• Environmental Analysis Health and Toxicology
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• v.15 no.4
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• pp.123-130
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• 2000

2-Bromopropane, important industrial chemical, specially in electronic industry at Yangsan in Korea has been reported to cause amenorrhea for female and azoospermia, oligozoospermia or reduced sperm motility for male. 2-BP was investigated through 21 days of repeated dose in male Sprague-Dawley rats. The dose levels per body weight were 0 (control), 250,500 and 1,000 mg/kg. 2-BP dissolved in vehicle olive oil was injected into the intraperitoneum 6 times per week for 3 weeks, but 1,000 mg/kg dose group was 2 weeks because of serious illness. Male rats showed significant decreases in body weight and right and left testis showed typical weight losses depending on the 2-BP. The number of white blood cell and red blood cell , percentage of monocytes, and hemoglobin decreased significantly in high dose (P< 0.05). Red cell volume distribution width increased significantly in the high dose (P< 0.05). Histopathological findings of testes showed a decrease of spermatogenic cells, exfoliation of spermatid and spermatocyte, vacuolization of Sertoli cells and hyperplasia of Leydig cells. Protein band density between 113,000 dalton ($\beta$-galactosidase) and 53,900 dalton (ovalbumin) has decreased in 250 mg/kg dose group, but it has gradually increased to the higher density in 1,000 mg/kg dose group than in control group.

• Toxicological Research
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• v.27 no.4
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• pp.261-267
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• 2011

Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found in Korea and used as a traditional medicine to treat liver disease. AIP1, a water-soluble carbohydrate fraction from Artemisia iwayomogi, showed anti-tumor and immuno-modulating activities in animal studies. A subacute toxicological evaluation of AIP1 was performed for 4 weeks in ICR mice. After administration of AIP1 (0, 20, 100, 500 mg/kg/day), the clinical signs, mortalities, body weight changes, hematology, blood clinical biochemistry, urinalysis, organ histopathology, organ weights and gross finding were examined. The results showed that there were no significant differences in body weight changes, food intakes, water consumptions, or organ weights among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally treated with AIP1 and the control group, there was no statistical significance in hematological test or serum biochemical values. Histopathological examination showed no abnormal changes in AIP1 groups. These results suggest that no observed adverse effect level (NOAEL) of the oral administration of AIP1 for 4 weeks was considered to be more than 500 mg/kg/day in mice under the condition investigated in current study.

• Korean Journal of Environmental Agriculture
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• v.33 no.4
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• pp.395-402
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• 2014

BACKGROUND: Azadirachta indica Extract(AIE) containing azadirachtin as active ingredient have been used worldwide as environment-friendly organic material having pest control properties. However, the extracts prepared with different solvent and from different plant site is very diverse and have different toxicity. METHODS AND RESULTS: In this study, the four week repeated oral dose toxicity test of aqueous AIE in Sprague-Dawley rats was carried out to investigate the toxic effect of liver, main toxicity target organ of AIE. The male and female rats were divided into 4 groups, respectively; control(0 g/Kg bw), low-dose group(0.5 g/Kg bw), middle-dose(1.0 g/Kg bw) and high-dose group(2.0 g/Kg bw). As a results, relative liver weight increased with dose-dependent of AIE(p<0.05). Serum LDH in all AIE-treated groups were significantly lower than the control in male rats(p<0.05). However, serum GOT and GPT were significantly increased in all male AIE-treated groups in male rats(p<0.05) and, in particular, increase of serum GPT in dose-dependent manner raise the possibility of liver damage. Even through serum GLU was increased significantly in high-dose group in male rats compared to control, there were no significant differences of urinary GLU among all groups(p<0.05). In addition, histopathological examination of the liver did not reveal any lesions in all AIE-treated groups. CONCLUSION: In conclusion, 4 weeks of the repeated oral administration of AIE 2.0 g/Kg to rats has resulted no toxic response in liver. Therefore, AIE was no indicated to have any toxic effect in the SD rats, when it was orally administrated below the dosage 2.0 g/Kg/day for 4weeks.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1118-1126
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• 2007

The purpose of this study was to examine the anti allergic effect in vivo and in vitro, and to observe single and four weeks repeated toxicity in mice of Bangpung-galgeun-tang (BGT). We investigated anti DNP IgE-mediated passive cutaneous anaphylaxis in rodents and compound 48/80-induced active systemic anaphylatic shock in mice after oral administration with BGT of 0.4 g/kg and 0.8 g/kg for 8 days, and also examined MTT assay, ${\beta}-hexosaminidase$ activity, IL-4 and $TNF-{\alpha}$ from RBL-2H3 and $TNF-{\alpha}$ from Raw264.7 after pre-treatment with BGT of 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml and 2 mg/ml. To ascertain safety and toxicity of BGT, we divided into single and four weeks repeated administration test. In single test, three groups were administrated different dosages and routes (2 g/kg/i.p., 4 g/kg/i.p. and 15 g/kg /p.o.) of BGT, and in four weeks repeated test, 0.8 g/kg BGT was administrated. Control groups were administrated with only saline according to on Korean Food and Drug Administration, respectively. We observed attentively motality, abnormal clinical sign, body weight change, organ weight, AST and ALT of mice after BGT administration. BGT inhibited passive cutaneous anaphylaxis and active systemic anaphylatic shock by oral administration. All the concentrations of BGT from 0.25 to 2 mg/ml didn't have an effect on cell viability and cytotoxicity. In RBL-2H3, ${\beta}-hexosaminidase$ release, IL-4 and $TNF-{\alpha}$, and in Raw264.7, $TNF-{\alpha}$ were significantly reduced by treated all concentrations of BGT. During toxicity experiment period, there was no difference in body weight change, organ weight, AST and ALT among different dose groups. Death were found 3 mice from day 2 to day 3 in single test i.p. group. (2 g/kg, 4 g/kg). Several individuals of single test i.p. group were observed that decreased locomotor activity, exophthalmos, bloodshot eyes, loss of eyesight and so on in early period after administration. But there was no difference in clinical signs among p.o. group. These results indicate that BGT have inhibition effects on allergy and suggest that no observable effect level of the test orally administration was considered to be more than 2 g/kg in mice under the conditions employed in this study.

• YAKHAK HOEJI
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• v.40 no.4
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• pp.449-455
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• 1996

Betaine is one of the major water-soluble components in Lycii Fructus. In the present study the effect of repeated betaine treatment on the hepatotoxicity and the cytochrome P-4 50-dependent enzyme system was examined in adult female rats. Administrations of betaine (100 or 1,000mg/kg/day, ip) to rats repeatedly for 4 or 9 days did not evoke hepatotoxic response as determined by increases in glutamic pyruvic transaminase(GPT) and glutamic oxaloacetic transaminase(GOT) activities measured 24 hours following the final dose of betaine. The activities of aminopyrine N-demethylase, p-nitroanisole O-demethylase and p-nitrophenol hydroxylase as well as the contents of cytochrome P-450 were determined in hepatic microsomes of rats treated with betaine(1,000mg/kg/day, ip) for 4 or 9 days. Repeated treatment of rats with betaine for a period of 4 days induced a marginal decrease in the contents of cytochrome P-450, but did not influence the activities of p-nitrophenol hydroxylase, p-nitroanisole O-demethylase, or aminopyrine N-demethylase. Extension of the betaine treatment to 9 consecutive days failed to alter the parameters for hepatic drug metabolizing activity determined in the present study. Since repeated large doses of betaine were demonstrated to be tolerated by rats without showing any toxicity or changes in drug metabolizing enzyme activities in the liver, this compound appears to be relatively safe to animals upon long-term ingestion.

• Journal of Life Science
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• v.15 no.1 s.68
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• pp.1-8
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• 2005

The purpose of this study was to investigate the potential subacute toxicity of dimethyl disulfide by 3 weeks inhalation in F344 rats. The test article, dimethyl disulfide was exposed by inhalation to male and female rats at dose levels of 0, 5, 25, or 125 ppm/6 hrs/ day for 3 weeks. Five rats/ sex/ group were sacrificed on day 4 after the initiation of treatment, while 5 rats/ sex/ group were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. Slight decreases in body weight gain were noted in both sexes of the highest dose group in a dose dependent manner but were only statistically different from the control animals in males of the group. A slight non-significant reduction in food consumption were also noted in the both sexes of the highest dose group. There were no adverse effects on mortality, clinical signs, hematology, serum biochemistry, and necropsy findings at any dose tested. Based on these results, it was concluded that the 3 weeks repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at 125 ppm of both sexes. In the present experimental conditions, the target organ was not determined in rats. The no­observed-adverse-effect level (NOAEL) was considered to be 25 ppm/6 hrs/day for both sexes.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.93-98
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• 2009

Stephania delavayi Diels. has been used as an immune activator or an anti-inflammatory drug in China. We examined the immune modulation effect and 7-days repeated-dose toxicity to validate its biological safety and efficiency. Mice were repeatedly administrated with 50 mg/kg S. delavayi Diels. daily by I.P for 7 days. S. delavayi Diels. induced B cell activation but had no effect on other immune cells such as T cell, natural killer (NK) cell, and macrophage ($M{\varphi}$). S. delavayi Diels.-treated group exhibited no statistical significance from the control group in physical conditions; body weight, complete blood count (CBC), serum biochemical indexes etc. There was no difference between the control group and S. delavayi Diels.-treated group in gross findings such as histopathological alteration. In conclusion, S. delavayi Diels. is safe above the dose of immune modulation.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.05a
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• pp.55-55
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• 2003

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.43-44
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• 2003

The subacute toxicity and toxicokinetics of a type IV phosphodiesterase inhibitor, CJ-10882, were evaluated after single (on the 1st day) and 4-week (on the 27th day) oral administration of the drug, in doses of 0 (to serve as a control), 2, 10 and 50 mg/kg/d, to male and female dogs (n = 3 for male and female dogs for each dose). During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathology were examined.(omitted)

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.128-128
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• 2002