• Title/Summary/Keyword: repeated oral toxicity

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A 90-Day Repeated Oral Dose Toxicity Study of Alismatis Rhizoma Aqueous Extract in Rats

  • Lee, Mu-Jin;Jung, Ho-Kyung;Lee, Ki-Ho;Jang, Ji-Hun;Sim, Mi-Ok;Seong, Tea-Gyeong;Ahn, Byung-Kwan;Shon, Jin-Han;Ham, Seong-Ho;Cho, Hyun-Woo;Kim, Yong-Min;Park, Sung-Jin;Yoon, Ji-Young;Ko, Je-Won;Kim, Jong-Choon
    • Toxicological Research
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    • v.35 no.2
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    • pp.191-200
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    • 2019
  • Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.

Thirteen-week Repeated Oral Dose Toxicity Study of WK-38 in Rats (랫트에서 WK-38에 대한 13주 반복경구투여 독성에 관한 연구)

  • Chang, Bo-Yoon;Kim, Yoon-Chul;Kang, Dae-Gill;Lee, Ho-Sub;Kim, Sung-Yeon
    • Journal of Food Hygiene and Safety
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    • v.23 no.2
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    • pp.169-176
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    • 2008
  • The subcronic toxicity of WK-38, a herbal preparation for the atherosclerosis, was examined in male and female Sprague-Dawley rats. WK-38 is composed of Rhei Rhizoma, Magonoliae Cortx, Moutan Cortex Radicis. Rats were treated with the test substance at a dose of 5 mg/kg, 50 mg/kg and 500 mg/kg intragastrically for 13 weeks. Control rats were treated with vehicle only. No death and abnormal clinical signs were observed throughout the administration period. Also there was no difference in net body weight gain, food and water consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of the WK-38. Hematological findings and biochemical examination revealed no evidence of specific toxicity related to WK-38. The results suggested that under the condition employed in this study no observation effect level (NOEL) of WK-38 would be 500 mg/kg/day.

Single- and Repeated-Dose Oral Toxicity in Rats and Bacterial Reverse Mutation Test of Morus alba L. Extracts (상지추출물의 단회/반복투여 독성 및 복귀돌연변이능 평가)

  • Han, Taewon;Um, Min Young;Lim, Young Hee;Kim, Jeong-Keun;Kim, In-Ho
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.10
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    • pp.1406-1413
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    • 2016
  • This study was carried out to evaluate the toxicity of ethanolic extracts of Morus alba L. branch (ME). In the reverse mutation test, Salmonella Typhimurium TA98, TA100, TA1535, TA1357, and Escherichia coli WP2uvrA were used to estimate the mutagenic potential of ME. Sprague-Dawley rats were orally administered ME at levels of 1,250, 2,500, and 5,000 mg/kg for the single-dose toxicity test and 500, 1,000, and 2,000 mg/kg/d for the repeated-dose toxicity test for 28 consecutive days. As expected, reverse mutation was not detected at any concentration of ME, regardless of application of the metabolic activation system with or without S9 mix. In the single-dose toxicity test, ME caused neither significant visible signs of toxicity nor mortality in rats, and $LD_{50}$ was estimated to be over 5,000 mg/kg. In the repeated-dose toxicity test, ME administration at 500, 1,000, and 2,000 mg/kg for 28 days to male or female rats did not result in mortality. Similarly, no toxicologically significant treatment-related changes in body weight, food intake, or organ weights were noted. Several hematological and biochemical parameters in both genders showed significant differences, but these were within normal ranges. These results support the safe use of ME.

Safety Evaluation of Ethanol Extract from Unripe Fruit of Bitter Melon (Momordica Charantia L.) in Sprague-Dawley Rats (랫드를 이용한 여주 추출물의 안전성 평가)

  • Ryu, Hyeon Yeol;Lee, Somin;Ahn, Kyu Sup;Yong, Yeon;Kim, Hye Jin;Kim, Seong-Eun;Lee, Hak Sung;Hong, Su-Young;Kim, Hyun-Kyu;Hwang, In Guk;Song, Kyung Seuk
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.490-500
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    • 2017
  • This study was performed to evaluate repeated dose oral toxicity upon administration of the test substance 1,2-benzisothiazolin-3-one for 90 days and to determine NOAEL (no observed adverse effect level) and target organs in Sprague-Dawley rats. Single, 2-week repeated, and 13-week repeated oral dose toxicity studies were conducted in Sprague-Dawley rats. The dose levels of groups were 1,250, 2,500, and 5,000 mg/kg/d. All dose groups were compared with the vehicle control group. The animals were observed for clinical signs and weekly body weight. Urinalysis, hematology, and serum biochemistry analyses were conducted. Subsequently, animals were sacrificed and subjected to histopathological examination. For the result, NOAEL of ethanol extract from unripe fruit of bitter melon had an optimal dose of 5,000 mg/kg/d and acceptable daily intake up to 3,000 mg/man. There was no target organ detected. Therefore, bitter melon, which contains a variety of bioactive substances, could be widely used as a health functional food ingredient.

Initial Risk Assessment of Acetanilide in OECD High Production Volume Chemical Program

  • Park, Hye-Youn;Park, Yoonho;Sanghwan Song;Kwon, Min-Jeoung;Koo, Hyun-Ju;Jeon, Seong-Hwan;Na, Jin-Gyun;Park, Kwangsik
    • Toxicological Research
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    • v.18 no.1
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    • pp.13-22
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    • 2002
  • In Korea, 2,320 tonnes of acetanilide were mostly wed as intermediates for synthesis in phar-maceuticals or additives in synthesizing hydrogen peroxide, varnishes, polymers and rubber. Only small amount of 120 kg were wed as a stabilizer for hydrogen peroxide solution for hair colouring agents in 1998. Readily available environmental or human exposure data do not exist in Korea at the present time. However, potential human exposures from drinking water, food, ambient water and in work places are expected to be negligible because this chemical is produced in the closed system in only one company in Korea and the processing factory is equipped with local ventilation and air filtering system. Acetanilide could be distributed mainly to water based on EQC model. This substance is readily biodegradable and its bioaccumulation is low. Acute toxicity of acetanilide is low since the L $D_{50}$ of oral exposure in rats is 1,959 mg/kg bw. The chemical is not irritating to skin, but slightly irritating to the eyes of rabbits. horn repeated dose toxicity, the adverse effects in rats were red pulp hyperplasia of spleen, bone marrow hyperplasia of femur and decreased hemoglobin, hematocrit and mean corpuscular hemoglobin concentration. The LOAEL for repeated dose toxicity in rats was 22 mg/kg/day for both sexes. Acetanilide is not considered to be genotoxic. In a reproductive/developmental toxicity study, no treatment-related changes in precoital time and rate of copulation, impregnation, pregnancy were shown in all treated groups. The NOAELs for reproduction and developmental toxicity (off-spring toxicity) are considered to be 200 mg/kg bw/day and 67 mg/kg bw/day, respectively. Ecotoxicity data has been generated in a limited number of aquatic species of algae (72 hr- $E_{b}$ $C_{50}$; 13.5 mg/l), daphnid (48hr-E $C_{50}$ > 100 mg/l) and fish (Oryzias latipes, 96hr-L $C_{50}$; 100 mg/l). Form the acute toxicity values, the predicted no effect concentration (PNEC) of 0.135 mg/1 was derived win an assessment factor of 100. On the basis of these data, acetanilide was suggested as currently of low priority for further post-SIDS work in OECD.in OECD.D.

Experimental Study for Construction of Mouth Care in Chemotherapy Patients (화학요법을 받는 암환자의 구강간호전략을 위한 연구)

  • 변영순;김애경
    • Journal of Korean Academy of Nursing
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    • v.26 no.2
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    • pp.428-442
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    • 1996
  • Stomatitis is a common toxicity associated with the administration of certain cancer chemotherapeutic agents used in the treatment of malignant tumors. It represents one of the most distressing side effects of cancer chemotherapy and can interfere with the patient's ability to eat, be the cause of much pain and discomfort, and require the use of potent analgesics. The situation also creates favorable conditions for local infection which may lead to septicemia. Several authors have identified the need to establish protocols for the control and treatment of the oral discomfort associated with oral mucositis as a result of chemotherapy. Thus this study attempted to development of oral care protocol for chemotherapy patients. The effects of the mouth care using sterile normal saline, nystatine solution on oral stomatitis were investigated in 30 patients on chemotherapy. The subsect were divided into three groups : control group : not gargling experimental group A : normal saline gargling (4 times a day) experimental group B : nystatine solution gargling(4 times a day) The Oral Assessment Guide (OAG) was used to assess oral status three times(once in the prechemotherapy period, on 5th, 10th day of post chemotherapy) Oral culture was used to assess oral infection on 5th day of postchemotherapy. Data was analyzed on SAS program which used repeated ANOVA, t-test, X/sup²test. The results are as follows : 1. The incidence of stomatitis was higher in the control group and experimental group A than in experimental group B.(X/sup²=0.002 P=0.001). The grade of stomatitis(mean of total score) for patients in the experimental group B were significantly lower than in the experimental group A F=1.96 P=0.0024). In incidence of tongue change, control group, experimental group B were significantly higher than experimental group B(F=6.84 P=0.0039). In control group and experimental group A. oral infection due to pathogenic bacteria were identified. In conclusion, mouth care with nystatine solution four times a day could reduce the incidence of stomatitis and secondary oral infection due to stomatitis. Thus active mouth care protocol which used to nystatine solution gargling need to prevention of stomatitis in chemotherapy patients.

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Toxicity Assessment and Establishment Acceptable Daily Intake of Pyrimisulfan (피리미설판(Pyrimisulfan)의 독성평가와 일일섭취허용량 설정)

  • Jeong, Mi-Hye;Park, Kyung-Hun;Park, Jae-Eup;Kwack, Seung-Jon;Kim, Young-Bum;Han, Bum-Seok;Son, Woo-Chen
    • The Korean Journal of Pesticide Science
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    • v.15 no.2
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    • pp.208-217
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    • 2011
  • Pyrimisulfan is a herbicide. In order to register this new pesticide, the series of toxicity data on animal testing were reviewed to evaluate its hazards to consumers and also to determine its acceptable daily intake. Pyrimisulfan was excreted mostly by feces. It has low acute oral toxicity while it has no dermal, ocular irritation and skin sensitization (As the result of subchronic and chronic toxicity and carcinogenicity showed changes of hematology and liver.). Two-generation reproduction toxicity, genotoxicity, carcinogenicity and prenatal development toxicity were not proven. Therefore, the ADI for Pyrimisulfan is 0.1 mg/kg/ bw/day, based on the NOAEL of 10 mg/kg/ bw/day of 90-days repeated dose oral toxicity study in dogs while applying an uncertainty factor of 100.

Single and 14-Day Repeated Oral Toxicity Studies of 70% Ethanol Extract of Lindera Obtusiloba Blume Leaves (생강나무(Lindera obtusiloba Blume) 잎 70% 에탄올 추출물의 단회와 14일 반복투여 독성시험의 안전성 평가)

  • Hong, Chung-Oui;SeoMun, Young;Koo, Yun-Chang;Nam, Mi-Hyun;Lee, Hyun-Ah;Kim, Ji-Hoon;Wang, Zeng;Yang, Sung-Yong;Lee, Sung-Hee;No, Su-Hwan;Lee, Kwang-Won
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.10
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    • pp.1324-1330
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    • 2009
  • Lindera obtusiloba Blume (LO), which is widely distributed in Korea, Japan and China, has traditionally been used as a popular folk medicine for the treatment of fever, abdominal pain, bruise and extravation. The purpose of this study was to examine the toxicities of the single and 14-day repeated doses in Sprague-Dawley rats orally administrated with LO at doses of 0, 500, 1000, 2000 (14-day repeated toxicity test) and 5000 (single toxicity test) mg (dry weight)/kg of body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or organ weight among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally administered LO and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no evidences of histopathological alteration as well as abnormal gross finding mediated by single and 14 days treatments with LO. These results suggest that no observed adverse effect level (NOAEL) of the oral application of LO was considered to be more than 2000 mg/kg in rats under the conditions employed in this study.

Pharmacological Studies on Powdered Whole Part of Unossified Antler (분말녹용의 약물활성 연구(I))

  • Shin, Kuk-Hyun;Lee, Eun-Bang;Kim, Jea-Hyun;Chung, Myong-Sook;Cho, Sung-Ig
    • Korean Journal of Pharmacognosy
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    • v.20 no.3
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    • pp.180-187
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    • 1989
  • Systematic pharmacological studies on powdered whole part of unossified antler obtained from Cervus nippon Temminck var. mantchuricus have been carried out in mice and rats. Powdered antler, with a single oral administration, showed a very weak acute and subacute toxicity; its MLD being >5g/kg orally in mice. On daily oral treatments of the antler for 14 days, it did not cause any significant differences in body weight gain, various organ weights and serum transaminase activities compared to those of the control rats. Powdered antler, with a single oral administration, showed a remarkable analgesic activity as evaluated by writhing syndrome and tail-pressure test, a weak CNS depressant activity as well as a weak immunopotentiating action as evaluated by carbon clearance test in mice. Powdered antler, with repeated treatments, showed a moderate antifatigue effect against immobilized stress and showed significant increases in both adrenal weight and its ascorbic acid content in rats, suggesting that the mode of antifatigue effect of antler is related to adrenal and its components.

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TOXICOLOGICAL STUDIES ON RAW AND PROCESSED (PREBREWED) ACONITI TUBERS; ACUTE, SUBACUTE TOXICITY STUDIES AND ASSAY OF ACONITINE ALKALOIDS (生附子와 修治附子에 관한 毒性연구 : 급성 및 아급성 독성과 Aconitine 알칼로이드 함량분석)

  • Park, Han-Soo;Kim, Seung-Hee;Kim, Pu-Young;Chang, Il-Moo
    • Toxicological Research
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    • v.6 no.1
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    • pp.41-49
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    • 1990
  • Aconiti Tuber is the root of Aconitum sp (Ranunclaceae) which has been considered as one of the most important medicinal plant having cordiotonic, diuretic and analgesic effect. On the other hand, it has been known that Aconiti Tuber contained toxic agent, aconitine alkaloids so that only processed Aconiti Tubers have been used as herbal drug traditionally. For the safety evaluation of processed Aconiti Tuber, quantitative determination of aconitine and acute, subacute toxicity test were performed on 5 commercial processed Aconiti Tubers. Arapid and precise method using HPLC has been developed for the separation and determination of aconitine. Samples were extracted with hydrochloric acid (pH3) and hot water decoction. In case of d-HCL extracts, the contents of aconitine were from 0.08 mg/g to trace. But in case of hot water decoction extracts, the contents of aconitine were not detected. For the investigation of Aconiti Tuber toxicity in rats, hot water decoction samples and methanol extracts were tested. 1) Acute toxicity test Hot water decoction sample and methanol extracts from Aconiti Tuber did not show any toxic effects in rats by an oral administration. $LD_50values of 2 extracts were above 10.0 g/kg. 2) Subacute toxicity study In the repeated administration study, hot water decoction samples were given orally to Sprague-Dawlay rats for 2 week at daily doses of 5.0 g/kg. The results are as follows; No toxic manifestation, body weight changes and lethality were observed during wxperimental period. There were no significant changes in serum enzyme activities such as GOT, GPT, LDH, ALP between treated and control groups. However CPK values were decreased in the Subuja-treated group. (P<0.01). In addition, no gross and microscopic changes were noted in Aconiti Tuber-treated groups.

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