Influence of exposure dose, complex mixture, and ultraviolet radiation on skin absorption and bioactivation of polycyclic aromatic hydrocarbons ex vivo

  • Etienne Bourgart
  • Renaud Persoons
  • Marie Marques
  • Alex Rivier
  • Franck Balducci
  • Anne von Koschembahr
  • David Béal
  • Marie-Thérèse Leccia
  • Thierry Douki
  • Anne MaitreEmail author
Toxicokinetics and Metabolism


Combined exposure to complex mixtures of polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UVR) is suspected to enhance PAH skin permeability and skin cancer risk depending on PAH bioactivation. The impact of PAH mixtures (exposure dose, composition, and complexity) and UVR was assessed for PAH cutaneous absorption and metabolism using realistic exposure conditions and human skin explants. PAH complex mixtures were extracted from the industrial products coal tar pitch (CTP-I) and petroleum coke (PC-I). The synthetic mixture (CTP-S) was identically reconstituted using PAH standards. The applied dose was adjusted to 1 (PC-I, CTP-I) or 10 nmol (CTP-I, CTP-S) of benzo[a]pyrene (B[a]P). Unmetabolized PAHs were recovered from the skin surface, skin and medium, and then quantified by HPLC-fluorescence detection. PAH metabolites were collected from the medium and analyzed by GC–MS/MS. B[a]P and PAH penetration was lower for the highest B[a]P dose, industrial mixtures, and CTP-I compared to PC-I. Skin irradiation increased PAH penetration only for CTP-I. PAH uptake was poorly influenced by the different experimental conditions. PAH metabolism markedly decreased in the application of mixtures, leading to unmetabolized PAH accumulation in human skin. PAH metabolism was similar between CTP-I and PC-I, but was lower for the highest dose and the industrial mixtures, suggesting a saturation of xenobiotic metabolizing enzymes, as confirmed in a time-course study. UVR strongly inhibited all PAH metabolism. Altogether, these results underline the necessity to consider the reality of human exposure (PAH complex mixtures and UVR) during in vitro experiments to properly estimate skin absorption and metabolism.


Polycyclic aromatic hydrocarbons Mixtures Toxicological interactions Ultraviolet radiation Biotransformation Skin absorption 



This work was funded by the French National Institute of Health and Medical Research (INSERM) (Grant number ENV201412) and the Agence Nationale de Sécurité Sanitaire, de l’alimentation, de l’environnement et du travail (ANSES) (Grant number EST-2014/1/176). The authors wish to thank the team of the “Service de Chirurgie Plastique et Maxillo-faciale CHU Grenoble Alpes” for skin sample collection.


This work was funded by the French National Institute of Health and Medical Research (INSERM) (Grant number ENV201412) and the Agence Nationale de Sécurité Sanitaire, de l’alimentation, de l’environnement et du travail (ANSES) (Grant number EST-2014/1/176). These funders had no role in study design, in the collection, analysis or interpretation of data, in the writing of the report, and in the decision to submit the article for publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Experiments were conducted in accordance with the article L1245-2 of the French Public Health Code on the use of surgical wastes for research purposes. Collection, storage and use of human skin samples were made anonymously, declared to the French authorities and validated in the CODECOH DC-2008-444 document.

Informed consent

Informed consent was obtained from all skin donors.

Data availability

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

204_2019_2504_MOESM1_ESM.docx (2.1 mb)
Supplementary material 1 (DOCX 2197 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Etienne Bourgart
    • 1
  • Renaud Persoons
    • 1
    • 2
  • Marie Marques
    • 1
  • Alex Rivier
    • 1
  • Franck Balducci
    • 1
  • Anne von Koschembahr
    • 3
  • David Béal
    • 3
  • Marie-Thérèse Leccia
    • 4
  • Thierry Douki
    • 3
  • Anne Maitre
    • 1
    • 2
    Email author
  1. 1.Equipe Environnement et Prédiction de la Santé des Populations, Laboratoire TIMC-IMAG (UMR 5525 UGA-CNRS)Université Grenoble Alpes, Faculté de MédecineLa Tronche CedexFrance
  2. 2.Laboratoire de Toxicologie Professionnelle et Environnementale, Service de Biochimie Biologie moléculaire Toxicologie EnvironnementaleIBP, CHU Grenoble AlpesGrenoble Cedex 09France
  3. 3.Univ. Grenoble Alpes, CEA, CNRS, INAC-SyMMES-CIBESTGrenoble Cedex 09France
  4. 4.Clinique de DermatologieAllergologie et Photobiologie, CHU Grenoble AlpesGrenoble Cedex 09France

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