Applications toxic metabolism studies

To select and define the target analytes for the residue analysis of crops in a field trial, applicants should consider metabolites/degradation products of the test materials by conducting plant and animal metabolism studies and by assessing toxicity of the metabolites/degradation products. 

Besides their utilization in the production of many compounds with therapeutic, diagnostic, and immunizing applications, animal cell cultures have undoubted utility in the performance of in vitro cytotoxicity tests. They can be used for the evaluation of potential anti-neoplastic agents and assessment of the safety of various products, such as pharmaceuticals, cosmetics, alimentary additives, pesticides, and industrial chemical products. Cell culture systems are frequently employed in the cancer chemotherapy field, in which their potential value for viability and cytotoxicity tests is largely accepted. Animal models play an important role in toxicity testing, but the pressure to adopt in vitro tests is growing since they present considerable economical advantages over in vivo tests. The use of animal models is limited to human metabolism studies, and there are... 

Pharmacokinetics is the study of kinetics of absorption, distribution, metabolism and excretion (ADME) of drugs and their corresponding pharmacologic, therapeutic, or toxic responses in man and animals" (American Pharmaceutical Association, 1972). Applications of pharmacokinetics studies include ... 

This area covers a wide range of applications from studies of biosynthesis, metabolism, and toxicity in living cells, to studies of metabolism in perfused whole organs and tissues, right through to imaging and metabolism studies of human beings and animals. 

A route-to-route extrapolation includes an examination of whether knowledge resulting from smdies involving one exposure route can be applied to another exposure route. It is only applicable for the evaluation of systemic effects, especially if the substance has a relatively long half-life for the evaluation of local effects, only results from toxicity studies performed with the route under consideration can be used. Not only the degree of absorption but also the metabolism should be considered. 

Once the IND application is accepted, three phases of human trials must be conducted. Phase I studies are typically performed on a small number of normal subjects, usually not more than 30 volunteers, generally by clinical pharmacologists. The purpose of the phase I smdy is to determine the metabolism of the drug in humans and a safe dosage range, and to search for any extremely common toxic effects that were not detected in the prior animal studies. 

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