• 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.

• 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.

• 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).

• Journal of Environmental Health Sciences
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• v.34 no.4
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• pp.271-278
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• 2008

Dialkylated phthalates have been commonly used as plasticizers and a variety of applications. Phthalate diesters have been shown to be developmental and reproductive toxicants. It is very difficult to exactly estimate the dose of dialkylated phthalates taken up by the general population because of environmental contamination. Urinary metabolites of phthalates enabled to estimate internal exposure. The objective of this study was quantitative determination of phthalate metabolites by LC/MS/MS with on-line cleanup method to analyze phthalate metabolites in Korean children's urine. We employed LC/MS/MS with on-line enrichment and column-switching techniques for this biological monitoring. Metabolites determined were 4 primary metabolites; MEHP, MnBP, MiBP, MEP and 2 secondary metabolites of DEHP; 5-OH-MEHP), 5-oxo-MEHP. We analyzed children's urine from 30 boys and 30 girls. The method detection limit of phthalate metabolites were 0.03 ng/mL for MEP, 1.05 ng/mL for MBP, 0.22 ng/mL for MEHP, 0.15 ng/mL for 5-OHMEHP and 0.16 ng/mL for 5-oxo-MEHP, respectively. Switching Column LC/MS/MS was proven to be a useful tool to determine metabolites of phthalate diesters in human urine. The correlation among phthalate metabolites was very high and statistically significant, except MEP. The children's age (months) was negatively correlated to the concentration of phthalate metabolites. The geometric mean concentration of phthalate metabolites (mg/g creatinine) in children's urine were 25.5 for MEP, 130.3 for MnBP, 56.8 for MiBP, 19.5 for MEHP, 85.6 for 5-OH-MEHP and 83.1 for 5-oxo-MEHP, respectively. Levels of estimated daily intake of parent phthalate compounds (${\mu}g$/kg bw/day) were 0.8 for DEP, 5.0 for DnBP, 1.9 for DiBP and $8.9{\sim}14.2$ for DEHP, respectively. Estimated daily intake for DEP and DiBP were lower than those of other studies but the value for DEHP was higher than that of other study.

• Journal of Environmental Health Sciences
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• v.39 no.4
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• pp.360-368
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• 2013

Objectives: Phthalates are used in a large variety of products including as coatings of pharmaceutical tablets, film formers, stabilizers, dispersants, emulsifying agents, and suspending agents. They have been the subject of great public concern in recent years. The extensive uses of this material have attracted attention and issues regarding its safety have been raised. Methods: In this study, three types of phthalate skin permeation were studied using matrixes such as ointments, creams and lotions in vitro. The absorption of phthalate diesters [Dimethyl phthalate (DMP), Di-n-propyl phthalate (DPP) and Di-n-pentyl phthalate (DNPP)] using film former has been measured in vitro through rat skin. Epidermal membranes were set up in Franz diffusion cells and their permeability to PBS measured in order to establish the integrity of the skin before the phthalates were applied to the epidermal surface. Results: Absorption rates for each phthalate ester were determined and permeability assessment made to quantify any irreversible alterations in barrier function due to contact with the esters. Types of phthalate in vitro experimental results quickly appeared in the following order DMP > DPP ${\geq}$ DNPP. Conclusions: In the experimental results, lotion> cream> ointment, and the permeation rate of lotion with a great amount of moisture was the fastest. Skin permeation rate is generally influenced by the chemical characteristics of a given chemical, such as molecular weight and lipophilicity. As the esters became more lipophilic and less hydrophilic, the rate of absorption decreased.