• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.512-519
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• 2018

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.299-305
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• 2007

The endocrine disrupting chemical, di (2-ethylhexyl) phthalate (DEHP) is a plasticizer used in polyvinyl chloride products ubiquitous in our daily lives. DEHP has potentially adverse effects on the liver, kidney, lung, heart, reproductive organs and endocrine systems. Many toxicological data on the DEHP toxicity have been stated, but complete protein profiles have not yet been reported. In this study, DEHP-induced oxidative DNA damage in rat lymphocyte was evaluated by Comet assay (single-cell gel electrophoresis) for the first time. Moreover, DEHP-induced protein profile alterations were examined in rat liver by using toxicoproteomic tools. 34 protein spots in the liver were identified to be significantly deregulated by DEHP on the 2-dimensional gel. Among them, 20 spots were up-regulated and 14 spots down-regulated by DEHP.

• 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.

• YAKHAK HOEJI
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• v.33 no.4
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• pp.211-218
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• 1989

Twenty-six injectable drug products, many of which are administered by i.v. infusion, were studied for loss from aqueous solutions stored in polyvinyl chloride (PVC) infusion bags for various periods of time. The PVC infusion bags were stored in the dark room at room temperature for up to one month. Drugs stored in glass bottle served as controls. The solutions were assayed Spectrophotometrically at regular intervals. The effect of drug concentration and pH on the loss of drug from solution were studied. Octanol-water partition coefficients were used as a guage of lipid solubility of drugs. The elution of di(2-ethylhexyl)phthalate(DEHT) from PVC infusion bags was studied. For most of the drug studied, minimal loss from the aqueous solutions were observed over periods of storage time. Six of the drug products - Thiopental sodium, Hydralazine HCl, Thioridazine HCl, Trifluoperazine 2HCl, Metronidazole, Chlorpromazine HCl - were found to be lost a substantial extent. DEHP was found to be migrating from PVC infusion bags.

• Development and Reproduction
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• v.22 no.1
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• pp.85-94
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• 2018

Endocrine disruptors have been concerned in toxicology but now challenged as physiological point especially concerned with exposing dose and period. In this study the low-dose chronic administration of di(2-ethylhexyl) phthaltae (DEHP) during reproductive period was examined to evaluate the possible roles. Adult male and female CD-1 mice were exposed to DEHP with drinking water containing $133{\mu}g/L$ and $1,330{\mu}g/L$ DEHP in water according to OECD 433 guide line and sacrificed just after weaning. The weights of uterus and ovary were decreased by drinking of $1,330{\mu}g/L$ DEHP water. There was not adverse effects on either accumulated mating rate and mating rate depend on estrus stage, pregnancy duration, and sex ration at birth. However, the accumulated rate of successful delivery and litter size were significantly high at $1,330{\mu}g/L$ DEHP water. The number of epididymal sperm was significantly increased by drinking of $1,330{\mu}g/L$ DEHP water. In addition, the number of follicles (primary, secondary, tertiary) were more many than control at $1,330{\mu}g/L$ DEHP water drunk mother. Though further studies are needed to identify what are the mechanism of DEHP in folliculogenesis and spermatogenesis. From this study we firstly report the effect of low-dose chronic administration of DEHP with drinking could change the ovarian follicle population size and spermatogenesis rate. Put together, those finding is different from previous high-dose effects and suggest the physiological role of DEHP in gonads and uterus.

• Journal of Food Hygiene and Safety
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• v.22 no.3
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• pp.218-222
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• 2007

Di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) were screened for estrogenic activity using a recombinant yeast screening system consisted with estrogen receptors and ${\beta}-galactosidase$ as reporter gene. The chemicals showed estrogenic activity in ranges of $1{\times}10^{-10}\;to\;1{\times}10^{-7}M(DEHP)\;and\;of\;1{\times}10^{-9}M\;to\;1{\times}10^{-6}M(DBP)$ respectively. $17{\beta}-estradiol$, as a positive control of, showed maximal activity at $1{\times}10^{-9}M$. The concentration of half-maximal estrogenic activity was $1{\times}10^{-9}M$ for both chemicals. However, the concentration of maximal estrogenic activity was $1{\times}10^{-7}M$ for DEHP and $1{\times}10^{-8}M$ M for DBP. These results suggested that DBP was higher in relative potencies and more sensitive than DEHP. In conclusion, DEHP and DBP were both estrogenic, even though DBP was more reactive to estrogen receptor.

• Journal of Food Hygiene and Safety
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• v.20 no.4
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• pp.199-204
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• 2005

Three hundred sixty-eight samples of domestic PVC food packaging were analyzed fir DEHP(di-(2-ethyhexyl) phthalate) used in plasticizer by GC/FID and GC/MSD. The number of samples collected were 47(2000), 143(2001), 88(2002) and 89(2004) from local markets in Gyeonggi-Do. In $2000\∼2001$, DEHP was highly detected in 86 out of 190 samples and the level of DEHP were ranged from 1.3 g/kg to 82.8 g/kg. In 2002, meanwhile, DEHP was detected in 8 out ot 88 samples and the level of DEHP were shown to from 1.3 g/kg to 51.5 g/kg. In 2004, DEHP was detected in only one out of 89 samples and the amount was 30.5 g/kg. As a result of this study, it was made clear that the detection rates of DEHP in PVC food packaging were rapidly decrease every year.

• Journal of Environmental Health Sciences
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• v.29 no.2
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• pp.7-15
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• 2003

Di-2-ethylhexyl phthalate (DEHP), is a widely used plasticizer known to be a suspected endocrine disrupter, but its exact effects on aquatic organisms are not yet known. When Japanese medaka (Oryzias latipes) were exposed from the time of hatching to 3 months of age to an aqueous DEHP solution at nominal concentrations of 1, 10, and 50 $\mu\textrm{g}$/l, DEHP treated female fish showed distinct reproductive effect. And the midge (Chironomus riparius.). an aquatic invertebrate, was exposed to DEHP to evaluate the effects on reproductive processes via sediment toxicity. The test endpoints included emergence, sex ratio, fecundity, and the viability of F1 offspring egg ropes. The result implied that the normal developmental and/or reproductive processes in C. riparius had been disrupted when exposed to DEHP, the effect also being displayed in the next generation. In summary, DEHP hinders the development of reproductive organs in the female Japanese medaka and C. riparius.

• Natural Product Sciences
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• v.19 no.4
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• pp.366-371
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• 2013

Seventeen compounds (1 - 17), ${\beta}$-sitosterone (1), lupenone (2), arborinone (3), ${\beta}$-sitosterol (4), lupeol (5), epi-lupeol (6), taraxerol (7), betulinic acid (8), 24R-methyllophenol (9), germanicol (10), hexatriacontane (11), nonacosan-1-ol (12), benzoic acid (13), tetradecyl(E)-ferulate (14), di(2-ethylhexyl) phthalate (15), trilinolein (16) and monopalmitin (17), were isolated from the methylene chloride-soluble fraction of the cork of Euonymus alatus Sieb. The structures of these compounds were elucidated on the basis of spectroscopic evidence. Compounds 6, 11, 13 and 14 were isolated for the first time from this plant. Compound 4 showed moderate cytotoxic activity with an $IC_{50}$ value of 6.22 ${\mu}M$ in HL-60 cell line. Compound 9 exhibited moderate cytotoxic activity with $IC_{50}$ values of 63.31, 15.45, 15.14 and 21.72 ${\mu}M$ in four kinds of human cancer cell lines, Jurkat T, HeLa, HL-60 and MCF-7, respectively. Compound 17 showed moderate cytotoxic activity with an $IC_{50}$ value of 70.71 ${\mu}M$ in Jurkat T cell line. In addition, compounds 2, 3, 14 and 16 exhibited weak antioxidant activity with $IC_{50}$ values of 151.76, 170.79, 137.46 and 139.37 ${\mu}M$, respectively.

• Journal of Korean Society of Water and Wastewater
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• v.30 no.6
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• pp.673-682
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• 2016

In this study, we investigated influent and effluent water pollutants in 53 Public Sewage Treatment Works (PSTWs) where industrial wastewater or landfill leachate is combined four times for two years from 2014 to 2015. Also, we analyzed the characteristics of heavy metals and volatile organic carbons at influent and effluent of these PSTWs caused by sewage treatment combined with industrial wastewater or landfill leachate. As a result, six heavy metals such as barium, copper, iron, manganese, nickel and zinc, and four volatile organic carbons (VOCs) including phenols, di(2-)ethylhexyl phthalate (DEHP), formaldehyde and toluene were observed above detection limits in most of PSTWs. Also, it was revealed that six heavy metals such as hexavalent chromium, mercury, cadmium, chromium, nickel and selenium, and four VOCs including 1,1-dichloroethylene, vinyl chloride, naphthalene, and epichlorohydrin were observed more frequently according to precipitation. As a result of reviewing the monitoring data on "Water Quality Monitoring Networks" in lower watersheds of PSTWs, both heavy metals and VOCs were below detection limits, indicating that the effluent water had little influence on the watershed. Nevertheless for the better management of influent and effluent pollutants in PSTWs, it is necessary to establish the advanced management plans for water pollutants in PSTWs, which include a list of priority substances management, monitoring plans, and guidelines for industrial wastewater and landfill leachate combined in PSTWs.