Effects of diethylenetriamine dihydrochloride following 13 weeks of dietary dosing in fischer 344 rats

Fischer 344 rats were fed a diet containing the dihydrochloride salt of diethylenetriamine (DETA.2HCI) at concentrations of 1000, 7500 or 15,000 ppm for 90 consecutive days. Based on food consumption and body weight, the mean corresponding dosages were 70, 530 and 1060 mg/kg/day for the males and 80, 620 and 1210 mg/kg/day for the females. Decreases in food consumption were observed intermittently throughout the dosing period in both sexes at 15,000 ppm. Dose-related decreases in body weight or weight gain were observed for both sexes at 7500 and 15,000 ppm. Changes in clinical pathology measurements observed at 7500 and 15,000 ppm included increases in mean corpuscular volume and mean corpuscular haemoglobin in males, and increases in mean corpuscular volume, total leucocytes and urinary pH, and a decrease in serum glucose concentration in females. The relative kidney, brain and testes weights were increased in the 15,000 ppm males. In the females, the relative kidney, brain and liver weights were increased at 7500 and 15,000 ppm, and the relative heart and adrenal weights were elevated at 15,000 ppm. There were no treatment-related clinical signs, gross autopsy or histopathological findings for either sex at any dose level. Animals improved only slightly from the effects of treatment following a 4-wk recovery period. A no-observable-effect level of 1000 ppm DETA.2HCI in the diet was established in this subchronic toxicity study.