SUBCHRONIC AND DEVELOPMENTAL TOXICITY STUDIES OF VAPORIZED DIISOPROPYL ETHER IN RATS

Two inhalation studies were performed with a vaporized sample of commercial-grade diisopropyl ether (DIPE). In the subchronic study, Sprague-Dawley rats (14/sex) were exposed to 0 (both untreated and sham-exposed controls), 480, 3300, or 7100 ppm DIPE for 6 h/d, 5 d/wk, for ~90 d. DIPE itself accounted for 91-95% of the vapors, with the remainder being a mixture of 27-29 compounds. Exposure to DIPE did not adversely affect clinical signs, body weight, serum chemistry, hematology, or the number of sperm or spermatids. Exposure of males to 7100 ppm resulted in hypertrophy of liver cells associated with increased liver weight and in increased kidney weight with an increased incidence of hyaline droplets in proximal tubules of the kidney. Females had increased weight of both liver and kidney, although kidney increased only in relation to sham-exposed controls and no morphological changes were observed in either organ. At 3300 ppm, weights of liver and kidney were again increased in males; the liver weights were increased in females only compared to sham-exposed controls and not untreated controls. No abnormalities were observed morphologically. No changes were observed with 480 ppm. In the developmental toxicity study, pregnant Sprague-Dawley rats (22/group) were exposed to 0 (both untreated and sham-exposed controls), 430, 3095, or 6745 ppm for 6 h/d on gestation d 6-15. Animals were sacrificed on gestation d 20. With 6745 ppm, dams had a slight reduction in body weight gain and a significant decrease in food consumption. A concentration-related increase in the incidence of rudimentary 14th ribs was observed, but its significance was uncertain. There was no apparent toxicity, either maternal or fetal, at the lowest exposure concentration. Both studies indicated a low order of toxicity for DIPE.