There are growing concerns about human health effects of dioxin and dioxin like compounds such as polychlorinated dibenzo-p-dioxins (PCDDS), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs), Earlier studies recognized that 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) and structually related dioxin like compounds invoke a number of common toxic responses that are mediated through a high-affinity cytosolic receptor protein, the AhR. Based on studies that Indicate th pivotal role of AhR in mediating most, if not all, of the dioxin toxicity, TCDD equivalency factor (TEF) approach was developed. This approach allowed the expression of toxic potential of a complex mixture as one integrated parameter, the toxic equivalency (TEQ) value.

Methylmercury (MeHg) is a ubiquitous environmental toxicant that can be exposed to humans by ingestion of contaminated food including fish and bread. MeHg has been suggested to exert its toxicity through its high reactivity to thiols, generation of arachidonic acid and reactive oxygen species (ROS), and elevation of intracellular $Ca^{2+}$ levels (［$Ca^{2+}$］$_{i}$). However, the precise mechanism has not been fully defined. Here we show that phosphatidylcholine-specific phospholipase C (PC-PLC) is a critical pathway for MeHg-induced toxicity. MeHg activated the acidic form of sphingomyelinase (A-SMase) and group IV cytosolic phospholipase $A_2$ ($cPLA_2$) downstream of PC-PLC, but these enzymes as well as protein kinase C were not linked to MeHg's toxicity. Furthermore, MeHg produced ROS, which did not cause the toxicity. However, D6O9, an inhibitor of PC-PLC, significantly reversed the toxicity in a time- and dose-dependent manner in MDCK and SH-5YSY cells. Addition of EGTA to culture media resulted in partial decrease of [$Ca^{2+}$］$_{i}$ and partially blocked cell death. In contrast, D609 completely prevented cell death with parallel decreases in diacylglycerol and ［$Ca^{2+}$］$_{i}$. Together, our findings indicated that MeHg-induced toxicity was caused by elevation of ［$Ca^{2+}$]$_{i}$ through activation of PC-PLC. The toxicity was not attributable to the signaling pathways such as $cPLA_2$, A-SMase, and PKC, or to the generation of ROS.

The goal of this study is to develop a biomarker used in monitoring abnormal behaviors of Japanese medaka (Oryzias latipes) as a model organism caused by hazardous chemicals. Japanese medaka was treated by copper and fluoranthene of appropriate sublethal concentrations after starvation for 48 hr. In this study we investigated neural toxicity of copper and fluoranthene in Japanese medaka (Oryzias latipes) along with comparative analysis of corresponding behavioral responses. The untreated individuals showed common behavioral characteristics (i.e., smooth and linear movements). Locomotive activity of the fish was monitored using an image processing and automatic data acquisition system. When treated with copper (100 ppb), the fish showed shaking patterns more frequently. As the concentration of copper increased to 1,000 ppb, activity decreased, and the fish showed an erratic movement. The treated with fluoranthene, however, showed stopping and abrupt change of orientation (100 ppb), and severely reduced locomotive activity and enhanced surfacing activity (1,000 ppb).

Lake Texoma is located on the border of southern Oklahoma and northern Texas. It has 93,000 surface acres, and is a focus of the recreation, and farming industries in the region. There are potential stressors around the Lake Texoma watershed that may cause adverse ecological effects in the lake. System assimilative capacity (SAC) is the ability of abiotic and biotic processes to atteuniate the stressors. SAC Exceeded indicates potential of occuring adverse eco-effects. A number of representative chemical release sites and stressor sources in the surrounding watershed were characterized, and several impact sites having stressors sources, such as being near agriculture, landfills, housing areas, oil production fields and heavy use recreational activity, were selected for surface water, sediment, and groundwater monitoring. A paired reference site, having similar physical characteristics as its impact site, was also chosen based on its proximity to the impact site. Lake water samples were collected at locations identified as marina entrance, gasoline filling station, and boat dock at five marinas selected on Lake Texoma from September 1999 to December 2001. Paired water and sediment samples were also collected. Groundwater samples were collected at about 70 producing monitoring wells. Water quality parameters measured were inorganics (nitrate, nitrite, orthophosphate, ammonia, sulfate, and chloride), dissolved methane, total organic carbon (TOC) (or DOC), volatile organic compounds (VOCs) such as methyl tert-butyl ether (MTBE) and BTEX, and a suite of metals. Biotic communities were evaluated at impact and reference sites. Five basic components were measured; two terrestirial components (plants and bird comminitires) and three aquatic components (benthic inverbrates, litteral-zone fishes, ecosystem attribures). Potential impacts to these comminites were evaluated.

A dynamic multimedia model with 2-dimensional spatial resolution, POPsME (Persistent Organic Pollutants in Multimedia Environments), was evaluated by comparing predicted relative concentrations with those measured. A total of 12 polycyclic aromatic hydrocarbons (PAHs) were tested (phenanthrene, anthracene, fluoranthene, pyrene, chrysene, benz (a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, dibenz(a,h)anthracene, benzo(g,h,i)perylene, and indeno(1,2,3-c,d)pyrene). The concentrations were measured in air particulates, water (dissolved phase and suspended solids (ss)), soil, sediment, and leaves of Pinus koraiensis and Prunus serrulata at seven sites in the Seoul and neighboring area (150km x 150km), Korea.

Korea has different agricultural pattern from western countries and in particular, pesticide application has been performed by individual farmer. Such situations can result in pesticide exposure to worker at significant level. Thiophanate-methyl is a benzimidazole fungicide, which has been used for the wide range of fungal pathogens in field crops and fruits in Korea. It is insoluble In water, and is stable in neutral, aqueous solution at room temperature. It is a carbendazim precursor and systemic fungicide with protective and curative action. Toxicity to mammalian is low as ADI value is 0.08mg/kg b.w. (Tomlin 2000).

Through the five years analysis of monitoring data on pesticide residues from 1998 to 2002, current status on pesticide residues on commercial agricultural products in Seoul area was evaluated. The rate of over maximum residue limits(MRLs) has been decreased into 5.8% in 1998, 2.5% in 1999, 1.6% in 2000, 1.4% in 2001, and 1.5% in 2002 gradually, where as total sample numbers analyzed increased 1,300 in 1998, 4,200 in 1999, 5740 in 2000, 6,160 in 2001, and 5,440 in 2002 annually, The pesticide which frequently detected in samples were endosulfan, procymidone, chlorotalonil, vinclozolin, and chlorpyriphos and pesticide found over MRLs were procymidone, vinclozolin, endosulfan and etc.

It is well known that many pesticides possess hormonal activity, and affect the developments of wildlife and mammals including human. Currently, pyrethroid insecticides are in worldwide use to control in and outdoor pests, providing potential far environmental exposure. Hormonal activities of these pyrethroid insecticides, however, have been little studied, and the developmental effects of them were no reported. Therefore, we firstly examined the potential estrogenic activities of some pyrethroid insecticides (permethrin, cypermethrin, tetramethrin, deltamethrin, sumithrin, fenvalerate and bioallethrin) by immature rat uterotrophic assay, luciferase reporter gene assay and Calbindin-D$\sub$9k/ (CaBP-9k) gene expression assay. Uterine wet weights were increased by permethrin and the permethrin-induced weights were inhibited by ICI 182780 in the uterolrophic assay. On the other hand tetramethrin significantly reduced uterine and vaginal wet weights, and also inhibited the E2-induced weight increases at all doses tested. Cypermethrin and sumithrin had a tendency to increase uterine weights, although not statistically significant. Permethrin and cypermethrin dose-dependently increased the luciferase activity in reporter gene assay. Northern blot analysis showed that permethrin induced CaBP-9k mRNA expression whereas tetramethrin inhibted. Subsequent studies were conducted to investigate the possible developmental effects of four pyrethroid insecricides (permethrin, cypermethrin, sumithrin and teramethrin). Either diethlbestrol (DES) or 17${\beta}$ -estradiol (E2) was used as a reference control in this study. Pyrethroid insecticides were administered to Sprague Dawley rats via subcutaneous injection at 6 to 18 days of gestation or 1 to 5 days after birth. In utero treatment of permethrin (10mg/kg/day) in female rat resulted in significant increases in uterine and ovarian weights while significant decreases in serum E2 concentration, uterine and ovarian ER${\alpha}$ mRNA levels. Sumithrin and permethrin led to acceleration in vaginal opening of female rat, while delay in preputial separation of male after neonatal treatment. Anogenital distances of PND 18 were significantly reduced in sumthrin-treated, and permerhrin-treated male rats after neonatal treatment. All the pyrethroid insecticides tested caused significant increases in uterine weights on PND 18, while significant reductions in the first diestrus phase when neonataly treated. In addition, exposure to pyrethroids in neonatal period led to significant reduction in relative brain weight in female rat on PND 18, but its weight was recovered in diestrus phase. In summary, Our experimental data demonstrate the possibilities of developmental effects of pyrethroid insecticides via estrogenic or antiestrogenic activity.

It has been estimated that the equivalent of approximately $US 50 billion has been spent on research on the behavior and fate of pesticides in the environment since Rachel Carson published “Silent Spring” in 1962. Much of the resulting knowledge has been summarized explicitly in computer algorithms in a variety of empirical, deterministic, and probabilistic simulation models. These models describe and predict the transport, degradation and resultant concentrations of pesticides in various compartments of the environment during and after application. In many cases the known errors of model predictions are large. For this reason they are typically designed to be “conservative”, i.e., err on the side of over-prediction of concentrations in order to err on the side of safety. These predictions are then compared with toxicity data, from tests of the pesticide on a series of standard representative biota, including terrestrial and aquatic indicator species and higher animals (e.g., wildlife and humans). The models' predictions are good enough in some cases to provide screening of those compounds which are very unlikely to do harm, and to indicate those compounds which must be investigated further. If further investigation is indicated a more detailed (and therefore more complicated) model may be employed to give a better estimate, or field experiments may be required. A model may be used to explore “what if” questions leading to possible alternative pesticide usage patterns which give lower potential environmental concentrations and allowable exposures. We are currently at a maturing stage in this research where the knowledge base of pesticide behavior in the environmental is growing more slowly than in the past. However, innovative uses are being made of the explosion in available computer technology to use models to take ever more advantage of the knowledge we have. In this presentation, current developments in the state of the art as practiced in North America and Europe will be presented. Specifically, we will look at the efforts of the ‘Focus’ consortium in the European Union, and the ‘EMWG’ consortium in North America. These groups have been innovative in developing a process and mechanisms for discussion amongst academic, agriculture, industry and regulatory scientists, for consensus adoption of research advances into risk management methodology.

통합 순위 목록과 여러 가지 지표에 의거한 개별순위 목록을 비교한 결과, 전반적으로 통합 순위 목록과 잘 일치하고 있었다. 또한 각각의 개별 순위 목록은 세부적인 목적에 따라, 충분히 활용될 수 있다. 이 연구에서는 EDCs에 포함되는 농약에 대해서는 우선 순위 목록(Priority List 2)을 분리하여 제시하였다. 이미 이들 물질은 국책 사업으로 충분한 관심을 가지고 연구가 진행되고 있기 때문에 현재 사용중인 농약을 중심으로 우선 순위 목록(Priority List 1)을 작성하고 분석하였다. 자료의 결손이 크면 클 수록, 우선 순위 결과에 대한 불확실성도 커진다. 따라서 이들 자료의 결손을 합리적인 방법으로 채워나가는 것이 매우 시급한 과제이다 그러나 이들 자료의 결손이 채워지면 일부 농약의 경우는 순위가 변할 수 도 있지만, 크게 일정한 범위 밖으로는 이탈하지 않은 것으로 생각된다. 따라서 통합 우선 순위중 1∼20순위를 우선적으로 관심을 가지고 관리해야 할 물질(high priority)로 구분하고, 그 다음으로는 21∼40순위를 그 다음으로 관심을 가지고 관리해야할 물질(Medium priority)로서, 나머지 물질을 Low priority물질(41∼52순위)로 분류할 수 있다(Figure 2 참조). 여기서 Low는 이들 물질에 대한 위험성이 낮다는 것을 의미하는 것이 아니고 상대적으로 High 보다 낮다는 의미이다.

The registration of a pesticide for use in the gardens or a farmer's field requires assessment of the potential negative effects of that pesticide on human health. To anticipate how a pesticide might impact human health, laboratory animals such as mice and rats are exposed to varying dosages in their foods -from very minimal to extremely high levels. Toxicologists then evaluate the observable effect(s) of consuming known quantities of that specific pesticide on acute, subchronic, chronic, mutational, reproduction and neurological effects. Information gained from such test is evaluated by toxicologists and medical experts to determine potential human effects

During the past decade a reduced risk pesticide registration program has been in operation in the United States (Racke, 1992). The general principle of the reduced risk pesticide registration program in the U.S. is to give registration priority and accelerated approval to products with the most favorable characteristics as compared to currently available alternatives (EPA, 1997). The overall objective is to accelerate the introduction of these types of products so that marketplace choices rather than increased regulatory restrictions can lead to replacement of older products and technologies with newer ones. Under the program, pesticides classified as “reduced risk” products must meet several or all of the following criteria as compared with currently available alternatives: $\textbullet$ Reduced risks to human health $\textbullet$ Reduced risks to non-target organisms (e.g., fish, birds) $\textbullet$ Reduced potential for contamination of environmental resources (water, air, soil) $\textbullet$ Broadened adoption of integrated pest management

It's about three in the morning in a little farming village near the thriving metropolis of Sao Paulo in Brazil. Miguel, a 14-year-old schoolboy is fast asleep. Miguel was worried when he climbed into bed and drew the covers up. He was concerned about his homework - not that he had not done it. But rather what he had discovered while doing it. His homework was to interview his father, a tomato farmer, about how he uses pesticides and what precautions he takes to use them safely.

In the case of POPs (persistence organic. compounds) that have been release into environment, the goal of exposure assessment is to estimate the individual's total intake through various contact media and exposure pathways. The objective of this study was to estimate human exposure to environmental pollutants using a multimedia/multiroute scenario in an urban area of Korea.

A new technique is proposed for the determination of alkylphenols, chlorophenols and bisphenol A in tap water. The sample preparation consists of a solid phase extraction (SPE) of alkylphenols, chlorophenols and bisphenol A from a water sample with XAD-4 and subsequent conversion to isobutyloxycarbonyl (isoBOC) derivatives or tert.-butyldimethylsilyl (TBDMS) derivatives for sensitive analysis with the GC/MS-SIM mode. The recoveries were 86.6∼105.2 % (isoBOC derivatization) and 97.6∼484.5 % (TBDMS derivatization), respectively. The limit of quantitation of alkylphenols, chlorophenols and bisphenol A for SIM were 0.001∼0.050 $\mu\textrm{g}$/l (isoBOC derivatization) and 0.003∼0.050 $\mu\textrm{g}$/l (TBDMS derivatization). The SIM responses were linear with the correlation coefficient varying 0.9755∼0.9981 (isoBOC derivatization), and 0.9908∼0.9996 (TBDMS derivatization). The derivative methods and their application to tap water samples will be disscussed.

The objective of this study was to describe the distribution of metals concentrations in blood of adults who were not occupationally exposed in Korea. The blood samples were obtained between February and August 2001 from volunteer adults in urban area of Korea. 66 male participants were 46 (20-75) years of age and 74 female were 40 (20-69) years of age. The levels of metals in blood were observed the log-normal distribution, and we calculated geometric mean (GM) and geometric standard deviation (GSD). The GM levels of metals in blood of the men were 65.88$\mu\textrm{g}$/$\ell$, 1.01$\mu\textrm{g}$/$\ell$, 0.23$\mu\textrm{g}$/$\ell$ and 0.15$\mu\textrm{g}$/$\ell$, for Pb, Cr, Ni and Cd, respectively. The GM levels of the women were 58.49$\mu\textrm{g}$/$\ell$, 1.66$\mu\textrm{g}$/$\ell$, 0.30$\mu\textrm{g}$/$\ell$ and 0.10$\mu\textrm{g}$/$\ell$, for Pb, Cr, Ni and Cd, respectively. The levels of Pb-B and Cd-B were significantly higher non-smoker than smoker, whereas those of Cr-B and Ni-B were not different by smoking habit.

토양에 방치된 농업용 폐비닐은 거의 분해가 되지 않으며, 수분과 공기의 유통을 차단하고 토양 내 미생물들의 흐름을 막아 토양을 더욱 황폐화시키게 된다. 불법적인 소각 때는 산불의 위험에다 다이옥신, 염소 및 염화수소가스 등을 배출해 대기오염을 유발시킨다. 폐비닐을 열분해과정으로 처리하여 아주 작은 입자로 미분쇄하고 겔상태로 용융된 원료물질속으로 완전히 균일하게 혼합하여 골재로 활용하는 과정에서 가스상과 액상의 여러 가지 중간생성물질이 발생하게 되며, 농약의 살포에 의한 잔류농약 둥 인체에 유해가능한 요소들이 있을 수 있다. 본 연구에서는 개발공정이나 제품에서 인체에 영향을 미칠 수 있는 물질에 대하여 유해성을 평가하고 용응 겔 및 가스와 오일에 함유된 화학성분을 분석하였기에 보고하고자 한다 시험동물의 혈액생화학적 검사에서는 농업용 폐비닐물질 및 열분해 파생물질의 혈청 Cholesterol, 혈청 Alanine aminotranseferse와 Aspartate aminotransferse, Albumin 수치, LDH, Glucose, Uric acid, A/C 비 등의 생화학적 활성도를 측정한 결과들에서는 농업용 폐비닐물질을 투여한 시험군에서 나타난 결과와 비교하여 열분해 파생물질을 투여한 시험군에서 나타난 결과가 감소된 통계결과를 보였다. 이 결과들은 농업용 폐비닐물질을 투여한 시험군보다 열분해 파생물질을 투여한 시험군의 외부독성물질 투여에 의한 생체독성의 영향과 생체에 가해진 스트레스강도가 작았음을 의미하는 것이다. 잔류농약분석에서는 시료로부터 농약을 추출하는 용매추출과정, 시료추출물 중 공존하는 방해성분을 제거하는 정제과정, 폐비닐물질 및 열분해 파생물질 성분을 100mg/kg 이상군의 투여 후 시험동물의 부검시 모든 투여군에서 독성소견이 인정되지 않았다. 이와 같은 결과로 열분해 및 연소과정에서 발생하는 파생물질의 분석결과를 응용하여 대기오염을 방지하고 인체 유해물질을 차단하는 공해 방지 설계의 기초자료를 제안하고자 한다.

The majority of the SKYBIO will be used in the treatment of water in food processing plants, swimming pools and cooling towers, in the manufacture fabric softeners in Australia. Most will eventually be released into domestic sewage system as a consequence of product use. The SKYBIO is not readily biodegradable (0% over 28 days), and is expected to have a low partition coefficient and high water solubility (285 g/L), all indicating that the material would be mobile in both aquatic and terrestrial compartment. The PEC/PNEC ratio for the aquatic environment is 56. This value is significantly greater than 1, indicating an immediate concern to the aquatic compartment. However as a consequence of it's cationic character, the SKYBIO will be expected to associate to negatively charged organic matter in soil and sediment.

In Korea, the number of municipal and hazardous waste incinerators have been increasing since the 1980s. In addition, municipal waste incinerators (MWI) are almost always located in residential areas. Therefore, the human health risk caused by dioxin has become a growing public concern in Korea. In this report, we describe the results of study in which serum levels of PCDDs/PCDFs in a group of workers at the MWI were compared to those in a comparison group of community residents who had never worked at the MWI.

호소 퇴적물은 일반 하천에 비해, 입자성물질의 침강속도가 느리고 한번 퇴적된 물질의 교반이 잘 일어나지 않는 안정된 상태를 유지한다. 그러므로, 퇴적토질의 변화는 수질 변화의 추이를 대변해 줄 가능성이 높다. 소양호는 유역면적 2,703$\textrm{km}^2$, 유로연장 166.2km, 만수면적 70$\textrm{km}^2$으로 국내 최대 상수원 인공호이다. 본 연구에서는 담수 퇴적토의 오염 여부를 판단할 수 있는 생물학적 시험기법들을 활용하여 소양호의 표층 퇴적토질을 평가하였고, 주변잠재오염원의 분포와 비교하였다.

지금까지 국내에서는 해양과 하천, 호소 둥을 포함한 수생환경의 오염을 평가하기 위하여 COD 등 20여 가지의 일반수질항목을 조사하는 이화학적 분석 기술만을 사용하여 왔다 그러나 이러한 이화학적 분석 결과는 중금속이나 유기화합물 등 다양한 유해물질의 생태계에 대한 위해성을 정확하게 반영하는 데에 많은 한계가 있다 이에 따라 선진국에서는 생물을 이용하여 환경내 유해물질의 위해성을 평가할 수 있는 다양한 생물검정법을 개발하여 널리 이용하고 있다. 국내에서도 최근 여러 종류의 생물검정법을 개발하여 오염평가에 이용하고자하는 노력이 있어왔다. 이러한 노력의 일환으로 본 연구진은 다양한 국내산 생물을 이용하여 수생환경내 유해물질의 생물독성 평가기술을 개발하고있다. 본 연구에서는 기수역 어류인 황복의 독성평가 시험생물로서의 적합성을 평가하고 이 생물을 이용한 독성평가기술의 표준화를 위하여 다양한 유해 물질에 농도별로 실험 생물을 노출하는 일련의 급성 독성 평가를 수행하였다.

Bioassays using gametes of sea urchins are widely used in ecotoxicological assessments of marine environments. Since most of sea urchin species in Korean coastal water spawn from spring to autumn, bioassay with them during the winter is impossible. In the course of developing standard methods for bioassays with Korean species, we found a winter-spawning starfish, Asterias amurensis, Since reproductive mode of asteroids is similar to echinoids, the bioassay protocol for sea urchins could be applied similarly to the starfish. Here, we tested and determined several conditions for the acceptability of bioassay with A. amurensis. The least required time for formation of fertilization membrane of fertilized eggs to be easily distinguished from unfertilized ones was 60 min. The threshold of sperm to egg ratio that could make acceptable fertilization rates in controls was 3000. The allowed time for manipulation of sperm after dilution in seawater was at most 3 hr. The optimal exposure time of sperms when the response against toxicant solution was relatively stable was in the range of 20-60 min. The tolerance range of sperms to the salinity of test solution was 26-38 psu. The sensitivity of A. amurensis sperm was intermediate among marine organisms commonly used in aquatic toxicity tests. The sperm bioassay with A. amurensis can be satisfactorily applied to toxicity assessments of marine environments.

Comet assay is a potential monitoring tool because DNA strand breakage may be produced by a wide range of agents. The comet assay, also called the single-cell gell electrophoresis (SCGE) assay, is rapid and sensitive method for the detection of DNA damage in cells. This study was performed for the identification of DNA damage in the cells from flounders and clams exposed to PAHs. As a control experiments, flounder and clam cells were exposed to $H_2O$$_2$. The cells exposed to $H_2O$$_2$ were displayed a typical nuclei movement DNA damage of cells were significantly increased when the isolated cells from the blood of flounders and the tissue of clams were in vitro exposed to the different concentrations (5, 10, 50, 100 ppb) of five kinds of PAHs (benzo[a]pyrene, pyrene, fluoranthene, anthrancene, and phenanthrene). For the in vivo test, flounders and clams were exposed to the different concentrations of BaP for 4 days. The results showed that DNA strand breakage was effected by the concentration of BaP and the duration of exposure. In high concentration of BaP, the mean tail lengths of nuclei was longer than it In low concentration, while the mean size of head DNA decreased. In this research, both in vitro and in vivo genotoxicity of PAHs could be biomonitored by the comet assay. Especially, clams and flounders seem to be useful as materials for monitoring genotoxic damage by comet assay.

In Korea, 1, 357 tonnes of benzoyl peroxide was produced as a white granule with purities ranging 22 to 95％ in 2001. 75% of benzoyl peroxide is mainly used in the manufacture of expandable styrene polymer and other resins as initiators of polymerization and also been used in the treatment of acne vulgaris and the medical product contains mainly 5 to 10% of it. A very small portion of benzoyl Peroxide is used as flour bleaching agent, Potential human exposure from workplaces is expected to be negligible because this chemical is produced in closed system in only one company in Korea and when a production facility monitors its workplace for the worker exposure annually, the concentration of airborne aerosols at the personal sampling has been less than 1mg/㎥.

The Eco-2 Project presents a win-win strategy for the environment and for the economy (ECO-2 is an abbreviation of Ecology and Economy), The project was initiated by the Korean Ministry of the Environment to promote the development of an environmental industry technology as a means of driving national development in this sector. Our project work belongs to the category of integrated environment management technology, and is described as a development and utilization of risk assessment and analysis system for integrated environmental management in municipal and industrial areas. The goal of our project is to develop available system software in health and ecological risk assessment and to offer it as Decision Support System (DSS) to aid the effective management of environmental risk in municipal and industrial areas in Korea.

환경 중 오염물질 중에는 발암물질로 판명된 물질이 수 종 포함되어 있으며, 여러 선진국에서는 방대한 연구를 통하여 오염수준을 파악하고, 위해성 평가에 근거한 관리대책을 펴가고 있다. 하지만 여러 선진국에서는 이러한 인체 위해성 평가결과만을 사용하여 환경 정책을 결정하기에는 그 결과가 반영하는 시야(scope)가 협소함을 느끼고, 다양한 측면(생태, 사회ㆍ경제, 삶의 질 등)을 함께 고려해야한다고 강조하고 있다. 이 중 인체 위해성 평가 결과를 경제성 평가와 더불어 화폐가치화 하는 연구는 정책 결정자들과 일반인들에게 위해성 평가 결과를 쉽게 인지시키고, 비교를 더욱 편이하게 할 수 있다는 장점이 있으며, 현재 많은 연구가 진행되고 있다.

In Korea, there is no CRA studies and has not well known CRA and not well established their methodologies. Therefore, objectives of this study is to establish the framework of CRA consisting of health risk, economic risk and perceived risk and the detail methodologies of three main component of estimating and comparing those risks for on the three environmental problems of air pollution, indoor air pollution and drinking water contamination which being subjective to the eight sub-problems of hazardous ai. pollutants (HAPs), regulated pollutants (representative as PM10) and Dioxins (PCDDS/ PCDFs) in air pollution, and indoor ai. pollutants (IAPs) and Radon in indoor air pollution, and drinking water pollutants (DWPs), disinfection-by- products(DBPs) and radionuclides in drinking water contamination in Seoul, Korea. And then, their problems set priorities by individual and integrated risk. As a results, ranking of health risk were the following order of indoor air pollution, air pollution and then drinking water contamination, in three environmental problems and of radon, PM10, IAPs, HAPs, DWPs, Dioxins, DBPs, and then radionuclides in eight sub-problems. And that of economic risk were the same order. In the contrary, ranking of perceived risk were the following order of air pollution, drinking water contamination, and then indoor air pollution, and of HAPs, Dioxins, radionuclides, PM10, DWPs, IAPs, Radon and then DBPs.

An initial study has been conducted with Korea Institute of Geoscience and Mineral resources and National Institute of Environment Research to evaluate the distribution of radon levels and their risk levels of groundwater in Korea. Probability distribution of 616 samples was log-normal one with 1,867pCi/L as arithmetic value, 920pCi/L as median and 40,010pCi/L as maximum during iou. years(1999-2002). In addition, 10% of total samples are in excess of 4,000pCi/L, 20% in excess of 2,700pCi/L, and 30% in excess of 1,700pCi/L, and 15 samples exceeds 10,000pCi/L. Total samples are grouped into 10 areas and 5 rocks unit, and difference of concentrations among areas and rocks are statistically significant(respectively, p<0.0001). The highest area is Daejeon located in ogcheon metamorphic rocks and granitic rocks, and most of all sites with high concentration sites are located in granitic rocks. The lowest area is Jeju located in volcanic rocks. We have estimated excess cancer risks of radon based on these data. To estimate risks, first of all, use patterns of groundwater are categorized with 6 groups: for drinking, household, farming, washing cars, raising stock, and others. We considered risk only for drinking water and household water because radon is rapidly dispersed before it of other use reach human respiratory organs. We select 565 samples for risk analysis, and applied unit risk which is 6.6210-7 per pCi/L to be recommended by NAS committee. Unit risk was derived from considering radon ingestion and radon inhalation from water use. When estimating risk, we analyzed PDF of concentration and represented risk as 50 and 95 percentile values to consider uncertainty with Monte-Carlo simulation. It results in 10-4 level of their excess cancer risk and in 10-2 level in some areas with high concentration of radon. It must be monitor periodically and take adequate actions in these risky sites. We recommend that it needs to take more survey and finally set guideline for radon regulation in groundwater.

전국 주요 산단 지역에서 현재 유통되고 있는 화학물질의 스크리닝 수준에서의 생태 위해성 평가를 수행하고 체계적인 위해도 분석 시스템을 구축하기 위한 생태 위해성 예측 모형을 개발하였으며, 모형의 분석과 모니터링을 통하여 모형을 검증하고 수정, 보완하는 연구를 수행하였다. 전국 118개 공단중에서 10개의 산단 (시화반월, 전주, 대전, 대구, 청주, 울산, 구미, 여천, 대구 성서, 신평장림공단)을 대상 지역으로 하였고 이들 공단에서 사용되고 있는 약 1900 여종의 화학물질들의 물리화학적 특성 자료와 생태 독성값의 문헌치, 추정치를 포함한 database를 구축하였다. 모형 결과의 정확성을 높이기 위해서는 배출량의 정확한 산출이 필요하므로 본 연구에서는 유럽의 우선순위 선정 프로그램인 EURAM의 방법에 근거하여 화학물질의 산업 및 용도별 분류로부터 각각의 배출계수를 적용하여 사용량을 배출량으로 산출하는 방법을 이용하였다 구축된 database를 활용하여 산단별, 화학물질별 생태 위해도를 비교한 결과 어류 급성의 위해도는 울산>여천>대전의 순이었고, 물벼룩 급성의 위해도는 울산>여천>시화반월>청주의 순이었다. 울산을 제외한 대부분의 지역의 위해도는 1이하로 나타나 스크리닝 수준에서의 오염은 우려할 정도가 아닌 것으로 나타났다. 생태 위해성 프로그램의 validation을 위하여 대구 지역을 대상으로 문헌치 독성값을 위주로 하는 RQ가 0.1 이상인 물질들의 검출 가능성과 화학물질들의 특성을 파악하였고, Butylacrylate, Xylene, N,N-Dimethylformamlde, 1,2-Benzenedicarboxylic acid dibutylester, 2-Amino-4-methylphenol, Toluene, 2,2-Oxybisethanol의 7가지 물질들을 분석대상물질로 선정하여 분석을 수행할 예정이다. 본 연구에서는 분석 대상 지역을 확대하여 모형의 신뢰성과 타당성을 확인하고 모형을 수정, 보완하여 생태 위해성 예측 프로그램의 신뢰도를 높이고자 한다.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a prototype of many halogenated aromatic hydrocarbons, is a ubiquitous, persistent environmental contaminant and displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic and tumor promoter. In this study, we investigated the tumor promotion effect of TCDD on the two-stage skin chemical carcinogenesis using hairless mouse (SKH1). We induced papillomas after treatment with N-methyl -N'-nitro-N-nitorsoguanidine (MNNG) as a initiator and TCDD as a promoter for 30 weeks. We found that the incidence or multiplicity of papillomas and hyperplastic nodules was maximally induced at MNNG-TCDD group compare to control, MNNG, and TCDD alone. These results suggesting that TCDD can acts as a potent promoter in the hairless mouse skin. In addition, we used cDNA microarray to detect the differential gene expression in normal, tumor surrounding, and tumor regions induced in hairless mouse skin by MNNG plus TCDD protocol. We found that 49 and 42 genes out of 5,592 genes associated with protein synthesis, cell organization, lipid transport and oxidative stress in tumor and surrounding regions were up- or down- regulated two fold or more, respectively. We are currently investigating how these genes play a role in TCDD-mediated chemical carcinogenesis.

With the introduction of DNA microarrays, a high throughput analysis of gene expression is now possible as a replacement to the traditional time-consuming Southern-blot analysis. This cDNA microarray should be ahighly favored technology in the area of molecular toxicology or analysis of environmental stresses.In this study, therefore, we developed a novel cDNA microarray for analyzing stress-specific responses in japanese Medaka fish. In the design and fabrication of this stress specific functional cDNA microarray, 123 different genes in Medaka fish were selected from eighteen different stress responsive groups and spotted on a 25${\times}$75 mm glass surface. After exposure of the fish to bisphenol A which is the one of the well-known endocrine disrupting chemicals (EDCs), over 1 or 10 days, the responses of the DNA chip were found to show distinct expression patterns according to the mode of toxic actions from environmental toxicants. As a results, they showed specific gene expression pattern to bisphenol A, additionally, the chemical spesific biomarkers could be suggested based on the chip analysis data. Therefore, this chip can be used to monitor stress responses of unknown and/or known toxic chemicals using Medaka fish and may be used for the further development of biomarkers by utilizing the gene expression patterns for known contaminants.

There are many synthetic chemicals, such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), used in chemical reaction processes in industry. The establishment of toxicity and detection of synthetic chemicals that may pose a genetic hazard in our enviornment is subjects of great concern at present DEHP, a ubiquitous phthalate plasticizer, induces a wide range of developmental and reproductive toxicities in mammals. DEHP belongs to the large diverse class of peroxisome proliferator compounds, which include herbicides, hypolipidemic drugs. DBP is a plasticizer used to products containing nitrocellulose, polyvinyl acetate, and polyvinyl chloride such as food wraps and blood bags. DBP is also used in cosmetics as a solvent and fixative for perfumes, a suspension agent for solids, an antifoamer, a skin emollient, and hair spray The present study was performed to examine patterns of gene expression in MCF-7 cells following DEHP and DBP exposure. Changes in gene expression were determined by microarray analysis using KISTCHIP-400 including 401 endocrine related genes based on public database and research papers. Of the genes analysis, we determined that genes detected by array showed a 2-fold or greater change in their expression level(increase or decrease). The results of this study demonstrate that a number of genes were differentially expressed in MCF-7 cells but these changes were not significant. Therefore, we keep going this study using microarray analysis and future studies will examine changes of gene expression on time-course and does treatment in variable cell lines.

Phthalocyanine, a water soluble porphyrin derivative and dye, is known to inhibit the mutagenic and carcinogenic actions of compounds having polycyclic structures, e.g. heterocyclic amines. There is evidence that this adsorbent effect shows by a complex formation between the porphyrin-like structure of phthalocyanine and the planar molecular surfaces of theses compounds. That phthalocyanine can form an insoluble material when mixed with chitosan, a polyglucosamine, and that the solid chitosan-phthalocyanine, named Eco-Blue, thus prepared can efficiently adsorb polycyclic mutagenic compounds. The adsorption was experimented by UV/VIS spectrometry. The adsorbent effects of mutagens and carcinogens was identified by Gas chromatography (GC) and Ames Test. The adsorbed polycyclic mutagens were elutable with buffer, but only to small extents. Chitosan-phthalocyanine may be expected to be useful as an adsorbent against polycyclic mutagens and carcinogens.

Methylmercury is known to have devastating effects on the mammalian nervous system. When human neuroblastoma SH-SY5Y cells were treated with methylmercury at sublethal concentrations (6.25 uM), up-regulated genes (39) ＆ down-regulated genes (19) were identified by human 8k cDNA microarray. These genes are related with microtubule process, signal transduction pathway and cell death (apoptosis), Apoptosis-associated genes, HSP70, CDK inhibitor 1, FOS-like antigen were up-regulated and microtubule related genes like villin and dynein down-regultaed. To confirm the presence of apoptosis in cultured SH-SY5Y cells treated 6.25 and 1 uM methylmercury, we applied Annexin V-FITC assay followed by flow cytometric measurements after 6 and 24h. Studies on transcriptional and molecular effect by methylmercury may provide an insight into the neurotoxic effects of methylmercury in human neuronal cells and a possibility to develop more efficient and exact monitoring system of heavy metals as ubiquitous environmental pollutants.

Methylmercury (MeHg) is a well-known neurotoxicant that causes severe damage to the central nervous system in humans. Many reports have shown that MeHg is poisonous to human body through contaminated foods and has released into the environment. Despite many studies on the pathogenesis of MeHg-induced central neuropathy, no useful mechanism of toxicity has been established so far. In this study, suppressive subtractive hybridization (SSH) was performed to identify differentially expressed genes on human neuroblastoma cell line, SH-SY5Y treated with DMSO and MeHg (6.25 uM) for 6 hr. Differentially expressed cDNA clones were sequenced and were screened by dot blot to eliminate false positive clones. 13 of 35 screened genes were confirmed using real time RT-PCR. These genes include EB1,90-kDa heat-shock protein, chromosome condensation-related SMC-associated protein and brain peptide Al, etc. Analysis of these genes may provide an insight into the neurotoxic effects of MeHg in human neuronal cells and a possibility to develop more efficient and exact monitoring system of heavy metals as ubiquitous environmental pollutants.

Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this Is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to ＋64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. Here, we developed luciferase reporter gene assay system to detect SXR-based CYP 3A4 transcriptional activity. We have used CYP3A4-Luc plasmid that contains proximal promoter of human CYP3A4 gene upstream of the luciferase gene. We did transient transfection of 3A4-luciferase gene and SXR. In the HepG2 cells transfected with CYP3A4-Luc, when rifampicin treatment was combined with histone deacetylase inhibitor (HDAC Inhibitor), such as Trichostatin A, Hc-toxin and IN 2001 of the luciferase activity was induced 10-20 fold over control.

Exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a variety of biological and toxicology effects, most of which are mediated by aryl hydrocarbon receptor (AhR). The ligand-bound AhR as a heterodimer with AhR nuclear translocator (ARNT) binds to its specific DNA recognition site, the dioxin-responsive element (DRE), and it results in increased transcription of CYP1A1 gene. Retinoic acid (RA) regulates the transcription of various genes for several essential functions through binding to two classes of nuclear receptors, the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Constitutive androstane receptor (CAR) also regulates the transcription of gene. In this study, we have examined how RAR, RXR and CAR regulated CYP1A1 in rainbow trout hepatoma cell (RTH 149) using luciferase reporter gene assay system. We did transient transfection with CYP1A1 luciferase reporter gene and treated with TCDD, all-trans RA, 9-cis RA and phenobarbital. Treatment of all-trans RA, 9-cis RA or phenobarbital decreased the TCDD induced transcription of CYP1A1. When we did transient cotransfection with CYP1A1 luciferase reporter gene and RXR, as increase of RXR concentration, the TCDD induced transcription of CYP1A1 was decreased. Transfection with CAR also decreased the TCDD induced transcription of CYP1A1 in RTH 149 cells.

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER Positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47B and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

We have studied the mechanism of action of TCDD on CYP1A1 promoter activity in both Hepa Ⅰ and MCF-7 cells using transient transfection system with p1A1-Luc reporter gene. When HDAC inhibitors, such as trichostatin A, HC toxin and a novel HDAC inhibitor, IN2001 were cotreated with TCDD to the cells transfected with plAt-Luc reporter gene, the basal promoter activity of CYP1A1 was increased by HBAC inhibitors. Also, in MCF-7 human breast cancer cells, HDAC inhibitors, such as IN2001 and trichostatin A increased the basal activity of CYP1A1 promoter but TCDD stimulated CYP1A1 promoter activity was not changed by HDAC inhibitors. And, in stably-transfected Hepa Ⅰ cells with p1A1-Luc, HDAC inhibitors increased the basal promoter activity only Also, we have investigated the effects of HDAC inhibitors on the human breast and prostate cancer cells in terms of cell proliferation and apoptosis based on SRB assay. IN2001 as well as trichostatin A inhibited the MCF-7, MDA-MB-231, MDA-MB-468, T47D, ZR75-1, PC3 cell growth dose-dependently. The growth inhibition of these cells with HDAC inhibitors was associated with profound morphological change, which suggests the HDAC inhibitors induced apoptosis of cells. The result of cell cycle analysis after 24h exposure of IN2001 showed G2/M cell cycle arrest in MCF-7 cells and apoptosis in T47D and MDA-MB-231 cells.

1.연구목적 : Cr $O_3$은 금속 도금용, 페인트 둥에 많이 사용되며 독성이 강하여 그동안 근로자 건강장해 및 직업병 사례가 많이 발생하였다. 그러나 산화크롬의 흡입에 의한 연구자료는 매우 부족하다. 이에 흡입챔버를 이용 Rats에 흡입노출을 통하여 유해성을 평가하고 각 장기에 흡수되는 크롬의 농도평가와 회복기간에 따라 각 장기별로 흡수된 크롬의 소실속도 둥을 연구하였으며 더불어 회복기간과 제거율의 상관관계 및 체내 반감기 등을 연구하였다. 2. 연구방법 : Cr $O_3$를 폐내 침착율 및 흡수율이 높은 0.5～5$\mu\textrm{m}$ 크기의 aerosol형태로 SD Rats 수컷에 전신폭로 하였다. 노출농도는 0.00, 0.20, 0.50, 1.25mg/㎥(Cr)으로 하여 1일 6시간, 주 5일, 13주간 반복 노출하였고 회복군은 시험물질 종료일을 기준으로 2주, 8주 경과 후 조직장기와 전혈, 혈장 및 적혈구내, 뇨 중 각각의 크롬농도를 분석하였으며 혈액 및 혈액 생화학적 검사도 병행하였다 3. 연구결과 : 혈액검사에서 0.20, 0.50 mg/㎥ 농도군 실험동물의 RBC와 HGB, HCT 둥은 감소의 경향을 보였으나 농도 의존적이지는 않았다. 신장의 절대중량은 대조군에 비해 유의하게 (p<0.05) 감소하고 폐장의 경우는 대조군에 비해 유의한(p<0.05) 절대중량 증가를 보였다 시험물질 노출 후 혈액 중 전혈, 혈장, 적혈구의 회복기간(x)별 크롬농도(y)의 소실속도 상관계수 (노출농도 0.50mg/㎥군의 경우)는 y = 66.51 $e^{0.057}$x/, y = 67.2 $e^{0.101}$x/, y = 70.01 $e^{0.030}$x/, 반감기는 12.0, 6.86, 23.0 일이고 폐장, 간장, 신장의 회복기간(x)별 크롬농도(y)의 소실속도 상관계수 (노출농도 0.50 mg/㎥군의 경우)는 y = 1808 $e^{0.004}$93x/, y = 12.02 $e^{0.029}$7x/, y = 67.61 $e^{0.029}$2x/ 반감기는 140.6, 23.3, 23.7 일로 평가되었다. 4. 고찰 : 실험동물의 전혈, 혈청, 뇨에서의 크롬농도와 시험물질 노출농도는 밀접한 상관을 가졌으나 농도에 정비례하지는 않았다. 뇨 중 흡수된 크롬의 경우 회복기간 초기 (12시간 내)에 대부분 배설이 일어나는 것으로 나타났다. 폐장이 간장, 신장 등 다른 장기에 비해 높은 축적량을 보였으며 축적된 크롬농도가 높을수록 크롬의 소실속도는 현저히 저하하는 경향을 보였다. 노출농도가 높을수록 각 장기조직 내 크롬의 소실속도 (clearance)는 크게 감소경향이 있었으며 이는 체내 과부하시 자정작용이 감소하는 것으로 판단되었다. 본 연구 결과 SD rat를 이용 반복흡입노출의 경우 생체의 무유해영향농도 (NOAEL)는 0.2mg/㎥이하이며 발암물질을 감안하여 안전계수를 100으로 할 경우 사람에 대한 NOAEL은 0.002mg/㎥이하로 판단되었다. 특히 호흡기와 폐장에 강한 유해성을 나타내는 것으로 확인되었다. 것으로 확인되었다.