Subchronic 90-day oral toxicology of Di(2-ethylhexyl) terephthalate in the rat

Abstract

Di(2-ethylhexyl) terephthalate (DEHT), the 2-ethylhexyl diester of terephthalic acid (1,4-benzenedicarboxylic acid) was administered in the diet to groups of 20 male and female Sprague-Dawley rats for 90 days at 1.0, 0.5, 0.1 or 0.0% by weight. No major organ or systemic toxicity resulted from consumption of the diets in any group of animals. Changes that were observed included slight effects on some haematology parameters including haemoglobin, haematocrit, mean corpuscular volume and mean corpuscular haemoglobin at the 1.0% dose; and slight increases in relative liver weights (11.2% in the males, 8.9% in the females), also at the 1.0% dose level. Marginal changes of less than 3% in some red blood cell indices were observed at the 0.5% dietary dose level; however no anaemia or changes in relative liver weights were observed at this dose level. Thus, no significant adverse effects attributable to the test material were identified in animals consuming the two lower doses. In a morphometric study of liver sections, DEHT was found not to induce hepatic peroxisomes at the 1.0% dose level. The positive control material (2-ethylhexanol at 1000 mg/kg, 5 days/wk for 3 wk), produced a 30% increase in liver-to-body weight ratio, and increases in peroxisome cell fraction, and in peroxisome density. The no-effect levels of DEHT in rats consuming the material for 90 days in the diet were 277 and 309 mg/kg/day in males and females, respectively. These results are contrasted with those reported for di(2-ethylhexyl) phthalate (DEHP) in similar feeding studies. While DEHP at 1% in the diet is reported to produce significant effects on the liver, testes, kidney, brain, stomach and adrenal weights, DEHT has been shown in this study to have only a minor effect on liver weight in 90 days at 1.0% in the diet.