K-약침(藥鍼)의 급성(急性) 아급성(亞急性) 독성실험(毒性實驗) 및 항암효과(항암효과)에 관(關)한 실험적(實驗的) 연구(硏究)

김광호,권기록,Kim, Kwang-Ho,Kwon, Ki-Rok 대한약침학회 2003 Journal of pharmacopuncture Vol.6 No.1

Objectives : The purpose of this study was to investigate Acute$\cdot$Subacute Toxicity and Anti-cancer Effect of K-Herbal-acupuncture in mice and rats. Methods : Balb/c mice were injected intraperitoneally with K-herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with K-herbal-acupuncture for subacute toxicity test. K-Herbal-acupuncture was injected on abdomen of mice with S-180 cancer cell line. Result : 1. $LD_{50}$ of K-Herbal-acupuncture was limited $4{\times}10^{-3}$ml/kg~$2{\times}10^{-3}$ml/kg by the test. 2. In acute toxicity test, all of mice were down to the moving reflex, but the weight of mice was increased in treatment group, compared with the normal group. (P<0.05) 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment II group, total cholesterol was increased both treatments.(P<0.05) 4. In subacute toxicity test, the clinical signs of toxication was down to the moving reflex, but it is not severe like acute toxicity test, and observed weight loss at the treatments. 5. In subacute toxicity test, liver weight was decreased compared with the normal group. (P<0.05) 6. In subacute toxicity test of complete blood count test (CBC) of rat, HCT was decreased in treatments, compared with the normal group.(P<0.05) 7. In subacute toxicity test of serum biochemical values of rat, uric acid and triglyceride were decreased, and glucose was increased in treatment groups compared with the control group. (P<0.05) 8. Median survival time was increased about $45\%$ in treatment groups compared with the control group.(P<0.05) 9. Natural killer cell activity was increased in B16F10 lung cancer model, but it was not in sarcoma-180 abdomen cancer. 10. In interleukin-2 productivity test, treatment groups didn't show significant change in lung cancer and abdomen cancer, compared with the normal group.(P<0.005) 11. In making an examination of metastatic cancer with the naked eye, melanoma metastasized in the Lung of C57BL/6 mice. The treated group showed more Melanoma than the control in the numbers and volume. Conclusion : According to the result, K-herbal-acupuncture need further study to know the function and effect in cancer.

정맥주입용(靜脈注入用) 산양산삼(山養山蔘) 증류약침(蒸溜藥鍼)의 급성(急性).아급성(亞急性) 독성실험(毒性實驗) 및 Sarcoma-180 항암효과(抗癌效果)에 관(關)한 실험적(實驗的) 연구(硏究)

권기록,조아라,이선구,Kwon, Ki-Rok,Cho, A-La,Lee, Sun-Gu 대한약침학회 2003 Journal of pharmacopuncture Vol.6 No.2

Objective : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled) in mice and rats. Method : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute $LD_{50}$ toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture caused negligible toxicity, and had anti-tumor effects in mice.

Acute toxicity assessment of nine organic UV filters using a set of biotests

Marcin Stec,Aleksander Astel 한국독성학회 2023 Toxicological Research Vol.39 No.4

UV filters in environmental compartments are a source of concern related to their ecotoxicological effects. However, little is known about UV filters’ toxicity, particularly those released into the environment as mixtures. Acute toxicity of nine organic UV filters benzophenone-1, benzophenone-2, benzophenone-3, 4-methoxy benzylidene camphor, octocrylene, ethylhexyl methoxycinnamate, 2-ethylhexyl salicylate, homosalate, and butyl methoxydibenzoylmethane was determined. UV filter solutions were tested as single, binary, and ternary mixtures of various compositions. Single solutions were tested using a set of bio tests, including tests on saline crustaceans (Artemia franciscana), freshwater crustaceans (Daphnia magna), marine bacteria (Aliivibrio fischeri), and freshwater plants (Lemna minor). The tests represent different stages of the trophic chain, and hence their overall results could be used to risk assessment concerning various water reservoirs. The toxicity of binary and ternary mixtures was analyzed using the standardized Microtox ® method. Generally, organic UV filters were classified as acutely toxic. Octocrylene was the most toxic for Arthemia franciscana ( LC50 = 0.55 mg L– 1) and Daphnia magna ( EC50 = 2.66–3.67 mg L– 1). The most toxic against freshwater plants were homosalate ( IC50 = 1.46 mg L– 1) and octocrylene ( IC50 = 1.95 mg L– 1). Ethylhexyl methoxycinnamate ( EC50 = 1.38–2.16 mg L– 1) was the most toxic for marine bacteria. The least toxic for crustaceans and plants were benzophenone-1 ( EC50 = 6.15–46.78 mg L– 1) and benzophenone-2 ( EC50 = 14.15–54.30 mg L– 1), while 4-methoxy benzylidene camphor was the least toxic for marine bacteria ( EC50 = 12.97– 15.44 mg L– 1). Individual species differ in their sensitivity to the tested organic UV filters. An assessment of the toxicity of mixtures indicates high and acute toxicity to marine bacteria after exposition to a binary mixture of benzophenone-2 with octocrylene, 2-ethylhexyl salicylate, or homosalate. The toxicity of mixtures was lower than single solutions predicting antagonistic interaction between chemicals.

Toxicity and Safety Profiles of Methanolic Extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar Rats

Gotmi Sharwan,Parag Jain,Ravindra Pandey,Shiv Shankar Shukla 대한약침학회 2016 Journal of pharmacopuncture Vol.19 No.3

Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/ kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD – 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single- dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases.

Identification of toxicity variations in a stream affected by industrial effluents using Daphnia magna and Ulva pertusa

Yoo, J.,Ahn, B.,Oh, J.J.,Han, T.,Kim, W.K.,Kim, S.,Jung, J. Elsevier Scientific Pub. Co 2013 Journal of hazardous materials Vol.260 No.-

A comprehensive toxicity monitoring study from August to October 2011 using Daphnia magna and Ulva pertusa was conducted to identify the cause of toxicity in a stream receiving industrial effluents (IEs) from a textile and leather products manufacturing complex. Acute toxicity toward both species was observed consistently in IE, which influenced toxicity of downstream (DS) water. A toxicity identification evaluation (TIE) confirmed that both Cu and Zn were key toxicants in the IE, and that the calculated toxicity based on Cu and Zn concentrations well simulated the variation in the observed toxicity (r<SUP>2</SUP>=0.9216 and 0.7256 for D. magna and U. pertusa, respectively). In particular, U. pertusa was sensitive enough to detect acute toxicity in DS and was useful to identify Zn as a key toxicant. Activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and malondialdehyde were induced significantly in D. magna, although acute toxicity was not observed. In addition, higher levels of antioxidant enzymes were expressed in DS than upstream waters, likely due to the Cu and Zn from IE. Overall, TIE procedures with a battery of bioassays were effective for identifying the cause of lethal and sub-lethal toxicity in effluent and stream water.

Toxicity and Safety Profiles of Methanolic Extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar Rats

Sharwan, Gotmi,Jain, Parag,Pandey, Ravindra,Shukla, Shiv Shankar KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.3

Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD - 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single-dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases.

환경생물에 대한 Herbicidin의 급성독성

박연기,전경미,이환,김보선,양애리,유아선,김영숙,최정섭 한국농약과학회 2019 농약과학회지 Vol.23 No.3

Herbicidin에 대한 물벼룩, 송사리, 잉어, 미꾸리, 지렁이, 그리고 꿀벌에 대한 급성독성시험을 수행하였다. 물벼룩 급성독성시험결과, 시험농도 100 mg/L에서 24시간과 48시간 모두 물벼룩 유영저해 및 치사가 나타나지 않았다. 따라서 48시간 EC50값은 100 mg/L 이상이었다. 어류 급성독성시험결과, 시험농도 100 mg/L에서 24시간, 48시간, 72시간 그리고 96시간에서 송사리, 잉어, 미꾸리 모두 치사개체와 이상증상이 없었다. 따라서 송사리, 잉어, 미꾸리에대한 96시간 LC50값은 모두 100 mg/L 이상이었다. 지렁이 급성독성 시험결과, 시험농도 1,000 mg/kg에서 7일과 14 일 모두 이상증상과 치사 개체는 관찰되지 않았다. 따라서 지렁이 14일 LC50값은 1,000 mg/kg 이상이었다. 꿀벌 급성 접촉 및 섭식독성 시험결과, 시험농도 100 μg/bee 농도에서 24시간과 48시간 모두 치사 개체가 없었다. 따라서 꿀벌 접촉 및 섭식독성 48시간 LD50값은 모두 100 μg/bee 이상으로 나타났다. 결론적으로 Herbicidin의 물벼룩, 어류, 지렁이 그리고 꿀벌에 대한 독성은 거의 없는 것으로 나타났다. Acute toxicity tests of daphnia (daphnia magna), fish (Cyprinus carpio, Oryzias latipes, Misgurus anguillicaudatus), earthworm (Eisenia fetida), and honey bee (Apis mellifera) on herbicidin were performed. The daphnia acute toxicity test showed no swimming inhibition or lethal at 100 mg/L for both 24 and 48 hours. Therefore, the daphnia 48h-EC50 value was more than 100 mg/L. The fish acute toxicity test showed all no mortality or abnormalities at 100 mg/L for 24, 48, 72 and 96 hours. Therefore, the fish 96h-LC50 values were all more than 100 mg/L. The earthworm acute toxicity test showed no mortality or abnormalities at 1,000 mg/kg for both 7 and 14 days. Therefore, the earthworm 14d-EC50 value was more than 1,000 mg/kg. The honey bee acute contact and oral toxicity test showed no mortality at 100 μg/bee for both 24 and 48 hours. Therefore, both acute contact and oral toxicity of honey bee 48h-LD50 values were more than 100 μg/ bee. In conclusion, acute toxicity of herbicidin to daphnia, fish, earthworm and honey bee are practically non toxic.

구피(Poecilia reticulata)에서 수산용의약품 oxolinic acid, neomycin-oxytetracycline, florfenicol의 급성독성 및 Aeromonas salmonicida에 대한 약효 평가

배준성 ( Jun Sung Bae ),이채원 ( Chae Won Lee ),양찬영 ( Chan Yeong Yang ),정은하 ( Eun Ha Jeong ),김아름 ( Areum Kim ),채영식 ( Young-sik Chae ),박정진 ( Jung-jin Park ),박관하 ( Kwan Ha Park ) 한국어병학회 2023 한국어병학회지 Vol.36 No.2

This study evaluated the acute toxicity induced by oxolinic acid (OA), neomycin-oxytetracycline combination (NEO-OTC) and florfenicol (FF) administered to guppy (Poecilia reticulata) by comparing standard formulations with commercial preparations (COOaqua curinpotion, COOaqua terafinpotion and COOaqua profenpotion, respectively) for ornamental fish at concentrations of 2-4%. NEO-OTC exhibited the highest acute toxicity in guppy, with no difference observed between the pstandard formulation and commercial preparation (LC₅₀ = 126.08 mg/L and 112.44 mg/L, respectively). OA acute toxicity was assessed in the form of sodium salt, with an LC₅₀ of 504.61 mg/L for the standard formulation and a slightly increased toxicity of 316.11 mg/L for the commercial preparation. In contrast, no mortality was observed during the 96-hour exposure period with the standard formulation in the form of oxolinic acid. The acute toxicity of FF was measured to be above 1,000 mg/L for the standard formulation; however, the commercial preparation significantly increased to 158.53 mg/L. These results indicate that toxicity can significantly increase in commercial formulations, especially those with low levels of active ingredients. This is presumed to be attributed to the organic solvents or solubilizing agents present in the commercial preparations, which may enhance toxicity. Additionally, guppy infected with Aeromonas salmonicida were effectively protected against mortality by administering OA, NEO-OTC and FF at concentrations of 50 mg/L, 100 mg/L and 15 mg/L, respectively, for 2 hours and at half the dose for 24 hours. This result indicates that liquid formulations containing low concentrations of antibiotics may partially increase toxicity, but there is no problem in effectively treating diseases in ornamental fish.

H-약침(藥鍼)의 급성(急性).아급성(亞急性) 독성실험(毒性實驗) 및 항암효과(抗癌效果)에 관(關)한 실험적(實驗的) 연구(硏究)

김태희,권기록,이선구,Kim, Tae-Hui,Kwon, Ki-Rok,Lee, Seon-Goo 대한약침학회 2002 Journal of pharmacopuncture Vol.5 No.2

Objectives : The purpose of this study is to investigate Acute and Subacute Toxicity, and Anti-cancer Effect of H Herbal-acupuncture on mice and rats. Methods : Balb/c mice were injected intraperitoneally with H Herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were experimented in the same way for subacute toxicity test. H Herbal-acupuncture was injected into abdomen of mice having S-180 cancer cell line. Result : 1. During the test, $LD_{50}$ could not be counted since there was no expired subjects. 2. In an acute toxicity test, the loss of motility and reflex action was observed, but weight increased in the treatment group, compared with those in the normal group (P<0.05). 3. In an acute toxicity test of serum biochemical values of mice, glucose increased in the treatment group II while total cholesterol was increased in the all treatment groups (P<0.05). 4. In a subacute toxicity test, a little loss of motility and reflex action was observed in the treatment group. Weight of mice in the treatment group decreased on the 28th day. 5. In a subacute toxicity test, liver weight was decreased but lung weight of mice increased in the all treatment groups (P<0.05). 6. As a result of measuring Complete Blood Count test (CBC) of rat, HCT was decreased in treatments even though it was not significant, compared with the normal group (P<0.05). 7. In a serum biochemical value test of subacute toxicity, total protein and albumin decreased in the all treatment groups. Creatinine, glucose, GOT increased in the treatment group I compared with the control group. Alkaline phos-phatase decreased in treatment II group, compared with the control group (P<0.05). 8. Median survival time that was measured in the rats treated with sarcoma-180 cancer cell Median decreased in the treatment group, compared with the control group (P<0.05). 9. Natural killer cell activity showed significant reduction at 100:1 and 10:1 E/T ratio while it increased at 50:1 E/T ratio. It is inferred that there was an error in the experiment (P<0.05). 10. In an interleukin-2 productivity test, even though it decreased in lung cancer, and increased in abdomen cancer, but it was only a small difference (P<0.005). 11. After injecting B16F10 cell into a capillary vessel of C57BL/6 mice and generating metastasized lung cancer, the lung was examined with the naked eye. It was not possible to see metastasized cancer in the all groups on the seventh day but the cancer was viewed on the fourteenth day. The number and volume of metastasized cancer in the treatment group enlarged in the treatment group, compared with the control group. Conclusion : According to the results, H herbal-acupuncture took no effects in cancer.

WHW®의 랫드에서의 반복경구투여 독성에 관한 연구

오태우,배효상,윤철호,박용기 대한본초학회 2010 大韓本草學會誌 Vol.25 No.3

Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 ㎎/㎏/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity. Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 ㎎/㎏/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.