• 약학회지
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• 제40권5호
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• pp.491-500
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• 1996

The organ distribution and pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), were compared after single and repeated subcutaneous administration ( 50${\mu}$/kg, 10${\mu}g$Ci/kg of $^{125}I$-DWP401, twice a day for 7 consecutive days) to rats. The pharmacokinetic parameters such as AUC and terminal half-life were similar between two different administration. During repeated administration, the plasma concentration of DWP401 seemed to be constant when the plasma was collected at 15 min after each dosing. The TCA-precipitated radioactivities in thyroid, liver, kidney, and stomach were higher than those of other organs studied after both single and repeated administration. The TCA-precipitated radioactivities after repeated administration in several organs, such as thyroid, stomach, prostate, adrenal, eye ball, and testis were higher than those after single administration. But, according to the observations using gel filtration chromatography and antibody binding assay, the radioactivities in thyroid and stomach were not primarily due to the intact DWP401 or its metabolites but due to the $^{125}I$-thyroxine binding protein. In conclusion, it can be suggested that DWP401 is metabolized to each amino acid or small polypeptides, and there was no significant changes in pharmacokinetics or any indications for accumulation of DWP401 in rat plasma and organs after repeated treatment.

• Journal of Radiation Protection and Research
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• 제26권2호
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• pp.93-99
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• 2001

해부학적으로 단순한 수학적인형팬텀의 한계를 극복하기 위한 voxel 머리팬텀을 제작하고 BNCT(Boron Neutron Capture Therapy) 시행 시 선량분포를 계산하였다. 일반목적 몬테칼로 코드인 MCNP4B의 반복구조 알고리즘을 이용하여 voxel 몬테칼로 계산체계를 수립하였고 두 가지 물질로 구성된 예시적 voxel 팬텀과 기하체조합팬텀의 계산값 비교를 통해 계산체계를 검증하였다. 미국 NLM(National Library of Medicine)에서 제공하는 VHP man 인체단층사진에 대한 분할 및 색인작업을 통해 voxel 머리팬텀을 제작하여 AP 및 PA 방향에서 입사하는 넓고 평행한 광자 및 중성자빔에 대한 선량값을 MIRD 팬텀의 계산값과 비교한 결과 중성자빔 AP 방향조사 시 MIRD 팬텀에서는 볼 수 없는 안구로 인한 중성자 감쇠현상을 확인할 수 있었다. 3차원 정밀계산이 필요한 BNCT 시술시 선량분포계산을 위해 뇌 중앙에 직경 5cm의 구형 뇌종양 체적을 정의하고 뇌와 종양의 붕소 함량을 조정하여 10keV 및 40keV 상부입사 중성자에 의한 장기별 흡수선량을 계산한 결과 종양에 $30{\mu}g/g$, 정상세포에 $3{\mu}g/g$의 붕소를 주입한 경우 붕소함량이 없을 때에 비해 2배 가량 큰 선량을 보였다. 본 연구를 통해 voxel몬테칼로기법을 이용한 선량평가체계를 수립하였고 정밀한 선량계산을 필요로 하는 치료방사선분야 선량계산에 실제 인체에 가까운 voxel팬텀의 응용가능성을 제시하였다.

• 대한수의학회지
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• 제45권1호
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• pp.29-37
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• 2005

13-week orally repeated dose toxicity was investigated to ascertain the toxic effects of Aristolochiae radix in F344 rats at dose levels of 0, 1 (0.003 AA, aristolochic acid, mg/kg), 5 (0.014 AA mg/kg), 25 (0.068 AA mg/kg), 125 (0.34 AA mg/kg), and 500mg/kg (AA 1.36 mg/kg). No mortalities were found in any of the dose groups including vehicle control groups of both sexes during the study period. Hematologic and serum biochemical examinations revealed no changes related to the test item in any of the dose groups of both sexes. However, gross findings at necropsy implicated thickening of the stomach wall. In histopathological examinations, prominent findings related to the test item treatment were observed in the stomach and urinary bladder. There were squamous cell papilloma, squamous cell hyperplasia, ulceration and erosion observed in the non-glandular stomach. Squamouse cell hyperplasia was observed at dose levels of more than 125 mg/kg in both sexes and squamous cell papilloma was observed at dose level of 500 mg/kg in both sexes. The incidence and severity of these proliferating lesions including squamous cell hyperplasia and squamous cell papilloma increased with dose dependency. Transitional cell hyperplasia was also observed in the urinary bladder at dose levels of more than 25 mg/kg in both sexes and the incidence and severity of the lesion increased with dose dependency. In conclusion, the toxic changes related to the test item treatment were observed in the stomach and urinary bladder, and the no-observed-adverse-effect level (NOAEL) was estimated to be 5 mg/kg/day for both males and females in F344 rats.

• 대한본초학회지
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• 제36권5호
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• pp.109-115
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• 2021

Objectives : 'Johyun' yulmoo which is a new variety of Coix lacryma-jobi var. ma-yuen Stapf sprout was developed and registered by Rural development administration in 2004. This variety was derived from the cross between single cross of Suwon-6 and Okayama and UCN300-25 as F1. It is characterized by early maturity, short plant height, a strong resistance, and a superior yield and is suitable for the central and northern regions. Accordingly, we were performed and evaluated single oral dose toxicity test of 'Johyun' yulmoo sprout (JYS) in Sprague-Dawley (SD) rats. Methods : Single oral dose toxicity test was performed using with male and female rats. Rats were divided into two groups: Group 1, vehicle-treated rats (Control); Group 2, JYS 5000 mg/kg-treated rats. JYS was orally administered to male and female rats at dose levels of 5000 mg/kg. Animals were monitored on the mortality, clinical signs, body weight changes, and necropsy findings for 14 days. groups : Group 1, vehicle-treated rats (Control); Group 2, JYS 5000 mg/kg-treated rats. JYS was orally administered to male and female rats at dose levels of 5000 mg/kg. Animals were monitored on the mortality, clinical signs, body weight changes, and necropsy findings for 14 days. Results : After oral treatment of JYS, we could not find any mortality at 5000 mg/kg. Compared with the control group, there were also no significant differences in clinical sign, weight changes, weight gain, and gross abnormalities in JYS 5000 mg/kg-treated group. Conclusions : Taken together, these results suggest that approximate lethal dose of JYS was considered as over 5000 mg/kg. Results from this study provide scientific evidence for the safety of JYS. Moreover, this study could be used as a basis for dose-setting data of the repeated dose 13-week oral toxicity test of JYS.

• 대한임상독성학회지
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• 제1권1호
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• pp.21-26
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• 2003

Methamphetamine (MA) is a major drug of abuse in Korea. Currently preliminary evidence suggests that MA dependence may cause long-term neural damage in human. Repeated exposure to psychostimulants such as methamphetamine results in behavioral sensitization, a paradigm thought to be relevant to drug craving and addiction in human. Sensitization alters neural circuitry involved in normal processes of incentrive, motivation, and reward. However the precise mechanism of this behavioral sensitization has not yet been fully elucidated. Repeated use of high dose MA causes neurotoxicity which is characterized by a long-lasting depletion of striatal dopamine (DA) and tyrosin hydroxylase activity of DA, DA-transporter binding sites in the striatum. The loss of DA transporters correlates with memory problems and lack of motor coordination. DA fuels motivation and pleasure, but it' s also crucial for learning and movement. This selective review provides a summary of studies that assess the neurobiological mechanisms of MA.

• Biomolecules & Therapeutics
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• 제11권1호
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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.

• 한국식품영양과학회지
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• 제46권4호
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• pp.490-500
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• 2017

본 연구에서는 항당뇨에 유효성이 있는 천연물질인 여주 추출물을 이용하여 여주에 포함된 독성물질인 vicine의 분석과 경구투여에 따른 독성을 조사하기 위하여 단회 경구투여 독성시험과 13주 반복 경구투여 독성시험을 진행하였다. 본 시료는 여주 미숙과 열매추출물로 vicine의 분석 결과 존재하지 않거나 극미량일 것으로 판단된다. 단회 경구투여 독성 시험과 시험물질에 의한 이상증상과 사망동물은 발생하지 않아 여주 추출물의 ALD는 암수 모두 5,000 mg/kg/d 이상으로 판단된다. 13주 반복 경구투여 독성시험의 투여용량을 결정하기 위하여 0, 1,250, 2,500 및 5,000 mg/kg/d의 투여용량으로 2주 반복투여 용량결정시험을 실시한 결과, 모든 시험군에서 시험물질에 의한 이상증상 및 독성 변화가 관찰되지 않아 동일한 용량으로 13주 반복 경구투여 독성시험을 진행하였다. 실험기간 동안 사망률, 일반증상, 체중 변화, 사료섭취량, 안검사, 요검사, 혈액학적 검사, 혈액응고시간 검사, 혈액생화학적 검사, 부검소견, 장기중량 및 조직병리학적 소견을 관찰한 결과, 시험물질에 의한 전신적인 독성학적 변화는 관찰되지 않았다. 따라서 여주 추출물의 NOAEL은 5,000 mg/kg/d로 판단되었고, 표적장기는 관찰되지 않았다. 본 연구의 결과로 볼 때 여주 추출물은 투여 가능한 최대 용량에서도 독성이 나타나지 않는 안전한 천연물로 확인하였고, 본 시험 결과를 바탕으로 ADI는 3,000 mg/man으로 판단된다. 따라서 기능성 식품으로서의 개발 가능성을 확인하였다.

• Natural Product Sciences
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• 제21권1호
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• pp.34-41
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• 2015

The objective of this study is to characterize a toxicity of Epimedii Herba (EH) in F344 rats and to find a dose levels for the 13 weeks toxicity study. EH is well known as medicinal herb in many Asian countries for traditional medicines of antibacterial and antiviral effects, estrogenic and antiestrogenic effects, and for treatment of osteoporosis, hypotensives, fatigue, kidney disorders, and related complications. However, the indispensable and basic information of toxicological evaluation of EH extract is insufficient to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and MFDS guideline in this study. The extract of EH was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed of 5 male and female rats. In this study, there were no treatment of EH-related adverse changes in clinical observations, mortality, body weights, food consumption, urinalysis, gross finding at necropsy, and organ weight examination. Total red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, total cholesterol, and phospholipid were decreased in males and females at 5000 mg/kg/day compared to the control animals. Mean corpuscular volume and reticulocyte counts were increased in males and females at 5000 mg/kg/day compared to control animals. Therefore, we recommend that dose level of 5000 mg/kg/day is a highest treatment group in 13-week EH extract exposure study for further toxicity assessment.

• Toxicological Research
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• 제24권3호
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• pp.219-225
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• 2008

A screening study of the acute toxicity of organic arsenics such as arsenobetaine and arsenocholine, a product of arsenic methylation metabolite, and inorganic arsenic was carried out to examine hematological and serum biochemical parameters in cynomolgus monkeys(Macaca fascicularis). We found soft and liquid feces, and vomiting in all treated groups with inorganic and organic arsenics. The monkeys in inorganic arsenic-treated group showed a significant increase in vomiting frequency compared with those in three organic arsenics-treated groups. These results suggest that inorganic arsenic might be more toxic than three other organic arsenics tested. The monkeys in inorganic arsenic-treated group showed a decrease in platelet and an increase in monocyte on day 4 and the monkeys in arsenocholine-treated group showed an increase in reticulocyte percentage on day 8. The monkeys in inorganic-treated group also showed decreases in AST and ALT values and the monkeys in arsenobetaine-treated group showed a decrease in AST value and an increase in T-CHO value. However, these hematological and biochemical changes were within the physiological ranges, showing that the single dose of inorganic and organic arsenics did not affect at least hematological and serum biochemical parameters. The present study of toxicity with single dose of arsenics provides valuable indicators for longer term study of toxicity of repeated doses of arsenics in primates.

• Natural Product Sciences
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• 제22권3호
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• pp.180-186
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• 2016

This research is to estimate the toxicity of Atractylodis Rhizoma Alba (ARA) in F344 rats and to find a dose level for the 13 weeks toxicity study. A hot water extract of ARA (ARWE) was administered orally to F344 rats at dose levels of 0 (vehicle control), 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed to five male and five female F344 rats. According to the result, there were no ARWE-related adverse changes in mortality, body weights, food consumption, urinalysis, hematology, clinical chemistry, gross finding at necropsy, and organ weight examination. Salivation was observed in 3500 and 5000 mg/kg/day in male and female rats but it could not have found any relationship with ARWE administration. Based on our findings, ARWE may not cause toxicity in rats under the experimental conditions. Therefore, dose level of 5000 mg/kg/day as a highest treatment group in 13-week exposure study is recommended for further toxicity assessment.