Critical review on the withdrawal period calculation for injection site residues

This review concerns a statistical method for calculating withdrawal period for injection site residues. A recently adopted Committee for Medicinal Products for Veterinary Use/European Agency for the Evaluation of Medicinal Product (CVMP/EMEA) guideline recommends to apply the same method for the calculation of withdrawal period for injection site residues as for other edible tissues. For reasons in this study developed below, this approach is deemed to be inappropriate for the injection site residues. The injection site residues often violate regression assumptions with regard to homoscedasticity (same variance in residue concentrations for different slaughter times) and linearity (of the mean depletion curve in log(e)-scale). The currently recommended method cannot adequately handle these aspects. An alternative pragmatic method taking into account the last slaughter time with all data below the reference threshold, combined with a safety span, is proposed for injection site residues. A nonparametric approach for calculating the withdrawal period is also presumed to be a sound alternative. The references commonly used are the Maximum Residue Limit (MRL) and the Acceptable Daily Intake (ADI). Unfortunately these references are not relevant to the acute risk exposure associated with injection site consumption. The use of alternative references, such as the Acceptable Single Dose Intake (ASDI) or the Acute Reference Dose (ARD) are thought to be more appropriate.