• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.132-132
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• 2002

• 한국수산과학회지
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• 제22권6호
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• pp.424-428
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• 1990

Mulletts, Mugil cephalus were exposed to artificial sea water containing $50{\mu}g/\iota\;of\;^{14}C-la-belled$ di-2-ethylhexyl phthalate(DEHP) during 15 days and returned to the DEHP free sea water in order to know bioconcentration and depuration of DEHP in the fish. Bioaccumulative process of DEHP in the fish was rather fast, and bioconcentration level of $9.7\~14{\mu}g/g$ and a bioconcentration factor of $220\~270$ were reached after one any of exposure. The biological half-life of DEHP in fish was 1.8 days. Five intermediate metabolites of DEHP were detected in the benzene and ethyl acetate fraction of fish by TLC.

• Toxicological Research
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• 제21권3호
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• pp.187-193
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• 2005

The rodent Hershberger assay is considered as a potential short term in vivo screening method for the detection of androgenic or anti-androgenic compounds. The objective of this study was to evaluate the anti-androgenic activities of di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and butylbenzyl phthalate (BBP). A 10-day Hershberger assay was performed using immature Sprague-Dawley male rats castrated at 6 weeks of age. Tastosterone propionate (TP, 0.4 mg/kg/day) was administered s.c. to castrated male rats and followed by flutamide (1, 5, 10, or 20 mg/kg/day) treatment for 10 days by oral gavage. Similarly, DEHP, DBP, or BBP were also administered by oral gavage at 250, 500, or 1000 mg/kg/day after TP (0.4 mg/kg/day) administration. As expected, flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1 mg/kg/day and above, and Cowper's glands and glans penis at 5 mg/kg/day and above. DEHP significantly (p<0.05) decreased the seminal vesicles, ventral prostate, LABC and Cowper's glands weights at 1000 mg/kg/day. BBP at 1000 mg/kg/day significantly inhibited TP-induced re-growth of the LABC in the immature castrated male rats, whereas ventral prostate, seminal vesicles, and Cowper's glands weights were unaffected. In contrast to DEHP, DBP did not affect accessory sex organ weights at any concentration. Body weights, combined adrenal glands, and kidney weights were not affected, but liver weights were significantly increased at high dosages in the DEHP, DBP, and BBP treatment groups. Our observations strongly suggest that DEHP acts as an androgen antagonist at the high dose (i.e., 1000 mg/kg/day).

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.149-156
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• 2005

Di (n-ethylhexyl) phthalate (DEHP) is thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. DEHP is used in numerous consumer products, especially those made of flexible polyvinyl chloride and have been reported to be weakly estrogenic. In this study, DEHP were tested for estrogenic properties in vitro models and with microarray analysis. First, the E-screen assay was used to measure the proliferation of DEHP in MCF-7 cells, a human breast cancer cell line. DEHP induced an increase in MCF-7 cell proliferation at concentration of $10^{-4}M$. Second, we carried out a microarray analysis of MCF-7 cells treated with DEHP using human c-DNA microarray including 401 endocrine system related genes. Of the genes analyzed, 60 genes were identified showing significant changes in gene expression resulting from DEHP. Especially, 4 genes were repressed and 4 genes were induced by DEHP compared to $17{\beta}-estradiol$. Among these genes, trefoil factor 3 (intestinal), breast cancer 1, early onset and CYP1B1 are involved in estrogen metabolism and regulation. Therefore it suggests that these genes may be associated with estrogenic effect of the DEHP on transcriptional level. The rationale is that, as gene expression is a sensitive endpoint, alterations of these genes may act as useful biomarkers to define more precisely the nature and level of exposure to kinds of phthalates.

• Journal of Ginseng Research
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• 제46권4호
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• pp.592-600
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• 2022

Background: Di-(2-ethylhexyl) phthalate (DEHP) is the most common endocrine disrupting chemical used as a plasticizer. DEHP is associated with the development of endometrium-related diseases through the induction of inflammation. The major therapeutic approaches against endometrial cancer and endometriosis involve the suppression of inflammatory response. Korean Red Ginseng (KRG) is a natural product with anti-inflammatory and anti-carcinogenic properties. Thus, the purpose of this study is to investigate the effects of KRG on DEHP-induced inflammatory response in endometrial cancer Ishikawa cells and a mouse model of endometriosis. Methods: RNA-sequencing was performed and analyzed on DEHP-treated Ishikawa cells in the presence and absence of KRG. The effects of KRG on DEHP-induced cyclooxygenase-2 (COX-2) mRNA levels in Ishikawa cells were determined by RT-qPCR. Furthermore, the effects of KRG on the extracellular signal-regulated kinases (ERKs) pathway, COX-2, and nuclear factor-kappa B (NF-kB) p65 after DEHP treatment of Ishikawa cells were evaluated by western blotting. In the mouse model, the severity of endometriosis induced by DEHP and changes in immunohistochemistry were used to assess the protective effect of KRG. Results: According to the RNA-sequencing data, DEHP-induced inflammatory response-related gene expression was downregulated by KRG. Moreover, KRG significantly inhibited DEHP-induced ERK1/2/NF-κB/COX-2 levels in Ishikawa cells. In the mouse model, KRG administration significantly inhibited ectopic endometriosis growth after DEHP-induced endometriosis. Conclusions: Overall, these results suggest that KRG may be a promising lead for the treatment of endometrial cancer and endometriosis via suppression of the inflammatory response.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.128-128
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• 2003

• Toxicological Research
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• 제27권3호
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• pp.185-190
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• 2011

Di-(2-ethylhexyl)-phthalate (DEHP), the most widely utilized industrial plastizer and a ubiquitous environmental contaminant, can act on peroxisome proliferators-activated nuclear hormone receptor family (PPAR) isoforms. To understand the contribution of sphingolipid metabolism to DEHP-induced hepatotoxicity, effect of DEHP exposure on activities of sphingolipid metabolic enzymes in rat liver was investigated. DEHP (250, 500 or 750 mg/kg) was administered to the rats through oral gavage daily for 28 days. The activities of acidic and alkaline ceramidases were slightly increased in 250 mg/kg DEHP-administered rat livers and significantly elevated in 500 mg/kg DEHP-administered ones, although the level of 750 mg/kg DEHP-administered ones was not increased. Neutral ceramidase, acidic and neutral sphingomyelinases, sphingomyeline synthase and ceramide syhthase were not changed at all by DEHP exposure. Therefore, acidic and alkaline ceramidases might play important roles in DEHP-induced hepatotoxicity.

• Toxicological Research
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• 제26권1호
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• pp.75-82
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• 2010

This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2(ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), butylbenzyl phthalate (BBP), dimethyl phthalate (DMP), di-isodecyl phthalate (DIDP), diundecyl phthalate (DUP), and di-isononyl phthalate (DINP) and five phthalate monoesters including mono- (2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBuP), monobenzyl phthalate (MBeP), monoethyl phthalate (MEP), monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats. Animals were administered 250 mg/kg/day (monoesters and PA) or 500 mg/kg/day (diesters) of phthalate for two weeks. All animals were examined for body and organ weights, blood hematology, serum biochemistry, and urine analysis. The body weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP, MBuP, and PA than that of control. Liver weights were significantly increased in the DEHP, DBP, DnOP, DIDP, and MEHP groups as compared to the control group. Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP-treated groups as compared to the control. Significant differences in hematological changes were not observed in any treatment groups. Significant increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP groups. Aspartate aminotransferase (AST) levels were significantly increased in the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT) levels were significantly increased only in the DEHP and MEHP groups. Serum ALP levels were significantly higher in phthalate diester (500 mg/kg/day)-treated rats as compared to control. However, the total cholesterol level was significantly reduced in the DEHP- and DIDP-treated groups, whereas serum triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated groups. These results suggest that short term toxicity of phthalate monoesters produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.

• 분석과학
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• 제15권2호
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• pp.172-179
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• 2002

빗물, 증류수, 정수기 물, 지하수, 수돗물, 시판생수에 포함된 주요 환경호르몬 물질로 알려진 nonylphenol(NP), octylphenol(OP), di(2-ethylhexyl)phthalate(DEHP)를 OASIS 카트리지로 추출한 후 GC/MS를 이용하여 정량하였다. Octylphenol 은 어느 물 시료에서도 검출되지 않았으나, nonylphenol 의 경우는 그 존재량이 빗물<정수기 물<증류수<지하수<수돗물<시판생수의 순으로 증가하였으며, 시판생수의 경우 최고 $0.44{\mu}g/L$(ppb)가 포함되어 있었다. Di(2-ethylhexyl)phthalate는 모든 물 시료에 포함되어 있었으며 빗물의 경우 $1.7{\sim}2.9{\mu}g/L$, 증류수는 $8.7{\sim}31.7{\mu}g/L$, 정수기 물은 $0.6{\sim}5.6{\mu}g/L$(평균: $2.5{\pm}0.3{\mu}g/L$)로 다른 값에 비하여 매우 안정한 값을 나타냈고, 전주근교 지하수는 $1.1{\sim}6.0{\mu}g/L$, 수돗물은 평균 $3.1{\sim}5.7{\mu}g/L$, 시판생수는 $0.5{\sim}67.6{\mu}g/L$ 이였으며 시중의 시판 생수 중 40% 이상이 USEPA기준을 초과하고 있었다.

• 한국식품과학회지
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• 제33권4호
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• pp.492-496
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• 2001

혈청 중성지질 저하작용을 가지고 있는 것으로 알려진 OA식 및 DEHP식을 각각 투여한 흰쥐의 간장 및 소장에서 MTP 활성과 mRNA 수준을 검토하였다. 간장 중성지질 농도는 대조군에 비교해서 OA군에서 유의하게 증가하였으나, DEHP군에서는 유의한 차이가 없었다. 혈청 중성지질 농도는 대조군에 비해서 OA군 및 DEHP군에서 유의하게 감소하였는데, 이러한 저하는 OA군에서 더욱 현저하였다. 간세포에서의 MTP 활성과 mRNA 수준은 대조군에 비해서 OA군에서 유의하게 저하하였으나, 소장에서의 MTP 활성은 증가하였다. 그러나, 간장 및 소장의 MTP 활성과 mRNA 수준은 대조군과 DEHP군 사이에서는 유의적인 변화가 없었다. 간장에 있어서 중성지질 합성의 중요 조절효소인 microsomal PAP 활성은 대조군에 비해 OA군에서 유의하게 증가하였으나, DEHP군에서는 cytosolic PAP 활성이 감소하였다. 이상의 결과로부터, OA에 의한 혈청 중성지질 저하 작용에는 간장 MTP 활성과 mRNA 유전자 발현이 깊이 관여하였으나, DEHP에 의한 혈청 중성지질 저하 작용에는 MTP 대사와는 무관한 것으로 사료되었다.