Toxicokinetics/toxicodynamics with damage feedback improves risk assessment for tilapia and freshwater clam exposed to arsenic.

It has been proposed that irreversible responses of organisms exposed to contaminants are due to a systems-level feedback. Here we tested this hypothesis by reanalyzing the published data on toxicokinetics and survival probability based on a systems-level threshold damage model (TDM) incorporating with a positive damage feedback to explore the steady-state response and dynamic behavior of damage for tilapia and freshwater clam exposed to waterborne arsenic (As). We found that ultrasensitivity appeared in As-tilapia and freshwater clam systems with Hill coefficient n ≥ 4, indicating that the positive damage feedback mechanism has been triggered. We confirmed that damage can trigger a positive feedback loop that together with As stressor increases irreversibility. This study also showed that TDM with positive feedback gave a much better predictability than that of TDM at As concentrations ranging from 100 to 500 mg l(-1) for freshwater clam, whereas for tilapia, two models had nearly same performance on predictability. We suggested that mortality-time profile derived Hill coefficient could be used as a new risk indicator to assess the survival probability for species exposed to waterborne metals. We anticipated that the proposed toxicokinetics/toxicodynamics with a positive damage feedback may facilitate our understanding and manipulation of complex mechanisms of metal susceptibility among species and improve current risk assessment strategies.