Evaluation of In Vitro-based simulations of toluene uptake and metabolism in rats.
The uptake of toluene in the rat from a closed exposure chamber was simulated with a physiologically based pharmacokinetic (PB-PK) model. Six different parameter sets for toluene biotransformation in vitro were subsequently substituted in the model while keeping all other model parameters constant. Simulations of toluene uptake and metabolism based on these six in vitro-derived biotransformation parameter sets were compared with two empirical in vivo data sets on the decrease of toluene concentrations in closed exposure chambers. It was observed that simulations based on in vitro-derived biotransformation parameters gave similar or better results than simulations across these two in vivo data sets. It is concluded that the results from most studies on toluene biotransformation in vitro resulted in adequate simulations of uptake and metabolism of toluene in vivo. These results support earlier findings on application of in vitro techniques to derive parameters for PB-PK models.
Dejongh
J
J
Research Institute of Toxicology (RITOX), PO Box 80.176, 3508 TD Utrecht, The Netherlands.
Blaauboer
B J
BJ