Setting Residue Concentrations Allowed in Food

Residues are evaluated to determine the extent of uptake of the veterinary drug, its distribution throughout the body, and its elimination. Normally, contemporary residue depletion studies establish tissue concentrations in a radiolabeled drug study, in which total residues and parent compound are determined at several pre-determined times between zero time and a time beyond the proposed withdrawal time. As well as total residues, which include free and bound components, the study quantifies major metabolites. These are compounds contributing 10% or more of total radioactivity or that are present at a concentration of 0.10 mg/kg. Metabolism studies enable identification of the marker residue and target tissue. The marker residue must give assurance that, when its concentration is at or below the MRL, total residues satisfy ADI requirements. 

because the marker residue is unlikely to be the only compound of toxicological concern, its depletion must ensure that other residues have depleted to concentrations considered to be safe prior to that of the marker residue. 

Some authorities, such as the United States, establish a target tissue to monitor the safety of the entire carcass. The target tissue is chosen to monitor the safety of all edible (meat) tissues and is usually that tissue with the slowest rate of depletion. Some authorities, including the EU, consider all edible tissues as possible target tissues because control can be performed not only on the entire carcass but also on pieces of meat, isolated marketed offal, and other substances. 

The ADI provides the bright line between exposures that are safe and those that are unsafe. Because it is a primary (i.e., a non-derived) food safety standard, it is easily interpretable across a range of regulatory situations. However, with the exception of residue determinations made using bioassays, because the ADI reflects total residues of concern, it cannot provide a standard for regulatory enforcement. Maximum residue limits (MRLs) and tolerances (in the USA) provide that enforcement standard. 

Both MRLs and tolerances, following adjustments for specific tissue consumptions and analytical performance capabilities, are referable back to the ADI. As a consequence, both MRLs and tolerances may be considered as derived food safety standards. However, the exact way in which this connection back to the ADI is made differs for MRLs and tolerances. 

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