Chronic toxicity of diethyl phthalate in male Wistar rats--a dose-response study.

Diethyl phthalate (DEP) is widely used in personal care products, plastics and medical devices at various concentrations, but its information is limited on its toxicity associated with exposure at high as well as low doses for a prolonged period. Therefore, a study was undertaken to understand the dose-response toxic effect of DEP in male Wistar rats. Control rats were fed on normal diet and water ad libitum. Rats were given DEP dissolved individually in corn oil mixed with the diet at 10, 25 and 50 mg/kg of the diet/day, which is equal to 0.57, 1.425 and 2.85 mg/kg body wt/day. After 5 months of treatment animals were sacrificed, enzymes and other biochemical parameters in the serum and liver were assessed. Liver weight to body weight ratio showed a significant increase only in 10 ppm DEP treated rats. A significant increase was observed in the serum ACP, LDH, ALT enzyme levels of 10 mg/kg treated rats as compared to control, 25 and 50 mg/kg treated rats. Other biochemical parameters like glycogen, total cholesterol, total triglycerides and lipid peroxidation were also increased in the liver of all the three treated groups. In the 10 and 50 mg/kg diet/day treated rats, there was a significant decrease in liver total GSH as compared to controls and 25 mg/kg treated rats. Histology of liver showed severe vacuolations, fatty degeneration and loss of hepatic architecture in the 10mg/kg treated rats, whereas in the 25 and 50 mg/kg treated rats only loss of hepatic architecture and granular deposits in the hepatocytes was predominant. Histology of liver by electron micrographs showed a significant dose-dependent proliferation of mitochondria in the hepatocytes, while the 10mg/kg treated rats showed increased number of peroxisomes in the hepatocytes. It is evident from this study that treatment with higher concentrations of DEP results in mitochondrial proliferation as well as accumulation of glycogen, cholesterol and triglycerides within the liver, but exposure to lower concentrations for longer periods results in increase in peroxisome numbers leading to severe hepatocellular changes which can be confirmed by significantly increased liver weights, elevated enzyme levels in the serum and liver and impaired metabolism of glycogen, cholesterol and triglyceride as well as altered liver histology.