Response predictions for organisms water-exposed to metal mixtures: a meta-analysis.

To develop a multimetal toxicity model requires insight into the relationships between the composition of metal mixtures and their toxicological effects on organisms. As a first step in developing such a model, quantitative data from binary and higher mixture studies of Cu, Cd, and Zn were compiled and used to assess trends in toxicological effects on various organisms. The findings of this meta-analysis show relatively little occurrence of additive effects compared with antagonistic and synergistic effects. This observation held true irrespective of test species, environmental compartment, or metal concentrations in the mixture. However, the type of effect was significantly correlated with the metal combination tested and the selected toxicological endpoint. It was also found that different methods were used for assessing deviation from additivity in the various individual studies. For robust comparison, standardization on this point is required. Toxicological responses of organisms to metal mixtures were shown to be hard to predict and were often slightly less than or slightly more than additive. The interactions observed could not be explained by metal-metal interactions alone. We therefore conclude that with current scientific knowledge it is not yet possible to predict responses to metal mixtures in individual cases; at best this is possible only in terms of general patterns. Nevertheless, in the context of environmental risk policy, the assumption of additivity produces a conservative prediction of toxicity, because toxicity of a metal mixture will be either predicted correctly or overpredicted by default in approximately 75% of all cases. The use of models based on noninteraction is satisfactory from this regulatory perspective.