title: In vitro mammalian mutagenicity of complex polycyclic aromatic hydrocarbon mixtures in contaminated soils.
abstract: This study employed an in vitro version of the lacZ transgenic rodent mutation assay to assess the mutagenicity of nonpolar neutral and semipolar aromatic soil fractions from 10 PAH-contaminated sites, and evaluated the assumption of dose additivity that is routinely employed to calculate the risk posed by PAH mixtures. Significant mutagenic activity was detected in all nonpolar neutral fractions, and 8 of 10 semipolar aromatic fractions (nonpolar > semipolar). Mutagenic activity of synthetic PAH mixtures that mimic the PAH content of the soils (i.e., 5-PAH or 16-PAH mix) were greater than that of the PAH-containing soil fractions, with 5-PAH mix >16-PAH-mix. Predictions of mutagenic activity, calculated as the sum of the contributions from the mutagenic mixture components, were all within 2-fold of the observed activity of the nonpolar neutral fractions, with one exception. Observed differences in mutagenic activity are likely the result of dynamic metabolic processes, involving a complex interplay of AhR agonsim and saturation of metabolic machinery by competitive inhibition of mixture components. The presence of hitherto unidentified polar compounds present in PAH-contaminated soils may also contribute to overall hazard; however, these compounds are generally not included in current contaminated site risk assessment protocols.
authors.affiliation: Mechanistic Studies Division, Environmental Health Science and Research Bureau, Health Canada, 50 Columbine Driveway, Tunney's Pasture 0803A, Ottawa, Ontario Canada , K1A 0K9.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Lemieux
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Long
authors.forename: Iain B
authors.initials: IB
authors.lastname: Lambert
authors.forename: Staffan
authors.initials: S
authors.lastname: Lundstedt
authors.forename: Mats
authors.initials: M
authors.lastname: Tysklind
authors.forename: Paul A
authors.initials: PA
authors.lastname: White
mesh_terms: D000818:Animals; D002460:Cell Line; D007763:Lac Operon; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D012989:Soil Pollutants / Q000633:toxicity*; D019076:Transgenes
chemical_list: D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D012989:Soil Pollutants