Environmental Context. There is a considerable interest in predicting cadmium (Cd) toxicity to aquatic organisms, largely stemming from environmental Cd pollution and the need to establish water quality criteria to protect aquatic ecosystems. Chemistry-orientated models have been developed over the past decades to predict Cd toxicity, focusing on identifying which Cd forms are present in the aquatic environment, and investigating their interaction with the biological site of action. Understanding the cellular fates of Cd may provide an alternative method to predict Cd toxicity, as the complex cellular interactions of Cd within the organisms can, in this way, be addressed.

Abstract. The internal metal sequestration strategies of different aquatic organisms are complex and variable; thus it is a formidable task to predict metal toxicity. Metals accumulated by aquatic organisms are associated with different subcellular compartments (i.e. heat-sensitive proteins, heat-stable proteins (metallothioneins), granules, cellular debris, and organelles). Such subcellular partitioning is dynamic in response to metal exposure and other environmental conditions, and is metal- and organism-specific. Previous models predicting metal toxicity have relied on the free ion metal activity (i.e. the free ion activity model) or more recently on the metal binding with the proposed toxicological site of action (i.e. the biotic ligand model). Neither of these models considers the complexity of internal metal subcellular fractionation, which may significantly affect metal toxicity in aquatic organisms and subsequent trophic transfer of metals to consumers. Recent studies in small aquatic organisms have revealed that the subcellular partitioning model (SPM) may provide an improved method to predict Cd toxicity, but more studies are needed in the future.