Mechanisms of toxicity/carcinogenicity and Superfund decisions

Heavy metals that contaminate soils and water usually exist in various oxidation states and form a number of compounds with different physical and chemical characteristics. These differences are often reflected in dramatic variation in toxicokinetic and biologic properties. Such variation in properties, critical in determining intrinsic toxicity, often causes a great deal of uncertainty in analyses of public health risks at sites where metal exposure is evaluated. In the Superfund program, such uncertainties may substantially undermine attempts to characterize potential impacts to populations exposed to metals from improperly disposed waste. In the case of chromium, risk assessment uncertainties can be considerable and fall generally into two categories. First, there is almost no information on potential health effects due to chronic oral exposure to chromium-containing compounds, and a nonquantifiable and probably large uncertainty exists in establishing no-effect levels. In fact, reference doses (RfDs) for CrIII and CrVI are based on chronic studies in which no adverse effects were seen even at the highest dose. Considerations of bioavailability, deduced from site characterization data, and acute toxicity indicate that general application of these RfDs may lead to highly inaccurate estimations of risk. Second, because of the ready reduction of CrVI in biological systems, it has not been possible to separate effects of CrVI from those of CrIII. Thus, data on the relative toxicity and carcinogenicity of these two species is sparse and difficult to interpret. Moreover, kinetic considerations make it difficult to determine the site and rates of reduction of CrVI. This makes prediction of target site concentrations of the two species difficult.(ABSTRACT TRUNCATED AT 250 WORDS)