Test No. 417: Toxicokinetics
This Test Guideline describes in vivo studies that provide information on mass balance, absorption, bioavailability, tissue distribution, metabolism, excretion, and basic toxicokinetic parameters [e.g. AUC], as well as supplemental approaches that may provide useful information on toxicokinetics. Information from toxicokinetic studies helps to relate concentration or dose to the observed toxicity and to understand its mechanism of toxicity. The test substance ("unlabelled" or "radiolabelled" forms) is normally administered by an oral route, but other routes of administration may be applicable. Single dose administration of the substance (preferably a minimum of two dose levels) may be adequate, but repeated dose may be needed in some circumstances. Toxicokinetic studies should preferably be carried out in the same species as that used in other toxicological studies performed with the substance (normally the rat, a minimum of 4 animals of one sex for each dose). Initial estimation of absorption can be achieved by mass balance determination, but further investigations such as intravenous (IV) administration and biliary excretion studies might be necessary. Bioavailability can be determined from plasma/blood kinetics of oral and IV groups. The percent of the total dose in tissues should at a minimum be measured at the termination of experiment,but additional time points may also be needed. Metabolites present at 5 % or greater of the administered dose should be identified. The rate and extent of excretion of the administered dose should be determined by measuring the percent recovered dose from urine, faeces and expired air.
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