| Abstract |
The ability of di-2-ethylhexyl adipate to induce morphological transformation in the BALB/3T3 mouse cell line (Cell Transformation Assay) was evaluated. Based on preliminary clonal toxicity determinations (exposure time=72 hrs), di-2-ethylhexyl adipate, in 0.5% acetone, was tested at 3.38, 6.75, 13.5, and 27.0 nl/ml, with cell survival ranging from 89.0-31.7% relative to the solvent control. The material did not induce the appearance of a significant number of transformed foci (Bailey's modification of Student's t-test).The morphological transforming potential of 96, 144, or 180 nl/ml 2- ethyl hexanol (purity not reported) administered in vitro to Balb/C-3T3 cells in the presence of freshly isolated rat liver hepatocytes was evaluated. 2-ethyl hexanol did not induce the appearance of a statistically significant (by use of Bailey modified Students t-test) number of transformed foci at the concentrations tested. In a concomitant cytotoxicity test, the test range was found to include survival rates of approximately 72.0% at the low dose, to 3.7% at the high dose.C14-Di(2-ethylhexyl)phthalate was administered to three groups (12 rats/group) of male Fischer-344 rats at nominal concentrations of 1000, 6000 or 12000 ppm in the diet for 24 hrs, after 0, 6 or 20 days prior exposure to equal concentrations of unlabeled DEHP in the diet. The percentage of the dose excreted in urine increased with dose, from 53% at 1000 ppm to 62-69% at 6000 and 12000 ppm, with the initial ca. 10-15% being excreted during the first 24 hrs. At all dose levels and exposure times, 24-38% of the dose consumed was excreted via the fecal route. Fecal excretion occurred primarily during the second 24 hrs, (11-19% of the dose). The percentage of the dose excreted in feces decreased with increased dose from 35-38% at 1000 ppm, to 24-30% at 6000 ppm. As with urinary excretion, prior exposure to DEHP did not affect the extent or rate of fecal excretion. DEHP equivalents were detectable at low concentrations in the liver, 112 hrs after the start of administration. Total recoveries of the 14C-DEHP radioactivity consumed were less than 100% for all animals. Total recoveries of radioactivity were not affected by dose or by prior exposure to DEHP. Evaluation of Di-2-ethylhexyl-adipate in the in Vitro Transformation of Balb/3t3 Cells Assay Addendum to the Final Report of Setpember 1982 Contract No. Pe-140-mut-lb. Evaluation of 2-ethylhexanol in the in Vitro Transformation of Balb/3t3 Cells with Metabolic Activation by Primary Rat Hepatocytes Addendum to the Final Report of July 1983 Contra. Exhibit Iv Dehp Metabolism Studies Protocol i Dose Dependence of and Effect of Prior Exposure on the Metabolism of Dehp Administered in the Diet to Rats. |
