Genotoxicity of complex mixtures: strategies for the identification and comparative assessment of airborne mutagens and carcinogens from combustion sources

Abstract

Two strategies for assessment of the toxicity of complex mixtures are described and illustrated with examples from genotoxicity studies of complex combustion mixtures. The first, a strategy for identifying biologically active compounds or compound classes in complex mixtures, is called bioassay-directed fractionation and characterization. The identification and assessment of mutagens and potential carcinogens in complex mixtures has been significantly advanced by the use of short-term genetic bioassays. Bioassay-directed fractionation coupled with new analytical characterization methods has provided the tools needed to more efficiently identify potential carcinogens in complex combustion emissions and urban air samples. These studies have shown that a significant portion of the mutagenicity in combustion emissions and urban air is found in fractions more polar than polynuclear aromatic hydrocarbons (PAHs). A second strategy, the comparative potency method, provides an approach to evaluating the relative toxicities of a series of mixtures. The comparative mutagenicity and carcinogenicity of a series of combustion emissions has been assessed using dose-response studies in bacteria, mammalian cells, and rodents. Comparative mutagenic and tumorigenic emission rates or emission factors provide a means to directly compare the relative hazard of the sources. This data base has also been used to develop a comparative risk assessment methodology for combustion emissions.