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Preliminary data on the disposition of Benzo[c]fluorene in rat

Abstract : Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and food contaminants. Part of them is mutagenic/genotoxic in vitro and in vivo and has shown clear carcinogenic effects in mammals. Therefore, these chemicals are of public health concern and require appropriate hazard characterization. The genotoxic process resulting in the carcinogenicity of PAHs is due to the formation of highly reactive metabolites, produced through different metabolic pathways. Among the PAH found in food samples, benzo[c]fluorene (B[c]F) was demonstrated to be carcinogenic in rodents 1,2 and the occurrence of corresponding pulmonary adducts has been demonstrated3. JECFA4 and EFSA5 recently highlighted the need for additional occurrence and toxicological data regarding this compound. In this context, we started to study B[c]F distribution and biotransformation in Sprague Dawley rats exposed to a single oral dose of radiolabelled B[c]F (20 µg/kg body weight). Extraction protocols of B[c]F residues from rats tissues, fluids, and excreta were developed with the aim to analyze both parental B[c]F and metabolites. Metabolic profiles were determined by radio-HPLC. Analysis of 0-24h urine samples showed an extensive renal excretion and the presence of many metabolites (>20). Liquid-solid extractions from liver samples excised 24h post-dose resulted in more than 50% unextractable radioactivity suggesting the presence of bound residues. Radio-HPLC profiles of extracts indicated the presence of approximately 30% of unmetabolized B[c]F, as well as several polar metabolites. Experimental developments and analyses of additional tissues and fluids are in progress, with the aim to better understand the metabolic mechanisms that trigger the carcinogenicity of this molecule. Our data will be used to develop a PBPK model in order to describe the toxicokinetics of B[c]F in rats and ultimately to extrapolate the toxicokinetics to humans.
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https://hal-ineris.archives-ouvertes.fr/ineris-00971113
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Submitted on : Wednesday, April 2, 2014 - 3:58:59 PM
Last modification on : Tuesday, August 11, 2020 - 12:06:24 PM

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  • HAL Id : ineris-00971113, version 1
  • INERIS : EN-2012-496

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Marianne Chopard-Lallier, Daniel Zalko, Elisabeth Perdu, Anne Hillenweck, Florence Blas-Y-Estrada, et al.. Preliminary data on the disposition of Benzo[c]fluorene in rat. 4. Health Food Symposium (SAS 2012), Jul 2012, Toulouse, France. ⟨ineris-00971113⟩

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