랫드에서 Compound K (CK)의 단회 및 반복투여독성 평가

변종신 ( Jong Shin Byeon ),박지현 ( Ji Hyeon Park ),최순진 ( Soon Jin Choi ),지유근 ( Yu Guen Ji ),최학주 ( Hak Joo Choi ),김동희 ( Dong Hee Kim ),황석연 ( Seock Yeon Hwang ) 대전대학교 한의학연구소 2013 한의학연구소 논문집 Vol.22 No.1

Single-and repeated-dose toxicities of Compound K (CK) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity study, CK was dissolved in drinking water, orally administered and examined for 14 days. As results, CK up to a dose of 5,000 ㎎/㎏, the limited dose, neither induced death, clinical signs and necropsy findings, nor affected body weight gain and organ weights, in which 10% lethal dose could not be estimated. Based on the results of single-dose toxicity test, CK was administered at doses of 500, 1,000 or 2,000 ㎎/㎏ for 28 days for the evaluation of repeated-dose toxicity. All doses including the limited dose (2,000 ㎎/㎏) of CK did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology, blood biochemistry. Rather, high doses (1,000 - 2,000 ㎎/㎏) of CK reduced the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Thus, both maximum tolerable dose (MTD) and no observed adverse effect level (NOAEL) were not determined. The results indicate that long-term intake of high-dose CK might not induce general adverse effects.

마황윤폐탕(麻黃潤肺湯) 추출물의 수컷 SD Rats에서 경구 단회투여 독성 평가

조동희,박미연,최해윤,김종대,전귀옥,Cho, Dong-Hee,Park, Mee-Yeon,Choi, Hae-Yun,Kim, Jong-Dae,Jeon, Kwi-Ok 대한한방내과학회 2006 大韓韓方內科學會誌 Vol.27 No.1

Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

ACM의 비글견을 이용한 단회 경구투여 용량증가 독성 시험 및 4주 반복 경구투여 용량 결정 시험

임정화 ( Jung Hwa Lim ),이상룡 ( Sang Ryong Lee ),정인철 ( In Chul Jung ) 대한한방신경정신과학회 2013 동의신경정신과학회지 Vol.24 No.1

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.

Tensolin-F^® (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험

김근수,박성민,이남진,표형배,채희열,정유리,임춘매,김선희,이혜영,강종구,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 한국독성학회 2007 Toxicological Research Vol.23 No.4

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.

Single-Dose Intramuscular Toxicity of Mahwangcheonoh Pharmacopuncture in a Rat Model - Toxicity of Mahwangcheonoh Pharmacopuncture in SD Rats -

Sung, Heejin,Lee, Eunyong KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.4

Objectives: This study was conducted to analyze the single-dose toxicity and the safety of Mahwangcheonoh pharmacopuncture extracts. Methods: Six-week-old Sprague-Dawley rats were used for this study. Doses of Mahwangcheonoh pharmacopuncture extracts were set at 0.25 mL (low-dose), 0.5 mL (medium-dose) and 1.0 mL (high-dose) for the test groups. A dose of 1.0 mL of normal saline solution was set for the control group. During 14 days, general symptoms, mortalities, and changes in hematology, blood biochemistry and histopathology of all rats were observed. Results: No death was observed in all test groups. Any abnormal symptom was not observed in all of the groups. No significant changes in weight between the control group and the test groups were observed. In addition, no significant differences in the hematology signs, the blood biochemistry levels and the histopathological signs related to the Mahwangcheonoh pharmacopuncture extracts injection were observed. Conclusion: The findings of this study indicate that Mahwangcheonoh pharmacopuncture at doses of 1.0 mL or less may be consider safe and non-toxic. So, it can be used for therapy of obesity sufficiently. But further studies on this subject must be performed to confirm and verify this conclusion.

마우스 및 랫드에서 botulinum toxin type A의 단회 및 28일 반복투여 독성시험

전태원,김지영,현선희,김남희,이상규,김춘화,우희동,양기혁,정현호,정태천,Jeon, Tae-Won,Kim, Ji-Young,Hyun, Sun-Hee,Kim, Nam-Hee,Lee, Sang-Kyu,Kim, Chun-Hwa,Woo, Hee-Dong,Yang, Gi-Hyeok,Jung, Hyun-Ho,Jeong, Tae-Cheon 대한수의학회 2003 大韓獸醫學會誌 Vol.43 No.1

Single and 28-day repeated dose toxicity studies of botulimnn toxin type A were carried out in ICR mice and Sprague-Dawley rats, respectively. In the single dose toxicity study, botulinwn toxin was injected intraperitoneally to male and female mice at a single dose of 40, 59, 89 133 and 200 ng/10 ml saline/kg. All animals died from 59 ng/kg group. Some clinical signs, such as decrease in locomotor activity, dyspnea, prone position and ptosis, were observed in most of both sexes from 59 ng/kg group, but no signs were seen in all animals at 40 ng/kg group. The results showed that the median lethal dose of botulinum toxin might be in the range of 40-59 ng/kg in both sexes. In the repeated dose toxicity study, the test material was administered intradermally for 28 days at doses of 0 (vehicle-treated control), 1.25, 2.5, 5.0 and $10.0ng/head/50{\mu}{\ell}$ saline in male and female rats. No test material-related changes were noted in survivals, clinical signs, food and water consumptions and gross finding in any group. Botulinum toxin treatment significantly decreased the body weight gain rate in male of 5.0 ng/head group and over and in female of 10.0 ng/head group compared to vehicle-treated control. One or more relative organ weights (i.e., spleen, thymus, liver and kidney) were increased significantly from 5.0 ng/head group compared to vehicle-treated control in both sexes. Serum biochemistry revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase, total protein and albumin in male, and increases in AST and ALT and decreases in $K^+$ and $Cl^-$ in female without dose-pendent manners. In the histopathological study, physical stimulation by needle caused slight inflammations of dennis. In addition, botulinum toxin treatment induced denervation of nerve cell and disuse of muscle, resulting in atrophy of skeletal muscle in both sexes from 2.5 ng/head group. When the antibodies to toxin were determined in all animals, a significant increase in serum antibodies was observed from 5.0 ng/head group. The results showed that the NOAEL of botulinum toxin might be 1.25 ng/head for 28-day repeated dose toxicity in rats.

Single and Five-Week Oral Dose Toxicity Studies of Calcitriol and Alendronate Mixtures in Rats

Moon, Sung Won,Jin, Ji Yun,Lee, Jin Hee,Sim, Sang Soo,Kim, Chang Jong Korean Society of ToxicologyKorea Environmental Mu 2004 Toxicological Research Vol.20 No.3

The purpose of this study was to assess the single and 5 week oral dose toxicity of calcitriol and alendronate combination (1 : 10,000) treatment for osteoporosis or Paget's disease in male and female rats. In single dose oral toxicity study, the values of $LD_{50}$ of calcitriol and alendronate mixture were 750.075 mg/kg in male rats and 775.0775 mg/kg in female rats, respectively. Body weight and food consumption were continuously increased after adminstration of calcitriol and alendronate mixtures, and there was no significant changes in body weight and food consumption in all groups. In five-week oral toxicity study of calcitriol and alendronate mixture at a dose of 0.2 $\mu\textrm{g}$ + 2 mg, 1 $\mu\textrm{g}$ + 10 mg, 5 $\mu\textrm{g}$ + 50 mg and 25 $\mu\textrm{g}$ + 250 mg, respectively, there was no mortality, abnormal behavior and appearance in all groups throughout the administration period (5 weeks) and recovery period (2 weeks). Dose-dependent changes in parameters of urinalysis and hematological analysis were not observed in male and female rats treated with calcitriol and alendronate mixtures. All the values of the parameters appeared to be in the normal range. These data indicate that both calcitriol and alendronate are drugs having low toxicity in rats. NOAEL of calcitriol and alendronate mixtures were 50.005 mg/kg in 5-week oral toxicity.

Evaluation of General Toxicity and Genotoxicity of the Silkworm Extract Powder

Hyun-Suk Heo,Jae-Hun Choi,Jung-Ja Oh,Woo-Joo Lee,Seong-Sook Kim,Do-Hoon Lee,Hyun-Kul Lee,Si-Whan Song,Kap-Ho Kim,Yang-Kyu Choi,Kang-Sun Ryu,Boo-Hyon Kang 한국독성학회 2013 Toxicological Research Vol.29 No.4

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent α-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

Tensolin-F<SUP>®</SUP> (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험

김근수(Keun-Su Kim),박성민(Sung-Min Park),이남진(Nam-Jin Lee),표형배(Hyeong-Bae Pyo),채희열(Hee-Yul Chai),정유리(Yu-Ri Jung),임춘매(Chun-Mai Lin),김선희(Sun-Hee Kim),이혜영(Hye-Young Lee),강종구(Jong-Koo Kang) 한국독성학회 2007 Toxicological Research Vol.23 No.2

This study was to investigate single and repeated-dose toxicities of Tensolin-F<SUP>®</SUP>, 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 ㎎/㎏. No dead animals and abnormal necropsy findings were found in control and Tensolin-F<SUP>®</SUP> treated group. Therefore, the approximate lethal dose of Tensolin-F<SUP>®</SUP> was considered to be higher than 2,000 ㎎/㎏ 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 ㎎/㎏/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 ㎎/㎏, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 ㎎/㎏, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 ㎎/㎏. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 ㎎/㎏ 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<SUP>®</SUP> to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 ㎎/㎏ body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-F<SUP>®</SUP> in ICR mice following gavage for at least 4-week is higher than 100 ㎎/㎏/day.

의이엽(薏苡葉)의 Sprague-Dawley 랫드를 이용한 단회경구투여 독성시험

김민주 ( Min Ju Kim ),이정훈 ( Jeong Hoon Lee ),신미래 ( Mi-rae Shin ),노성수 ( Seong-soo Roh ) 대한본초학회 2021 大韓本草學會誌 Vol.36 No.5

Objectives : ‘Johyun’ yulmoo which is a new variety of Coix lacryma-jobi var. ma-yuen Stapf sprout was developed and registered by Rural development administration in 2004. This variety was derived from the cross between single cross of Suwon-6 and Okayama and UCN300-25 as F1. It is characterized by early maturity, short plant height, a strong resistance, and a superior yield and is suitable for the central and northern regions. Accordingly, we were performed and evaluated single oral dose toxicity test of ‘Johyun’ yulmoo sprout (JYS) in Sprague-Dawley (SD) rats. Methods : Single oral dose toxicity test was performed using with male and female rats. Rats were divided into two groups: Group 1, vehicle-treated rats (Control); Group 2, JYS 5000 mg/kg-treated rats. JYS was orally administered to male and female rats at dose levels of 5000 mg/kg. Animals were monitored on the mortality, clinical signs, body weight changes, and necropsy findings for 14 days. groups : Group 1, vehicle-treated rats (Control); Group 2, JYS 5000 mg/kg-treated rats. JYS was orally administered to male and female rats at dose levels of 5000 mg/kg. Animals were monitored on the mortality, clinical signs, body weight changes, and necropsy findings for 14 days. Results : After oral treatment of JYS, we could not find any mortality at 5000 mg/kg. Compared with the control group, there were also no significant differences in clinical sign, weight changes, weight gain, and gross abnormalities in JYS 5000 mg/kg-treated group. Conclusions : Taken together, these results suggest that approximate lethal dose of JYS was considered as over 5000 ㎎/㎏. Results from this study provide scientific evidence for the safety of JYS. Moreover, this study could be used as a basis for dose-setting data of the repeated dose 13-week oral toxicity test of JYS.