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

  • Toxicokinetics and Metabolism
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Abstract

The aim of this study was to determine the percutaneous absorption flux of BaP (20 μg/cm2 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 μg/cm²/h was determined by killing groups of rats, following exposure time of 4.5 and 24 h. [14C] skin content was 3.1 μg/cm2, 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.

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Abbreviations

BaP:

Benzo(a)pyrene

3-OHBaP:

3-Hydroxybenzo(a)pyrene

BSA:

Bovine serum albumin

PAH:

Polycyclic aromatic hydrocarbons

i.v.:

Intravenous

HPLC:

High performance liquid chromatography

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Acknowledgments

We would like to thank P. Maxant and P. Sibille for their help in conducting this study and M. C. Grandclaude for her technical assistance. This study was part of the “Evaluation and prediction of dermal absorption of toxic chemicals” project (QLRT-2000-00196), supported by the 5th Framework Program of the European Commission.

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Authors and Affiliations

  1. Institut National de Recherche et de Sécurité (I.N.R.S.), Rue du Morvan, 54501, Vandoeuvre Cedex, France

    Jean-Paul Payan, Patrice Simon, Fabrice Marquet, Catherine Champmartin-Gendre, Dominique Beydon, Ludivine Wathier & Elisabeth Ferrari

  2. 14 Grand Rue, 54360, Vigneulles, France

    Michel Lafontaine

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  1. Jean-Paul Payan
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  2. Michel Lafontaine
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Correspondence to Jean-Paul Payan.

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Payan, JP., Lafontaine, M., Simon, P. et al. 3-Hydroxybenzo(a)pyrene as a biomarker of dermal exposure to benzo(a)pyrene. Arch Toxicol 83, 873–883 (2009). https://doi.org/10.1007/s00204-009-0440-0

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  • DOI: https://doi.org/10.1007/s00204-009-0440-0

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