Optimal design and mathematical model applied to establish bioassay programs.

Bioassays can be used to estimate the initial intake I for the case of an acute intake exposure for an individual worker. To evaluate the effective dose, apart from I, we need to know other parameters such as activity median aerodynamic diameter (AMAD) or the fraction absorption ( f(1)) in the blood from the GI tract, but in an accident situation these parameters are often unknown. The bioassay measurement values can be used to estimate by fitting the parameters unknown. In this paper, optimal designs for the estimation of the unknown parameters are developed. The efficiency of the design will depend on the number of samples and the measurement accuracy. The method described applies D-optimality that maximises the determinant of the Fisher information matrix to find the best moments where the bioassay measurements should be taken. It requires obtaining the analytical solution of the biokinetic model as a function of the parameters to be fitted. The method has been implemented in a computer program.