• Biomolecules & Therapeutics
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• 제26권4호
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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.

• 대한물리치료과학회지
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• 제9권4호
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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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• 제18권1호
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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.

• 한국식품위생안전성학회지
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• 제22권2호
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• pp.110-115
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• 2007

살균소독제, 크레오콤플렉스 (4-chloro-m-cresol(10%), didecyldimethyl ammonium chloride(10%), glutaraldehyde (10%))에 대하여 토끼와 기니픽을 이용하여 피부 자극성 및 감작성 평가를 각각 수행하였다. 토끼의 등 부위의 털을 제거하고 찰과부위와 비찰과 부위에 여러 농도로 크레오콤플렉스를 도포한 후, 피부 자극성을 확인한 결과 10% 크레오콤플렉스의 1차 자극지수가 0.13으로 비자극성 물질로 분류되었다. 기니픽을 이용한 피부 감작성 시험에서는 1, 2차 감작 후, 2주 후 10% 크레오콤플렉스로 감작을 유도한 결과, 어떠한 알러지 반응도 보이지 않아, 감작성이 매우 약한 물질로 분류되었다. 따라서, 본 연구를 통하여, 10% 크레오콤플렉스는 피부자극성과 감작성을 야기하지 않는 물질로 평가되었다.

• 한국식품위생안전성학회지
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• 제36권1호
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• pp.17-23
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• 2021

본 연구는 닭 진드기 구제를 목적으로 개발된 살비제인와구잡이 II® (WGJB, 편백정유 : 계피정유 = 20 : 56)에 대하여 토끼와 기니픽을 이용하여 피부 자극성 및 감작성 평가를 각각 수행하였다. 일차피부자극시험에서 토끼의 피부에 WGJB를 24시간 동안 처리한 후 피부 자극성을 확인한 결과, WGJB는 비찰과 부위에서 홍반과 부종과 같은 어떠한 부작용도 일으키지 않았으나, 몇몇 토끼의 찰과 부위에서 매우 약한 홍반과 부종을 나타내어 WGJB의 1차 피부자극 지수는 0.625이었다. 따라서 WGJB는 약한 자극성이 있는 물질로 분류되었다. 피부감작성 시험에서 기니픽에 0.1 mL의 WGJB을 피내주사한 후 24시간 동안 감작시켰다. 감작 1주일 후 WGJB를 함유한 패취를 주사부위에 부착하여 48시간 동안 처리한 다음, 2주 후에 WGJB를 함유한 패취를 부착하여 감작을 야기시켰다. WGJB는 어떠한 알러지 반응도 나타내지 않았다. 따라서, 본 연구를 통하여 WGJB는 약한 피부 자극성을 가지며 감작성을 야기하지 않는 물질로 평가되었다.

• Toxicological Research
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• 제16권1호
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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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• 제3권1호
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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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• 제21권3호
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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.

• 농약과학회지
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• 제16권3호
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• pp.261-266
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• 2012

농약을 포함한 화학물질의 독성을 평가하기 위하여 많은 실험동물이 사용되고 있다. 최근 동물실험에 대한 규제 강화와 실험동물의 윤리적 보호를 위해 동물실험을 대체하려는 동물대체시험법 연구가 활발히 진행되고 있다. 우리나라에서 화학농약 등록 시 급성경구독성시험, 급성경피독성시험, 피부자극성시험 등 여러 시험에서 실험동물을 이용하여 인축독성평가를 하고 있다. 세계적인 추세에 맞춰 농약의 안전성 평가를 위한 동물대체시험법 연구제시와 규제가 시급한 실정이다. 본 연구는 국제적으로 승인된 대체시험법 중 인공피부모델을 이용한 피부자극성평가 적용 가능성을 검토하기 위하여 실시하였다. 시험물질은 기존의 토끼를 이용한 피부자극성시험에서 피부반응을 평점화하여 산출한 피부 1차 자극지수(P. I. I.) 0-7(구분:없음-강도) 값을 가진 농약제품 16종을 선발, 인공피부(KeraSkin$^{TM}$)를 이용하여 피부자극성평가를 수행하였다. 그 결과, 중도이상의 농약인 경우 세포생존율 50% 이하로 자극성 물질로 나타났으며, 경도 이하의 농약인 경우 세포생존율 50% 이상으로 비자극성 물질로 나타났다. 피부의 자극성이 있는 경도에서 강도의 농약의 경우 현재 농촌진흥청 고시 농약표시 기준에 따라 주의사항을 표시하게 되어 있고(RDA, 2012b), 농약의 피부자극성의 경우 민감도가 사람에 따라 많은 차이를 보이기 때문에 피부자극성 대체시험법 적용여부는 추후 추가적인 검토가 필요할 것으로 판단되며, 앞으로 농약안전성평가를 위한 동물실험을 대체할 수 있는 시험법 검증연구를 통해 농약등록 시험기준과 방법을 개선할 필요성이 있다고 사료된다.

• 융합신호처리학회논문지
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• 제22권1호
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• pp.14-19
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• 2021

본 연구는 오존화 올리브오일이 피부 질환에 우수한 치료효과를 가진다는 연구 결과가 알려지면서 오존을 피부 질환치료에 사용하려는 다양한 시도가 있어 왔지만, 적절한 계측 절차가 수립되지 않아 국내에서는 임상적으로 가치가 있는 양질의 데이터를 확보할 수 없었다. 일반적으로 화장품의 성능확인을 위한 목적으로 동물실험을 통해 실측 데이터 계측을 진행하는 경우는 많지 않지 않으나, 독성실험의 경우 피부의 반응을 정확히 계측하는 것이 반드시 필요한 사항으로 권고되고 있어 본 실험이 실시되었다. 본 실험에서는 실험 Rabbit에 대한 오존화오일(고농도)에 대한 피부자극 평가를 위하여 오존화오일(고농도)을 털을 제거하여 피부가 노출된 Rabbit의 등 부위에 도포한 후 24시간 동안 영상처리장치와 육안 검사를 통해 피부 반응을 관찰하여 피부자극 평가를 위한 데이터를 확보하고자 하였고 오존화오일(고농도)의 의한 일반적인 반응, 사망과 같은 반응을 함께 측정하는 과정을 진행하였다. 총 24시간 이내의 결과에서 실험에 사용된 동물들 모두에서 시험물질 처치 부위의 육안관찰, 영상촬영을 통한 이상 반응은 관찰되지 않았고 사망과 같은 돌발적인 이상반응 역시 확인되지 않아 오존화오일(고농도)의 생체 안전성을 확인할 수 있었다.