Short-term toxicity study of di-(2-ethylhexyl) phthalate in rats

Groups of 15 male and 15 female rats were given diet containing 0 (control), 0·2, 1·0 or 2·0% di-(2-ethylhexyl) phthalate (DEHP) for 17 wk. At the two higher treatment levels there was a reduced rate of body-weight gain and food intake. A paired-feeding study showed that the reduced food intake did not account fully for the reduced growth rate. There was a decreased packed cell volume in both sexes given 1 or 2% DEHP, and in the male rats given these levels the haemoglobin concentration was also reduced. However, there was no decrease in the total erythrocyte count. Renal concentrating and diluting ability was reduced in the females receiving 2% DEHP. There were no differences between treated and control rats in the results of the serum analyses. With the exception of the liver weights, which were higher, the absolute weights of most organs in the rats given 1 or 2% DEHP were lower than those of the controls, while the relative values were greater. This pattern was considered to be related to the lower body weights at autopsy. At these treatment levels, the relative testis weight was markedly decreased and histopathological examination revealed severe seminiferous tubular atrophy and cessation of spermatogenesis. The testis weight of the rats fed 0·2% DEHP was not reduced, but histologically there was evidence of decreased spermatogenesis. At wk 17, castration cells were observed in the pituitary at all treatment levels, the incidence being dose-related. There were no other histopathological changes attributable to DEHP treatment. In view of the testicular changes and the increase in liver weight at all treatment levels, it was not possible to establish a no-untoward-effect level for DEHP in this study.