Disease relevance of 3,4-dioctylbenzene-1,2-dicarboxylic acid

• Cessation of exposure to DEHP initiated partial to complete recovery from toxicity in most cases [1].
• Studies in the rat indicated that exposure to doses of 1/6 and 1/12 of the LD50 per day of DEHP resulted in a reduced gain in body weight compared to controls [2].
• Both DEHP and MEHP induced 8AG/6TG-resistant mutation, chromosomal aberrations and morphological transformation in the embryonic cells of the Syrian golden hamster [3].
• Prolonged exposure to the peroxisome proliferator, DEHP, causes hepatic hyperplasia and liver tumors in rats and mice [4].
• The data indicate that high levels of peroxisome proliferation and hepatomegaly are associated with DEHP hepatocarcinogenesis in rodent liver, and that the tumorigenic process may be arrested by cessation of DEHP treatment, suggesting that extended treatment with DEHP acts to promote tumor growth [5].

High impact information on 3,4-dioctylbenzene-1,2-dicarboxylic acid

• The nongenotoxic carcinogens methylclofenapate and DEHP cause an initial hyperplastic response due to the rapid conversion of binucleated cells to mononucleated tetraploids by amitotic cytokinesis following S phase [6].
• The mRNA levels of HMG-CoA reductase were not changed by either DEHP or fat diet, while DEHP increased cytosolic HMG-CoA synthase 2.5-fold [7].
• DEHP did not change the mRNA levels for fatty acid synthase [7].
• Rats fed with a fat diet significantly increased the expression of mitochondrial HMG-CoA synthase, CPT I and CPT II 3-fold in all cases, while 2-(diethylhexyl)phthalate (DEHP) produced increases in the expression of these genes (5-, 4- and 12-fold, respectively) [7].
• Wy-14643 was also stronger than DEHP in stimulating c-jun expression, whereas both PPs were fairly strong inducers of jun-B and jun-D [8].

Chemical compound and disease context of 3,4-dioctylbenzene-1,2-dicarboxylic acid

• The metabolism and toxicity of the ubiquitous plasticizer, bis-(2-ethylhexyl) phthalate (DEHP), and its principal metabolite, mono-(2-ethylhexyl) phthalate (MEHP), have been extensively investigated [9].
• From the culture broth of a fungus, two metabolites have been isolated: bis(2-ethylhexyl)phthalate (DEHP) precedently isolated from Streptomyces sp. and 2-(4-hydroxyphenyl)-2-oxoacetaldehyde oxime (PHBA) here reported as a natural compound in the (E)-s-cis configuration [10].
• Between 1998 and 2000 an Expert Panel convened by the National Toxicology Program's Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) reviewed information related to the developmental and reproductive toxicity of seven phthalate esters; DBP, BBP, DnHP, DEHP, DnOP, DINP, and DIDP [11].
• The results suggest use of vitamin E to prevent harmful effects of repeated transfusion of DEHP containing blood as in thalassemia patient [12].

Biological context of 3,4-dioctylbenzene-1,2-dicarboxylic acid

• These estimates, however, could be high due to the simultaneous excretion of DEHP remaining from previous transfusions or arising from uncontrolled environmental exposures [13].
• DEHP was administered orally in dosages of 0.05 ml/kg to 30.0 mg/kg on day 6, 7, 8, 9 or 10 of gestation [14].
• In separate experiments, DEHP did not induce sister chromatid exchange (SCE) or DNA damage in Chinese hamster ovary (CHO) cells [2].
• Effects of bis(2-ethylhexyl) phthalate (DEHP) on secondary sex ratio of mice in a cross-mating study [15].
• However, in 1982 the National Toxicology Program reported a significantly increased incidence of hepatocellular carcinoma in rats and mice exposed to high doses of DEHP over a period of two years [16].

Anatomical context of 3,4-dioctylbenzene-1,2-dicarboxylic acid

• Dietary exposure of adult male F344 rats to 0, 320, 1250, 5000, or 20,000 ppm DEHP for 60 consecutive days resulted in a dose-dependent reduction in total body, testis, epididymis, and prostate weights at 5000 and 20,000 ppm [1].
• Together with the CHO and micronucleus data, these findings suggest that DEHP has a low probability of causing genetic damage capable of being transmitted through the male germ line [2].
• Transfusion of these platelets into six adult patients with leukemia resulted in peak blood plasma levels of DEHP ranging from 0.34 to 0.83 mg/dl (approximately 0.02 mg/dl plasma per mg DEHP administered per square meter of surface area) [13].
• Labeling of liver tissue from DEHP-treated rats with rabbit immune IgG made to the purified microsomal hydratase followed by gold conjugated goat anti-rabbit IgG suggested a single subcellular site for the bifunctional hydratase--the peroxisomal organelle [17].
• The alpha-, beta- and p120-catenins were detected in the basal compartment of seminiferous tubules in similar localization and IF pattern for DEHP and control groups [18].

Associations of 3,4-dioctylbenzene-1,2-dicarboxylic acid with other chemical compounds

• After 4 hr incubation in vitro, dioctylphthalate and benzylbutylphthalate significantly inhibited vasopressin-stimulated water flow in toad bladder [19].
• Rat liver peroxisomes were markedly proliferated by administration of dioctyl phthalate (DEHP) for 2 weeks [20].
• The present study explored whether the antiandrogenic action of DEHP occurs by (1) inhibiting testosterone (T) production, or by (2) inhibiting androgen action by binding to the androgen receptor (AR) [21].
• Mono(2-ethylhexyl)phthalate (MEHP), the primary metabolite of the plasticizer bis(2-ethylhexyl)phthalate (DEHP), was given to guinea pigs and mice and the methods for the isolation, separation and analysis of its metabolites in urine were developed [22].
• Maximum and minimum mean concentrations in the total diet samples were: 0.09-0.19 mg DBP/kg, 0.017-0.019 mg BBP/kg, 0.11-0.18 mg DEHP/kg and 0.13-0.14 mg DEHA/kg [23].

Gene context of 3,4-dioctylbenzene-1,2-dicarboxylic acid

• Using northern analysis, RNase protection assay, and RT-PCR, we show that the Cyp2f2 mRNA levels are decreased in mouse liver following DEHP treatment [4].
• In contrast, DEHP increased Cyp3a11 in both wild-type and PPARalpha-null mice [24].
• This study investigated the effect of DEHP exposure on N-cadherin and alpha-, beta- and p120-catenin immunoreactivities in the rat testis [18].
• The highest effects are seen in catalase activity (50-60% with PFOA and ASA), pUDPGT (55% with PFOA), pST (55% with PFOA) and QR (50% with DEHP) [25].
• Testis weight, sperm number, and numbers of morphologically abnormal sperm were unaffected by DEHP following treatment [2].

Analytical, diagnostic and therapeutic context of 3,4-dioctylbenzene-1,2-dicarboxylic acid

• In mice, DEHP at 1/6 LD50 significantly depressed body weight gain for up to 12 weeks after treatment, and reduced epididymal sperm number by 4 weeks [2].
• The LD50 and the nonfetolethal maximum dosage of DEHP in its single, oral administration was 592 mg/kg and 64 mg/kg, respectively [14].
• The adulterants were separated by capillary gas chromatography and the ubiquitous pollutant dioctylphthalate was identified by its low resolution electron impact mass spectrum [26].
• The plasticizer DEHP but not DEHS exerted a weak promoting effect in a 12-week rat liver foci bioassay, using weanling female Sprague-Dawley rats [27].
• In order to determine the total percentage of extractables, supercritical fluid extraction (SFE) was used, and off-line gas-chromatography-flame-ionization detection (GC-FID) was employed for identification and quantitation of bis-(2-ethyl hexil)phthalate (DEHP) [28].

References