Teratogenicity of 2-methoxyethanol applied as a single dermal dose to rats.
2-Methoxyethanol (2-ME) was applied as a single dermal dose on the backs of collared, pregnant Sprague-Dawley rats on Gestation Days (GD) 10, 11, 12, 13, or 14 at doses of 0 and 2000 mg/kg, and at doses of 0, 250, 500, and 1000 mg/kg on GD 12. Except for a transient loss in body weight observed the day after 2-ME administration, no signs of maternal toxicity were observed. On GD 20, dams were necropsied and the fetuses evaluated for normal development. Resorptions were significantly (p less than 0.05) increased in dams exposed to 2-ME on GD 10. Fetal body weights were reduced at dose levels of 1000 and 2000 mg/kg, but statistically significant differences were found only on GD 10 and 12. Significant increases in external, visceral, and skeletal malformations were observed in fetuses exposed to 2-ME at dose levels of 500 mg/kg or greater. Defects of the cardiovascular and urinary systems were the prominent visceral malformations observed. Limb defects (especially those pertaining to the digits) and vertebral column defects (primarily of the tail) were the most frequently observed skeletal defects. At the 2000 mg/kg dose level, 2-ME was teratogenic regardless of the GD of administration. Based on the results of this study, the no observed adverse effect level for developmental toxicity for a single dermal dose of 2-ME applied on GD 12 was determined to be 250 mg/kg.
Feuston
M H
MH
Mobil Environmental and Health Science Laboratory, Mobil Oil Corporation, Princeton, New Jersey 08543-1029.
Kerstetter
S L
SL
Wilson
P D
PD
D000014:Abnormalities, Drug-Induced; D000279:Administration, Cutaneous; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D006330:Heart Defects, Congenital / Q000139:chemically induced; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens; D014551:Urinary Tract / Q000002:abnormalities
D005026:Ethylene Glycols; D013723:Teratogens; C005219:methyl cellosolve