• 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.

• Korean Journal of Pharmacognosy
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• v.42 no.1
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• pp.76-81
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• 2011

The study of irritation and toxicity of honeybee(Apis mellifera. L) venom collected by a bee venom collector applied topically to the skin and mucous membrane were carried out to prove the safety of honeybee venom in clinical use. Animal for the research was the rabbit and the solution for the test was made from honeybee venom. Six animals were used for the skin test and nine animals were used for the eye mucous membrane test. In results, both tests proved that honeybee venom makes no irritable reaction on skin and eye mucous membrane of rabbit. We consider that this result is helpful for saying about the safety of honeybee venom in clinical use.

• Journal of Pharmacopuncture
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• v.3 no.1
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• pp.53-63
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• 2000

Carthami tinctorii Fructus is known for its good effect on diseases such as fracture, menorrhalgia, menoschesis, puerperium aneilema and so on. The study of irritation and toxicity of Carthami oil aquapuncture solution applied topically to the skin and the eye mucous membrane were carried out to prove the safety of Carthami oil aquapuncture solution in clinical use. Animal for the research was the rabbit and the solution for the test was made from Carthami semen. 6 animals were used for the skin test and 9 animals were used for the eye mucous membrane test. In results, both tests proved that Carthami oil aquapuncture solution makes no irritable reaction on skin and eye mucous membrane of rabbit. We consider that this result is helpful for saying about the safety of Carthami oil aquapuncture solution in clinical use.

• Herbal Formula Science
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• v.24 no.4
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• pp.289-300
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• 2016

Objectives : Taglisodog-eum(TSE), a poly herbal formula, has been widely used to improve carbuncles by removing inflammation of the lymphatic channels in Traditional Korean Medicine. We previousely reported the action mechanism of TSE on experimental atopic dermatitis and the establishment of formulation for TSE ointment. In this study, we examined the toxicity test on skin and eye irritation by TSE ointment to prove the safety of Taglisodog-eum ointment in clinical use. Methods : Acute skin toxicity of the TSE ointment was evaluated in Sprague-Dawley(SD) rats. After dermal administration of TSE ointment(2,000mg/kg), body weight, mortality, and clinical signs of the rats were observed for 14days. Primary skin irritation and ocular irritation tests for TSE ointment were performed in male New Zealand White Rabbits. In dermal and ocular irritation test, body weight, mortality, clinical signs, Primary Irritation Index(P.I.I.), and The Index of Acute Ocular Irritaion(I.A.O.I.) of rabbit were observed after applying at abraded skin and eye balls with Taglisodog-eum ointment. Results : In the results of acute skin toxicity, no significant differences were found in body weight, the clinical sign and the mortality between control and TSE ointment treated group. In primary dermal irritation test, body weight, the clinical sign and the mortality were not significantly changed and Primary Irritation Index(P.I.I.) was 0.8, indicating TSE ointment as weak irritant material. In ocular irritation test, The Index of Acute Ocular Irritaion was 0.0, indicating TSE ointment as non-irritating to the eye of the rabbits. To evaluate toxicity of the TSE ointment in animal test, body weight, the clinical signs, the skin and eye irritation check were conducted; TSE ointment was considered to be weak dermal irritant in test animals. The no response of eye irritation test was observed in this experimental condition. Conclusions : According to the above toxicity test, We consider that this results is helpful for saying about the safety of TSE ointment in clinical use.

• Journal of the Korean Applied Science and Technology
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• v.35 no.4
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• pp.1407-1412
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• 2018

This study suggests that ozonated olive oil can kill a wide variety of microorganisms while being less toxic but in the case of administration or abdominal administration, the human body is harmless. In Korea, there is no animal stability test yet. In this study, ozonated olive oil was used to test the stability of the animal through the eye. Specific experiments were performed to evaluate animal Ocular irritation safe test of ozonized oil (high concentration) in rabbits. and Observation of the treatment point on the test substance, ozonated olive oil showed no Ocular irritation in both the non-washing group and the washing group.

• Journal of Biomedical Engineering Research
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• v.40 no.5
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• pp.143-150
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• 2019

To evaluate the toxicity of ophthalmic drug, the Draize test and Bovine Corneal Opacity and Permeability (BCOP) test commonly used. In Draize test, experimental animals were under stress and pain due to long-term exposure of drug. In addition, regarding physiological functions, animal model is not perfectly reflected a human eye condition. Although some models such as $EpiOcular^{TM}$, HCE model, LabCyte Cornea-Model, and MCTT $HCE^{TM}$ were already presented advanced cornea ex-vivo model to replace animal test. In this sense, cornea tissue structure mimicked ex-vivo toxicity model was fabricated in this study. The corneal epithelial cells (CECs) and keratocytes (CKs) isolated from rabbit eyeball were seeded on non-patterned silk film (n-pSF) and patterned silk film (pSF) at $32,500cells/cm^2$ and $6,500cells/cm^2$. Sequentially, n-pSF and pSF were stacked to mimic a multi-layered stroma structure. The thickness of films was about $15.63{\mu}m$ and the distance of patterns was about $3{\mu}m$. H&E stain was performed to confirm the cell proliferation on silk film. F-actin of CKs was also stained with Phalloidin to observe the cytoskeletal alignment along with patterns of the pSF. In the results, CECs and CKs were shown the good cell attachment on the n-pSF and pSFs. Proliferated cells expressed the specific phenotype of cornea epithelium and stroma. In conclusion, we successfully established the ex-vivo cornea toxicity model to replace the eye irritation tests. In further study, we will set up the human ex-vivo cornea toxicity model and then will evaluate the drug screening efficacy.

• Toxicological Research
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• v.18 no.1
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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.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.150-157
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• 1997

Capsaicin cream has been used to attenuate the pain associated with diabetic neuropathy, rheum-atoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, local irritation, limits the use of it and there is still a need for a new analgesic devoid of this side effect. This study was conducted to compare the local irritant effect of DA-5018, a new capsaicin derivative, with that of capsaicin in various animal models and human beings. Capsaicin, applied topically to the mouse ear, produced dose-dependent increase of ear volume and the frequency of ear scratching behavior in mice. Neither ear volume nor scratching behavior was affected by DA-5018. In eye wiping test of rat, DA-5018 was 10 times less irritant than capsaicin. Capsaicin administered intradermally into the rat paw elicited paw lick/lift response with a potency which was three times that of DA-5018. Zostrix-HP (0.075% capsaicin cream), but not DA-50180.3% cream, increased ear volume of rat and induced thermal hyperalgesia in normal and carrageenan inflamed paws. Six day-treatment of Zostrix-HP failed to develop tolerance against this thermal hyperalgesia. In human beings, Zostrix-HP produced burning sensation and itching in more than 90% of volunteers involved and its maximum irritant effect was significantly higher than that of DA-5018 cream. These results suggest that local irritation and burning sensation produced by DA-5018 is much less than capsaicin.

• Journal of Conservation Science
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• v.33 no.4
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• pp.255-266
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• 2017

Chemically derived pesticides have been used to prevent biological damage to domestic cultural property. However, their use is gradually being restricted due to the harmful effects on the human body and environment. Therefore, there is a growing interest in the search for new antifungal biopharmaceuticals whose safety has been confirmed by toxicity evaluation through animal experiments. This paper presents methods of toxicity evaluation of natural biocides using Sprague-Dawley rats and New Zealand White (NZW) rabbits. Safety of the natural biocide extract of Asarum sieboldii was evaluated using single-dose oral and dermal toxicity tests in Sprague-Dawley rats, and eye and skin irritation tests in NZW rabbits. The extract has proven antimicrobial and insecticidal activities against wood-rotting fungi and termites. After single oral administration to rats, the $LD_{50}$ values were determined to be over 4,000 and 2,000 mg/kg for males and females, respectively. After single dermal administration to rats, the $LD_{50}$ values exceeded 10,000 mg/kg for both males and females. The extract was identified to be non-irritant to the rabbit eye, and only slightly irritant to the rabbit skin. In this study, we confirmed the safety of the A sieboldii extract through animal testing. Due to the harmfulness of humidifier disinfectants, focus is on the safety of chemical pesticides, and toxicity evaluation is suggested as the basic method for hazard evaluation.