• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
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• pp.133-134
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• 2004

• Toxicological Research
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• 제18권3호
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• pp.285-292
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• 2002

The repeated toxicity of Gleditschia-saponin produced and provided by S.S. Bio-Tech Bench Co. was evaluated in Sprague-Dawley rats. Gleditschia-saponin was administered to rats by oral route at dose levels of high (180 mg/kg/day), medium (90 mg/kg/day) and low (45 mg/kg/day) once a day for 14 days. Saline was administered to another group of rats as control. Each group was consisted of 5 male and female rats. There were no dose-related changes in clinical findings, food and water consumption, organ weights, urine analysis, biochemical examination and hematological findings in all groups of animals treated with Gleditschia.- saponin, except body weights. Body weighs in male and female rats were increased significantly (p < 0.05) from day 4 to 14 in low, middle and high dose groups than control group. Body weight in high dose group was increased higher than control or low, middle dose groups on day 14. Gross and histopathological findings revealed no evidence of specific toxicity to Gleditschia.-saponin. Therefore, it was concluded that Gleditschia-saponin had no toxic or side effects in Sprague-Dawley rats in an repeated oral toxicity tests.

• 한방비만학회지
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• 제18권1호
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• pp.36-49
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• 2018

Objectives: The study is aimed at evaluating the possible toxicity in 90-day repeated oral administration of modified Samjung-hwan (mSJH) in Sprague-Dawley (SD) rats. This study was conducted to detect the no-observed adverse effect level (NOAEL). Methods: Modified SJH extract was administered orally in male and female SD rats at dose of 0, 1,000, 2,000, 4,000 mg/kg. Each group consisted of 10 rats of each gender. The modified SJH extract was given once a day for 90 days. We monitored the changes of mortalities, clinical signs, body weight changes, food consumption, ophthalmologic findings, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histological markers of all animals treated with modified SJH extract during the study period. Results: There were no toxicologically significant changes in mortalities, clinical signs, body weight gains, food consumption, ophthalmologic findings, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histological markers in any of rats tested. Conclusions: The NOAEL of the modified SJH extract in male rats and no observed effect level (NOEL) in female rats are considered 4,000 mg/kg.

• 생명과학회지
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• 제26권10호
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• pp.1153-1162
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• 2016

계종버섯(Thermitomyces albuminosus)의 안정성을 입증하기 위하여 사료에 계종버섯의 분말을 5%, 2.5%, 1.25%, 0%를 혼합하여 90일 동안 랫드에 자유 급이 시켜 실험동물의 일반증상, 체중변화, 혈액학적 검사, 부검소견, 임상병리, 조직병리학적 검사의 결과를 토대로 독성을 평가하였다. 독성판정기준은 독성의 정도와 양상에 따라 weight-based classification (독성 강도에 따른 분류)로 분류 하였는데 비시험물질-유래 변화인 NOEL, 시험물질-유래 경미한 변화는 NOAEL, 시험물질-유래 중요한 변화는 LOAEL을 기준으로 나누었다. 시험결과, 수컷 좌, 우측 신장 중량이 용량의존적으로 증가하여 고용량군에서는 12%, 8% 증가 하였다. 하지만 임상, 조직병리학적 결과 독성으로 판단되는 소견이 관찰되지 않아 시험물질-유래 경미한 변화로 판단으로 분류하였다. 따라서 판정기준에 따라 수컷은 NOAEL 암컷은 NOEL이 식이함량 5%로 추정되지만 식약처고시에 따라 암수 모두 NOAEL이 식이함량의 5%로 추정할 수 있다. 따라서 계종버섯은 식품 또는 기능성식품으로의 개발에 문제가 없을 것으로 사료된다.

• 한방안이비인후피부과학회지
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• 제27권1호
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• pp.79-90
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• 2014

Objectives : This study was carried out to evaluate the repeated dose oral toxicity of Alismatis Rhizoma in Sprague-Dawley(SD) rats. Methods : Male and female rats were administered orally with Alismatis Rhizoma water extract of 500 mg/kg(low dosage group), 1,000 mg/kg(middle dosage group) and 2,000 mg/kg(high dosage group). We daily observed number of deaths, clinical signs and gross findings for 14 days(twice a day). After 14 days, we measured body and organs weight. Also we analyzed hematological changes. Results : No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. In addition no significant changes of gross body and individual organs weight. Conclusions : These results suggest that water soluble extract of Alismatis Rhizoma has not repeated dose oral toxicity and oral LD50 value was over 2,000 mg/kg in SD rats. As a result, we can determine Alismatis Rhizoma is a relatively safe substance.

• Toxicological Research
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• 제27권3호
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• pp.133-135
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• 2011

The FDA guidance focuses on the use of the NOAEL to establish the maximum recommended starting dose. The majority of NOAEL has been described inaccurately or incompletely in final reports for 90-days repeated dose toxicity test based on GLP (good laboratory practice) regulation. This is the most serious one of reasons for why most pharmaceutical companies targeting global markets have disregarded the final report produced from GLP facilities in Korea. The problems in deciding NOAEL reflected in the final reports are mainly due to the followings; 1) Inaccurate description or use of NOEL, NOAEL and LOAEL, 2) Insufficient and inappropriate interpretations in findings from toxicity test. This paper is intended to provide the insight into distinguishing NOAEL from NOEL and LOAEL, and into classifying findings from toxicity test. Here, the three step method is newly suggested by applying the weight-based classification to the NOEL, NOAEL and LOAEL based on the findings.

• 대한한의학방제학회지
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• 제31권4호
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• pp.327-339
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• 2023

Objectives : This study conducted a repeated dose 90-day oral toxicity test in order to up-cycling Schisandra fruit extract powder(SFEP) using discarded Schisandra chinensis by-products and evaluated the NOAEL of SFEP. Methods : SD-rats were orally administered SFEP at concentrations of 0, 62.5, 125, and 250 mg/kg once daily for 90 days. Body weights and clinical signs were observed during the administration period. After completion of the experiment, the experimental animals were autopsied to observe necropsy findings and organ weights changes, and hematological parameters and blood chemistry values were measured. Results : During the SFEP administration period, clinical signs such as salivation, wounds, and erosion were sporadically observed in 1 to 2 animals. In the SFEP 250 mg/kg administered group, weights of the liver and thyroid gland significantly increased compared to the control group, but no significant changes were observed in organ weights according to body weights. As a result of measuring hematological parameters and blood chemistry values, a decrease in RDW, T-BIL, and TBA, and an increase in TP, ALB, and Ca were observed due to SFEP administration. However, these changes following SFEP administration were accidental and not dose-dependent. Additionally, no correlation was found between gender and other parameters. Conclusions : Therefore, the NOAEL of SFEP was confirmed to be 250 mg/kg.

• 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.

• 한국식품영양과학회지
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• 제40권6호
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• pp.824-831
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• 2011

본 연구에서는 방사선을 조사한 홍삼 메탄올 추출물의 안전성을 검토하고자 식품의약안전청의 의약품 등의 독성시험기준에 따라 ICR계열의 암수 마우스에 시험물질을 0, 125, 250 및 500 mg/kg/day의 용량으로 90일간 반복경구 투여한 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 체중 감소 또한 나타나지 않았으며, 상기 이외의 육안적인 부검소견에서도 시험물질 투여에 기인한 어떠한 이상소견도 발견되지 않았다. 혈액학적 분석 결과 일부 시험물질 투여군에서 총 백혈구 수 등의 수치가 유의적인 변화를 보였으나, 정상범위 내에서의 변화로 방사선조사에 의해 야기된 독성은 아니었다. 간장과 신장의 조직학적인 관찰에서 시험물질 투여에 의한 변화는 관찰되지 않았다. 따라서 방사선 구조변환 홍삼 추출물을 3개월간 ICR 마우스에 섭취시킨 경우, 시험한 최고 농도인 500 mg/kg/day에서는 독성이 없는 것으로 판명되었다.

• Toxicological Research
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• 제35권2호
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• pp.191-200
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• 2019

Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.