The hepatic effects of orally administered di-(2-ethylhexyl) phthalate in the ferret.

The phthalate ester di-(2-ethylhexyl) phthalate is extensively used as a plasticizer in polyvinyl chloride formulations, where it may constitute up to 40% of the weight of the finished product (Autian, 1973). Di-(2-ethylhexyl) phthalate is widely distributed in the environment, having been detected in various forms of marine life (Mayer et al., 1972), soil samples (Ogner & Schnitzer, 1970) and both animal (Nazir et al., 1971) and human (Jaeger & Rubin, 1972) tissues. Although a number of toxicological investigations into the effects of di-(2-ethylhexyl) phthalate have been conducted in various rodent species, relatively few investigations have been made in non-rodent species. In the context of assessing the use of the ferret as a non-rodent species for toxicological studies, we have investigated the hepatic effects produced by di-(2-ethylhexyl) phthalate administration to this animal. The administration of a 1 % (w/w) di-(2-ethylhexyl) phthalate diet for a period of 14 months to male adult albino ferrets produced marked liver enlargement (Table 1). However, the enzyme activities of succinate dehydrogenase (EC 1.3.99.1), aniline 4-hydroxylase and glucose 6-phosphatase (EC 3.1.3.9) were significantly decreased to 61,78 and 37 % of control values respectively. Histochemical examination of the livers of the di-(2-ethylhexyl) phthalate-treated ferrets revealed extensive losses of aniline 4-hydroxylase and glucose 6-phosphatase activities from groups of cells sited near the centrilobular area of the liver lobule. The depression of succinate dehydrogenase activity was observed in cells associated with both the centrilobular and mid-zonal areas of the liver lobule. Further, marked lysosomal disturbances were observed in the liver lobules of the phthalate-treated animals. These changes consisted of a loss of acid phosphatase (EC 3.1.3.2) activity from the centrilobular region with increased activity in the mid-zonal and periportal areas. Although there was no change in the microsomal cytochrome P-450 content, a small but statistically insignificant increase in the microsomal protein content was observed. Ultrastructural examination of liver cells from the di-(2-ethylhexyl)