Toxic interactions among environmental pollutants: corroborating laboratory observations with human experience.

Combined exposures to multiple chemicals may result in interactions leading to a significant increase or decrease in the overall toxicity of the mixture compared to the summation of the toxicity of the components. A large number of chemical interactions have been described in animal studies by administering high doses of chemicals by routes and scenarios often different from anticipated human exposures. Though limited, there is some evidence for the occurrence of several supra-additive (the combined effects are greater than the simple summation of the individual effects) and infra-additive (the combined effects are smaller than the simple summation of the individual effects) chemical interactions in humans. For example, toxicokinetic interactions between several solvents have been found to occur in the workplace, whereas those involving pesticides have been reported less frequently, especially during accidental exposures. Toxic interactions involving nutritionally important metals and metalloids appear to occur more frequently, since several of them have an important role in a variety of physiological and biochemical processes. On the contrary, there is not much evidence to confirm the occurrence of toxic interactions among the commonly encountered inorganic gaseous pollutants in humans. Overall, the majority of chemical interactions observed in animal studies have neither been investigated in humans nor been extrapolated to humans based on appropriate mechanistic considerations. Future research efforts in the chemical interactions arena should address these issues by focusing on the development of mechanistically and biologically based models that allow predictions of the extent of interactions likely to be observed in humans.