• Title/Summary/Keyword: 14-day repeated dose toxicity

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Fourteen-day Repeated-dose Oral Toxicity Study of the Ethanol Extracts Isolated from Oplopanax elatus in Sprague-Dawley Rat (흰쥐에서 땃두릅 에탈올 추출물의 14일 반복경구토여에 의한 독성시험)

  • Kwon, Hyuck-Se;Kim, Dae-Hwan;Shin, Hyun-Kyung;Yu, Chang-Yeon;Kim, Myong-Jo;Lim, Jung-Dae;Park, Jae-Kun;Kim, Jin-Kyung
    • Korean Journal of Food Science and Technology
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    • v.39 no.4
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    • pp.470-475
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    • 2007
  • Oplopanax elatus (O. elatus) is a tall deciduous shrub that has traditionally been used for σ eating a variety of ailments such as diabetes, coughling, rheumatism, gastro-intestinal disorders, and wounds. In order to examine the safety of the ethanol extracts of O. elatus, we performed a 14-day repeated-dose toxicity study with Sprague-Dawley rats. The rats were treated with daily doses of the D. elatus ethanol extracts by gavage at 0, 500, 1000, and 2000 mg/kg/day for 14 consecutive days. We recorded clinical signs of toxicity, body weight, hematology, organ weights, gross and histological changes in target organs, and clinical chemistry analysis data for all rats. There were no significant changes in body and organ weights during the experimental period. The hematological analysis and clinical blood chemistry data revealed no toxic effects from the O. elatus ethanol extracts. Pathologically, neither gross abnormalities nor histopathological changes were observed between the control and treated rats of both sexes. Collectively, these data suggest that the ethanol extracts of O. elatus have a high margin of safety.

Oral Etoposide for Platinum-Resistant and Recurrent Epithelial Ovarian Cancer: a Study by the Anatolian Society of Medical Oncology

  • Kucukoner, Mehmet;Isikdogan, Abdurrahman;Yaman, Sebnem;Gumusay, Ozge;Unal, Olcun;Ulas, Arife;Elkiran, Emir T.;Kaplan, Muhammed A.;Ozdemir, Nuriye;Inal, Ali;Urakci, Zuhat;Buyukberber, Suleyman
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3973-3976
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    • 2012
  • Background: The aim of this study was to evaluate the efficacy and toxicity of long-term, low-dose oral etoposide as an advanced treatment option in patients with platinum resistant epithelial ovarian cancer. Materials and Methods: For the purposes of this study, 51 patients with histologically-confirmed, recurrent or metastatic platinum-resistant epithelial ovarian cancer (EOC) treated at six different centers between January 2006 and January 2011 were retrospectively evaluated. Patients were treated with oral etoposide (50 mg/day for a cycle of 14 days, repeated every 21 days). Results: Among the 51 platinum-resistant patients, 17.6% demonstrated a partial response and 25.5% a stable response. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.1-5.7), while the median overall survival was 16.4 months (11.8.20.9). No significant relationship was observed between the pre-treatment CA 125 levels, post-treatment CA-125 levels and the treatment response rates (p=0.21). Among the 51 patients who were evaluated in terms of toxicity, grade 1 or 4 hematologic toxicity was observed in 19 (37.3%); and grade 1-4 gastrointestinal toxicity occurred in 15 patients (29.4%). Conclusions: Chronic low-dose oral etoposide treatment is generally effective and well-tolerated in platinum-resistant ovarian cancer patients.

Safety Evaluation of Kyungokgo-gamibang Administration Based on Hematological, Biochemical, Protein, and Lipid Profiles in Dogs

  • Song, Doo-won;Lee, Ga-won;Ro, Woong-bin;Kim, Heyong-seok;Kang, Hyun-min;Kim, Jong-won;Park, Soo-bin;Moon, Yang-seon;Na, Chang-su;Park, Hee-myung
    • Journal of Veterinary Clinics
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    • v.38 no.1
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    • pp.7-15
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    • 2021
  • Kyungokgo-gamibang, Kyungokgo with Iksuyongjingo and Sparassis crispa, is a traditional Korean medicine used for restorative effects. This study aimed to evaluate the safety of Kyungokgo-gamibang in healthy beagle dogs. In the single-dose oral toxicity study, three beagle dogs were orally administered 2,000, 1,000, and 500 mg/kg of Kyungokgo-gamibang and were observed for 14 days. In the repeated-dose oral toxicity study, nine healthy dogs were orally administered 0.2g/kg of Kyungokgo-gamibang (n = 3, low-dose group), 1 g/kg of Kyungokgo-gamibang (n = 3, high-dose group), or normal saline (n = 3, control group) twice a day for 8 weeks. The hematological, serum biochemical, urine, protein, and lipid profiles were evaluated to investigate the adverse effects of the Kyungokgo-gamibang. During the study period, the dogs demonstrated no clinical signs and the hematological, serum biochemical, urine, protein, and lipid analyses revealed unremarkable findings. The study results suggest that Kyungokgo-gamibang can be safely administered to dogs without any adverse effects.

Study on the Acute and Sub-Acute Inhalation Toxicity of 1-Bromopropane in SD Rats (Rat를 이용 1-Bromopropane의 급성 및 아급성 흡입독성 연구)

  • Kim, Hyeon-Yeong;Jeong, Jae-Hwang;Chung, Yong-Hyun;Lee, Yong-Muk;Sur, Gil-Soo
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.8 no.2
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    • pp.272-288
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    • 1998
  • The purpose of this study was to investigate the acute(4 hrs) and repeated-dose(6 hrs a day, 5 days a week, 8 weeks) toxic effects of 1-bromopropane(1-BP) on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows ; 1. The median lethal concentration($LC_{50}$) was estimated 14,374 ppm(confidence limit 95% ; 13,624~15,596 ppm) in acute inhalation. Abnormal clinical signs related to the 1-BP were not observed with the acute inhalation dose. Gross findings of necropsy revealed no evidence of specific toxicity related to the 1-BP. 2. By sub-acute inhalation the body weights of male and female were significantly reduced(p<0.001) by the dose of 1,800 ppm compared with control group, while the relative weights of liver were significantly increased(p<0.001) in both sexes. However there were no significant variation in food consumption, urine biochemistry, hematology and blood biochemistry for the exposed rats compared with the control rats. Abnormal clinical signs and gross findings of necropsy related to the 1-BP were not shown. No toxicologic lesions were observed by the histopathological test.

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Toxicokinetics and oral toxicity of Maesil-cheongs with reduced amygdalin levels (아미그달린 저감화 매실청의 독성동태학적 및 경구독성 연구)

  • Kim, Hyeon-Jin;Go, Mi-Ran;Yu, Jin;Hwang, Ji-Soo;Choi, Hyun Woo;Kim, Hyun-Seok;Choi, Soo-Jin
    • Korean Journal of Food Science and Technology
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    • v.50 no.6
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    • pp.629-635
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    • 2018
  • In this study, the safety aspect of Maesil-cheongs with reduced amygdalin levels was investigated in terms of toxicokinetics and repeated oral toxicity. Plasma or UVC treatment was utilized to obtain Maesil-cheongs with reduced amygdalin levels. The toxicokinetic study demonstrated that the oral absorption of amygdalin decreased remarkably after a single-dose oral administration of both plasma- and UVC-treated Maesil-cheongs. The fourteen-day repeated oral toxicity study revealed that plasma- or UVC-treated Maesil-cheongs did not cause changes in body weight, food intake, water consumption, and absolute and relative organ weights. No significant effects on hematological and serum biochemical parameters were found. Histopathological examination showed no abnormality or toxicological change. These findings suggest that plasma- and UVC-treated Maesil-cheongs have no toxicity potential, and these processes will be useful to obtain products with safe, reduced amygdalin levels.

Safety Evaluation of Korean Mistletoe Extract (한국산 겨우살이 추출물의 안전성 평가)

  • Kim, Inbo;Jeong, Ju-Seong;Yoon, Taek Joon;Kim, Jong Bae
    • The Korean Journal of Food And Nutrition
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    • v.26 no.3
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    • pp.383-390
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    • 2013
  • Mistlero C was shown to be non-genotoxic in a series of genotoxicity tests, including a bacterial reverse mutation test and a combined in vivo mammalian erythrocyte micronucleus test. In a bacterial reverse mutation assay, no significant increases in the number of revertant colonies, compared to the negative control, was detected in $5,000{\mu}g/plate$ of Mistlero C. In addition, with Mistlero C, no changes were shown in the number of micronucleated polychromatic erythrocytes (MNPCE) among 2,000 polychromatic erythrocytes compared to the negative control. Mistlero C was administered orally in rats to investigate acute toxicity. The $LD_{50}$ values in rats were above 2,000 mg/kg. In a repeated dose, 13-week, oral toxicity study conducted in rats, no compound-related adverse effects were shown at doses of Mistlero C of up to 1,000 mg/kg body weight/day. The results of these studies support the safe use of Mistlero C in food for human consumption.

Residual Level, Histology, and Blood Biochemistry of Tebuconazole: A Repeated Dose 28-Day Oral Toxicity Study in Pigs

  • Jeong, Jin Young;Kim, Minji;Park, Seol Hwa;Kim, Byeonghyeon;Oh, Sang-Ik;Kim, Eunju;Jung, Hyunjung
    • Food Science of Animal Resources
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    • v.42 no.4
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    • pp.712-722
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    • 2022
  • In this study, we investigated the residual properties of tebuconazole-treated pigs. Twenty pigs were treated with different concentrations (0.25, 1.25, 2.5, 12.5, and 25 mg/kg bw/d) of tebuconazole for 28 d. Blood biochemistry, histology, and residual levels were analyzed using the VetTest analyzer, Masson's trichrome staining kit, and liquid chromatography-mass spectrometry, respectively. The final body weights were not significantly different between the control and treatment groups. Alkaline phosphatase, blood urea nitrogen, cholesterol, and gamma-glutamyl transpeptidase levels were significantly different from those of the control after exposure for 14 d. However, alanine aminotransferase levels showed changes only after exposure to pesticides for 28 d. The biochemical parameters were separated during the experimental period (14 d versus 28 d) by principal component analysis. Based on variable importance plots, blood urea nitrogen/creatinine ratio, blood urea nitrogen, glucose, and gamma-glutamyl transpeptidase are candidate biomarkers for tebuconazole exposure. The residual levels were observed at T4 (12.5 mg/kg bw/d) and T5 (25 mg/kg bw/d) in the liver and fat tissues, respectively. Fibrosis increased in the liver, kidney, and fat tissues, depending on the tebuconazole concentration. In conclusion, the residue limits of tebuconazole and the physiological changes caused by dietary tebuconazole in pigs provide important information for establishing maximum residue limits of pork and pork products.

Combined Modality Treatment in Nasopharyngeal Carcinoma (비인강암의 병합요법)

  • Yun, Sang-Mo;Kim, Jae-Cheol;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.100-106
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    • 2001
  • Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.

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