• 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.

• Journal of Applied Biological Chemistry
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• v.60 no.3
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• pp.245-248
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• 2017

Saline groundwater was obtained from a 100-m deep basalt layer into which seawater had infiltrated. This groundwater is known to contain various minerals. Like deep seawater, saline groundwater is expected to have various applications due to the presence of biologically beneficial minerals. In Korea, saline groundwater is mainly obtained from the coastal area of Jeju. Before applying saline groundwater to various products, however, its biological safety needs to be examined. In the present study, skin and eye irritation tests were performed to assess the safety of saline groundwater according to the guidelines of the Korea Food and Drug Administration. When compared to control, Jeju saline groundwater showed no level of eye and skin irritation. These results suggest that Jeju saline groundwater induces no irritation, and is therefore sufficiently safe to be applied to the eye and skin of people.

• Journal of the Korean Society of Tobacco Science
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• v.24 no.1
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• pp.13-20
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• 2002

This study was conducted to evaluate the prediction of sensory attributes of tobacco smoke by the use of volatile oil components of tobacco. For analytical and sensory evaluations, twelve aging tobaccos (i.e., 3 crop years; 1998, 1999, 2000, and 4 stalk positions) were prepared in flue-cured and burley tobaccos. 61 volatile oil components and 5 sensory attributes such as irritation, impact, after taste, bitter and green were investigated. Irritation of flue-cured tobacco, and irritation and impact of burley tobacco were significantly increased with the ascending stalk position, whereas after taste of burley tobacco was significantly decreased. Significantly positive correlations among irritation, impact, and bitter were observed in flue-cured tobacco. A significantly positive correlation between irritation and bitter was observed, significantly negative correlations between after taste and irritation and between after taste and impact were observed in burley tobacco. Except for green of burley tobacco, all probabilities of multiple linear regression equations between volatile oil components of tobacco and sensory attributes of tobacco smoke were significant(P$\leq$0.05). This study suggests that the multiple linear regression equations may be useful to predict the sensory attributes of tobacco smoke with a few selected volatile oil components of tobacco.

• Toxicological Research
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• v.12 no.1
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• pp.87-91
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• 1996

LB00013, a newly developed recombinant human Interferon $\beta$, was tested for primary eye and skin irritation in male New Zealand White rabbits. In the primary eye irritation test, 0.1 ml of a solution of LB00013 was instilled into the eye. In the rinsing group, the eye was washed with water at 30 seconds after instillation. No reaction was produced at the cornea, iris and conjunctivae by LB00013. In the primary skin irritation test, LB00013 was applied to the back of rabbits for 24 hours. Primary irritation index was "0" in test and control sites of all animals. Thus LB00013 was evaluated as a non-irritant on the basis of the criteria of Draize et al. (1944).l. (1944).

• YAKHAK HOEJI
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• v.38 no.5
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• pp.562-567
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• 1994

Now para-phenylenediamine(PPDA) is generally used as component of most hairdyes because it can be used more conveniently and effectively than the others. But PPDA become known to cause side effects such as skin sensitization, contact dermatitis and eye irritation. So this study was done to restudy the safety of hairdyes containing PPDA. The results of experiment were as follows. 1. As a result of primary skin irritation test and eye irritation test in white rabbits, the solution containing 5% PPDA(in saline) were classified as weak irritant but four kinds of commercial hairdyes containing PPDA were proved not to have any irritation. 2. As a result of skin sensitization test in guinea pig, four kinds of commercial hairdyes were classified as Calss I(week irritant) but three kinds of commercial hairdyes induced skin sensitization for guinea pig to 5% in test groups. These results indicate that the actual toxicity of commercial hairdyes(four kinds) is negligible. But based on the results of experiment, it is thought that there is possibility of some commercial hairdyes to induce skin sensititization.

• Toxicological Research
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• v.18 no.1
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• pp.79-85
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• 2002

YHB216 is one of new recombinant human erythropoietins (rHu-EPO) developed by Yuhan Research Institute. The rHu-EPO products are widely being used for the treatment of various types of anemia. As a series of safety studies on YHB216, we performed the local irritation test (dermal & ocular application) in male New Zealand White rabbits and micronucleus test in male ICR mice. In the skin irritation test, 0.5 ml of YHB216 10,000 IU/ml solution was applied to the back skin of rabbits for 24 hours and sub-sequent observation was performed. There was no induced response after the treatment and the primary irritation index (P.I.I.) was‘0’. In the eye irritation test, 0.1 ml of YHB216 10,000 IU/mL solution was instilled into the conjunctiva of the eye. No treatment-related reaction was observed at the cornea, iris, and conjunctiva. In the micronucleus test, YHB216 was administered intravenously to male mice (6 mice per group) at dose levels of 0, 6,250, 12,500, and 25,000 IU/kg. Bone marrow cells were collected at 24 hours after the treatment. YHB216 treated groups showed no significant difference in the P/N (polychromatic erythrocyte/ normochromatic erythrocyte) ratio and in the number of micronucleated polychromatic erythrocyte com-pared with the control. In conclusion, YHB216 was found to be a non-irritating material up to 10,000 IU/ml in the local irritation test and to be a non-mutagen up to 25,000 IU/kg in the micronucleus test.

• 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.

• 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.

• Korean Journal of Veterinary Research
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• v.45 no.1
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• pp.39-43
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• 2005

The present study was carried out to investigate the skin irritation potential of oregano 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. Treatment-related toxic symptoms, as evidenced by anorexia and decreased locomotor activity, were observed in all rabbits tested. Two rabbits out of the 6 total died on day 2 after the application of test article due to treatment-related toxicity. The mean body weight of test animals decreased progressively during the 72 h observation period. All animals showed very slight edema at 24 h and then recovered at 72 h. These animals also showed very slight to severe erythema and/or slight eschar formation at both 24 h and 72 h. The eschar formation induced by oregano oil was not recovered at the end of additional 11-day recovery period. Based on these results, it was concluded that a single dermal application of the undiluted oregano oil caused an increased incidence of clinical signs and death and a decrease in the body weight and showed a primary irritation index score of 2.79 indicating moderate irritation.

• 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.