• 대한한방내과학회지
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• 제35권3호
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• pp.223-243
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• 2014

Objectives: To provide information on the safety of GST (GamiSasangja-tang; CnidiiFructus, Sophora Root, Angelica Gigas Root, Clematidis Radix, Stemonae Radix, Spirodelae Herba), we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of GST in Sprague-Dawley rats. Methods: Female and male rats were treated with GST at oral doses of 1,250, 2,500, and 5000 mg/kg. The GST was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. The rats were then monitored for 4 extra weeks to determine recovery time after the study period. Results: We found no mortality or abnormalities among clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights or histological markers in any of the rats tested. Conclusions: The no-observed adverse effects level (NOAEL) is considered as over 5000 mg/kg for male and female rats.

• 동의신경정신과학회지
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• 제23권3호
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• pp.143-160
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• 2012

Objectives : To provide information on the safety of ACM, we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of ACM in Sprague-Dawley rats. Methods : Female and male rats were treated with ACM with oral doses of 800, 2000, and 5000 mg/kg. The ACM was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. Moreover, the rats were monitored for 4 extra weeks to determine recovery time after the study period. Results : We found no mortality and no abnormalities in clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers in any of the rats tested. Conclusions : The no-observed adverse effects level (NOAEL) was considered as over 5000 mg/kg for male and female rats.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.133-149
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• 1997

4-week repeated dose toxicity of DA-5018, a new capsaicin analogue analgesic agent, was examined in 5D rats at dosage levels of 0,0.4,2, 10 and 50 mg/kg/day. DA-5018 was administered orally to 17 males and 17 females per group at doses of 0, 10 and 50 mg/kg and to 12 males and 12 females per group at doses of 0.4 and 2 mg/kg. After the administration period, 5 males and 5 females at the 0, 10 and 50 mg/kg were placed on withdrawal for 2 weeks. Treatment-related clinical signs were observed at 10 and 50 mg/kg. Clinical signs observed immediately after the administration of DA-5018 were grooming, sedation or depression, lacrimation, atacia, reddening of extremities and ears, ventral or lateral recumvincy, respiratory distress, cyanosis and convulsion. Delayed-type clinical signs including focal scabbing and depilation around nose were also observed 1 or 2 weeks after the start of administration of DA-5018. Only at the 50 mg/kg group, corneal opacities, reduced body weight gain (male) and death (male 6/17, female 3/17) were noted. In blood biochemical analysis, serum levels of glucose and triglyceride decreased at 10 and 50 mg/kg. In hematological examination, there were increases in the number of red blood cell, hemoglobin content and percent of hematocrit at 10 and 50 mg/kg. Pulmonary enlargement and hemorrhagic spot, focal scabbing and depilation around nose and corneal opacities were seen at the necropsy of the animals died during the dosing of DA-5018 50 mg/kg. Focal scabbing and depilation around nose were observed in the animals terminally necropsied at doses of 10 and 50 mg/kg. Histopathological examination revealed pulmonary hemorrhage, focal necrosis in the scabbed area, corneal necrosis, fibrosis and neovasculization in the stroma. At 0.4 and 2 mg/kg, there were no significant toxic changes attributable to the administration of DA-5018. In conclusion, target organs following to 4-week repeated dose of DA-5018 in the rat were determined to be lung, skin and eyes. Definite toxic dose and no-observed-adverse-effect-level (NOAEL) were estimated to be 50 and 2 mg/kg/day, respectively.

• 약학회지
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• 제58권1호
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• pp.62-70
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• 2014

A 28-day repeated-dose oral toxicity test was performed to determine the no-observed-effect level (NOEL) and establish an optimum dose of the highly toxic Aconiti Ciliare Tuber (ACT) used as a folk remedy. Repeated oral doses of 1,250, 2,500, and 5,000 mg/kg/day of the hot water extract of ACT were administered to five male and five female Sprague-Dawley rats in each group for 4 weeks. The indicators for toxicity included results of examination of common symptoms and changes in weight and feed intake, eye test, urinalysis, hematological and serum biochemical analyses, and post-mortem weight measurement of organs, and visual inspections. All animals survived at the end of the experiment; in addition, we observed no specific test substance-mediated symptoms. We observed no test substance-mediated changes in body weight and feed intake. We observed statistically significant changes in male OB and pH levels (p<0.05). Further, the biochemical test showed statistically significant changes in the IP value of male rats and $CL^-$valueoffemalerats (p<0.05). However, all changes were within historical data. The post-mortem examinations showed no test substance-mediated changes. Moreover, statistically significant changes under the test conditions were confirmed to have been caused by factors other than the test substance. Thus, the maximum NOEL of ACT extract in rats was estimated to be 5,000 mg/kg/day.

• 한국식품과학회지
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• 제46권2호
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• pp.249-255
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• 2014

본 연구에서는 사용된 가시오가피 영지버섯 발효물과 가시오가피 상황버섯 발효물에 대한 열수추출물을 최고 2 g/kg의 농도로 단회 투여한 SD-rats에 체중 변화, 임상증상 등에서 어떠한 독성도 관찰할 수 없었으며, 1 g/kg 이하의 농도로 4주간 반복 투여한 SD-rats에서도 체중변화, 임상증상, 장기 무게, 혈액학적 성상, 혈액생화학적 성상 등에서 어떠한 독성과 비정상적인 소견을 관찰할 수 없었다. 따라서, 본 연구의 결과로 볼 때 가시오가피 영지버섯 발효물 열수추출물(FM-5111)과 가시오가피 상황버섯 발효물 열수추출물(FM-5131)은 본 연구에서 사용한 농도 내에서의 안전성을 확인할 수 있었다. 황 함유 아미노산의 결핍은 여러 가지 간질환 등의 증상을 야기한다(27). 또한, Choi와 Ahn(28)은 오가피 부위별 50% (v/v) 메탄올 추출액의 전자공여능은 줄기 추출물에서 90.21%, 뿌리 추출물에서 85.71%로 높은 활성을 보고하여 오가피의 항산화능을 규명하였다. 따라서, 본 연구에 사용된 시료 또한 항산화능과 같은 기능성을 가질것으로 사료되며, 추가 연구로 아미노산 분석을 통해 황 함유 아미노산의 함량 변화를 분석하고 간 기능 개선 효능을 평가하여 안전성이 확보된 기능성 식품소재 개발 연구를 진행할 계획이다.

• Toxicological Research
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• 제15권1호
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• pp.9-17
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• 1999

This study was performed to evaluate the subacute toxicity of CJ-50002 (Vibrio Vaccine) in SPF Spraqur-Dawley (SD) rats. Vibrio vaccine was administered orally at a dose level of high (167mg/kg/day), medium (16.7mg/kg/day), and low (16.7mg/kg/day) once a day and repeated fro 4 weeks. Ten males and female rats were assigned to each group. After 4 week administration, no significant dose-dependent changes in body weight, water and food consumption rate or organ weight were noted dependent changes in body weight, water and food consumption rate or organ weight were noted among 4 groups. Urinanalysis, hematology, and serum chemistry, also fail to detect any dose-related change among 4 groups tested. During necropsy and histopathological examination, no specific toxicity related to treated material was found. The result of this study demonstrated that vibrio vaccine when administered orally for 4 weeks at a high dose of 167mg/kg/day, no dose-related toxicity was found in treated make and female rats.

• 대한한의학회지
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• 제30권5호
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• pp.102-114
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• 2009

Objectives: HMCO5 is an extract obtained from 8 different herbal mixtures. We undertook a safety evaluation of HMCO5 for a dose range finding (DRF) toxicity test in specific pathogen free (SPF) Sprague-Dawley (SD) male and female rats. Methods: The male and female rats were divided into 4 groups, respectively; G(0), treated with distilled water: G(1), treated with 222 mg/kg HMC05: G(2), treated with 667 mg/kg HMC05, and G(3), treated with 2,000 mg/kg HMC05; HMC05 was administered orally for 4 weeks. The safety evaluation examined clinical signs, mortality, body weight, food consumption, water consumption, ophthalmic findings, urinalysis, hematological values, absolute & relative organ weights, and necropsy findings during the tests. Results: There were no changes in clinical signs, mortality, body weight, food consumption, water consumption, and ophthalmic findings examined during the test periods. In serum biochemical values, triglyceride was increased in male group G(3) and Na$^+$ decreased significantly in male groups G(2), G(3) and G(4). In male group G(4), spleen weight decreased relatively and increases of absolute & relative left ovary weights were found. In addition, an adhesion of liver to diaphragm was found in male group G(2). However, we could not find any dose-interrelationships in these changes. Conclusions: These results indicate that HMC05 extract did not show any toxicity in the DRF toxicity study. Therefore, it suggests that establishment of 1,000, 333 and 111 mg/kg dosages are moderate in a repeated dose 26-week oral toxicity study of HMC05.

• The Korean Journal of Pain
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• 제27권2호
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• pp.125-132
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• 2014

Background: To improve residual pain management in acute cervical radiculopathy treated with NSAIDs, the feasibility of early and repeated low-dose interscalene brachial plexus block (IS-BPB) needs to be assessed. Methods: This was a prospective study on patients receiving NSAIDs (loxoprofen) for cervical radiculopathy of ${\leq}2$-week onset. Pain was assessed using the visual analogue scale (VAS). A low-dose ultrasonography (USG)-guided IS-BPB (dexamethasone [1.65 mg; 0.5 ml] and mepivacaine [1%; 3.0 ml]) was performed at baseline and weekly thereafter for 4 weeks in an outpatient setting for the intervention group. All patients were evaluated using a visual satisfaction score (VSS) at week 4. Patients with baseline VAS scores < 70 (mild to moderate pain; MM group) and ${\geq}70$ (severe pain; SE group) were compared to the controls receiving NSAIDs. Results: A total of 316 IS-BPBs were performed in the intervention group. There was a significant difference in the decline in the VAS from week 0 to week 3 in the MM and SE groups (P < 0.05); however, from week 3 to week 4, the therapeutic effect exhibited no significant difference. Thirteen patients at week 2 (15.5%; MM: 27.7%; SE: 0%), 43 at week 3 (51.2%; MM: 83.0%; SE: 10.8%), and 47 at week 4 (56.0%; MM: 85.1%; SE: 18.9%) achieved a VAS score of ${\leq}20$. Patient satisfaction was high, and the decrease in VAS scores in both groups was significant (P < 0.05) compared to the controls. Conclusions: Weekly, low-dose, USG-guided IS-BPB can be implemented for early pain relief in acute cervical radiculopathy, with high patient satisfaction.

• 한국임상수의학회:학술대회논문집
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• 한국임상수의학회 2008년도 추계학술대회
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• pp.159-159
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• 2008

• 한국식품영양과학회지
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• 제36권8호
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• pp.975-982
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• 2007

본 연구는 H. pyroli 억제능을 지닌 김치 유래 유산균인 Pediococcus pentosaceus MD1을 가지고 궤양 예방효과를 지닌 김치를 개발하기 위한 선행연구로서 독성평가 실험을 수행하고자 4주 반복 투여 독성시험을 실시하였다. 본 시험에서 설정한 최고 용량 투여군인 2,000 mg/kg에서도 일반증상관찰, 체중변화, 사료섭취량 및 물 섭취량을 측정한 결과, 모두에서 시험물질과 관련된 유의성 있는 변화가 관찰되지 않았다. 또한 혈액학적, 혈액생화학적 검사 및 장기의 육안적 관찰 및 장기 중량변화에서도 대조군과 유의성이 있는 차이를 보이는 항목이 없었으며, 모두 정상범위를 벗어나지 않아 시험물질에 기인하는 이상소견을 발견할 수 없었으므로, 최대 무해 용량은 2,000 mg/kg 이상일 것으로 추정되었다. 이상의 결과 4주 반복 투여 독성시험 결과 H. pyroli 억제능을 지닌 유산균인 Pediococcus pentosaceus MD1은 저독성물질로 판정되었으며, 유산균이 기능성식품 소재로서의 안전성 확인을 통하여 소비자들에게 소화성 궤양 예방효과를 지닌 안전하고 차별화된 경쟁력 있는 김치를 개발할 수 있을 것으로 사료된다.