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Toxicology Lab

"Rien ne se perd, rien ne se crée, tout se transforme."

("Nothing is lost, nothing is created, everything is transformed.")

Traité Elémentaire de Chimie (Elementary Treatise of Chemistry) Antoine Lavoisier, 1789

Solvents

Thousands of toxicants are continuously emitted into the environment and, as a consequence, the general population is exposed to a large number of pollutants inhaled via air, ingested with food, and adsorbed through skin. The pollutants benzene, toluene, ethylbenzene, xylenes (BTEX), methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and naphthalene represent an important group of airborne contaminants. BTEX (monocyclic aromatic chemicals), and MTBE and ETBE (oxygenated compounds belonging to the class of ethers) are mainly used as additives in gasoline to enhance octane rating, in replacement of alkyl-lead compounds, and to improve the combustion process. The presence of the aforementioned chemicals in outdoor air has been largely associated with fuels, as components of both vehicular exhaust fumes and vapors. Moreover, toluene, ethylbenzene and xylene are components of several household products for cleaning, personal care, and painting, and therefore represent additional indoor air contaminants. BTEX and naphthalene are also present in main- and side-stream tobacco smoke, which provides one of the largest sources of personal exposure to air pollutants.

The interest of our group in the biomonitoring of the exposure to solvents is documented in several publications starting from 1995. Below the study chemicals are reported in details.

BENZENE

Benzene is a known carcinogen to humans, and evidence indicates that benzene causes hematotoxicity at exposure levels below 1 ppm. Research on benzene was devoted to develop specific and sensitive methods to quantify both urinary benzene [Fustinoni et al., 1999; Perbellini et al., 1999] and urinary metabolites of benzene [Buratti et al., 1996; Buratti et al., 2001], comparing their intrinsic characteristics and suitability to assess exposure at occupational and environmental levels [Fustinoni, 2010d; Fustinoni et al., 2011; Lovreglio et al., 2011]. The exposure to benzene was evaluated in traffic wardens [Fustinoni et al.,1995; Campo et al., 2011], in petrol station attendants [Fustinoni et al., 2005c; Farmer et al., 2005; Fustinoni et al., 2005d], in petrochemical workers [Fustinoni et al., 2012a], in solvent workers [Waidianatha et al., 2001], in office workers [Carrer et al., 2000], and in the general population [Fustinoni et al., 2012a; Campagna et al., 2012; Campagna et al., 2014; Ranzi et al., 2013]. The epigenetic changes related to benzene exposure were also studied [Bollati et al., 2007; Hoxha et al., 2009; Carugno et al., 2012; Zhu et al., 2012; Fustinoni et al., 2012b].

TOLUENE, ETHYLBENZENE, AND XILENE

Toluene, ethylbenzene, and xilenes are very common chemicals, widely used as solvents in paints, coatings and many consumer products, as synthetic intermediates and as additives in fuel. From a toxicological point of view, these chemicals are neurotoxic. Specific methods for the quantification of both urinary or blood compounds [Fustinoni et al., 1999] and their urinary metabolites [Buratti et al., 2001; Fustinoni et al., 2005b] were developed and the different biomarkers were evaluated for their characteristics [Fustinoni et al., 2000; Fustinoni et al., 2007; Fustinoni et al., 2009]. Environmental and biological monitoring of exposure to these compounds was assessed in workers such as rotogravure printing workers [Fustinoni et al., 2005b], office workers [Carrer et al., 2000; Fustinoni et al., 2005d; Campo et al., 2011b], and in the general population [Fustinoni et al., 2010b; Fustinoni et al., 2005d; Ranzi et al., 2013].

MTBE and ETBE

Oxygenated hydrocarbons, such as ethers (MTBE and ETBE) and alcohols, are blended into petrol in any proportion up to 15% by volume as additives to improve the fuel combustion and enhance octane rating. MTBE is classified as not carcinogenic to humans. A specific method to quantify ethers in urine has been developed [Scibetta et al., 2007] and MTBE has been evaluated as a biomarker of exposure to urban traffic in traffic wardens [Campo et al., 2011] and in the general population [Fustinoni et al., 2010b].

STYRENE

Styrene is an important industrial chemical that is used primarily in the production of plastics, resin, and synthetic rubber. Occupational exposures to styrene are accompanied by co-exposures to low levels of styrene-(7,8)-oxide (StyOX), which is produced from oxidation of styrene during the production of plastics. Styrene and StyOX are classified as possible and probable human carcinogens, respectively. Research of our group on styrene has been devoted to elucidate the relationships between blood-protein adducts and other styrene biomarkers [Fustinoni et al. 1998], and to compare several potential biomarkers of exposure to styrene and StyOX taking in account the influence of cigarette smoking and genetic polymorphisms as potential confounders and using a repeated measurement sampling design [Fustinoni et al., 2008a] to assess the variability of the studied biomarkers [Fustinoni et al., 2010a].

1,3-BUTADIENE (BD)

BD is a chemical widely used for rubber, resin, and latex production. Besides exposures in occupational settings, BD is a ubiquitous pollutant; major sources of exposure in the general population are cigarette smoke and automobile exhausts. BD is classified as a probable carcinogen to humans. The research on BD was focused on evaluating the influence of genetic polymorphisms of enzymes involved in BD metabolism on the excretion of urinary metabolites and the levels of hemoglobin adducts in workers exposed to low levels of BD and in unexposed subjects [Begemann et al., 2001; Fustinoni et al., 2002; Fustinoni et al., 2004], and on evaluating the genotoxic effect of BD exposure [Lovreglio et al., 2006; Buckvic et al., 2009], the glutathione transferase activities, and the levels of glutathionylated hemoglobin [Primavera et al., 2008].