• Toxicological Research
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• v.26 no.1
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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.

• Journal of Environmental Science International
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• v.12 no.1
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• pp.81-86
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• 2003

The study was carried out to evaluate the new analytical method of phthalate esters(diethylphthalate, di-n-butylphthalate, butylbenzylphthalate, bis(2-ethylhexyl)phthalate), one of the endocrine disruptors, which were performed by GC/MS-SIM(selected ion monitoring). The phthalate esters were extracted from water samples using solid-phase extraction on $C_{18}$ columns. It investigated that the extraction recovery rate of phthalate esters with different solvents and solvent volume. The optimal solvent was dichloromethane and proper volume of dichloromethane for recovery of phthalate esters was 4 mL. There were good linearities(above $R^2$=0.9975) in the range 0.01~0.50mg/L, and the detection limits were below 0.01~0.03$\mu\textrm{g}$/L. The recovery rates, RSD and MDLs for phthalate esters were 80~114%, 5.0~8.1% and 0.03~0.11$\mu\textrm{g}$/L, respectively. This method shows a good precision of phthalate esters.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.106-113
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• 2006

Phthalate analogues are a plasticizer and solvent used in industry. Phthalates were classified in the category of "suspected" endocrine disruptors. The purpose of our study was to screen and elucidate the endocrine disrupting activity of seven phthalate analogues. E-screen assay was performed in MCF-7 human breast cancer cells with seven phthalate analogues. In this cell proliferation assay, benzyl butyl phthalate (BBP) and dibutyl phthalate (DBP) showed high estrogenic activity. Their relative proliferation efficiencies (RPE) were 109 and 106%, respectively. In vitro estrogen receptor (ER) binding assay, BBP, di-n-octyl phthalate (DOP) and dinonyl phthalate (DNP) showed weak relative binding affinity (RBA: 0.02%) compared to $17{\beta}-estradiol\;(E2)$ (RBA: 100%). In uterotrophic assay, E2 produced a significant increase, whereas four tested phthalate analogues had potential estrogenic effects in vitro did not increased in uterus weight in immature rats. From these results, we demonstrated that phthalate analogues exhibit weak estrogenic activity in vitro assays at high concentrations. Although phthalates induced an increase in MCF-7 cell proliferation by an estrogenic effect, they could not induce a uterus weight increase in vivo. From these, we may suggest that these phthalate analogues are easily metabolized to inactive forms in vivo. Further investigation in other in vitro and in vivo experimental systems might be required.

• Macromolecular Research
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• v.11 no.3
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• pp.178-182
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• 2003

The thermal decomposition of phthalate alone and with poly(vinyl chloride) (PVC) was carried out under a nitrogen atmosphere in a 4-necked separable flask. The thermal decomposition of phthalate in the presence of PVC began at 150$^{\circ}$, about 10$0^{\circ}C$ lower than the decomposition of phthalate alone. The formation of octyl chloride indicated an interaction reaction between phthalate and PVC. From the analysis of the composition of commercially plasticized PVC sheet (film and board), the phthalates (dibutyl phthalate, dihexyl phthalate) and di(2-ethylhexyl) phthalate), 2-ethyl-1-hexanol, phthalic anhydride, and 2-ethylhexyl hydrogen phthalate were identified. The mutage-nicities of these decomposition products were higher than those of phthalic diesters (phthalates).

• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.164-168
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• 2002

Phthalate analogues are a plasticizer and solvent used in industry and were reported to be a potential carcinogen classified in the category of suspected endocrine disruptors. Most common human exposure to these compounds may occur with contaminated food. They may migrate into food from plastic wrap or may enter food from general environmental contamination. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of phthalates that possibly threaten the public health. To determine whether seven phthalate analogues i.e. diallyl phthalate, diisodecyl phthalate, di-n-nonyl phthalate, butyl benzyl phthalate, di-n-octyl phthalate, di-tridecyl phthalate, and dibutyl phthalate, can induce DNA strand breakage that is one of the various factors related to the mechanism of carcinogenicity, the comet assay which has been widely used for the detection and measurement of DNA strand breaks, was conducted in L5178Y mouse lymphoma cells. From these results, seven phthalates revealed dose-dependent decrease of cell viability, however, no remarkable cytotoxicity was observed even at high concentration of 100 $\mu\textrm{g}$/$m\ell$ phthalates. And also, the results showed that the induction of DNA strand breaks by seven phthalates was not significantly different from the control in this study.

• Journal of Environmental Health Sciences
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• v.42 no.3
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• pp.169-188
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• 2016

Objectives: Although information on the toxicity of phthalate diesters is readily available, little is known about phthalate alternatives. The present article provides a summary of available information on the toxicity of phthalate diesters and their alternatives, with a special focus on estrogenicity and androgenicity. Methods: We collected a battery of in vitro and in vivo assay data from the literature to assess the estrogenicity/anti-estrogenicity and androgenicity/anti-androgenicity of 15 phthalate diesters and 21 phthalate alternatives. Results: A number of in vitro studies show that certain phthalate diesters can bind to estrogen receptors and have a weak estrogenic potential. However, this potential was not seen in in vivo studies. Phthalate diesters produced anti-androgenic effects in animals by reducing testosterone production. Among them, di-(2-ethyl-hexyl) phthalate (DEHP) was the most potent. While almost all phthalate alternatives have a lower toxic potential than does DEHP, evidence of reproductive toxicity and estrogenic potential were found in several substances. Conclusion: Significant data gaps exist for phthalate alternatives regarding reproductive endocrine disruption, requiring further investigation.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.147-152
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• 2000

The rodent uterotrophic assay is currently recommended as one of the primary in vivo assays far endocrine disrupting chemicals by the Organization for Economic Cooperation and Development (OECD) and Endocrine Disruptor Screening and Testing Advisory Committee (US EPA EDSTAC). Generally, this assay relies on the rapid increase in uterus and vagina weights when exposed to estrogenic compounds. Phthalate esters have been used extensively as a plasticizer in the manufacture of plastic products such as PVC films and medical devices. Recently, phthalate esters have been shown to induce endocrine system mediated responses. However, a flew studies have been conducted for the screening of their estrogenic activity. In this study the estrogenic activity of seven phthalate esters, butyl benzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), di-n-butylphthalate (DBP), diethylphthalate (DEP), di-n-pentylphthalate (DPF), di-n-propylphthalate (DPrP) and dicyclohexylphthalate (DCHP), was examined in uterotrophic assay. Phthalate esters dissolved in corn oil were administered to ovariectomized (OVX) female Sprague-Dawley rats by sub-cutaneous injection for three consecutive days. fiats were sacrificed 24h after final treatment, and then uterus and vagina weights were deter mined. All phthalate esters tested in this assay did not change talc uterus and vagina weights at dosage levels up to 200 mg/kg/day treatment. These results demonstrated that phthalate esters did not exhibit estrogenic activity in vivo uterotrophic assay.

• KOREAN JOURNAL OF PACKAGING SCIENCE & TECHNOLOGY
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• v.6 no.1
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• pp.41-46
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• 2000

The level of plasticizer such as diethyl phthalate (DEP), di-n-propyl phthalate (DprP), di-n-butyl phthalate (DBP), di-n-pentyl phthalate (DPP), butylbenzyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP), dicyclohexyl phthalate (DCHP) and di-(2-ethylhexyl) adipate (DEHA) was determined in disposable sanitary gloves. Samples of disposable sanitary gloves were taken at retail shops, and their overall extractions in carbon tetrachloride were measured, after establishment of soxhlet appratus in 6 hours. All of 8 samples of disposable sanitary gloves at retail shops were polyethylene (PE). All of the manufactures was voluntarily labelled their boxes of gloves in line Korea Food Code. The level of phthalate esters and DEHA in all of 8 samples were not exceed the detection limit. The detection limits of DEP, DprP, DBP, DPP, BBP, DEHP, DCHP and DEHA were 1.8, 1.9, 1.3, 1.1, 0.9, 0.7, 2.1 and 0.8 mg/L, respectively.

• Toxicological Research
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• v.16 no.2
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• pp.141-146
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• 2000

Phthalate esters are used extensively as a plasticizer in the manufacture of plastic products such as PVC bags and medical devices. Recently, phthalate esters have been shown to induce endocrine system mediated responses. However. only a Jew studies have been conducted for estrogenic activity of phthalate esters. In this study estrogenic activities of seven phthalate esters. butyl benzyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), di-n-butylphthalate (DBP), diethylphthalate (DEP), di-n-pentylphthalate (DPP), di-n-propylphthalate (DPrP) and dicyclohexylphthalate (DCHP), were examined in vitro using E-screen assay and competitive binding assay. From the E-screen assay, BBP. DEHP. DBP and DEP showed weak estrogenic activity at the concentration of 5 $\mu\textrm{M}$. The relative proliferative effect (RPE) and the relative proliferative potency (RPP) were 50~70% and 0.01%. respectively, when compared with 500 pM of 17$\beta$-estradiol (E2). In competitive binding assay with the rat uterine estrogen receptor (ER), BBP and DEP showed weak binding potency ［(l/$10^4$~1/$10^5$ of E2］ while DEHP and DBP scarcely bound to ER. These results suggest that some phthalate esters have weak estrogenic activities in vitro.

• Safety and Health at Work
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• v.2 no.1
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• pp.57-64
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• 2011

Objectives: Although phthalates like dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are commonly used as plasticizers and their metabolites are especially suspected of reproductive toxicity, little is known about occupational exposure to those phthalates. The aim of this study was to assess the utility of measuring the metabolite concentrations of DBP and DEHP in serum and urine samples as an indicator of occupational exposure to those phthalates. Methods: Phthalate metabolites were analyzed by using column-switching high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: We detected phthalate metabolites in serum and urine matrices at approximately 10-fold lower than the limit of detection of those metabolites in the same matrix by LC-MS/MS without column switching, which was sufficient to evaluate concentrations of phthalate metabolites for industrial workers and the general population. Conclusion: The accuracy and precision of the analytical method indicate that urinary metabolite determination can be a more acceptable biomarker for studying phthalate exposure and adverse health outcomes.