US EPA

5139660 

Technical Report 

Benzo(a)pyrene Metabolism in Mice Exposed to Diesel Exhaust: II. Metabolism and Excretion 

Cantrell, ET; Tyrer, HW; Peirano, WB; Danner, RM 

1980 

The metabolic disposition of benzo(a)pyrene (50328) (BP) in the tissues of mice, either exposed or not exposed to diesel exhausts (DE), after instillation of BP in the trachea was investigated. Male strain A-mice were exposed to DE for 9 months and instilled intratracheally with a bolus containing tritium labeled BP. The mice were killed 2, 24 or 168 hours (hr) later, and homogenates of liver, lungs and testes were centrifuged and processed for reverse phase high pressure liquid chromatography and scintillation counting. There was no difference in the time course of disappearance of soluble metabolites between DE exposed and control mice. However, the amount of residual bound BP in lungs of DE exposed mice was significantly higher than in unexposed mice. BP was metabolized in all three of the organs examined. Two hours after instillation the majority of radioactivity in the lung was unmetabolized BP. In contrast, more than half of the radioactivity in the liver and testes represented metabolites with a substantial degree of secondary metabolism to conjugates. The DE exposed animals appeared to have less free BP in tissues, perhaps reflecting the induction of enzymes for primary metabolism of polycyclic hydrocarbons. In the 24 and 168hr groups, BP was principally in the form of metabolites, with a substantial degree of conjugation. The principal primary metabolite of BP found in liver was 2-hydroxybenzo(a)pyrene (56892309). The authors conclude that the only meaningful difference in mice exposed to DE compared to controls is the suppressed ability to clear the small amount of BP, which they suggest is adsorbed to smoke particles.