Division 3.2.1 Metabolic and residue studies

The establishment of the metabolic fate of the additive in the target species is a determinant step in the identification and quantification of the residues in the edible tissues or products derived from the animals given the feed or water containing the additive. Studies must be submitted concerning the absorption, distribution, metabolism and excretion of the substance (and its metabolites).

Studies must be carried out using internationally validated test methods and shall be performed in accordance with F1F2assimilated law or OECD Guidelines for methodological details and according to the principles of GLP. The study shall respect the rules on animal welfare laid down by F3assimilated law, and they shall not be repeated if not necessary.

Metabolic and residue studies on the target animal(s) shall be performed with the active substance incorporated in the feed (not given by gavage unless it is properly justified).

Structural identification of metabolites representing more than 10 % of the total residues in the edible tissues and products and more than 20 % of the total residues in the excreta shall be established. If the metabolic pathway of the active substance raises any toxicological concerns, metabolites below the above limits shall be identified.

Kinetic studies of the residues will form the basis for the calculation of consumer exposure and the establishment of a withdrawal period and MRLs, if necessary. A proposal for a marker residue shall be provided.

For some additives, depending on their nature or use, it may not always be necessary to carry out metabolic and residues studies.