Dose-, route-, and sex-dependent urinary excretion of phenol metabolites in B6C3F, mice
- Chemical Industry Institute of Toxicology, Research Triangle Park, NC (United States)
Phenol is the major oxidized metabolite of benzene, a known human leukemogen and ubiquitous environmental pollutant. Unlike benzene, phenol does not induce tumors in mice following oral exposure; benzene also exhibits sex-related differences in genotoxicity to bone marrow cells that are not observed following phenol administration. We studied the urinary excretion of phenol metabolites in mice as a means to further investigate the metabolic basis for differences in benzene- and phenol-induced toxicity. Male and female B6C3F, mice (n = 3/group) were exposed to 15, 40, 100, or 225 {mu}mol [{sup 14}C]phenol/kg by iv tail vein injection (6 {mu}Ci/mouse). First-pass intestinal metabolism of phenol was evaluated by comparison of urinary excretion of phenol metabolites following iv administration with additional groups of male mice that received the same dose levels by oral gavage. Mice were placed in glass metabolism cages, and urine was collected over dry ice for 48 h. Urinary metabolites were separated by high-pressure liquid chromatography (HPLC) and quantified by liquid scintillation spectrometry. Urinary excretion of conjugated metabolites of phenol was dose-dependent in both male and female mice administered phenol by iv injection or gavage. The major urinary metabolites of phenol were phenol sulfate (PS), phenol glucuronide (PG), and hydroquinone glucoronide (HQG). Sulfation was the dominant pathway at all dose levels, but decreased as a percent of the excreted dose with a concomitant increase in glucorodination as the dose level increased. Male mice consistently excreted a higher proportion of phenol as the oxidized conjugated metabolite, HQG, compared to female mice, suggesting that male mice oxidize phenol to hydroquinone more rapidly than female mice. 31 refs., 6 figs., 2 tabs.
- OSTI ID:
- 68611
- Journal Information:
- Journal of Toxicology and Environmental Health, Journal Name: Journal of Toxicology and Environmental Health Journal Issue: 2 Vol. 44; ISSN 0098-4108; ISSN JTEHD6
- Country of Publication:
- United States
- Language:
- English
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