• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.114-114
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• 2001

Di-n-butyl phthalate (DBP) is not only a plasticizer and solvent used in industry but also one of endocrine disruptor chemicals, a low level contaminant found in a wide variety of different media ranging from drinking water to infant formulae. To evaluate the cytotoxic function of NK cells in mice after contact with DBP, C57BL/6 female mice were orally dosed with di-n-butyl phthalate (250, 500, or 750 mg/kg body weight) for 14 consecutive days, and the control mice were administered vehicle (corn oil).(omitted)

• Development and Reproduction
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• v.24 no.2
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• pp.71-78
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• 2020

Endometriosis is a common gynecologic disease, worldwide, whose true prevalence is uncertain because it is a difficult disease to diagnose. Endometriosis is a common cause of chronic pelvic pain, dysmenorrhea, and infertility, and is also associated with ovarian cancer. Although the risk factors for endometriosis are unclear, there is increasing evidence that exposure to environmental contaminants, especially phthalates, could affect the pathogenesis of endometriosis. Phthalates are industrial chemicals, used to make flexible plastics, and are present in numerous common plastic products, including medical devices and materials. Several in vitro studies have suggested a positive association between exposure to phthalate, or phthalate metabolites, and the risk of endometriosis. Since the 2000s, studies based on human plasma and urinary concentrations of various phthalate metabolites have been published, but there are still limitations to our understanding of the pathophysiology of phthalates and endometriosis. This report aims to review the current state of knowledge about a possible role of phthalates in the pathogenesis of endometriosis based on cell culture, animal models, and human data.

• Analytical Science and Technology
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• v.18 no.2
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• pp.147-153
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• 2005

Benzophenone (BP) which is one of endocrine disrupting chemicals is suspected to contaminate waters (river, lake and industrial drainage) and soils (ground soil and sediment). Analytical method for determination of BP in soil and water was developed by gas chromatography/mass spectrometry. Water sample (100 mL) was extracted with n-hexane, and soil (10 g) was extracted with methanol and n-hexane. Recovery for BP was >71.4% in water and 86.5-94.7% in soil with coefficient variation of less than 19.8%. Calibration curves showed a good linearity ($r^2$ >0.998). In water, soil and sediment collected at nation-wide sites, BP was detected at 5 sites among 43 water sites at the concentration range of 30-200 ng/L. No BP was found in the soil and sediment samples. It is suggested that this method will be useful to the determination of BP in the environmental matrices such as waters, soils and sediments in minute quantities.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.519-526
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• 2020

Background: Bisphenol A (BPA), known as an endocrine disruptor, is widely used in the world. BPA is reported to cause inflammation-related diseases. Korean Red Ginseng (KRG) has been used safely in human for a long time for the treatment of diverse diseases. KRG has been reported of its mitigating effect on menopausal symptoms and suppress adipose inflammation. Here, we investigate the protective effect of orally administered KRG on the impacts of BPA in the liver and uterus of menopausal mice model. Methods: The transcriptome analysis for the effects of BPA on mice liver was evaluated by Gene Expression Omnibus (GEO) database-based data (GSE26728). In vivo assay to evaluate the protective effect of KRG on BPA impact in ovariectomized (OVX) mice were designed and analyzed by RNA sequencing. Results: We first demonstrated that BPA induced 12 kinds of gene set in the liver of normal mice. The administration of BPA and KRG did not change body, liver, and uterine weight in OVX mice. KRG downregulated BPA-induced inflammatory response and chemotaxis-related gene expression. Several gene set enrichment analysis (GSEA)-derived inflammatory response genes increased by BPA were inhibited by KRG in OVX mice. Conclusion: Our data suggest that BPA has commonly influenced inflammatory response effects on both normal and OVX mice. KRG protects against BPA impact of inflammatory response and chemotaxis in OVX mouse models. Our comparative analysis will provide new insight into the efficacy of KRG on endocrine disrupting chemicals and OVX mouse.

• Journal of Animal Science and Technology
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• v.56 no.7
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• pp.26.1-26.10
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• 2014

Background: Endocrine disruptors are exogenous substance, interfere with the endocrine system, and disrupt hormonal functions. However, the effect of endocrine disruptors in different species has not yet been elucidated. Therefore, we investigated the possible effects of $17{\beta}$-estradiol (E2), progesterone (P4), genistein (GEN) and 4-tert-octylphenol (OP), on capacitation and the acrosome reaction in bovine, mouse, and porcine spermatozoa. In this in vitro trial, spermatozoa were incubated with $0.001-100{\mu}M$ of each chemical either 15 or 30 min and then assessed capacitation status using chlortetracycline staining. Results: E2 significantly increased capacitation and the acrosome reaction after 30 min, while the acrosome reaction after 15 min incubation in mouse spermatozoa. Simultaneously, capacitation and the acrosome reaction were induced after 15 and 30 min incubation in porcine spermatozoa, respectively. Capacitation was increased in porcine spermatozoa after 15 min incubation at the lowest concentration, while the acrosome reaction was increased in mouse spermatozoa after 30 min (P < 0.05). E2 significantly increased the acrosome reaction in porcine spermatozoa, but only at the highest concentration examined (P < 0.05). P4 significantly increased the acrosome reaction in bovine and mouse spermatozoa treated for 15 min (P < 0.05). The same treatment significantly increased capacitation in porcine spermatozoa (P < 0.05). P4 significantly increased capacitation in mouse spermatozoa treated for 30 min (P < 0.05). GEN significantly increased the acrosome reaction in porcine spermatozoa treated for 15 and 30 min and in mouse spermatozoa treated for 30 min (P < 0.05). OP significantly increased the acrosome reaction in mouse spermatozoa after 15 min (P < 0.05). Besides, when spermatozoa were incubated for 30 min, capacitation and the acrosome reaction were higher than 15 min incubation in E2 or GEN. Furthermore, the responsiveness of bovine, mouse and porcine spermatozoa to each chemical differed. Conclusions: In conclusion, all chemicals studied effectively increased capacitation and the acrosome reaction in bovine, mouse, and porcine spermatozoa. Also we found that both E2 and P4 were more potent than environmental estrogens in altering sperm function. Porcine and mouse spermatozoa were more responsive than bovine spermatozoa.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.216-221
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• 2009

Bisphenol A (BPA) is commonly used in the production of pharmaceutical, industrial, and housing epoxy, as well as polycarbonate plastics. Owing to its extensive use, BPA can contaminate the environment either directly or through derivatives of these products. BPA has been classified as an endocrine disruptor chemicals (EDCs), and the primary toxicity of these EDCs in males involves the induction of reproductive system abnormality. First, in order to evaluate the direct effects on the Y chromosome associated with reproduction, we evaluated Y chromosome abnormalities using a Y chromosome microdeletion detection kit. However, we detected no Yq abnormality as the result of BPA exposure. Secondly, we performed high-density oligonucleotide array-based comparative genome hybridization (CGH) to assess genomic alteration as a component of our toxicity assessment. The results of our data analysis revealed some changes in copy number. Seven observed features were gains or losses in chromosomal DNA (P-value<1.0e-5, average log2 ratio>0.2). Interestingly, 21 probes of chr7:7312289-10272836 (qA1-qA2 in cytoband) were a commonly observed amplification (P-value 3.69e-10). Another region, chr14:4551029-10397399, was also commonly amplified (P-value 2.93e-12, average of log2 ratios in segment>0.3786). These regions include many genes associated with pheromone response, transcription, and signal transduction using ArrayToKegg software. These results help us to understand the molecular mechanisms underlying the reproductive effects induced by BPA.

• Toxicological Research
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• v.33 no.2
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• pp.165-171
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• 2017

Bisphenol A (BPA) is a monomer used in a polymerization reaction in the production of polycarbonate plastics. It has been used in many consumer products, including plastics, polyvinyl chloride, food packaging, dental sealants, and thermal receipts. However, there is little information available on the inhalation toxicity of BPA. Therefore, the aim of this study was to determine its inhalation toxicity and effects on the estrous cycle, spatial learning, and memory. Sprague-Dawley rats were exposed to 0, 10, 30, and $90mg/m^3$ BPA, 6 hr/day, 5 days/week for 8 weeks via whole-body inhalation. Mortality, clinical signs, body weight, hematology, serum chemistry, estrous cycle parameters, performance in the Morris water maze test, and organ weights, as well as gross and histopathological findings, were compared between the control and BPA exposure groups. Statistically significant changes were observed in serum chemistry and organ weights upon exposure to BPA. However, there was no BPA-related toxic effect on the body weight, food consumption, hematology, serum chemistry, organ weights, estrous cycle, performance in the Morris water maze test, or gross or histopathological lesions in any male or female rats in the BPA exposure groups. In conclusion, the results of this study suggested that the no observable adverse effect level (NOAEL) for BPA in rats is above $90mg/m^3$/6 hr/day, 5 days/week upon 8-week exposure. Furthermore, BPA did not affect the estrous cycle, spatial learning, or memory in rats.

• Korean Journal of Environmental Agriculture
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• v.26 no.1
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• pp.62-68
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• 2007

Concerns about endocrine disrupting chemicals emitted from humans and animals have been increased because these compounds are detected at very low levels in environment and adversely affect on indigenous fauna. To date, there is little information regarding the concentration of these compounds in animal wastes. In this study, the female hormones, $17\beta-estradiol$ (E2), estrone (E1) and estriol, were measured to provide baseline data in animal wastes. Samples were collected from animal waste storage, methane digester and sludge separated wastewater and analyzed by gas chromatography-mass spectrometry. To measure the mass ratios of estrogen to macronutrients, nitrogen and phosphorous were also determined. Sample collected from animal waste storage had the highest estrogen concentration (98.7 ${\mu}g/L$), while sludge separated wastewater had the lowest concentration (3.4 ${\mu}g/L$). The mean concentrations of E2 and E1 in waste storage sample were (6.8 ${\mu}g/L$) and (68.7 ${\mu}g/L$), respectively. In sludge separated wastewater, the mean concentration of both E2 and E1 were reduced to (2.6 ${\mu}g/L$) and (1.9 ${\mu}g/L$), respectively. However, estriol was not detected in any of the samples collected. Mean ratios of E2 and E1 to macronutrients were significantly different between the methane wastewater and sludge separated wastewater owing to elimination of solid particles.

• Development and Reproduction
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• v.10 no.2
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• pp.147-154
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• 2006

Phthalates such as di(2-ethyl hexyl)phthalate(DEHP) are industrial chemicals with wide-ranging human exposures because of their use in plastics and other common consumer products. Consequently, their adverse effects as endocrine disruptor in the reproductive physiology of both laboratory rodents and human have been studied extensively. The present study was undertaken to examine whether prepubertal exposure to DEHP affects on the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in female rats. DEHP(100mg/kg/day) was administered daily from postnatal day 25(PND 25) through the day when the first vaginal opening(VO) was observed, and the animals were sacrificed on the next day. Gross anatomy and weight of reproductive tissues were compared to test the DEHP's effects on the cell proliferation. Furthermore, histological studies were performed to assess the structural alterations in the tissues. Specific radioimmunoassay was carried out to measure serum LH levels. To determine the transcriptional changes in progesterone receptor(PR), total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a result, delayed VO was shown in the DEHP group(PND $37.3{\pm}0.7$) compared to the control group(PND $35.3{\pm}0.7$; p<0.05). DEHP treatment significantly decreased the wet weight of ovaries and uteri compared to the control group(p<0.05). Interestingly, elevation of serum LH levels was shown in the DEHP group(p<0.05). Graafian follicles and corpora lutea were observed only in the ovaries from the control animals. Numerous primary, secondary follicles and small atretic follicles were observed in the ovaries from DEHP-treated animals. Similarly, hypotrophy of luminal and glandular uterine epithelium was found in the DEHP-treated group. These effects were probably due to the inhibitory effects of DEHP on the synthesis and secretion of estrogen from granulosa cells. In the semiquantitative RT-PCR studies, the transcriptional activities of PR in both ovary(p<0.05) and uterus(p<0.01) from DEHP-treated animals were significantly lower than those from the control animals. The present studies demonstrated that the acute exposure to DEHP during the critical period of prepubertal stage could inactivate the reproductive system resulting delayed puberty in female rats.