Evaluation of Mixtures: Laboratory Tests

Simultaneous exposure of humans to a number of chemicals may produce toxicity which is different than that seen if the exposure to these compounds were sequential. If there is more than one toxic compound in the mixture, their toxicity may be greater than additive, additive, or less than additive. Which of these alternatives occurs depends on a complex set of factors among which are the ability of one or more of these toxic (and non-toxic) compounds present in the mixture to change the metabolism, excretion, or binding to receptors of others in the mixture. One way of determining the potential toxic effects in humans of exposure to the mixture is to carry out laboratory tests in experimental animals using the chemical mixture to which humans are exposed. In a number of instances, humans will be exposed to a highly complex mixture of chemicals, some of which will be present in very low concentrations. Also, some of the compounds in the mixture may have physical or chemical properties which suggest they may pose less risk to human health than others in the mixture. In these cases, consideration should be given to restricting the laboratory tests to compounds present above some minimal concentration, or possessing chemical or physical properties which suggest they pose a greater human risk. This approach could be used in assessing the potential toxicity of chemical mixtures to which humans were exposed by ingestion, inhalation, or dermal contact.