• Title/Summary/Keyword: Dose recovery test

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Study on a 4-Week Recovery Test of Sweet Bee Venom after a 13-Week, Repeated, Intramuscular Dose Toxicity Test in Sprague-Dawley Rats

  • Kang, Hyunmin;Lim, Chungsan;Lee, Seungbae;Kim, Byoungwoo;Kwon, Kirok;Lee, Kwangho
    • Journal of Pharmacopuncture
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    • v.17 no.2
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    • pp.18-26
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    • 2014
  • Objectives: This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV) in Sprague-Dawley (SD) rats. Methods: Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: (1) Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2) The rats in the high-dose group showed no significant changes in weight compared to the control group. (3) No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs), and biochemistry were observed among the recovery groups. (4) No changes in organ weights were observed during the recovery period. (5) Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion: The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

A 13-Week Repeated Oral Dose Toxicity Test and a 4-Week Recovery Test of Standardized Cornus officinalis and Psoralea corylifolia L . in Sprague-Dawley Rats (산수유(山茱萸)와 보골지(補骨脂) 복합추출물의 Sprague-Dawley 랫드를 이용한 13 주 반복경구투여 독성시험 및 4 주 회복시험)

  • Sim, Seo-Ah;Kang, Sung-Chul;Jin, Bo-Ram;Kim, Min-jeong;Yeo, Sujung;Park, In-hwa;Jerng, Ui Min;Cha, Yun-yeop;Ahn, Ji-Hye;An, Hyo-Jin
    • The Korea Journal of Herbology
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    • v.36 no.6
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    • pp.27-37
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    • 2021
  • Objectives : In the current study, we performed the 13-week repeated oral dose toxicity test and a 4-week recovery test of standardized Cornus officinalis Sieb. et Zucc. and Psoralea corylifolia L. 30 % ethanol extract (SCP) in Sprague-Dawley (SD) rats owing to aims for verifying no observed adverse effect level (NOAEL). Methods : The animal study was performed according to OECD guidelines for the testing of chemicals section 4 health effects test No.408 repeated dose 90-day oral toxicity study in rodents (03 October 2008). In the repeated dose toxicity study, SCP was orally administered to female and male rats at dose levels of 1,000, 2,000, and 4,000 mg/kg/day for 13-week. The control group and high dose (4,000 mg/kg/day) group were then monitored for 4 extra weeks to determine recovery time after the study period. 1) Results : Compared with the control group, there were no treatment-related adverse effects in clinical signs, body weight, hematology, serum biochemistry (Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, 𝛾-Glutamyl transpeptidase, Blood urea nitrogen, Creatinine, Glucose, Total cholesterol, Total protein, Creatine phosphokinase, Albumin, Total bilirubin, Triglyceride, Inorganic phosphorus, Albumin/Globulin ratio, Calcium ion, Sodium ion, Potassium ion, Chloride ion), necropsy findings and organ weight (Ovary, Adrenal gland, Pituitary, Thymus, Prostate, Testis, Epididymis, Spleen, Kidney, Heart, Lung, Brain, Liver) at any dose tested. Conclusions : Taken together, these results suggest that the NOAEL of SCP in both genders was considered as over 4,000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

A Thirteen Week Repeated Oral Dose Toxicity Test and A Four Week Recovery Test of GST in Sprague-Dawley Rats (GST 추출물의 Sprague-Dawley Rat를 이용한 13주 반복 경구투여 독성시험 및 4주 회복시험)

  • Kim, Yoon-Ha;Kim, Jun-Young;Han, Jong-Min;Lee, Hye-Yeong;Jung, In-Chul;Jin, Mi-Rim;Kim, Seong-Hyeong;Park, Yang-Chun
    • The Journal of Internal Korean Medicine
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    • v.35 no.3
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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.

A Thirteen Week Repeated Oral Dose Toxicity Test and A Four Week Recovery Test of ACM(Added Chongmyung-tang) in Sprague-Dawley Rats (ACM의 Rat를 이용한 13주 반복 경구투여 독성시험 및 4주 회복시험)

  • Park, Dae-Myung;Lee, Sang-Ryong;Lim, Jong-Soon;Kim, Seung-Hyung;Jung, In-Chul
    • Journal of Oriental Neuropsychiatry
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    • v.23 no.3
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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.

28-day Repeated-dose Toxicity Study of Flutamide, an Anti- androgenic Agent, in Rats: Establishment of Screening Methods for Endocrine Disruptors (내분비계 장애물질 검색법의 확립을 위한 항안드로젠성 물질 flutamide의 랫드 28일 반복투여 독성실험)

  • 정문구;김종춘;임광현;하창수
    • Toxicological Research
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    • v.16 no.2
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    • pp.163-172
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    • 2000
  • Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. DECD is developing screening programs using validated test systems to determine whether certain substances may have an effect in humans. In the present study. the establishment oj repeated-dose toxicity test method was tried. Flutamide. an anti-androgenic agent. was administered by gavage to Sprague-Dawley rats for 28 days at dose levels of 0. 0.5. 3 and 18 mg/kg body weight (10-15 rats/sex/group) to examine the effects on general findings. especially reproductive and endocrine parameters. Clinical signs. body weights, food consumption, and sexual cycle were checked and measured. For the gross and microscopic examinations. 10 rats/sex/group were sacrificed at the end of dosing period and the remaining animals of control and high dose groups (5 each) were sacrificed after 14 days recovery. Examinations for hematology and clinical chemistry were carried out at necropsy. There were no treatment-related changes in clinical signs. body weights, food consumption. gross necropsy. hematology and clinical chemistry at all doses of both sexes. The period and regularity of sexual cycle were not adversely affected at all doses by the test agent. At 18 mg/kg. both decreased weights of prostate, seminal vesicle and epididymis in males and increased weights of spleen and thymus in females were observed. In addition, decreased number of spermatids and sperms. increased serum testosterone concentration and increased incidence (100%) of interstitial cell hyperplasia were seen in males. At 18 mg/kg of the recovery group. decreased prostate weight. reduced sperm count and increased incidence (20%) of interstitial cell hyperplasia in males and increased thymus weight in females were observed. At 3 mg/kg. reduced sperm count was found. There were no adverse effects on parameters examined at 0.5 mg/kg of both sexes. The results suggested that the potential target organs of flutamide may be accessory sexual glands including testes for males and spleen and thymus for females. Taken together. this test method was found to be a useful screening test system for endocrine disrupting chemicals.

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Development of a prototype TL/OSL reader for on-site use in a large-scale radiological accident

  • Hyoungtaek Kim;Chang-Young Park;Sang In Kim;Min Chae Kim;Jungil Lee
    • Nuclear Engineering and Technology
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    • v.56 no.6
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    • pp.2113-2119
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    • 2024
  • This study presents the development and characterization of a prototype TL/OSL reader for the retrospective dose assessment of individuals in radiological emergencies. The reader is portable, semi-automatic, and capable of accurate measurements. The dimension of the reader is 25 × 25 × 37 cm3 and the weight is about 15 kg. The reader consists of a sample moving stage, a heating module, an optical stimulation module, a detection module, a data acquisition (DAQ) unit, a nitrogen gas control module, and a PC with a GUI program. The reader has three measurement modes: TL, CW_OSL, and custom mode. The reader was characterized using commercial thermal luminescence dosimeters (TLD, LiF:Mg,Cu,Si) and optically stimulated dosimeters (OSLD, Al2O3:C), as well as fortuitous materials, such as display glasses and resistors of mobile phone. The results showed that the reader is capable of measuring signals with a detection limit of up to 0.02 mGy using a commercial dosimeter. In the dose recovery test using fortuitous materials, the reconstructed doses obtained three days post-irradiation closely aligned with the initially administered doses. As a result, this study suggests that the developed TL/OSL reader is a promising instrument for emergency dose assessment at accident sites.

Effect of Whole-body gamma-Irradiation on Blood Picture in Mice (Cobalt-60 gamma선(線) 전신조사(全身照射)가 생쥐의 혈액상(血液像)에 미치는 영향(影響))

  • Sung, Jai Ki;Cheong, Chang Kook
    • Korean Journal of Veterinary Research
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    • v.15 no.2
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    • pp.153-159
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    • 1975
  • In order to investigate the effect of cobalt-60 gamma irradiation on the blood picture, the mice were subjected to single whole-body gamma irradiation externally. In this experiment 42 of 12 weeks old white mice were used and animals were allotted to group of three. On of chose groups served as control and the others as test groups that were exposed to single dose of 370 Rads (group I) and 500 Rads (group II). The exposure dose rate were averaged 33 Rads per Minute. The results obtained in this experiment were as follows: 1. Erythrocyte counts in both test groups dropped to the lowest level at 4 weeks postirradiation, returning towards the control level, but in recovery, group I showed rather prumpt compared with group II. Erythrocyte count in group II was significantly lower than that of group I. 2. Total leukocyte counts dropped to the lowest loved at 2 weeks postirradiation and group I recovered to normal level at 4 weeks postirradiation. Recovery group II was very slow and it reached to the control level on 12 weeks postirradiation. Leukocyte count was significantly different between group I and II. 3. Neutrophil count was increased to the highest level at 2 weeks postirradiation, with recovery to normal value after 8 weeks in group I and 12 weeks in group II, respectively. Neutrophil count was significantly different between group I and II. 4. Lymphocyte count dropped to the lowest level at 2 weeks postirradiation, with recovery to normal average after 8 weeks in group I and 12 weeks in group II, respectively. Lymphocyte count was significantly different between group I and II. 5. The other leukocyte count was increased after the irradiation and recovered at 12 weeks postirradiation in both test groups. The other leukocyte count was significantly different between group I and II.

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Hair-Growth Effect and Single Dose Oral Toxicity Test of Illite Powder (Illite 분제 원액의 육모 활성 시험 및 단회 투여 경구 독성시험)

  • 박형섭;임동술;정재훈;이충재;김박광
    • Biomolecules & Therapeutics
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    • v.9 no.4
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    • pp.307-310
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    • 2001
  • The hair-growth effect of Illite was suggested by some people who were using Illite as a beautifying material. We investigated the hair-growth effect of Illite powder. The hair-growth effects were investigated by two methods; the activity of hair-growth after shaving the hairs on the black mouse (C57BL/6) and the recovery activity of hair-growth after hair-loss induced by cyclophosphamide treatment. Suspension of Illite powder was applied to the back of the black mouse by method of skin paste. Illite promoted significantly the hair growth of mouse in both conditions of shaving and hair-loss. And then we investigated the toxicity which may be induced by Illite when it was administrated orally as a single dose. We could not fond out any significant toxicity induced by single dose oral administration of Illite.

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Effect of CJ-50001 (rG-CSF) on the Recovery of the Neutrophil Numbers in the Mice with Bone Marrow Transplantation BMT) (CJ-50001 (rG-CSF)의 골수이식모델 마우스에 대한 호중구수 회복 촉진효과)

  • 임동문;조효진;김종호;김달현;고형곤;김제학;김현수
    • Biomolecules & Therapeutics
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    • v.5 no.4
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    • pp.376-379
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    • 1997
  • The peripheral neutrophil recovery test was conducted to determine the efficacy of CJ-50001, a drug developed in Cheil Jedang R&D center as a recombinant granulocyte-colony stimulating factor (rG-CSF). Grasin was used as control drug. CJ-50001 and Gratin were subcutaneously administered to ${\gamma}$-ray irradiated mice for 21 days at a dose of 10$\mu$g/kg after bone marrow transplantation and the recovery of neutrophil number was examined on the days of 9, 13, 17, and 21 after the drug administration. It was observed that the peripheral neutrophil number of the vehicle control group was recovered to the normal level on the day of 13 after the transplantation whereas the group administered with CJ-50001 and Grasin respectively, showed the normal level of peripheral neutrophil number on 9th day after the bone marrow transplantation. The number of peripheral neutrophils reached the highest level on the 21 st day of drug administration, and was recovered to the normal level on the 4th day after ceasing of the drug administration (on the 25th day of the transplantation). Thus, it was presumed that CJ-50001 showed efficacy similar to Grasin on the peripheral neutrophil recovery after bone marrow transplantation.

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Evaluation of Variation Method to Improve the Sensitivity of Immunoradiometric Assay (면역방사계수측정법의 민감도 향상을 위한 변법의 평가)

  • Won-Hyun Kwon;Mi-Ji Kang;;Ji-Sol Park;Jung-In Kim;Kyung-Jae Lee
    • The Korean Journal of Nuclear Medicine Technology
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    • v.27 no.1
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    • pp.29-35
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    • 2023
  • Purpose The concentration of PSA (Prostate Specific Antigen) after radical prostatectomy in prostate cancer patients is a predictor of biochemical recurrence, and the AUA (American Urological Association) is defined as biochemical recurrence when the concentration of PSA is measured at 0.2 ng/mL or more, and when the concentration is measured at 0.2 ng/mL or more at the retest. This standard is also applied our hospital. In this laboratory, the PSA reagent using IRMA (Immunoradiometric Assay) is used, and the sensitivity at a very low value was not as good as the reagent used in the department of laboratory medicine. This study aims to increase the reliability of the results by improving the precision and sensitivity of very low values. Materials and Methods As a reagent for the study, PSA reagent using IRMA was used. As a method to improve the precision and sensitivity of very low values, a variation method on the serum volume(25 uL, 50 uL, 100 uL, 200 uL) was studied, and variation usefulness evaluation was conducted. The evaluation items were compared the results of precision, analytical sensitivity, recovery rate, dilution test, high-dose hook effect test, parallel test and very low concentration values(n = 20). Results The validation results were displayed in the order of 25 uL, 50 uL, 100 uL, 200 uL. As the serum volume increased, it was confirmed that CV (Coefficient of Variation)(%) improved. Analytical sensitivity(ng/mL) was 0.038, 0.041, 0.017, 0.015 and recovery rate(%) was 101±3, 101±3, 99±2, 97±4. very low concentration values(ng/mL) between each volume(n=20) were 0.135±0.068, 0.076±0.050, 0.048±0.034, 0.046±0.034. and high dose hook effect appeared as the serum volume increased. Conclusion Through the variation usefulness evaluation, it was confirmed that as the serum volume increased, the precision and sensitivity improved at very low concentration values. However, it is necessary to pay special attention to the occurrence of high-dose hook effect as the serum volume increases. In the case of tests that requires very low concentration values, it is thought that the reliability of the result will be increased if the variation method is properly used after the variation usefulness evaluation.

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