Studies on absorption, distribution, excretion and metabolism in mammals (toxicokinetics)

Objective of the study

The tests should provide sufficient data to permit:

• an evaluation of the rate and extent of absorption,
• the tissue distribution and the rate and extent of excretion of the test substance and the relevant metabolites,
• the identification of metabolites and the metabolic pathway.

The effect of dose level on these parameters and whether results are different after single versus repeated doses, should also be investigated.

Circumstances in which the study is recommended to be required

The study should be conducted when chronic or carcinogenicity studies are recommended (generally if the pesticide is used on food and feed). The study may be recommended if significant adverse effects are seen in available toxicology studies and these effects can be further elucidated by metabolism studies.

Test organism

The study is normally conducted in rats. It may be necessary in some cases to perform additional studies on another species (such as goat or chicken).

Test substance

Pure active ingredient or radio-labelled pure active ingredient

Typical endpoints of the study

Various endpoints should be considered, such as (but not limited to): rate and extent of absorption, tissue distribution, potential for accumulation, rate and extent of excretion, metabolic pathways(s) in animals, toxicologically significant metabolites.

Test guidelines

The following test guidelines may be used for the determination of toxicokinetics:

• OECD Guidelines for the Testing of Chemicals. Test No. 417: Toxicokinetics
• US EPA Health Effects Test Guidelines. OPPTS 870.7485: Metabolism and pharmacokinetics
• EC Testing Method B.36. Toxicokinetics. Council Regulation (EC) No 440/2008.