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Lecture 7

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BIOL 354
Bruce Greenberg

BIOL354 – Environmental Toxicology I Spring 2012 Lecture 7 – Toxicokinetics - Review: K owis octanol-water partition coefficient, vessel w/ octanol & water + sample -> centrifuge -> [] Toxicity Pathways (Exposure -> Toxicity) - Bioaccumulation: Net accumulation per organism from all sources. Exposure route (Air, Water, Soil/sediments, and Food) is specie specific. o Bioaccumulation Phase: Max [Toxicant] per tissue increase until a steady state plateau. o Depurination Phase: [Toxicant] per tissue decreases through depuration of DNA, sharply at first, slows down as the [Toxicant] decreases. - Bioconcentration: Net accumulation per organism from water only. (Aquatic toxicology) o ( ) ⁄ o Fish exposed to chemical (constant over time), monitor chemical in tissue until equilibrium o Lipophilicity/owof the contaminant -> Bioconcentration @ adipose & liver tissues  Chemicals: Hydrophilic/Lipophobic, Hydrophobic/Lipophilic, Amphipathic (both)  Usually the major factor that determines BCF  High Kow Partitions preferentially to lipids (e.g. Dioxins, PCBs, MeHg -> High BCF until bioavailability limited by solubility of the compound)  Low Kow Partitions preferentially to water (e.g. Metals -> Low BCF) - Biomagnification o [Toxicant] increases as trophic level increases o Toxicant must be able to bioconcentrate & persists within in tissues of the prey - Toxicokinetics (ADBE): Relationship b/w systemic exposure of [Toxicant] in an organism & its toxicity o Absorption/Uptake -> Distribution (systemic) -> Biotransformation -> Excretion/Elimination Absorption/Uptake - Mechanisms for Uptake (4): Gills (Low Kow, Guts (High Kow, Lungs (Low Kow, & Skin/Mucus membrane o Route of uptake depends on the organism, the contaminant & the external environment o The chemical/toxicant must interact with tissues/cells - Pathways after Uptake (3): o Pathway & Speed of transportation after uptake depends on the chemical’s hydrophilicity, lipophilicity ow ) & molecular size 1) Lipid: Passive diffusion across the phospholipid bilayer 2) Aqueous: Passive or active transport via integral membrane transport proteins i. Channel proteins: Non-specific (e.g. Calcium Channels) [Passive] 1. Physically blocked by ligands that are similar in radii 2. Cd permeability low, few enters, rest blocks & -Ca uptake significantly ii. Carrier proteins: Specific -> conformational change (e.g. Porin -> Sucrose) [Active] 3) Endocytotic: Active ingestion of large polar molecules (*Ingested Contaminants) i. Invagination of plasma membrane -> formation of intracellular vesicles Distribution via circulatory system - Lipophilic (High ow) associates with blood cells ostHydrophilic (LoowK ) dissolved in plasma/cytoplasm - Physiochemical properties of toxicant determines 1 tissue they interact with => destination o Liver, Kidney, Adipose tissue & Rarely Bones o Vertebrates: All blood from GI go to the hepatic portal system of the liver 1 for filtration  If owis high (Lipophilic), toxicant biotransformed/metabolized by hepatocytes to increase solubility (2 phases), secreted into the intestines for excretion BIOL354 – Environmental Toxicology I
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