Abstract
Studies on the lung retention of polycyclic aromatic hydrocarbons (PAH) after inhalation have indicated that, in general, the PAH are rapidly cleared from the respiratory tract. Clearance of the PAH from the lungs is best described as bi-phasic, with the long-term component of the clearance curve having a half-time of greater than 24 h. The purpose of this study was to determine whether a relationship exists between the lipophilicity (as measured by the octanol/water partition coefficient, P) of various PAH and the short-term and long-term clearance half-times of PAH in rat lungs. Female F344/ Crl rats were administered intratracheally 1 nmol of 14C-labelled anthracene (AN), benz[ a]anthracene (BA), 1-nitropyrene (NP), 6-nitrobenzo[ a]pyrene (6-NBP), or dibenzo[ c, g]carbazole (DBC). At various times after instillation rats were sacrificed and the amount of 14C remaining in the lungs was determined. Octanol/water partition coefficients were experimentally determined for each of the PAH used. Clearance of 14C from rat lungs following instillation of the different PAH was biphasic. In all cases, greater than 85% of the initial dose instilled was cleared with a half-time of less than 1 h. The half-times for clearance of the residual 14C (1–15% of the dose) were 26, 30, 36, 53 and 63 h for AN, NP, 6-NBP, BA and DBC, respectively. The log of the octonol/water partition coefficients for the different PAH examined ranged from 4.1 (AN) to 6.05 (DBC). Plots of the octanol/water coefficients vs. the long-term clearance half-time for the PAH indicated a linear correlation ( p < 0.001; r 2 = 0.96). The results from this study indicate that the greater the lipophilicity of the PAH, the slower the long-term clearance of a small fraction (1–15%) of PAH from the rat lungs. These data suggest that predictions of long-term lung clearance can be made for PAH with log octanol/water partition coefficients between 4 and 6.
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