Understanding combined effects for metal co-exposure in ecotoxicology

Organisms in the environment experience exposure to mixtures of metals as a rule rather than an exception. Observational as well as experimental evidence shows that such co-exposure may give rise to combined effects that are different from what can be attributed to considering the effects of chemicals one by one. The two established reference models, concentration addition and response addition, therefore derive explicit expectations of a joint effect from the biological activities of the mixture constituents. The current empirical evidence of metal mixture effects in various mainly aquatic species shows, that while the reference models provide reasonable tools for analyzing combined effects, their actual predictions for binary mixtures compared to what has been observed show often somewhat less than additive combined effects. As the bioavailability of metals is governed by several environmental factors as well as biosystem properties, the different processes involved provide ample opportunities for interaction which may confound non-interactive combined effects. The biotic ligand model offers scope to address these issues on a more mechanism-focussed basis in the near future. Furthermore, the toxicodynamics of metals is highly compound-specific, considering the various specific metalloid transporters, regarding the essential functions of metals in metabolism and taking account of the organisms' efforts to maintain homeostasis for some metals. This and the diversity of already known molecular interferences with cellular metabolism offer scope to unravel potentially adverse interactive outcomes. Thus, for improving our predictability of combined effects from metal co-exposure, we require more quantitative insight into and models for the processes governing the toxicokinetics and dynamics of metals in environmental organisms.