Predicting the survival of zebrafish larvae exposed to fluctuating pulses of lead and cadmium.

Aquatic organisms are often exposed to time-varied concentrations of contaminants due to pulsed inputs in natural water. Traditional toxicology experiments are usually carried out in a constant exposure pattern, which is inconsistent with the actual environment. In this study, a refined toxicokinetic-toxicodynamic (TK-TD) model was used to study the toxic effects of Pb and Cd on zebrafish larvae under three pulse exposures with 2, 4, and 6 h, respectively. The parameter sensitivity analysis showed that JM, max had the greatest impact on the output of the model. Cd or Pb pulse exposure resulted in less death than constant exposure at the same time-weighted average (TWA) concentrations. Survival fraction in larvae under 6 h interval between two pulses of Pb or Cd was larger than that under 2 h and 4 h interval. Toxicity under constant exposure of Cd or Pb was greater than that under 2, 4, and 6 h interval pulse exposure because the cumulative Cd or Pb concentration in the body under constant exposure was greater than that under pulse exposure. The results also showed that the stochastic death (SD) model was more suitable than the individual tolerance (IT) model for predicting the survival fraction of larvae under pulse exposure to Pb and Cd, which was indicated by higher R2 (0.670-0.940) in SD model than that (0.588-0.861) in IT model. Our model provides approaches for laboratory toxicity testing and modeling approaches for addressing the toxicity of heavy metal pulsed exposure.