• Title/Summary/Keyword: Repeated four-week oral toxicity

Search Result 23, Processing Time 0.025 seconds

Single-Dose Toxicity and Four Week Repeated-Dose Toxicity Study on Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen) (Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험)

  • Kim, Keun-Su;Park, Sung-Min;Lee, Nam-Jin;Pyo, Hyeong-Bae;Chai, Hee-Yul;Jung, Yu-Ri;Lin, Chun-Mai;Kim, Sun-Hee;Lee, Hye-Young;Kang, Jong-Koo
    • Toxicological Research
    • /
    • v.23 no.4
    • /
    • pp.405-413
    • /
    • 2007
  • This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

Four-Week Oral Toxicity Study of CJ-50002 (Vibrio Vaccine) in Rats (CJ-50002(비브리오백신)의 랫드에 대한 4주간 경구 반복투여 독성연구)

  • 윤병일;정수연;김달현;이영수;김대용
    • Toxicological Research
    • /
    • v.15 no.1
    • /
    • pp.9-17
    • /
    • 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.

  • PDF

Four-Week Repeated Oral Toxicity Study of Leuconostoc citreum GR1 in Rats (김치에서 분리한 Leuconostoc Citreum GR1의 흰쥐에 대한 반복투여독성)

  • Kim, Ah-Ra;Lee, Myung-Yul;Chang, Hae-Choon;Lee, Jae-Joon
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.42 no.4
    • /
    • pp.600-607
    • /
    • 2013
  • This study was performed to investigate the repeated-dose toxicity of Leuconostoc citreum GR1 (Leuc. citreum GR1), a lactic acid bacterium isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four group (ten animals in each group) and Leuc. citreum GR1 was administered daily by gavage to rats at dosage levels of 0, 500, 1,000, or 2,000 mg/kg/day for four weeks. There were no bacterial-related deaths or abnormal clinical signs in either gender of rats during the observation period. Furthermore, no differences were found between the control and treatment groups in terms of body weight, food intake, and water consumption. Hematological parameters, serum biochemical analysis, and histopathological examination also showed insignificant dose-dependent alterations. There were also no alterations in organ weights upon administration of Leuc. citreum GR1 alone. These results suggest the oral application of Leuc. citreum GR1, up to a dosage level of 2,000 mg/kg, causes no adverse effects in both male and female rats.

Repeated-dose oral toxicity study of crude antifungal compounds produced by Lactobacillus plantarum AF1 in rats (Lactobacillus plantarum AF1이 생성한 조항진균 물질의 흰쥐에 대한 반복투여독성)

  • Lee, Hwan;Lee, Myung-Yul;Chang, Hae-Choon;Lee, Jae-Joon
    • Food Science and Preservation
    • /
    • v.20 no.3
    • /
    • pp.394-403
    • /
    • 2013
  • This study was performed to investigate the four-week repeated-dose toxicity of the crude antifungal compounds produced by Lactobacillus plantarum AF1 (Lb. plantarum AF1), a lactic acid bacterium isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four groups, with 10 animals in each group. The test article was administered once daily by gavage to rats at dosage levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. There were no test-article-related deaths or abnormal clinical signs in both the male and female rats during the observation period. Furthermore, no differences in the body weight changes, food intake and water consumption levels of the control and treatment groups were found. The hematological parameters, serum biochemical analysis results, histopathological examination results and all other findings also showed no significant or dose-dependent changes. There were also no changes in the organ weights upon the administration of the crude antifungal compounds produced by Lb. plantarum AF1. These results suggest that the oral administration of the crude antifungal compounds produced by Lb. plantarum AF1 had no adverse effects up to a dosage level of 2,000 mg/kg in both male and female rats.

Four-week Oral Toxicity Study of DA-5018, a New non-narcotic Analgesic Agent (비 마약성 진통제 DA-5018의 랫드에 대한 4주 경구투여 아급성독성)

  • 강경구;김옥진;백남기;안병옥;김원배;양중익
    • Biomolecules & Therapeutics
    • /
    • v.5 no.2
    • /
    • pp.133-149
    • /
    • 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.

  • PDF

26-Week Repeated Dose Oral Toxicity Study of KCHO-1 in Sprague-Dawley Rats

  • Yang, Muhack;Lee, Seongjin;Wang, Tingting;Cha, Eunhye;Jang, Jongwon;Kim, Dongwoung;Song, Bong-Keun;Son, Ilhong;Kim, Joonyup;Kang, Hyung Won;Kim, Sungchul
    • Journal of Pharmacopuncture
    • /
    • v.22 no.3
    • /
    • pp.192-199
    • /
    • 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.

PRECLINICAL TOXICITY STUDY OF A NEW PHOSPHODIESTERASE-5 INHIBITOR (II) FOUR-WEEK SUBACUTE TOXICITY STUDY IN RATS

  • Hyeon Cho;Kim, Dong-Hwan;Kang, Kyung-Koo;Ahn, Byoung-Ok;Kim, Won-Bae
    • Proceedings of the Korean Society of Toxicology Conference
    • /
    • 2001.05a
    • /
    • pp.128-128
    • /
    • 2001
  • Toxic effects of a new phosphodiesterse-5 inhibitor, DA-8159, were investigated in Sprague-Dawley rats by repeated oral administration. Four groups of 10 male and 10 female rats were treated with DA-8159 at a dose of 0, 40, 80, or 320 mg/kg/day for 4 weeks.(omitted)

  • PDF

Four-Week Repeated Oral Toxicity Study of AIP1, a Water-soluble Carbohydrate Fraction from Artemisia iwayomogi in Mice

  • Ryu, Sung-Ha;Jo, Hae-Ran;Kim, Ji-Won;Youn, Hyun-Joo;Kim, Kyu-Bong
    • Toxicological Research
    • /
    • v.27 no.4
    • /
    • pp.261-267
    • /
    • 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.

Four-week Oral Toxicity Study of DA-9601, an Antiulcer Agent of Artemisia spp. Extract, in Rats (애엽추출물 항궤양제 DA-9601의 랫드에 대한 4주 경구 반복투여 독성연구)

  • 김옥진;강경구;김동환;백남기;안병옥;김원배;양중익
    • Biomolecules & Therapeutics
    • /
    • v.4 no.4
    • /
    • pp.354-363
    • /
    • 1996
  • This study was conducted to investigate the repeated dose toxicity of DA-9601, an antiulcer agent of Artemisia app. extract, in rats. DA-9601 was administered orally once a day for 4 weeks to 10 males and 10 females per group at doses of 0(vehicle control), 125, 500 or 2000 mg/kg/day. Throughout the study, no treatment-related deaths and clinical signs were observed. In female rats receiving 125 mg/kg of DA-9601, water consumption increased slightly on day 4, 11 and 25. Hematological examination showed a decrease of MCV and an increase of PLT in male rats at the doses of 500 and 2000 mg/kg groups. Blood biochemistry revealed slight decreases of cholesterol, BUN and Na in male rats and decreases of total bilirubin and creatinine and slight increases of globulin and Cl in female rats. The organ weights at the end of 4 weeks showed slight changes in some organs of treated groups. But, all these changes were not considered to be of toxicological importance, because they did not show dose-response relationship and relevance to gross and microscopic findings. Histopathologically, abnormal treatment-related changes were not observed in any organ and target organs were not detected. On the basis of these results, the NOAEL(no-observed-adverse-effect level) of DA-9601 was estimated to be more than 2000 mg/kg/day under the conditions tested.

  • PDF

Repeated-Dose Oral Toxicity Study of Lactobacillus Plantarum AF1 Isolated from Kimchi in Rats (김치에서 분리한 Lactobacillus plantarum AF1의 흰쥐에 대한 반복투여독성)

  • Lee, Jae-Joon;Kim, Ah-Ra;Chang, Hae-Choon;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.41 no.5
    • /
    • pp.612-620
    • /
    • 2012
  • This study was performed to investigate the 4-week repeated-dose toxicity of $Lactobacillus$ $plantarum$ AF1 ($Lb.$ $plantarum$ AF1), a lactic acid bacteria isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four groups, with 10 animals in each group. The test article was administered once daily by gavage to rats at dosage levels of 0, 0.5, 1.0, and 2.0 g/kg/day for 4-weeks. There were no test articlerelated deaths or abnormal clinical signs in either gender of rat during the observation period. Furthermore, no differences were found between the control and treatment groups in terms of body weight changes, food intake, and water consumptions. Hematological parameters, serum biochemical analysis, and any other findings also showed no significant or dose-dependent alterations. There were no alterations in organ weights upon administration of $Lb.$ $plantarum$ AF1. These results suggest that there were no adverse effects of oral application of $Lb.$ $plantarum$ AF1 up to a dosage level of 2.0 g/kg in both male and female rats.