Subchronic Inhalation Toxicology of Ethylene Glycol Monoethyl Ether in the Rat and Rabbit

The subchronic inhalation toxicology of ethylene glycol monoethyl ether (EGEE) was evaluated in rats and rabbits using a 13-week exposure regimen. Groups of 20 rabbits (10 M, 10 F) and 30 rats (15 M, 15 F) were exposed to a vapor of 25 ppm, 100 ppm, or 400 ppm, 6 hr/day, 5 days/week. The control groups received air only. Physical examinations and body weight measurements were conducted on all animals pretest and weekly throughout the study. Ophthalmoscopic examination was performed pretest and at termination. Evaluation of hematology and clinical chemistry was conducted on 10 animals per sex per group from each species after 13 weeks of study. Histopathological changes were assessed for all animals from the high-dose and control groups. In addition, selected tissues were examined from all animals from the mid- and low-dose groups. Both species exhibited an increased incidence of lacrimation and mucoid nasal discharge, but the response was not consistently dose-related. Rats exposed to EGEE showed no compound-related effects except for a decrease in pituitary to body weight ratio for high-dose males and a decrease in absolute spleen weight for all female animals. The spleen to body weight ratio was also less than controls for the females in the low- and high-dose groups. Pathological changes supportive of these organ weight changes were not observed. The rabbit is the more sensitive species to the subchronic toxicological effects from EGEE. Mean body weight values for low- and high-dose animals were decreased; the mid-dose animals, however, showed no change. Absolute weight and organ to body weight ratio for the testes were decreased for the high-dose group. Microscopic examination of the testes in animals from this group revealed slight focal seminiferous tubule degeneration in 3 out of 10 rabbits. Hematocrit, hemoglobin concentration and erythrocyte count were decreased in the high-dose group of rabbits compared to controls. The level at which no biologically significant effects are observed from subchronic inhalation exposure to EGEE is 400 ppm for rats and 100 ppm for rabbits.