Sub-acute and sub-chronic toxicity of mono-2-ethylhexyl phthalate in the rat.

Abstract

Groups of six male Sprague-Dawley rats were administered single oral doses of mono-2-ethylhexyl phthalate (MEHP) at 50, 100 or 200 mg/kg or di-2-ethylhexyl phthalate (DEHP) at 2,000 mg/kg in 2% gum acacia and were observed clinically for seven days. Body weight and food consumption were not affected by treatment. The liver weight increased in the groups receiving 100 mg or 200 mg mono-2-ethylhexyl phthalate and 2,000 mg diethylhexyl phthalate. Hepatic microsomal aniline hydroxylase activity was not altered by treatment. In a subsequent 28-day experiment, groups of ten weanling Sprague Dawley rats were fed diets containing 0, 25, 100, 400, 1,600 or 6,400 ppm of mono-2-ethylhexyl phthalate. Decreased growth rate occurred in the group receiving the highest dose level. Increased heart and liver weights were observed in animals from the 1,600 and 6,400 ppm groups. Minor alterations in serum biochemical values included decreased SDH and calcium levels, and elevated alkaline phosphatase activity in some treated groups. A mild reduction in red cells saturation and hematocrit was noted in some groups. In 3-month and 6-month feeding studies, groups of ten male and female weanling Sprague-Dawley rats were fed diets containing 1, 5, 25, 125 or 625 ppm of mono-2-ethylhexyl phthalate. Growth rate and food consumption were not affected at any dose level or time interval. Relative organ weights of rats of both sexes were not altered in the 3-month period, but the liver weights of female rats in the 6-month experiment were increased. Changes in clinical chemistry and hematological values were mild. These included lower LDH, SGOT, hemoglobin, and hematocrit values in male rats at the 3-month period and reduced potassium content at the 6-month period. Histological changes were mild in both male and female rats at both time intervals. Treatment-related lesions were found in the liver, heart, and adrenals. Alteration in the liver consisted of midzonal and periportal eosinophilic cytoplasmic inclusions and vacuolations with isolated binucleated and necrotic hepatocytes. There was a mild enlargement of myocardial nuclei and segmental deregistration of myocardial striations in test animals. The adrenal glands exhibited vacuolation of the zona fasciculata which was less severe in the 6-month period than the 3-month counterpart. In conclusion, mono-2-ethylhexyl phthalate is similar to its parent compound diethylhexyl phthalate in that it possesses a low order of oral toxicity in rats.