Metabolism and disposition of ethylene carbonate in male Fischer 344 rats.
Ethylene carbonate (EC) has a toxicity profile which resembles that of ethylene glycol (EG). To determine whether the toxicity of EC could be explained on the basis of its metabolism to EG, male Fischer 344 rats were given 200 mg/kg of uniformly labeled [14C]EC in water by gavage and the disposition of the radiolabel was then followed for 72 hr. EC was rapidly metabolized, with approximately 57 and 27% of the administered dose eliminated in the expired air as 14CO2 and in the urine, respectively; the remainder was found in the carcass. Separation of the urinary metabolites using liquid chromatography revealed a single radioactive peak. This metabolite was unequivocally identified as ethylene glycol via gas chromatography-mass spectrometry with the aid of 13C enrichment of the EC dose. Measurement of whole blood levels of EC and EG in rats given 200 mg/kg of EC by gavage revealed blood levels of EG approximately 100-fold higher than the levels of EC in these same animals, with a half-life of EG in blood of 2 hr, indicating rapid conversion of EC to EG. In a separate group of animals administered an equimolar dose of [14C]EG (141 mg/kg), approximately 37% of the dose was expired as 14CO2 and 42% was excreted in the urine as parent compound. When expressed on the basis of the ethanediol moiety, the disposition of EC was identical to that of EG. In view of the rapid and extensive biotransformation of EC to EG and the similarity of the existing (though limited) toxicity data base of EC compared to EG, utilization of the extensive EG systemic toxicity data base for assessing the safety of EC appears justified.
Hanley
T R
TR
Mammalian and Environmental Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674.
Schumann
A M
AM
Langvardt
P W
PW
Rusek
T F
TF
Watanabe
P G
PG
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004148:Dioxolanes / Q000378:metabolism* / Q000493:pharmacokinetics; D004149:Dioxoles / Q000378:metabolism*; D019855:Ethylene Glycol; D005026:Ethylene Glycols / Q000652:urine; D006868:Hydrolysis; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002250:Carbon Radioisotopes; D004148:Dioxolanes; D004149:Dioxoles; D005026:Ethylene Glycols; D019855:Ethylene Glycol; C031133:ethylene carbonate