Metabolism and disposition of n-butyl acrylate in male Fischer rats. 1988

J M Sanders, and L T Burka, and H B Matthews
National Toxicology Program, National Institute of Environmental Health Sciences Research, Triangle Park, NC 27709.

Butyl acrylate (BA) is one of the major monomers used in the manufacture of polymers and resins. Because little is known regarding its metabolic fate in animals, it was of interest to study the metabolism and disposition of BA in the rat. After oral administration, butyl [2,3-14C]acrylate was rapidly absorbed and metabolized. The acrylate moiety was metabolized primarily to CO2, accounting for elimination of up to 75% of the administered radiolabel. Elimination in urine and feces accounted for approximately 10 and 2% of the dose, respectively. Initial clearance of radioactivity from the tissues was very rapid and then decreased to a negligible rate 2 hr after iv administration. Total radioactivity in the major tissues was relatively constant from 2 to 24 hr. The majority of the radioactivity in the blood at 24 hr was found to be covalently bound to the protein fraction of the red blood cell membranes. There was some evidence of a first-pass effect when BA was administered by gavage because iv administration resulted in less metabolism to CO2 and quantitative differences in urinary metabolites. The two major metabolites in urine were identified as N-acetyl-S-(2-carboxyethyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine-S-oxide. Results of this study indicated that the major portion of a BA dose was hydrolyzed to acrylic acid, which was further metabolized to compounds available for oxidative metabolism. Radiolabeled carbons from the BA molecule were excreted as CO2 or incorporated in trace amounts into lipids, proteins, and other products of de novo synthesis. A smaller portion of the BA dose was conjugated with endogenous glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D008297 Male Males
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000179 Acrylates Derivatives of acrylic acid (the structural formula CH2
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001646 Bile An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum. Biliary Sludge,Sludge, Biliary
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions

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