3-Hydroxybenzo(a)pyrene as a biomarker of dermal exposure to benzo(a)pyrene.

The aim of this study was to determine the percutaneous absorption flux of BaP (20 microg/cm(2) in ethanol) and the usefulness of urinary 3-OHBaP as a bio-indicator of dermal exposure to BaP. The percutaneous absorbed dose and absorption flux were estimated by comparison with intravenous administration of BaP (0.01 and 0.05 mg/kg in Cremophor) as reference way. A percutaneous absorption flux of 0.37 microg/cm(2)/h was determined by killing groups of rats, following exposure time of 4.5 and 24 h. [(14)C] skin content was 3.1 microg/cm(2), after 24 h exposure to BaP. Total urinary 3-OHBaP accounted for 0.4% of the real absorbed dose, which was fourfold higher than the percentage of an intravenous dose excreted as 3-OHBaP. This finding reveals that percutaneous absorption of BaP, based on the ratio of urinary excretion of 3-OHBaP following percutaneous exposure compared to percutaneous absorption following intravenous administration of BaP, is overestimated in the rat. In vitro, BaP was intensively metabolised by rat skin. Unchanged BaP and 3-OHBaP in receptor fluid accounted for 50 and 30% of the total radioactivity. This percutaneous first past effect of BaP in rats could, in part, explain the higher urinary excretion ratio of 3-OHBaP compared to the value based on intravenous administration of BaP. Conversely, BaP was largely lower metabolised as 3-OHBaP during percutaneous absorption by humans, so BaP absorption flux should be overestimated to a lesser extent in humans than in rats.

In vivo and in vitro percutaneous absorption of [14C]pyrene in Sprague Dawley male rats: skin reservoir effect and consequence on urinary 1-OH pyrene excretion.

The skin reservoir effect of [14C]pyrene (in vivo and in vitro) on percutaneous absorption was determined in male Sprague Dawley rats. The urinary 1-OHpyrene (1-OHPy) excretion was compared between dermal exposure and intravenous administration. In vivo, the percutaneous absorption flux of [14C]pyrene (200 microg/cm(2); 50 microL/cm(2) of ethanol) determined by sacrificing batches of rats after different exposure times over 4.5 h was 1.0 +/- 0.1 microg/cm(2) h(-1). During exposure, penetration flux was twofold higher than absorption flux, indicating a gradual accumulation of pyrene in the skin. [14C] skin content at the end of exposure was 16 microg/cm(2), which decreased gradually over time to 2 microg/cm(2) 68 h after the end of exposure. The total absorbed dose during exposure was threefold lower than that after exposure, indicating a high contribution of pyrene skin content to the systemic availability of the compound. Similar results were obtained in vitro. The apparent elimination rate of [14C]pyrene (23 h) contained in the skin after an exposure of 4.5 h was similar to the apparent urinary excretion half life of 1-OHPy (21 h). These values are threefold higher than the urinary excretion half life of 1-OHPy after an intravenous administration of pyrene (0.5 mg/kg). In conclusion, absorbed dose and percutaneous absorption flux were well estimated from the 1-OHPy urinary excretion rate. For risk assessment purposes, the penetration flux rather than the absorption flux should be taken into account for topical pyrene exposure.