• Title/Summary/Keyword: No-observed adverse effect level

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Study on the Safety of Kamikaekyuk-tang Ethanol Extract (가미계격탕 주정추출물의 안전성에 대한 연구)

  • Lee, Eun-Ok;Seo, Nam-Jun;Jung, Hee-Jae;Kang, Jong-Gu;Kim, Sung-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.4
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    • pp.799-804
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    • 2009
  • Kamikaekyuk-tang(KMKKT), a formula of ten Oriental herbs, was orientally designed to promote vital energy, to remove blood stasis, and to decrease inflammation for treating cancers. KMKKT and its component had potent antiandrogen and androgen receptor activities in prostate cancer and also inhibited angiogenesis induced by basic fibroblast growth factor (bFGF) in human umbilical vein endothelial cells and suppressed the tumor growth in LLC-bearing mice, and liver metastasis of colon 26-L5 cancer cells, suggesting a potent cancer preventive agent. Nevertheless, there is no safety study of KMKKT before clinical trial so far. Thus, in the current study, we investigated the toxicity about ethanol-extracted KMKKT. Male and female Spraque Dawley (SD) rats were given orally by KMKKT at 250, 500, and 1000 mg/kg for 4 weeks. Mortality, clinical signs and measured change of body weight, food consumption and water consumption were observed. In addition, we performed ophthalmologic, urinary, hematological, blood serum biochemical and histopathological examination. Any general toxicity was not found in KMKKT treated group. Also, there were no significant differences in the parameters such as body weight, food consumption and water consumption, a lot of urine and blood factor levels except WBC, MCHC and Ca level compared with control group. Although WBC and MCHC were elevated in female rats and Ca level was decreased in male rats, these were within normal ranges. Finally, we determined that maximum tolerated dose (MTD) was 1000 mg/kg and no observed adverse effect level (NOAEL) was 500 mg/kg. Taken together, these results demonstrated that KMKKT is very safe to SD rats.

Effects of persimmon peel supplementation on pork quality, palatability, fatty acid composition, and cholesterol level

  • Lee, Sang Moo;Kim, Ik Heon;Choi, Young Min
    • Journal of Animal Science and Technology
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    • v.58 no.8
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    • pp.32.1-32.7
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    • 2016
  • Background: The objectives of this study were to investigate the effects of persimmon peel (PPM) supplementation on carcass performance, pork quality, eating quality, fatty acid composition, and cholesterol concentration of the porcine longissimus dorsi muscle. Results: No adverse effects of PPM supplementation were observed on carcass and meat quality characteristics among the treatment groups (P > 0.05), whereas pork loins from pigs fed a diet supplemented with 0.9 % persimmon peel (T3) showed more tender meat than did pork loins from pigs fed a control diet (P < 0.01), even though no significant difference was observed between the control and T1 group. The T3 group had higher ratio of polyunsaturated fatty acids relative to saturated fatty acids (0.33 vs. 0.28, P < 0.05) and lower total cholesterol concentration (94.4 vs. 99.1 mg/g, P < 0.05) compared to the control group. Persimmon peel appeared to have beneficial effects on fatty acid composition and cholesterol concentration, probably leading to a hypocholesterolemic effect. Conclusions: Animal diets fortified with persimmon peel represents an efficient and useful method for improving the nutritional quality of pork without impairing growth performance and eating quality properties.

Reproductive Toxicity Study of LBO0014, A New Recombinant Human Erythropoietin: Teratogenicity Study in Rats (새로운 인체 재조합 적혈구 조혈인자 LB00014의 생식독성연구: 랫드 최기형성시험)

  • 정문기;양병철;김종춘;송시환;이상구
    • Biomolecules & Therapeutics
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    • v.6 no.1
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    • pp.82-88
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    • 1998
  • LBO0014, a new recombinant human erythropoietin, was at dose levels of 0, 120, 600, and 3,000 IU/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. All dams were subjected to caesarean section on day 20 of pregnancy, Effects of test substance on dams and embryonic development of Fl fetuses were examined. No treatment-related changes in clinical signs, body weight, and food consumption were observed at all doses tested. At necropsy spleen enlargement was found at 3,000 lU/kg. There was an ulcrease in the spleen weight at 600 and 3,0007/kg. Developmental toxicity was evident as increased resorptions at 3,000 lU/kg. At 600 and 3,000 RJ/kg, retarded ossification of fetuses occurred at an incidence of 31.3% and 64.7%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae at 600 and 3,000 lU/kg. A decrease in the number of metacarpi and metatarsi was also seen at 3,000 nJ/kg. The results show that the no observed adverse effect dose level (NOAEL) for material toxicity was over 3,000 IU/kg/day and the NOAEL for developmental toxicity was 120 IU/kg/day.

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Toxicity Study of AS6, a Triterpenoid Derivative: 4-Week Repeated Oral Administration in Rats

  • Lee, Michael;Cha, Shin-Woo;Im, Doo-Hyun;Yang, Byung-Chul;Lim, Kwang-Hyeon;Cha, Kyung-Hoi;Kim, Jong-Choon;Chung, Moon-Koo;Han, Jung-Hee
    • Biomolecules & Therapeutics
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    • v.11 no.1
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    • pp.72-79
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    • 2003
  • The present study was conducted to investigate the potential subacute toxicity of AS6, [(3$\beta$, 4$\alpha$)-3,23-dihydroxyurs-12-en-28-oic acid], by a 4-week repeated oral administration in Sprague-Dawley rats. To test the subacute toxicity, AS6 was administered once daily by gavage to rats at dose levels of 0, 250, 500, and 1000 mg/kg/day for 4 weeks. There were no treatment-related effects on mortality, clinical signs, body weight, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathology in any treatment group. In the condition of this study, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was considered to be 1000 mg/kg/day for both male and female rats.

Effect of Dietary Inclusion of Dehydrated Food Waste Products on Taiwan Native Chicken (Taishi No. 13)

  • Chen, Kuo-Lung;Chang, Hwang-Jen;Yang, Ching-Ke;You, Shanq-Huei;Jenq, Horng-Der;Yu, Bi
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.5
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    • pp.754-760
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    • 2007
  • The effect of dehydrated food waste product (DFWP) inclusion in diets of Taiwan native chickens on the growth performance, carcass traits, clinical blood chemistry and nutrient digestibility was investigated with 320 male Taishi Native Chickens (Taishi No. 13). They were randomly allocated into four levels of DFWP inclusion (0, 5, 10, or 20%) treatment. Each treatment had 80 chickens with four replicates. At 15 weeks of age, 8 chickens were selected from each group for the nutrient digestibility trial. The results showed that body weight gain during the 0 to 4 week period decreased as the feed intake and feed conversion rate (FCR) increased linearly with increasing level of DFWP inclusion. During the 4 to 8 week period, greater body weight gains were recorded for the birds on the 5% DFWP inclusion level than for the control (p<0.05). During 8 to16 weeks, the feed intake and FCR increased linearly (p<0.05). Interestingly too, results of the carcass analysis showed that DFWP inclusion up to 20% in the diet significantly decreased the relative abdominal fat weight but increased the relative proventriculus and gizzard weights of the birds. However, other carcass parameters, meat quality and sensory scores were not significantly influenced by the dietary DFWP inclusion levels (p>0.05). Higher serum aspartate aminotransferase, ${\gamma}$-glutamyltransferase activity and crude protein digestibility, and lower gross energy digestibility were observed in the 20% DFWP group compared to the control (p<0.05). Dietary DFWP inclusion was inappropriate during the 0 to 4 week period. During 4 to 8 weeks, there was no adverse effect on chicken performance in the 20% group. There was no disadvantage on carcass properties and in the meat panel test. This result would not affect consumer determination.

Subcutaneous Toxicity Evaluation of a Combination Vaccine against Hantaan and Puumala Viruses in Rats for 4 Weeks

  • Lee, Su-Hae;Jung, Eun-Yong;No, Kyong-Ok;Sin, Ji-Soon;Ahn, Chang-Nam;Kim, Dae-Joong;Nam, Sang-Yoon;Kang, Jong-Koo
    • Toxicological Research
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    • v.18 no.2
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    • pp.139-147
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    • 2002
  • Hantaan (HTNV) and Puumala (PUUV) viruses cause hemorrhagic fever with renal syndrome in human. In the present study, the repeated dose toxicity of the HTNV-PUUV combination vaccine was evaluated in Sprague-Dawley rats. Animals were injected subcutaneously for 28 days with dosages of 0, 0.017, 0.17 and 1.7 dose/kg body weight per day, respectively. No any significant changes of body weight, food and water consumptions were shown. There were no death and clinical findings during the experimental period. In both male and female rats, there were not significant changes in hematological and serum biochemical analysis, urinalysis, and ophthalmoscopic and histopathological examination. These results indicate that the HTNV-PUUV combination vaccine may have no toxic effects and no observed adverse effect level (NOAEL) may be over 1.7 dose/kg/day at subcutaneous route in rats.

Reproductive and Developmental Toxicity Screening Test of Ethyl Hydrogen Adipate in Rats

  • Nam, Chunja;Hwang, Jae-Sik;Han, Kyoung-Goo;Jo, Eunhye;Yoo, Sun-kyoung;Eom, Ig-Chun;Kang, Jong-Koo
    • Toxicological Research
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    • v.32 no.4
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    • pp.327-335
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    • 2016
  • This study aimed to evaluate the potential toxicity and safety of ethyl hydrogen adipate (EHA) by determining its effect on the reproductive function and development of Sprague-Dawley (SD) rats at dose levels of 0 (control), 200, 400, and 800 mg/kg/day. One male and five females of the 800 mg/kg/day died. Body weight loss was observed in the males of the 800 mg/kg/day and in females of the 400 and 800 mg/kg/day. In addition, mating indices decreased and pre-implantation loss rates increased in parental animals of the 400 and 800 mg/kg/day. The gestation index decreased in the male and female rats of the 800 mg/kg/day. Moreover, the body weight of the pups from the 800 mg/kg/day group decreased on post-parturition day 4. These results indicated that the no-observed-adverse-effect level of EHA for parental males and females was 400 mg/kg/day and 200 mg/kg/day, respectively, and that for pups was 400 mg/kg/day.

Effect of repeated Paecilomyces japonica treatment on rats (Paecilomyces japonica의 반복투여가 랫드에 미치는 영향)

  • Kim, Yong-Bum;Hong, Da-Hae;Cho, Eun-Sang;Im, Wanjung;Kim, Il-Hwan;Son, Hwa-Young
    • Korean Journal of Veterinary Research
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    • v.54 no.1
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    • pp.31-38
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    • 2014
  • Cordyceps is a fungus used as a traditional medicine in China, Japan, and Korea. Paecilomyces (P.) japonica is a new cordyceps that was recently cultivated on silkworm pupae in Korea. The present study evaluated the toxicological effects of P. japonica in rats. Forty rats were treated with oral doses of P. japonica (0, 20, 100, or 500 mg/kg/day) for 4 weeks. Twenty additional rats were treated with 0 or 500 mg/kg/day of P. japonica for 4 weeks and then maintained for 2 weeks without treatment. Clinical signs, body weight, food and water consumption, and organ weight as well as hematology, serum biochemistry, and histopathology data were examined. Body weight gain of the group treated with 500 mg/kg/day was significantly reduced. Microscopically, karyomegaly, single cell necrosis, and mitosis were observed in the renal tubular epithelium of all treated groups. In conclusion, P. japonica caused a reduction of body weight and renal injury in rats. The no observed adverse effect level (NOAEL) of P. japonica was less than 20 mg/kg/day.

Effect of Dioxin on the Change of Mitochondrial Inner Membrane Potential and the Induction of ROS (다이옥신이 미토콘드리아 내막의 전위차 변화 및 ROS 생성에 미치는 영향)

  • Cho, Il-Young;Sheen, Yhun-Yhong
    • Environmental Analysis Health and Toxicology
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    • v.24 no.1
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    • pp.33-41
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    • 2009
  • Among the toxicants in the environment dioxin-like compounds, including TCDD(2,3,7,8-Tetrachlorodibenzo-p-Dioxin), are well known as carcinogen and teratogen. TCDD the most toxic of these compounds, may result in a wide variety of adverse health effects in humans and environment, including carconogenesis, hepatotoxicity, teratogenesis, and immunotoxicity. Also TCDD increases superoxide, peroxide radicals and induces oxidative stress that leads to breakage of DNA single-strand and mitochondrial dysfunction. Recently, there have been reports that persistent organic pollutants(POPs) may be causing metabolic disease through mitochondrial toxicity. In order to examine if dioxin brings about toxicity on mitochondria directly, we measured the change of the mitochondrial membrane potential after exposure to TCDD using JC-1 dye. After short time exposure of dioxin, mitochondrial depolarization was observed but it recovered to the control level immediately. This TCDD effect on mitochondrial membrane potential was not correlated either to the production of reactive oxygen species(ROS) or extracellular $Ca^{2+}$ by TCDD. Less than 2 hours exposure of TCDD did not show any change in ROS production but 0.25 nM TCDD for 48 hours or 0.5 nM TCDD for 12 hours exposure did increase in ROS production. Under these conditions of ROS production by TCDD, no changes in the mitochondrial membrane potential by TCDD was observed.

Assessment of the Single Oral dose Toxicity of Glycyrrhiza New Variety Extract in Sprague-Dawley Rats (Sprague-Dawley rats에서 감초 신품종 추출물의 단회투여 독성 평가)

  • Dong-Gu Kim;Jeonghoon Lee;Wonnam Kim;yo-Jin An;Jong-Hyun Lee;Jaeki Chang;Sa-Haeng Kang;Young-Jae Song;Yong-Deok Jeon;Jong-Sik Jin
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.65-66
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    • 2021
  • Glycyrrhiza species (Licorice) are one of the most commonly used medicinal plants in Asian countries such as China, India and Korea. It has been traditionally used to treat many disease including cough, cold, asthma, fatigue, gastritis and respiratory tract infections. Glycyrrhiza new variety, Wongam (WG), have been developed by Korea Rural Development Administration and revealed several pharmacological effects. However, limited data are available on the potential adverse effects of the WG. Here, we evaluated the general toxicity of the WG extract through single oral dose toxicity study in Sprague-Dawley rats. After single oral dose administration, there was no mortality up to 5000 mg/kg during experiment period. In addition, there was no clinical signs including body weight change, gross findings and necropsy findings up to 5000 mg/kg during experiment period. To conclude, the no-observed-adverse-effect level (NOAEL) of WG was higher than 5000 mg/kg and no target organs were identified in male and female Sprague-Dawley rats.

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