Heavy metal pollution is a serious threat to ecosystem functioning. Different approaches have been developed to relate the exposure of heavy metals to their accumulation and toxicity. One approach is to relate metal toxicity to the concentrations of the metals in the whole body or a specific target tissue instead of the external exposure concentrations. To test the usefulness of this approach, the relationship between cadmium exposure, accumulation, and toxicity was investigated using an oligochaete worm and kinetic modeling. The uptake and elimination of cadmium by the aquatic oligochaete Tubifex tubifex from the aqueous phase was studied as function of time at different exposure concentrations using both radioactive and non-radioactive cadmium. A two-compartmental pharmacokinetic model was constructed and parametrized by fitting the model to the measured cadmium body concentrations during exposure to different cadmium concentrations. The uptake rate constants were dependent on the cadmium exposure concentration, and this relation could be well-described by incorporation of Michaelis-Menten type uptake kinetics. The toxicity of cadmium was analyzed by determining the lethal exposure concentration associated with a mortality of 50% (LC50) at different time points. LC50 values decreased with increasing exposure time reaching the incipient lethal level after 15 d. Critical body concentrations (CBC) associated with 50% mortality were calculated by combining the model-predicted pharmacokinetic parameters and the measured LC50 values. The predicted mean CBC (0.32 mumol/g wet weight +/- 0.02) was in good agreement with the experimentally obtained CBC for cadmium found in T. tubifex (0.37 mumol/g wet weight +/- 0.07) and appeared to be independent of exposure time and exposure concentration. Our results show that a pharmacokinetic modeling approach provides a tool to link metal exposure to availability, accumulation, and toxicity under variable exposure scenarios taking into account the kinetics of the processes.