| dc.description.abstract | Complex chemical mixtures may be released into the environment from a variety
of sources including hazardous waste sites. Components of chemical mixtures and their
metabolites may be genotoxic leading to cancer and heritable gene mutations. Chemical
analysis alone does not always provide the most accurate information from which to
estimate the risk of adverse effects associated with exposure to mixtures. Current
methods to estimate the human health risk for complex mixtures assume additive effects
of the components. Although it is assumed that this approach is protective of human and
ecological health, it is also recognized that chemical mixtures may induce a variety of
interactions including potentiation, synergism, and antagonism. A combined testing
protocol, using chemical analysis coupled with a battery of in vitro, in vivo, and in situ
bioassays, provides the most accurate information from which to estimate risk. Such a
combined testing protocol provides information to describe the major organic and
inorganic constituents, as well as the pharmacokinetics and potential interactions of
chemical mixtures. This research was conducted to investigate the potential genotoxic
effects of complex chemical mixtures of polycyclic aromatic hydrocarbons (PAHs) and
polychlorinated aromatics (PCA) using microbial bioassays (Salmonella/microsome
assay and the E. coli prophage induction assay), the 32P-postlabeling assay in mice, and
in situ measurements of genotoxicity using flow cytometry. Samples of environmental
media and wildlife tissues were collected from four National Priority List Superfund
sites within the United States. In general, chemical analysis was not always predictive
of mixture toxicity. Although biodegradation reduced the concentration of total and
carcinogenic PAHs in soils and groundwater, the genotoxicity of extracts from environmental media did not display a corresponding reduction. Mixtures of
polychlorinated biphenyls (PCBs) extracted from sediments were found to inhibit the
genotoxicity of PAH mixtures when administered dermally to rodents. This inhibition
exhibited a dose-response relationship, with the adduct frequency reduced at increasing
doses of sediment extract. Finally, PAH concentrations in environmental media and
tissues were found to correlate with DNA damage in wildlife receptors. An integrated
approach, combining in vitro and in vivo methods to characterize genotoxicity provides
more accurate information from which to estimate uptake and risk associated with
exposure to complex mixtures and should be considered in both the human and
ecological risk assessment process. | en |
