• 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.

• 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.

• 농약과학회지
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• 제14권4호
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• pp.490-498
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• 2010

살균제 isotianol의 독성을 평가하고 일일섭취허용량을 설정하기 위하여 급성독성시험 등 시험성적서를 검토하였다. Isotianil은 소변과 대변을 통해 빠르게 대사되었다. 급성경구독성은 저독성이었으며 피부자극, 안점막자극성은 없는 것으로 나타났다. 피부감작성은 약한 감작성으로 판단되었으며, 유전독성은 없었다. 랫드와 개 만성독성시험 결과 간의 무게, 혈액학 및 임상생화학적 변화가 관찰되었다. 또한 생식독성과 기형독성에는 영향이 없었다. Isotianil은 12개월 만성독성시험의 최대무작용량이 2.83 mg/kg/bw/day로 가장 민감하였고, 안전계수 100을 적용하여 일일섭취허용량을 0.028 mg/kg/bw/day로 설정하였다.

• 대한환경공학회지
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• 제33권1호
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• pp.60-70
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• 2011

본고에서는 현재 시행중인 해양오염퇴적물질 관리용 유해화학물질 정화지수($CI_{HC}$)를 대상으로, $CI_{HC}$은 동일하나 유해 물질별 함량이 다른 해저퇴적물들이 같은 생물위험을 보이는가를 판단하려 하였다. 이를 위해 5개의 가상 오염퇴적물을 설정하고, 퇴적물 위험평가를 위한 트로픽트레이스 모형($TrophicTrace^{(R)}$ model)을 이용하여, 이 가상 퇴적물이 쥐노래미(Hexagrammos otakii)에 대해 미치는 생물위험을 최대무작용량에 기반한 독성지수(NOAEL TQ)와 최소작용량에 기반한 독성지수(LOAEL TQ)로 평가하였다. 쥐노래미에 대한 NOAEL TQ의 합계는 5개 가상 오염퇴적물에서 0.69~1.54의 범위였고, LOAEL TQ의 합계는 0.111~0.261로 약 2배 이상의 차이가 났다. 이는 퇴적물 유해물질 환경기준이 해양저서무척추동물군집에 대한 영향만을 고려하고 사람으로 연결되는 식용의 쥐노래미에 대한 영향을 반영하지 않기 때문으로 사료된다. 인체에 대한 비발암위험지수(HI) 값은 PCB의 경우 9.8~47.1로 매우 위험한 것으로 나타났다. PCB의 발암위험도는 5개 퇴적물에서 $39{\sim}190{\times}10^{-5}$으로 높게 나타났으며 As의 경우에도 $8.1{\sim}18.0{\times}10^{-5}$으로 높게 나타났다. 유해화학물질정화지수가 8로 동일한 5개 가상 오염퇴적물에서 비발암위험지수(HI) 및 발암위험도가 서로 매우 다르게 나타난 것은 각 오염물질별로 인체에 악영향을 미치는 정도가 다르기 때문이다.

• Biomolecules & Therapeutics
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• 제6권3호
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• pp.328-336
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• 1998

The subacute oral toxicity study of DWP-311 was carried out in Sprague-Dawley rats of both sexes. We daily examined clinical signs, body weights, hematological and biochemical parameters, and histopathological examinations for 30 days after administration of DWP-311 with different dose levels (0, 0.04, 0.2, and 1.0 g/kg). There were no clinical signs and pathological changes compared with control group except slight decreases in spontaneous motor activities and locomotions at high dose group of DWP-311. Body weights were not significantly changed in animals treated with DWP-311, In histopathological examinations, there were 2 cases of pneumonia in control group for one male and one female, but it was not directly related to DWP-311. These results indicate that subacute oral toxicities of DWP-311 were low and the no-observed a dverse effect level (NOAEL) was considered to be 1.0 g/kg in rats.

• Biomolecules & Therapeutics
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• 제6권3호
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• pp.317-327
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• 1998

The subchronic toxicity study of rHuEPO, a newly developed recombinant erythropoietin, was investigated for 13 weeks in Beagle dogs intravenously treated with doses of 100, 500 and 2,500 lU/kg/day. There were no significant changes in body weight, food intake, physical and opthalmic examination, urine analysis, etc. Any toxic response was not observed except for enlarged spleen and extramedullary hematopoiesis. These results indicate that the no-observed adverse effect level (NOAEL) of rHuEPO is 100 lU/kg in Beagle dogs.

• 한국산업보건학회지
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• 제23권1호
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• pp.20-26
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• 2013

Objectives: This study was conducted to evaluate the health risk of workers exposed to butyl glycidyl ether to prevent them from developing occupational diseases. Methods: The workplaces that coat floor with epoxy were selected and the samples were collected and analyzed with NIOSH 1616 Method. We calculate workplace reference concentration using with NOAEL estimated by the study of Anderson et al. in 1978. Risk was calculated by the ratio of exposure to workplace reference concentration. Monte-Carlo simulation was performed to derivate the median, cumulative 90%, and cumulative 95% value by using Crystal Ball. Results: Butyl glycidyl ether is a skin, eye irritator and can result in central nervous system depression, allergic reaction. NOAEL was 38 ppm and workplace reference concentration was calculated as 0.73 ppm corrected with uncertainty factors. Geometric mean was 1.152 ppm and geometric standard deviation was 1.522 by the workplace environment measurement. The median, cumulative 90%, and cumulative 95% value of risk were calculated as 1.617, 1.934, and 2.092, respectively. Conclusions: Not only cumulative 90% and cumulative 95% value but also the median of risk is higher than 1.0 by the risk characterization, so it can do a lot of harm to workers. Therefore, the process of derivating workplace reference concentration and the appropriacy of the uncertainty factors should be re-examined.

• Toxicological Research
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• 제35권4호
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• pp.371-387
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• 2019

Although the dried root of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae) is a popular medicinal plant in East Asia, there has been no systemic toxicological evaluation of a water extract of Saposhnikoviae Radix (SRE). In this experiment, an oral acute and 13-week subchronic toxicological evaluations of SRE (500-5,000 mg/kg body weight) were performed in both sexes of Crl:CD(SD) rats. Based on the results from mortality, clinical signs, effects on body weight and organ weight, clinical biochemistry, hematology, urinalysis, and histopathology, significant acute, 4-week repeated dose range finding (DRF) and 13-week subchronic toxicity of SRE was not observed in either sex of rats; thus, the no observed adverse effect level (NOAEL) was 5,000 mg (kg/day). To identify anti-hyperuricemia potential of SRE, the suppressive effect of SRE was determined in mice challenged with potassium oxonate (PO; 250 mg/kg) via intraperitoneal injection for 8 days (each group; n = 7). SRE supplementation suppressed the uric acid level in urine through significant xanthine oxidase (XO) inhibitory activity. Kidney dysfunctions were observed in PO-challenged mice as evidenced by an increase in serum creatinine level. Whereas, SRE supplementation suppressed it in a dose-dependent manner. Collectively, SRE was safe up to 5,000 mg (kg/day) based on NOAEL found from acute and 13-week subchronic toxicological evaluations. SRE had anti-hyperuricemia effect and lowered the excessive level of uric acid, a potential factor for gout and kidney failure.

• 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.

• Journal of Dairy Science and Biotechnology
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• 제34권2호
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• pp.117-135
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• 2016

본 시험은 sialic acid가 23%를 함유하도록 제조한 유청가수분해단백분말제제(whey protein of hydrolysis)의 기능성 식품원료로 개발을 위한 동물안전성을 평가에 연구목표를 두었다. 시험물질은 sialic acid 23%(v/v)와 원료인 GMP(glycomacropeptide)가수분해 단백질이 87%(v/v)로 구성되어 있었다(시험명: 23%-GNANA). 시험물질의 독성 유무는 한국식품의약안전청(KFDA, 2014)과 OECD(2008)의 의약품 등의 독성시험 기준에 따라 실시하였다. 평가방법으로서, 시험물질의 투여용량을 0, 1,250, 2,500 및 5,000 mg/kg/day하여 SPF Sprague-Dawley 계열 암수 랫드에 90일 동안 반복경구투여하였을 때 나타나는 독성 여부를 평가하였다. 평가항목으로서는 사망률, 일반증상관찰, 체중 변화, 사료섭취량 측정, 안검사, 요검사, 혈액학적 및 혈액생화학적 검사, 부검 시 장기의 중량 측정, 부검 시 육안적 및 조직병리학적 검사 등을 평가하였다. 결과로서, 시험물질로 인한 일반증상 및 사망동물은 발생하지 않았다. 또한, 안과학적 검사, 요검사 그리고 혈액학적 및 혈액이화학적 이상 여부와 부검 시 육안적 검사 및 조직병리학적 검사에서 대조군 대비 특이한 변화는 관찰되지 않았다(P<0.05). 이외의 평가 항목에서, 암컷은 사료섭취량과 증체율이 다소 감소하였고, 그리고 수컷에서는 요의 SG와 PRO 및 고환 무게가 다소 증가하는 경향을 보였지만, 시험물질-유래 경미한 변화(non-adverse effect)가 고용량군(5,000 mg/kg/day)만 확인되었다. Weight-based classification(독성 강도에 따른 분류)를 적용한 최종 독성평가 결과는 다음과 같다. 수컷의 경우, NOEL(No Observed Effect Level)은 5,000 mg/kg/day 그리고 암컷의 경우는 NOAEL(No Observed Adverse Effect Level)은 5,000 mg/kg/day로 최종 확인되었다. 따라서, 암수 모두에서 시험물질의 NOAEL은 투여최대용량인 5,000 mg/kg/day로 확인되었다. 결론적으로, 시험물질인 유청가수분해단백분말제제는 건강기능식품의 특성상 임상허용용량인 1,000 mg/kg/day의 5배 수준에서 안전함을 확인되었다.