In vivo metabolism of nasally instilled benzo[a]pyrene in dogs and monkeys

Metabolism of inhaled materials deposited in the nasal cavity potentially influences their biological fate and toxicity. Metabolic enzymes, including cytochrome P-450-dependent monooxygenases, are not evenly distributed throughout the nasal cavity. The purpose of this study was to determine whether benzo[a]pyrene (BaP) deposited in the nasal cavity could be metabolized and cleared by the nasal tissue in the ethmoid and maxillary turbinate regions of Beagle dogs and cynomolgus monkeys. Nasopharyngeal mucus was collected at frequent intervals during periodic nasal instillations of BaP (and for dogs 24 h after instillation) for analysis of BaP and its metabolites. During and up to 48 h after nasal instillation of [14C]BaP, blood, urine and feces were collected to determine BaP clearance from the nose. High pressure liquid chromatographic analysis of organic phase extracts of nasopharyngeal mucus demonstrated that [14C]BaP instilled in either turbinate region was metabolized to dihydrodiols, quinones, phenols and tetrols in both species. Phenols were the major metabolic product, although all treated animals produced trans-7,8-dihydrobenzo[a]pyrene-7,8-diol. The dog mucus sampled at 24 h had no detectable radioactivity. The excreta from both species contained only small amounts of the instilled radioactivity. There was no distinctive pattern of metabolite production based on instillation site.