Physiologically based toxicokinetic model for dichlorvos in Rattus norregicus

A physiologically based toxicokinetic(PBTK) model was applied to simulate the process of absorption, distribution and metabolism of dichlorvos in Rattus norregicus' body after oral ingestion. The PBTK model for dichlorvos contained four compartments: liver, kidney, rapidly perfused tissues and slowly perfused tissues. The change rate of dichlorvos concentration in the compartments was described by the mass balance differential equation. The toxicokinetic data were simulated according to Euler's method of numerical integration. The concentrations of dichlorvos in the liver and blood and the changing of AChE activity in blood were predicted after exposing to 10, 25 and 50 mg/kg b.w. dichlorvos. In order to validate this method, the simulation values and experimental values of the dichlorvos concentration in Rattus norregicus' blood following oral ingestion of 35 mg/kg b.w.dichlorvos was compared, the blood AChE activity changing in Rattus norregicus following oral ingestion of 10 mg/kg b.w.dichlorvos was also compared. It was found that the simulation results obtained had no significant difference with the experimental values. The results suggested that PBTK model could predict the toxicokinetics of oral ingestion of dichlorvos in Rattus norregicus, and provided a new route for assessing the deliverated dose of human being exposed to hazards.