• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.213-224
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• 2016

Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

• Environmental Analysis Health and Toxicology
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• v.17 no.1
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• pp.81-93
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• 2002

There were no specific effects for test materials on Sprague-Dawiey (S.D.) rats in clinical symptoms, amounts of food intakes, weight changes, laboratory findings, and pathology after whole body 1, 1-Dichloro-1-fluoroethane (used as coolant, metal cleaner and solvents) exposure (0, 1,500, 3,000, and 6,000 ppm) for 13 weeks (6 hour/day, 5 days/week). However, the loss of capillary vessels in eyeball (pupil) was observed in a female rat among 6,000 ppm group. Though there was a tendency for MCHC (Mean Corpuscular Hemoglobin Concentration) in rat to be decreased (p<0.05), it was not regarded as abnormal because the values were within normal limits. In asthma-stimulation related evaluations. there was also a tendency for inflammatory cell counts in bronchoalveolar lavages to be increased. But it had no statistical significance, and also no dependency on sex and the exposed concentration . Based on this result, the non observed effect level (NOEL) induced by 1, 1-Dichloro-1-fluoroethane inhalation was evaluated in groups with 3,000 ppm below (S.D. Rats, 13 weeks). Finally, it was concluded that the short term exposal of 1, 1-Dichloro-1-fluoroethane is not considered as a asthma stimulant by inhalation despite of some study limitations such as test animals use and short-term exposure.

• The Korean Journal of Pesticide Science
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• v.7 no.4
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• pp.280-287
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• 2003

To assess the risk of pesticides on earthworm, the acute toxicities of 10 pesticides were investigated and their toxicity exposure ratios(TERs) were calculated. As the TERs of paraquat dichloride and pendimethalin were more than 100, their risks were rated negligible. Risk of benfuracarb, cadusafos, chlorpyrifos-methyl, endosulfan, isazofos and parathion which have TERs of $10\sim100$ were rated low. However, risk of imidacloprid and phorate which have TER of less than 10 were estimated highly to need a reproduction study. Earthworms were exposed to twenty two pesticides including dazomet 98% GR having PECs of more than $5mg{\cdot}kg^{-1}$ in artificial soil at standard and double dose for 14 days. All the earthworms exposed to dazomet 98% GR and metam-sodium 25% SL were died to show their high risk, while no serious adverse effects were observed in the soil treated with 15 pesticides, calcite 95% WP, calcium polysulfide 36% CF, chlorothalonil 75% WP, daminozide 85% WP, dichlonil 6.7% GR, etridiazole 25% EC, fosetyl-Al 80% WP, glyphosate 41 % SL, hymexazol 30% SL, iprodione 50% WP, machine oil 95% EC, mancozeb 75% WP, propineb 70% WP, terbuthylazine 80% WP and triazophos 40% EC. In case of thiophanate-methyl 70% WP, copper hydroxide 77% WP, dimethoate 46% EC, tolclofos-methyl 50% WP and propamocarb hydrochloride 67% SL, any effect did not show clearly, suggesting an additional subchronic toxicity study. The risk of thiophanate-methyl 70% WP to earthworm was estimated high, considering its subchronic effect, while effects of copper hydroxide 77% WP, dimethoate 46% EC, tolclofos-methyl 50% WP and propamocarb hydrochloride 67% SL to earthworms were negligible, considering no adverse effects in subchronic tests.

• Toxicological Research
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• v.34 no.2
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• pp.111-125
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• 2018

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of $356mg/m^3$ (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions.

• Korean Journal of Environmental Agriculture
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• v.4 no.2
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• pp.118-125
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• 1985

To establish an evaluation system of aquatic toxicity of chemicals at no-effect level, flow through and early life stage toxicity test were performed on a freshwater fish, the medaka (Oryzias latipes). The characteristics of medaka as a bioassay organism for the chronic toxicity test were discussed. Maximum acceptable toxicant concentration(MATC) of butachlor for the madaka in soft water was estimated using survival, growth, and reproduction as indicators of toxic effects. During a 3-month period, the fry of medaka were exposed to butachor concentrations ranging from 0.16 to 0.0l mg/liter and the DO concentration, temperature, and pH in the exposure chamber were measured to check the test condition. The highest concentration showed slight decrease of growth rate in medaka and reduced hatchability of spawning egg. Survival, growth, and reproductive success of adults in butachlor concentration of 0.04 and 0.01 mg/liter were not different from those of the control. The MATC was estimated to be between 0.04 and 0.16 mg/liter for medaka.

• Journal of the Korean Society of Tobacco Science
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• v.30 no.1
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• pp.66-76
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• 2008

생물학적으로 활성이 있는 물질들의 생체 내 대사를 이해하고 인체 독성 및 질환의 발현을 예측할 수 있는 가장 좋은 시험방법은 생체 내 독성 평가법이다. 담배연기의 생체 내 독성 평가법에는 14일 흡입독성시험, 90일 흡입독성 시험 및 피부도말 종양발생 시험 등이 있다. 90일 흡입독성 시험은 담배의 일반적인 독성 정보를 제공한다. 생체 내 독성평가는 담배 첨가물, 재료품 또는 제품 설계를 변경할 경우 담배연기 독성이 증가 또는 감소되었는 지를 평가할 수 있으며 이 결과는 제품보증에 활용될 수 있다. 캐나다의 독성평가자료 제출 및 EU 등의 담배첨가물에 대한 규제는 향 후 이런 생체 내 시험에 대한 지속적이고도 구체적인 요구를 할 것으로 사료된다.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.198-198
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• 2002

• Proceedings of the Korean Environmental Health Society Conference
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• 2005.06a
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• pp.303-305
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• 2005

3-Monochloro-1,2-propanediol (3-MCPD) is a contaminant of acid-hydrolyzed vegetable protein. Several reports have suggested that chronic exposure to 3-MCPD could produce neurotoxicity in vitro or neurobehavioral effects inaspects of experimental animals. Disturbance of the nitric oxide signaling pathway by chronic exposure to 3-MCPD may be a causal factor of neurological disorders in rats. In order to investigate the relationship between 3-MCPD administration and expression of inducibal nitric oxide synthase (iNOS), the numbers and distribution patterns of iNOS-immunoreactive neurons were examined. At the all three bregma level examined, the optical density of iNOS-postive neurons was significantly increased following exposure to 3-MCPD. The change was more severe in the upper layer than in deep layer of the cortex. These data suggest that 3-MCPD toxicity may be mediated through disturbances to the nitric oxide signaling pathway.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.198-198
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• 2002

Occurrence of Chinese Herbs Nephropathy (CHN) has been reported in young women who had taken a slimming pills containing some chinese herbs. Aristolochic acid (AA) known as a carcinogen, was suspected as the major causal factor of CHN. AA is major component of fruit of A. contorta was used in Korean Traditional Medicine.(omitted)

• Journal of Sasang Constitutional Medicine
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• v.9 no.2
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• pp.203-225
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• 1997

Jihwangbakhotang(地黃白虎楊) is made by Li Je Ma, the creator of the Four Constitutional Medicine. Single and 13 weeks oral repeated dose toxicity studies were conducted in Sprague Dawley rats of both sexes to elucidate the potential acute and subchronic toxicity of JBT extract and reversibility of any effects. In the single dose study, JBT extract was administered orally to rats with the dose of 2 g/kg and 8 g/kg. In the long term administration of 13 weeks, the JBT extract of 125 mg/kg/day, 500 mg/kg/day, 2000 mg/kg/day was administered to rats. The change of blood weight, urine volume, electrolyte in urine, hematological change, the change of blood chemistry, autopsy finding, and histological observation were researched, the results were as follows; 1. The lethal dose of JBT extract seems to be over 10 g/kg, the single administration of JBT extract 8 g/kg showed no toxical signs except little increase of urine volume. 2. The change of body weight had the trend of decrease in the group of, but has no significance, and also the consumption of food and water had no changes. 3. The hematological changes induced by the 13 weeks administration of JBT extract showed the significance in the item of Hb, MCH, MCV, WBC in the group of 125 mg/kg/day. 4. In the test of blood chemistry, total cholesterol showed little decrease and A/G ratio showed little increase, but the change was not clear, and the standard error was large. So the result was obtained insignificantly and the toxicity of JBT extract was not observed. 5. In the male group after recovery period, the level of cholesterol and triglyceride decreased slightly, but the result was not significant. 6. In the urine test, the little change of electrolyte was appeared, but it seemed not to be the result induced by the toxicity of JBT extract. 7. In each group of male and female rats, the weight change of organ and the serum histological changes was observed, but the result did not showed the dose dependent toxicity. So the toxicity of JBT extract was not regarded. In the conclusion, the toxicity of JBT extract was not observed in the single dose treatment and long term repetitive administration of JBT extract.