• Title/Summary/Keyword: repeated dose

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Toxicity Study of Red Ginseng Acidic Polysaccharide (RGAP) : Single and 2-week Repeated Oral Dose Toxicity Study in Rats

  • Park, Jong-Dae;Song, Yong-Bum;Kwak, Yi-Seong;Kim, Jong-Choon;Im, Doo-Hyun;Junghee Han
    • Toxicological Research
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    • v.19 no.3
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    • pp.173-180
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    • 2003
  • The present study was conducted to investigate the single and 2-week repeated dose toxicity of red ginseng acidic polysaccharide (RGAP) in Sprague-Dawley rats. The test article was administered orally to rats at dose levels of 0, and 2000 mg/kg/day for single dose toxicity study and at dose levels of 0, 250, 500, and 1000 mg/kg/day for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated RGAP. Based on these results, it was concluded that the 2-week repeated oral dose of RGAP may have no toxic effect in rats at a dose level of 1000 mg/kg/day. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 1000 mg/kg/day for both sexes.

Single and Two-Week Repeated] Oral Dose Toxicity Study of DHP2, a Hydrophobic Drug Delivery Vehicle in Mice

  • Han, Jung-Hee;Chung, He-Sson;Lee, Jong-Hwa;Suh, Jeong-Eun;Lee, Gab-Soo;Kim, Jong-Choon;Kang, Boo-Hyon
    • Toxicological Research
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    • v.20 no.2
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    • pp.123-129
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    • 2004
  • The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals treated DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.

Single Oral Dose-increasing Toxicity Test and Four Weeks Repeated Oral Dose Determinating Test of ACM (Added Chongmyung-tang) in Beagle Dogs (ACM의 비글견을 이용한 단회 경구투여 용량증가 독성 시험 및 4주 반복 경구투여 용량 결정 시험)

  • Lim, Jung-Hwa;Lee, Sang-Ryong;Jung, In-Chul
    • Journal of Oriental Neuropsychiatry
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    • v.24 no.1
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    • pp.131-144
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    • 2013
  • Objectives : To provide information on the safety of ACM, we carried out a single oral dose-increasing toxicity and 4-weeks repeated oral dose determining test of ACM in beagle dogs. Methods : In a single oral dose-increasing toxicity test, beagles were treated with ACM orally increasing dose level (1,000, 2,000, 5,000 mg/㎏) at interval of 3 days. After administration, signs of toxicity were observed for two weeks. In 4-weeks repeated oral dose determinating test, beagles were treated with ACM with oral dose 500, 1,000, 2,000 mg/kg for 4 weeks. Mortality, clinical signs, body weight changes, food consumption, urinalysis, hematological and biochemical parameters, organ weights, necropsy findings, and histological findings were monitored during the study period. Results : In a single oral dose-increasing toxicity test, we found no mortality, abnormalities in clinical signs, body weight, and necropsy findings during the study period. In 4-weeks repeated oral dose determinating test, we found no mortality, abnormalities in clinical signs, body weight, food consumption, urinalysis, hematological and biological parameters, gross findings, organ weights, necropsy findings, and histopathological findings in any of the beagles tested. Conclusions : The results obtained in these studies suggest that maximum tolerated dose (MTD) of ACM in male and female beagle dogs was supposed to be over 5,000 mg/kg. For the future studies of toxicity, it is advisable that high dose and low dose are set at 2000 mg/kg and 500 mg/kg, respectively.

Single and Four-Week Subcutaneous Toxicity Studies of a Bee Venom Extracts (F1, F3) In Rats (봉독 추출물(Fl, F3)의 랫드에 대한 단회 및 4주 반복 피하 투여 독성시험)

  • 박기수;조성대;안남식;정지원;양세란;박준석;홍인선;서민수;조은혜
    • Toxicological Research
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    • v.19 no.1
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    • pp.51-66
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    • 2003
  • This study was performed to evaluate single and repeated-dose toxicities of Bee Venom Extracts (F1, F3) in Spraque-Dawley. F1 was injected subcutaneously to rat at dose levels of 0, 0.0002, 0.002, 0.02 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. F3 was injected subcutaneously to rat at dose level of 0, 0.003, 0.03, 0.3 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. In both studies, there were no dose related changes in mortality, clinical sign, body weight change, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with Bee Venom (F1, F3). Gross and histopathological findings revealed no evidence of specific toxicity related to Bee Venom (F1, F3). These results suggest that the subcutaneous NOEL (No Observed Effect Level) of Bee Venom (F1, F3) may be over F1 -0.02 mg/kg, F3-0.3 mg/kg.

Single and 28-Day Repeated Intramuscular dose Toxicity Studies of Botulinum Toxin Type a in Rats

  • Woo S. Koh;Moon-K. Chung;Kim, Yong B.;Chang S. Ha;Gi H. Yang;Hyun H. Chung;Tae C. Jeong
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.150-150
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    • 2003
  • Botulinum toxin type A was intramuscularly administered to Sprague-Dawley rats in both single and 28-day repeated dose toxicity studies. In the single dose toxicity study performed at 25, 50, 100, and 200 ng/kg, LD50 was estimated to be 70.71 ng/kg for males and 97.63 ng/kg for females.(omitted)

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Single-dose and 4-week repeated dose Toxicity of Aconitum Sinomontanum Nakai Pharmacopuncture: An Experimental Study

  • Woo, Sang Ha;Lee, Jung Hee;Lee, Cho-in;Lee, Yun Kyu;Lee, Hyun-Jong;Kim, Jae Soo
    • Journal of Acupuncture Research
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    • v.38 no.1
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    • pp.47-59
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    • 2021
  • Background: This study aimed to assess the toxicity of Aconitum sinomontanum Nakai (ASN) pharmacopuncture. Methods: To investigate the toxicity of ASN pharmacopuncture, single and 4-week repeated dose toxicity experiments were conducted on BALB/c mice. In the single-dose toxicity experiment, mice were assigned 1 of 4 groups (5 males, 5 females per group). Then, 31.25, 62.5, and 125 mg/kg of ASN pharmacopuncture were administered to the mice in the experimental groups at acupoint ST36, while 0.2 mL of normal saline was administered to the control group at ST36. After a 4-week repeated dose regimen, the mice were assigned into 4 groups (5 males, 5 females per group). Then, 15.625, 31.25, and 62.5 mg/kg of ASN pharmacopuncture at ST36 were administered to the mice in the experimental groups, while 0.2 mL of normal saline was administered to the control group at ST36. Mortality, morbidity, general body and organ weight changes (after 4 weeks repeated dose), serum hematological and biochemical values, and histopathological changes in the liver and kidney were observed. Results: In both single and 4-week repeated dose toxicity experiments, no deaths or symptoms occurred in any of the groups. There were no significant differences between groups in terms of body and organ weights, serum hematological and biochemical values, and specific organ histopathological changes. Conclusion: ASN pharmacopuncture injection did not demonstrate significant toxicity in BALB/c mice compared with the control group, with a no-observed-adverse-effect level for a single dose of >125 mg/kg, and for 4 weeks repeated dose it was more than 62.5 mg/kg/day.

Single and Four-Week Repeated Oral Toxicity Study of CJ-11555 in Sprague-Dawely Rats (CJ-11555의 Sprague-Dawely 랫드를 이용한 단회 및 4주 반복경구투여 독성시험)

  • 김일환;이성학;최재묵;박지은;김덕열;노현정;김택로;이상호;김영훈
    • Toxicological Research
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    • v.20 no.2
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    • pp.143-151
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    • 2004
  • This study was to investigate single and repeated-dose toxicities of CJ-11555, an anticirrhotic agent, in Sprague-Dawley (SO) rats. In single-dose oral toxicity study, the test article were administered once by gavage to males and females at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and CJ-11555 treated group. Therefore, the approximate lethal dose of CJ-11555 was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test article was administered once daily by gavage to male and female rats at dose levels of 0, 10, 50 and 200 mg/kg/day for 4-weeks. In clinical signs, yellow-colored urine and yellow hair coat were observed in the 50 and 200 mg/kg male and female groups. In hematology, erythrocyte count and hemoglobin were significantly decreased in the 200mg/kg male and female groups. In serum biochemistry, total cholesterol was significantly increased and aspartate aminotransferase (AST) was significantly decreased in the 50 or 200 mg/kg male and female groups. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver, congestion and pigmentation in the spleen, hyaline droplets in the kidney were observed in the 50 and 200 mg/kg male and female groups. In toxicokinetic study, CJ-11555 was dose-dependent in systemic exposure and showed better absorption in female with minimum accumulation after multidosing. Based on these results, it was concluded that the 4-week repeated oral dose of CJ-11555 resulted in the suppression of AST activity and centrilobular hepatocellular hypertrophy in both sexes at a dose level of 50 or 200 mg/kg/day. The target organ was estimated to be liver, spleen and male's kidney. The no-observed-adverse-effect level (NOAEL) for CJ-11555 in rats following gavage for at least 4-week is 10 mg/kg/day.

A Comparison of Noise Level by Noise Measuring Methods (소음측정방법에 따른 평가소음도 비교)

  • Shim, Chur Goo;Roh, Jae hoon;Park, Jung Gyun
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.5 no.2
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    • pp.128-136
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    • 1995
  • The purpose of this study is to evaluate the difference of noise level according to noise measuring methods in the noisy working environments. Sound pressure level(SPL), equivalence sound level(Leq) and personal noise exposure dose(Dose) in the fifty-nine unit workplaces of the twenty-eight industries were measured and relating factors which were affected noise level were investigated. The results were as follows ; 1. The noise levels were $88.70{\pm}5.68dB(A)$ by SPL, $89.07{\pm}5.41dB(A)$ by Leq and $89.07{\pm}5.69$ by Dose. The differences of noise levels by three measuring methods were statistically significant(P<0.001) by repeated measure ANOV A. 2. Comparing with noise levels by general classes of noise exposure, noise levels of continuous noise were $89.14{\pm}5.19dB(A)$ by SPL, $89.45{\pm}4.65dB(A)$ by Leq and $90.04{\pm}5.09$ by Dose. Noise levels of intermittent noise were $87.90{\pm}6.52dB(A)$ by SPL, $88.40{\pm}6.63dB(A)$ by Leq and $90.10{\pm}6.80$ by Dose. The differences noise level of noise measuring methods by general classese of noise exposure were statistically not significant by repeated measure ANOV A. 3. Interaction between general classese of noise exposure and noise measuring methods for noise level was not statistically significant by repeated measure ANOVA. And the noise level by noise measuring methods were statistically significant by repeated measure ANOV A(P<.001) 4. Comparing with noise levels by unit workplace size, noise levels of large unit workplace were $90.73{\pm}5.87dB(A)$ by SPL, $91.32{\pm}5.50dB(A)$ by Leq and $91.82{\pm}6.06$ by Dose and noise levels of middle unit workplace were $88.31{\pm}5.26dB(A)$ by SPL, $88.41{\pm}4.83dB(A)$ by Leq and $89.69{\pm}5.05$ by Dose. And noise levels of small unit workplace were $94.89{\pm}4.10dB(A)$ by SPL, $85.35{\pm}4.11dB(A)$ by Leq and $86.87{\pm}4.98$ by Dose. The noise level differences of noise measuring methods by unit workplace size were statistically significant by repeated measure ANOV A(P<.05). 5. The noise level by noise measuring methods were statistically significant by repeated measure ANOV A(P<.001). But Interaction between workplace size and noise level measuring methods for noise level was not statistically significant by repeated measure ANOVA. According to the above results, there was a difference of the noise level among the three measuring methods. Therefore we must use the personal noise exposure dose using by noise dose meter, possible, to prvent occupational hearing loss in noisy working environment.

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Single Oral Dose Toxicity Test and Four Weeks Repeated Oral Dose Determination Test of Crude Antifungal Compounds Produced by Bacillus subtilis SN7 in Rats (Bacillus subtilis SN7이 생성한 조항균 물질의 단회 경구투여 독성 시험 및 4주 반복 경구투여 용량 결정 시험)

  • Chang, Hae-Choon;Koh, Sang-Bum;Lee, Jae-Joon
    • The Korean Journal of Community Living Science
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    • v.27 no.3
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    • pp.437-449
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    • 2016
  • To provide information on the safety of crude antifungal compounds produced by Bacillus subtilus SN7 isolated from Meju, we carried out an acute (single) oral dose toxicity test and 4 week repeated oral dose determination test on crude antifungal compounds in male and female Sprague Dawley rats. In the acute toxicity test, rats were treated with crude antifungal compounds produced by Bacillus subtilus SN7 orally at increasing dose levels (500, 1,000, and 2,000 mg/kg) and observed for 2 weeks. In the repeated-dose 28-day oral dose determination study, rats were orally administered doses of 500, 1,000, and 2,000 mg/kg daily for 4 weeks. There were no test article-related deaths or abnormal clinical signs in the two studies. In the 4 week repeated oral dose determination test, there were also no significant differences in clinical signs, body and organ weight changes, or any other hematological and biochemical parameters between the control and treated groups. The results suggest that the crude antifungal compounds produced by Bacillus subtilus SN7 up to a dosage level of 2,000 mg/kg are not toxic in male and female rats.

3 Months Repeated Dose Toxicity Studies of the Bamboo Salt(Jukyum) in Rats (죽염에 대한 3개월 반복투여 독성시험연구)

  • 김준규;서경원;이봉훈;박미경;박창원;신동환;홍충만;한범석;김윤정
    • Toxicological Research
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    • v.18 no.2
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    • pp.149-157
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    • 2002
  • Though the bamboo salt, called as "JUKYUM" has been widely used in Korea as panacea, it's toxicity was not screened completely. To investigate the toxicity of bamboo salt, we compared with the toxicity of crude salt and reagent-grade NaCl by performing repeated dose (3 month's) oral toxicity test in SD rats. Crude salt, natural sun-dried salt (crude salt) production, was purchased from the western seashore of Korean peninsular and reagent-grade NaCl was purchased from Sigma company. Results of repeated dose oral toxicity tests for 3 months (bamboo salt; 750, 1500, 3000 mg/kg/day, crude salt : 3000 mg/kg/day, reagent-grade NaCl; 3000 mg/kg/day) suggested that the bamboo salt treated group show no significant toxicological findings with body weights and organ weighs changes, and hematological, serum bio-chemical and histopathological findings compared with other groups.er groups.