Bacterial mutagenicity of polycyclic aromatic hydrocarbons in reconstituted mixtures and crude coal tar extracts and fractions

Abstract

Although polycyclic aromatic hydrocarbons (PAHS) are one of the most ubiquitous carcinogens in the environment, little is known regarding their potential mutagenic interactions. Risk assessment of complex PAH mixtures utilizes toxic equivalency factors which assume additive interactions between individual PAHS. The mutagenic interactions of PAH mixtures were investigated using the Salmonellalmicrosome assay. Two groups of samples included PAH mixtures modeling a coal tar and an environmental crude coal tar extract and its fractions. The PAH mixtures were prepared in 2-, 3-, 4-ring and total reconstituted groups in the same percentages as a model coal tar. The environmental coal tar was extracted and separated into PAH fractions. Each sample was tested at 5 consecutive dose levels with and without metabolic activation in the Salmonella/microsome assay using tester strains TA98 and TAIOO. The reconstituted mixture elicited the maximum mutagenic response of 1,089 revertants at a dose of 1.8mg/mL. At the four lower dose levels (0.09mg/mL to 1.8mg/mL), the reconstituted induced a higher response than the 4-ring mixture. At the highest dose level (18mg/mL), the reconstituted showed a lower response that the 4-ring. These results suggest enhanced mutagenic responses at lower dose levels, with inhibition at higher doses. The mutagenicity of the PAH mixtures was evaluated in combinations as 2-:3-, 3-:4-, and 2-:4-ring mixtures. The 2-:4-ring, and 3-:4-ring combinations induced lower mutagenic responses than the 4-ring alone, suggesting inhibition by the 2-and 3-ring PAHS. Inhibition was also observed when benzo[a]pyrene was tested 935 net revertants, while the benzo[a]pyrene:reconstituted mixture induced 349 net revertants. The methylene chloride extract of a coal tar induced 385 net TA98 and 589 net TAIOO revertants with high metabolic activation (30%). Fractions from the coal tar extract and binary mixtures of individual chemicals with a reconstituted coal tar extract induced additive responses. These data indicate that mixtures of PAHs exhibit a variety of mutagenic interactions. The interactive responses appear controlled by concentration and metabolism of the PAHS. Research of this nature may aid in establishing a clearer understanding of risks and interactions which occur from exposure to PAHS.