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AGE RELATED CHANGE IN DISPOSITION AND METABOLISM OF BENZENE IN MALE C57B/6N MICE
Citation:
McMahon, T. AND L. Birnbaum. AGE RELATED CHANGE IN DISPOSITION AND METABOLISM OF BENZENE IN MALE C57B/6N MICE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/374 (NTIS PB93107191).
Description:
Benzene disposition and metabolism were examined as a function of age in male C57BL/6N mice aged 3 and 18 months. ice received a single oral dose of either 10 or 200 mg/kg 14-C benzene (approximately 24 uCi/kg). xcretion of 14C derived benzene radioactivity (RA) was monitored in urine, feces, and as exhaled 14CO2 from 0-72 hr, and as exhaled unmetabolized benzene from 0-6 hr. t 10 mg/kg 14C benzene, urinary elimination was the major route of excretion in both 3 and 18 month mice. rinary excretion of 14C derived benzene RA was significantly decreased in 18 vs 3 month mice at 4, 6, 24, and 48 hr, while fecal excretion was significantly increased at 72 hr. limination of 14C benezene as 14CO2 and unmetabolised 14C benzene was also increased in 18 vs 3 month mice at this dose. ydroquinone glucuronice (MQG), phensylsulfate (PS), and muconic acid (MUC) were the major urinary metabolites at 10 mg/kg 14C benzene in both 3 and 18 mont mice, representing approximately 40, 28, and 15% of an administered dose of 14C benzene. maller amounts of phenyl glucuronide (4.)%), pre-phenyl mercapturic acid (1.2%), and catechol glucoronide (0.5%) were also detected. o significant differences were found with age in the percentage of an administered dose of benzene excreted as the various metabolites at 10 mg/kg. t 200 mg/kg 14C benzene, the total percentage of 14C derived benzene RA eliminated in urine within 72 hr was not significantly different with age, but elimination at early time points (4,6, and 8 hr) was significantly decreased in 18 vs 3 month mice. ecal elimination was significantly increased at 48 and 72 hr in 18 month mice, while excretion of unmetabolized benzene was decreased in this age group. he percentage of water soluble metabolites as MUC at 200 mg/kg 14C benzene was significantly decreased in 3 and 18 month mice, while the percentage as HQG remained constant with age at this dose. n contrast, formation of phenyl-glucuronide (PB) was significantly increased with dose in 3 month mice, whil PS formation was significantly increased with dose in 18 month mice. he results of these experiments indicate that total metabolism of benzene as well as metabolism to specific metabolites is affected by aging.
