Explain the role of biotransformation in toxicokinetics. • Describe how biotransformation facilitates elimination of toxicants. • Distinguish between Phase I and Phase II reactions. • Define bioactivation or toxication. | Biotransformation and Elimination of Toxicants Principles of Environmental Toxicology Instructor Gregory Möller . University of Idaho Principles of Environmental Toxicology Learning Objectives Explain the role of biotransformation in toxicokinetics. Describe how biotransformation facilitates elimination of toxicants. Distinguish between Phase I and Phase II reactions. Define bioactivation or toxication. 2 Principles of Environmental Toxicology Learning Objectives 2 Identify tissues and factors involved in biotransformation. Summarize the role of elimination in toxicokinetics. Describe processes occurring in the kidney liver and lung related to the elimination of toxicants. 3 Principles of Environmental Toxicology Metabolism Sum of biochemical rxns occurring to a molecule within the body. - Anabolism - build-up - Catabolism - break-down Occurs in the cytoplasm or at specific organelles within the cell. Storage affects the body s ability to biotransform and eliminate. - Bone lipid. 4 Principles of Environmental Toxicology Biotransformation Process that changes substances from hydrophobic to hydrophilic to aid in elimination grease to salt . - Hydrophilic molecules are less able to cross cellular membranes hence fluid filterable kidneys . - Major elimination routes are feces biliary and urine. - Biological half-life T allows comparison of rates of removal. Principles of Environmental Toxicology Biotransformation Reactions Grouped as Phase I functional group modification and Phase II conjugation . Goals - Produce water soluble metabolites. - Activate natural endogenous compounds for normal function. Some compounds undergo bioactivation. - The biotransformed metabolite is more toxic than the original compound. 6 5 1 Principles of Environmental Toxicology Results of Biotransformation Increase toxicity via a toxic metabolite. Decrease toxicity via metabolism of a toxic parent compound. No effect on toxicity. Present to metabolize endogenous compounds. Principles of .