• 대한예방한의학회지
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• 제17권2호
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• pp.139-155
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• 2013

Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

• Toxicological Research
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• 제31권1호
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• pp.69-75
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• 2015

The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatment-related changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material.

• Toxicological Research
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• 제27권4호
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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.

• 농약과학회지
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• 제15권2호
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• pp.104-113
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• 2011

본 연구는 혹명나방 저항성 유전자 변형 낙동벼(GMO)의 식품으로서의 안전성을 평가하고자 13주 경구 반복투여 독성시험을 수행하였다. SD 랫드를 0, 5, 20%의 유전자 변형 낙동벼와 20% 낙동벼(Non-GMO)를 투여군으로 분리하여 13주간 투여한 후 체중, 사료섭취량, 요, 혈액 및 혈액생화학, 부검 및 조직병리학적 검사를 수행하였다. 시험종료시까지 모든 동물은 생존하였으며, GMO 벼의 투여와 관련된 독성은 관찰되지 않았다. 따라서 혹명나방 저항성 유전자 변형 낙동벼의 무독성량은 10,000 mg/kg/day 이상일 것으로 판단되며, 13주 경구 반복투여 독성은 없는 것으로 평가되었다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.128-128
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• 2001

Toxic effects of a new phosphodiesterse-5 inhibitor, DA-8159, were investigated in Sprague-Dawley rats by repeated oral administration. Four groups of 10 male and 10 female rats were treated with DA-8159 at a dose of 0, 40, 80, or 320 mg/kg/day for 4 weeks.(omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.54-54
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• 2003

1,3-Dichloro-2-propanol(1,3-DCP), together with 3-monochloro-propane -1,2-diol(3-MCPD), is a well-known contaminant of acid-hydrolysed vegetable protein. 1,3-DCP has also been found to occur in a range of other foods and ingredients, most notable in soy sauce. The objective of the study was to determine the toxicity of the 1,3-DCP in the rat following oral administration for 13 weeks. (omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.53-53
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• 2003

Certain chlorinated propanols occur as contaminants in hydrolysed vegetable proteins. Processing of defatted vegetable proteins by traditional hydrochloric acid hydrolysis leads to the formation of 3-monochloro-1, 2-propanediol(3-MCPD). The objective of this study was to determine the toxicity of 3-MCPD in the rat following oral(gavage) administration for 13 weeks. (omitted)

• 동의생리병리학회지
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• 제21권5호
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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.

• Toxicological Research
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• 제22권4호
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• pp.445-452
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• 2006

Aralia elata, a common medicinal and culinary herb, has beer consumed for centuries without any reported adverse effects. However, due to its limited safety information, we decided to investigate the repeated-dose toxicity of ethanolic extract of Aralia elata. The test was administered once daily by the gavage to male and female rats at doses of 0, 250, 500 and 1,000 mg/kg/day for four weeks. Throughout the study, no treatment-related deaths or clinical signs were observed. Also, no apparent changes were detected in ophthalmoscopy, urinalysis, serum biochemistry, hematology and gross necropsy. The test result showed a significant decrease in body and heart weight of males treated with 250 mg/kg of extract of Aralia elata compared to normal control, a significant increase in relative brain weight and adrenal weight in females treated with 250 mg/kg of extract compared to normal control. However, all these changes were not considered toxicologically important due to irrelevant dose-response relationship to gross and microscopic findings. Histopathologically, abnormal changes were not observed in any target organs. On the basis of these results, the NOAEL of extract of Aralia elata was estimated to be more than 1,000 mg/kg/day under the tested conditions.

• 한국식품영양과학회지
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• 제40권5호
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• pp.704-711
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• 2011

연구에서는 임상에서 암 치료의 보조제로 사용하고 있는 겨우살이의 독성성분의 구조적인 변화를 유도하여 겨우살이의 기능성을 향상시키는 하나의 방법으로, 감마선을 조사한 겨우살이 냉수 추출물의 안전성을 검토하고자 ICR계 열의 암수 마우스에 시험물질을 0, 20, 100 및 500 mg/kg/day의 용량으로 90일간 반복 경구투여한 후, 사망률, 일반증상, 체중변화, 혈액 및 혈액생화학적 변화, 부검소견, 조직학적인 변화를 관찰하였다. 시험기간 중 암수 모든 군에서 시험물질 투여에 기인한 일반적인 증상변화는 관찰되지 않았고, 시험물질의 반복 투여로 인한 사망례 역시 관찰되지 않았다. 시험물질의 투여에 기인한 유의적인 체중감소 또한 나타나지 않았으며, 상기 이외의 육안적인 부검소견에서도 시험물질 투여에 기인한 어떠한 이상소견도 발견되지 않았다. 혈액학적 분석 결과 일부 시험물질 투여군에서 총 백혈구 수와 림프구, 중성구, 단핵구, 헤모글로빈, 혈중 적혈구 비율, 평균 헤모글로빈의 함량, 평균헤모글로빈 농도, 적혈구 크기 분포폭, 혈소판의 수치가 유의적인 변화를 보였으나, 정상범위 내에서의 변화로 감마선조사에 의해 야기된 독성이라고 판단하기는 어렵다. 또한 혈청 중의 alanine aminotransferase, aspartate aminotransferase, 중성지방, 콜레스테롤 수치가 대조군과 비교할 때에 통계학적으로 유의성 있는 변화를 나타냈으나 정상 생리 범위 내에서의 변화로 시험물질에 의한 독성이라 판단하기는 어렵다. 간장과 신장의 조직학적인 관찰에서 시험물질 투여에 의한 변화는 관찰되지 않았다. 이상의 독성 시험 결과, 20 kGy 감마선 조사 겨우살이 냉수 추출물을 3개월간 ICR 마우스에 섭취시 킨 경우, 시험한 최고 농도인 $500{\mu}g$/kg/day에서는 독성이 없는 것으로 판명되었다.