Qualitative assessment of human exposure to consumption of injection site residues.

The recent adoption of the guideline on injection site residues in food producing animals by the Committee for Medicinal Products for Veterinary Use (CVMP) raised the question on the risk specifically related to injection site consumption. As noted in this guideline, residues at injection sites commonly deplete erratically. For the calculation of withdrawal time, treating residues at the injection site like those that occur in other tissues is questionable. An assessment of the risk related to the consumption of a whole or part of an injection site during a year was performed using a probabilistic approach. The risk assessment was modelled on the regimen of a 7-day antibiotic treatment, and was calculated on the scale of the European Union (EU) as a whole or of each European country. Our analysis indicated a maximal risk of 4 days of injection site consumption during a year in the EU. It also indicated that 37% of consumers would never eat an injection site in the same period. These results suggest that the risk of injection site consumption belongs more appropriately to an acute exposure risk than to a chronic one which is usually posed by the residues present in other edible tissues.

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.