Developmental toxicity of diethylene glycol monomethyl ether (diEGME).
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 in distilled 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 less than 0.05), and 80.0% (2165 mg/kg/day, p less than 0.001) of litters. Cardiovascular malformations occurred in 0.0, 4.8, and 71.4% (p less than 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.
Hardin
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Goad
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Burg
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D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities; D004305:Dose-Response Relationship, Drug; D005026:Ethylene Glycols / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D012997:Solvents / Q000633:toxicity*
D005026:Ethylene Glycols; D012997:Solvents; C048214:diethylene glycol monomethyl ether; C005219:methyl cellosolve