, Les données ont été analysées au moyen d'un modèle de régression linéaire à effet mixte afin d'évaluer l'effet de la dose, du temps et de l'âge sur la pénétration, le métabolisme et la diffusion

, Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer, vol.92, pp.1-853, 2010.

S. O. Baek, M. E. Goldstone, P. Kirk, J. N. Lester, and R. Perry, Phase distribution and particle size dependency of polycyclic aromatic hydrocarbons in the urban atmosphere, Chemosphere, vol.22, issue.5, pp.503-523, 1991.

S. Fustinoni, L. Campo, P. E. Cirla, I. Martinotti, M. Buratti et al., Dermal exposure to polycyclic aromatic hydrocarbons in asphalt workers, Occupational and environmental medicine, vol.67, issue.7, pp.456-63, 2010.

J. G. Vanrooij, M. M. Bodelier-bade, and F. J. Jongeneelen, Estimation of individual dermal and respiratory uptake of polycyclic aromatic hydrocarbons in 12 coke oven workers, British Journal of Industrial Medicine, vol.50, issue.7, pp.623-655, 1993.

K. Förster, R. Preuss, B. Roßbach, T. Brüning, J. Angerer et al., 3-Hydroxybenzo[a]pyrene in the urine of workers with occupational exposure to polycyclic aromatic hydrocarbons in different industries, Occupational and environmental medicine, vol.65, issue.4, pp.224-233, 2008.

E. Pukkala, J. I. Martinsen, E. Weiderpass, K. Kjaerheim, E. Lynge et al., Cancer incidence among firefighters: 45 years of follow-up in five Nordic countries, Occupational and environmental medicine, vol.71, issue.6, pp.398-404, 2014.

P. Boffetta, N. Jourenkova, and P. Gustavsson, Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons, Cancer Causes & Control, vol.8, issue.3, pp.444-72, 1997.

J. G. Vanrooij, E. M. Van-lieshout, M. M. Bodelier-bade, and F. J. Jongeneelen, Effect of the reduction of skin contamination on the internal dose of creosote workers exposed to polycyclic aromatic hydrocarbons, Scandinavian Journal of Work, vol.1993, issue.3, pp.200-207

S. Nesnow, M. J. Mass, J. A. Ross, A. J. Galati, G. R. Lambert et al., Lung tumorigenic interactions in strain A/J mice of five environmental polycyclic aromatic hydrocarbons, Environmental Health Perspectives, vol.106, issue.6, pp.1337-1383, 1998.

I. Chu, D. Dick, R. Bronaugh, and L. Tryphonas, Skin reservoir formation and bioavailability of dermally administered chemicals in hairless guinea pigs, Food and Chemical Toxicology, vol.34, issue.3, pp.267-76, 1996.

C. Jacques, E. Perdu, H. Duplan, E. L. Jamin, C. Canlet et al., Disposition and biotransformation of 14C-Benzo(a)pyrene in a pig ear skin model: ex vivo and in vitro approaches, Toxicology letters, vol.199, issue.1, pp.22-33, 2010.

K. M. Ng, I. Chu, R. L. Bronaugh, C. A. Franklin, and D. A. Somers, Percutaneous absorption and metabolism of pyrene, benzo[a]pyrene, and di(2-ethylhexyl) phthalate: comparison of in vitro and in vivo results in the hairless guinea pig, Toxicology and applied pharmacology, vol.115, issue.2, pp.216-239, 1992.

B. Moorthy, C. Chu, and D. J. Carlin, Polycyclic aromatic hydrocarbons: from metabolism to lung cancer. Toxicological sciences : an official journal of the Society of Toxicology, vol.145, pp.5-15, 2015.

W. Xue and D. Warshawsky, Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: A review, Toxicology and applied pharmacology, vol.206, issue.1, pp.73-93, 2005.

J. Brinkmann, K. Stolpmann, S. Trappe, T. Otter, D. Genkinger et al., Metabolically competent human skin models: activation and genotoxicity of benzo[a]pyrene. Toxicological sciences : an official journal of the Society of Toxicology, vol.131, pp.351-360, 2013.

F. Oesch, E. Fabian, K. Guth, and R. Landsiedel, Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models, Archives of Toxicology, vol.88, issue.12, pp.2135-90, 2014.

F. Oesch, E. Fabian, and R. Landsiedel, Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models, Archives of Toxicology, 2018.

M. Timo-partanen-phd, P. Boffetta-md, M. Partanen, T. Boffetta, and P. , Cancer risk in asphalt workers and roofers: Review and meta-analysis of epidemiologic studies1994, p.p

H. Dickel, O. Blome, B. Dickel, T. Bruckner, E. Stockfleth et al., Occupational syncarcinogenesis in the skin -combined effects of two carcinogens from the German occupational disease list, JDDG: Journal der Deutschen Dermatologischen Gesellschaft, vol.14, issue.12, pp.1284-96, 2016.

J. S. Stenehjem, T. E. Robsahm, M. Bråtveit, S. O. Samuelsen, J. Kirkeleit et al., Aromatic hydrocarbons and risk of skin cancer by anatomical site in 25 000 male offshore petroleum workers, American Journal of Industrial Medicine, vol.60, issue.8, pp.679-88, 2017.

K. E. Burke and H. Wei, Synergistic damage by UVA radiation and pollutants. Toxicology and industrial health, vol.25, pp.219-243, 2009.

. Iarc and . Radiation, IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer, vol.100, pp.7-303, 2012.

B. L. Diffey, Sources and measurement of ultraviolet radiation, Methods, vol.28, issue.1, pp.4-13, 2002.

, IARC monographs on the evaluation of carcinogenic risks to humans. Solar and ultraviolet radiation. IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer, vol.55, pp.1-316, 1992.

V. T. Natarajan, P. Ganju, A. Ramkumar, R. Grover, and R. S. Gokhale, Multifaceted pathways protect human skin from UV radiation, Nature Chemical Biology, vol.10, p.542, 2014.

M. Svoboda, Z. Bílková, and T. Muthný, Could tight junctions regulate the barrier function of the aged skin, Journal of dermatological science, vol.81, issue.3, pp.147-52, 2016.

K. Biniek, K. Levi, and R. H. Dauskardt, Solar UV radiation reduces the barrier function of human skin, Proceedings of the National Academy of Sciences of the United States of America, vol.109, issue.42, pp.17111-17117, 2012.

D. I. Pattison and M. J. Davies, Actions of ultraviolet light on cellular structures, EXS, issue.96, pp.131-57, 2006.

L. Rittie and G. J. Fisher, Natural and sun-induced aging of human skin, Cold Spring Harb Perspect Med, vol.5, issue.1, p.15370, 2015.

C. Gelis, A. Mavon, M. Delverdier, N. Paillous, and P. Vicendo, Modifications of in vitro skin penetration under solar irradiation: evaluation on flow-through diffusion cells, Photochem Photobiol, vol.75, issue.6, pp.598-604, 2002.

C. F. Hung, C. L. Fang, S. A. Al-suwayeh, Y. Sy, and J. Y. Fang, Evaluation of drug and sunscreen permeation via skin irradiated with UVA and UVB: comparisons of normal skin and chronologically aged skin, Journal of dermatological science, 2012.

L. J. Mortensen, S. Jatana, R. Gelein, D. Benedetto, A. et al., Quantification of quantum dot murine skin penetration with UVR barrier impairment, Nanotoxicology, vol.7, issue.8, pp.1386-98, 2013.

D. J. Mcauliffe and I. H. Blank, Effects of UVA (320-400 nm) on the barrier characteristics of the skin, J Invest Dermatol, vol.96, issue.5, pp.758-62, 1991.

Q. Ma, Influence of light on aryl hydrocarbon receptor signaling and consequences in drug metabolism, physiology and disease, Expert Opin Drug Metab Toxicol, vol.7, issue.10, pp.1267-93, 2011.

S. K. Katiyar, H. Mukhtar, and M. S. Matsui, Ultraviolet-B Exposure of Human Skin Induces Cytochromes P450 1A1 and 1B1, Journal of Investigative Dermatology, vol.114, issue.2, pp.328-361, 2000.

P. H. Villard, E. Sampol, J. L. Elkaim, F. Puyoou, D. Casanova et al., Increase of CYP1B1 Transcription in Human Keratinocytes and HaCaT Cells after UV-B Exposure, Toxicology and applied pharmacology, vol.178, issue.3, pp.137-180, 2002.
URL : https://hal.archives-ouvertes.fr/hal-01773794

R. Saladi, L. Austin, D. Gao, Y. Lu, R. Phelps et al., The Combination of Benzo[a]pyrene and Ultraviolet A Causes an In Vivo Time-related Accumulation of DNA Damage in Mouse Skin ¶, Photochemistry and Photobiology, vol.77, issue.4, pp.413-422, 2003.

A. Von-koschembahr, A. Youssef, D. Béal, C. Calissi, E. Bourgart et al., Solar simulated light exposure alters metabolization and genotoxicity induced by benzo[a]pyrene in human skin, Scientific Reports, vol.8, issue.1, p.14692, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01903708

H. Yu, Environmental carcinogenic polycyclic aromatic hydrocarbons: photochemistry and phototoxicity, J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, vol.20, issue.2, pp.149-83, 2002.

P. P. Fu, Q. Xia, X. Sun, and H. Yu, Phototoxicity and environmental transformation of polycyclic aromatic hydrocarbons (PAHs)-light-induced reactive oxygen species, lipid peroxidation, and DNA damage, J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, vol.30, issue.1, pp.1-41, 2012.

Q. Xia, H. M. Chiang, J. J. Yin, S. Chen, L. Cai et al., UVA photoirradiation of benzo[a]pyrene metabolites: induction of cytotoxicity, reactive oxygen species, and lipid peroxidation, Toxicology and industrial health, vol.31, issue.10, pp.898-910, 2015.

N. B. Hopf, P. Spring, N. Hirt-burri, S. Jimenez, B. Sutter et al., Polycyclic aromatic hydrocarbons (PAHs) skin permeation rates change with simultaneous exposures to solar ultraviolet radiation (UV-S), Toxicology letters, vol.287, pp.122-152, 2018.

E. Bourgart, D. Barbeau, M. Marques, A. Von-koschembahr, D. Béal et al., A realistic human skin model to study benzo[a]pyrene cutaneous absorption in order to determine the most relevant biomarker for carcinogenic exposure, Archives of Toxicology, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01903702

A. Dufresne, J. Lesage, and G. Perrault, IARC. Bitumens and bitumen emmissions, and some N-and S-heterocyclic polycyclic aromatic hydrocarbons: World Health Organization, American Industrial Hygiene Association Journal, vol.48, issue.2, pp.160-166, 1987.

Z. Li, Y. Wu, Y. Zhao, L. Wang, H. Zhu et al., Analysis of coal tar pitch and smoke extract components and their cytotoxicity on human bronchial epithelial cells, Journal of Hazardous Materials, vol.186, issue.2, pp.185-97, 1993.

J. E. Storm, S. W. Collier, R. F. Stewart, and R. L. Bronaugh, Metabolism of xenobiotics during percutaneous penetration: role of absorption rate and cutaneous enzyme activity, Fundamental and applied toxicology : official journal of the Society of Toxicology, vol.15, issue.1, pp.132-173, 1990.

M. Mcclean, R. Rinehart, and R. Herrick, Dermal Exposure and Urinary 1-Hydroxypyrene Among Asphalt Roofing Workers, Epidemiology, vol.17, issue.6, pp.134-139, 2006.

J. Gundel and J. Angerer, High-performance liquid chromatographic method with fluorescence detection for the determination of 3-hydroxybenzo[a]pyrene and 3-hydroxybenz[a]anthracene in the urine of polycyclic aromatic hydrocarbon-exposed workers, Journal of chromatography B, Biomedical sciences and applications, vol.738, issue.1, pp.47-55, 2000.

X. Xu, J. Zhang, L. Zhang, W. Liu, and C. P. Weisel, Selective detection of monohydroxy metabolites of polycyclic aromatic hydrocarbons in urine using liquid chromatography/triple quadrupole tandem mass spectrometry. Rapid communications in mass spectrometry : RCM, vol.18, pp.2299-308, 2004.

N. Grova, F. Faÿs, E. M. Hardy, and B. Appenzeller, New insights into urine-based assessment of polycyclic aromatic hydrocarbon-exposure from a rat model: Identification of relevant metabolites and influence of elimination kinetics, Environmental Pollution, vol.228, pp.484-95, 2017.

M. C. Macleod, B. K. Mansfield, and J. K. Selkirk, Time course of metabolism of benzo[e]pyrene by hamster embryo cells and the effect of chemical modifiers, Chemico-biological interactions, vol.40, issue.3, pp.275-85, 1982.

D. C. Spink, S. J. Wu, B. C. Spink, M. M. Hussain, D. D. Vakharia et al., Induction of CYP1A1 and CYP1B1 by benzo(k)fluoranthene and benzo(a)pyrene in T-47D human breast cancer cells: roles of PAH interactions and PAH metabolites, Toxicology and applied pharmacology, vol.226, issue.3, pp.213-237, 2008.

E. J. Lavoie, S. S. Hecht, S. Amin, V. Bedenko, and D. Hoffmann, Identification of mutagenic dihydrodiols as metabolites of benzo(j)fluoranthene and benzo(k)fluoranthene. Cancer research, vol.40, pp.4528-4560, 1980.

C. S. Cooper, O. Ribeiro, A. Hewer, C. Walsh, K. Pal et al., The involvement of a 'bay-region' and a non-'bay-region' diol-epoxide in the metabolic activation of benz(a)anthracene in mouse skin and in hamster embryo cells, Carcinogenesis, vol.1, issue.3, pp.233-276, 1980.

S. S. Hecht, S. G. Carmella, P. W. Villalta, and J. B. Hochalter, Analysis of Phenanthrene and Benzo[a]pyrene Tetraol Enantiomers in Human Urine: Relevance to the Bay Region Diol Epoxide Hypothesis of Benzo, Carcinogenesis and to Biomarker Studies. Chemical research in toxicology, vol.23, issue.5, pp.900-908, 2010.

D. A. Dankovic, C. W. Wright, R. C. Zangar, and D. L. Springer, Complex mixture effects on the dermal absorption of benzo[a]pyrene and other polycyclic aromatic hydrocarbons from mouse skin, Journal of applied toxicology : JAT, vol.9, issue.4, pp.239-283, 1989.

P. Sartorelli, L. Montomoli, A. G. Sisinni, R. Bussani, D. Cavallo et al., Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from coal dust, Toxicology and industrial health, vol.17, issue.1, pp.17-21, 2001.

J. G. Vanrooij, E. Vinke, D. Lange, J. Bruijnzeel, P. L. Bodelier-bade et al., Dermal absorption of polycyclic aromatic hydrocarbons in the blood-perfused pig ear, Journal of applied toxicology : JAT, vol.15, issue.3, pp.193-200, 1995.

T. Sousa, R. Paterson, V. Moore, A. Carlsson, B. Abrahamsson et al., The gastrointestinal microbiota as a site for the biotransformation of drugs, International Journal of Pharmaceutics, vol.363, issue.1, pp.1-25, 2008.

J. K. Chipman, P. C. Hirom, G. S. Frost, and P. Millburn, The biliary excretion and enterohepatic circulation of benzo (a)pyrene and its metabolites in the rat, Biochemical Pharmacology, vol.30, issue.9, pp.937-981, 1981.

B. Sen, B. Mahadevan, and D. M. Demarini, Transcriptional responses to complex mixtures-A review, Mutation Research/Reviews in Mutation Research, vol.636, issue.1, pp.144-77, 2007.

H. Líbalová, S. Kr?ková, K. Uhlí?ová, A. Milcová, J. Schmuczerová et al.,

, AhR-mediated activity of PAHs is inhibited by other components of complex mixtures of ambient air pollutants, Toxicology letters, vol.225, issue.3, pp.350-357, 2014.

H. Líbalová, K. Uhlí?ová, J. Kléma, M. Machala, R. J. ?rám et al., Global gene expression changes in human embryonic lung fibroblasts induced by organic extracts from respirable air particles, Particle and Fibre Toxicology, vol.9, issue.1, p.1, 2012.

T. Shimada, N. Murayama, K. Tanaka, S. Takenaka, Y. Imai et al., Interaction of Polycyclic Aromatic Hydrocarbons with Human Cytochrome P450 1B1 in Inhibiting Catalytic Activity. Chemical research in toxicology, vol.21, pp.2313-2336, 2008.

D. D. Vakharia, N. Liu, R. Pause, M. Fasco, E. Bessette et al., Polycyclic Aromatic Hydrocarbon/Metal Mixtures: Effect on PAH Induction of CYP1A1 in Human HepG2 Cells, Drug Metabolism and Disposition, vol.29, issue.7, pp.999-1006, 2001.

I. Nisbet and P. K. Lagoy, Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs)

, Regulatory Toxicology and Pharmacology, vol.16, issue.3, pp.290-300, 1992.

I. Jarvis, K. Dreij, Å. Mattsson, B. Jernström, and U. Stenius, Interactions between polycyclic aromatic hydrocarbons in complex mixtures and implications for cancer risk assessment, Toxicology, vol.321, pp.27-39, 2014.

S. J. Jiang, A. W. Chu, Z. F. Lu, M. H. Pan, D. F. Che et al., Ultraviolet B-induced alterations of the skin barrier and epidermal calcium gradient, Exp Dermatol, vol.16, issue.12, pp.985-92, 2007.

Z. I. Garcia-berrios and R. Arce, Photodegradation mechanisms of 1-nitropyrene, an environmental pollutant: the effect of organic solvents, water, oxygen, phenols, and polycyclic aromatics on the destruction and product yields, J Phys Chem A, vol.116, issue.14, pp.3652-64, 2012.

F. Feo, L. Pirisi, R. Pascale, L. Daino, S. Frassetto et al., Modulatory mechanisms of chemical carcinogenesis: the role of the NADPH pool in the benzo(a)pyrene activation, Toxicol Pathol, vol.12, issue.3, pp.261-269, 1984.

J. Soeur, J. Belaïdi, C. Chollet, L. Denat, A. Dimitrov et al., Photo-pollution stress in skin: Traces of pollutants (PAH and particulate matter) impair redox homeostasis in keratinocytes exposed to UVA1, Journal of dermatological science, vol.86, issue.2, pp.162-171, 2017.

T. Douki, Z. Ksoury, C. Marie, A. Favier, J. Ravanat et al., Genotoxicity of Combined Exposure to Polycyclic Aromatic Hydrocarbons and UVA-A Mechanistic Study, Photochemistry and Photobiology, vol.84, issue.5, pp.1133-1173, 2008.
URL : https://hal.archives-ouvertes.fr/hal-01973135

, Des études complémentaires sont nécessaires pour déterminer le devenir du réservoir cutané des HAP, car l'effet des mélanges sur la biotransformation des HAP est inconnu à long terme, mais ces résultats soulignent là encore l'importance des équipements de protection et de la décontamination de la peau afin d

H. I. Abdel-shafy and M. Mansour, A review on polycyclic aromatic hydrocarbons: Source, environmental impact, effect on human health and remediation, Egyptian Journal of Petroleum, vol.25, issue.1, pp.107-123, 2016.

J. I. Ademola, L. E. Sedik, R. C. Wester, and H. I. Maibach, In vitro percutaneous absorption and metabolism in man of 2-chloro-4-ethylamino-6-isopropylamine-s-triazine (Atrazine), Archives of Toxicology, vol.67, issue.2, pp.85-91, 1993.

J. I. Ademola, R. C. Wester, and H. I. Maibach, Absorption and Metabolism of 2-Chloro-2,6-diethyl-N-(butoxymethyl)acetanilide (Butachlor) in Human Skin in Vitro, Toxicology and applied pharmacology, vol.121, issue.1, pp.78-86, 1993.

I. Afsse and A. , Ultra-violets -Etat des connaissances sur l'exposition et les risques sanitaires, p.191, 2005.

E. Aklillu, S. Øvrebø, I. V. Botnen, C. Otter, and M. Ingelman-sundberg, Characterization of Common CYP1B1 Variants with Different Capacity for Benzo[a]pyrene-7,8-Dihydrodiol Epoxide Formation from Benzo[a]pyrene, Cancer research, vol.65, issue.12, pp.5105-5111, 2005.

M. R. Albert and K. G. Ostheimer, The evolution of current medical and popular attitudes toward ultraviolet light exposure: Part 1, Journal of the American Academy of Dermatology, vol.47, issue.6, pp.930-937, 2002.

M. R. Albert and K. G. Ostheimer, The evolution of current medical and popular attitudes toward ultraviolet light exposure: Part 2, Journal of the American Academy of Dermatology, vol.48, issue.6, pp.909-918, 2003.

M. R. Albert and K. G. Ostheimer, The evolution of current medical and popular attitudes toward ultraviolet light exposure: part 3, Journal of the American Academy of Dermatology, vol.49, issue.6, pp.1096-1106, 2003.

D. Ali, A. Verma, F. Mujtaba, A. Dwivedi, R. K. Hans et al., UVB-induced apoptosis and DNA damaging potential of chrysene via reactive oxygen species in human keratinocytes, Toxicology letters, vol.204, issue.2, pp.199-207, 2011.

H. Alomirah, S. Al-zenki, A. , and S. , Concentrations and dietary exposure to polycyclic aromatic hydrocarbons (PAHs) from grilled and smoked foods, Food Control, vol.22, issue.12, pp.2028-2035, 2011.

S. Amin, K. Huie, and S. S. Hecht, Mutagenicity and tumor initiating activity of methylated benzo[b]fluoranthenes, Carcinogenesis, vol.6, issue.7, pp.1023-1028, 1985.

S. Amin, N. Hussain, H. Brielmann, and S. S. Hecht, A study of chemical carcinogenesis. 57. Synthesis and mutagenicity of dihydrodiol metabolites of benzo[b]fluoranthene, The Journal of Organic Chemistry, vol.49, issue.6, pp.1091-1095, 1984.

S. Amin, E. J. Lavoie, and S. S. Hecht, Identification of metabolites of benzo[b]fluoranthene, Carcinogenesis, vol.3, issue.2, pp.171-175, 1982.

J. T. Andersson and C. Achten, Time to Say Goodbye to the 16 EPA PAHs? Toward an Upto-Date Use of PACs for Environmental Purposes, Polycyclic Aromatic Compounds, vol.35, issue.2-4, pp.330-354, 2015.

J. Angerer, U. Ewers, and M. Wilhelm, Human biomonitoring: State of the art, International Journal of Hygiene and Environmental Health, vol.210, issue.3, pp.201-228, 2007.

J. Angerer, C. Mannschreck, J. Gundel, and . Institute, Occupational exposure to polycyclic aromatic hydrocarbons in a graphite-electrode producing plant : biological monitoring of 1-hydroxypyrene and monohydroxylated metabolites of phenanthrene, International archives of occupational and environmental health, vol.69, issue.5, pp.323-331, 1997.

R. Araujo, R. S. Dyer, and R. C. Fortmann, A Conceptual Framework for U.S. EPA's National Exposure Research Laboratory, 2009.

, ATSDR (1995) Toxicological profile for Polycyclic Aromatic Hydrocarbons (PAHs)

, :Department of Health and Human Services, Public Health Service

H. Autrup, C. C. Harris, B. F. Trump, and A. M. Jeffrey, Metabolism of Benzo(a)pyrene and Identification of the Major Benzo(a)pyrene-DNA Adducts in Cultured Human Colon, Cancer research, vol.38, issue.11, pp.3689-3696, 1978.

T. Backhaus, H. Blanck, and M. Faust, Hazard and Risk Assessment of Chemical Mixtures under REACH State of the Art, Gaps and Options for Improvement Swedish Chemicals Agency-www. kemi. se Hazard and Risk Assessment of Chemical Mixtures under REACH State of the Art, Gaps and Options for Improv, 2010.

S. O. Baek, M. E. Goldstone, P. Kirk, J. N. Lester, and R. Perry, Phase distribution and particle size dependency of polycyclic aromatic hydrocarbons in the urban atmosphere, Chemosphere, vol.22, issue.5, pp.503-520, 1991.

W. M. Baird, L. A. Hooven, and B. Mahadevan, Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action, Environmental and molecular mutagenesis, vol.45, issue.2-3, pp.106-114, 2005.

C. Barba, C. Alonso, M. Martí, A. Manich, and L. Coderch, Skin barrier modification with organic solvents, Biochimica et Biophysica Acta (BBA) -Biomembranes, vol.1858, issue.8, pp.1935-1943, 2016.

D. Barbeau, (a)pyrene as biomarker of exposure to polycyclic aromatic hydrocarbons, p.3, 2013.
URL : https://hal.archives-ouvertes.fr/tel-01061819

D. Barbeau, S. Lutier, L. Choisnard, M. Marques, R. Persoons et al., (a)pyrene as the most relevant biomarker for assessing carcinogenic polycyclic aromatic hydrocarbons exposure, Environ Int, vol.8, pp.147-155, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01903042

D. Barbeau, A. Maitre, and M. Marques, Highly sensitive routine method for urinary 3-hydroxybenzo[a]pyrene quantitation using liquid chromatography-fluorescence detection and automated off-line solid phase extraction, Analyst, vol.136, issue.6, pp.1183-1191, 2011.
URL : https://hal.archives-ouvertes.fr/hal-01903163

A. Baroni, E. Buommino, D. Gregorio, V. Ruocco, E. Ruocco et al., Structure and function of the epidermis related to barrier properties, Clinics in Dermatology, vol.30, issue.3, pp.257-262, 2012.

H. Bartsch, U. Nair, A. Risch, M. Rojas, H. Wikman et al., Genetic Polymorphism of CYP Genes, Alone or in Combination, as a Risk Modifier of Tobacco-related Cancers, Cancer Epidemiology Biomarkers & Prevention, vol.9, issue.1, pp.3-28, 2000.

N. Bartsch, J. Heidler, B. Vieth, C. Hutzler, and A. Luch, Skin permeation of polycyclic aromatic hydrocarbons: A solvent-based in vitro approach to assess dermal exposures against benzo[a]pyrene and dibenzopyrenes, Journal of Occupational and Environmental Hygiene, vol.13, issue.12, pp.969-979, 2016.

E. Berardesca and H. Maibach, Ethnic skin: Overview of structure and function, S139-S142 doi, vol.48, 2003.

D. J. Beriro, M. R. Cave, J. Wragg, R. Thomas, G. Wills et al., A review of the current state of the art of physiologically-based tests for measuring human dermal in vitro bioavailability of polycyclic aromatic hydrocarbons (PAH) in soil, Journal of Hazardous Materials, vol.305, pp.240-259, 2016.

N. Berry, C. Charmeil, and C. Goujon, A Clinical, Biometrological and Ultrastructural Study of Xerotic Skin, International Journal of Cosmetic Science, vol.21, issue.4, pp.241-252, 2001.

T. A. Bertram, J. W. Ludlow, J. Basu, and S. Muthupalani, Haschek and Rousseaux's Handbook of Toxicologic Pathology, pp.2277-2359, 2013.

K. Biniek, K. Levi, and R. H. Dauskardt, Solar UV radiation reduces the barrier function of human skin, Proceedings of the National Academy of Sciences of the United States of America, vol.109, issue.42, pp.17111-17117, 2012.

B. Binkova, I. Chvatalova, and Z. Lnenickova, PAH-DNA adducts in environmentally exposed population in relation to metabolic and DNA repair gene polymorphisms. Mutation Research/Fundamental and Molecular Mechanisms of, Mutagenesis, vol.620, issue.1, pp.49-61, 2007.

L. Bláha, P. Kapplová, J. Vondrá?ek, B. Upham, and M. Machala, Inhibition of gap-junctional intercellular communication by environmentally occurring polycyclic aromatic hydrocarbons, Toxicological Sciences, vol.65, issue.1, pp.43-51, 2002.

C. Blanpain and E. Fuchs, Epidermal Stem Cells of the Skin, Annual review of cell and developmental biology, vol.22, pp.339-373, 2006.

P. Boffetta, N. Jourenkova, and P. Gustavsson, Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons, Cancer Causes & Control, vol.8, issue.3, pp.444-472, 1997.

M. Boniol, A. Koechlin, and M. Boniol, Occupational UV Exposure in French Outdoor Workers, Journal of Occupational and Environmental Medicine, vol.57, issue.3, pp.315-320, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01262236

J. D. Bos and M. Meinardi, The 500 Dalton rule for the skin penetration of chemical compounds and drugs, Experimental Dermatology, vol.9, issue.3, pp.165-169, 2000.

C. Boström, P. Gerde, and A. Hanberg, Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambient air, Environmental Health Perspectives, vol.110, issue.3, pp.451-488, 2002.

C. Botta, D. Giorgio, C. Sabatier, A. S. , D. Meo et al., Effects of UVA and visible light on the photogenotoxicity of benzo[a]pyrene and pyrene, Environ Toxicol, vol.24, issue.5, pp.492-505, 2009.

M. Bouchard, L. Normandin, and F. Gagnon, Repeated measures of validated and novel biomarkers of exposure to polycyclic aromatic hydrocarbons in individuals living near an aluminum plant in Quebec, Canada. Journal of toxicology and environmental health Part A, vol.72, issue.23, pp.1534-1583, 2009.

C. C. Bourguet, H. Checkoway, and B. S. Hulka, A case-control study of skin cancer in the tire and rubber manufacturing industry, American Journal of Industrial Medicine, vol.11, issue.4, pp.461-473, 1987.

J. A. Bouwstra, G. S. Gooris, M. Vries, J. A. Van-der-spek, and W. Bras, Structure of human stratum corneum as a function of temperature and hydration: A wide-angle X-ray diffraction study, International Journal of Pharmaceutics, vol.84, issue.3, pp.205-216, 1992.

E. Boyland and P. Sims, The metabolism of benz[a]anthracene and dibenz[a,h]anthracene and their 5,6-epoxy-5,6-dihydro derivatives by rat-liver homogenates, The Biochemical journal, vol.97, issue.1, pp.7-16, 1965.

E. Braithwaite, X. Wu, and Z. Wang, Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts: involvement of two excision repair mechanisms in vitro, Carcinogenesis, vol.19, issue.7, pp.1239-1246, 1998.

H. Brandt and W. P. Watson, Monitoring Human Occupational and Environmental Exposures to Polycyclic Aromatic Compounds, The Annals of occupational hygiene, vol.47, issue.5, pp.349-378, 2003.

J. Brinkmann, K. Stolpmann, and S. Trappe, Metabolically competent human skin models: activation and genotoxicity of benzo[a]pyrene. Toxicological sciences : an official journal of the Society of, Toxicology, vol.131, issue.2, pp.351-360, 2013.

R. L. Bronaugh and H. I. Maibach, Methods for in vitro percutaneous absorption studies IV: The flow-through diffusion cell, Percutaneous Absorption: Drugs, Cosmetics, Mechanisms, Methods, vol.74, pp.64-71, 1985.

R. L. Bronaugh and R. F. Stewart, Methods for In Vitro Percutaneous Absorption Studies V: Permeation Through Damaged Skin, Journal of pharmaceutical sciences, vol.74, issue.10, pp.1062-1066, 1985.

R. L. Bronaugh, R. F. Stewart, E. R. Congdon, and A. L. Giles, Methods for in vitro percutaneous absorption studies I. Comparison with in vivo results, Toxicology and applied pharmacology, vol.62, issue.3, pp.474-480, 1982.

R. L. Bronaugh, R. F. Stewart, and J. E. Storm, Extent of cutaneous metabolism during percutaneous absorption of xenobiotics, Toxicology and applied pharmacology, vol.99, issue.3, pp.90160-90169, 1989.

M. K. Buening, W. Levin, and A. W. Wood, Tumorigenic activity of benzo(e)pyrene derivatives on mouse skin and in newborn mice, Cancer research, vol.40, issue.2, pp.203-209, 1980.

M. K. Buening, W. Levin, and A. W. Wood, Tumorigenicity of the dihydrodiols of dibenzo(a,h)anthracene on mouse skin and in newborn mice, Cancer research, vol.39, issue.4, pp.1310-1314, 1979.

R. Buesen, M. Mock, H. Nau, A. Seidel, J. Jacob et al., Human intestinal Caco-2 cells display active transport of benzo[a]pyrene metabolites, Chemico-Biological Interactions, vol.142, issue.3, pp.201-221, 2003.

M. E. Burczynski, H. Lin, and T. M. Penning, Isoform-specific Induction of a Human Aldo-Keto Reductase by Polycyclic Aromatic Hydrocarbons (PAHs), Electrophiles, and Oxidative Stress: Implications for the Alternative Pathway of PAH Activation Catalyzed by Human Dihydrodiol Dehydrogenase, Cancer research, vol.59, issue.3, pp.607-614, 1999.

M. E. Burczynski and T. M. Penning, Genotoxic Polycyclic Aromatic Hydrocarbon ortho-Quinones Generated by Aldo-Keto Reductases Induce CYP1A1 via Nuclear Translocation of the Aryl Hydrocarbon Receptor, Cancer research, vol.60, issue.4, pp.908-915, 2000.

D. L. Busbee, J. O. Norman, and R. L. Ziprin, Comparative uptake, vascular transport, and cellular internalization of aflatoxin-B1 and benzo(a)pyrene, Archives of Toxicology, vol.64, issue.4, pp.285-290, 1990.

L. Campo, F. Rossella, and S. Fustinoni, Development of a gas chromatography/mass spectrometry method to quantify several urinary monohydroxy metabolites of polycyclic aromatic hydrocarbons in occupationally exposed subjects, Journal of chromatography B, Analytical technologies in the biomedical and life sciences, vol.875, issue.2, pp.531-571, 2008.

L. Campo, F. Rossella, and S. Pavanello, Urinary profiles to assess polycyclic aromatic hydrocarbons exposure in coke-oven workers, Toxicology letters, vol.192, issue.1, pp.72-80, 2010.

D. Castro, K. Slezakova, C. Delerue-matos, A. Mdc, S. Morais et al., Polycyclic aromatic hydrocarbons in gas and particulate phases of indoor environments influenced by tobacco smoke: Levels, phase distributions, and health risks, Atmospheric Environment, vol.45, issue.10, pp.1799-1808, 2011.

E. L. Cavalieri and E. G. Rogan, The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation, 1992.

, Pharmacology & Therapeutics, vol.55, issue.2, p.90015

E. L. Cavalieri, E. G. Rogan, P. Cremonesi, and P. D. Devanesan, Radical cations as precursors in the metabolic formation of quinones from benzo[a]pyrene and 6-fluorobenzo[a]pyrene: Fluoro substitution as a probe for one-electron oxidation in aromatic substrates, Biochemical Pharmacology, vol.37, issue.11, pp.2173-2182, 1988.

L. Celleno and F. Tamburi, Structure and Function of the Skin A2 -Tabor, Aaron. In: Blair RM (ed) Nutritional Cosmetics, pp.3-45, 2009.

K. Chaloupka, M. Steinberg, M. Santostefano, L. V. Rodriguez, L. Goldstein et al., Induction of Cyp1a-1 and Cyp1a-2 gene expression by a reconstituted mixture of polynuclear aromatic hydrocarbons in B6C3F1 mice, Chemico-Biological Interactions, vol.96, issue.3, pp.207-221, 1995.

R. L. Chang, W. Levin, and A. W. Wood, Tumorigenicity of the diastereomeric bayregion benzo(e)pyrene 9,10-diol-11,12-epoxides in newborn mice, Cancer research, vol.41, issue.3, pp.915-923, 1981.

M. Chen, P. Tsai, and Y. Wang, Assessing inhalatory and dermal exposures and their resultant health-risks for workers exposed to polycyclic aromatic hydrocarbons (PAHs) contained in oil mists in a fastener manufacturing industry, Environment International, vol.34, issue.7, pp.971-975, 2008.

L. Chi, J. Xue, P. Tu, Y. Lai, H. Ru et al., Gut microbiome disruption altered the biotransformation and liver toxicity of arsenic in mice, Archives of Toxicology, 2018.

J. K. Chipman, P. C. Hirom, G. S. Frost, and P. Millburn, The biliary excretion and enterohepatic circulation of benzo (a)pyrene and its metabolites in the rat, Biochemical Pharmacology, vol.30, issue.9, pp.937-944, 1981.

I. Chu, D. Dick, R. Bronaugh, and L. Tryphonas, Skin reservoir formation and bioavailability of dermally administered chemicals in hairless guinea pigs, Food and Chemical Toxicology, vol.34, issue.3, pp.112-115, 1996.

J. C. Chuang, P. J. Callahan, C. W. Lyu, and N. K. Wilson, Polycyclic aromatic hydrocarbon exposures of children in low-income families, Journal of exposure analysis and environmental epidemiology, vol.9, issue.2, pp.85-98, 1999.

H. S. Chun, H. J. Kim, Y. Kim, and H. J. Chang, Inhibition of the benzo[a]pyrene-induced toxicity by allyl sulfides in human epidermal keratinocytes, Biotechnology Letters, vol.26, issue.22, pp.1701-1706, 2004.

, Final Safety Assessment of Coal Tar as Used in Cosmetics, International Journal of Toxicology, vol.27, pp.1-24, 2008.

C. S. Cooper, O. Ribeiro, and A. Hewer, The involvement of a 'bay-region' and a non-'bay-region' diol-epoxide in the metabolic activation of benz(a)anthracene in mouse skin and in hamster embryo cells, Carcinogenesis, vol.1, issue.3, pp.233-243, 1980.

R. Crebelli, P. Carta, and C. Andreoli, Biomonitoring of primary aluminium industry workers: detection of micronuclei and repairable DNA lesions by alkaline SCGE, Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol.516, issue.1, pp.63-70, 2002.

P. Cremonesi, E. L. Cavalieri, and E. G. Rogan, One-electron oxidation of 6-substituted benzo[a]pyrenes by manganic acetate. A model for metabolic activation, The Journal of Organic Chemistry, vol.54, issue.15, pp.3561-3570, 1989.

L. Cui, Y. Jia, and Z. Cheng, Advancements in the maintenance of skin barrier/skin lipid composition and the involvement of metabolic enzymes, Journal of Cosmetic Dermatology, vol.15, issue.4, pp.549-558, 2016.

D. A. Dankovic, C. W. Wright, R. C. Zangar, and D. L. Springer, Complex mixture effects on the dermal absorption of benzo[a]pyrene and other polycyclic aromatic hydrocarbons from mouse skin, Journal of applied toxicology : JAT, vol.9, issue.4, pp.239-283, 1989.

M. Denda, Epidermis as the "Third Brain, Dermatologica Sinica, vol.33, issue.2, pp.70-73, 2015.

M. Denda, M. Nakatani, K. Ikeyama, M. Tsutsumi, and S. Denda, Epidermal keratinocytes as the forefront of the sensory system, Experimental Dermatology, vol.16, issue.3, pp.157-161, 2007.

M. F. Denissenko, A. Pao, M. Tang, and G. P. Pfeifer, Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53, Science, vol.274, issue.5286, pp.430-432, 1996.

H. Dickel, O. Blome, B. Dickel, T. Bruckner, E. Stockfleth et al., Occupational syncarcinogenesis in the skin -combined effects of two carcinogens from the German occupational disease list, JDDG: Journal der Deutschen Dermatologischen Gesellschaft, vol.14, issue.12, pp.1284-1296, 2016.

B. L. Diffey, Sources and measurement of ultraviolet radiation, Methods, vol.28, issue.1, pp.204-213, 2002.

B. L. Diffey and J. M. Elwood, Tables of ambient solar ultraviolet radiation for use in epidemiological studies of malignant melanoma and other diseases, Epidemiological Aspects of Cutaneous Malignant Melanoma, pp.81-105, 1994.

S. Dong, H. M. Hwang, C. Harrison, L. Holloway, X. Shi et al., UVA light-induced DNA cleavage by selected polycyclic aromatic hydrocarbons, Bulletin of environmental contamination and toxicology, vol.64, issue.4, pp.467-474, 2000.

T. Douki, Z. Ksoury, C. Marie, A. Favier, J. Ravanat et al., Genotoxicity of Combined Exposure to Polycyclic Aromatic Hydrocarbons and UVA-A Mechanistic Study, Photochemistry and Photobiology, vol.84, issue.5, pp.1133-1140, 2008.
URL : https://hal.archives-ouvertes.fr/hal-01973135

K. Dreij, K. Rhrissorrakrai, K. C. Gunsalus, N. E. Geacintov, and D. A. Scicchitano, Benzo[ a ]pyrene diol epoxide stimulates an inflammatory response in normal human lung fibroblasts through a p53 and JNK mediated pathway, Carcinogenesis, vol.31, issue.6, pp.1149-1157, 2010.

B. Dréno, Anatomie et physiologie de la peau et de ses annexes, S247-S251 doi, vol.136, 2009.

R. R. Driskell, C. Jahoda, C. Chuong, F. M. Watt, and V. Horsley, Defining dermal adipose tissue, Experimental Dermatology, vol.23, issue.9, pp.629-631, 2014.

B. Ebert, A. Seidel, and A. Lampen, Identification of BCRP as transporter of benzo[ a ]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ahreceptor agonists, Carcinogenesis, vol.26, issue.10, pp.1754-1763, 2005.

L. Eckhart, S. Lippens, E. Tschachler, and W. Declercq, Cell death by cornification, Biochimica et Biophysica Acta (BBA) -Molecular Cell Research, vol.1833, issue.12, pp.3471-3480, 2013.

F. S. Ehrenhauser, I. Pah, and . Nomenclature, Polycyclic Aromatic Compounds, vol.35, issue.2-4, pp.161-176, 2015.

S. Ekunwe, R. D. Hunter, and H. Hwang, Ultraviolet radiation increases the toxicity of pyrene, 1-aminopyrene and 1-hydroxypyrene to human keratinocytes, International journal of environmental research and public health, vol.2, issue.1, pp.58-62, 2005.

Z. Erbagci and S. Erkiliç, Can smoking and/or occupational UV exposure have any role in the development of the morpheaform basal cell carcinoma? A critical role for peritumoral mast cells, International Journal of Dermatology, vol.41, issue.5, pp.275-278, 2002.

M. Esteban and A. Castaño, Non-invasive matrices in human biomonitoring: A review, Environment International, vol.35, issue.2, pp.438-449, 2009.

F. Fallone, P. Villard, and L. Decome, PPAR? activation potentiates AhR-induced CYP1A1 expression, Toxicology, vol.216, issue.2, pp.122-128, 2005.

M. A. Farage, K. W. Miller, P. Elsner, and H. I. Maibach, Structural Characteristics of the Aging Skin: A Review, Cutaneous and Ocular Toxicology, vol.26, issue.4, pp.343-357, 2007.

S. Farahmand and H. I. Maibach, Transdermal drug pharmacokinetics in man: Interindividual variability and partial prediction, International Journal of Pharmaceutics, vol.367, issue.1-2, pp.1-15, 2009.

K. R. Feingold and P. M. Elias, Role of lipids in the formation and maintenance of the cutaneous permeability barrier, Biochimica et Biophysica Acta (BBA) -Molecular and Cell Biology of Lipids, vol.1841, issue.3, pp.280-294, 2014.

R. J. Feldmann and H. Maibach, Feldman RJ, Maibach HIRegional variation in percutaneous penetration of 14C cortisol in man, J Invest Dermatol, vol.48, pp.181-183, 1967.

K. W. Fent, J. Eisenberg, and J. Snawder, Systemic Exposure to PAHs and Benzene in Firefighters Suppressing Controlled Structure Fires, Annals of Occupational Hygiene, vol.58, issue.7, pp.830-845, 2014.

F. Feo, L. Pirisi, and R. Pascale, Modulatory mechanisms of chemical carcinogenesis: the role of the NADPH pool in the benzo(a)pyrene activation, Toxicol Pathol, vol.12, issue.3, pp.261-269, 1984.

S. Fernando, L. Shaw, and D. Shaw, Evaluation of Firefighter Exposure to Wood Smoke during Training Exercises at Burn Houses, Environmental Science & Technology, vol.50, issue.3, pp.1536-1543, 2016.

G. E. Flaten, Z. Palac, A. Engesland, J. Filipovi?-gr?i?, ?. Vani? et al., In vitro skin models as a tool in optimization of drug formulation, European Journal of Pharmaceutical Sciences, vol.75, pp.10-24, 2015.

P. Flecknell, Replacement, reduction and refinement, Altex, vol.19, issue.2, pp.73-78, 2002.

K. Förster, R. Preuss, B. Roßbach, T. Brüning, J. Angerer et al., 3-Hydroxybenzo[a]pyrene in the urine of workers with occupational exposure to polycyclic aromatic hydrocarbons in different industries, Occupational and environmental medicine, vol.65, issue.4, pp.224-229, 2008.

P. P. Fu, Q. Xia, X. Sun, and H. Yu, Phototoxicity and environmental transformation of polycyclic aromatic hydrocarbons (PAHs)-light-induced reactive oxygen species, lipid peroxidation, and DNA damage, J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, vol.30, issue.1, pp.1-41, 2012.

S. Fustinoni, L. Campo, and P. E. Cirla, Dermal exposure to polycyclic aromatic hydrocarbons in asphalt workers, Occupational and environmental medicine, vol.67, issue.7, pp.456-463, 2010.

S. Gattu and H. I. Maibach, Enhanced Absorption through Damaged Skin: An Overview of the in vitro Human Model, Skin Pharmacology and Physiology, vol.23, issue.4, pp.171-176, 2010.

J. E. Geddie, S. Amin, K. Huie, and S. S. Hecht, Formation and tumorigenicity of benzo[b]fluoranthene metabolites in mouse epidermis, Carcinogenesis, vol.8, issue.11, pp.1579-84, 1987.

S. L. Gelhaus, O. Gilad, W. Hwang, T. M. Penning, and I. A. Blair, Multidrug resistance protein (MRP) 4 attenuates benzo[a]pyrene-mediated DNA-adduct formation in human bronchoalveolar H358 cells, Toxicology letters, vol.209, issue.1, pp.58-66, 2012.

C. Gelis, A. Mavon, M. Delverdier, N. Paillous, and P. Vicendo, Modifications of in vitro skin penetration under solar irradiation: evaluation on flow-through diffusion cells, Photochem Photobiol, vol.75, issue.6, pp.598-604, 2002.

C. Genies, A. Maître, E. Lefèbvre, A. Jullien, M. Chopard-lallier et al., The Extreme Variety of Genotoxic Response to Benzo[a]pyrene in Three Different Human Cell Lines from Three Different Organs, PloS one, vol.8, issue.11, p.78356, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01903135

H. J. Gibb and C. W. Chen, Multistage Model Interpretation of Additive and Multiplicative Carcinogenic Effects1, Risk Analysis, vol.6, issue.2, pp.167-170, 1986.

H. P. Gies, C. R. Roy, S. Toomey, R. Maclennan, and M. Watson, Solar UVR Exposures of Three Groups of Outdoor Workers on the Sunshine Coast, Photochemistry and Photobiology, vol.62, issue.6, pp.1015-1021, 1995.

H. Glatt, A. Seidel, and W. Bochnitschek, Mutagenic and cell-transforming activities of triol-epoxides as compared to other chrysene metabolites, Cancer research, vol.46, issue.9, pp.4556-65, 1986.

M. C. Gonzalez, C. Marteau, J. Franchi, and D. Migliore-samour, Cytochrome P450 4A11 expression in human keratinocytes: effects of ultraviolet irradiation, British Journal of Dermatology, vol.145, issue.5, pp.749-757, 2008.

J. Grainger, W. Huang, D. G. Patterson, and J. , Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites, Environmental research, vol.100, issue.3, pp.394-423, 2006.

G. Grimaldi, S. Rajendra, and J. Matthews, The aryl hydrocarbon receptor regulates the expression of TIPARP and its cis long non-coding RNA, TIPARP-AS1. Biochemical and Biophysical Research Communications, vol.495, issue.3, pp.2356-2362, 2018.

G. Grimmer, G. Dettbarn, K. W. Naujack, and J. Jacob, Excretion of Hydroxy Derivatives of Polycyclic Aromatic Hydrocarbons of the Masses 178, 202, 228 and 252 in the Urine of Coke and Road Workers, International Journal of Environmental Analytical Chemistry, vol.43, issue.2-3, pp.177-186, 1991.

G. Grimmer, J. Jacob, G. Dettbarn, and K. W. Naujack, Determination of urinary metabolites of polycyclic aromatic hydrocarbons (PAH) for the risk assessment of PAH-exposed workers, International archives of occupational and environmental health, vol.69, issue.4, pp.231-240, 1997.

N. Grova, G. Salquebre, and B. M. Appenzeller, Gas chromatography-tandem mass spectrometry analysis of 52 monohydroxylated metabolites of polycyclic aromatic hydrocarbons in hairs of rats after controlled exposure, Analytical and bioanalytical chemistry, vol.405, issue.27, pp.8897-911, 2013.

N. Grova, G. Salquebre, H. Schroeder, and B. M. Appenzeller, Determination of PAHs and OH-PAHs in rat brain by gas chromatography tandem (triple quadrupole) mass spectrometry, Chemical research in toxicology, vol.24, issue.10, pp.1653-67, 2011.

G. Grubauer, K. R. Feingold, and P. M. Elias, Relationship of epidermal lipogenesis to cutaneous barrier function, Journal of Lipid Research, vol.28, issue.6, pp.746-52, 1987.

Y. Guéguen, K. Mouzat, and L. Ferrari, Les cytochromes P450 : métabolisme des xénobiotiques, régulation et rôle en clinique, Annales de Biologie Clinique, vol.64, issue.6, p.13, 2006.

J. Gundel and J. Angerer, High-performance liquid chromatographic method with fluorescence detection for the determination of 3-hydroxybenzo[a]pyrene and 3-hydroxybenz[a]anthracene in the urine of polycyclic aromatic hydrocarbon-exposed workers, Journal of chromatography B, Biomedical sciences and applications, vol.738, issue.1, pp.47-55, 2000.

E. Gy?rffy, A. L. Gy?ri, and Z. , DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by 32 P-postlabelling and immunoassay, Carcinogenesis, vol.25, issue.7, pp.1201-1209, 2004.

J. Hadgraft and M. E. Lane, Skin permeation: The years of enlightenment, International Journal of Pharmaceutics, vol.305, issue.1, pp.2-12, 2005.

M. Hall, D. K. Parker, A. J. Hewer, D. H. Phillips, and P. L. Grover, Further metabolism of diolepoxides of chrysene and dibenz[a,c]anthracene to DNA binding species as evidenced by 32P-postlabelling analysis, Carcinogenesis, vol.9, issue.5, pp.865-873, 1988.

B. Halliwell and S. Chirico, Lipid peroxidation: its mechanism, measurement, and significance, The American Journal of Clinical Nutrition, vol.57, issue.5, pp.715-725, 1993.

R. G. Harvey, Activated metabolites of carcinogenic hydrocarbons, Accounts of Chemical Research, vol.14, issue.7, pp.218-226, 1981.

R. G. Harvey, Polycyclic Aromatic Hydrocarbons Chemistry and Carcinogenicity. Cambridge Monographs on Cancer Research, 2011.

S. S. Hecht, S. G. Carmella, P. W. Villalta, and J. B. Hochalter, Analysis of Phenanthrene and Benzo[a]pyrene Tetraol Enantiomers in Human Urine: Relevance to the Bay Region Diol Epoxide Hypothesis of Benzo, Carcinogenesis and to Biomarker Studies. Chemical research in toxicology, vol.23, issue.5, pp.900-908, 2010.

S. S. Hecht, A. Rivenson, and S. Amin, Mammary carcinogenicity of diol epoxide metabolites of benzo[j]fluoranthene in female CD rats, Cancer letters, vol.106, issue.2, pp.251-256, 1996.

T. Henriksen, A. Dahlback, S. Larsen, and J. Moan, Ultraviolet-radiation and skin cancer, Photochemistry and Photobiology, vol.51, issue.5, pp.579-582, 1990.

S. Hessel, A. Lampen, and A. Seidel, Polycyclic aromatic hydrocarbons in food -Efflux of the conjugated biomarker 1-hydroxypyrene is mediated by Breast Cancer Resistance Protein (ABCG2) in human intestinal Caco-2 cells, Food and Chemical Toxicology, vol.62, pp.797-804, 2013.

R. M. Hodgson, A. Seidel, W. Bochnitschek, H. R. Glatt, F. Oesch et al., Metabolism of the bay-region diol-epoxide of chrysene to a triol-epoxide and the enzymecatalysed conjugation of these epoxides with glutathione, Carcinogenesis, vol.7, issue.12, pp.2095-2103, 1986.

R. M. Hodgson, A. Weston, and P. L. Grover, Metabolic activation of chrysene in mouse skin: evidence for the involvement of a triol-epoxide, Carcinogenesis, vol.4, issue.12, pp.1639-1682, 1983.

N. B. Hopf, T. Carreón, and G. Talaska, Biological Markers of Carcinogenic Exposure in the Aluminum Smelter Industry-A Systematic Review, Journal of Occupational and Environmental Hygiene, vol.6, issue.9, pp.562-581, 2009.

N. B. Hopf, P. Spring, and N. Hirt-burri, Polycyclic aromatic hydrocarbons (PAHs) skin permeation rates change with simultaneous exposures to solar ultraviolet radiation (UV-S), Toxicology letters, vol.287, pp.122-130, 2018.

W. T. Hsu, E. J. Lin, P. P. Fu, R. G. Harvey, and S. B. Weiss, Comparative reactivities of diolepoxide metabolites of carcinogenic hydrocarbons with ØX174 viral DNA, Biochemical and Biophysical Research Communications, vol.88, issue.1, pp.91723-91729, 1979.

R. Huggenberger and M. Detmar, The Cutaneous Vascular System in Chronic Skin Inflammation, Journal of Investigative Dermatology Symposium Proceedings, vol.15, issue.1, pp.24-32, 2011.

C. F. Hung, C. L. Fang, S. A. Al-suwayeh, Y. Sy, and J. Y. Fang, Evaluation of drug and sunscreen permeation via skin irradiated with UVA and UVB: comparisons of normal skin and chronologically aged skin, Journal of dermatological science, vol.68, issue.3, pp.135-183, 2012.

R. J. Hung, P. Boffetta, and P. Brennan, GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population, International Journal of Cancer, vol.110, issue.4, pp.598-604, 2004.

C. Hwa, E. A. Bauer, and D. E. Cohen, Skin biology, Dermatologic Therapy, vol.24, issue.5, pp.464-470, 2011.

, World Health Organization IARC (1992) IARC monographs on the evaluation of carcinogenic risks to humans. Solar and ultraviolet radiation. IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, Polynuclear Aromatic Compounds, Part 4, Bitumens, Coal-tars and Derived Products, Shale-oils and Soots, vol.35, pp.1-316, 1985.

, World Health Organization IARC (2010) Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer, vol.82, pp.1-853, 2002.

, Radiation. IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer, vol.100, pp.7-303, 2012.

, Bitumens and bitumen emmissions, and some N-and S-heterocyclic polycyclic aromatic hydrocarbons, vol.103, 2013.

S. A. Ibrahim and S. K. Li, Effects of solvent deposited enhancers on transdermal permeation and their relationship with Emax, Journal of Controlled Release, vol.136, issue.2, pp.117-124, 2009.

, Guidelines on Limits of Exposure to Ultraviolet Radiation of Wavelenght between 180 nm and 400 nm (Incoherent Optical Radiation), Health Physics, vol.87, issue.2, pp.171-186, 2004.

, ICNIRP statement-Protection of Workers Against Ultraviolet Radiation, Health Physics, vol.99, issue.1, pp.66-87, 2010.

O. C. Ifegwu and C. Anyakora, Chapter Six -Polycyclic Aromatic Hydrocarbons: Part I. Exposure. In: Makowski GS, vol.72, pp.277-304, 2015.

G. Iliakis, H. Wang, and A. R. Perrault, Mechanisms of DNA double strand break repair and chromosome aberration formation, Cytogenetic and Genome Research, vol.104, issue.1-4, pp.14-20, 2004.

A. J. Ingram, R. Lee, and J. C. Phillips, Factors affecting the bioavailability of benzo[a]pyrene from oils in mouse skin: Oil viscosity, grooming, activity and its prevention, Journal of Applied Toxicology, vol.15, issue.3, pp.175-182, 1995.

A. J. Ingram and J. C. Phillips, The dermal bioavailability of radiolabelled benzo[a]pyrene from acetone or from oils of differing viscosity, assessed by DNA and protein binding, Journal of Applied Toxicology, vol.13, issue.1, pp.25-32, 1993.

R. Intarakumhaeng and S. K. Li, Effects of solvent on percutaneous absorption of nonvolatile lipophilic solute, International Journal of Pharmaceutics, vol.476, pp.266-276, 2014.

J. Carrell, C. Carrell, H. Glusker, J. Abu-shaqara, E. Cortez et al., Bay-and fjordregion distortions in dibenz[ a,j ]anthracene and tetrabenzo, vol.15, 1995.

J. Jacob, G. Grimmer, G. Raab, M. Emura, M. Riebe et al., Comparison of chrysene metabolism in epithelial human bronchial and Syrian hamster lung cells, Cancer letters, vol.38, issue.1-2, pp.171-80, 1987.

J. Jacob, A. Schmoldt, and G. Grimmer, Benzo[e]pyrene metabolism in rat liver microsomes: dependence of the metabolite profile on the pretreatment of rats with various monooxygenase inducers, Carcinogenesis, vol.4, issue.7, pp.905-915, 1983.

U. Jacobi, M. Kaiser, and R. Toll, Porcine ear skin: an in vitro model for human skin, Skin Research and Technology, vol.13, issue.1, pp.19-24, 2007.

C. Jacques, E. Perdu, C. Dorio, D. Bacqueville, A. Mavon et al., Percutaneous absorption and metabolism of [14C]-ethoxycoumarin in a pig ear skin model, Toxicology in Vitro, vol.24, issue.5, pp.1426-1434, 2010.

C. Jacques, E. Perdu, and H. Duplan, Disposition and biotransformation of 14C-Benzo(a)pyrene in a pig ear skin model: ex vivo and in vitro approaches, Toxicology letters, vol.199, issue.1, pp.22-33, 2010.

C. Jacques, E. Perdu, and E. L. Jamin, Effect of Skin Metabolism on Dermal Delivery of Testosterone: Qualitative Assessment using a New Short-Term Skin Model, Skin Pharmacology and Physiology, vol.27, issue.4, pp.188-188, 2014.

I. Jakasa, S. Kezic, and P. J. Boogaard, Dermal uptake of petroleum substances, Toxicology letters, vol.235, issue.2, pp.123-139, 2015.

P. James and J. Whitlock, Induction of Cytochrome P4501A1, Annual Review of Pharmacology and Toxicology, vol.39, issue.1, pp.103-125, 1999.

I. Jarvis, K. Dreij, Å. Mattsson, B. Jernström, and U. Stenius, Interactions between polycyclic aromatic hydrocarbons in complex mixtures and implications for cancer risk assessment, Toxicology, vol.321, pp.27-39, 2014.

B. Jernström, M. Funk, H. Frank, B. Mannervik, and A. Seidel, CARCINOGENESIS: Glutathione S-transferase A1-1-catalysed conjugation of bay and fjord region diol 234 epoxides of polycyclic aromatic hydrocarbons with glutathione, Carcinogenesis, vol.17, issue.7, pp.1491-1498, 1996.

S. J. Jiang, J. Y. Chen, Z. F. Lu, J. Yao, D. F. Che et al., Biophysical and morphological changes in the stratum corneum lipids induced by UVB irradiation, Journal of dermatological science, vol.44, issue.1, pp.29-36, 2006.

S. J. Jiang, A. W. Chu, Z. F. Lu, M. H. Pan, D. F. Che et al., Ultraviolet B-induced alterations of the skin barrier and epidermal calcium gradient, Exp Dermatol, vol.16, issue.12, pp.985-92, 2007.

F. J. Jongeneelen, Benchmark guideline for urinary 1-hydroxypyrene as biomarker of occupational exposure to polycyclic aromatic hydrocarbons, The Annals of occupational hygiene, vol.45, issue.1, pp.3-13, 2001.

R. Kammer, H. Tinnerberg, and K. Eriksson, Evaluation of a tape-stripping technique for measuring dermal exposure to pyrene and benzo(a)pyrene, Journal of Environmental Monitoring, vol.13, issue.8, pp.2165-2171, 2011.

J. Kao, J. Hall, and G. Helman, In vitro percutaneous absorption in mouse skin: influence of skin appendages, Toxicology and applied pharmacology, vol.94, issue.1, pp.93-103, 1988.

J. Kao, F. K. Patterson, and J. Hall, Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: an in vitro study with benzo[a]pyrene and testosterone, Toxicology and applied pharmacology, vol.81, pp.502-518, 1985.

A. Karan, A. Alikhan, and H. I. Maibach, Toxicologic implications of cutaneous barriers: a molecular, cellular, and anatomical overview, Journal of Applied Toxicology, vol.29, issue.7, pp.551-559, 2009.

P. Kasemsarn, J. Bosco, and R. L. Nixon, The role of the skin barrier in occupational skin diseases Skin Barrier Function, vol.49, pp.135-143, 2016.

S. K. Katiyar, H. Mukhtar, and M. S. Matsui, Ultraviolet-B Exposure of Human Skin Induces Cytochromes P450 1A1 and 1B1, Journal of Investigative Dermatology, vol.114, issue.2, pp.328-333, 2000.

J. H. Kim, H. Sk, N. J. Walker, M. A. Trush, P. T. Strickland et al., Metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-diol by human cytochrome P450 1B1, Carcinogenesis, vol.20, issue.3, pp.515-515, 1999.

H. King, M. H. Thompson, and P. Brookes, The role of 9-hydroxybenzo(a)pyrene in the microsome mediated binding of benzo(a)pyrene to dna, International Journal of Cancer, vol.18, issue.3, pp.339-344, 1976.

P. Kolarsick, M. A. Kolarsick, and C. Goodwin, Anatomy and Physiology of the Skin, Journal of the Dermatology Nurses' Association, vol.3, issue.6, p.366, 2011.

H. C. Korting and M. Schäfer-korting, Carriers in the Topical Treatment of Skin Disease, Schäfer-Korting M, pp.435-468, 2010.

M. Kubasiewicz and Z. Starzynski, Case-referent study on skin cancer and its relation to occupational exposure to polycyclic aromatic hydrocarbons. I. Study design, POL J OCCUP MED, vol.2, issue.3, pp.221-228, 1989.

M. Kubasiewicz, Z. Starzynski, and W. Szymczak, Case-referent study on skin cancer and its relation to occupational exposure to polycyclic aromatic hydrocarbons. II. Study results, International Journal of Occupational Medicine and Environmental Health, vol.4, issue.2, pp.141-147, 1991.

S. Labib, A. Williams, and C. H. Guo, Comparative transcriptomic analyses to scrutinize the assumption that genotoxic PAHs exert effects via a common mode of action, Archives of Toxicology, vol.90, issue.10, pp.2461-2480, 2016.

C. Lahmann, A. R. Young, K. Wittern, and J. Bergemann, Induction of mRNA for Matrix Metalloproteinase 1 and Tissue Inhibitor of Metalloproteinases 1 in Human Skin in vivo by Solar Simulated Radiation ¶, Photochemistry and Photobiology, vol.73, issue.6, pp.657-663, 2001.

Q. Lan, J. L. Mumford, and M. Shen, Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions, Carcinogenesis, vol.25, issue.11, pp.2177-2181, 2004.

E. J. Lavoie, S. Amin, S. S. Hecht, K. Furuya, and D. Hoffmann, Tumour initiating activity of dihydrodiols of benzo[b]fluoranthene, benzo[j]fluoranthene, and benzo[k]fluoranthene, Carcinogenesis, vol.3, issue.1, pp.49-52, 1982.

E. J. Lavoie, Z. He, Y. Wu, C. L. Meschter, and E. H. Weyand, Tumorigenic Activity of the 4,5-and 9,10-Dihydrodiols of Benzo[j]fluoranthene and Their <em>syn</em>-and <em>anti</em>-Diol Epoxides in Newborn Mice, Cancer research, vol.54, issue.4, pp.962-968, 1994.

E. J. Lavoie, S. S. Hecht, S. Amin, V. Bedenko, and D. Hoffmann, Identification of mutagenic dihydrodiols as metabolites of benzo(j)fluoranthene and benzo(k)fluoranthene, Cancer research, vol.40, issue.12, pp.4528-4560, 1980.

S. Lecoq, F. Perin, M. J. Plessis, H. Strapelias, and M. Duquesne, Comparison of the in vitro metabolisms and mutagenicities of dibenzo[a,c]anthracene, dibenzo[a,h]anthracene and dibenzo[a,j]anthracene: influence of norharman, Carcinogenesis, vol.10, issue.3, pp.461-470, 1989.

C. Lee, Y. Ito, and Y. Yanagiba, Pyrene-induced CYP1A2 and SULT1A1 may be regulated by CAR and not by AhR, Toxicology, vol.238, issue.2, pp.147-156, 2007.

P. A. Lehman, S. G. Raney, and T. J. Franz, Percutaneous Absorption in Man: In vitro-in vivo Correlation, Skin Pharmacology and Physiology, vol.24, issue.4, pp.224-230, 2011.

R. E. Lehr, S. Kumar, and W. Levin, The Bay Region Theory of Polycyclic Aromatic Hydrocarbon Carcinogenesis Polycyclic Hydrocarbons and Carcinogenesis, ACS Symposium Series, vol.283, pp.63-84, 1985.

S. Lesko, W. Caspary, R. Lorentzen, &. Ts, and . Pop, Enzymic formation of 6-oxobenzo[a]pyrene radical in rat liver homogenates from carcinogenic benzo[a]pyrene, Biochemistry, vol.14, issue.18, pp.3978-3984, 1975.

W. Levin, D. R. Thakker, and A. W. Wood, Evidence That Benzo(a)anthracene 3,4-Diol-1,2-Epoxide Is an Ultimate Carcinogen on Mouse Skin, Cancer research, vol.38, issue.6, pp.1705-1710, 1978.

W. Levin, A. W. Wood, and R. L. Chang, Evidence for bay region activation of chrysene 1,2-dihydrodiol to an ultimate carcinogen, Cancer research, vol.38, issue.6, pp.1831-1835, 1978.

J. Lewtas, Air pollution combustion emissions: Characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects, Mutation Research/Reviews in Mutation Research, vol.636, issue.1, pp.95-133, 2007.

C. Li, Y. Lin, W. Lee, and P. Tsai, Emission of polycyclic aromatic hydrocarbons and their carcinogenic potencies from cooking sources to the urban atmosphere, Environmental Health Perspectives, vol.111, issue.4, pp.483-487, 2003.

J. Li, M. Tang, B. Liu, X. Shi, and C. Huang, A critical role of PI-3K/Akt/JNKs pathway in benzo[a]pyrene diol-epoxide (B[a]PDE)-induced AP-1 transactivation in mouse epidermal Cl41 cells, Oncogene, vol.23, p.3932, 2004.

X. Li, Y. Feng, and H. Deng, The dose-response decrease in heart rate variability: any association with the metabolites of polycyclic aromatic hydrocarbons in coke oven workers?, PloS one, vol.7, issue.9, p.44562, 2012.

Z. Li, C. D. Sandau, and L. C. Romanoff, Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population, Environmental research, vol.107, issue.3, pp.320-351, 2008.

H. Líbalová, S. Kr?ková, and K. Uhlí?ová, Genotoxicity but not the AhR-mediated activity of PAHs is inhibited by other components of complex mixtures of ambient air pollutants, Toxicology letters, vol.225, issue.3, pp.350-357, 2014.

H. Líbalová, K. Uhlí?ová, and J. Kléma, Global gene expression changes in human embryonic lung fibroblasts induced by organic extracts from respirable air particles, Particle and Fibre Toxicology, vol.9, issue.1, p.1, 2012.

C. Liddle, B. J. Goodwin, J. George, M. Tapner, and G. C. Farrell, Separate and Interactive Regulation of Cytochrome P450 3A4 by Triiodothyronine, Dexamethasone, and Growth Hormone in Cultured Hepatocytes1, The Journal of Clinical Endocrinology & Metabolism, vol.83, issue.7, pp.2411-2416, 1998.

S. Lutier, Development and selection of Polycyclic Aromatic Hydrocarbons urinary metabolites as exposure biomarkers for human biomonitoring, 2017.
URL : https://hal.archives-ouvertes.fr/tel-01564471

Q. Ma, Influence of light on aryl hydrocarbon receptor signaling and consequences in drug metabolism, physiology and disease, Expert Opin Drug Metab Toxicol, vol.7, issue.10, pp.1267-93, 2011.

M. C. Macleod, G. M. Cohen, and J. K. Selkirk, Metabolism and Macromolecular Binding of the Carcinogen Benzo(<em>a</em>)pyrene and Its Relatively Inert Isomer Benzo(<em>e</em>)pyrene by Hamster Embryo Cells, Cancer research, vol.39, issue.9, p.3463, 1979.

M. C. Macleod, W. Levin, and A. H. Conney, Metabolism of benzo(e)pyrene by rat liver microsomal enzymes, Carcinogenesis, vol.1, issue.2, pp.165-73, 1980.

M. C. Macleod, B. K. Mansfield, and J. K. Selkirk, Time course of metabolism of benzo[e]pyrene by hamster embryo cells and the effect of chemical modifiers, Chemico-biological interactions, vol.40, issue.3, pp.275-85, 1982.

A. D. Macnicoll, P. L. Grover, and P. Sims, The metabolism of a series of polycyclic hydrocarbons by mouse skin maintained in short-term organ culture, Chemico-Biological Interactions, vol.29, issue.2, pp.169-188, 1980.

B. M. Magnusson, Y. G. Anissimov, S. E. Cross, and M. S. Roberts, Molecular Size as the Main Determinant of Solute Maximum Flux Across the Skin, Journal of Investigative Dermatology, vol.122, issue.4, pp.993-999, 2004.

B. Mahadevan, C. P. Marston, and A. Luch, Competitive inhibition of carcinogenactivating CYP1A1 and CYP1B1 enzymes by a standardized complex mixture of PAH extracted from coal tar, International Journal of Cancer, vol.120, issue.6, pp.1161-1168, 2007.

B. Mahadevan, H. Parsons, and T. Musafia, Effect of artificial mixtures of environmental polycyclic aromatic hydrocarbons present in coal tar, urban dust, and diesel exhaust particulates on MCF-7 cells in culture, Environmental and molecular mutagenesis, vol.44, issue.2, pp.99-107, 2004.

N. Manevski, P. Swart, and K. K. Balavenkatraman, Phase II Metabolism in Human Skin: Skin Explants Show Full Coverage for Glucuronidation, Sulfation, N-Acetylation, Catechol Methylation, and Glutathione Conjugation, Drug Metabolism and Disposition, vol.43, issue.1, pp.126-139, 2015.

M. Manno, C. Viau, and J. Cocker, Biomonitoring for occupational health risk assessment (BOHRA), Toxicology letters, vol.192, issue.1, pp.3-16, 2010.

L. L. Marchand, L. Sivaraman, and L. Pierce, Associations of CYP1A1, GSTM1, and CYP2E1 Polymorphisms with Lung Cancer Suggest Cell Type Specificities to Tobacco Carcinogens, Cancer research, vol.58, issue.21, pp.4858-4863, 1998.

C. Marie, M. Bouchard, R. Heredia-ortiz, C. Viau, and A. Maitre, A toxicokinetic study to elucidate 3-hydroxybenzo(a)pyrene atypical urinary excretion profile following intravenous injection of benzo(a)pyrene in rats, Journal of applied toxicology : JAT, vol.30, issue.5, pp.402-412, 2010.
URL : https://hal.archives-ouvertes.fr/hal-01903188

L. C. Marr, K. Dzepina, and J. L. Jimenez, Sources and transformations of particle-bound polycyclic aromatic hydrocarbons in Mexico City, Atmos Chem Phys, vol.6, issue.6, pp.1733-1745, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00295925

M. V. Marshall, Z. M. He, E. H. Weyand, J. E. Rice, and E. J. Lavoie, Mutagenic activity of the 4,5-and 9,10-dihydrodiols of benzo[j]fluoranthene and their syn-and anti-dihydrodiol epoxides in Salmonella typhimurium, Environmental and molecular mutagenesis, vol.22, issue.1, pp.34-45, 1993.

C. P. Marston, C. Pereira, and J. Ferguson, Effect of a complex environmental mixture from coal tar containing polycyclic aromatic hydrocarbons (PAH) on the tumor initiation, PAH-DNA binding and metabolic activation of carcinogenic PAH in mouse epidermis, Carcinogenesis, vol.22, issue.7, pp.1077-1086, 2001.

F. N. Marzulli, J. F. Callahan, and D. Brown, Chemical structure and skin penetrating capacity of a short series of organic phosphates and phosphoric acid, Journal of Investigative Dermatology, vol.44, issue.5, pp.339-344, 1965.

M. J. Mass, A. Abu-shakra, and B. C. Roop, Benzo[b]fluoranthene: tumorigenicity in strain A/J mouse lungs, DNA adducts and mutations in the Ki-ras oncogene, Carcinogenesis, vol.17, issue.8, pp.1701-1705, 1996.

D. J. Mcauliffe and I. H. Blank, Effects of UVA (320-400 nm) on the barrier characteristics of the skin, J Invest Dermatol, vol.96, issue.5, pp.758-62, 1991.

M. Mcclean, R. Rinehart, and R. Herrick, Dermal Exposure and Urinary 1-Hydroxypyrene Among Asphalt Roofing Workers, Epidemiology, vol.17, issue.6, pp.134-135, 2006.

M. D. Mcclean, R. D. Rinehart, and L. Ngo, Urinary 1-hydroxypyrene and polycyclic aromatic hydrocarbon exposure among asphalt paving workers, Annals of Occupational Hygiene, vol.48, issue.6, pp.565-578, 2004.

K. D. Mccoull, D. Rindgen, I. A. Blair, and T. M. Penning, Synthesis and Characterization of Polycyclic Aromatic Hydrocarbon o-Quinone Depurinating N7-Guanine Adducts, Chemical research in toxicology, vol.12, issue.3, pp.237-246, 1999.

V. J. Melendez-colon, A. Luch, A. Seidel, and W. M. Baird, Cancer initiation by polycyclic aromatic hydrocarbons results from formation of stable DNA adducts rather than apurinic sites, Carcinogenesis, vol.20, issue.10, pp.1885-1891, 1999.

T. Mensing, B. Marczynski, and B. Engelhardt, DNA adduct formation of benzo[a]pyrene in white blood cells of workers exposed to polycyclic aromatic hydrocarbons, International Journal of Hygiene and Environmental Health, vol.208, issue.3, pp.173-178, 2005.

S. R. Miselnicky, J. L. Lichtin, A. Sakr, and R. L. Bronaugh, The influence of solubility, protein binding, and percutaneous absorption on reservoir formation in skin, Journal of the Society of Cosmetic Chemists, vol.39, issue.3, pp.169-177, 1988.

N. Mishra, G. A. Ayoko, and L. Morawska, Atmospheric polycyclic aromatic hydrocarbons in the urban environment: Occurrence, toxicity and source apportionment, Environmental Pollution, vol.208, pp.110-117, 2016.

B. E. Moen, R. Nilsson, and R. Nordlinder, Assessment of exposure to polycyclic aromatic hydrocarbons in engine rooms by measurement of urinary 1-hydroxypyrene, Occupational and environmental medicine, vol.53, issue.10, pp.692-696, 1996.

W. Montagna, P. F. Parakkal, N. Monteiro-riviere, D. Gardner, A. Hayes et al., Contaminated soils (I): In vitro dermal absorption of benzo[a]pyrene in human skin, The Structure & Function of Skin, vol.70, pp.1858-65, 1974.

R. P. Moody, B. Nadeau, and I. Chu, In vivo and in vitro dermal absorption of benzo[a]pyrene in rat, guinea pig, human and tissue-cultured skin, Journal of dermatological science, vol.9, issue.1, pp.48-58, 1995.

R. P. Moody, A. V. Tytchino, A. Yip, and S. Petrovic, A Novel "By Difference" Method for Assessing Dermal Absorption of Polycyclic Aromatic Hydrocarbons from Soil at Federal Contaminated Sites, vol.74, 2011.

R. P. Moody, A. Yip, and I. Chu, Effect of Cold Storage on In Vitro Human Skin Absorption of Six 14C-Radiolabeled Environmental Contaminants: Benzo[a]Pyrene, Ethylene Glycol, Methyl Parathion, Naphthalene, Nonyl Phenol, and Toluene, Journal of Toxicology and Environmental Health, Part A, vol.72, issue.8, pp.505-517, 2009.

B. Moorthy, C. Chu, and D. J. Carlin, Polycyclic aromatic hydrocarbons: from metabolism to lung cancer, Toxicological sciences : an official journal of the Society of Toxicology, vol.145, issue.1, pp.5-15, 2015.

M. Moreau and M. Bouchard, Comparison of the kinetics of various biomarkers of benzo[ a ]pyrene exposure following different routes of entry in rats, Journal of Applied Toxicology, vol.35, issue.7, pp.781-790, 2014.

M. Moreau, N. Ouellet, P. Ayotte, and M. Bouchard, Effects of Intravenous Benzo[a]Pyrene Dose Administration on Levels of Exposure Biomarkers, DNA Adducts, and Gene Expression in Rats, vol.78, 2015.

W. L. Morison, L. J. Mortensen, S. Jatana, and R. Gelein, Quantification of quantum dot murine skin penetration with UVR barrier impairment, Nanotoxicology, vol.7, issue.8, pp.1386-98, 2005.

S. Motta, M. Monti, S. Sesana, L. Mellesi, R. Ghidoni et al., Abnormality of water barrier function in psoriasis: Role of ceramide fractions, Archives of Dermatology, vol.130, issue.4, pp.452-456, 1994.

S. F. Mujtaba, A. Dwivedi, and N. Yadav, Superoxide mediated photomodification and DNA damage induced apoptosis by Benz(a)anthracene via mitochondrial mediated pathway, Journal of Photochemistry and Photobiology B: Biology, vol.142, pp.92-102, 2015.

B. Muñoz and A. Albores, DNA damage caused by polycyclic aromatic hydrocarbons: mechanisms and markers Selected Topics in DNA Repair, 2011.

P. Myllynen, T. Kurttila, L. Vaskivuo, and K. Vähäkangas, DNA damage caused by benzo(a)pyrene in MCF-7 cells is increased by verapamil, probenecid and PSC833, Toxicology letters, vol.169, issue.1, pp.3-12, 2007.

V. T. Natarajan, P. Ganju, A. Ramkumar, R. Grover, and R. S. Gokhale, Multifaceted pathways protect human skin from UV radiation, Nature Chemical Biology, vol.10, p.542, 2014.

D. W. Nebert, T. P. Dalton, A. B. Okey, and F. J. Gonzalez, Role of aryl hydrocarbon receptormediated induction of the CYP1 enzymes in environmental toxicity and cancer, Journal of Biological Chemistry, vol.279, issue.23, pp.23847-23850, 2004.

S. Nesnow, M. J. Mass, and J. A. Ross, Lung tumorigenic interactions in strain A/J mice of five environmental polycyclic aromatic hydrocarbons, Environmental Health Perspectives, vol.106, issue.6, pp.1337-1346, 1998.

S. Nesnow, J. A. Ross, G. D. Stoner, and M. J. Mass, Mechanistic linkage between DNA adducts, mutations in oncogenes and tumorigenesis of carcinogenic environmental polycyclic aromatic hydrocarbons in strain A/J mice, Toxicology, vol.105, issue.2-3, pp.403-416, 1995.

K. M. Ng, I. Chu, R. L. Bronaugh, C. A. Franklin, and D. A. Somers, Percutaneous absorption and metabolism of pyrene, benzo[a]pyrene, and di(2-ethylhexyl) phthalate: comparison of in vitro and in vivo results in the hairless guinea pig, Toxicology and applied pharmacology, vol.115, issue.2, pp.216-239, 1992.

K. Ng, R. L. Bronaugh, C. A. Franklin, and D. A. Somers, Percutaneous absorption/metabolism of phenanthrene in the hairless guinea pig: Comparison of in vitro and in vivo results, Fundamental and Applied Toxicology, vol.16, issue.3, pp.517-524, 1991.

A. Nicolaou, S. M. Pilkington, and L. E. Rhodes, Ultraviolet-radiation induced skin inflammation: dissecting the role of bioactive lipids, Chemistry and Physics of Lipids, vol.164, issue.6, pp.535-543, 2011.

I. Nisbet and P. K. Lagoy, Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs), Regulatory Toxicology and Pharmacology, vol.16, issue.3, pp.290-300, 1992.

M. Nordqvist, D. R. Thakker, and W. Levin, The highly tumorigenic 3,4-dihydrodiol is a principal metabolite formed from dibenzo[a,h]anthracene by liver enzymes, Molecular pharmacology, vol.16, issue.2, pp.643-55, 1979.

M. Nordqvist, D. R. Thakker, and K. P. Vyas, Metabolism of chrysene and phenanthrene to bay-region diol epoxides by rat liver enzymes, Molecular pharmacology, vol.19, issue.1, pp.168-78, 1981.

O. Potts, R. Guy, R. Fabian, E. Guth, K. Landsiedel et al., Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models, Predicting Skin Permeability, vol.9, issue.12, pp.2135-2190, 1992.

F. Oesch, E. Fabian, and R. Landsiedel, Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models, Archives of Toxicology, 2018.

F. Oesch, E. Fabian, B. Oesch-bartlomowicz, C. Werner, and R. Landsiedel, Drug-Metabolizing Enzymes in the Skin of Man, Rat, and Pig, Drug Metabolism Reviews, vol.39, issue.4, pp.659-698, 2007.

F. Onyemauwa, S. M. Rappaport, J. R. Sobus, D. Gajdosova, R. Wu et al., Using liquid chromatography-tandem mass spectrometry to quantify monohydroxylated metabolites of polycyclic aromatic hydrocarbons in urine, Journal of chromatography B, Analytical technologies in the biomedical and life sciences, vol.877, pp.1117-1142, 2009.

M. Osanai and G. H. Lee, Enhanced expression of retinoic acid-metabolizing enzyme CYP26A1 in sunlight-damaged human skin, Med Mol Morphol, vol.44, issue.4, pp.200-206, 2011.

N. T. Palackal, M. E. Burczynski, R. G. Harvey, and T. M. Penning, The Ubiquitous Aldehyde Reductase (AKR1A1) Oxidizes Proximate Carcinogen trans-Dihydrodiols to o-Quinones: Potential Role in Polycyclic Aromatic Hydrocarbon Activation, Biochemistry, vol.40, issue.36, pp.10901-10910, 2001.

A. Pannatier, P. Jenner, B. Testa, and J. C. Etter, The Skin as a Drug-Metabolizing Organ, Drug Metabolism Reviews, vol.8, issue.2, pp.319-343, 1978.

A. Paris, J. Ledauphin, P. Poinot, and J. Gaillard, Polycyclic aromatic hydrocarbons in fruits and vegetables: Origin, analysis, and occurrence, Environmental Pollution, vol.234, pp.96-106, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02122572

J. Park, S. Gopishetty, L. M. Szewczuk, A. B. Troxel, R. G. Harvey et al., Formation of 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-Oxo-dGuo) by PAH o-Quinones: Involvement of Reactive Oxygen Species and Copper(II)/Copper(I) Redox Cycling, Chemical research in toxicology, vol.18, issue.6, pp.1026-1037, 2005.

J. Park, A. B. Troxel, R. G. Harvey, and T. M. Penning, Polycyclic Aromatic Hydrocarbon (PAH) o-Quinones Produced by the Aldo-Keto-Reductases (AKRs) Generate Abasic Sites, Oxidized Pyrimidines, and 8-Oxo-dGuo via Reactive Oxygen Species, Chemical research in toxicology, vol.19, issue.5, pp.719-728, 2006.

T. Partanen and P. Boffetta, Cancer risk in asphalt workers and roofers: Review and metaanalysis of epidemiologic studies, vol.26, 1994.

M. Paschke, C. Hutzler, J. Brinkmann, F. Henkler, and A. Luch, Polycyclic Aromatic Hydrocarbons in Newspaper Inks: Migration, Metabolism, and Genotoxicity in Human Skin, Polycyclic aromatic compounds : PAC, vol.35, issue.1, pp.32-40, 2015.

D. I. Pattison and M. J. Davies, Actions of ultraviolet light on cellular structures, EXS, issue.96, pp.131-57, 2006.

J. Payan, M. Lafontaine, and P. Simon, 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, Archives of Toxicology, vol.82, issue.10, p.739, 2008.

J. P. Payan, M. Lafontaine, and P. Simon, 3-Hydroxybenzo(a)pyrene as a biomarker of dermal exposure to benzo(a)pyrene, Arch Toxicol, vol.83, issue.9, pp.873-83, 2009.

T. M. Penning, Human Aldo-Keto Reductases and the Metabolic Activation of Polycyclic Aromatic Hydrocarbons, Chemical research in toxicology, vol.27, issue.11, pp.1901-1917, 2014.

T. M. Penning, Genotoxicity of ortho-quinones: reactive oxygen species versus covalent modification, Toxicology Research, vol.6, issue.6, pp.740-754, 2017.

O. Perin-roussel, S. Saguem, B. Ekert, and F. Zajdela, Binding to DNA of bay region and pseudo bay region diol-epoxides of dibenzo[a,e]fluoranthene and comparison with adducts obtained with dibenzo[a,e]fluoranthene or its dihydrodiols in the presence of microsomes, Carcinogenesis, vol.4, issue.1, pp.27-32, 1983.

D. H. Phillips, A. Hewer, and P. L. Grover, Formation of DNA adducts in mouse skin treated with metabolites of chrysene, Cancer letters, vol.35, issue.2, pp.207-221, 1987.

M. R. Pittelkow, H. O. Perry, S. A. Muller, W. Z. Maughan, O. &apos;brien et al., Skin cancer in patients with psoriasis treated with coal tar: A 25-year follow-up study, Archives of Dermatology, vol.117, issue.8, pp.465-468, 1981.

A. Pivarcsi, L. Kemény, and A. Dobozy, Innate Immune Functions of the Keratinocytes, Acta Microbiologica et Immunologica Hungarica, vol.51, issue.3, pp.303-310, 2004.

I. Plakunov, T. A. Smolarek, D. L. Fischer, J. C. Wiley, J. Baird et al., Separation by ionpair high-performance liquid chromatography of the glucuronide, sulfate and glutathione conjugates formed from benzo[a]pyrene in cell cultures from rodents, fish and humans, Carcinogenesis, vol.8, issue.1, pp.59-66, 1987.

D. Potter, E. D. Booth, and H. Brandt, Studies on the dermal and systemic bioavailability of polycyclic aromatic compounds in high viscosity oil products, Archives of Toxicology, vol.73, issue.3, pp.129-140, 1999.

E. Pukkala, J. I. Martinsen, and E. Weiderpass, Cancer incidence among firefighters: 45 years of follow-up in five Nordic countries, Occupational and environmental medicine, vol.71, issue.6, pp.398-404, 2014.

S. R. Raja, S. Garcia, M. Isseroff, and R. , Wound re-epithelialization: Modulating keratinocyte migration in wound healing, vol.12, 2007.

R. King, J. Monteiro-riviere, and N. A. , Effects of organic solvent vehicles on the viability and morphology of isolated perfused porcine skin, Toxicology, vol.69, issue.1, pp.11-26, 1991.

K. Ravindra, R. Sokhi, and R. Van-grieken, Atmospheric polycyclic aromatic hydrocarbons: Source attribution, emission factors and regulation, Atmospheric Environment, vol.42, issue.13, pp.2895-2921, 2008.

M. Rehwagen, A. Müller, L. Massolo, O. Herbarth, and A. Ronco, Polycyclic aromatic hydrocarbons associated with particles in ambient air from urban and industrial areas, Science of The Total Environment, vol.348, issue.1, pp.199-210, 2005.

A. E. Reif, Synergism in Carcinogenesis, JNCI: Journal of the National Cancer Institute, vol.73, issue.1, pp.25-39, 1984.

J. Rembiesa, T. Ruzgas, J. Engblom, and A. Holefors, The Impact of Pollution on Skin and Proper Efficacy Testing for Anti-Pollution Claims, Cosmetics, vol.5, issue.1, p.4, 2018.

A. G. Renwick and B. S. Drasar, Environmental carcinogens and large bowel cancer, Nature, vol.263, p.234, 1976.

J. E. Rice, N. G. Geddie, and E. J. Lavoie, Identification of metabolites of benzo[j]fluoranthene formed in vitro in rat liver homogenate, Chemico-Biological Interactions, vol.63, issue.3, pp.227-237, 1987.

J. E. Rice, E. H. Weyand, N. G. Geddie, M. C. Defloria, and E. J. Lavoie, Identification of tumorigenic metabolites of benzo[j]fluoranthene formed in vivo in mouse skin, Cancer research, vol.47, issue.23, pp.6166-70, 1987.

M. Richelle, H. Steiling, and I. Castiel, Chapter 6 -Bioavailability and Skin Bioefficacy of Vitamin C and E, pp.115-138, 2009.

L. Rittie and G. J. Fisher, Natural and sun-induced aging of human skin, Cold Spring Harb Perspect Med, vol.5, issue.1, p.15370, 2015.

B. I. Ro and T. L. Dawson, The Role of Sebaceous Gland Activity and Scalp Microfloral Metabolism in the Etiology of Seborrheic Dermatitis and Dandruff, Journal of Investigative Dermatology Symposium Proceedings, vol.10, issue.3, pp.194-197, 2005.

F. Rossella, L. Campo, S. Pavanello, L. Kapka, E. Siwinska et al., Urinary polycyclic aromatic hydrocarbons and monohydroxy metabolites as biomarkers of exposure in coke oven workers, Occupational and environmental medicine, vol.66, issue.8, pp.509-525, 2009.

R. Saladi, L. Austin, and D. Gao, The Combination of Benzo[a]pyrene and Ultraviolet A Causes an In Vivo Time-related Accumulation of DNA Damage in Mouse Skin ¶, Photochemistry and Photobiology, vol.77, issue.4, pp.413-419, 2003.

P. Sartorelli, A. Cenni, G. Matteucci, L. Montomoli, M. T. Novelli et al., Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from lubricating oil, International archives of occupational and environmental health, vol.72, issue.8, pp.528-532, 1999.

P. Sartorelli, L. Montomoli, A. G. Sisinni, R. Bussani, D. Cavallo et al., Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from coal dust, Toxicology and industrial health, vol.17, issue.1, pp.17-21, 2001.

H. Schaefer, A. Zesch, and G. Stättgen, Skin Permeability Skin Permeability, pp.541-845, 1982.

K. Scharffetter, M. Wlaschek, and A. Hogg, UVA irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo, Archives of Dermatological Research, vol.283, issue.8, pp.506-511, 1991.

S. Scher and . Scenihr, Opinion on the Toxicity and Assessment of Chemical Mixtures, 2012.

G. Scherer, S. Frank, K. Riedel, I. Meger-kossien, and T. Renner, Biomonitoring of Exposure to Polycyclic Aromatic Hydrocarbons of Nonoccupationally Exposed Persons, Cancer Epidemiology Biomarkers & Prevention, vol.9, issue.4, pp.373-380, 2000.

A. H. Schinkel and J. W. Jonker, Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview, Advanced Drug Delivery Reviews, vol.55, issue.1, pp.3-29, 2003.

D. Schwarz, P. Kisselev, I. Cascorbi, W. H. Schunck, and I. Roots, Differential metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1 variants, Carcinogenesis, vol.22, issue.3, pp.453-462, 2001.

A. Scott-claire, K. David, and P. , Key functions for gap junctions in skin and hearing, Biochemical Journal, vol.438, issue.2, pp.245-254, 2011.

B. Sen, B. Mahadevan, and D. M. Demarini, Transcriptional responses to complex mixtures-A review, Mutation Research/Reviews in Mutation Research, vol.636, issue.1, pp.144-177, 2007.

H. Shen, Y. Huang, and R. Wang, Global atmospheric emissions of polycyclic aromatic hydrocarbons from 1960 to 2008 and future predictions, Environmental science & technology, vol.47, issue.12, pp.6415-6424, 2013.

T. Shimada, Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons, Drug metabolism and pharmacokinetics, vol.21, issue.4, pp.257-76, 2006.

T. Shimada and Y. Fujii-kuriyama, Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and 1B1, Cancer science, vol.95, issue.1, pp.1-6, 2004.

T. Shimada, C. L. Hayes, and H. Yamazaki, Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1, Cancer research, vol.56, issue.13, pp.2979-84, 1996.

T. Shimada, N. Murayama, and K. Tanaka, Interaction of Polycyclic Aromatic Hydrocarbons with Human Cytochrome P450 1B1 in Inhibiting Catalytic Activity, Chemical research in toxicology, vol.21, issue.12, pp.2313-2323, 2008.

Y. Shirakata, Regulation of epidermal keratinocytes by growth factors, Journal of dermatological science, vol.59, issue.2, pp.73-80, 2010.

M. Shou, K. W. Krausz, F. J. Gonzalez, and H. V. Gelboin, Metabolic activation of the potent carcinogen dibenzo[a,h]anthracene by cDNA-expressed human cytochromes P450, Archives of biochemistry and biophysics, vol.328, issue.1, pp.201-208, 1996.

L. K. Siddens, A. Larkin, and S. K. Krueger, Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse, Toxicology and applied pharmacology, vol.264, issue.3, pp.377-386, 2012.

C. L. Silva, D. Topgaard, V. Kocherbitov, J. Sousa, A. Pais et al., Stratum corneum hydration: Phase transformations and mobility in stratum corneum, extracted lipids and isolated corneocytes, Biochimica et Biophysica Acta (BBA) -Biomembranes, vol.1768, issue.11, pp.2647-2659, 2007.

P. Sims, The metabolism of some aromatic hydrocarbons by mouse embryo cell cultures, Biochemical Pharmacology, vol.19, issue.1, pp.285-297, 1970.

P. Sims, Qualitative and quantitative studies on the metabolism of a series of aromatic hydrocarbons by rat-liver preparations, Biochemical Pharmacology, vol.19, issue.3, pp.90243-90244, 1970.

D. K. Singh and T. Gupta, Effect through inhalation on human health of PM1 bound polycyclic aromatic hydrocarbons collected from foggy days in northern part of India, Journal of Hazardous Materials, vol.306, pp.257-268, 2016.

M. Sjögren, L. Ehrenberg, and U. Rannug, Relevance of different biological assays in assessing initiating and promoting properties of polycyclic aromatic hydrocarbons with respect to carcinogenic potency. Mutation Research/Fundamental and Molecular Mechanisms of, Mutagenesis, vol.358, issue.1, pp.175-178, 1996.

T. J. Slaga, E. Huberman, J. K. Selkirk, R. G. Harvey, and W. M. Bracken, Carcinogenicity and mutagenicity of benz(a)anthracene diols and diol-epoxides, Cancer research, vol.38, issue.6, pp.1699-704, 1978.

K. Slezakova, D. Castro, C. Delerue-matos, A. Mdc, S. Morais et al., Impact of vehicular traffic emissions on particulate-bound PAHs: Levels and associated health risks, Atmospheric Research, vol.127, pp.141-147, 2013.

C. J. Smith, C. J. Walcott, W. Huang, V. Maggio, J. Grainger et al., Determination of selected monohydroxy metabolites of 2-, 3-and 4-ring polycyclic aromatic hydrocarbons in urine by solid-phase microextraction and isotope dilution gas chromatography-mass spectrometry, Journal of chromatography B, Analytical technologies in the biomedical and life sciences, vol.778, issue.1-2, pp.157-64, 2002.

G. Smith, C. R. Wolf, and Y. Y. Deeni, Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases, The Lancet, vol.361, issue.9366, pp.13081-13085, 2003.

L. H. Smith and J. M. Holland, Interaction between benzo[a]pyrene and mouse skin in organ culture, Toxicology, vol.21, issue.1, pp.90015-90024, 1981.

J. R. Sobus, M. D. Mcclean, and R. F. Herrick, Comparing Urinary Biomarkers of Airborne and Dermal Exposure to Polycyclic Aromatic Compounds in Asphalt-Exposed Workers, Annals of Occupational Hygiene, vol.53, issue.6, pp.561-571, 2009.

J. Soeur, J. Belaïdi, and C. Chollet, Photo-pollution stress in skin: Traces of pollutants (PAH and particulate matter) impair redox homeostasis in keratinocytes exposed to UVA1, Journal of dermatological science, vol.86, issue.2, pp.162-169, 2017.

A. E. Solomon and N. J. Lowe, Percutaneous absorption in experimental epidermal disease, British Journal of Dermatology, vol.100, issue.6, pp.717-722, 1979.

T. Sousa, R. Paterson, V. Moore, A. Carlsson, B. Abrahamsson et al., The gastrointestinal microbiota as a site for the biotransformation of drugs, International Journal of Pharmaceutics, vol.363, issue.1, pp.1-25, 2008.

J. Sowada, L. Lemoine, K. Schön, C. Hutzler, A. Luch et al., Toxification of polycyclic aromatic hydrocarbons by commensal bacteria from human skin, Archives of Toxicology, vol.91, issue.6, pp.2331-2341, 2017.

J. Sowada, A. Schmalenberger, I. Ebner, A. Luch, and T. Tralau, Degradation of benzo[a]pyrene by bacterial isolates from human skin, FEMS Microbiology Ecology, vol.88, issue.1, pp.129-139, 2014.

F. Sparber, Langerhans cells: an update, JDDG: Journal der Deutschen Dermatologischen Gesellschaft, vol.12, issue.12, pp.1107-1111, 2014.

E. Sparr and H. Wennerström, Responding Phospholipid Membranes-Interplay between Hydration and Permeability, Biophysical Journal, vol.81, issue.2, pp.75759-75760, 2001.

D. C. Spink, S. J. Wu, and B. C. Spink, Induction of CYP1A1 and CYP1B1 by benzo(k)fluoranthene and benzo(a)pyrene in T-47D human breast cancer cells: roles of PAH interactions and PAH metabolites, Toxicology and applied pharmacology, vol.226, issue.3, pp.213-237, 2008.

S. K. Srivastava, S. C. Watkins, E. Schuetz, and S. V. Singh, Role of glutathione conjugate efflux in cellular protection against benzo[a]pyrene-7,8-diol-9,10-epoxide-induced DNA damage, Molecular Carcinogenesis, vol.33, issue.3, pp.156-162, 2002.

K. Srogi, Monitoring of environmental exposure to polycyclic aromatic hydrocarbons: a review, Environmental Chemistry Letters, vol.5, issue.4, pp.169-195, 2007.

K. A. Steinmetz and J. D. Potter, Vegetables, Fruit, and Cancer Prevention, Journal of the American Dietetic Association, vol.96, issue.10, pp.1027-1039, 1996.

J. S. Stenehjem, T. E. Robsahm, M. Bråtveit, S. O. Samuelsen, J. Kirkeleit et al., Aromatic hydrocarbons and risk of skin cancer by anatomical site in 25 000 male offshore petroleum workers, American Journal of Industrial Medicine, vol.60, issue.8, pp.679-688, 2017.

E. Stogiannidis and R. Laane, Source Characterization of Polycyclic Aromatic Hydrocarbons by Using Their Molecular Indices: An Overview of Possibilities. In: Whitacre DM (ed) Reviews of Environmental Contamination and Toxicology, pp.49-133, 2015.

J. E. Storm, S. W. Collier, R. F. Stewart, and R. L. Bronaugh, Metabolism of xenobiotics during percutaneous penetration: role of absorption rate and cutaneous enzyme activity, Fundamental and applied toxicology : official journal of the Society of Toxicology, vol.15, issue.1, pp.132-173, 1990.

I. Stumpe-v?ksna, V. Bartkevi?s, A. Kuk?re, and A. Morozovs, Polycyclic aromatic hydrocarbons in meat smoked with different types of wood, Food Chemistry, vol.110, issue.3, pp.794-797, 2008.

C. Surber, K. P. Wilhelm, H. I. Maibach, L. L. Hall, and R. H. Guy, Partitioning of chemicals into human stratum corneum: implications for risk assessment following dermal exposure, Fundamental and applied toxicology : official journal of the Society of Toxicology, vol.15, issue.1, pp.99-107, 1990.

M. Svoboda, Z. Bílková, and T. Muthný, Could tight junctions regulate the barrier function of the aged skin, Journal of dermatological science, vol.81, issue.3, pp.147-152, 2016.

J. Szaniszlo and G. Ungvary, Polycyclic aromatic hydrocarbon exposure and burden of outdoor workers in Budapest, Journal of toxicology and environmental health Part A, vol.62, issue.5, pp.297-306, 2001.

S. Takenaka, T. Itoh, and R. Fujiwara, Expression pattern of human ATP-binding cassette transporters in skin, Pharmacology research & perspectives, vol.1, issue.1, pp.5-00005, 2013.

M. Tauchi, A. Hida, and T. Negishi, Constitutive expression of aryl hydrocarbon receptor in keratinocytes causes inflammatory skin lesions, Molecular and cellular biology, vol.25, issue.21, pp.9360-9368, 2005.

D. R. Thakker, W. Levin, and H. Yagi, Metabolism of benzo[a]anthracene to its tumorigenic 3,4-dihydrodiol, Molecular pharmacology, vol.15, issue.1, pp.138-53, 1979.

S. C. Tilton, L. K. Siddens, and S. K. Krueger, Mechanism-Based Classification of PAH Mixtures to Predict Carcinogenic Potential, Toxicological Sciences, vol.146, issue.1, pp.135-145, 2015.

P. E. Tolbert, Oils and cancer, Cancer Causes & Control, vol.8, issue.3, pp.386-405, 1997.

I. Tolosa, J. M. Bayona, and J. Albaigés, Aliphatic and Polycyclic Aromatic Hydrocarbons and Sulfur/Oxygen Derivatives in Northwestern Mediterranean Sediments: Spatial and Temporal Variability, Fluxes, and Budgets. Environmental Science & Technology, vol.30, issue.8, pp.2495-2503, 1996.

P. Tsai, H. Shieh, W. Lee, and S. Lai, Health-risk assessment for workers exposed to polycyclic aromatic hydrocarbons (PAHs) in a carbon black manufacturing industry, Science of The Total Environment, vol.278, issue.1, p.643, 2001.

I. Tsakovska, I. Pajeva, A. Sharif, and M. , Quantitative structure-skin permeability relationships, Toxicology, vol.387, pp.27-42, 2017.

E. Tung, N. A. Philbrook, C. L. Belanger, S. Ansari, and L. M. Winn, Benzo[a]pyrene increases DNA double strand break repair in vitro and in vivo: A possible mechanism for benzo[a]pyrene-induced toxicity, Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol.760, pp.64-69, 2014.

J. Unwin, J. Cocker, E. Scobbie, and H. Chambers, An Assessment of Occupational Exposure to Polycyclic Aromatic Hydrocarbons in the UK. The Annals of occupational hygiene, vol.50, pp.395-403, 2006.

P. Upadhyaya, J. B. Hochalter, S. Balbo, E. J. Mcintee, and S. S. Hecht, Preferential Glutathione Conjugation of a Reverse Diol Epoxide Compared with a Bay Region Diol Epoxide of Benzo[a]pyrene in Human Hepatocytes, Drug Metabolism and Disposition, vol.38, issue.9, pp.1397-1402, 2010.

D. D. Vakharia, N. Liu, and R. Pause, Polycyclic Aromatic Hydrocarbon/Metal Mixtures: Effect on PAH Induction of CYP1A1 in Human HepG2 Cells, Drug Metabolism and Disposition, vol.29, issue.7, pp.999-1006, 2001.

J. Van-de-sandt, J. A. Van-burgsteden, and S. Cage, In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study, Regulatory Toxicology and Pharmacology, vol.39, issue.3, pp.271-281, 2004.

J. Van-smeden, J. Bouwstra, J. Van-smeden, M. Janssens, G. S. Gooris et al., The important role of stratum corneum lipids for the cutaneous barrier function, Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients, vol.49, pp.295-313, 2014.

J. G. Vanrooij, M. M. Bodelier-bade, and F. J. Jongeneelen, Estimation of individual dermal and respiratory uptake of polycyclic aromatic hydrocarbons in 12 coke oven workers, British Journal of Industrial Medicine, vol.50, issue.7, pp.623-632, 1993.

J. G. Vanrooij, E. M. Van-lieshout, M. M. Bodelier-bade, and F. J. Jongeneelen, Effect of the reduction of skin contamination on the internal dose of creosote workers exposed to polycyclic aromatic hydrocarbons, Scandinavian Journal of Work, issue.3, pp.200-207, 1993.

J. G. Vanrooij, E. Vinke, D. Lange, and J. , Dermal absorption of polycyclic aromatic hydrocarbons in the blood-perfused pig ear, Journal of applied toxicology : JAT, vol.15, issue.3, pp.193-200, 1995.

J. Vanrooij, M. M. Bodelier-bade, D. Looff, A. Dijkmans, A. Jongeneelen et al., Dermal exposure to polycyclic aromatic hydrocarbons among primary aluminium workers, La Medicina del lavoro, vol.83, issue.5, pp.519-529, 1992.

J. Vanrooij, J. De-roos, M. M. Bodelier-bade, and F. J. Jongeneelen, Absorption of polycyclic aromatic hydrocarbons through human skin: Differences between anatomical sites and individuals, Journal of Toxicology and Environmental Health, vol.38, issue.4, pp.355-368, 1993.

R. T. Veenhuis, J. Van-horssen, R. P. Bos, R. B. Anzion, and P. G. Van-der-valk, Highly increased urinary 1-hydroxypyrene excretion rate in patients with atopic dermatitis treated with topical coal tar, Archives of Dermatological Research, vol.294, issue.4, pp.168-171, 2002.

D. Vernez, A. Koechlin, and A. Milon, Anatomical UV Exposure in French Outdoor Workers, Journal of Occupational and Environmental Medicine, vol.57, issue.11, pp.1192-1196, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01262215

C. Viau, G. Carrier, A. Vysko?il, and C. Dodd, Urinary excretion kinetics of 1-hydroxypyrene in volunteers exposed to pyrene by the oral and dermal route, Science of The Total Environment, vol.163, issue.1, pp.179-186, 1995.

K. P. Vijayalakshmi and C. H. Suresh, Theoretical studies on the carcinogenicity of polycyclic aromatic hydrocarbons, Journal of Computational Chemistry, vol.29, issue.11, pp.1808-1817, 2008.

P. H. Villard, E. Sampol, and J. L. Elkaim, Increase of CYP1B1 Transcription in Human Keratinocytes and HaCaT Cells after UV-B Exposure, Toxicology and applied pharmacology, vol.178, issue.3, pp.137-143, 2002.
URL : https://hal.archives-ouvertes.fr/hal-01773794

M. Vinceti, G. Pellacani, and C. Malagoli, A population-based case-control study of diet and melanoma risk in northern Italy, Public Health Nutrition, vol.8, issue.8, pp.1307-1314, 2007.

G. Virich, V. Gudi, and A. Canal, Extramammary Paget's disease &#x2013; occupational exposure to used engine oil and a new skin grafting technique, Journal of Plastic, Reconstructive & Aesthetic Surgery, vol.61, issue.12, pp.1528-1529, 2008.

A. Von-koschembahr, A. Youssef, and D. Béal, Solar simulated light exposure alters metabolization and genotoxicity induced by benzo[a]pyrene in human skin, Scientific Reports, vol.8, issue.1, p.14692, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01903708

C. Wang, S. Wu, S. Zhou, Y. Shi, and J. Song, Characteristics and Source Identification of Polycyclic Aromatic Hydrocarbons (PAHs) in Urban Soils: A Review, Pedosphere, vol.27, issue.1, pp.17-26, 2017.

H. Wang, W. Chen, and H. Zheng, Association between plasma BPDE-Alb adduct concentrations and DNA damage of peripheral blood lymphocytes among coke oven workers, Occupational and environmental medicine, vol.64, issue.11, pp.753-758, 2007.

R. Wang, G. Liu, and J. Zhang, Variations of emission characterization of PAHs emitted from different utility boilers of coal-fired power plants and risk assessment related to atmospheric PAHs, Science of The Total Environment, vol.538, pp.180-190, 2015.

S. Wang, Y. Sheng, and M. Feng, Light-induced cytotoxicity of 16 polycyclic aromatic hydrocarbons on the US EPA priority pollutant list in human skin HaCaT keratinocytes: relationship between phototoxicity and excited state properties, Environ Toxicol, vol.22, issue.3, pp.318-345, 2007.

Y. Wang, D. Gao, and D. P. Atencio, Combined subcarcinogenic benzo[a]pyrene and UVA synergistically caused high tumor incidence and mutations in H-ras gene, but not p53, in SKH-1 hairless mouse skin, International Journal of Cancer, vol.116, issue.2, pp.193-199, 2005.

Y. Wei, U. Rannug, and A. Rannug, UV-induced CYP1A1 gene expression in human cells is mediated by tryptophan, Chemico-Biological Interactions, vol.118, issue.2, pp.127-140, 1999.

L. M. Weis, A. M. Rummel, S. J. Masten, J. E. Trosko, and B. L. Upham, Bay or baylike regions of polycyclic aromatic hydrocarbons were potent inhibitors of Gap junctional intercellular communication, Environmental health perspectives, vol.106, issue.1, pp.17-22, 1998.

A. Weston, R. M. Hodgson, A. J. Hewer, R. Kuroda, and P. L. Grover, Comparative studies of the metabolic activation of chrysene in rodent and human skin, Chemico-biological interactions, vol.54, issue.2, pp.223-265, 1985.

E. H. Weyand, S. Amin, and K. Huie, Effects of fluorine substitution on the DNA binding and tumorigenicity of benzo[b]fluoranthene in mouse epidermis, Chemicobiological interactions, vol.71, issue.2-3, pp.279-90, 1989.

E. H. Weyand, P. Bryla, Y. Wu, Z. M. He, and E. J. Lavoie, Detection of the major DNA adducts of benzo[j]fluoranthene in mouse skin: nonclassical dihydrodiol epoxides, Chemical research in toxicology, vol.6, issue.1, pp.117-141, 1993.

E. H. Weyand, Z. W. Cai, Y. Wu, J. E. Rice, Z. M. He et al., Detection of the major DNA adducts of benzo[b]fluoranthene in mouse skin: role of phenolic dihydrodiols, Chemical research in toxicology, vol.6, issue.4, pp.568-77, 1993.

E. H. Weyand, N. Geddie, J. E. Rice, A. Czech, S. Amin et al., Metabolism and mutagenic activity of benzo[k]fluoranthene and 3-, 8-and 9-fluorobenzo[k]fluoranthene, Carcinogenesis, vol.9, issue.7, pp.1277-81, 1988.

E. H. Weyand, S. Patel, E. J. Lavoie, B. Cho, and R. G. Harvey, Relative tumor initiating activity of benzo[a]fluoranthene, benzo[b]fluoranthene, naphtho[1,2-b]fluoranthene and naphtho[2,1-a]fluoranthene on mouse skin, Cancer letters, vol.52, issue.3, pp.229-262, 1990.

R. R. Wickett and M. O. Visscher, Structure and function of the epidermal barrier, S98-S110 doi, vol.34, 2006.

E. Wincent, L. Bihanic, F. Dreij, and K. , Induction and inhibition of human cytochrome P4501 by oxygenated polycyclic aromatic hydrocarbons, Toxicology Research, vol.5, issue.3, pp.788-799, 2016.

J. R. Withey, F. Law, and L. Endrenyi, Percutaneous uptake, distribution, and excretion of pyrene in rats, Journal of Toxicology and Environmental Health, vol.40, issue.4, pp.601-612, 1993.

A. W. Wood, R. L. Chang, and M. T. Huang, Mutagenicity of benzo(e)pyrene and triphenylene tetrahydroepoxides and diol-epoxides in bacterial and mammalian cells, Cancer research, vol.40, issue.6, pp.1985-1994, 1980.

A. W. Wood, W. Levin, and R. L. Chang, Tumorigenicity of five dihydrodiols of benz(a)anthracene on mouse skin: exceptional activity of benz(a)anthracene 3,4-dihydrodiol, Proceedings of the National Academy of Sciences of the United States of America, vol.74, issue.8, pp.3176-3185, 1977.

A. W. Wood, W. Levin, and D. R. Thakker, Biological activity of benzo[e]pyrene. An assessment based on mutagenic activities and metabolic profiles of the polycyclic hydrocarbon and its derivatives, The Journal of biological chemistry, vol.254, issue.11, pp.4408-4423, 1979.

M. Wu, S. Yan, D. J. Patel, N. E. Geacintov, and S. Broyde, Relating repair susceptibility of carcinogen-damaged DNA with structural distortion and thermodynamic stability, Nucleic acids research, vol.30, issue.15, pp.3422-3432, 2002.

E. L. Wynder and D. Hoffmann, The carcinogenicity of benzofluoranthenes, Cancer, vol.12, issue.6, pp.1194-1199, 1959.

Q. Xia, H. M. Chiang, and J. J. Yin, UVA photoirradiation of benzo[a]pyrene metabolites: induction of cytotoxicity, reactive oxygen species, and lipid peroxidation, Toxicology and industrial health, vol.31, issue.10, pp.898-910, 2015.

S. Xu, J. Weerachayaphorn, S. Cai, C. J. Soroka, and J. L. Boyer, Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression, American Journal of Physiology-Gastrointestinal and Liver Physiology, vol.299, issue.1, pp.126-135, 2010.

X. Xu, J. Zhang, L. Zhang, W. Liu, and C. P. Weisel, Selective detection of monohydroxy metabolites of polycyclic aromatic hydrocarbons in urine using liquid chromatography/triple quadrupole tandem mass spectrometry. Rapid communications in mass spectrometry, RCM, vol.18, pp.2299-308, 2004.

W. Xue and D. Warshawsky, Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: A review, Toxicology and applied pharmacology, vol.206, issue.1, pp.73-93, 2005.

J. J. Yang, T. A. Roy, A. J. Krueger, W. Neil, and C. R. Mackerer, In vitro and in vivo percutaneous absorption of benzo[a]pyrene from petroleum crude-fortified soil in the rat, Bulletin of environmental contamination and toxicology, vol.43, issue.2, pp.207-221, 1989.

J. J. Yang, T. A. Roy, and C. R. Mackerer, Percutaneous absorption of benzo[a]pyrene in the rat: comparison of in vivo and in vitro results, Toxicology and industrial health, vol.2, issue.4, pp.409-425, 1986.

M. Yang, A Current Global View of Environmental and Occupational Cancers, Journal of Environmental Science and Health, Part C, vol.29, issue.3, pp.223-249, 2011.

D. Yu, J. A. Berlin, T. M. Penning, and J. Field, Reactive Oxygen Species Generated by PAH o-Quinones Cause Change-In-Function Mutations in p53, Chemical research in toxicology, vol.15, issue.6, pp.832-842, 2002.

H. Yu, Environmental carcinogenic polycyclic aromatic hydrocarbons: photochemistry and phototoxicity, J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, vol.20, issue.2, pp.149-83, 2002.

D. Zalko, C. Jacques, H. Duplan, S. Bruel, and E. Perdu, Viable skin efficiently absorbs and metabolizes bisphenol A, Chemosphere, vol.82, issue.3, 2011.

U. M. Zanger and M. Schwab, Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation, Pharmacology & Therapeutics, vol.138, issue.1, pp.103-141, 2013.

L. Zhang, Y. Jin, M. Huang, and T. M. Penning, The Role of Human Aldo-Keto Reductases in the Metabolic Activation and Detoxication of Polycyclic Aromatic Hydrocarbons: Interconversion of PAH Catechols and PAH o-Quinones, Frontiers in pharmacology, vol.3, pp.193-193, 2012.

Y. Zhang and S. Tao, Global atmospheric emission inventory of polycyclic aromatic hydrocarbons (PAHs) for, Atmospheric Environment, vol.43, issue.4, pp.812-819, 2004.

Y. Zhang, X. Wu, D. Guo, O. Rechkoblit, N. E. Geacintov et al., Two-step error-prone bypass of the (+)-and (?)-trans-anti-BPDE-N2-dG adducts by human DNA polymerases ? and ?. Mutation Research/Fundamental and Molecular Mechanisms of, Mutagenesis, vol.510, issue.1, pp.23-35, 2002.

H. Zhao, M. R. Spitz, K. M. Gwyn, and X. Wu, Microsomal epoxide hydrolase polymorphisms and lung cancer risk in non-Hispanic whites, Molecular Carcinogenesis, vol.33, issue.2, pp.99-104, 2002.

Y. Zhong, S. G. Carmella, J. B. Hochalter, S. Balbo, and S. S. Hecht, 10-tetrahydrobenzo[a]pyrene in Human Urine: A Biomarker for Directly Assessing Carcinogenic Polycyclic Aromatic Hydrocarbon Exposure plus Metabolic Activation, Chemical research in toxicology, vol.9, issue.1, pp.73-80, 2011.

C. C. Zouboulis, Human Skin: An Independent Peripheral Endocrine Organ, Hormone Research in Paediatrics, vol.54, issue.5-6, pp.230-242, 2000.

E. Bourgart, D. Barbeau, and M. Marques, Anne Von Koschembahr

, , 2018.

A. Von-koschembahr, A. Youssef, D. Béal, C. Calissi, and E. Bourgart, Solar simulated light exposure alters metabolization and genotoxicity induced by benzo[a]pyrene in human skin, Scientific Reports, vol.8, issue.1, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01903708

E. Bourgart, R. Persoons, M. Marques, A. Rivier, F. Balducci et al., Influence of Exposure dose, Complex Mixture and Ultraviolet Radiation on Skin Absorption and Bioactivation of Polycyclic Aromatic Hydrocarbons
URL : https://hal.archives-ouvertes.fr/hal-02180840

, Congrès scientifiques internationaux : ? Communications orales

E. Bourgart, M. Marques, A. V. Koschembahr, D. Béal, and R. Persoons,

, 20th International Congress on In Vitro Toxicology (ESTIV2018), 2018.

E. Bourgart, D. Barbeau, M. Marques, D. Béal, and M. Leccia,

, Realistic Human Skin Model for the Understanding of Polycyclic Aromatic Hydrocarbons Cutaneous Absorption and Metabolism. 16th Perspectives in Percutaneous Penetration Conference, 2018.

, Métabolisme cutané et biomarqueurs d'exposition aux mélanges d'hydrocarbures aromatiques polycycliques

, Après la mise au point des méthodes d'extraction et d'analyse adéquates, la toxico-cinétique et le métabolisme cutané de faibles doses de B[a]P ont été étudiés. La pénétration cutanée et le métabolisme du B[a]P sont inversement proportionnels à la dose appliquée. Cependant, les voies de métabolisation sont impactées différemment. Alors que la production du 3-OHB[a]P issu des voies de détoxication est dose-dépendante, la formation du B[a]P-tétraol, produit de l'hydrolyse du métabolite cancérogène ultime du B[a]P, est rapidement saturée. Le B[a]P-tétraol est donc le biomarqueur le plus pertinent pour estimer le risque cancérogène au B[a]P. De plus, la proportion de B[a]P non-métabolisé traversant la peau est extrêmement limitée indiquant que la toxicité de ce composé s'exprime essentiellement localement. La deuxième partie de ce travail a consisté en une synthèse bibliographique centrée sur la biotransformation de 7 autres HAP cancérogènes permettant d'identifier 16 métabolites d'intérêt commercialisés. In fine, le dosage de 10 de ces métabolites, impliqués dans les voies de bioactivation ou de détoxication de 5 HAP, a pu être développé en GC-MS/MS. Le dosage urinaire de ces nouveaux biomarqueurs devrait permettre d'améliorer la SBE des populations aux HAP cancérogènes. Dans la dernière partie de ce travail, l'impact de la composition de mélanges synthétiques ou industriels (extraits de brai de houille et de coke de pétrole) à différentes doses sur l'absorption et le métabolisme cutanés des HAP furent évalués en présence ou non de rayonnements ultraviolets (UV). La pénétration des HAP diminue quand la complexité du mélange et la dose augmentent. Alors que les UV amplifient la pénétration des HAP lors de l'application des mélanges industriels, ils n'ont pas d'effet sur le B[a]P appliqué seul ou sur les mélanges synthétiques. Leur bioactivation décroit sous l'influence des mélanges et des UV, provoquant une accumulation de HAP non-métabolisés dans la peau ce qui pourrait retarder la survenue des effets génotoxiques, Les hydrocarbures aromatiques polycycliques (HAP) sont des cancérigènes ubiquitaires, produits en mélanges complexes dont la composition varie en fonction de la source d'émission. Classées substances prioritaires de par leur abondance et leur génotoxicité, l'exposition aux HAP des populations se fait notamment par voie cutanée au cours des activités professionnelles

, To assess Benzo[a]pyrene (B[a]P) exposure, which is classified as carcinogenic to human, quantification of 3-hydroxybenzo[a]pyrene (3-OHB[a]P) and (±)trans-anti-B[a]P-tetrol (B[a]P-tetrol) was recently proposed. This PhD thesis aimed at studying the skin absorption and metabolism of B[a]P and PAH mixtures to improve the understanding of their genotoxicity and develop relevant biomarker for health risk assessment. The first part of this work consisted in developing a simple and realistic skin model from human skin explants. Further to the development of adequate extraction and analytical methods, cutaneous toxicokinetic and metabolism from low B[a]P doses were studied. B[a]P skin penetration and metabolism were inversely proportional to applied dose. Nevertheless, metabolic pathways are impacted differently. While 3-OHB[a]P production formed during detoxification was dose-dependent, the formation of B[a]P-tetrol, resulting from the hydrolysis of B[a]P ultimate carcinogenic metabolite, saturates rapidly. Therefore, B[a]P-tetrol is the most relevant biomarker for estimating B[a]P carcinogenic risk. In addition, unmetabolized B[a]P poorly diffused through skin indicating that B[a]P toxicity is mainly local. The second part of this work consisted of a literature review focusing on 7 other carcinogenic PAH biotransformation to identify 16 marketed metabolites of interest. In fine, GC-MS/MS analysis was developed for 10 previously identified metabolic intermediates that are either involved in bioactivation or detoxification pathways of 5 PAH. Urinary quantification of those new biomarkers should improve the biomonitoring of populations to carcinogenic PAH. Finally, we evaluated the impact of synthetic or industrial mixtures (coal tar pitch and petroleum coke extracts) composition at different doses on carcinogenic PAH skin absorption and metabolism combined or not with ultraviolet radiations (UVR). PAH penetration diminished when mixture complexity and dose increased. While UVR increased PAH penetration when industrial complex mixtures were applied, no effect was observed on pure B[a]P or synthetic mixtures. PAH bioactivation decreased with mixtures and UVR, inducing unmetabolized PAH accumulation in the skin which may delay the occurrence of genotoxic effects, Mots clefs : Métabolisme cutané, Indicateurs biologiques d'exposition, Hydrocarbures aromatiques polycycliques, Mélanges. Cutaneous Metabolism and biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons Mixtures Polycyclic aromatic hydrocarbons (PAH) are ubiquitous carcinogens emitted as complex mixtures whose composition depends on emission sources