MSK1 regulates RANKL-induced NFATc1 expression through CREB and c-Fos

Jeongim Ha, Jung Hye Hwang, Seul Gi Kwon, Da Hye Park, Tae Wan Kim, Deok Gyeong Kang, Kyung Hee Kang, Il-Suk Kim, Chul Wook Kim 충북대학교 동물의학연구소 2015 Journal of Biomedical and Translational Research Vol.16 No.2

Osteoclasts originated from hematopoietic stem cells are multi-nucleated cells that can resorb the bone matrix. Receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) signaling pathway is crucial for the differentiation and activation of osteoclasts. In this study, we investigated for the first time whether or not RANKL induced mitogen- and stress-activated kinase 1 (MSK1) phosphorylation at Ser 376. Activation of MSK1 was detected as soon as 5 min after RANKL stimulation and sparsely detected at 30 min after stimulation. RANKL-induced MSK1 phosphorylation occurred in a dose-dependent manner. MSK1 is known as a downstream signaling molecule of cAMP-dependent protein kinase (PKA). Treatment with the PKA inhibitor H89 significantly suppressed c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) induction upon RANKL stimulation. In addition, cAMP response element-binding protein (CREB) phosphorylation was extremely inhibited by H89 treatment. Mitogen-activated protein kinases (MAPKs) have been investigated for induction of MSK1 phosphorylation. Specific signaling pathway inhibitors for p38 and extracellular signal-regulated kinases (ERKs) significantly blocked RANKL-induced MSK1 activation. Finally, as a downstream effector of the p38-MSK1 pathway, c-Fos transcriptional activity was determined. RANKL-mediated elevation of c-Fos transcriptional activity was significantly suppressed by p38 inhibitor. Moreover, a dominant negative form of CREB suppressed activation of NFATc1. In conclusion, RANKL-stimulated MSK1 phosphorylation could play a role in induction of NFATc1 through CREB and c-Fos activation as a downstream molecule of p38, ERK MAPKs, and PKA. Our results support basic information for the development of osteoclast specific inhibitors.

Effect of C/N Ratio on Composting Treatment of TNT-Contaminated Soil

Jeongim Park,Hyunjoo Bae 한국환경보건학회 2006 한국환경보건학회지 Vol.32 No.5

Health benefits from implementing air quality control measures were assessed using the Environmental Benefits Mapping and Analysis Program (BenMAP). BenMAP developed by US EPA is a GIS-based software tool that estimates the health impacts and associated economic values connected with changes in ambient air pollution. Once a set of BenMAP-required data was collected, the health benefits from implementing Seoul Air Quality Management Plan (SAQMP), an official AQ improvement plan for Seoul Metropolitan Area, was assessed using BenMAP. The PM10 concentrations assuming the SAQMP implemented successfully were predicted with the MM5 (Mesoscale Meteorological model version 5)/CMAQ (Community Multiscale Air Quality) model. A PM10 exposure related premature mortality function was adopted from a well-known epidemiology study. Economic valuation functions driven from benefit transfer methods were utilized. Through the SAQMP, PM10 concentrations were estimated to be lowered by 15g/m3 to 75 g/m3 depending on air quality modeling grids. 5,569 premature deaths (95% CI 3,264~7,809 deaths) could be avoided in the Seoul Metropolitan Area. The economic value of the deaths avoided was estimated to $13.2 billion (95% CI $890 million~$28.2 billion) using the benefit transfer value.BenMAP could be a useful tool for developing effective air quality improvement policy, enabling the policy makers to anticipate the effects of regulatory changes on peoples health and the economy.

Distribution of Korean safety and health professionals from the perspective of gender equality

Jeongim Park,Sohyeon Choi,Yeji Sung,Jinjoo Chung,Sangjun Choi 대한직업환경의학회 2022 대한직업환경의학회지 Vol.34 No.-

Environmental Risk Assessment of Pharmaceuticals - Model Application for Estimating Pharmaceutical Exposures in the Han River Basin : 의약물질의 환경위해성 관리방안 연구 - 한강수계의 의약물질 농도예측 모형연구를 중심으로

Jeongim Park,Myung-Hyun Kim,Kyungho Choi,Young-Hee Kim,Min-Young Kim 한국환경정책평가연구원 2007 한국환경정책평가연구원 연구보고서 Vol.- No.RE-06

의약물질은 질병을 치료하고 삶의 질을 향상시키기 위해 없어서는 안되는 중요한 물질이다. 동물용 의약품은 질병치료 목적 뿐만 아니라 축산의 생산성 향상을 위하여 광범위하게 사용되고 있다. 그러나 아무리 우리 생활에 이로운 물질이라도 의약물질을 사용하는 동안 인체용 또는 동물용 의약물질은 환경 중으로 흘러들어갈 우려가 있다. 최근 들어, 물환경에 존재하는 의약물질로 인한 환경위해성은 대중적인 관심의 대상이 되었다. 환경 중에 존재하는 의약물질로 인한 생태영향은 다음과 같은 두 가지 측면에서 가장 우려가 된다; 1) 환경 중으로 유출된 항생물질로 인하여 항생제 내성균이 출현할 위험이 커지거나 내성유전자의 확산이 촉진될 우려가 증가한다는 점, 2) 내분비계에 영향을 미치는 물질이 자연에 존재할 경우 생태계의 교란을 초래할 수 있다는 점 등이다. 환경위해성평가(Environmental Risk Assessment)는 어떤 오염물질이 생태계나 지역사회에 미칠 수 있는 잠재된 영향을 평가하기위한 가장 과학적인 접근방법이다. 이를 위해서는 문제 구체화, 노출평가, 영향평가, 위해 특성평가 등 4단계를 거치게 되는데, 정확한 노출평가야말로 환경위해성평가의 핵심단계라 할 수 있다. 하지만 환경 중 의약물질 문제의 경우 ppt 수준의 매우 낮은 농도를 측정해야하기 때문에 기술적인 어려움, 비용 등의 문제로 노출평가가 쉽지 않다. 또한 현장시료를 분석하여 얻은 농도는 노출의 전체 그림이 아니라 한 순간의 농도값만을 보여주는 데에서 오는 제한점도 있다. 따라서 의약물질의 환경 중 노출을 평가하기 위해서는 노출모형을 활용하는 것이 필수적이다. 본 연구의 첫 번째 목적은 한강과 경안천을 대상으로 인체용 및 동물용의약물질의 환경농도를 노출모형을 이용하여 추정하는 것이다. 모형 운용에 가용한 자료, 연구자의 선행 경험, 모형의 접근성 등을 고려하여 P hATETM 와 SWMM 모형이 본 연구에 적합한 것으로 선정되었다. 이 모형들은 실제농도를 정확히 예측하는 것이 목적이 아니라 의약물질의 환경 중 잠재된 거동을 빠르게 추정하는 것을 목적으로 하는 Screening 단계의 모형이다. 모형을 통하여 추정된 농도값을 본 연구 또는 선행연구에서 측정한 환경 중 농도값과 비교하였다(보고서 제2-4장). 두 번째 목적은 PhATE™와 SWMM 모형 결과를 통합함으로써 인체용과 동물용에 공통으로 사용되는 의약물질의 농도를 추정하는 것이다. 물론 동물용 의약물질의 환경 중 유입경로가 인체용 의약물질과는 전혀 다르지만 결국 환경중으로 유입된 의약물질은 지표수에서 만나게 될 것이다. 따라서 지표수에서 의약물질 농도를 추정할 때 인체에 사용된 분량만을 근거로 추정하거나 동물용 사용 부분만을 고려하여 추정하는 것은 실제 환경 중 예상농도를 과소추정할 우려가 있다. 본 연구에서는 인체와 동물에 모두 사용되는 의약물질의 환경 중 예상농도 추정의 방법을 제안하였다(보고서 제5장). 마지막으로 일부 의약물질에 대하여 환경위해성 평가를 실시하였다. 의약물질의 환경독성은 표준시험법으로 시험하여 도출하였고, 부족한 경우 문헌값을 활용하였다. 모형으로 추정한 예측농도(PEC)와 실제 측정농도(MEC) 각각에 대하여 위해성평가를 실시하여 비교하였다. 이로써 환경 중 의약물질의 환경위해성 평가에 노출모형을 활용하는 것이 적절함을 제시하였다. 또한 분자수준의 바이오마커 Pharmaceuticals are indispensable as they cure those who suffer from disease and their availability improves the quality of life. Veterinary medicines are also widely used to treat disease and improve the productivity of livestock farming. However, during their use, human and veterinary pharmaceuticals have the potential of being released into the environment. In recent years, the possible environmental (ecological) risk of pharmaceuticals in the aquatic environment has become a matter of increasing public concern. Potential ecological effects from the presence of pharmaceuticals in the environment have generally focused on the following two concerns: 1) the release of antibiotics into the environment increases the chance of antibioticresistant microorganisms and promotes the spread of resistant genes, and 2) when drugs affecting hormonal systems reach organisms in nature, it may result in a reproductive disturbance in the ecosystem. Environmental risk assessment (ERA) is considered the best scientifically based approach for evaluating the potential effects of contaminants on communities and ecosystems. The process includes problem formulation, exposure assessment, effects assessment, and risk characterization. Accurate exposure assessment is a key element of ERA. However, exposure assessment has been hampered by the continuing difficulties and expense involved in measuring the low ppt concentrations of pharmaceuticals in the environment. In addition, real?time monitoring data provides only snapshots of contaminant concentrations. Thus, when faced with the task of assessing the environmental exposure of pharmaceuticals, the utilization of exposure models becomes essential. The first objective of this report is to apply computerized exposure models to assess the environmental concentration of human and veterinary pharmaceuticals in the Han River and the Kyungahn stream, a major branch of the Han River. PhATETM and SWMM are identified as appropriate exposure models for this study based on data availability, researchers’ previous experience with models, and accessibility to models. The models investigated in this study intend to provide rapid predictions regarding the potential environmental fate of a compound. In this study, model?predicted PECs are compared to field data that either have been published previously or were empirically measured during this study (Chapters 2, 3, and 4). A second objective of this study is to estimate the total environmental concentration of pharmaceuticals, from both human and animal use, by integrating the simulation results from PhATE™ and SWMM. Although the introduction routes into the environment for veterinary pharmaceuticals are different from those for human use, both human and animal pharmaceuticals eventually end up reaching surface water. Therefore, estimating the environmental concentration of such pharmaceuticals based solely on either human consumption or animal consumption results in an underestimation of environmental exposure. In this study, a workable framework to estimate PECs for these dual?usage pharmaceuticals is suggested (Chapter 5). Finally, a third objective is to perform an environmental risk assessment (ERA) for selected pharmaceuticals. Hazard quotients (the ratio of EC to PNEC) based on PECs are compared to those based on MECs. This exercise will demonstrate the applicability of modeling approaches in the risk assessment of pharmaceuticals in the environment. The potential benefit of using molecular level biomarkers to assess pharmaceutical toxicity is also discussed and methods are presented (Chapter 6). In order to minimize the deposition of pharmaceuticals into the environment, potential risk management actions are suggested; disposal labeling on pharmaceutical products, discharge guidelines for pharmaceutical manufacturing facilities, pretreatment of hos

Assessing the Health Benefits of the Seoul Air Quality Management Plan Using BenMAP

Jeongim Park,Hyunjoo Bae 한국환경보건학회 2006 한국환경보건학회지 Vol.32 No.5

Health benefits from implementing air quality control measures were assessed using the Environmental Benefits Mapping and Analysis Program (BenMAP). BenMAP developed by US EPA is a GIS-based software tool that estimates the health impacts and associated economic values connected with changes in ambient air pollution. Once a set of BenMAP-required data was collected, the health benefits from implementing Seoul Air Quality Management Plan (SAQMP), an official AQ improvement plan for Seoul Metropolitan Area, was assessed using BenMAP. The PM10 concentrations assuming the SAQMP implemented successfully were predicted with the MM5 (Mesoscale Meteorological model version 5)/CMAQ (Community Multiscale Air Quality) model. A PM10 exposure related premature mortality function was adopted from a well-known epidemiology study. Economic valuation functions driven from benefit transfer methods were utilized. Through the SAQMP, PM10 concentrations were estimated to be lowered by 15g/m3 to 75 g/m3 depending on air quality modeling grids. 5,569 premature deaths (95% CI 3,264~7,809 deaths) could be avoided in the Seoul Metropolitan Area. The economic value of the deaths avoided was estimated to $13.2 billion (95% CI $890 million~$28.2 billion) using the benefit transfer value.BenMAP could be a useful tool for developing effective air quality improvement policy, enabling the policy makers to anticipate the effects of regulatory changes on peoples health and the economy.

MSK1 regulates RANKL-induced NFATc1 expression through CREB and c-Fos

Jeongim Ha,Jung Hye Hwang,Seul Gi Kwon,Da Hye Park,Tae Wan Kim,Deok Gyeong Kang,Kyung Hee Kang,Chul Wook Kim,Il-Suk Kim 충북대학교 동물의학연구소 2015 Journal of Biomedical and Translational Research Vol.16 No.2

Osteoclasts originated from hematopoietic stem cells are multi-nucleated cells that can resorb the bone matrix. Receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) signaling pathway is crucial for the differentiation and activation of osteoclasts. In this study, we investigated for the first time whether or not RANKL induced mitogen- and stress-activated kinase 1 (MSK1) phosphorylation at Ser 376. Activation of MSK1 was detected as soon as 5 min after RANKL stimulation and sparsely detected at 30 min after stimulation. RANKL-induced MSK1 phosphorylation occurred in a dose-dependent manner. MSK1 is known as a downstream signaling molecule of cAMP-dependent protein kinase (PKA). Treatment with the PKA inhibitor H89 significantly suppressed c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) induction upon RANKL stimulation. In addition, cAMP response element-binding protein (CREB) phosphorylation was extremely inhibited by H89 treatment. Mitogen-activated protein kinases (MAPKs) have been investigated for induction of MSK1 phosphorylation. Specific signaling pathway inhibitors for p38 and extracellular signal-regulated kinases (ERKs) significantly blocked RANKL-induced MSK1 activation. Finally, as a downstream effector of the p38-MSK1 pathway, c-Fos transcriptional activity was determined. RANKL-mediated elevation of c-Fos transcriptional activity was significantly suppressed by p38 inhibitor. Moreover, a dominant negative form of CREB suppressed activation of NFATc1. In conclusion, RANKL-stimulated MSK1 phosphorylation could play a role in induction of NFATc1 through CREB and c-Fos activation as a downstream molecule of p38, ERK MAPKs, and PKA. Our results support basic information for the development of osteoclast specific inhibitors.

A Case of Polymyositis Presenting as Bent Spine Syndrome

( Jeongim Choi ),( Dam Kim ),( Jae-bum Jun ),( Seunghun Lee ),( Seung Sam Paik ),( Yoon-kyoung Sung ) 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.4

Polymyositis (PM) is a subset of idiopathic inflammatory myopathies. The muscles involved with PM are typically proximal and distal limb muscles, but paraspinal muscles are rarely affected. The primary PM clinical symptom is gradual proximal muscle weakness but unusually abnormal trunk posture. Bent spine syndrome (BSS), also referred to camptocormia, is defined as an abnormal flexion of the trunk, appearing in standing position. An idiopathic axial myopathy is the most common cause of primary BSS. A few cases of inflammatory myopathy, a secondary BSS, have been reported. We describe a 59-year.old polymyositis patient with normal finding on an magnetic resonance imaging femur scan who presented with BSS only, myopathic findings on electromyography and elevation of muscle enzymes. (J Rheum Dis 2016;23:261-265)

Developing a Video-based Smart Mastery Learning through Adaptive Evaluation

Jeongim Kang,Moonhee Kim,Seong Baeg Kim 보안공학연구지원센터 2014 International Journal of Software Engineering and Vol.8 No.11

This paper proposes to develop a novel e-learning model based on dynamic formative evaluation. In case of the evaluation of the existing e-learning, repetitive learning to achieve mastery, causes learners to degrade immersion and become neglectful of learning. The dynamic formative evaluation proposed is able to supplement the limitations of the existing approaches. Since a repetitive learning method does not provide perfect feedback, this paper puts an emphasis on dynamic formative evaluation that is able to maximize learning achievement. Through the dynamic formative evaluation, the instructor is able to refer to the evaluation result when making an assessment about the learner. For our model that shows the flow chart of learning, based on dynamic formative evaluation, we prove its effectiveness and validity by implementing our model and analyzing it.

Pharmaceuticals in the Environment and Management Approaches in Korea

Jeongim Park 한국환경정책평가연구원 2005 한국환경정책평가연구원 연구보고서 Vol.2005/re-12 No.-

의약품으로 인한 환경오염문제에 대한 우려가 제기되고 있다. 환경 중에서 측정된 의약물질의 농도 수준이 ng/L 에서 ㎍/L 정도로 아주 미량인 것으로 보고되고 있다고는 하나, 측정된 수준의 농도가 환경에 미치는 영향의 크기는 제대로 파악되지 못하고 있는 실정이다. 본 연구의 목적은 우리나라에서는 아직까지 드러나지 않았던 새로운 환경 문제인 의약물질로 인한 환경오염 문제를 제기하는 것이다. 의도적이든 비의도적이든 환경 중에 존재할 수 있는 의약물질은 크게 인체의 질병을 치료하거나 건강을 개선할 목적으로 사용되는 인체의약품과 동물의 질병 치료 및 사료보조제로 사용되는 동물의약품으로 나누어 볼 수 있다. 인체의약품과 동물의약품은 설사 그 성분이 동일한 경우라 할지라도 환경으로 유입되는 경로가 매우 다르기 때문에 본 연구에서는 연구의 범위를 인체의약품(human pharmaceuticals)으로 제한하였다. 본 보고서에서는 의약물질이 환경으로 유입되는 다양한 경로, 기존의 해외 연구 결과 환경 중에서 검출된 의약물질의 종류 및 농도 수준, 의약품의 환경 중 거동에 관한 문헌을 고찰하였다. 또한 유럽, 캐나다, 미국 등에서 이미 실시하고 있는 의약품의 환경위해성 평가 방법 및 관련 제도를 정리하였다. 기존의 의약품 환경위해성 평가방법을 우리나라에 적용하기에 앞서 우리나라에서 생산되고 있는 의약품을 대상으로 환경에 부정적인 영향을 미칠 가능성이 있는 물질을 선정하기 위한 인체의약물질의 성분별 데이터베이스를 구축하였다. 또한, 환경 중 의약품의 위해성을 평가하기 위해 필요한 연구 분야와 그 위험을 최소화하기 위해 필요한 조치들을 제안하였다. 의약물질은 특정한 약리효과를 목적으로 개발되고 생산되는 생리활성 물질이며 대개의 경우 그 작용이 강력하다. 또한 약리작용을 유지하기 위하여 의도적으로 물에 잘 녹지만 생분해는 잘 이루어지지 않도록 만들어지는 경우도 있다. 따라서 약물 본래의 물리화학적 특성과 생물학적 특성을 고려한다면, 의약품이 환경 중으로 배출 되었을 경우 인간 및 생태계에 심각한 영향을 미칠 수 있을 것으로 우려된다. 인구가 증가하고 약의 수요가 증가함에 따라 점차 다양한 종류의 의약물질이 더 많이 환경 중으로 배출될 수 있다. 인체의약물질이 환경 중으로 유입되는 경로는 매우 다양하다. 의약물질은 원형 그대로, 또는 대사산물이나 결합체 (conjugate)의 형태로 소변이나 대변으로 배설된다. 배설된 의약물질은 일반적으로 하수처리장으로 모이게 되는데, 하수처리 과정에서 분해되거나, 하수 슬러지에 흡착되거나, 또는 처리되지 않고 남은 의약물질은 지표수로 흘러 들어 희석될 수 있다. 어떤 의약물질의 경우 하수처리 공정을 통해 적절히 처리되지 못하고 그대로 지표수로 흘러 들어갈 수 있다. 슬러지에 흡착된 의약품들은 토양으로 유입되고, 따라서 지표수 및 지하수에 도달하기도 한다. 사람이 먹은 의약물질이 체외로 배설되는 것 뿐 아니라, 제약공장의 방류수, 다양한 약물을 비교적 높은 농도로 포함할 수 있는 병원 폐수, 가정에서 쓰고 남은 의약품 또는 유효기간이 지난 의약품의 무단 배출 등이 의약물질이 환경 중으로 유입되는 주요 경로이다. 다양한 경로를 통해 환경 중으로 유입된 의약물질이 환경에 어떠한 영향을 미칠 것인가를 예측하는 것이 필요하다. 의약품이 환경에 부정적인 영향을 미 The occurrence of pharmaceuticals in the environment is a growing concern. The number of reports on measurable concentrations of pharmaceuticals found in the environment is growing. Despite the numerous reports on environmental occurrence of pharmaceuticals at levels in the range of ng to low g/L, the environmental significance is largely unknown. The purpose of this research was to provide new perspectives on a previously hidden environmental concern, or Pharmaceuticals in the Environment in Korea. The scope of this study was limited to human pharmaceuticals. This report provided an overview of issues pertaining to the input, occurrence and fate of pharmaceuticals in the environment, the risks they pose, as well as the environmental risk assessments developed for regulatory purposes in the EU, Canada, and the US. A database of pharmaceutical products was compiled in order to predict a pharmaceutical compound's potential to cause adverse effects in the environment in advance to applying a complicated assessment protocol. This study also proposed a list of necessary approaches for managing human pharmaceuticals in the environment. Pharmaceutical compounds are developed and manufactured for specific biological effects. Because of their physicochemical and biological properties, when released into the environment, it may be possible for such drugs to cause serious impacts on non-target species. With a growing population and an increased demand for medicine, the amount of pharmaceuticals entering into the environment is steadily growing. Pharmaceuticals enter into the environment through various routes. Pharmaceutical compounds, including their metabolites and conjugates, are mainly excreted in urine or feces. They enter municipal sewage treatment systems where they can be degraded, absorbed to sewage sludge, or eventually diluted into surface water. Sewage treatment facilities are not always effective in removing active pharmaceuticals from wastewater. Pharmaceuticals that adsorb into sludge can reach the terrestrial environment and reach surface water and groundwater, and eventually into the aquatic environment. In addition to the excretion from human bodies, effluent from pharmaceutical plants, hospital wastewater containing various pharmaceuticals at relatively high levels, direct dumping of excess or expired medication from households can be significant sources of pharmaceuticals in the environment. It is desirable to be able to predict a pharmaceutical's potential for environmental significance. In order to estimate the probability of a pharmaceutical causing undesirable environmental effects, an environmental risk assessment (ERA) is required for new medical compounds in the United States, EU, and Canada. In the United States, the National Environmental Policy Act of 1969 (NEPA) requires all federal agencies to assess environmental impacts of their actions and ensure that the interested and affected public is informed of environmental analyses. The Food and Drug Administration (FDA) is therefore required under NEPA to consider the environmental impacts of approving drug and biologics applications as an integral part of its regulatory process. Specific product types are given in the ""Guidance for Industry: Environmental Assessment of Human Drug and Biologics Applications"" (FDA 1998) and ,in particular, some pharmaceuticals anticipated no expected impact on the environment are categorically excluded from assessment and data requirements. In the European Union, an application for the marketing authorization for a medicinal product for human use shall include an ERA (Council Directive 2001/83/EC as amended by Council Directive 2004/27/EC). ERA procedures for pharmaceuticals, based on principles already applied in the ERAs of chemicals, have been developed for regulatory purposes in the EU. In order to arrive at reliable ERAs, adequate data on environmental exposure and ecotoxic potency of pharmaceutical compo

An Approach for Developing Aquatic Environmental Risk Assessment Framework for Pharmaceuticals in Korea

Jeongim Park 한국환경정책평가연구원 2006 한국환경정책평가연구원 연구보고서 Vol.- No.RE-05

의약품은 인체의 질병을 치료하고 건강을 개선하는 데 없어서는 안될 중요한 물질이다. 또한 축산에서도 동물의 질병치료와 사료첨가제로 사용되는 필수적인 물질이다. 이러한 의약품의 편익에 가려 의약품을 사용한 이후 환경에 미치는 영향은 최근까지 간과되어 왔다. 그러나 환경적인 관점에서 본다면 의약물 질도 화학물질의 일종이기 때문에 수질에 나쁜 영향을 끼칠 수 있는 잠재적 오염물질로서 문제를 내포한다. 본 연구에 앞서 KEI는 “Pharmaceuticals in the environment and management approaches in Korea (KEI 기본연구과 제보고서, 2005년)”에서 이미 환경 중 의약물질의 잠재된 위해성에 관하여 전반적으로 문제를 제기한 바 있다. 즉, 의약물질의 환경 중으로의 유입, 환경 중검출과 환경 매체간의 거동, 잠재된 환경위해성 및 EU, 미국, 캐나다 등에서 적용 또는 개발 중인 의약물질의 환경위해성평가 관련 규제에 관하여 정리하였다. 또한 환경 중 인체의약물질을 적극적으로 관리하기위한 방안을 제안하기도 하였다. 본 연구의 목적은 물환경 중 환경위해성평가가 필요한 의약물질의 우선순위를 정하는 것과 몇 가지 사례 의약물질을 대상으로 환경위해성평가를 수행하는 것이다. 본 연구보고서는 두 부분으로 나뉘어져 있다. 제2장과 3장에 해당하는 앞 부분은 환경위해성평가가 필요한 의약물질 선정에 관한 내용이고, 4장부터 6장까지는 일부 항생물질에 대하여 환경위해성평가를 시범적으로 실시함으로써 본 연구에서 제안한 환경위해성평가 전략의 타당성을 검증하는 내용이다. 우선, 미국, 캐나다 및 유럽 등지에서 화학물질의 위해성 관리를 위하여 개발되어 사용중인 우선순위선정 기법에 관하여 검토하였다 (제2장). CHEMS-1 와 EURAM의 체계를 비교한 결과 이들은 노출과 독성을 점수화하는 일부지수들만을 제외하고는 일반적인 접근법에 있어서는 매우 유사하였다. 그러나, 이들 방법을 환경위해성 평가가 필요한 의약물질의 우선순위를 정하는 데에 직접 적용하기에는 원칙적인 부분에 몇 가지 제한이 있는 것으로 판단되었다. 즉, 의약물질의 체내대사율 및 하수처리효율이 이들 모형에는 고려되지 않았다는 점, 의약물질의 물리화학적인 성질이 전통적인 잔류성 화학물질과는 다르다는 점 등이 그 예이다. 따라서 의약물질의 환경 중 거동을 현실적으로 반영하기 위해서는 잔류성 유기화학물질과는 다른 의약물질 고유의 노출모형이 필요하다. 또한 의약물질의 경우 일반 화학물질보다 매우 높은 급성-만성 독성비율 acute-to-chronic ratios (ACRs) 을 나타내는 경향이 있으므로 급성독성에만 전적으로 의존하는 독성평가 방식은 의약물질의 위해성을 심하게 과소평가할 우려가 있다. 따라서 앞서 열거한 제한점과 특성을 제대로 반영하는 의약물질 고유의 우선순위 선정방법이 필요함을 알 수 있다. 의약품에 사용되는 모든 성분에 대하여 환경 중 노출을 감시하고 환경위해성 평가를 실시하는 것은 불가능하다. 따라서 관심을 기울여야 할 필요가 있는 의약물질을 선정하고 우선 순위를 정하는 것이 타당하다. 본 연구를 통하여 우리나라에서 우선 고려되어야 할 인체 의약물질과 동물의약물질의 목록(안)이 도출되었다(제3장). 인체 의약물질의 경우 활성의약성분의 생산량을 계산한 후 이에 근거하여 환경 중에 존재할 가능성의 순위를 매겼다. 유럽의 EMEA와 미국의 FDA 가이드라인에 따르면 의약품의 생 Pharmaceuticals are very beneficial to people’s quality of life and cure to disease. Animal drugs are also indispensable for successful livestock farming. The environmental consequences of using pharmaceuticals have been generally ignored because of advantages of using drugs. As chemical products, however, pharmaceuticals face unique environmental challenges. We are currently recognizing pharmaceutical substances as yet another group of potentially harmful water pollutants. Prior to this report, “Pharmaceuticals in the Environment and Management Approaches in Korea (KEI, 2005)” provided an overview of issues related to the input, occurrence and fate of pharmaceuticals in the environment, the risks, as well as reviewing the environmental risk assessments developed for regulatory purposes in the EU, Canada, and the US. The study also proposed a list of proactive agendas for managing human pharmaceuticals in the environment. This study aims to prioritize pharmaceutical substances for aquatic environment risk assessment (ERA) and to provide a basis for developing the most proper and sensible strategy for pharmaceutical ERA. This report consists of two sections. The first section (Chapters 2 and 3) is about prioritizing pharmaceuticals for aquatic environment risk assessment in Korea, and the second section (Chapters 4 through 6) is devoted to conducting an ERA for selected antibiotics in order to assess the preliminary ERA strategy. The foremost chemical risk management ranking and scoring systems in the US, Canada, and European countries were reviewed. Upon examining and comparing CHEMS-1 and EURAM, both systems were found to be very similar in their general approach. Only certain parameters used for scoring exposure and toxicity were different. However, when utilizing these systems for prioritizing potentially hazardous pharmaceutical products, several intrinsic limitations were encountered. Metabolic rates and STP removal efficiencies are not considered in these exposure models. In addition, the physicochemical characteristics of pharmaceuticals differ from those of conventional persistent chemicals. Therefore, to assess the fate and transport of pharmaceuticals realistically in the environment a unique exposure modeling scheme which is different from the one used for persistent organic compounds is required. Toxicity information that focuses almost exclusively on acute toxicity data may also result in significant underestimations in the risk assessment of pharmaceuticals, since very high acute-to-chronic ratios (ACRs) are often noted for pharmaceuticals. Therefore, a novel CRS system, which addresses these issues, is required to appropriately rank the priority of pharmaceuticals for environmental evaluation. Since it may be nearly impossible to monitor and evaluate the occurrences and potential environmental risks of all active pharmaceutical ingredients, it is prudent to attempt to identify and develop a list of pharmaceuticals that deserve more immediate attention. A preliminary list of the primary pharmaceuticals of concern was developed from an inventory of human and veterinary pharmaceuticals manufactured in Korea. For human pharmaceuticals, the net amount of active ingredient produced was determined and used to rank its potential to exist in the environment. According to both EMEA and US FDA guidelines, the amount of drug produced is important in the initial screening process. For veterinary pharmaceuticals, drug production amount along with its potential to enter the environment were considered in determining priority. Three antibiotics including roxithromycin, trimethoprim, and chloramphenicol were chosen from among the top ranked pharmaceuticals of interest for further environmental risk assessment. Sampling studies were conducted to measure the concentration levels of these pharmaceuticals at various sites in Korea. The study results