Subcellular partitioning links BLM-based toxicokinetics for assessing cadmium toxicity to rainbow trout

The purpose of this article was to develop an integrated-scale toxicological model to investigate the impact of cadmium (Cd) toxicity on rainbow trout (Oncorhynchus mykiss) based on recent published experimental data. This model was generated from three different types of functional relationship: biotic ligand model (BLM), damage assessment model (DAM), and subcellular partitioning model (SPM), both of key toxicological determinants involved and of functional connections between them. Toxicokinetic parameters of uptake rate constant (k(1)) and elimination rate constant (k(2)) in gill, liver, and subcellular fractions were derived. A negative correlation between gill binding fraction of Cd and bioaccumulation factor was found. Detoxifying ability (% detoxified in liver metabolically detoxified pool (MDP)) and k(2) were negatively correlated, indicating that increasing % detoxified in MDP can compensate for lower k(2). This finding suggests a potential tradeoff between the abilities of elimination and detoxification for Cd. Yet, compensation between the ability to eliminate Cd and the ability to recover Cd-induced damage was not found. However, changes in k(2) and recovery rate constant (k(r)) can shift the dynamics of Cd susceptibility probability. This analysis implicates that once k(2) is determined experimentally, the values of k(r) and % detoxified in MDP can be predicted by the proposed k(2)-k(r) and k(2)-% detoxified relationships. This study suggests that the mechanistic linking of BLM-based DAM and SPM can incorporate the organ- and cell-scale exposure experimental data to investigate the mechanisms of ecophysiological response for aquatic organisms exposed to metal stressors.