STUDIES ON THE LIVER ENLARGEMENT INDUCED BY DIETARY ADMINISTRATION OF DI-(2-ETHYLHEXYL) PHTHALATE (DEHP).

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) was mixed into diet and given to Wistar male rats for 16 days. A significant and dose-dependent increase in the relative liver weight (RLW) was observed in the rats fed DEHP at dietary levels greater than 0.1%. The RLW increased progressively with the duration of the treatment, reaching its maximun in two weeks. Biochemical analysis of the principal hepatic components has shown that the increase in RLW induced by DEHP was due to an increase in the total amounts of protein, water, lipid, and nucleic acids. The increase in protein was most marked and was due mainly to the increase in non-collagen protein. The total amounts of glycogen and collagen did not change. However, most of these components were found to be unchanged or reduced in their contents per liver weight, except that of protein. The increase in RLW is caused equally by the increase in cell number and in the cell volume, the nuclear DNA content being unaffected. The content of cytochrome P-450 in microsomes increased in the rats of both sex fed a 0.5% DEHP-diet for 16 days. However, the activities per mg of microsomal protein or per g of liver of aminopyrine N-demethylase and aniline hydroxylase decreased in male rats but increased in female rats. Total activities of these enzymes increased markedly in both sex of animals. Glucose 6-phosphatase, acid phosphatase and cytochrome c oxidase were reduced significantly in their activities per liver weight but glucose 6-phosphate dehydrogenase was unchanged. The significance of the liver enlargement induced by DEHP is discussed in relation to the physiological response of liver and to possible pathological changes of liver.