• Toxicological Research
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• 제26권1호
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• pp.1-8
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• 2010

The process of new drug development consists of several stages; after identifying potential candidate compounds, preclinical studies using animal models link the laboratory and human clinical trials. Among many steps in preclinical studies, toxicology and safety assessments contribute to identify potential adverse events and provide rationale for setting the initial doses in clinical trials. Gene modulation is one of the important tools of modern biology, and is commonly employed to examine the function of genes of interest. Advances in new drug development have been achieved by exploding information on target selection and validation using genetically modified animal models as well as those of cells. In this review, a recent trend of genetically modified methods is discussed with reference to safety assessments, and the exemplary applications of gene-modulating tools to the tests in new drug development were summarized.

• Toxicological Research
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• 제31권2호
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• pp.157-163
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• 2015

Nanotechnology has advanced at an extremely rapid pace over the past several years in numerous fields of research. However, the uptake of nanoparticles (NPs) into the body after administration through various routes may pose a risk to human health. In this study, we investigated the potential ocular toxicity of 20-nm, negatively- charged zinc oxide (ZnO) NPs in rats using micro-computed tomography (micro-CT) and histopathological assessment. Animals were divided into four groups as control group, ZnO NPs treatment group (500 mg/kg/day), control recovery group, and ZnO NPs treatment and recovery group. Ocular samples were prepared from animals treated for 90 days (10 males and 10 females, respectively) and from recovery animals (5 males and 5 females, respectively) sacrificed at 14 days after final treatment and were compared to age-matched control animals. Micro-CT analyses represented the deposition and distribution of foreign materials in the eyes of rats treated with ZnO NPs, whereas control animals showed no such findings. X-ray fluorescence spectrometry and energy dispersive spectrometry showed the intraocular foreign materials as zinc in treated rats, whereas control animals showed no zinc signal. Histopathological examination revealed the retinopathy in the eyes of rats treated with ZnO NPs. Neuronal nuclei expression was decreased in neurons of the ganglion cell layer of animals treated with ZnO NPs compared to the control group. Taken together, treatment with 20-nm, negatively-charged ZnO NPs increased retinopathy, associated with local distribution of them in ocular lesions.

• 한국의료질향상학회지
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• 제22권2호
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• pp.43-73
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• 2016

Purpose: The aims of this study were to assess the presence of core patient safety practices in Korean hospitals and assess the differences in reporting and learning systems of patient safety, infrastructure, and safe practices by hospital characteristics. Methods: The authors developed a questionnaire including 39 items of patient safety staffing, health information system, reporting system, and event-specific prevention practices. The survey was conducted online or e-mail with 407 tertiary, general and specialty hospitals. Results: About 90% of hospitals answered the self-reporting system of patient safety related events is established. More than 90% of hospitals applied incidence monitoring or root cause analysis on healthcare-associated infection, in-facility pressure ulcers and falls, but only 60% did on surgery/procedure related events. More than 50% of the hospitals did not adopted present on admission (POA) indicators. One hundred (80.0%) hospitals had a department of patient safety and/or quality and only 52.8% of hospitals had a patient safety officer (PSO). While 82.4% of hospitals used electronic medical records (EMRs), only 53% of these hospitals adopted clinical decision support function. Infrastructure for patient safety except EMRs was well established in training, high-level and large hospitals. Most hospitals implemented prevention practices of adverse drug events, in-facility pressure ulcers and falls (94.4-100.0%). But prevention practices of surgery/procedure related events had relatively low adoption rate (59.2-92.8%). Majority of prevention practices for patient safety events were also implemented with a relatively modest increase in resources allocated. Conclusion: The hospital-based reporting and learning system, EMRs, and core evidence-based prevention practices were implemented well in high-level and large hospitals. But POA indicator and PSO were not adopted in more than half of surveyed hospitals and implementation of prevention practices for specific event had low. To support and monitor progress in hospital's patient safety effort, national-level safety practices set is needed.

• 한국환경농학회지
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• 제30권2호
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• pp.166-172
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• 2011

본 연구를 통해 신규농약인 isotianil의 쌀에 대한 잔류허용기준과, 기준이 확대되는 21종 농약에 대해 26개의 농약잔류허용기준을 제시하였다. Iisotianil의 쌀에 대한 MRL은 0.1 mg/kg으로 설정하였고, ADI대비 TMDI의 비율 1.54%로 안전한 수준으로 판단된다. 기준이 확대되는 21종의 농약의 경우 dinotefuran, idoxacarb, trifumizole을 제외한 나머지 농약은 ADI대비 TMDI의 비율이 50% 미만으로 안전성에 문제가 없는 수준으로 판단된다. Trifumizole은 재평가를 통해 미등록된 작물의 기준을 폐지하면, 현재의 ADI대비 TMDI 비율 절반 수준인 30% 미만으로 감소될 것으로 예측된다.

• 대한한의학회지
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• 제30권3호
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• pp.79-85
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• 2009

Aim : To evaluate the pharmaceutical safety of the herbal formula Myelophil, composed of Astragali Radix and Salviae Radix, via systemic subacute toxicological study using SD rats. Methods : Forty male and 40 female SD rats were fed with Myelophil (5000, 2500 or 1250 mg/10 mL/kg) or distilled water for four weeks. Adverse effects were examined intensively by comparing the differences between normal and drug-administered groups using clinical signs, necropsies, histopathologic findings, hematology, urinalysis, and blood biochemical analysis. Results : No altered clinical symptoms including body weight, diarrhea, anorexia, death, and abnormal necropsy of major organs were observed in male or female rats. No drug-induced abnormalities in histopathological finding, hematological values, urinalysis, and blood biochemical values were found at any doses of Myelophil. Conclusion : Myelophil should be very safe when used in a clinical application with a wide therapeutic index.

• 대한한의학회지
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• 제40권2호
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• pp.94-105
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• 2019

Objectives: The correlation between medicinal herbal formulas and a risk of cardiotoxicity has been controversial. Thus, this study investigated cardiac safety assessment of 52 most commonly used medicinal herbal formulas. Methods: We evaluated the in vitro effects of medicinal herbal formulas on recombinant human embryonic kidney 293 (HEK 293) cell line expressing human ether-a-go-go-related gene (hERG) potassium channel. Results and Conclusion: Our results demonstrated that all of 52 medicinal herbal formulas did not show inhibition of hERG current in hERG-HEK 293 recombinant cells. In conclusion, these safety data suggest that 52 medicinal herbal formulas were not associated with an increased risk of cardiotoxicity in hERG-HEK 293 recombinant cells.

• 한국환경과학회지
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• 제16권11호
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• pp.1287-1293
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• 2007

To obtain the risk assessment of hazardous materials in Rehmanniae Radix Preparata, the residual pesticides and heavy metals in samples on the Korea and China are surveyed. Group I ($BHC-{\delta}$, $BHC-{\beta}$, Fenitrothion, Penthoate, Endosulfan-${\alpha}$, Dieldrin, Endosulfan-${\beta}$ and Endosulfan-sulfate), Group II (BHC-${\gamma}$, Aldrin, DDD, DDT-p,p Permethrin and Fenvalerate), Group III(BHC-${\alpha}$, Chlorpyrifos, Tolyfluanid, Captan and DDT-o,p) and Group IV(Quintozene, Vinclozolin, DDE and Chlorfenapyr) could analysed on gas chromatography-ECD for evaluation of residual pesticides. Qualified detection concentration on the GC-ECD are $0.45 ng/g{\sim}2.50 ng/g$. Group I, Group II, Group III and Group IV are not detected in Rehmanniae Radix Preparata on the Korea and China. Concentration of As, Cd and Pb in Rehmanniae Radix Preparata. on the Korea are 3.06%, 7.00% and 5.78% for Korea Food & Drug Administration(KFDA). Concentration of As, Cd and Pb in Rehmanniae Radix Preparata. on the China are 5.16%, 5.33% and 6.50% for Korea Food & Drug Administration(KFDA). The hazardous materials in Rehmanniae Radix Preparata on the Korea and China were verified the safety of the residual heavy metals and pesticides compare with Korea Food & Drug Administration (KFDA) advisory level.

• 한국식품위생안전성학회지
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• 제27권4호
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• pp.388-394
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• 2012

본 연구에서는 버섯류의 비소 및 수은 함량 실태조사를 통해 우리나라 국민이 식품으로써 버섯을 섭취할 경우의 중금속 위해성을 평가하였다. 국내 유통 버섯류 17개 품목, 536건을 분석하였으며, 비소 함량은 생물버섯의 경우 0.003(새송이)~1.952(송이) mg/kg이었고 건조버섯은 0.015(차가)~16.95(송이) mg/kg이었다. 수은 함량은 생물버섯의 경우 0.001(새송이)~0.030(송이) mg/kg이었고 건조버섯은 0.004(느타리)~0.588(송이) mg/kg이었다. 국내 유통 버섯류의 중금속 함량은 타 문헌과 유사하거나 낮은 수준이었다. 식품으로써 버섯을 섭취할 경우, 전체국민의 비소 노출량은 $0.151{\mu}g$/day으로 위해도는 0.005% 수준이었으며, 수은 노출량은 $0.022{\mu}g$/day으로 위해도는 0.071% 수준이었다. 따라서, 우리나라 국민은 국내 유통되는 버섯에 존재하는 비소 및 수은의 위해성으로부터 안전한 것으로 판단된다.

• 보건의료기술평가
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• 제1권1호
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• pp.22-26
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• 2013

Objectives: Balancing benefits and risks through the drug life cycle has been discussed for many decades. The objective of this study was to review the processes and tools currently proposed for benefit-risk assessment of medicinal drugs. It aimed to establish scientific and efficient drug safety management system based on the synthetic analysis of benefit-risk evidence. Methods: We conducted a review of exiting literatures published by regulatory agencies or initiatives. Not only quantitative methodologies but also qualitative method were compared to understand their key characteristics for the benefit and risk assessment of drugs. Results: Recently, benefit-risk assessments have more structured approaches to decision making as part of regulatory science. Regulatory agencies such as European Medicines Agency, FDA have prepared plans to apply benefit-risk assessment to regulatory decision making. Also many initiatives such as IMI (Innovative Medicine Initiative) have conducted research and published reports about benefit-risk assessment. For benefit-risk assessment, four kinds of methods are necessary. Frameworks such as BRAT (Benefit Risk Action Team) framework, PrOACT-URL provide guidance for the whole process of decision-making. Metrics are measurements of risk benefit. The estimation techniques are methods to synthesis and combine evidences from various sources. The utility survey techniques are necessary to explicit preferences of various outcome from stakeholders. Conclusion: There is the lack of widely accepted, validated model for benefit-risk assessment. Nor there is an agreement among academia, industry, and government on methods for the quantitative valuation. It is also limited by available evidence and underlying assumptions. Nevertheless, benefit-risk assessment is fundamental to improve transparency, consistency and predictability for decision making through the structured systematic approaches.

• 한국식품위생안전성학회지
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• 제28권3호
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• pp.222-226
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• 2013

Chloropicrin은 국내에서는 사용되지 않으며, 잔류허용기준이 불검출로 설정된 농약이다. 그러나 중국에서는 훈증제, 살균제, 살선충제 및 저장 곡물의 살충제로 사용되고 있으며, 잔류허용기준이 설정되어 있다. 따라서 본 연구에서는 중국 등에서 수입하는 식품 중 국내에서 사용하지 않는 농약에 대한 안전성을 확보하기 위하여 해당 농약을 신속하고 빠르게 검출할 수 있는 시험법을 개발하고자 하였다. Chloropicrin은 분자량이 작고 휘발성이 큰 화합물이므로 헤드스페이스 추출법을 활용하여 검체 추출액을 직접 GC에 주입하는 시험법을 개발하였으며, 확립된 시험법을 검증한 결과 회수율이 77.7~79.3%로 조사되어 코덱스 국제가이드라인(CAC/GL 40)에 적합함을 확인하였다. 정량한계 또한 0.05 mg/kg 이하로 매우 우수한 감도를 가지고 있음을 확인하였으며, GC-MS를 이용한 재확인과정을 추가로 확립하여 본 시험법의 신뢰도를 높였다. 확립된 시험법은 식품에 잔류할 수 있는 농약의 기준 준수여부에 대한 적합성을 판단하기 위한 공정시험법으로 활용되고 있다.