Since toxicity is time dependent, short-term toxicity tests may overlook mixture effects, because chemical accumulation within an organism takes time. We therefore studied the effects of cadmium on the toxicokinetics of pyrene and its metabolites in the soil-dwelling collembolan Folsomia candida exposed through Lufa 2.2 soil. Single pyrene was rapidly taken up and steady state was reached within the 337-h exposure period. Simultaneous exposure to cadmium significantly decreased the pyrene uptake and elimination rate, resulting in a prolonged half life. Kinetics of the first phase metabolite OH-pyrene was also significantly influenced by cadmium. Cadmium increased the hydroxylation rate of pyrene but slowed down its further metabolization, again resulting in a prolonged half life. We showed that pyrene accumulation and metabolization are significantly influenced by the presence of cadmium. Our results suggest that mixture effects may be dependent on exposure time.
In this research we will show the advantages of using a time-independent dose metric in a mechanistic model to evaluate toxic effects for different narcotic compounds on different species. We will show how different already existing QSARs can be combined within a mechanistic framework to 1) make predictions of lethal thresholds; 2) show some limitations in the use of existing QSARs; 3) show how a mechanistic framework solves some conceptual problems in current approaches and 4) show how such a framework can be used to be of aid in an experimental setup in predicting the outcome of a survival experiment. The approach we chose is based on the simplest mechanistic model available, a scaled one-compartment model to describe uptake and elimination and hazard model to link the exposure to effects on survival. Within this theoretical framework a prediction for an internal threshold for effects on survival of 3 mmol/kg bw can be made, which should be similar for different species and independent of the partitioning characteristics of the toxicant. To demonstrate this, a threshold for 51 different species was derived, which indeed appeared to lie in a relatively small range, typically between 1 and 10 mmol/kg bw.
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