The developmental toxicity of diethylene-glycol-monomethyl-ether (111773) (diEGME) was studied in the rat. Range finding studies were conducted on pregnant Sprague-Dawley-rats given diEGME between through 16 of gestation. Dams were killed on day 21 and live fetuses were counted. In subsequent studies of teratogenicity doses of 0, 720 or 2,165mg/kg were given by gavage on days 7 to 16 of gestation. Rats were killed on day 21 and fetuses were examined for gross external malformations and weighed. Subsequent internal examinations were made. The incidence of fetal malformation was two of nine treated females. There were no live fetuses at 5,175mg/kg or for six of nine rats given 3,345mg/kg. Live fetuses as a percentage of implants decreased in a clear dose related manner. Maternal toxicity was not apparent at either of the selected doses for the teratology study. Both fetal weight and litter size were significantly reduced at 2,165mg/kg and 2 of 23 litters were completely resorbed at that dose. None were so affected in the control and 720mg/kg groups. Average fetal weight was slightly reduced at that dose. Skeletal, usually rib, malformations were significantly increased at 2,165mg/kg per day on the basis of percent of fetuses affected. On the basis of litters affected, malformations were elevated in both treatment groups. Visceral malformations affected 46 percent of fetuses and 71 percent of litters at the higher dose; malformations were predominantly in the cardiovascular system. At 720mg/kg, 52 percent of litters were affected. At 2,165mg/kg, 90 percent of litters were affected. The authors conclude that the malformations induced by diEGME are similar to those induced by ethylene-glycol-monomethyl-ether although they are less frequent. In doses not toxic to the dam, diEGME is teratogenic, embryotoxic, and fetotoxic.
Division of Biomedical and Behavioral Science, NIOSH, U.S. Department of Health and Human Services, Cincinnati, Ohio, 23 pages, 17 references