• 대한약침학회지
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• 제22권3호
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• pp.192-199
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• 2019

Objectives: KCHO-1(Mecasin), also called Gamijakyakgamchobuja-tang originally, is a combination of some traditional herbal medicines in East Asia. This medicine has been used mainly for alleviating neuropathic pains for centuries in Korean traditional medicine. KCHO-1 was developed to treat pain, joint contracture and muscular weakness in patients with amyotrophic lateral sclerosis. This study was carried out to investigate the chronic toxicity of KCHO-1 oral administration in rats for 26 weeks. Methods: Sprague-Dawely rats were divided into four groups and 10 rats were placed in the control group and the high-dose group, respectively. Group 1 was the control group and the remaining groups were the experimental groups. In the oral toxicity study, 500 mg/kg, 1,000 mg/kg, and 2,000 mg/kg of KCHO-1 were administered to the experimental group, and 10 ml/kg of sterile distilled water was administered to the control group. Survival rate, body weight, feed intake, clinical signs, and visual findings were examined. Urinalysis, ophthalmologic examination, necropsy, organ weight, hematologic examination, blood chemical examination and histopathologic examination were performed. Results: Mortality and toxicological lesions associated with the administration of test substance were not observed in all groups. Conclusion: NOAEL(No observed adverse effect level) of KCHO-1 is higher than 2000 mg/kg/day. And, the above findings suggest that treatment with KCHO-1 is relatively safe.

• Toxicological Research
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• 제27권4호
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• pp.261-267
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• 2011

Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found in Korea and used as a traditional medicine to treat liver disease. AIP1, a water-soluble carbohydrate fraction from Artemisia iwayomogi, showed anti-tumor and immuno-modulating activities in animal studies. A subacute toxicological evaluation of AIP1 was performed for 4 weeks in ICR mice. After administration of AIP1 (0, 20, 100, 500 mg/kg/day), the clinical signs, mortalities, body weight changes, hematology, blood clinical biochemistry, urinalysis, organ histopathology, organ weights and gross finding were examined. The results showed that there were no significant differences in body weight changes, food intakes, water consumptions, or organ weights among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally treated with AIP1 and the control group, there was no statistical significance in hematological test or serum biochemical values. Histopathological examination showed no abnormal changes in AIP1 groups. These results suggest that no observed adverse effect level (NOAEL) of the oral administration of AIP1 for 4 weeks was considered to be more than 500 mg/kg/day in mice under the condition investigated in current study.

• Biomolecules & Therapeutics
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• 제6권2호
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• pp.204-212
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• 1998

This study was conducted to evaluate the repeated dose toxicity of DA-1131/betamipron, newly developed carbapenem antibiotic, in rats. DA-1131/ betamipron was administered intravenously once a day for 4 weeks to 10 males and 10 females per group at the doses of 0(control),40, 160 and 640 mg/kg. Throughout the study period, all rats survived. The administration of DA-1131/betamipron induced soft stool or diarrhea in rats of both sexes receiving 160 or 640 mg/kg. The water consumption was increased with a statistical significance in 640 mg/kg during observation period. At the end of administration, hematological and serum biochemical examination showed no toxicological changes in DA-1131/betamipron treated groups compared with control group. Histopathologic examination revealed inflammatory cell infiltration, tubular dilatation and focal necrosis of kidney in two males and three females in 640 mg/kg. On the basis of these results, the noobserved-adverse-effect-level of DA-1131/betamipron was estimated to be 40 mgtg under the present test condition.

• Toxicological Research
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• 제31권4호
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• pp.371-392
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• 2015

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

• 대한한의학회지
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• 제30권3호
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• pp.79-85
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• 2009

Aim : To evaluate the pharmaceutical safety of the herbal formula Myelophil, composed of Astragali Radix and Salviae Radix, via systemic subacute toxicological study using SD rats. Methods : Forty male and 40 female SD rats were fed with Myelophil (5000, 2500 or 1250 mg/10 mL/kg) or distilled water for four weeks. Adverse effects were examined intensively by comparing the differences between normal and drug-administered groups using clinical signs, necropsies, histopathologic findings, hematology, urinalysis, and blood biochemical analysis. Results : No altered clinical symptoms including body weight, diarrhea, anorexia, death, and abnormal necropsy of major organs were observed in male or female rats. No drug-induced abnormalities in histopathological finding, hematological values, urinalysis, and blood biochemical values were found at any doses of Myelophil. Conclusion : Myelophil should be very safe when used in a clinical application with a wide therapeutic index.

• 한국환경농학회지
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• 제33권4호
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• pp.395-402
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• 2014

님추출물은 유효성분(active ingredient)으로 azadirachtin을 함유하여 전세계적으로 충해방제용 유기농업자재로 널리 사용되고 있다. 그러나, 님추출물은 님 원료부위 및 추출용매에 따라 종류가 매우 다양하고 안전성에 크게 차이가 난다고 보고되고 있다. 본 연구에서는 우리나라에서 유기농업자재 제품의 원제로 사용되는 수용성 님추출물이 주요 독성기관인간에 미치는 영향에 대해서 살펴보고자 SD 랫드를 이용하여 4주 반복경구독성시험을 수행하였다. 시험결과, 님추출물 시험물질의 투여 농도가 증가함에 따라 간의 상대중량이 증가하였다(p <0.05). 혈액 생화학분석 결과, 수컷에서 대조군에 비해 시험물질 처리시 혈중 LDH는 감소하였으나 GOT와 GPT가 증가하였으며(p <0.05), 특히 GPT가 시험물질에 농도 의존적으로 증가함에 따라 수컷에서 간 손상의 가능성을 나타내었다. 또한, 고농도로 님추출물 시료를 처리한 경우 수컷의 혈중 GGT가 급격히 증가하였으며 혈중 GLU도 유의적으로 증가하였으나(p <0.05), 뇨 중 GLU는 님추출물의 처리농도증가에 따른 변화가 나타나지 않았다. 간의 조직병리학적 변화를 살펴본 결과 님추출물 시료 처리에 따른 간의 병변도 확인되지 않았다. 따라서 본 시험에 사용된 수용성 님추출물 시료는 혈액 생화학적 분석 결과 수컷에서 간손상의 가능성은 있었으나 조직병리학적 변화는 관찰되지 않았다. 따라서, 수용성 님추출물 2.0 g/Kg 을 4주간 랫드에 경구투여한 결과 간에 독성을 미치지 않고 안전한 것으로 판단된다.