• Journal of Ginseng Research
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• v.48 no.3
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• pp.333-340
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• 2024

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats. Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines. Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity. Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day.

• Toxicological Research
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• v.17 no.1
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• pp.65-71
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• 2001

The key targets of endocrine disruptors are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. A yeast-based steroid hormone receptor gene trascription assay was previously developed for the evaluation of chemicals with endocrine modulating activity. The yeast transformants used in this assay contain the human estrogen receptor along with the appropriate steroid response elements upstream of the $\beta$-galactosidase reporter gene. We tried to evaluate several natural and synthetic steroids of their potential to interact directly with the steroid receptor. Some putative endocrine disruptors, including nonylphenol, are weakly estrogenic. But the combined treatment oj these chemicals with di-(2-ethylhexyl)phthalate (DEHP) significantly increased the $\beta$-galactosidase activity in the yeast transformant. These results suggest that we also have to consider the synergistic effects of endocrine disruptors. In this study, we showed that yeast-based bioassay is a valuable tool for screening potential endocrine disruptors and quantitative determination of estrogenicity. And the possibility that the estrogen receptor binds multiple environmental chemicals adds another level of complexity to the interaction between the endocrine disruptors and the human hormone system.

• Proceedings of the Korean Environmental Health Society Conference
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• 2004.06a
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• pp.185-187
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• 2004

The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP showed significant organ weight changes in liver, spleen exposed during lactational periods. But the dams exposed during lactational periods showed significant organ weight changes not only in liver, spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However no clear synergistic effects of BPA and BBP could be found. Estrogen receptor ${\alpha}$ expression by BPA and BBP in the uterus(dam, F1 female) and testis(F1 male) were studied. There was no significant different $ER{\alpha}$ expression pattern between control and treated groups. But $ER{\alpha}$ expression were increased in F1 male testis and female uterus. F1 male showed distinct $ER{\alpha}$ expression, especially in the group of lactational combined exposure. Synergistic $ER{\alpha}$ expression was found by combined treatment of BPA and BBP.

• Journal of Ecology and Environment
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• v.41 no.11
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• pp.318-327
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• 2017

Background: A typical sewage treatment plant is designed for organic and nutrient removal from municipal sewage water and not targeted to eliminate micropollutants such as pesticides, pharmaceuticals, and nano-sized metals which become a big concern for sustainable human and ecological system and are mainly discharged from sewage treatment plant. Therefore, despite contaminant removal by wastewater treatment processes, there are still remaining environmental risks by untreated pollutants in STP (sewage treatment plant) effluents. This study performed aquatic toxicity tests of raw wastewater and treated effluents in two sewage treatment plants to evaluate toxicity reduction by wastewater treatment process and analyze concentration of contaminants to reveal potential toxic factors in STP effluents. Methods: Water samples were collected from each treatment steps of two STPs, and acute and chronic toxicity tests were conducted following USEPA (United States Environmental Protection Agency) and OECD (Organization for Economic Cooperation and Development) guidelines. Endpoints were immobility for mortality and reproduction effect for estrogenicity. Results: Acute $EC_{50}s$ (median effective concentration) of influents for Seungki (SK) and Jungnang (JN) STPs are $54.13{\pm}32.64%$ and $30.38{\pm}24.96%$, respectively, and reduced to $96.49{\pm}7.84%$ and 100%. Acute toxicity reduction was clearly correlated with SS (suspended solids) concentration because of filter feeding characteristics of test organisms. Chronic toxicity tests revealed that lethal effect was reduced and low concentration of influents showed higher number of neonates. However, toxicity reduction was not related to nutrient removal. Fecundity effect positively increased in treated wastewater compared to that in raw wastewater, and no significant differences were observed compared to the control group in JN final effluent implying potential effects of estrogenic compounds in the STP effluents. Conclusions: Conventional wastewater treatment process reduced some organics and nutritional compounds from wastewater, and it results in toxicity reduction in lethal effect and positive reproductive effect but not showing correlation. Unknown estrogenic compounds could be a reason causing the increase of brood size. This study suggests that pharmaceutical residues and nanoparticles in STP effluents are one of the major micropollutants and underline as one of estrogenic effect factors.

• Environmental Analysis Health and Toxicology
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• v.19 no.2
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• pp.207-216
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• 2004

유기염소계 농약은 화학적으로 안정하고, 지용성이 크며 체내 대사에 대해 저항성을 가지고 있어서 인체 및 생태계의 생물체 중 축적성이 매우 크다. 또한 대부분 내분비계 장애물질로 분류되어 있어 관심의 대상이 되고 있다. 유기염소계 농약은 잔류성으로 인하여 사용이 금지되었음에도 불구하고 인체에서 검출되고 있으며 한국인의 지방조직을 분석한 결과 9종의 유기염소계 농약이 주로 축적되어 있음이 보고된 바 있다. 본 연구에서는 이들 유기염소계 농약의 에스트로겐 활성을 MCF-7 BUS cell을 이용한 E-screen assay competitive binding assay 및 pS$_2$ gene experession assay에 의해 조사하였다. o,p'-DDT,p, p'-DDT,p,p'-DDD,p,p'-DDE등 4종의 유기염소계 농약은 에스트로겐 수용체에 대한 ligand의존적인 작용기전에 의해 에스트로겐 활성을 가지며, $\alpha$-, $\beta$-, ${\gamma}$-, $\delta$-BHC, dieldrin등 5종의 유기염소계 농약은 lingand-비의존적 작용기전에 의해 에스트로겐 활성을 보였다. 또한 이들 유기염소계 농약을 혼합 투여하여 에스트로겐 활성을 관찰한 결과 DDT류의 경우에는 단독투여시 보다 그 대사체와 혼합 투여할 때 에스트로겐 활성에 상승적 효과가 나타났으며 o,p'-와 p,p'-DDT의 두 이성질체를 혼합 투여할 경우가 단독 투여시 보다 상승적 효과가 나타났다. 따라서 지방조직에서 검출되는 유기염소계농약은 상호작용에 의해 개별 물질이 나타내는 내분비계장애작용 보다 실제로는 강한 효과를 나타낼 것으로 추정되었다.

• Journal of Environmental Health Sciences
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• v.33 no.5
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• pp.379-385
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• 2007

This study was aimed to investigate the estrogenic activity of Di-(2-ethylhexyl) adipate (DEHA) using immatured type uterotrophic assay. SD rats were treated with DEHA (40, 200, 1000mg/kg/day), estradiol-3-benzoate (EB) $(1{\mu}g/kg/day)$ as positive control on the assay. In immatured-type uterotrophic assay, relative organ weights of kidney and reproductive organs such as ovary at high-dose group were significantly increased compared to those of vehicle control group. DEHA did not influence the levels of serum FSH and LH, and uterine morphological changes such as luminal epithelial height, myometrial thickness and numbers of uterine gland, and BrdU indices. In these results, there was no significant variation by DEHA treatment, suggesting that DEHA appears not to be a endocrine disrupter with estrogenic activity.

• Journal of Environmental Health Sciences
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• v.41 no.3
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• pp.147-162
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• 2015

Objectives: The objective of this review was to summarize the primary role of three representative endocrine axes in aquatic vertebrates and discuss the effects on endocrine systems and their interactions in teleost fish after exposure to environmental contaminants. Methods: We summarized individual traits and mechanisms for hormonal and transcriptional interactions between the hypothalamic-pituitary-gonad (HPG), hypothalamic-pituitary-thyroid (HPT), and hypothalamic-pituitary-adrenal (HPA) axes in fish. We also provided a brief discussion on the effects of nonylphenol-induced toxicity on endocrine systems and their interactions in fish as a demonstration of holistic explanation. Results: Currently-available data showed that thyroid dysfunction is associated with reproductive toxicity due to changes in steroidogenic gene expressions and sex hormone levels as well as gonad glands in fish. As an example, we demonstrated that exposure to nonylphenol could induce estrogenicity in male fish by decreasing thyroid hormones, which contributes to increased aromatase expression. Although the mechanisms are complicated and involved in multiple ways, a number of studies have shown that sex steroids influence the HPT axis or the HPA axis in fish, indicating bi-directional crosstalk. Critically missing is information on the primary target or toxicity mechanisms of environmental contaminants among the three endocrine axes, so further studies are needed to explore those possibilities. Conclusions: This review highlights the interactions between the HPG, HPT, and HPA axes in fish in order to better understand how these endocrine systems could interact with each other in situations of exposure to endocrine disrupting chemicals.

• Fisheries and Aquatic Sciences
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• v.19 no.9
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• pp.41.1-41.7
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• 2016

Background: The transgenic approach using estrogen-responsive regulator in fish has been given much attention as a potential means to detect and/or address estrogen-related aquatic pollutions. In order to address the development stage- and reproduction status-dependent expression patterns of the chgH-rfp transgene (red fluorescent protein transgene driven by choriogenin H promoter) in marine medaka Oryzias dancena, naturally occurring red fluorescent protein (RFP) signals under non-exposed conditions as well as the transgenically induced RFP signals under estrogen-exposed conditions were assayed. Results: Female transgenics begun to show naturally occurring RFP signals from the age of 7 weeks post hatching (WPH) without experimental estrogen exposure. Afterward, these RFP signals in female transgenics became robust with the progress of ovarian maturation. On the other hand, male transgenics did not show any naturally occurring RFP signal under non-exposed conditions irrespective of developmental stages and maturation statue. Upon exposures using estradiol-$17{\beta}$ (E2) and $17{\alpha}$-ethinylestradiol (EE2), RFP signals were significantly induced specifically in the livers of transgenic males. Conclusions: Male chgH-rfp transgenics were able to keep the "off" state of RFP expression during their entire life cycle unless exposed to exogenous estrogens. Owing to their tight regulation capability of estrogen-responsive transgene, transgenesis of chgH-rfp in male marine medaka could offer a useful model system for future ecotoxicogenomic studies regarding estrogenicity-related issues in aquatic and marine environments.

• Korean Journal of Environmental Biology
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• v.18 no.3
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• pp.291-298
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• 2000

Vitellogenesis, an important reproductive process in oviparous animals, includes the processes of hormonally regulated synthesis of yolk precursor protein, vitellogenin (Vg), and their deposition in ovarian oocytes as a vitellin which is an important energy source as well as buoyancy regulator of the egg. Vg genes consist of a gene family that encompasses a large number of lipoproteins and produce different Mr. Vg proteins in liver. The expression of Vg is largely dependent on the estrogen, and both reproductive cycle and temperature also influence Vg synthesis. Synthetic estrogens or estrogenic pollutants was sufficient to induce Vg in both sexes of oviparous vertebrates. Therefore, the estrogenic induction of vitellogenesis in male has been used for biological marker in the screening of estrogenicity of certain endocrine disrupting compounds and the monitoring the world-wide contamination of estrogenic compounds in wild life. In the studies on the biological hazard and influence of endocrine disrupting chemicals using the Vg induction in oviparous males, it is important to consider the reproductive cycle, zoogeography and biodiversity of the wild life animals in Korea.

• Korean Journal of Pharmacognosy
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• v.37 no.1 s.144
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• pp.21-27
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• 2006

Yeast based estrogenicity assay is the simplest and useful for the assay and the discovery of novel estrogenic substances in natural specimens, The estrogen receptor(ER) modulation activity of 50% EtOH extracts of 101 traditional medicinal herbs was assessed using a recombinant yeast assay system with both a human estrogen receptor expression plasmid and a receptor plasmid. Among them, 14 species proved to be active. Pureariae Flos (flower of Puerraria thunbergiana BENTH.) had the highest estrogenic relative potency$(7.75{\times}10^{-3})$ $(EC_{50}=9.39\;{\mu}g/ml)$. The $EC_{50}$ value of $17{\beta}-estradiol$ used as the positive control was $0.073\;{\mu}g/ml)$ (Relative Potency=1.00). There results demonstrated that some of the traditional medical herb may be useful in the therapy of estrogen replacement.