Toxicokinetic−toxicodynamic modeling of cadmium and lead toxicity to larvae and adult zebrafish

Abstract

Toxicity of hazard materials to organism is different between larvae and adult zebrafish. However, this different effect was seldom considered in toxicological modeling. Here, we measured Cd and Pb toxicity for larvae and adult zebrafish (Danio rerio) and assessed whether metal toxicity can be better simulated by the one-compartment or two-compartment toxicokinetic (TK) and toxicodynamic (TD) models with assumption of stochastic death (SD) and individual tolerance (IT), respectively. Results showed that, for larvae, the one-compartment model generally fitted the observed accumulation and survival better than two-compartment model. In contrast, for adult, the two-compartment model simulation satisfied the observed accumulation and survival better than one-compartment model. In addition, both the SD and the IT models generally described the Cd or Pb toxicity well, although the IT model predictions were slightly better than the SD model in adult fish, the opposite phenomenon was observed in larvae. Our results suggested that variations in both TK and TD parameters might be needed to quantify the toxicity sensitivity in larvae and adult zebrafish, and accounting these variations in mechanistic toxicological effect models (e.g. TK-TD) will allow more accurate predictions of hazard materials effects to organisms.