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Methylcellulose의 경구 및 정맥내 반복 투여가 SD랫드의 간장, 비장 및 신장에 미치는 독성학적인 영향
송시환,강부현,한상섭,노정구,이창업,Song, Si-whan,Kang, Boo-hyun,Han, Sang-seop,Roh, Jung-koo,Lee, Chang-eup 대한수의학회 1996 大韓獸醫學會誌 Vol.36 No.1
This experiment was carried out to study the toxic effect of solublized methylcellulose (MC). Sprague-Dawley rats were dosed with 1%(w/v) MC in 0.9% saline by gavage at a dose of 10ml/kg b.w/day or by intravenous injection at a dose of 5ml/kg b.w/day for 28 days. Clinical signs were observed once a day. Body weights, water and food consumptions were measured and urinalysis was performed several times during the experiment. Rats were sacrificed on days 3, 7, 15 and 28 for hematology, blood chemistry, organ weights and histopathology. The relative weight of the spleen and foamy cells of the spleen were increased in the gavage group. Body weight gain, food consumptions, the values of RBC, Hb, MCH, Hct, serum proteins, glucose, bilirubin, AST, and ALP were decreased in I.V. treatment group. On the other hand, water consumptions, the values of serum cholesterol, creatinine, and BUN were increased. Microscopic findings were granulomas, distended sinusoids, and hypertrophy of Kupffer cells with vacuoles in the liver. Spleen exhibited granuloma, increased extramedullary hematopoiesis, and congestion. Kidney exhibited foamy cells in the glomeruli, distension of the tubules. The findings appeared more severe when the treatment was extended. In conclusion, MC solution is not a safe vehicle for intravenous administration because of the toxic effects on the liver, kidney and spleen. In addition, a long-term and large dosage of oral administration of MC appears to be unsafe also and needs to be investigated further.
산삼배양추출물의 배양 Chinese Hamster Lung 세포를 이용한 염색체이상시험
송시환(Si-Whan Song),양덕춘(Deok Chun Yang),정세영(Se Young Choung) 한국독성학회 2005 Toxicological Research Vol.21 No.1
To investigate the mutant induction of wild ginseng culture extract, we performed chromosomal aberration assay with chinese hamster lung cell in vitro. The test concentration of the extract was decided for the standard with the 50% suppression of cell propagation in the cell. The concentrations for the chromosome test were 1,250, 2,500 and 5,000 ㎍/ml with metabolic activation (+S, 6 hours treatment), 1,100, 2,200 and 4,400 μg/ml without metabolic activation (-S, 6 hours treatment) 800, 1,600 and 3,200 ㎍/ml without metabolic activation (-S, 24 hours treatment). No significant increase in chromosome aberrations was observed at any of these concentrations both in the absence and presence of metabolic activation system. Cyclophosphamide monohydrate (CPA) and ethylmethanesulfonate (EMS) caused a significant increase in chromosome aberration. These results may be concluded that wild ginseng culture extract is not capable of inducing chromosome aberration in cultured chinese hamster lung cell regardless of metabolic activation and genotoxicity of that is negative under the present experimental condition.
산삼배양추출물의 비글견을 이용한 단회 경구투여 독성시험
송시환(Si-Whan Song),양덕춘(Deok Chun Yang),정세영(Se Young Choung) 한국독성학회 2005 Toxicological Research Vol.21 No.1
To investigate the acute toxicity of adventitious roots extract derived from wild ginseng, it was orally administered to beagle dogs with a single dose. In acute toxicity test, three groups (9 beagle dogs of male) were administered with different dosages of adventitious roots extract (prepared by Biopia Corp.) 500 mg/kg (G2), 1,000 mg/kg (G3), 2,000 mg/kg (G4) and one group (G1, 2 beagle dogs of male) were received by only capsule without the extract according to the Regulation on Korea Food and Drug Administration (1999. 12. 22). There were vomitus for a time and mucous stool at the day, and anorexia and mucous stool at the first day in the group of 2,000 mg/kg administration. There were mucous stool in one and anorexia for a while in two beagle dogs at the first day in the 1,000 mg/kg administration. But no death or abnormal clinical sign was observed through the study period. Therefore, the adventitious roots extract derived from wild ginseng is considered not to have the acute toxicity in the beagle dogs. These results suggest that LD_(50) value of the test substance was considered to be more than 2,000 mg/kg in the beagle dogs.
게르마늄 복합물인 STB-HO-BM에 대한 유전독성에 관한 연구
송시환(Si Whan Song),정연권(Winston Jung),홍동호(Dong Ho Hong) 한국독성학회 2006 Toxicological Research Vol.22 No.2
We have investigated the genotoxicity of STB-HO-BM using in vitro and in vivo system such as Ames reverse mutation test, chromosomal aberration test and micronucleus test. in Ames reverse mutation test, STB-HO-BM treatment at the dose range up to 5,000 ug/plate did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA102, TA1535, TA1537 and in Escherichia coli WP2 uvrA with and without metabolic activation. Any significant aberration wasn’t observed in chinese hamster lung (CHL) fibroblast cells treated with STB-HO-BM at the concentration of 12.5, 2.5, 5 ㎎/㎖ both in the absense and presence of metabolic activation system. In mouse micrnucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice orally administered with STB-HO-BM at the doses of 0.5, 1.0, 2.0 g/㎏. These results indicate that STB-HO-BM has no mutagenic potential under the condition in this study.
랫드에서 STB-HO-BM에 대한 13주 반복투여 독성연구
송시환(Si Whan Song),정연권(Winston Jung),홍동호(Dong Ho Hong) 한국독성학회 2006 Toxicological Research Vol.22 No.2
This study was performed to evaluate repeated-dose toxicities of STB-HO-BM in Sprague-Dawley rats. STB-HO-BM was administered orally to rats at dose levels of 0, 100, 300 and 1,000 mg/kg/day for 13 weeks. In recent study, there were no dose related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with STB-HO-BM. Gross and histopathological findings revealed no evidence of specific toxicity related to STB-HO-BM. These results suggest that the oral no observed adverse effect level (NOAEL) of STB-HO-BM may be over 1,000 mg/kg in rats.
게르마늄 복합물 STB-HO-BM의 랫드 및 비글견에서 단회투여 독성연구
송시환(Si Whan Song),정연권(Winston Jung),홍동호(Dong Ho Hong) 한국독성학회 2006 Toxicological Research Vol.22 No.2
The acute toxicity of STB-HO-BM was evaluated in Sprague Dawley (SD) rats and beagle dogs. STB-HO-BM was administered orally to rats at dose levels of 0 and 2,000 ㎎/㎏/day and to dogs at dose levels of 0, 500, 1,000 and 2,000 ㎎/㎏/day. In these experiments, there were no death and clinical changes which were related to STB-HO-BM administration. In addition, there were no significant changes between control and treated groups in body weights and autopsy findings. In conclusion, the administration of STB-HO-BM 2,000 ㎎/㎏ in SD rats and up to 2,000 ㎎/㎏ in beagle dogs was proved to be safe, and it is thought that STB-HO-BM may not show any toxicity in its clinical use.
비글견에 있어서 새로운 안트라싸이클린계 항암제 DA-125의 정소독성연구
김종춘,차신우,송시환,정문구,Kim, Jong-choon,Cha, Shin-woo,Song, Si-whan,Chung, Moon-koo 대한수의학회 1997 大韓獸醫學會誌 Vol.37 No.2
To assess the testicular toxicity induced by DA-125, a new anthracycline anticancer agent, the test substance was intraveneously administered to male beagle dogs at dose levels of 0, 0.0023, 0.0375, 0.15, and 0.6 mg/kg/day, 6 days a week for 26 weeks. At 0.6 mg/kg/day, 1 out of 3 dogs had died on day 42 of treatment and the other dogs were sacrificed on days 46 and 122 of treatment due to the increasingly severe clinical condition. Clinical signs considered to be related to treatment were included anorexia, vomiting, salivation, decreased activity, mucous and/or dark faeces, diarrhea, and swelling, abscess and/or ulceration of injection sites. Suppression in body weight gain, reduction in food intake, decreases in testicular weight and size, and hemorrhage of epididymis were also observed in male dogs. Microscopically, severe degenerative changes such as atrophy of seminiferous tubules, loss of germ cells, degeneration of germ cells, vacuolization of Sertoli cells, and hyperplasia of Leydig cells were observed in all dogs. Azoospermia in epididymal tubules, atrophy of epithelia in the cauda epididymis, and prostate atrophy were also found. At 0.15 mg/kg/day, anorexia, vomiting, salivation, diarrhea, and swelling of injection sites were observed. In addition, suppression in body weight gain and decreases in testicular weight and size were found in male dogs. Atrophy of seminiferous tubules, decrease of germ cells, degeneration, exfoliation and retention of germ cells, vacuolization of Sertoli cells, and hyperplasia of Leydig cells were observed by histopathological examination. Azoospermia in epididymal tubules and prostate atrophy were also found. At 0.0375 mg/kg/day, there were no clinical signs considered to be indicative of a reaction to treatment, but testicular size was significantly reduced. Microscopically, decreases in the number of spermatogonia and epidydimal speramtozoa were found. There were no evidences of general or testicular toxicity at 0.0023 mg/kg/day. These results indicate that DA-125 produces significant and persistent damage to the spermatogenic compartments of the testes in male beagle dogs.
복합항생제 SM-101 ( 설박탐 , 메탐피실린 ) 의 생식독성연구 랫트 수태능력시험
정문구(Moon Koo Chung),송시환(Si Whan Song),노정구(Jung Koo Roh) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.1
A new composite antibiotic, SM-101(sulbactam·metampicillin), was at dose levels of 0, 250, 500 and 1000 ㎎/㎏/day administered intravenously to Sprague-Dawley male rats from premating to mating period and to females from premating to early gestation period. Effects of test agent on general findings and reproductive performance of parent animals and embryonic development were examined. In male parents, two deaths occurred at 1000 ㎎/㎏. The increase in kidney weight of the 1000 ㎎/㎏ group were also observed. The decrease in body weight and food consumption were found at 500 and 1000 ㎎/㎏. The decrease in spleen weight were seen at 250, 500 and 1000 ㎎/㎏. In female parents, three deaths were found at 1000 ㎎/㎏. Mating performance and fertility of parent animals were not adversely affected by all doses tested. F1 fetuses showed no changes related to treatment of SM-101. The results show that the no effect dose level(NOEL) for general toxicity of parent animals is under 250 ㎎/㎏/day and NOELs for reproductive capability and fetal development are over 1000 ㎎/㎏/day.
DWP-301 (수산화알루미늄, 수산화마그네슘, Simethicone, Aceglutamide Aluminum)의 흰쥐에 대한 4주간 반복 경구투여 독연구
김은주(Eun Joo Kim),송시환(Si Whan Song) 대한약학회 1994 약학회지 Vol.38 No.1
Daily oral administration to Sprague Dawly rats for 4 weeks of DWP-301, at doses of 0, 500, 1000, 2000mg/kg presented following results; 1) No animals died and there were no significant differences in general signs, body weight, food consumption, urinalysis haematological, biochemical, gross pathological and histopathological examination between control and treated rats. 2) Water consumption, pH-, protein- urobilinogen-, ketone-values in urine were significantly increased in the treated male and female rats. It is supposed that these differences in animals are a consistent feature of repeated overdosage with test suspensions. The results indicate that the non toxic dose of test compounds in rats is over 2000mg/kg in this test system.