SUBCHRONIC TOXICITY OF DI(2-ETHYLHEXYL)PHTHALATE IN COMMON MARMOSETS - LACK OF HEPATIC PEROXISOME PROLIFERATION, TESTICULAR ATROPHY, OR PANCREATIC ACINAR CELL HYPERPLASIA

To evaluate the toxicological effect, di(2-ethylhexyl)phthalate (DEHP) was administered orally at 100, 500, and 2500 mg/kg to four male and four female marmosets in each group for 13 weeks. Its potentials of he patic peroxisome proliferation, testicular atrophy, and pancreatic aci nar cell hyperplasia were evaluated more closely. Clofibrate, which po tently causes peroxisome proliferation in rodents, was administered in like manner at 250 mg/kg as a reference drug. DEHP induced significan t suppression of weight gain in males at 2500 mg/kg. However, the incr ease in liver mass and hypertrophy of hepatocytes were not detected in organ weight measurements or histopathological examination. The numbe r of peroxisomes, volume density, peroxisome morphology, and peroxisom al enzyme activities were not different from those in the control grou p, though the males treated with 500 and 2500 mg/kg DEHP showed 1.3- a nd 1.4-fold increases in mean peroxisome volume, respectively. In cont rast, clofibrate induced 2.2 (in male)- and 1.9-fold (in female) incre ases in hepatic cyanide-insensitive acyl CoA oxidation system activity , 1.2 (in male)- and 1.7-fold (in female) increases in hepatic carniti ne-dependent acetyltransferase activity, and 1.8 (in male)- and 3.0-fo ld (in female) increases of carnitine-dependent palmitoyltransferase a ctivity. Cytochrome P-450 contents tended to increase in all males and females administered 500 and 2500 mg/kg of DEHP and clofibrate associ ated with the increase in hepatic microsomal protein content, suggesti ng a relationship with the treatment. The atrophic change in the testi s or proliferative change in the pancreatic acinar cells seen in roden ts were not seen histopathologically; also, no changes were observed i n testes weight, testicular zinc level, blood levels of testosterone a nd estradiol, pancreas weight, and blood levels of cholecystokinin. Fi nally, no changes considered to be due to the administration of DEHP w ere noted in blood chemical examination or pathological examination of other organs. (C) 1998 Society of Toxicology.