Developmental toxicity of diethylene glycol monomethyl ether (diEGME)

• Published in: Fundamental and applied toxicology 1986-04, Vol.6 (3), p.430-439
• Main Authors: Hardin, Bryan D., Goad, Phillip T., Burg, Jeann R.
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - etiology; Animals; Biological and medical sciences; Body Weight - drug effects; Bone and Bones - abnormalities; Dose-Response Relationship, Drug; Embryology: invertebrates and vertebrates. Teratology; Ethylene Glycols - metabolism; Ethylene Glycols - toxicity; Female; Fetus - drug effects; Fundamental and applied biological sciences. Psychology; Pregnancy; Rats; Rats, Inbred Strains; Skin Absorption; Solvents - toxicity; Teratology. Teratogens
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1016/0272-0590(86)90216-2

Diethylene glycol monomethyl ether (diEGME) was one of 15 glycols tested in CD-1 mice using a short-term in vivo reproductive toxicity assay (Chernoff/Kavlock test). Because results were strongly suggestive of potential reproductive toxicity, a teratology study was conducted in Sprague-Dawley rats. Time-mated females were orally dosed on Days 7–16 of gestation with diEGME indistilled water. Doses of 0, 1000, 1495, 2235, 3345, and 5175 mg/kg/day were used in a preliminary dose-finding study. At 5175 mg/kg/day, two of nine rats died, five of five litters were totally resorbed, and maternal extra gestational body weight gain was reduced. At 3345 mg/kg/day, six of nine litters were resorbed but there were no deaths and extra gestational body weight gain was not affected. Visceral and skeletal examinations revealed a dose-related increase in malformations, primarily of the ribs and cardiovascular system. Subsequently, pregnant rats were similarly dosed with 0, 720, or 2165 mg/kg/day. Neither dose was maternally toxic, but fetal body weights and the number of live implantations were significantly reduced at 2165 mg/kg/day. Rib malformations were seen in 9.1% (control), 42.9% (720 mg/kg/day, p < 0.05), and 80.0% (2165 mg/kg/day, p < 0.001) of litters. Cardiovascular malformations occurred in 0.0, 4.8, and 71.4% ( p < 0.001) of litters. Diethylene glycol monomethyl ether thus was teratogenic in rats at all doses tested, producing a dose-dependent series of malformations similar to those produced by other members of the glycol ether family.