Objective of the study

Metabolism of the pesticide includes the processes of transport or translocation within the organism as well as transformation to metabolites or degradation products.

Metabolism studies are conducted to determine the qualitative metabolic fate of the active ingredient and elucidate its metabolic pathway. Many pesticides undergo change during and after application to livestock. The composition of the terminal residue must, therefore, be determined before the residue analytical methodology can be developed and residues quantified.

In metabolism studies, the pesticide is applied to livestock in amounts and for durations of time that could occur in practice when the compound is used for pest control (i.e. the existing or intended good agricultural practices (GAPs)). In the case of livestock, milk and eggs are collected and in due course the animal is slaughtered for collection of meat and offal. The animal commodities are then examined for content of total residues produced by administration of the compound. Animal excreta and, in some cases, exhaled air are examined for elimination of the residue.

Further information on studies on metabolism of residues in livestock can be found in Chapters 3.2 and 5.3 of the JMPR Procedure Manual.

Worked examples on this topic are provided in Chapter 5 of the JMPR Training Manual

Circumstances in which the study is required

These studies are required whenever a pesticide is applied directly to livestock, to animal premises or housing, or where significant residues remain in crops or commodities used in animal feed, in forage crops, or in any plant parts that could be used in animal feeds.

Test organism or substrate

Separate farm animal feeding studies are required for ruminants (generally lactating goats or cows) and poultry (generally laying hens). It is generally not necessary to carry out metabolism studies with pigs since information on metabolism in a monogastric animal is available from studies with rats, except if the metabolic pathways differ significantly in the rat as compared to ruminants.

Test substance

The animals should be treated with radiolabelled active ingredient, preferably containing formulation ingredients typical of an end-use product as applied in the field.

Typical endpoints of the study

• Portion of extractable and non-extractable radioactivity in edible tissues, as % of total radioactive residues (TRR) and mg parent compound equivalent/kg sample material;
• Portion of characterised but not identified radioactivity in edible tissues and potential feed items;
• Identification of metabolites, described by their systematic chemical name – for all extractable residues at >10% TRR or at >0.05 mg/kg;
• Characterization of metabolites – for all extractable residues at <10% TRR or at 0.01- 0.05 mg/kg;
• Presence of metabolites in conjugated form, extractability of conjugated metabolites;
• Schematic diagram of the metabolic pathways in livestock with a brief explanation of the distribution and chemical reactions involved;
• Radioactivity in faeces, urine, cage wash as % of applied radioactivity;
• Presence of parent compound and identified major metabolites (> 10% of TRR) expressed as % of total radioactivity and mg/kg in milk, muscle, liver kidney, fat and eggs as appropriate.

Testing guidelines

The following testing guidelines may be used for determination of the nature of residues in meat, milk poultry or eggs:

• OECD Guidelines for the Testing of Chemicals. Test No. 503: Metabolism in livestock.
• USEPA-OCSPP Harmonized Test Guidelines. Test No. OPPTS 860.1300. Residue Chemistry Test Guidelines – Nature of the residue: plants, livestock.
• European Commission. Guidelines for Residue Data – Metabolism and distribution in domestic animals. (Technical Guidelines - Appendix F)