Disease relevance of Dioctyl phthalate

• The numbers of Leydig cells in the testis of DEHP-treated rats were 40-60% higher than in control rats, indicating induction of Leydig cell hyperplasia [1].
• In agreement with previous studies, hemolysis and microvesicle formation were also reduced in the presence of DEHP [2].
• Although toxicokinetics seem to play a certain unclear role in the course of DEHP-related toxicity, toxicodynamic factors appear more decisive [3].
• Also, DEHP fed for 24 weeks had no promoting effect on liver altered foci that were induced by FAA and produced little or no enhancement of the occurrence of FAA-induced liver neoplasms [4].
• In the rats fed DEHP, substantial hepatomegaly and peroxisome proliferation were induced [4].

High impact information on Dioctyl phthalate

• Daily human exposure to DEHP in the U.S. is significant, and occupational and clinical exposures from DEHP-plasticized medical devices, e.g., blood bags, hemodialysis tubing, and nasogastric feeding tubes, increase body burden levels [1].
• Pooled RCC was aliquoted into PL146 (PVC), PL732 (polyolefin), and PL732 (with added DEHP) bags with samples removed weekly for analysis of osmotic fragility, deformability, and DEHP concentration [5].
• The data are consistent with the hypothesis that DEHP inhibits the deterioration of the red blood cell membrane that results from the refrigerated storage of whole blood [6].
• When 300 micrograms/mL DEHP was added to stored blood containing erythrocytes predominantly in the echinocyte conformation, many of the cells reverted to the normal discoid morphology [6].
• In conclusion, when performed under conditions similar to the tumorigenicity studies, the degree of peroxisome proliferation correlated poorly with the relative hepatocarcinogenicity of DEHP and Wy-14,643 [7].

Chemical compound and disease context of Dioctyl phthalate

• The plasticizer di(2-ethylhexyl)phthalate (DEHP) and its main metabolite monethylhexylphthalate (MEHP) were investigated in several short-term in vitro assays, including mutagenicity in Salmonella typhimurium TA102, a strain sensitive to mutations arising as a cause of oxidative DNA damage [8].
• Comparative investigation of steroid transforming activity and ultrastructural changes of bis(2-ethylhexyl)phthalate (BEHP, phthalate) treated Mycobacterium sp. NRRL B-3805 cells was carried out [9].
• The absence of observable hepatic effects in monkeys at doses that produce hepatic effects in rodents suggests that DINP, DEHP, and clofibrate would also not elicit in primates other effects such as liver cancer [10].
• Atheroma in chronic dialysis subjects is still unexplained, but hepatitis probably caused by diethylphthalate from plastic was resolved when apparatus plasticised by DEHP alone was substituted [11].
• The antagonistic interaction may be due at least in part to the fact that both DEHP and chlorpyrifos are lipophilic, and the increase in the total lipophilic pool by the DEHP resulted in internal levels of toxicant below the toxicity threshold [12].

Biological context of Dioctyl phthalate

• The increase in osmotic fragility during storage was greater when RCC was stored without DEHP [5].
• When added to a CD diet, both BR931 and DEHP effectively protected against the diet-induced lipid peroxidation [13].
• Plasma membranes from DEHP-treated rats did not demonstrate phosphorylation of this Mr 40,000 protein [14].
• To evaluate this possible correlation, di(2-ethylhexyl)phthalate (DEHP) at 1.2% and [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) at 0.1% were fed to male F-344 rats for up to 365 days and hepatocytic peroxisome proliferation and DNA replication were measured [7].
• Our results suggest that changes in estrogen metabolism, receptor activity and activation of genes for cell proliferation are among the earliest metabolic alterations induced by DEHP [15].

Anatomical context of Dioctyl phthalate

• Labeling of hepatocyte nuclei with a single injection of tritiated thymidine revealed a rapid burst in replicative DNA synthesis in both DEHP and Wy-14,643-fed rats, with a return to control levels by 4 days [7].
• Furthermore, when rats were pretreated with dietary glycine, which inactivates Kupffer cells, DEHP did not increase radical signals [16].
• The present study describes the possible involvement of oxidative stress in the pathogenesis of atrophy of the rat testis induced by di(2-ethylhexyl)phthalate (DEHP) [17].
• Oxidative stress was selectively induced in germ cells, but not in Sertoli cells, treated with mono(2-ethylhexyl)phthalate (MEHP), a hydrolysed metabolite of DEHP [17].
• Lipofuscin, which was contained within lysosomes, was increased 3-fold after 39 days of DEHP and remained at this level up to 365 days of treatment [18].

Associations of Dioctyl phthalate with other chemical compounds

• The addition of this quantity of DEHP to blood had no significant effect on the course of storage-induced changes in erythrocyte adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), sodium or potassium concentrations [6].
• In the present study, the effects of 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-beta-hydroxyethyl)acetamid e (BR931) and di(2-ethylhexyl)phthalate (DEHP) on CD diet-induced liver membrane lipid peroxidation were investigated by determining the extents of conjugated diene formation [13].
• Upon treatment with DEHP, cholesterol decreased in the control but remained unchanged in the receptor-deficient mice [19].
• Furthermore, DEHP given with [(13)C(2)]dimethyl sulfoxide produced a 12-line electron spin resonance spectrum, providing evidence that DEHP stimulates (*)OH radical formation in vivo [16].
• Concentrations up to 0.5 mM mono(2-ethylhexyl)phthalate, a principal metabolite of DEHP, were also examined in the human hepatocyte assay [20].

Gene context of Dioctyl phthalate

• Site-directed mutagenesis experiments showed that a mutated activator protein 2-binding site markedly reduced the transcriptional activity of both promoters and abolished the minimal VLCAD promoter's response to DEHP treatment [21].
• The immunoreactivity for EC-GPX was also significantly decreased in the DEHP-treated kidney compared with the control [22].
• We conclude that DEHP is an inducer of the MDR1 gene in this cell line [23].
• To examine such a hypothesis, the effect of DEHP on SXR-mediated transcription of the MDR1 gene was studied in the human colon adenocarcinoma-derived cell line, LS174T cells, which endogenously express SXR [23].
• From the results, it is concluded that overexpression of PPARalpha or the transgene is not associated with the liver tumorigenesis induced by DEHP in rasH2 mice [24].

Analytical, diagnostic and therapeutic context of Dioctyl phthalate

• Furthermore, DEHP was investigated in two long-term bioassays with Syrian golden hamsters using both i.p. (max. total dose 54 g/kg) and inhalative (7-10 mg/kg) application [8].
• MEASUREMENTS AND MAIN RESULTS: All DEHP plasma concentrations were measured by gas chromatography [25].
• Daily plasma concentrations for DEHP were collected until 3 days after decannulation from bypass in the ECMO group [25].
• Serum concentrations of DEHP were determined from peripheral blood obtained before and after plateletpheresis, with gas chromatography-mass spectroscopy [26].
• Increase in serum DEHP was short-term as serum DEHP rapidly returned to levels obtained before apheresis within 3 hours after completion of the apheresis course [26].

References