed significantly greater repellency than a commercial formulation, N, N-diethyl-m-methylbenzamide (deet). In this study, skin and eye sensitivity of $\alpha$-terpinene (2%) was examined with bioassays using white New Zealand rabbits. There were somewhat gross and histological changes observed in these treatments. Eye irritancy assays examined gross changes to cornea, iris and conjuctiva, and histological changes to smear of ocular discharge and eye tissue. Treated rabbits were divided into two cohorts, a saline washed cohort (W) or a non-washed cohort (NW). Opacity of cornea and redness, chemosis and discharge of conjuctiva were observed in both cohorts, but disappeared within 4 and 10 days in W and NW, respectively. Main components of ocular discharges were fibrin, epithelial or epitheloid cells, lymphoid cells, erythrocytes and granulocytes. These abnormal cellular components disappeared within 4 days and 10 days in W and NW, respectively. No permanent histological differences were observed between the two cohorts. However, severe irritation was determined as 57.2 of I.I.O.I value on the first day after treatment. These findings indicate a spray-type solution containing 2% $\alpha$-terpinene may serve as an alternative mosquito repellent and further studies need to reduce the eye irritation with formulation changes.

• Toxicological Research
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• v.21 no.3
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• pp.249-253
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• 2005

The present study was carried out to investigate the skin irritation potential of lemon grass essential oil in rabbits. A volume of 0.5 ml of test article was applied to intact and abraded skins, respectively, for 24 h in 6 healthy male New Zealand White rabbits. Parameters measured during 72 h observation period were mortality, clinical signs, body weight changes, and local irritation. All rabbits showed severe edema at both 24 h and 72 h after the application of test article. These animals also showed very slight to severe erythema and/or slight eschar formation at both 24 h and 72 h. The edema and erythema induced by lemon grass essential oil were recovered on day 7 of additional 11-day recovery period, but the eschar formation was not recovered at the end of recovery period. On the other hands, there were no treatment-related adverse effects on clinical sign, body weight and gross finding in rabbits. Based on these results, it was concluded that a single dermal application of the undiluted lemon grass essential oil caused very slight to severe edema, erythema and eschar formation in rabbits and showed a primary irritation index score of 5.63 indicating severe irritation. The results of this study strongly suggest that lemon grass essential oil should be used with care and in highly diluted forms especially when directly applied to the skin.

• The Korean Journal of Pesticide Science
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• v.16 no.3
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• pp.261-266
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• 2012

It is common to use many experiment animals to evaluate the toxicity of chemicals including pesticides. For protecting animal, the concepts of 3R (Reduction, Replacement, Refinement) were introduced and in vitro alternatives methods actively have been developed all over the world. Many experimental animals for toxicological tests have been used, so that it is important to establish the alternative methods. In this study, the alternative method using reconstituted human skin model (Keraskin$^{TM}$) was conducted for classification of skin irritation on pesticides. Sixteen formulations selected on the basis of the degree of irritation were treated by Keraskin$^{TM}$ test. The percent of cell viability was measured into the culture medium collected after treatment of the pesticides for 24-72 hrs. The skin irritations of formulations were evaluated by the cell viability. In this study, The 4 formulations with mild irritation in rabbits were evaluated as nonirritant, the 6 formulations with moderate and severe irritation were evaluated as irritant in human skin model test. We suggest that the alternative test using Keraskin$^{TM}$ model could be used as toxicity evaluation for primary irritation index (P.I.I.) score of greater than or equal to 2.1 of pesticides. The further studies should be required to apply for hazardous assessment of pesticides on alternative skin irritation methods because of the interindividual variability of the sensitivity of skin irritation on pesticides.

• Journal of the Institute of Convergence Signal Processing
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• v.22 no.1
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• pp.14-19
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• 2021

This study has attempted to use ozone for the treatment of skin diseases as research results that ozonated olive oil has an excellent therapeutic effect on skin diseases are known. However, there is hardly any accurate data in Korea. Usually, animal tests related to cosmetics are not performed, but toxicity tests were conducted because they were absolutely necessary. In general, there are not many cases of measuring actual data through animal tests for the purpose of confirming the performance of cosmetics, but in the case of toxicity tests, it is recommended to accurately measure skin reactions, so this experiment was conducted. In this experiment, in order to evaluate the skin irritation of ozonated oil (high concentration) on the rabbit, the test substance was applied to the back of the rabbit for 24 hours, and then mortality, general symptoms and skin irritation were evaluated. Experimental Results As a result of evaluating the treatment site of the test substance after a certain period of time, no skin irritation was observed in all animals.