Benzo(a)pyrene disposition and metabolism in rats following intratracheal instillation.

肝肠循环 化学 毒物动力学 新陈代谢 苯并(a)芘 药理学 药代动力学 致癌物 生物化学 医学 有机化学
作者
Eric H. Weyand,David R. Bevan
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期刊:PubMed 卷期号:46 (11): 5655-61 被引量:53
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[3H]Benzo(a)pyrene [B(a)P] disposition and metabolism were investigated in male Sprague-Dawley rats. [3H]B(a)P, in a vehicle of triethylene glycol, was administered by intratracheal instillation (1 microgram/kg body weight), and the amount of radioactivity in various organs was determined at timed intervals between 5 and 360 min. Elimination of radioactivity from lungs was biphasic with half-lives of 5 and 116 min. Radioactivity in liver increased rapidly, reaching a maximum of 21% of the dose within 10 min after instillation and decreasing thereafter until less than 5% of the dose was detected at 360 min after instillation. The carcass accounted for 15-30% of the dose within the time intervals investigated. Toxicokinetic parameters to describe elimination of unmetabolized B(a)P from blood following intratracheal administration were found to be very similar to those calculated following i.v. administration. B(a)P metabolites in lung, liver, and intestinal contents were identified. Notably, quinones were at highest concentrations in both lung and liver 5 min after instillation, accounting for 12 and 7% of organic extractable material, respectively. B(a)P disposition was also investigated in animals with and without biliary cannulas. Distribution patterns among organs were similar though the amount excreted in bile and intestinal contents was 74 and 40% of the dose, respectively. Types of metabolites in bile and intestinal contents were identified and compared. Lower fractions of the administered dose were detected as thioether and glucuronic acid conjugates in intestinal contents than in bile, indicating that enterohepatic circulation of B(a)P metabolites was occurring.

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