• Biomolecules & Therapeutics
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• 제23권4호
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• pp.379-385
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• 2015

The eye irritation potential of drug candidates or pharmaceutical ingredients should be evaluated if there is a possibility of ocular exposure. Traditionally, the ocular irritation has been evaluated by the rabbit Draize test. However, rabbit eyes are more sensitive to irritants than human eyes, therefore substantial level of false positives are unavoidable. To resolve this species difference, several three-dimensional human corneal epithelial (HCE) models have been developed as alternative eye irritation test methods. Recently, we introduced a new HCE model, MCTT HCE$^{TM}$ which is reconstructed with non-transformed human corneal cells from limbal tissues. Here, we examined if MCTT HCE$^{TM}$ can be employed to evaluate eye irritation potential of solid substances. Through optimization of washing method and exposure time, treatment time was established as 10 min and washing procedure was set up as 4 times of washing with 10 mL of PBS and shaking in 30 mL of PBS in a beaker. With the established eye irritation test protocol, 11 solid substances (5 non-irritants, 6 irritants) were evaluated which demonstrated an excellent predictive capacity (100% accuracy, 100% specificity and 100% sensitivity). We also compared the performance of our test method with rabbit Draize test results and in vitro cytotoxicity test with 2D human corneal epithelial cell lines.

• 대한약침학회지
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• 제25권1호
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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.

• 대한화장품학회지
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• 제17권1호
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• pp.64-80
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• 1991

The SKINTEX Method is based on a two-compartment physico-chemical model which includes a Biomembrane Barrier in compartment one and an organized macromolecular matrix in compartment two. Test samples absorb onto or permeate through the keratin/collagen Biomembrane Barrier and then can interact with the organized macromolecular matrix. Changes in the integrity of the barrier release a dye indicator: Changes in the matrix can alter its transparency. The sum of these two responses is read spectrophotometrically at 470nm. An early investigation of 950 chemicals and formulations in the SKINTEX System produced results which were 89% concordance to in vivo Draize dermal irritation results obtained with 24-hour occluded application of test samples with-out abrasion and standard scoring. Alkaline materials were analyzed in a specialized SKINTEX AMA Protocol. In this early study, the model did not distinguish nonirritant test materials and formulation with PDII(Primary Dermal Irritation Index)in the range from 0 to 1.2, A High Sensitivity Assay Protocol(HSA)was developed to amplify the changes in both compartments of this model and provide more accurate calibration of these changes. A study of 60 low irritation test samples including cosmetics, household products, chemicals and petro-chemicals distinguished nonirritants with PDII $\leq$ 0.7 for 26 of 30 nonirritants. A second protocol was developed to evaluate the SKINTEX model predictability with respect to human irritation. The Human Response Assay (HRA )has been optimized based on differences in penetration and irritation responses in humans and rabbits. An additional 32 test materials with different mechanisms and degrees of dermal toxicity were evaluated by the HRA. These in vitro results were 86% concordant to human patch test results. In order to further evaluate this model, a Standard Chemical Labelling (SCL) Protocol was developed to optimize this system to predict Draize dermal irritation results after a 4-hour application of the test material. In a study of 52 chemicals including acids, bases, solvents, salts, surfactants and preservatives, the SCL results demonstrated 85% concordance to Draize results for a 4-hour application of test samples on non-abraded rabbit skin. The SKINTEX System, including three specialized protocols, provided results which demonstrated good correlation to the endpoint of dermal irritation in man and rabbits at different application times.

• 농약과학회지
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• 제14권2호
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• pp.79-85
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• 2010

2000년 이후 국내에 등록된 농약제품을 대상으로 원제 및 그 원제로 제조된 농약의 자극성 및 감작성에 대한 연관성을 연구하여 농약재등록, 신규등록 및 농약관리시 자극성 예측, 시험성적서 요구 결정 등에 대한 이용 가능성을 타진하고 농약관리의 기초 자료로 활용하기 위해 수행되었다. 농약의 자극성 및 감작성성적은 농약시험성적 정보집 및 농약등록 시 제출된 자료 등을 참고하여 원제 148성분 및 제품 149종의 자극성 및 감작성의 양성반응 빈도, 제형 간 반응차이, 원제와 제품간의 연관성 등을 조사 분석하였다. 원제 148성분 중 피부 자극성 133종, 안구 자극성 132종, 피부 감작성 97종의 성적이 이용되었으며, 항목별로 피부자극성 25(18.8%)종, 안구자극성 62(47%)종, 피부감작성 20(20.6%)종이 경도 이상의 양성반응을 보였다. 또한 149 품목 중 피부자극성 148종, 안구자극성 149종, 피부감작성 140종의 성적으로 분석한 결과 피부자극 22(14.9%), 안구자극 58(38.9%), 피부감작성 33(23.6%)품목이 경도 이상의 양성반응을 나타내었다. 동일제형 10품목 이상이 조사된 10종을 제형별, 독성반응별로 조사 분석하였다. 분석결과 원제와 제품간의 연관성은 피부자극성 73.1%, 안구자극성 44.7%, 피부감작성 66.2%로 분석되었으며, 성분함량간의 자극성 및 감작성은 아무런 상관성이 없는 것으로 판단되었다. 이상 원제와 제품간의 자극성 및 피부감작성에 관여하는 몇 가지 요인을 조사 분석한 결과 피부자극성 및 피부감작성은 원제와 제품간 각각 73.1%, 66.2%의 높은 상관성을 보였으나, 안구자극성은 제형 의존적인 것으로 판단되어 추후 더 많은 농약에 대하여 원제의 자극성성적, 제형특성 등을 참고하여 분석하면 자극성시험 수행 여부 결정을 위한 스크리닝 단계에 이용 가능할 것으로 판단되었다.

• 농약과학회지
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• 제14권4호
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• pp.339-346
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• 2010

본 연구는 생리활성이 높은 식물오일의(라벤더, 레몬유칼립투스 및 계피 오일) 친환경 살충소재의 활용가능성을 탐색하고자 급성독성(급성경구독성, 급성경피독성, 피부자극성 및 안점막자극성)시험을 수행하였다. 랫드를 이용한 급성경구독성시험결과 라벤더, 레몬 유칼립투스 및 계피 오일의 $LD_{50}$은 2,000 mg/kg bw 이상이었고, 급성경피독성시험결과 모든 시험물질의 $LD_{50}$이 4,000 mg/kg bw으로 나타났다. 피부자극성시험결과 라벤더와 레몬 유칼립투스 오일은 자극성이 없었고, 계피 오일은 중도의 자극성을 나타냈다. 안점막자극성시험결과 라벤더, 레몬 유칼립투스 오일은 자극성이 없었고, 계피오일은 중도의 자극성을 나타냈으나 세척시험 결과 자극성은 없었다. 따라서, 라벤더 및 레몬 유칼립투스 오일은 독성이 낮았으나, 계피 오일은 중도의 피부자극성 및 안점막자극성을 갖는 것으로 평가되었다.

• 대한화장품학회지
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• 제23권3호
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• pp.108-114
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• 1997

The skin permeation study has two meanings in cosmetics. One is how to promote the skin permeation of active meterials for improving their bioavailabilities and the other is how to decrease it of irritants for reducing their skin side effects. In this study, we selected methyl paraben, one of the preservatives, as a model irritant and tried to reduce the skin irritation by the decrease of skin permeation. Furthermore, the relationship between skin permeation and skin primary irritation was discussed. For in vitro skin permeation experiments, Franz type diffusion cells and the excised skin of female hairless mouse from 8 weeks old were used. The donor compartment was charged with oil only or O/W emulsion containing 0.3% MP. We selected 19 oils, including esters, triglycerides, plant oils, hydrocarbons, and alchols, which are broadly used in cosmetics. We evaluated with female guinea pig. The skin permeahility of MP from the oils showed following order: ester oils > triglycerides > plant oils > hydrocarbons > alcohols. We considered that this result was based on the different effect of each oil on the barrier function of stratum corneum. In O/W emulsion containing each oil, the skin permeability of MP decreased as the oil/water partition coefficient of MP increased. The skin primary irritation increased as the skin permeability of MP increased. In conclusion, we suggest that the skin irritation could be reduced by the decrease of skin permeability of MP, which may be obtained by the good selection of oils in cosmetic preparations.

• Toxicological Research
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• 제29권2호
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• pp.87-90
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• 2013

The potential role of topical valproate (VPA) in hair regrowth has been recently suggested. However, safety reports of VPA as a topical formulation are lacking. Therefore, in the present study, we investigated whether VPA causes skin irritation in humans. We first performed a cell viability test and showed that VPA did not exhibit toxicity toward HaCaT keratinocytes, fibroblasts, and RBL-3H mast cells. We then performed clinical patch test and skin irritation test through transdermal drug delivery with the help of microneedle rollers. No significant findings were obtained in the clinical patch test. In the skin irritation test, only 1 patient showed erythema at 1 hr, but the irritation reaction faded away within a few hours. Erythema and edema were not observed at 24 hr. We concluded that VPA has minimal potential to elicit skin irritation. Therefore, we consider that VPA can safely be applied to human skin.

• Toxicological Research
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• 제34권4호
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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.

• Biomolecules & Therapeutics
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• 제2권3호
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• pp.247-255
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• 1994

As a series of safety studies of DA-3030, a new rhO-CSF, its local irritancy was examined in the rabbits after the following treatment; application into the conjunctival sac of the eye(single), subcutaneous injection(single), intramuscular injection(single), and intravenous injection(8-day repeated). In addition, paravenous irritation of DA-3030 was investigated in mice. The results obtained were as follows. 1. In the result of ocular irritation test, 0.03% solution of DA-3030 could be considered as a non-irritating material. 2. The local irritation of DA-3030 by an injection of 0.5mι of its solution subcutaneously or intramuscularly was negligible and not so much different from that of saline. 3. In the vascular irritancy test, macro- and microscopic observations revealed that the irritating activity of DA-3030 in blood vessels was not different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 8 days.4. The paravenous administration of DA-3030 did not induce any abnormal changes at injection sites except mild swelling in 1 mouse at 3 hours after injection which was thought to be due to slow absorption. The above-mentioned results suggest that DA-3030 has no irritating activity when injected through intravenous or subcutaneous route for clinical practice as 0.03% solution.

• Toxicological Research
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• 제26권1호
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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.