• 한국발생생물학회지:발생과생식
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• 제27권4호
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• pp.213-220
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• 2023

Previously, we showed that a chronic-low-dose nonylphenol (NP) exposure resulted in histological changes with sexually dimorphic pattern in rat adrenal glands. We hypothesized that such structural changes are closely related to the hormonal secretory patterns. To test this hypothesis, we developed the short-term adrenal incubation method, and measured the levels of catecholamines and cortical steroids using the high-performance liquid chromatography with electrochemical detection (HPLC-ECD) and specific enzyme-linked immunosorbent assay, respectively. The norepinephrine (NE) levels in media from NP-treated female adrenal, except 100 pM NP, were significantly increased [control (CTL) vs 1 nM NP, p<0.001; vs 10 nM NP, p<0.05; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.01]. The NE secretion from male adrenal was higher when treated with 100 nM and 1 µM NP (CTL vs 100 nM NP, p<0.05; vs 1 µM NP, p<0.05, respectively). The aldosterone level in the female adrenal media treated with 100 pM NP was significantly decreased, on the other hand, that of media treated with 10 nM NP was significantly increased (CTL vs 100 pM NP, p<0.05; vs 10 nM NP, p<0.01). In male adrenal media, the aldosterone levels of 10 nM, 100 nM and 1 µM NP-treated media were significantly declined (CTL vs 10 nM NP, p<0.001; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.001). These results showed the NP treatment altered secretory pattern of aldosterone from adrenals of both sexes, showing sexual dimorphism. It may be helpful for understanding possible adrenal pathophysiology, and endocrine disrupting chemicals-related sexually dimorphic phenomena in adrenals.

• 한국발생생물학회지:발생과생식
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• 제12권3호
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• pp.251-259
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• 2008

플라스틱 가소제인 di(2-ethylhexyl)phthalate (DEHP)는 매우 잘 알려진 내분비계 장애물질(endocrine disrupting chemicals; EDCs) 중 하나로, 수컷 설취류와 인간의 생식과 발생 과정에 있어 강력한 항안드로겐성 작용을 하는 것으로 알려져 있다. 본 연구는 사춘기 이전에 수컷 흰쥐를 DEHP에 노출시킴으로써 부속 성기관의 성숙 과정 동안 나타나는 변화를 조사한 것이다. 결과로, DEHP 투여에 의한 체중, 혈중 T 수준, 저정낭과 전립선을 제외한 조직의 무게는 대조군과 비교하여 유의적인 변화가 없었다. 저정낭의 경우, 고농도(200 mg/kg)의 DEHP를 처리한 투여군의 무게가 대조군에 비해 유의하게 감소하였으며(p<0.05), 전립선의 경우, 저농도(20 mg/kg)와 고농도의 DEHP를 처리한 모든 투여군에서 대조군에 비해 유의한 무게의 감소를 나타내었다(p<0.05). 조직학적 연구 결과, DEHP 투여군의 저정낭은 대조군에 비해 점막층의 면적이 감소하였다. 또한, 전립선의 경우 대조군에서는 분비상피세포들이 입방형인데 비해 DEHP 투여군에서는 위중층상피세포 형태가 관찰되었다. 정량적 RT-PCR 연구에서, 저정낭에서의 ER-$\alpha$ 발현은 고농도 DEHP 투여에 의해 유의한 발현증가가 나타났으며(p<0.05), ER-$\beta$의 경우 저농도 DEHP 투여에 의해 유의한 발현 감소가 나타났다(p<0.05). 전립선에서의 ER-$\beta$ 수준은 저농도 DEHP 투여에 의해 유의하게 감소하나(p<0.05), 고농도 DEHP 투여에 의해서는 유의한 발현증가가 나타났다(p<0.01). 그러나 AR 발현의 경우, 저정낭과 전립선 모두에서 DEHP에 의해 유의한 차이가 나타나지않았다. 결론적으로, 본 연구는 (i) DEHP의 유해한 작용이 사춘기 이전 시기의 성적인 성숙을 교란할 수 있으며, (ii) 저정낭과 전립선이 사춘기 이전 시기 DEHP 노출에 대한 민감한 표적이 될 수 있고, (iii) DEHP의 유해한 작용이 ER과 연관된 기작을 통해 매개될 수 있음을 시사한다.

• 환경생물
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• 제22권
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• pp.47-53
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• 2004

광양만과 섬진강 하구에서 내분비계장애물질의 일종인 프탈레이트 화합물의 분포 특성을 국내에서는 처음으로 연구하였다. Di-butyl phthalate (DBP)와 di-2-ethylhexyl phthalate(DBHP)를 비롯한 9종의 프탈레이트 및 adipate를 분석 대상으로 선정했다. DBP와 DEHP가 가장 높은 빈도와 농도로 검출되었으며, 다른 화합물은 거의 검출되지 않았거나 검출한계 이하였다 광양만 표층퇴적물에서 DBP와 DEHP의 평균 농도는 각각 33.8 ng g$^{-1}$와 67.4 ng g$^{-1}$이었다. 섬진강 하구에서는 표층수에서 DBP가 62.7∼333.8 ng L$^{-1}$농도 범위로 검출되었으며, DEHP는 25.6∼l16.1 ng L$^{-1}$ 범위로 검출되었다. 섬진강 및 하구 표층 퇴적물 시료 중의 DBP의 농도는 9.1∼149.3 ng g$^{-1}$, DEHP는 46.3∼156.3 ng g$^{-1}$으로 검출되었다. 광양만에서 DBP와 DEHP는 공단 일대와 생활 하수가 배출되는 하천 주변부에서 높은 농도를 보였으며, 광양만 외해로 갈수록 농도가 적어지는 경향을 보였다. 섬진강에서는 안쪽에서 높은 농도를 보이다가 서서히 감소하지만 일부 정점에서 높은 농도로 검출되었다. 이러한 분포 경향은 하천을 통해 광양만으로 DBP와 DEHP가 유입되고 있음을 시사한다.

• 한국습지학회지
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• 제9권1호
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• pp.79-89
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• 2007

This paper provides a comprehensive overview of the present status of several environmental problems caused by emerging toxic substances such as persistent organic pollutants (POPs), endocrine disrupting chemicals (EDCs), and arsenic in various environmental media in Vietnam. Monitoring data reported during the 1990s demonstrated elevated contamination of DDTs in most of these compartments in Vietnam. Studies in frame of the Asia-Pacific Mussel Watch Program revealed that fish, mussels and resident birds from Vietnam contained higher concentrations of DDTs as compared to other countries in region, suggesting the role of Vietnamese environment as a significant emission source of DDT in the Southeast Asian region. The estimated dietary intakes of PCBs and DDTs for Vietnamese were relatively high among Asian developing countries, suggesting potential risk for humans posed by thesechemicals. Widespread contamination of some endocrine active compounds such as alkylphenols and phthalates was observed at various sites along the coasts of northern and middle Vietnam. The presence of significant source of bisphenol-A along Red River estuary was revealed with the concentrations comparable to those reported for developed nations. A case study on seasonal variation of alkylphenols and phthalates in surface water of river delta and estuary of north and middle Vietnam indicated the differences in distribution of these compounds between dry and rainy seasons. Higher concentrations of alkylphenols and phthalates were found in dry season in estuary; while the contrasting pattern was observed in the river delta, showing elevated residues in rainy season. This result suggests the different behavior of alkylphenols and phthalates in river delta and coastal environment. From ecotoxicological perspectives, concentrations of bis-phenol A and di(2-ethylhexyl)phthalates [DEHP] in surface water from some locations in Vietnam exceeded the guideline values for Ecotoxicological Effects and the Environmental Risk Limit, respectively, suggesting potential for toxic implications on aquatic wildlife. Widespread and elevated arsenic contamination was discovered inour recent surveys in groundwater in a large area of suburban areas of Hanoi city, the capital of Vietnam. The most recent investigation in 4 villages showed about more than 50 % of groundwater samples contained As concentrations exceeding 50 g/L (the WHO and Vietnamese standard). In particular, in Son Dong villages, 58 % of samples analyzed contained As concentrations higher than 200 g/L. Good correlations were found in As concentrations in water and hair and urine of peoples in corresponding families, suggesting the chronic exposure to As by people living in As-contaminated ground water areas. In Son Dong village, As levels in hair (mean: 1.7 mg/kg dry wt) and urine (g/g creatinine) exceeding the reference values recommended by WHO, suggesting potential for human risk posed by long term accumulation of As in human body. Future studies should be focused on the time trends of POPs and EDCs in biota in Vietnam in order to predict future trend of contamination and to reveal new clues for understanding possible toxic impacts on aquatic organisms. The issues of arsenic contamination in groundwater and their chronic toxic implications on human health should be systematically investigated in the future.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.148-148
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• 2003

This study is to investigate the environmental levels and trend of dioxins, which was the 3$\^$rd/ year of environmental monitoring research for endocrine disrupting chemicals since 1999. Total 282 samples were analyzed from 115 sites including 26 sites of airs, 43 sites of waters, 11 sites of sediments and 35 sites of soil, which were the same as those of investigated sites in 2000. Sampling period was from June 2001 to June 2002. Target chemicals were seventeen species of 2,3,7,8-chlorine-substituted PCDD and PCDF congeners and were analyzed by the standard methods, established by National Institute Environmental Research (NIER). The average concentration of dioxins in air decreased from 0.324 pg-TEQ/N㎥ in 2000 to 0.287 pg-TEQ/N㎥ in 2001, and those in water and soil were 0.073pg-TEQ/L and 1.703pg-TEQ/dry g, respectively, which was the less values detected in 2000. In sediment, however, the value was 0.086pg-TEQ/dry g, which was the increase from the value of the year 2000. The concentration range of dioxins in air for 26 sites in 17 regions detected were 0.013∼l.664pg-TEQ/N㎥, 4 sites from those were exceeded the Air Quality Standards of Dioxin in Japan (0.6 pg-TEQ/N㎥). The tolerable daily intake of dioxins was calculated at the highest level (1.664) in air, with referring the soil and food data from Japan, was calculated to be 2.85pg-TEQ/kg/day, which was below the level of 4 pg-TEQ/kg/day suggested in KFDA(Korea). While the average concentration of dioxins in 15 big cities was 0.190 pg-TEQ/N㎥, that in 8 medium/small cities constituting an industrial complex was 0.558 pg-TEQ/N㎥. In water, the concentration range detected were 0∼0.946pg-TEQ/L and the trend of the average concentrations shows an increase from those of 1999 but decreased from those of 2000, any sites however were not exceeded the Water Quality Standards of Dioxin in Japan (1 pg- TEQ/L). In soil. the detected range were 0∼43.333 pg-TEQ/dry g and the average concentration decreased, compared with the results of 2000. According to the monitoring results by land utilization, the detected range were 0∼43.333pg-TEQ/dry g in farmland, 0.017∼0.601 pg-TEQ/dry g in the industrial area, 0.005∼0.049pg-TEQ/dry g in the park and 0.008∼1.825 pg-TEQ/dry g in the rest. In sediment, the detected range increased from 0∼0.244 pg-TEQ/dry g to 0∼0.537 pg-TEQ/dry g, based on the results of 2000. For the proper control of dioxins, continuous monitoring needs to be performed and in addition, the dioxin inventory should be prepared for major sources through the dioxin emission survey. These results would provide sound and solid basis for proper decision making of dioxins management like establishment of environmental quality standards in Korea.

• 대한환경공학회지
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• 제29권7호
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• pp.771-777
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• 2007

가정계열과 공단계열로 분리하여 처리되는 하수처리장에서 에스트로겐 활성을 평가하기 위하여 yeast two-hybrid assay와 enzyme-linked immunosorbent assay(ELISA)를 이용하여 내분비계장애물질의 농도와 활성도를 측정하였다. 그 결과 가정계열 유입수 중에서 estrone (E1), 17$\beta$-estradiol(E2), 17$\alpha$-ethinylestradiol(EE2) 그리고 APE의 농도는 각각 최대 167.1, 39.7, 7.3, 145.4 ng/L까지 검출되었다. 활성슬러지법에 의한 처리로, 17$\beta$-estradiol의 평균제거율은 77.5%, 고도처리 공정인 모래여과와 오존산화를 거친 후에는 80.8%까지 제거되는 것으로 나타났다. 동시에 Yeast two-hybrid assay로 각 내분비계장애물질의 농도-반응곡선으로부터 반응식을 구하여, 에스트로겐 활성에 미치는 각 물질의 기여도를 분석한 결과, 가정계의 활성슬러지법에 의한 처리수에서 estrone, 17$\beta$-estradiol 17$\alpha$-ethinylestradiol, APE 가 각각 70.7, 23.3, 3.7, 2.32%로 나타났다. 즉, 생물학적 처리공정을 통해 배출된 처리수의 에스트로겐 활성에 영향을 미치는 주된 기여물질은 estrone과 17$\beta$-estradiol인 것으로 나타났다.

• 농약과학회지
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• 제16권1호
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• pp.62-68
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• 2012

본 연구에서는 내분비계 장애물질의 영향 및 생태계 건강성의 스크리닝 평가를 위해 미꾸리를 지표종으로 선정하여 대조지점(RA)과 농업지점(AS)에서 biomarker 4가지 항목과 bioindicator 4가지 항목을 포함하여 총 8가지 항목의 생물지표를 분석하였다. 생태계 건강성 평가를 위한 생물지표의 분석 결과 독성 화학물질의 영향을 나타내는 ethoxyresorufin-O-deethylase(EROD), acetylcholinesterase(AChE) 및 DNA damage 등의 생화학적 생물지표는 대조지점(RA)에 비해 유의한 차이가 있는 것으로 나타났다. 반면, 내분비계 장애물질의 영향을 반영하는 vitellogenin(VTG)는 농업지점(AS)에서 유의한 차이를 보이지 않았고, 개체수준의 생물지표(condition factor (CF), hepato-somatic index (HSI), gonado-somatic index (GSI)) 또한 유의한 차이를 보이지 않았다. 따라서 농업지점(AS)의 생태계 건강성은 내분비계 장애물질에 의한 영향은 미비한 것으로 판단되었으나, 농약, 중금속 등과 같은 독성을 보이는 화학물질이나 농업 지역의 특수성에 따른 서식지 환경 조건에 의해 일부 영향을 받은 것으로 사료되었다. 본 연구는 생화학적 생물지표와 개체수준의 생물지표를 이용한 스크리닝 평가로서 농업지역에 대한 종합적인 생태계 건강성 평가를 위해서는 생물지표 적용 항목을 확대하고, 개체군이나 군집 수준의 분석이 추가적으로 적용 되어야 하며 수생태계 내의 추정 오염물질에 대한 분석이 필요할 것으로 사료된다.

• Asian-Australasian Journal of Animal Sciences
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• 제14권3호
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• pp.402-413
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• 2001

Food safety is a term broadly applied to food quality that may adversely affect human health. These include zoonotic diseases and acute and chronic effects of ingesting natural and human-made xenobiotics. There are two major areas of concern over the presence of residues of antibiotics in animal-derived foodstuffs with regard to human health. The first is allergic reactions. Some antibiotics, such as penicillins can evoke allergic reactions even though small amounts of them are ingested or exposed by parenteral routes. The second is development of antibiotic resistance in gut bacteria of human. Recently multi-resistant pneumococcal, glycopeptide-resistant enterococci and gram negative bacteria with extended-spectrum $\beta$-lactamases have spread all over the world, and are now a serious therapeutic problem in human. Although it is evident that drugs are required in the efficient production of meat, milk and eggs, their indiscriminate use should never be substituted for hygienic management of farm. Drug should be used only when they are required. In addition to veterinary drugs, environmental contaminants that were contaminated in feed, water and air can make residues in animal products. Mycotoxins, heavy metals, pesticides, herbicides and other chemicals derived from industries can be harmful both to animal and human health. Most of organic contaminants, such as dioxin, PCBs and DDT, and metals are persistent in environment and biological organisms and can be accumulated in fat and hard tissues. Some of them are suspected to have endocrine disrupting, carcinogenic, teratogenic, immunodepressive and nervous effects. The governmental agencies concerned make efforts to prevent residue problems; approval of drugs including withdrawal times of each preparation of drugs, establishment of tolerances, guidelines regarding drug use and sanitation enforcement of livestock products. National residue program is conducted to audit the status of the chemical residues in foods. Recently HACCP has been introduced to promote food safety from farm to table by reducing hazardous biological, chemical and physical factors. Animal Production Food Safety Program, Quality Assurance Programs, Food Animal Residue Avoidance Databank are para- or non-governmental activities ensuring food safety. This topic will cover classification and usage or sources of chemical residues, their adverse effects, and chemical residue status of some countries. Issues are expanded to residue detection methodologies, toxicological and pharmacokinetic backgrounds of MRL and withdrawal time establishments, and the importance of non-governmental activities with regard to reducing chemical residues in food.

• 한국수정란이식학회지
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• 제28권2호
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• pp.157-162
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• 2013

Methoxychlor (MXC) was developed to be a replacement for the banned pesticide DDT. HPTE [2,2-bis (p-hydroxyphenyl)-1,1,1-trichloroethane], which is an in vivo metabolite of MXC, has strong oestrogenic and anti-androgenic effects. MXC and HPTE are thought to produce potentially adverse effects by acting through oestrogen and androgen receptors. Of the two, HPTE binds to sex-steroid receptors with greater affinity, and it inhibits testosterone biosynthesis in Leydig cells by inhibiting cholesterol side-chain cleavage enzyme activity and cholesterol utilisation. In a previous study, MXC was shown to induce Leydig cell apoptosis by decreasing testosterone concentrations. I focused on the effects of MXC on male mice that resulted from interactions with sex-steroid hormone receptors. Sex-steroid hormones affect other organs including the kidney and liver. Accordingly, I hypothesised that MXC can act through sex-steroid receptors to produce adverse effects on the testis, kidney and liver, and I designed our experiments to confirm the different effects of MXC exposure on the male reproductive system, kidney and liver. In these experiments, I used pre-pubescent ICR mice; the puberty period in ICR mice is from postnatal day (PND) 45 to PND60. I treated the experimental group with 0, 100, 200, 400 mg MXC/kg b.w. delivered by an intra-peritoneal injection with sesame oil used as vehicle for 4 weeks. At the end of the experiment, the mice were sacrificed under anaesthesia. The testes and accessory reproductive organs were collected, weighed and prepared for histological investigation. I performed a chemiluminescence immune assay to observe the serum levels of testosterone, LH and FSH. Blood biochemical determination was also performed to check for other effects. There were no significant differences in our histological observations or relative organ weights. Serum testosterone levels were decreased in a dose-dependent manner; a greater dose resulted in the production of less testosterone. Compared to the control group, testosterone concentrations differed in the 200 and 400 mg/kg dosage groups. In conclusion, I observed markedly negative effects of MXC exposure on testosterone concentrations in pre-pubescent male mice. From our biochemical determinations, I observed some changes that indicate renal and hepatic failure. Together, these data suggest that MXC produces adverse effects on the reproductive system, kidney and liver.

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2002년도 학술대회
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• pp.141-144
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• 2002

Environmental estrogens are natural or synthetic substances present in the aquatic environment, especially in effluent from sewage treatment. However, the adverse effects of these estrogenic substances on fish reproduction are unknown. Di-2-ethylhexyl phthalate (DEHP) is the most common phthalate, which Ps used as a plasticizer in polyvinylchloride (PVC), and it is widespread in the environment and has been found in aquatic organisms and sediments. Therefore, juvenile common carps (Cyprinus carpio) were exposed to nominal concentrations of 17$\beta$-estradiol (E2) (0.5, 5, 50 $\mu\textrm{g}$/L) and DEHP (10, 100, 500 $\mu\textrm{g}$/L) for 21 days, to determine the adverse reproductive effects of these compounds on plasma vitellogenin (VTG) induction, sex steroid level, and gonad weight. Electrophoresis (SDS-PAGE) revealed that much of VTG was induced in fish exposed to 5 and 50 E$_2$ $\mu\textrm{g}$/L, but none of DEHP exposure showed induction. Enzyme-linked immunosorbent assay (ELISA) revealed that VTG was significantly induced in fish exposed to 5 and 50 E$_2$ $\mu\textrm{g}$/L, and combination of 50 E$_2$ $\mu\textrm{g}$/L with 10 and 500 DEHP $\mu\textrm{g}$/L, but none of DEHP exposure showed induction. Analysis of sex steroid levels in some fish revealed that testosterone (T) was detected in both male and female fish of the control and DEHP exposures, but none of fish exposed to 22 concentrations had detectable testosterone level. On the other hand, E$_2$ exposure induced 17$\beta$-estradiol in plasma of male fish, but there was no induction of 17$\beta$-estradiol in plasma of male fish exposed to DEHP. Comparison of gonadosomatic index (GSI) revealed that maximal E$_2$ exposure inhibited ovarian growth, but maximal DEHP exposure stimulated testicular growth. The results indicated that those comparisons can be a useful bio-indicator for determining adverse reproductive effect of endocrine disrupting chemicals (EDCs).