• 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.

• Toxicological Research
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• v.17 no.2
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• pp.91-96
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• 2001

Phthalates are widely used as plasticizers to impart softness and flexibility to normally rigid polyvinylchloride products. However, there are not much studies jar dermal and ocular irritation toxicity of phthalates. So we investigated the skin or eye irritation effect of some phthalates which was not reported. The primary skin irritation of diethyl phthalate (DEP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), dipropyl phthalate (DPP) and dipropyl phthalate (DPrP) was studied. The ocular irritation of dibutyl phthalate(DBP), DIDP, DINP, DPP and DPrP was also studied. DEP, DIDP, DINP, DPP, and DPrP were found to be non-irritating to the skin of the test animals. DBP, DIDP, DINP and DPP were found to be non-irritating to the eye of the rabbits. DPrP caused the slight irritations to the eye in 1 or 2 days after treatment but irritation of the animals was soon recovered.

• Journal of Food Hygiene and Safety
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• v.6 no.3
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• pp.171-177
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• 1991

According to the Established Regulations of National Institute of Safety Research, the skin-irritation test of BST-SR (Lucky Ltd.) was perfonned for seven days in New Zealand White Rabbits. During treatment periods no significant clinical symptom was observed. Significant changes such as erythema, scar tissue and edema were not shown on the applicating sites. According to Primary Irritation Index of Draize, skin irritation rate was assessed as "Zero". The eye irritation of BST-SR (Lucky Ltd.) was examined in nine New Zealand White rabbits, based on the Established Regulation of National Institute of Safety Research. 0.1 ml of test material was dropped on right eye, and after 20~30 seconds, three rabbits' eyes were cleaned with wann saline for 1 minute. Other six rabbits' eyes were left uncleaned. The untreated left eyes were negative control. The lesions of cornea, iris and conjuntiva were assessed by the Grade table (from the Regulation of National Institute of Safety Research), and it is concluded that BST-SR has no eye-irritation.

• Toxicological Research
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• v.21 no.1
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• pp.39-43
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• 2005

The present study was carried out to investigate the antibacterial activity against Staphylococcus aureus with antibiotic-resistance in vitro and the skin irritation in rabbits with surfactin produced by Bacillus subtilus Complex BC1212. The antibacterial activities of selected antimicrobial agents (surfactin, amoxacillin, colistin, norfloxacin and streptomycin) were evaluated by using the broth microdilution method. As the results, the minimum inhibitory concentration (MIC) of the surfactin was less than 15.6 ㎍/ml. In the skin irritation test, two out of 4 rabbits showed very slight edema at 24 h after the administration of surfactin, and then recovered at 72 h. The change of body weight was normal during the skin irritation test. The primary irritation index in accordance with the Draize evaluation of topical reaction was calculated to be '0.125', which meant not irritating. Based on these results, it could be concluded that the test agent, surfactin, was a non-irritant. We could also think that the surfactin may be useful for the treatment of S. aureus infections such as bovine mastitis.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1213-1219
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• 2010

We evaluated the anti-aging potential and safety of black garlic extract for cosmeceutical ingredient. Black garlic was made by spontaneous fermentation for 40 days at $60{\sim}70^{\circ}C$, 85~95% RH without any additives. The 10% black garlic extract had sweet odor, antioxidant activities and inhibitory activities of skin againg enzymes such as tyrosinase and elastase. The skin safety was performed to evaluate of potential toxicity using the primary irritation test and skin sensitization test. The black garlic extract did not show any adverse reactions such as erythema and edema on intact skin sites at primary irritation test, but on abraded sites, some experimental animals showed very slight erythema. So, the black garlic extract was classified as a practically non-irritating material based on the score 0.23 of primary irritation index. The skin sensitization study was tested by the guinea pig maximization test (GPMT) and Freund's complete adjuvant (FCA) with intradermal injection of 10% black garlic extract. The skin sensitization test showed no skin sensitization. The allergic sensitization depends on tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6). The concentration of IL-6 on challenged tissue of treated with black garlic extract was not significantly different with negative control group (saline treated group). Based on this study, the potential for black garlic as a cosmeceutical ingredient was proven.

• Journal of Food Hygiene and Safety
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• v.27 no.2
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• pp.188-193
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• 2012

This study was designed to evaluate to acute oral toxicity and skin irritation of Chrysanthemum dye in Sprague-Dawley (SD) rats. SD rats were orally treated with Chrysanthemum dye at a dose of 0, 1 and 2 ml/kg body weight. After oral administration, the rats were observed for 14days. In primary skin irritation test, SD rats were dermally treated with Chrysanthemum dye and observed for 3 days. To ensure the safety of Chrysanthemum dye such as the following were observed and tested. We examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the histopathological test, the mortality and skin irritation. As a result, no significant differences were found in body weight, feed intake and histopathological test between control and Chrysanthemum dye treated group. In the result of skin irritation test, Chrysanthemum dye did not induce erythema and edema after topical application. Primary irritation index was "0" in the test. Therefore, it is suggested that Chrysanthemum dye has no effect on acute toxicity and side effect in SD rats and is non-irritant material based on the score "0" of primary irritation index.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.138-138
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• 2002

In recent years, the safety of sunscreens has been challenged based on the reports of its adverse effect on users; dermatitis, allergic contact dermatitis, photoallergic contact dermatitis. To investigate a correlation between sun protection factor (SPF) and the safety of sunscreens, we measured in vitro SPF index using homosalate as a standard and examined the toxicity tests on cosmetics; primary and cumulative skin irritation tests, ocular irritation test, and skin sensitization test.(omitted)

• Toxicological Research
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• v.18 no.3
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• pp.267-273
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• 2002

Fructose 1,6-diphosphate(FDP), a glycolytic metabolite, is reported to ameliorate inflammation and inhibit the nitric oxide production in murine macrophages stimulated with endotoxin. It is also reported that FDP has cytoprotective effects against hypoxia or ischemia/reperfusion injury in brain and heart, and may play a protective role in ultraviolet B (UVB, 280~320 nm)-injured keratinocyte by attenuating prostaglandin (PG)-E$_2$production and cyclooxygenase (COX)-2 expression, which are possibly through blocking the intracellular reactive oxygen species (ROS) accumulation. Therefore FDP is considered to act as a potent antioxidant especially in the skin. We conducted the several safety tests (single-dose toxicity, primary skin irritation test, eye irritation test, skin sensitization test, phototoxicity test, photosenitization test and human patch test) to see if FDP is safe in case used for the skin application. Our data obtained hitherto suggest that FDP is very safe if applied to the skin.

• 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.