• Toxicological Research
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• v.18 no.1
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• pp.47-57
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• 2002

The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study

• Toxicological Research
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• v.29 no.4
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• pp.263-278
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• 2013

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent ${\alpha}$-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

• Journal of Veterinary Clinics
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• v.27 no.2
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• pp.163-169
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• 2010

To evaluate of oral toxicity of Epimedium koreanum nakai (EKN) water extract, three doses of EKN water extract (10, 100 and 1000 mg/kg/day) were administered to healthy Sprague-Dawley rats for 4 weeks. The results showed that there are no abnormal signs during the experimental period. The weights of testis and epididymis were increased dose-dependently, but seminal vesicle was decreased compared with control group. In hematology and serum chemistry, changes were observed within the normal ranges. In histological finding, slight to moderated changes were found but those were commonly or rarely encountered in the normal rats. These results suggest that no observed adverse effect level (NOAEL) of the oral application of EKN was considered to be more than 1000 mg/kg in SD rats under the conditions employed in this study.

• Toxicological Research
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• v.29 no.4
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• pp.285-292
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• 2013

Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energygiving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day.

• Journal of Haehwa Medicine
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• v.22 no.1
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• pp.171-184
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• 2013

Single-and repeated-dose toxicities of Compound K (CK) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity study, CK was dissolved in drinking water, orally administered and examined for 14 days. As results, CK up to a dose of 5,000 mg/kg, the limited dose, neither induced death, clinical signs and necropsy findings, nor affected body weight gain and organ weights, in which 10% lethal dose could not be estimated. Based on the results of single-dose toxicity test, CK was administered at doses of 500, 1,000 or 2,000 mg/kg for 28 days for the evaluation of repeated-dose toxicity. All doses including the limited dose (2,000 mg/kg) of CK did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology, blood biochemistry. Rather, high doses (1,000 - 2,000 mg/kg) of CK reduced the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Thus, both maximum tolerable dose (MTD) and no observed adverse effect level (NOAEL) were not determined. The results indicate that long-term intake of high-dose CK might not induce general adverse effects.

• Toxicological Research
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• v.31 no.1
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• pp.69-75
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• 2015

The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatment-related changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material.

• Journal of Soil and Groundwater Environment
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• v.24 no.5
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• pp.1-10
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• 2019

The effects of liquid phase ozonation on seed dormant alleviation and subsequent seedling growth were studied using two plant seeds of Indian jointvetch (Aeschynomene indica L.) and Indian mallow (Abutilon avicennae Gaertn.). At a constant ozone concentration ($80g/m^3$), contact time varied from 10 to 60 min with 10 min interval. Germination rate, root length, and specific root length were compared after 3-day incubation on gel-medium. The germination rate increased significantly (p<0.05) in the 50 min treatment of Indian mallow by 30% compared to the control. Enhanced root elongation was observed in the seeds of 30 min treatment of Indian jointvetch and 30~50 min treatment of Indian mallow. Specific root length, an indicator of environmental change, did not show significant changes, suggesting the level of ozone treatment has no adverse effect on seedling development. The results indicate that liquid phase seed ozonation can be an effective on-site germination alleviation method in the application of phytoremediation.

• 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.

• Archives of Plastic Surgery
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• v.36 no.2
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• pp.127-134
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• 2009

Purpose: Adipose tissue injection as a free graft for the correction of soft - tissue deficiency or depression deformity is a widespread procedure in plastic surgery. This study is to analyze the changes and viability of cryopreserved adipose tissue and to find out efficient long - term storage period. Methods: After centrifugation of aspirated abdominal tissues, $10m{\ell}$ of packed Adipose tissue were freezed at $-20^{\circ}C$. For 2, 4, 6, 8 months, each frozen samples were taken and injected into scalp of SCID mice. After 15 weeks, injected Adipose tissue were sampled and analyzed at 2 months interval. We compared and analyzed each group about the weight of the injected fat, histologic impressions, activity of mitochondria, size of a fat cell and rate of survival. Results: Significant weight changes were observed in cryopreservation for 2 months(p<0.05). Histologic changes were observed, independent of the freezing period with H - E stain. Among cryopreservations for 2, 4, 6 months, no significant change were observed. The reduction of mitochondrial enzymatic activity was observed independent of time interval but activity of mitochondrial dehydrogenase was reduced less than 50% in MTT assay. Conclusion: Freezing in $-20^{\circ}C$ for 6 months has no adverse effect to Adipose tissue, but fragile adipocytes, damaged cell membrane during harvesting procedure, were disrupted within 1 - 2 month and the maximum volume reduction were followed less than 2 months. These results demonstrate that tissue preparation cells without membrane damage have the greatest viability level and cryopreservation less than 2 months has great volume effect and cryopreservation for 6 months has stable volume effect.

• Korean Journal of Acupuncture
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• v.36 no.2
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• pp.127-138
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• 2019

Objectives : This study was carried out in order to toxicity and safety of Drosera Rotundifolia L. pharmacopuncture in BALB/c mice. Methods : In order to investigate toxicity and safety of Drosera Rotundifolia L. pharmacopuncture, BALB/c mice were chosen in these studies and injected to ST36. In 50% Lethal Dose (LD 50) study, mice were divided into 8 groups. Doses of pharmacopuncture at 300, 600, 1,200, 2,400, 3,600, 4,800, 6,000, 7,200 mg/kg were given to the each group. we observed mortality and toxic signs for 7 days after injection. In single-dose toxicity, mice were divided into 4 groups. Doses of pharmacopuncture, 300, 600, 1,200 mg/kg, were administered to the experimental group. And a dose of normal saline, 0.2 ml was administered to the control group. We observed mortality and toxic signs for 14 days after injection. In repeated-dose toxicity for 4 weeks, mice were divided in 4 groups. Doses of pharmacopuncture, 150, 300, 600 mg/kg, were administered to the experimental group. And a dose of normal saline, 0.2 ml, was administered to the control group. We observed mortality, toxic signs, body weight, hematological values et al. Results : The LD 50 of Drosera Rotundifolia L. pharmacopuncture was 4,800 mg/kg. In single-dose toxicity, no deaths, no toxic signs occurred in any of groups. In repeated-dose toxicity for 4 weeks, no deaths, no toxic signs occurred in any of groups. Conclusions : No Observed Adverse Effect Level (NOAEL) of Drosera Rotundifolia L. pharmacopuncture injection for 4 weeks was more than 600 mg/kg.