Toxicity study of di(2-ethylhexyl)phthalate (DEHP) in combination with acetone in rats

In two separate studies with exposure duration 9 weeks or 4 weeks, male Wis tar rats were dosed with di(2-ethylhexyl)phthalate (DEHP) by gavage and exp osed to drinking water with or without acetone (0.5% wt/v in the 9-week stu dy, 1.0% wt/v in the 4-week study). In the 9-week study the doses of DEHP w ere 0, 125, 250, 500 or 1000 mg/kg b.wt. In the 4-week study the doses of D EHP were increased to 1000, 5000 and 10,000 mg/kg b.wt. In the 9-week study , the relative liver weight was increased in the rats exposed to 500 and 10 00 mg/kg b.wt. No interaction of DEHP and acetone was observed in any of th e measured parameters. In the 4-week study DEHP, at the highest dose level, resulted in severe general toxicity. The group exposed to DEHP in combinat ion with acetone was more affected. Male fertility was decreased. Body weig ht was decreased, and the relative weight of the liver, kidney, heart, brai n and adrenals increased. The relative weight of the testes decreased in th e 5000 and 10,000 mg/kg b.wt. groups. The weight of seminal vesicles and ep ididymals decreased at 10,000 mg/kg b.wt. In animals exposed to 5000 and 10 ,000 mg DEHP/kg b.wt. a severe atrophy of the seminiferous tubules and a sl ight diffuse Leydig's cell hyperplasia was observed. The cellular debris an d conglomerates of desquamated cells found in the lumen of the seminiferous tubules were immunostained positive for vimentin. This indicates that Sert oli cell cytoplasm is included in the conglomerates - an interesting findin g not previously described. No specific interaction of DEHP and acetone was observed in any of the measured parameters.