• YAKHAK HOEJI
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• v.40 no.5
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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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• v.26 no.2
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• pp.93-99
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• 2001

Voxel head phantom for overcoming the limitation of mathematical phantom in depleting anatomical details was constructed and example dose calculation for BNCT was performed. The repeated structure algorithm of the general purpose Monte Carlo code, MCNP4B was applied for yokel Monte Carlo calculation. Simple binary yokel phantom and combinatorial geometry phantom composed of two materials were constructed for validating the voxel Monte Carlo calculation system. The tomographic images of VHP man provided by NLM(National Library of Medicine) were segmented and indexed to construct yokel head phantom. Comparison of doses for broad parallel gamma and neutron beams in AP and PA directions showed decrease of brain dose due to the attenuation of neutron in eye balls in case of yokel head phantom. The spherical tumor volume with diameter, 5cm was defined in the center of brain for BNCT dose calculation in which accurate 3 dimensional dose calculation is essential. As a result of BNCT dose calculation for downward neutron beam of 10keV and 40keV, the tumor dose is about doubled when boron concentration ratio between the tumor to the normal tissue is $30{\mu}g/g$ to $3{\mu}g/g$. This study established the voxel Monte Carlo calculation system and suggested the feasibility of precise dose calculation in therapeutic radiology.

• Korean Journal of Veterinary Research
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• v.45 no.1
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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.

• The Korea Journal of Herbology
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• v.36 no.5
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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.

• Journal of The Korean Society of Clinical Toxicology
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• v.1 no.1
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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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• 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.

• 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.

• Natural Product Sciences
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• v.21 no.1
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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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• v.24 no.3
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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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• v.22 no.3
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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.