This study compares changes in the livers of rats treated with di(2-ethylhexyl)
phthalate (
DEHP) and its straight-chain analogs
di(n-hexyl) phthalate (
DnHP) and
di(n-octyl phthalate (DnOP). Groups of rats were fed diets containing 20,000 ppm of one of these compounds. Subgroups were killed after 3, 10, and 21 days, and the livers were examined by histological, cytological, and biochemical methods. The results show considerable differences between the effects of the branched-chain
phthalate ester DEHP and its straight-chain analogs. The major effects on the liver following administration of diets containing
DEHP were midzonal and periportal accumulation of small droplets of
lipid,
hepatomegaly accompanied by an initial burst of mitosis, proliferation of hepatic peroxisomes and of smooth endoplasmic reticulum accompanied by induction of peroxisomal
fatty acid oxidation, damage to the peroxisomal membranes as evidenced by increased leakage of
catalase to the cytosol, and centrilobular loss of
glycogen and falls in
glucose-6-phosphatase activity and in low-molecular-weight
reducing agents. In contrast, diets containing
DnHP or DnOP induced accumulation of large droplets of fat around central veins leading, by 10 days, to mild centrilobular
necrosis and a very slight induction of one peroxisomal
enzyme and an increase in liver weight, but no significant changes in any other parameters which were affected by
DEHP.