Age-related changes in the disposition of benzyl acetate. A model compound for glycine conjugation.
The in vivo metabolism and excretion of benzyl acetate (BA), a model compound for glycine conjugation, was examined in male Fischer 344 rats and C57BL/6N mice. Rats aged 3-4, 9, and 25 months received a single oral dose of either 5 or 500 mg/kg 14C-BA, while male mice aged 2, 13, and 25 months received a single oral dose of 10 mg/kg 14C-BA. Urine and feces were collected for 96 hr. Biliary excretion and plasma elimination were also examined in male Fischer rats after iv administration of 5 mg/kg 14C-BA. In both young and old rats and mice, hippuric acid (HA) was the major urinary metabolite after oral dosing of BA. No significant age-related difference was observed in rats in the urinary elimination of BA-derived radioactivity or in the percentage of the total dose excreted as hippuric acid (approximately 95%). Twenty-five-month old rats excreted a significantly higher percentage of the total dose as benzyl mercapturic acid (approximately 2%) than did 3- to 4-month-old rats (approximately 1%) at the 5 mg dose. Benzyl mercapturic acid excretion in 3- to 4-month-old rats was also increased significantly at 500 mg/kg BA vs. 5 mg/kg BA. Fecal excretion of BA-derived radioactivity declined significantly in 25-month-old rats at both the 5 and 500 mg dose. This decrease was reflected by an age-related decline in biliary excretion and higher plasma levels of BA-derived radioactivity. Examination of plasma metabolites revealed a significantly higher level of HA and benzoyl glucuronide in 25-month rats.(ABSTRACT TRUNCATED AT 250 WORDS)
McMahon
T F
TF
National Institute of Environmental Health Sciences, Systemic Toxicology Branch, Research Triangle Park, NC 27709.
Diliberto
J J
JJ
Birnbaum
L S
LS
D000284:Administration, Oral; D000375:Aging; D000818:Animals; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D005243:Feces / Q000032:analysis; D005998:Glycine / Q000378:metabolism*; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains
D001593:Benzyl Compounds; C046412:benzyl acetate; D005998:Glycine