TOXIC INTERACTIONS AMONG ENVIRONMENTAL-POLLUTANTS - CORROBORATING LABORATORY OBSERVATIONS WITH HUMAN-EXPERIENCE

Combined exposures to multiple chemicals may result in interactions le ading to a significant increase or decrease in the overall toxicity of the mixture compared to the summation of the toxicity of the componen ts. A large number of chemical interactions have been described in ani mal studies by administering high doses of chemicals by routes and sce narios often different from anticipated human exposures. Though limite d, there is some evidence for the occurrence of several supra-additive (the combined effects are greater than the simple summation of the in dividual effects) and infra-additive (the combined effects are smaller than the simple summation of the individual effects) chemical interac tions in humans. Fos example, toxicokinetic interactions between sever al solvents have been round to occur in the workplace, whereas those i nvolving pesticides have been reported less frequently, especially dur ing accidental exposures. Toxic interactions involving nutritionally i mportant metals and metalloids appear to occur more frequently, since several of them have an important role in a variety of physiological a nd biochemical processes. On the contrary, there is not much evidence to confirm the occurrence of toxic interactions among the commonly enc ountered 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 appro priate mechanistic considerations. Future research efforts in the chem ical interactions arena should address these issues by focusing on the development of mechanistically and biologically based models that all ow predictions of the extent of interactions likely to be observed in humans.