Understanding the effects of metal pre-exposure on the sensitivity of zebrafish larvae to metal toxicity: A toxicokinetics-toxicodynamics approach.

Organisms are increasingly tolerant to metal toxicity in the natural ecosystems, which did not match the results of the environmental risk assessment (ERA) of metals based on toxicity data from organisms in the laboratory. Studies have described the effects of pre-exposure to metals on metal toxicity tolerance in terms of the toxicokinetic (TK) process; however, the toxicodynamic (TD) process may be more susceptible to metal pre-exposure. Therefore, to determine whether pre-exposure to low concentrations of silver (Ag) or cadmium (Cd) affects the metal TK and TD processes of zebrafish (Danio rerio) larvae, we investigated four TK-TD model parameters that control tolerance and sensitivity to metal toxicity on the survival. Our results showed that the killing rate (k) of larvae exposed to high Cd concentrations was significantly lower following pre-exposure to 10 μg/L Cd than that of larvaenot pre-exposed. However, the k for high Ag concentrations was significantly higher in zebrafish larvae following pre-exposure to 2 μg/L Ag than in larvae not pre-exposed. In other words, a one-day pre-exposure to 2 µg/L Ag rendered the larvae more sensitive to Ag during a subsequent 4-day exposure to higher Ag concentrations, whereas a one-day pre-exposure to 10 µg/L Cd rendered the larvae more tolerance to Cd during a subsequent 4-day exposure to higher Cd concentrations. Our results further the current understanding of toxic metal tolerance mechanisms, both in TK and TD processes, and they will guide future laboratory studies to assess actual pre-exposure scenarios that occur in natural environments. Thus, our study can help reduce uncertainty in testing and improve ecological management concerning metal risk assessments.