Metabolism and disposition of ethylene carbonate in male Fischer 344 rats

Journal Article · Tue Aug 01 00:00:00 EDT 1989 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(89)90088-4· OSTI ID:5599411

Hanley, Jr, T R; Schumann, A M; Langvardt, P W; Rusek, T F; Watanabe, P G ^[1]

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1. Dow Chemical Company, Midland, MI (USA)

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 ({sup 14}C)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 ({sup 14}C)EG (141 mg/kg), approximately 37% of the dose was expired as {sup 14}CO{sub 2} 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.

• OSTI ID: 5599411
• Journal Information: Toxicology and Applied Pharmacology; (USA), Vol. 100:1; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ETHYLENE
METABOLISM
BIOLOGICAL HALF-LIFE
BLOOD
CARBON 13
CARBON 14 COMPOUNDS
CARBONATES
GAS CHROMATOGRAPHY
GLYCOLS
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
METABOLITES
ORAL ADMINISTRATION
TOXICITY
TRACER TECHNIQUES
ALCOHOLS
ALKENES
BIOLOGICAL MATERIALS
BODY FLUIDS
CARBON COMPOUNDS
CARBON ISOTOPES
CHROMATOGRAPHY
EVEN-ODD NUCLEI
HYDROCARBONS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MATERIALS
NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
SEPARATION PROCESSES
SPECTROSCOPY
STABLE ISOTOPES
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