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

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Study on Safety of Pyungwi-san in Sprague-Dawley Rats (Spargue-Dawley 랫드를 이용한 평위산의 안전성 연구)

  • Shin, In-Sik;Kim, Jung-Hoon;Ha, Hye-Kyung;Huang, Dae-Sun;Huh, Jung-Im;Shin, Hyeun-Kyoo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.3
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    • pp.426-429
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    • 2010
  • This study was conducted to investigate the acute toxicity and safety of Pyungwi-san (Pingwei-san) in Sprague-Dawley rat though the current regulatory guideline. The preliminary study showed that the single oral administration of Pyungwi-san (Pingwei-san) did not induce any toxic effect at a dose level of 2000 mg/kg. Based on the results, 2000 mg/kg was selected as the limited dose. In this study, 10 rats of each sex were randomly assigned to two groups of 5 rats each and were administrated singly by gavage at dose levels of 0 and 2000 mg/kg. After single administration, Mortalities, clinical signs, body weight changes, gross findings were observed for the 15-day period. Throughout the study period, no treatment-related deaths were observed. There were no adverse effects on clinical signs, body weight, and gross findings at all treatment groups. These results showed that the single oral adminstration of Pyungwi-san (Pingwei-san) did not cause any toxic effect at the dose levels of 2000 mg/kg in rats. In conclusion, the $LD_{50}$ of Pyungwi-san (Pingwei-san) was considered to be over 2000 mg/kg body for both sexes.

Oral Repeated-dose Toxicity Studies Especially in the Liver and Kidney of Rats Administered with Organic Germanium-fortified Yeasts

  • Lee, Sung-Hee;Oh, Kyeong-Nam;Rho, Sook-Nyung;Lee, Bok-Hee;Lee, Hyun-Joo
    • Preventive Nutrition and Food Science
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    • v.11 no.2
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    • pp.115-119
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    • 2006
  • The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

Dilemma of a small dam with large basin area under climate change condition

  • Jeong-Hyeok Ma;Chulsang Yoo;Tae-Sup Yun;Dongwhi Jung
    • Computers and Concrete
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    • v.33 no.5
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    • pp.559-572
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    • 2024
  • Problems of under-sized dams (small dams with large basin area) could get worse under the global warming condition. This study evaluates the possible change of these problems with the Namgang Dam, an under-sized dam in Korea. For this purpose, first, this study simulates the dam inflow data using a rainfall-runoff model, which are then used as input for the reservoir operation. As a result, daily dam storage, dam release, and dam water supply are derived and compared for both past observed period (1973~2022) and future simulated period (2006~2099) based on the global warming scenarios. Summarizing the results are as follows. First, the inflow rate in the future is expected to be increased significantly. The maximum inflow could be twice of that observed in the past. As a result, it is also expected that the frequency of the water level reaching the high level is increasing. Also, the amount and frequency of dam release are to be increased in the future period. More seriously, this increase is expected to be concentrated on rather extreme cases with large dam release volume. Simply, the condition for flood protection in the downstream of the Namgang Dam is becoming worse and worse. Ironically, the severity of water shortage problem is also expected to become much worse. As the most extreme case, the frequency of no water supply was zero in the observed period, but in the future period, it becomes once every five years. Both the maximum consecutive shortage days and the total shortage volume are expected to become more than twice in the future period. To prevent or mitigate this coming problem of an under-sized dam, the only countermeasure at this moment seems to be its redevelopment. Simply a bigger dam with larger dam reservoir can handle this adverse effect more easily.

Repeated Dose 90-Day Oral Toxicity Study of Dried Thermitomyces albuminosus Powder in Rats (Thermitomyces albuminosus powder의 랫드를 이용한 90일 경구투여독성시험)

  • An, Min Ji;Heo, Hye Seon;Lee, Ji Sun;Son, Hye Young;Lim, Hae Ok;Park, Gang Baek;Lee, Joon Heun;Jee, Jae Gyu;Park, Yeongchul
    • Journal of Life Science
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    • v.26 no.10
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    • pp.1153-1162
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    • 2016
  • Termitomyces albuminosus (Berk.) Heim is a well-known wild edible mushroom in the southern region of China. Novel cerebrosides, termed termitomycesphins, isolated from EtOH extract of T. albuminosus have shown significant neuritogenic activity. Neurotrophic factors have been targeted as potential therapeutic drugs for the treatment of neurodegenerative disorders. However, before expanding their applications to include food or therapeutic agents in Korea, a safety evaluation of T. albuminosus is needed. Herein, in a repeated-dose 90-day oral toxicity study, rats were exposed to a basal diet of powder ground from dried T. albuminosus at dose levels of 5%, 2.5%, 1.25%, and 0%. The following endpoints were evaluated: clinical observation, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Significant dose-dependent increases in the weight of the left kidney were observed, possibly due to the test substance. Based on toxicity-decision criteria for minor compound-related changes (no observed adverse effect level [NOAEL] and no observed effect level [NOEL]), NOAEL was observed in male rats at a dose of 5% of dried T. albuminosus powder, and NOEl was observed in female rats at the same dose. The results point to the safety and potential use of T. albuminosus as a nontoxic neurotrophic factor.

Toxicity and Safety Profiles of Methanolic Extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar Rats

  • Sharwan, Gotmi;Jain, Parag;Pandey, Ravindra;Shukla, Shiv Shankar
    • Journal of Pharmacopuncture
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    • v.19 no.3
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    • pp.253-258
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    • 2016
  • Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD - 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single-dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases.

Effects of Dietary Available Phosphorus Levels and Phytase Supplementation on Performance, Egg Quality and Serum Biochemical Parameters of Hy-Line Brown Laying Hens from 40 to 60 Weeks of Age

  • Lim, Chun Ik;Rana, Md Masud;Kang, Hwan Ku;Ryu, Kyeong Seon
    • Korean Journal of Poultry Science
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    • v.47 no.4
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    • pp.255-265
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    • 2020
  • This study was performed to evaluate the effects of available phosphorus (AP) levels with or without supplemental phytase on the performance, egg quality, and serum biochemical parameters of laying hens. A total of 540 laying hens (40-week-old) were housed in cages and assigned to 6 dietary treatments with 5 replicates each, for 20 weeks. The treatments consisted of 0.20%, 0.25%, and 0.30% AP diets with or without phytase supplementation. During the 20-week period, egg production was lowest in hens fed the 0.20% AP diet; however, phytase supplementation in the diet completely corrected the adverse effect (P<0.05). No consistent difference was observed in egg production between hens fed the 0.25% and 0.30% AP diets and those fed the 0.20% and 0.30% AP diets with phytase supplementation. Similarly, egg mass was lowest in the 0.20% AP diet-fed group, and no difference in egg mass was observed in the 0.25% and 0.30% AP diet as well as the phytase-supplemented diet groups; however, egg mass was improved in the phytase-supplemented diet groups(P<0.05). Egg quality traits did not differ with dietary treatments. Serum alkaline phosphatase level showed a linear decrease (P<0.05) in the phytase-treated groups with increasing AP levels; moreover, a numerically linear increase (P<0.05) in serum Ca and P levels was observed in the phytase-treated groups. The results of this study indicate that phytase supplementation in the diet of laying hens could increase egg production and may lead to greater mineral absorption.

Studies on the Safety of Artemisiae Capillaris Herba - With the Perinatal and Lactational Reproductive Toxicity - (인진의 안정성에 대한 연구 - 주산$\cdot$수유기 생식 독성을 중심으로 -)

  • Wang Wu-Hao;Park Jae-Hyun
    • The Journal of Korean Medicine
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    • v.26 no.2 s.62
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    • pp.32-51
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    • 2005
  • Objectives: To study the effect of Artemisiae Capillaris Herba extracts, that have been used as oriental medicine to treat liver disease, on the perinatal and lactational n;)productive toxicity of SD rats when administered by oral lavage. Methods: Female SD rats were dosed from 6 days of gestation to 3 weeks postpartum. This was conducted in accordance with the recommendations of the KFDA Guidelines for Detection of Toxicity to Reproduction for Medicinal Products. Results: No Artemisiae Capillaris Herba extracts treatment-related changes in clinical signs, mortalities, implantation number, dead fetus number, loss rate of fetus, number of live young, survival rate of fetus, sex ratio of live young, external anomalies, pregnancy periods, viability index, lactational index, survival rate of litters at 4 days after birth or delivery index were demonstrated in any dosed levels in this study. However, the body weight and gains, food consumption and absolute organ weights of brain, adrenal glands, liver, spleen, kidney, ovaries and heart were significantly increased in 2000 or 1000mg/kg-dosing groups and the relative organ Weights of adrenal glands were significantly increased in 2,000mg/kg-dosing groups. Therefore, it was concluded that this increase was natural according to growth. Also, no changes of gross findings, clinical signs, mortalities, body weight and gains, physical development results, necropsy findings, organ weight, faculty test, open filed test and water-filled simple T-maze test, copulation, fertility, pregnancy indices, body weight and gains during gestation periods, necropsy findings, corpora lutea number, implantation number, implantation rate, dead fetus number, post-implantation loss rate, live young, post-implantation survival rate, sex ratio of live young, external anomalies and individual body weights of live young were demonstrated in any dosed levels in this study. Conclusions: It is considered that the NOAEL (No-Observed-Adverse-Effect Level) for perinatal and lactational reproductive toxicity of Artemisiae Capillaris Herba extracts was up to 2000mg/kg/day because no changes of other perinatal and lactational reproductive indices were demonstrated.

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Reproductive Toxicity Study of CONP01, a New Antiarthritic Agent: Developmental Study in Rats (새로운 관절염 치료제 CONP01의 생식독성연구: 랫드 배 · 태자 발생시험)

  • Lee June-Suk;Hong Dong Ho;Kim Kwang-Ho;Zhang Hu-Song;Gil Gi Hyun;Han Myong Kyu;Yang Hyun Ju;Bae Jin-Sook;Kim Nam Du;Song Si Whan
    • Toxicological Research
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    • v.21 no.1
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    • pp.23-29
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    • 2005
  • A developmental study of CONP01, a new antiarthritic agent, was conducted in Sprague-Dawley rats. Dosage of CONP01 0, 111, 333, and 1000 mg/kg/day were administered to dams orally from day 6 to day 16 of gestation. Two-third of dams per group were subjected to caesarean section on day day 20 of pregnancy for examination of their fetuses, and the remaining one-third of dams per group were allowed to deliver naturally for postnatal examination of their offspring. There was no change in the dams body weights, food consumptions, specific clinical sings and gross findings. There was significant decrease only in the absolute and relative weights of right ovary in 111 mg/kg treatment group, when compared with the vehicle control, whereas other organ weights were not changed. Moreover, no increase in the frequencies of external, visceral and skeletal malformation of fetuses were observed in the treated groups. These results suggest that the oral NOAEL (no observed adverse effect level) of CONP01 may be over 1,000 mg/kg in dams and fetuses of rats.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

  • Han, So-Ri;Yun, Eun-Young;Kim, Ji-Young;Hwang, Jae Sam;Jeong, Eun Ju;Moon, Kyoung-Sik
    • Toxicological Research
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    • v.30 no.2
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    • pp.121-130
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    • 2014
  • The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

Acute and Subacute Toxicity Studies of l-Muscone in Rats (랫드에서 l-muscone의 급성독성 및 아급성독성시험 연구)

  • 오승민;연제덕;남혜윤;박대규;조명행;정규혁
    • Toxicological Research
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    • v.13 no.4
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    • pp.435-447
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    • 1997
  • l-Muscone is synthesized for use as substitutive material of musk which is the active ingredient of woohwangchungsimwon. The objective of this investigation was to evaluate the acute and subacute toxicity of l-muscone in rats. In oral acute toxicity test, SPF Sprague-Dawley male and female rats were gayaged with l-muscone of two doses(0, 5.0 g/kg). No dead animal and abnormal autopsy findings were found in control and treated group. Body weights were slightly decreased in both sexes of rats treated with 5.0 g/kg. Therefore, oral $LD_{50}$ of l-muscone was consider to be higher than 5.0 g/kg in male and female rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with dosages of 0, 1,000, 1,316, 1,732, 2,279 and 3.000 mg/kg. Decreased body weights and motor activities were observed at high dose group. Intraperitoneal $LD_{50}$ of l-muscone were 1,920 mg/kg in male and female rats. In the subacute study, l-muscone was administrated orally to both sexes of rats for 4 weeks as several doses(0, 10, 100 and 1,000 mg/kg). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysist and other findings. Above data suggest that no observed adverse effect level of l-muscone in rats might be over 1,000 mg/kg/day in this study.

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