• Toxicological Research
• /
• v.21 no.2
• /
• pp.115-119
• /
• 2005

In the present study, we evaluated the free radical scavenging and xanthine oxidase inhibitory activities exhibited by extracts obtained from the dried stems (and leaves) of Lespedeza bicolor We also assessed its potential irritation activities with regard to cosmetic use. When the DPPH radical scavenging activities of L. bicolor were assessed at six different concentrations (0, 50, 100, 250, 500 and 1000 ${\mu}g/ml$), the concentration of L. bicolor required to inhibit DPPH radical formation by $50\%$ was found to be $164.90{\mu}g/ml$. The effects of L. bicolor on the inhibition of xanthine oxidase were determined at seven different concentrations. The $50\%$ effective concentration was found to be $282.75{\mu}g/ml$. In the skin irritation test, all animals survived for the duration of the study, and all exhibited normal gains in body weight. The control sites exhibited no response to the control procedures. No edema, erythema, or eschar formation was observed in any of the tested rabbits. In the ocular irritation study, all of the rabbit eyes remained normal. In summary, L. bicolor extracts were considered to be non-irritating to the skin and eye.

• Toxicological Research
• /
• v.33 no.3
• /
• pp.191-203
• /
• 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 Pharmaceutical Investigation
• /
• v.30 no.3
• /
• pp.173-178
• /
• 2000

The purpose of this work is to develop a transurethral suppository containing prostaglandin $E_1\;(PGE_1)$, which stabilizes the drug, gives no irritation to physiological body and enhances the erectile response of $PGE_1.\;PGE_1$ transurethral suppositories were prepared with various amounts of compositions such as saturated polyglycolysed glyceride $(Suppocire^{\circledR}\;AP,\;SAP)$, polyoxyethylene hydrogenated castor oil (HCO-50) and ethanol. The melting points, viscosities and $PGE_1$ release of the suppositories were investigated. Ocular irritation test was carried out after application of $PGE_1$ suppository to rabbit's eye. The intracavernous pressure (ICP), penile length and duration of erectile response were determined after transurethral administration of $PGE_1$ suppository and compared with those after intracavernosal injection of $PGE_1$ solution to cats. HCO-50 hardly affected the melting points and viscosities of $PGE_1$ suppositories. Additionally, $PGE_1$ transurethral suppositories, whose melting point ranges was $34-35^{\circ}C$, was speedily melted in physiological body. HCO-50 significantly decreased the dissolution rates of $PGE_1$ from the suppositories. Dissolution mechanism analysis showed the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppositories by Fickian diffusion. The release rate of $PGE_1$ from $PGE_1$ suppository [PGE1/SAP/HCO-50/ethanol (1/94.5/2.5/2%)] was about 80% within 2 h. This $PGE_1$ suppository gave no significant irritation to the ocular tissue, expecting that it gave no irritation to the urethral tissue less sensive than ocular tissue. Furthermore, $PGE_1$ in this suppository was stable at $4^{\circ}C$ for 2 years. This suppository increased the ICP and penile erection similar to those of injectable $PGE_1$ solution. However, it gave 2.5-fold increased duration of erectile response than injectable $PGE_1$ solution. Our results suggested that it gave more effective erectile response than injectable $PGE_1$ solution in cats. It is concluded that this $PGE_1$ suppository with good safety, excellent stability and enhanced erectile response, could be a more effective and convenient transurethal delivery system of $PGE_1$.

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

• Toxicological Research
• /
• v.26 no.1
• /
• pp.9-14
• /
• 2010

The evaluation of eye and skin irritation potential is essential to ensuring the safety of human in contact with a wide variety of substances. Despite this importance of irritation test, little is known with respect to the irritation potency of lomefloxacin, a fluoroquinolone antibiotic, which has been known to cause phototoxicity with an abnormal reaction of the skin. Thus, to investigate the tendency of lomefloxacin to cause eye and skin irritation, we carried out in vitro eye irritation test using Balb/c 3T3, and in vitro skin irritation test using $KeraSkin^{TM}$ human skin model system. 3T3 neutral red uptake assay has been proposed as a potential replacement alternative for the Draize Eye irritation test. In this study, the $IC_{50}$ value obtained for lomefloxacin was 375 ${\mu}g$. According to the classification model used for determining in vitro categories, lomefloxacin was classified as moderately irritant. For evaluation of skin irritation, engineered epidermal equivalents ($KeraSkin^{TM}$) were subjected to 10 and 25 mg of lomefloxacin for 15 minutes. Tissue damage was assessed by tissue viability evaluation, and by the release of a pro-inflammatory mediator, interleukin- 1${\alpha}$. Lomefloxacin increased the interleukin-1${\alpha}$ release after 15 minutes of exposure and 42 hours of post incubation, although no decrease in viability was observed. Therefore, lomefloxacin is considered to be moderately irritant to skin and eye.

• Biomolecules & Therapeutics
• /
• v.2 no.3
• /
• pp.247-255
• /
• 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.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.195-195
• /
• 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 skin irritation tests, ocular irritation test, and skin sensitization test.(omitted)

• Journal of Korean Ophthalmic Optics Society
• /
• v.11 no.4
• /
• pp.299-310
• /
• 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
• /
• v.18 no.1
• /
• pp.79-85
• /
• 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
• /
• v.14 no.3
• /
• pp.393-400
• /
• 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.