Metabolism of 1-fluoropyrene and pyrene in marine flatfish and terrestrial isopods

Monofluorinated polycyclic aromatic hydrocarbons (F-PAHs) are useful reference compounds for a broad spectrum of PAH studies. The pyrene metabolite 1-hydroxypyrene is often used as a biomarker of PAH exposure. Two species, isopod (Porcellio scaber) and flatfish (Platichthys flesus), that produce 1-hydroxypyrene as the major intermediary metabolite and have distinct phase-II conjugates, were selected to investigate the cytochrome P450 catalyzed metabolism of 1-fluoropyrene. The fluorine atom blocks one of the four most favored carbon atoms, yielding different metabolite patterns and the results obtained in the selected species were compared with metabolite profiles obtained for unsubstituted pyrene. Charge densities in 1-fluoropyrene measured with (13)C-NMR were used to predict possible positions of hydroxylation, which were confirmed by (19)F-NMR. Additionally, the retention behaviour of conjugated 1-fluoropyrene metabolite isomers in reversed-phase liquid chromatography on a polymeric alkyl-bonded phase was interpreted based on the slot model. Whereas three phase-I metabolites were found in isopod hepatopancreas, only two were observed in flatfish bile. Phase-II metabolism appeared unaffected by the fluorine substituent. It was concluded that the phase-I enzyme cytochrome P450 is non-regioselective in the isopod: the activation is mostly influenced by the electron density distribution. In contrast, the enzymatic oxidation in the flounder is more selective. These differences will affect to what extent pyrene metabolite measurements can be used to assess the impact of PAHs to different species.