Determination of tetrahydroxylated metabolites in hair and DNA of rats under controlled exposure to a mixture of Polycyclic Aromatic Hydrocarbons: new biomarkers for assessing human exposure.

Introduction: Although the analysis of polycyclic aromatic hydrocarbon (PAHs) metabolites in urine has long been considered a reference biomarker of exposure to PAHs, hair analysis was also more recently demonstrated to enable the biomonitoring of PAH exposure with the advantage of wider windows of detection [1]. In addition to the " classically-analyzed " monohydroxylated metabolites, recent studies have shown the interest of the analysis of tetrahydrotetrols in urine for the assessment of human exposure to PAHs [2]. To obtain more comprehensive information on exposure, the range of OH-PAHs used as biomarkers was widened to include tetra-OH-PAH isomers in hair. This study hypothesized that these metabolites could constitute suitable biomarkers for the assessment of PAH exposure as they allow quantitative evaluation of the internal dose, appear more relevant than mono-hydroxylated forms for the measurement of heavy compounds and supply information about the toxicity of the parent compound linked to individual's specific metabolism. The present work therefore aims to develop a method for the determination of tetra-OH-HAPs in hair as new biomarkers of chronic PAH exposure. The suitability of the latter was evaluated by comparing the concentration measured in hair and the levels of DNA adduct found in a rat model exposed to a PAH mixture.