• Toxicological Research
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• v.13 no.1_2
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• pp.157-160
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• 1997

The primary skin and eye irritancy of the combined vaccine (KGCC-95VI) for the prophylaxis against Japanese encephalitis and Hantaan virus infection recently developed by Korea Green Cross Corporation was investigated. The KGCC-95VI was applied to the back skins of the New Zealand White rabbits. The rabbits were observed for 72 hours and did not exhibit erythema, eschar and edema. The eyes of the rabbits were exposed to the KGCC-95VI. The rabbits were observed for 7 days and did not exhibit any ocular findings on cornea, iris and conjuntivae. The KGCC-95VI is considered not to have the primary skin and eye toxicity in rabbits.

• Toxicological Research
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• v.12 no.1
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• pp.101-111
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• 1996

The local irritation studies of DA-3285, recombinant human erytropoietin(rHu-EPO), were carried out in rabbits after the following treatment; single application into the conjunctival sac of the eye, single subcutaneous injection, 7-day repeated subcutaneous injection and 8-day repeated infusion into the ear vein. Also, the local irritancy of DA-3285 leaked around vein was studied in mice by single perivascular injection. The results obtained were as follows. In the result of ocular irritation test, DA-3285 could be considered as a non-irritating material. In single and 7-day repeated subcutaneous irritation test, the irritancy of DA-3285 was not so much different from that of saline. The vascular irritancy of DA3285 by 8-day repeated infusion was negligible and similar to that of saline. And the irritancy of DA3285 by perivascular injection was comparable to that of saline. These results indicate that DA-3285 has no irritating activity when injected through subcutaneous or intravenous route for clinical practice as 3.5% solution.

• 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.

• Journal of Korean Ophthalmic Optics Society
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• v.10 no.4
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• pp.293-304
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• 2005

As the eye irritant test of lens washing agent, ReNu$^{TM}$ was analysed using Draize methods (1959) according to KFDA Guidelines. In addition, to test the potential toxicity of test articles the ratio of inflammatory cells and non-inflammatory epitheloid cells were also observed using smear cytology methods against ocular discharge. At test, the histopathological changes on the cornea, iris, retina and sclera were also observed in all animals. Slight irritancy of the cornea and conjunctiva were observed at 1, 2 and 3 days after dropping in non-washing group. The Mean Index of Ocular Irritation(MIOI) of these points are detected as 4.17, 3.00 and 1.33, respectively. In washing group, slight irritancy of the cornea and conjunctiva were observed at 1 and 2 days after dropping with MIOI as 0.67 and 1.33, respectively. Therefore, ReNu$^{TM}$ was considered as non-irritating materials because the MIOI is detected below 5.00 throughout the whole experimental periods in both washing and non-washing groups. The Index of Acute Ocular Irritation(IAOI) is also detected as 4.17(1 day after dropping). Except of the somewhat increase trend of the inflammatory cell ratios in ocular discharge at 1 day after dropping of non-washing group, but significances are not detected, on the other hand, no meaningful changes on smear cytology of ocular discharges are observed in this study. In addition, no abnormal histopathological changes on the cornea, iris, retina and sclera were also not detected in ReNu$^{TM}$ dropping group compared to that of non-treated control eyes.

• Journal of Korean Ophthalmic Optics Society
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• v.12 no.2
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• pp.67-78
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• 2007

The eye irritant test of lens washing agent, CLIWELL$^{TM}$ was conducted using Draize methods according to KFDA Guidelines. In addition, to test the potential toxicity of test articles, the ratio of inflammatory cells and non-inflammatory epitheloid cells was also observed using smear cytology methods against ocular discharge. At sacrifice, the histopathological changes on Cornea, Iris, Retina and Sclera were also observed in all animals. Slight irritancy of cornea and conjunctiva was observed at 1, 2 and 3 days after dropping in non-washing group. The MIOI of these points are detected as 4.50, 1.67 and 0.67, respectively. In washing group, slight irritancy of cornea and conjunctiva were observed at 1 and 2 days after dropping with MIOI as 0.67, respectively. Therefore, CLIWELL$^{TM}$ was considered as non-irritating materials because the MIOI is detected below 5.00 throughout the whole experimental periods in both washing and non-washing groups and the IAOI was also detected as 4.50. Except for significant increase of the inflammatory cell ratios in ocular discharge at 1 day after dropping of non-washing group compared to that non-treated intact eyes, no meaningful changes on smear cytology of ocular discharges are observed in this study. In addition, no abnormal histopathological changes on the cornea, iris, retina and sclera were also detected in CLIWELL$^{TM}$ dropping group compared to that of non-treated intact eyes.

• Journal of Korean Ophthalmic Optics Society
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• v.11 no.4
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• pp.299-310
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• 2006

The eye irritant test of lens washing agent, $SOLOCARE^{TM}$ was conducted using Draize methods according to KFDA Guidelines 1999-61. In addition, to test the potential toxicity of test articles the ratio of inflammatory cells and non-inflammatory epitheloid cells were also observed using smear cytology methods against ocular discharge. At sacrifice, the histopathological changes on Cornea, Iris, Retina and Sclera were also observed in all animals. Slight (1~2 degrees) irritancy of cornea and conjunctiva were observed at 1, 2 and 3 days after dropping in non-washing group. The MIOI of these points are detected as 4.33, 3.33 and 2.00, respectively. In washing group, slight irritancy of cornea and conjunctiva were restricted to 1 and 2 days after dropping with MIOI as 3.00 and 1.33, respectively. Therefore, $SOLOCARE^{TM}$ was also considered as non-irritating materials because the MIOI is detected below 5.00 throughout the whole experimental periods in both washing and non-washing groups and the IAOI is also detected as 4.33 (1 day after dropping). No meaningful changes on smear cytology of ocular discharges are observed in this study compared to that of non-treated intact eyes. In addition, no abnormal histopathological changes on the cornea, iris, retina and sclera were also detected in $SOLOCARE^{TM}$ dropping group compared to that of non-treated intact eyes.

• Toxicological Research
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• v.14 no.3
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• pp.393-400
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• 1998

As a series of safety studies on DA-3585, a recombinant human erythropoietin, its local irritancy was examined in rabbits after the following treatments; application into the conjunctival sac of the eye(single), subcutaneous injection (single and -day repeated)and intravenous injection (7-day repeated.)In addition, perivascular irritation of DA-3585 was investigated in mice. In the result of ocular irritation test, 10,000IU/ml solution of DA-3585 could be considered as a non-irritating material. The local irritation of DA-3585 by a single and 7-day repeated subcutaneous injection was negligible and not so much different from that of saline. In the vascular irritancy test, macro-and microscopic observations revealed that local irritation of DA-3585 was comparable to that of saline when injected into retroauricular vein of rabbits for 7 consecutive days. Furthermore the perivascular administration of DA-3585 upto the concentration of 10,000 IU/ml did not induce any morphological abnormalities at injection sites. The results obtained from the present study suggest that the local irritancy of DA-3585 is not different from that of saline when injected through intravenous or subcutaneous route for clinical practice.

• Biomolecules & Therapeutics
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• v.2 no.3
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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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• 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.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.364-372
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• 1996

The primary skin and eye irritation test of 0.3% DA-5018 cream, a capsaicin analogue, were carried out in rabbits. As control materials, Zostrix-HP cream (0.075% capsaicin cream) and the base of 0.3% DA-5018 cream were used in the same manners. In the primary skin irritation test, the Primary Irritation Index (P.I.I.) was 1.6, 1.9 and 0.5 in groups treated with 0.3% DA-5018 cream, Zostrix-HP cream and the base of 0.3% DA-5018 cream, respectively. The irritation ratings of 0.3% DA-5018 cream and Zostrix-HP cream were mildly irritating. The base of 0.3% DA-5018 cream was evaluated as a non-irritating material. In the eye irritation test, 0.3% DA-5018 cream and Zostrix-HP cream could be considered as mildly irritating materials. But, the base of 0.3% DA-5018 cream was a non-irritating material. These results suggest that 0.3% DA-5018 cream has mildly irritating activity and its irritancy is similar to that of Zostrix-HP cream.