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.
Payan
Jean-Paul
JP
Institut National de Recherche et de Sécurité, Vandoeuvre, France. payanjp@inrs.fr
Lafontaine
Michel
M
Simon
Patrice
P
Marquet
Fabrice
F
Champmartin-Gendre
Catherine
C
Beydon
Dominique
D
Wathier
Ludivine
L
Ferrari
Elisabeth
E
D000279:Administration, Cutaneous; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000378:metabolism*; D001580:Benzopyrenes / Q000008:administration & dosage / Q000378:metabolism*; D015415:Biomarkers / Q000652:urine; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
D001580:Benzopyrenes; D015415:Biomarkers; D002250:Carbon Radioisotopes; D002273:Carcinogens; D001564:Benzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene