• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
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• pp.122-122
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• 2004

• Toxicological Research
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• 제29권4호
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• pp.221-227
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• 2013

Embryonic stem (ES) cells have potential for use in evaluation of developmental toxicity because they are generated in large numbers and differentiate into three germ layers following formation of embryoid bodies (EBs). In earlier study, embryonic stem cell test (EST) was established for assessment of the embryotoxic potential of compounds. Using EBs indicating the onset of differentiation of mouse ES cells, many toxicologists have refined the developmental toxicity of a variety of compounds. However, due to some limitation of the EST method resulting from species-specific differences between humans and mouse, it is an incomplete approach. In this regard, we examined the effects of several developmental toxic chemicals on formation of EBs using human ES cells. Although human ES cells are fastidious in culture and differentiation, we concluded that the relevancy of our experimental method is more accurate than that of EST using mouse ES cells. These types of studies could extend our understanding of how human ES cells could be used for monitoring developmental toxicity and its relevance in relation to its differentiation progress. In addition, this concept will be used as a model system for screening for developmental toxicity of various chemicals. This article might update new information about the usage of embryonic stem cells in the context of their possible ability in the toxicological fields.

• Toxicological Research
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• 제22권2호
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• pp.127-133
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• 2006

Recently, we have reported that the environmental pollutant 2-bromopropane (2-BP) induces a significant embryo-fetal developmental toxicity in rats. However, the cause of developmental toxicity and the relationship between maternal and developmental toxicities could not be elucidated because the developmental toxicity of 2-BP was observed only in the presence of maternal toxicity The in vitro teratogenicity study using whole embryo culture was carried out to understand the teratogenic properties and the possible mechanism of teratogenicity induced by 2-BP in rats. Rat embryos aged 9.5 days were cultured in vitro for 48 hrs at medium concentrations of 0, 1, 3, or 10 mg/ml of 2-BP. Embryos were evaluated for growth, differentiation, and morphological alterations at the end of the culture period. At 10 mg/ml, 2-BP caused a delay in the growth and differentiation of embryos and an increase in the incidence of morphological alterations, including altered yolk sac circulation, abnormal axial rotation, craniofacial hypoplasia, open neuropore, absent optic vesicle and kinked somites. At 3 mg/ml, only a delay in the growth and differentiation of embryos was observed. There were no adverse effects on embryonic growth and development at the concentration of 1 mg/ml. The results showed that the exposure of 2-BP to rat embryos results in a developmental delay and morphological alterations at dose levels of 3 mg/ml culture media or higher and that 2-BP can induce a direct developmental toxicity in rat embryos.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2005년도 춘계 국제심포지엄 및 학술대회
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• pp.130-130
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• 2005

• Toxicological Research
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• 제21권4호
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• pp.271-278
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• 2005

Reproductive and developmental toxicology is concerned with various physical or chemical agents interfering with fertility in both gender or normal growth of offsprings. Reproductive and developmental toxicology is rather a complex science, with many fields, i.e., various endpoints are involved and many different mechanisms of action. For that reason, diverse aspects must be considered when attempting to assess possible adverse health effects in the area of reproductive and developmental toxicology. The thalidomide tragedy made it clear to regulatory authorities around the world that systematic, comprehensive evaluation of the reproductive cycle was needed to adequately evaluate the potential of medicinal drugs to impair the process of reproduction or the development of embryos, fetuses, and children. International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) and U.S. Food and Drug Administration (FDA) developed a guideline to assess the reproductive and developmental toxicity. Also these guidelines have since been applied to the detection and regulation of environmental toxicants, food additives, and so on. Although it was hoped that testing procedures of guideline would be updated constantly to reflect the current state of the science in reproductive and developmental toxicology, it was not until this decade that regulatory guidelines and testing methods have been altered in a significant way. In this paper, we would like to present the recommended approaches and recent trends for improvement of testing guidelines or experimental methods in reproductive and developmental toxicology.

• Toxicological Research
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• 제34권2호
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• pp.111-125
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• 2018

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of $356mg/m^3$ (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions.

• 한국가스학회지
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• 제18권2호
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• pp.55-61
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• 2014

본 연구는 고무 화학제품의 제조에 연화제로 많이 사용되며 국제암연구소(IARC)에 발암추정물질(2A)로 등록되어 있는 Biphenyl에 대해 국내 취급사업장에 대한 작업환경 측정과 근로자 노출량 산출, 그리고 유해성에 따른 위험성을 결정하였다. 노출시나리오를 바탕으로 노출량 산출 결과는 각각 $1.0{\times}10^{-2}$, $4.2{\times}10^{-4}$, $7.0{\times}10^{-6}mg/m^3$이었으며, 위해성 분류에 따라 산출한 $RfC_{work}$는 발암성 0.21, 표적독성(경구) 2.13, 표적독성(흡입) 0.53, 발달독성 $0.31mg/m^3$으로 산출되었다. 유해성 및 노출평가의 결과를 바탕으로 한 위험성은 발암성 0.57, 비발암성(발달독성) 0.39로 도출되어, 1이하의 비교적 낮은 위험도로 나타났으나, Biphenyl은 일부 유해성이 확인되었으며 사용량이 많고 취급 부주의시 근로자에 직접 노출될 수 있어 취급근로자의 건강장해 예방을 위해 노출 감시가 필요한 물질로 판단되었다.

• 환경생물
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• 제33권4호
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• pp.425-432
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• 2015

도심의 인구증가에 따른 수질오염은 양서류의 개체군에 악영향을 준다. 급감하는 양서류 개체군을 보호 또는 복원하기 위해 도심하천에서 양서류 입식이 진행되고 있다. 본 연구는 탄천수계에서 양서류의 입식을 목표로 본류 및 지류의 수질의 생물학적 안전성을 검증하고자 하수처리장 유입수 및 하수처리장 배출수를 포함한 12개 지점의 표층수를 채수하여 무당개구리 포배기 배아에 처리하고 생존율, 기형발생률, 성장률 등을 분석하였다. 탄천 본류의 생물학적 안전성이 지류보다 높았으며, 상관분석 결과 무당개구리 배아의 생존율은 총용존고형물 (total dissolved solid), 탁도 (turbidity), 전기전도도 (electrical conductivity)와 음의 상관관계를 보인 반면, 기형발생율과 성장률은 양의 상관관계를 보였다. 본 연구는 양서류 입식에 앞서 양서류 배아의 발생에 미치는 수질의 생물학적 안전성을 검증한 첫 사례로서, 향후 이러한 방법이 도심하천에 대한 양서류 서식지 및 재입식지 선택에 있어 유용하리라 사료된다.

• Journal of Preventive Medicine and Public Health
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• 제40권2호
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• pp.155-161
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• 2007

Objectives : Bisphenol A diglycidyl ether (BADGE) is the major component in commercial liquid epoxy resins, which are manufactured by co-reacting bisphenol A with epichlorohydrin. This study was performed to show the developmental effects of prenatal and postnatal exposures to BADGE in male rat offspring. Methods : Mated female rats were divided into four groups, each containing 12 rats. The dosing solutions were prepared by thoroughly mixing BADGE in corn oil at the 0, 375, 1500 and 3000 mg/kg/day concentrations. Mated females were dosed once daily by oral gavage on gestation day (GD) 6 - 20 and postnatal day (PND) 0 - 21. Pregnant female dams were observed general symptoms and body weight. Also, male pups were observed the general symptoms, body weight, developmental parameters (e.g. anogenital distance, pina detachment, incisor eruption, nipple retention, eye opening, testis descent), organ pathologic changes and hormone levels of plasma. Results : Pregnant rats treated with BADGE died at a rate of about 70% in the 1500 mg/kg/day group and all rats treated with 3000 mg/kg/day died. Body weight, for male pups treated with doses of 375 mg/kg/day, was significantly lower than in the control group at PND 42, 56, and 63 (p<0.05). Evaluation of body characteristics including; separation of auricle, eruption of incisor, separation of eyelid, nipple retention, descent of testis, and separation of the prepuce in the BADGE treated group showed no difference in comparisons with the control group. AGD and adjusted AGD (mm/kg) for general developmental items in BADGE 375 mg/kg/day treated pups tended to be longer than in controls, however, these differences were not statistically significant. Relative weights of adrenal gland, lung (p<0.05), brain, epididymis, prostate, and testis (p<0.01) were heavier than in control in measures at PND 9 weeks. There were no significant changes in comparisons of histological findings of these organs. Loss of spermatids was observed in the seminiferous tubule at PND 9 weeks, but no weight changes were observed. The plasma estrogen levels were similar in the control and treatment groups at PND 3, 6 and 9 weeks. The plasma testosterone levels in the control group tended to increase with age. However, in the BADGE 375 mg/kg/day treated male pups it did not tend to increase. Conclusions : These findings suggest that BADGE is a chemical that has developmental effects consistent with it being an endocrine disruptor.

• 한국산학기술학회논문지
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• 제17권11호
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• pp.701-707
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• 2016

열대지역과 같은 특정지역에서 오염물질의 독성평가 시, 그 지역의 생태환경에 적합한 위해성평가를 위해서는 그 지방 고유의 생물에 대한 독성실험이 요구된다. 따라서 본 연구는 열대에서 분리한 열대 요각류 Nitocra sp.를 독성실험생물로 사용하기 위해 이들을 안정적으로 배양/유지하기 위한 최적배양환경조건과 해양생태독성평가 가능성을 조사하였다. 최적 배양환경요인으로 수온, 염분 및 먹이에 대해 조사하였으며 생태독성평가는 급성독성과 만성독성 실험으로 나누어 실시하였다. 최적배양조건 실험데이터의 통계분석을 위해 One-way ANOVA test를 실시하였다. 최적배양환경조건을 조사한 결과, Nitocra sp.는 수온 $29^{\circ}C$, 염분 24~34‰에서 먹이로 Tetraselmis suecica를 공급하였을 때, 비교적 빠른 발달기간과 높은 생존율을 보였다. 최적배양조건을 바탕으로 구리와 비소에 대한 독성평가를 실시한 결과, 구리와 비소의 각 노출농도에 따라 민감하게 잘 반응해서 반수치사농도 즉 $LC_{50}$값과 영향을 미치지 않는 농도인 NOEC값을 얻을 수 있었다. 만성독성시험 결과, 구리와 비소노출 모두, 성비와 생산력은 유의적인 차이가 없었던 반면, 발달기간과 생존율은 농도에 따라 반응을 보였기 때문에 종말점으로 사용이 가능한 것으로 나타났다. 본 연구를 종합해 보았을 때, 열대 요각류인 Nitocra sp.는 열대 해양독성물질 평가를 위한 생태독성실험생물로 사용이 가능할 것으로 판단되며 차후 다양한 독성물질의 평가에 활용이 기대된다.