講義課件參考5113w6lec

1、Bioaccumulation General conceptBioaccumulationCInfluxEffluxCompartmentBioaccumulation vs. toxicityLinking the two is challenging.BioaccumulationToxicityPredictionGeneral TermsBioavailability (1): fraction available for uptake.Bioaccessible (2): released fraction.Target siteSourceGut environment12Gen

2、eral TermsBioconcentration: uptake from water.Bioaccumulation: uptake from water and food.Biomagnification: increase in conc at higher levels.General TermsEquilibrium: between compartments.Steady-state: within one compartment, in and out equal.C1C2C1k1k2k1k2General TermsElimination rateDepuration ra

3、teGeneral TermsAssimilation.Absorption.Adsorption.assimilationabsorptionExposure pathwaysWaterFoodSediments1014TransportmodelChemical transport Passive diffusion: from high to low conc, no ligand required. Facilitated transport: from high to low conc, ligand requiredActive transportFrom low to high

4、conc, energy required.EndocytosisPinocytosis and phagocytosis.ToxicokineticsToxicokinetic(s): uptake, distribution, and metabolism (how it reaches the site of action).Toxicodynamic(s): interaction at the site of action (how they interact to produce the toxicity).1920(Toxic effect)Toxicokinetics21Pro

5、cess of uptake: organic Passive diffusion dominates the uptake of xenobiotic compounds.Controlled by Kow, but there is no optimal Kow which favors rapid uptake in all situation.Other factors are also important (e.g., composition and T of lipophilic barriers).22(control)23Metabolism - biotransformati

6、on Initial (Phase I) metabolism: oxidation, hydrolysis, hydration, reduction, lead to hydroxyl groups for subsequent conjugation (phase II reaction)Both reactions lead to polar metabolites and increase water solubility. In some cases, metabolism leads to the increase in toxicity (activation), mainly

7、 as a result of production of reactive metabolites (oxidation). 24Metal transformationBiomethylation, Methyl-Hg, biotransformationMetallothionein,0)lnCt = -kt + lnCo d(lnCt)/dt = -kt1/2 is the bio half life ln2/kLook at conc. difference of initial and later time to calculate k(efflux constant)Modeling eliminationTwo compartmental. Ct = C1exp(-k1t) + C2exp(-k2t) (k1,k20) lnCt = ln( + )Back stripping technique (C2 first, then C1).Predict fate of certain conditionModeling elimination More complicated model C1,t = C1,oexp(-k10t