Disposition and metabolism of (2- UC)epichlorohydrin after oral administration to rats

Journal Article · Wed May 01 04:00:00 EDT 1985 · Drug Metab. Dispos.; (United States)

OSTI ID:6181726

Gingell, R; Mitschke, H R; Dzidic, I; Beatty, P W; Sawin, V L; Page, A C

A comprehensive disposition and metabolism study of epichlorohydrin (ECH) has not been previously reported. In this study, male Fischer 344 rats were dosed (6 mg/kg) orally with (2-14C)ECH (98% radiochemically pure) as an aqueous solution and killed after 3 days. Approximately 38% of the radioactive dose was exhaled as CO2, 50% was excreted as metabolites in the urine, and 3% was present in the feces. Radioactivity in tissues accounted for the remainder of the administered dose. When expressed per gram of tissue, radioactivity was highest in liver, kidney, and forestomach. The half-life of initial elimination of radioactivity in both the urine and exhaled air was about 2 hr, indicating that ECH was rapidly absorbed and metabolized. The major metabolites in the urine were identified as N-acetyl-S-(3-chloro-2-hydroxypropyl)-L-cysteine and alpha-chlorohydrin, about 36 and 4% of the administered dose, respectively. Finding these metabolites, which have not been previously reported, is consistent with the initial metabolic reactions being conjugation of the epoxide with glutathione and hydration of the epoxide.

• Research Organization: Shell Development Co., Houston, TX
• OSTI ID: 6181726
• Journal Information: Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 3; ISSN DMDSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BODY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARBON DIOXIDE
CARBON OXIDES
CHALCOGENIDES
DIGESTIVE SYSTEM
DRUGS
EPOXIDES
GLANDS
GLUTATHIONE
KIDNEYS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PEPTIDES
PHARMACOLOGY
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
VERTEBRATES