• Safety and Health at Work
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• 제1권2호
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• pp.192-200
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• 2010

Objectives: We have investigated the toxic effects of the inhalation of subchronic and acute levels of n-octane. Methods: The rats were exposed to n-octane of 0, 2.34, 11.68 and 23.36 mg/L (n = 5 rats/group/gender) in an acute inhalation test (Organization for Economic Co-operation and Development (OECD) TG 403), or to 0, 0.93, 2.62 and 7.48 mg/L (n = 10 rats/group/gender) for a subchronic inhalation test (OECE TG 413), to establish a national chemical management system consistent with the Globally Harmonized Classification System (GHS). Results: Acutely-exposed rats became lethargic but recovered following discontinuation of inhalation. Other clinical symptoms such as change of body weight and autopsy finds were absent. The LC50 for the acute inhalation toxicity of n-octane was determined to exceed 23.36 mg/L and the GHS category was 'not grouping'. Subchronically-treated rats displayed no significant clinical and histopathological differences from untreated controls; also, target organs were affected hematologically, biochemically and pathologically. Therefore, the no observable adverse effect level was indicated as exceeding 7.48 mg/L and the GHS category was 'not grouping' for the specific target organ toxicity upon repeated exposure. Conclusion: However, n-octane exposure should be controlled to be below the American Conference of Industrial Hygienists recommendation (300 ppm) to prevent inhalation-related adverse health effects of workers.

• Toxicological Research
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• 제31권4호
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• pp.393-402
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• 2015

This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats.

• Nutrition Research and Practice
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• 제11권6호
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• pp.452-460
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• 2017

BACKGROUD/OBJECTIVES: Turanose, ${\alpha}$-D-glucosyl-($1{\rightarrow}3$)-${\alpha}$-D-fructose, is a sucrose isomer which naturally exists in honey. To evaluate toxicity of turanose, acute and subchronic oral toxicity studies were conducted with ICR mice. MATERIALS AND METHODS: For the acute oral toxicity study, turanose was administered as a single oral dose [10 g/kg body weight (b.w.)]. In the subchronic toxicity study, ICR mice were administered 0, 1.75, 3.5, and 7 g/kg b.w. doses of turanose daily for 13 weeks. RESULTS: No signs of acute toxicity, including abnormal behavior, adverse effect, or mortality, were observed over the 14-day study period. In addition, no changes in body weight or food consumption were observed and the median lethal dose (LD50) for oral intake of turanose was determined to be greater than 10 g/kg b.w. General clinical behavior, changes in body weight and food consumption, absolute and relative organ weights, and mortality were not affected in any of the treatment group for 13 weeks. These doses also did not affect the macroscopic pathology, histology, hematology, and blood biochemical analysis of the mice examined. CONCLUSION: No toxicity was observed in the acute and 13-week subchronic oral toxicology studies that were conducted with ICR mice. Furthermore, the no-observed-adverse-effect level is greater than 7 g/kg/day for both male and female ICR mice.

• Toxicological Research
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• 제35권1호
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• pp.65-74
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• 2019

Tetrahydrocurcumin (THC) is a major metabolite of curcumin, which is obtained from Curcuma longa. THC has various benefits and overcomes the bioavailability issue of curcumin. To establish it as a pharmacologically active molecule, its safety profile has to be determined. Thus, the present study aimed to determine the preclinical safety profile of THC in a 90-day subchronic and reproductive/developmental toxicity study in Wistar rats. THC at oral doses of 100, 200, and 400 mg/kg was administered daily for 90 days. Rats in the recovery group were kept for 14 days after treatment termination. The animals were observed for treatment-related morbidity, mortality, and changes in clinical signs, clinical pathology, and histopathology. In the reproductive/developmental toxicity study, THC at 100, 200, and 400 mg/kg was administered orally to rats and the reproductive/developmental parameters in adult male and female rats and pups were observed. THC at up to 400 mg/kg/day of did not have any significant effect on all parameters in male and female rats in both toxicity studies. Thus, 400 mg/kg/day can be considered as the no-observed-adverse-effect-level of THC in rats.

• 대한약침학회지
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• 제11권4호
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• pp.25-37
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• 2008

Purpose The purpose of this study was to investigate sub-chronic toxicity of scolopendrid pharmacopuncture in mouse and method of increasing output of scolopendrid pharmacopuncture. Methods In order to prove the clinical safety of scolopendrid pharmacopuncture during 90 days, We have observed the physical reaction(side effect) and clinical pathology test after scolopendrid pharmacopuncture treatment and investigated method of increasing Output of scolopendrid pharmacopuncture for 90%, 80%, 70% ethanol. Results In subchronic toxicity test, there was no significant sign in clinical sign, opthalmological values, body weights, hematological values and urinalysis values. And we could see that food consumptions and water consumptions increased significantly, albumin, triglycerides, GPT in blood chemical values and Liver, Testis(right) in organ weights changed significantly in some groups, compared with those in the S1 group. But these changes were observed within the scope of physiology. So there was no sign of toxication in subchronic toxicity test, and we can tell that NOAEL(No Observed Adverse Effect Level) is above 0.286mg/kg/day. And 70% ethanol solution of scolopendrid was yielded the most amount of substance. Conclusions This study demonstrates that scolopendrid pharmacopuncture is to treatment of safety for a long time and we can obtain much amount from 70% ethanol solution of scolopendrid.

• Biomolecules & Therapeutics
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• 제4권2호
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• pp.138-147
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• 1996

DWP401, a recombinant human epidermal growth factor, was subcutaneously administered to ICR mice at the dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day (15rats/sex/group) in order to evaluate the subchronic toxicity. General observations, examinations for food and water consumption, ophthalmoscopy and urinalysis were carried out during the study. For the complete gross and microscopic examinations, 10 mice/ sex/group were sacrificed at the ends of the dosing period, and the remaining animals were sacrificed with a 5 week recovery period. Examinations for hematology and blood biochemistry were also carried out at the time of recovery period. Based on the results, it was thought that the target tissue or organs were mesothelial cell, injection site, spleen, adrenal gland, ovary and transitional epithelial cell of urinary tract, and no observed toxic level of DWP401 was 0.04 mg/kg while definite toxic dose level might be 0.2 mg/kg.

• 농약과학회지
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• 제7권4호
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• pp.271-279
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• 2003

IAP-3006 원제(지베렐린산)의 SD계 랫드에 대한 아급성 경구 독성시험을 위하여 랫드에 1,000, 10,000과 15,000 ppm의 시험물질을 분말사료에 혼입하는 방법으로 주 5일, 90일간 경구 투여하여 그 독성과 안전성을 조사하였다. 전 시험기간 동안 모든 시험군의 동물에서 어떠한 임상 증상과 사망동물은 관찰되지 않았으며, 또한 체중변화, 사료 음수섭취량, 안과학적 검사, 뇨 검사 및 부검소견에서도 유의성 있는 변화는 보이지 않았다. 비록 혈액학적 검사, 혈액생화학적 검사 및 장기중량에서 유의성 있는 변화를 보였으나 모두 정상 범위에서의 변화이고 용량 의존적으로 나타나지 않았으며, 병리학적 소견에 있어서도 대조군과 비교하여 특이하게 다른 병변은 관찰되지 않았다. 이상의 결과로부터 IAP-3006 원제는 최고 투여용량인 15,000 ppm 에서도 유의할 만한 독성이 유발되지 않았으므로 안전한 것으로 판단되었으며, 무해용량은 15,000 ppm 이상으로 추정되었다.

• 한국식품영양과학회지
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• 제44권9호
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• pp.1286-1294
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• 2015

본 연구에서는 방사선 조사식품의 규정을 확립하고 안전성을 입증하기 위해 1 kGy 감마선 조사 오렌지를 ICR 마우스에 투여 또는 섭취시켜 급성 및 아만성 독성시험을 실시하였다. 급성독성의 경우 시험물질을 0, 1,000, 2,000 mg/kg의 용량으로 설정하여 단회 투여한 후 14일간 사망동물, 일반 증상, 체중 변화, 부검소견, 혈액학적 및 혈액생화학적 검사를 수행한 결과 어떠한 이상도 관찰되지 않았으며, 통계학적으로도 유의적인 차이를 나타내지 않았다. 따라서 1 kGy 감마선 조사 오렌지의 대략의 치사량(approximate lethal dose)은 암수 ICR 마우스 모두 2,000 mg/kg을 상회하는 것으로 판명되었다. 아만성독성은 시험물질을 식이에 함유하도록 하여 3개월간 섭취시킨 후 사망동물, 일반증상, 체중 변화, 사료 섭취량, 장기 무게, 조직학적 검사, 혈액학적 및 혈액생화학적 검사를 수행하였다. 시험기간 동안 암수 ICR 마우스 모두에서 사망동물이나 이상증상은 발견되지 않았으며, 체중 변화, 사료 섭취량 및 장기 무게에서도 통계학적으로 유의적인 차이를 보이지 않았다. 혈액학적 및 혈액생화학적 검사에서도 암수 ICR 마우스 모두 정상적인 수치를 나타냈다. 또한 조직학적 검사에서 간, 신장 조직은 모두 정상적인 구조를 유지하고 있었으며, 염증, 괴사 등의 유의할만한 병적 변화도 관찰되지 않았다. 따라서 1 kGy 감마선 조사 오렌지를 ICR 마우스에 3개월간 섭취시켜도 본 시험조건에서는 독성이 없는 것으로 판명되었다.

• Safety and Health at Work
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• 제3권3호
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• pp.224-234
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• 2012

Objectives: This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. Methods: This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. Results: During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. Conclusion: The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS).

• Journal of Ginseng Research
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• 제44권5호
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• pp.717-724
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• 2020

Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.