• 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.

• 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.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.2.1-2.15
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• 2023

Background: Phthalates are endocrine disrupting chemicals that are widely used in the production of items of daily life such as in polyvinylchloride plastics, insecticides, and medical devices. This study aimed to determine the association between phthalate exposure and shellfish consumption using data from the Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017), which is a nationally representative survey. Methods: In this study, we analyzed the KoNEHS cycle 3 data of 3,333 (1,526 men and 1,807 women) adults aged more than 19 years. Data related to the variables of sociodemographic factors, health-related behaviors, dietary factors, seafood consumption frequency, and urinary phthalate metabolites concentrations were collected. The concentrations of urinary phthalate metabolites of all the participants were divided into quartiles to define high and low concentration groups based on the 75th percentile concentration. A χ² test was conducted to analyze the distribution of independent variables. To analyze the relationship between shellfish consumption and phthalate exposure, the odds ratios (ORs) were calculated using logistic regression analysis. Results: Total adults with shellfish consumption frequency of over once a week showed the following adjusted ORs for high concentrations of the following metabolites compared with the group that consumed shellfish once a week or less: 1.43 (95% confidence interval [CI]: 1.01-2.06) for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), 1.43 (95% CI: 1.01-2.03) for mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), 1.57 (95% CI: 1.10-2.24) for ∑di-2-ethylhexyl phthalate (∑DEHP), 2.01 (95% CI: 1.46-2.77) for mono-carboxyoctyl phthalate (MCOP), 1.56 (95% CI: 1.11-2.18) for mono-carboxy-isononly phthalate (MCNP), and 2.57 (95% CI: 1.85-3.56) for mono (3-carboxypropyl) phthalate (MCPP). Conclusions: The concentrations of urinary phthalate metabolites (MEOHP, MECPP, ∑DEHP, MCOP, MCNP, and MCPP) were higher in adults with a higher frequency of shellfish consumption.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.10
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• pp.1460-1466
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• 2012

The purpose of this study was to evaluate plasticizer pollution levels in mudflat solar salt, salt water and sea water of the nationwide saltpan. Also, it was analyzed the relationship between DEHP in solar salt and PVC mat following private period. DEP (ranging from 0.00 to 1.55 ppb), DIBP (0.00~2.38), DBP (0.00~4.90), DEHA (0.00~2.32), and BBP (0.00~1.45) in solar salt were shown a extremely low concentrations, and DEHP was present a concentrations ranging from 0.00 to 268.5 ppb in solar salt. Further, DMP, DPrP, DNPP, DNHP, and DCHP were not detected in all solar salt. Phthalate in sea water and salt water was present a infinitesimal amount levels. DEHP levels in sea water and salt water were not shown a high risk levels ranging from 0.00 to 3.4 ppb, and from 0.00 to 21.4 ppb, respectively. As expected in PVC mat of nationwide saltpan, the correlation between DEHP in solar salt and PVC mat private period showed a low positive correlation coefficient ($r^2$=0.0362).

• Journal of Embryo Transfer
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• v.25 no.4
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• pp.207-213
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• 2010

Thousands of new chemicals have been introduced to environment during last decades. Many of them and common consumer products have been shown to be the endocrine disrupting chemicals. One such chemical group is the phthalates, used in soft poly vinyl chloride (PVC) material and in a huge number of consumer products. The prevalence of these modem chemicals have a remarkable increase. Approximately 3.5 million tons of the main phthalate, di-(2-ethylhexyl) phthalate (DEHP), are produced annually worldwide and indeed, DEHP is considered a ubiquitous environmental contaminant. It has been demonstrated that high doses of phthalate can adversely affect adult and developing animals. In this review, we critically discuss the conclusions of recently original research papers and provide an overview of studies on reproductive disrupting effects of phthalates. In addition, we review the reproductive toxicity data of phthalates in some in vitro research and in both male and female reproductive systems in experimental and domestic animals. Finally, we point out some critical issues that should be addressed in order to clarify the implication of phthalates for human reproduction.

• Journal of Radiation Industry
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• v.8 no.2
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• pp.71-76
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• 2014

Endocrine disrupting chemicals (EDCs) and potential EDCs are mostly man-made, found in various materials such as pesticides, additives or contaminants in food, and personal care products. The high energy ionizing radiation has the ability to remove the EDCs with a very high degree of reliability and in a clean and efficient manner. The ionizing radiation interacts with EDCs both directly and indirectly. Direct interaction takes place with EDCs and the structure of EDCs is destroyed or changed. During indirect interaction, radiolysis products of water result in the formation of highly reactive intermediates which then react with the target molecules, culminating in structural changes. To confirm the radiation reduction of EDCs in industrial sludge, a pilot scale experiment up to 50 kGy of electron beam (EB) was conducted with samples from the textile dyeing industries. The experimental result showed the over 90% of reduction of Nonylphenol (NP) and Di(2-ethylhexyl) phthalate (DEHP) at around 10 kGy of absorbed doses.

• Journal of Environmental Health Sciences
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• v.36 no.6
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• pp.510-517
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• 2010

Phthalates, such as di (2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) have been proved to be teratogenics and endocrine disruptors, metabolized rapidly and excreted in the urine. In this study, a simultaneous analytical method for 10 phthalate metabolites, MnBP, MiBP, MBzP, MCHP, MEHP, MEHHP, MEOHP, MnOP, MiNP and MiDP, in human urines, based on switching system with on-line pretreatment column using HPLC-MS/MS has been developed. This method was validated according to the guideline of bioanalytical method validation of National Institute of Toxicological Research. Limits of detection range between 0.2 and 0.9 ng/ml for 10 phthalate metabolites. The calibration curves showed linearity in the range 0.997~0.999, and the results of the intra- and inter-day validations were in the range from 0.4 to 14.7% RSD and from 0.3 to 9.4% RSD, respectively. Recoveries of phthalate metabolites varied from 87.0 to 116.1%. This analytical method showed high accuracy and stable precision for all metabolites, and seems to be suitable for biomonitoring of phthalates in human urine.

• 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.

• Journal of Microbiology and Biotechnology
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• v.10 no.3
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• pp.293-299
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• 2000

Many methods have been developed for screening chemicals with hormonal activity. Using recombinant yeasts expressing either human estrogen receptor [Saccharomyces cerevisiae ER + LYS 8127 (YER)] or androgen receptor [S. cerevisiae AR + 8320 (YAR)], we evaluated the hormonal activities of several chemicals by induction of ${\beta}-galactosidase$ activity. The chemicals were $17{\beta}-estradiol$ (E2), testosterone (T), ${\rho}-nonylphenol$ (NP), bisphenol A (BPA), genistein (GEN), 2-bromopropane (2-BP), dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and butylparaben (BP). To assess the estrogenicity of NP, the result of the in vitro recombinant yeast assay was compared with an E-screen assay using MCF-7 human breast cancer cells and an uterotrophid assay using ovariectomized mice. In the YER yeast cells, E2, NP, BPA, GEN, and BP exhibited estrogenicity in a doseresponse manner, while TCDD did not. All the chemicals tested, except T, did not show androgenicity in the YAR yeast cell. The sensitivity of the yeast (YER) assay system to the estrogenic effect of NP was similar to that of the E-screen assay. NP was also estrogenic in the uterotrophic assay. However, in terms of convenience and costs, the yeast assay was superior to the E-screen assay or uterotrophic assay. These results suggest that the recombinant yeast assay can be used as a rapid tool for detecting chemicals with hormonal activities.

• Development and Reproduction
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• v.8 no.2
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• pp.77-84
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• 2004

The purpose of this experiment was to determine the effects of di(2-ethylhexyl) phthalate(DEHP) on reproductive characteristic, blood hematological and chemical values in mice. The male mice were intraperitoneally injected DEHP in negative control(no treatment), positive control(corn oil, 3ml/kg B.W), 0.5, 1.0 and 10.0mg DEHP/kg B.W and the female mice were injected DEHP in control(corn oil, 3ml/kg B.W), 0.5, 1.0 and 10.0mg DEHP/kg B.W with 5 times for 15 days on 3 days interval. The administration of DEHP in male mice were not affect on body weight, epididymis, vesicular gland and coagulating gland weight. The testis weight were slightly higher in DEHP treatment groups than in control. The semen characteristics(sperm concentration, viability, motility and abnormality) of male mice were not difference in all experimental groups. The RBC, Hb, HT, MCV, MCH, MCHC< PLT, albumin, BUN and total protein of blood hematological and chemical values were not affect the administration of DEHP in mice. The WBC values in 10.0mg DEHP group was slightly difference in all experimental group(P>0.05). The histological evaluation of testis, ovary and affevt the reproductive characteristic, blood hematological and chemical values.