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ASSESSMENT OF OCCUPATIONAL EXPOSURE DUE TO INTAKE OF RADIONUCLIDES. Biokinetic Models. Introduction. Biokinetic Models. First of all, the entrance of intake. Inhalation. Trough Skin. ICRP 66. No model but some ICRP’s…. Trough Wound. NCRP Report No. 156. Ingestion.
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ASSESSMENT OF OCCUPATIONAL EXPOSURE DUE TO INTAKE OF RADIONUCLIDES Biokinetic Models
Biokinetic Models First of all, the entrance of intake Inhalation Trough Skin ICRP 66 No model but some ICRP’s….. Trough Wound NCRP Report No. 156 Ingestion From ICRP 30 to ICRP 100 Excretion
Metabolic vs. Dosimetric models • Modeling - Mathematical descriptions used to describe the processes involved in physical movement of radionuclides in the body following intake, and the deposition of energy that constitutes exposure • Biokinetic modeling includes two types of models • Metabolic models • Dosimetric models
Biokinetic models C A B • Describe deposition and movement of radioactive material through the body • Depend on the intake mode, element, chemical form and physical form, and particle size (inhalation) • Tissues (including fluids) and organs, termed “Compartments” • Transfer routes • Transfer rates, • Excretion routes a Urine Intake b Faeces
Dosimetric models • Address the micro and macro distribution of the radionuclide within the tissues or organs where significant deposition may occur • Take into account the radiosensitivity of the deposition site tissues or organs - wT • Include consideration of wR, especially for alpha emitting radionuclides • Depend on the decay properties of the radionuclide - particle type and energy • Address contribution to other target organs
ICRP recommendations on biokinetics • ICRP Recommendations on: • Assessing radionuclide intake, and • Resulting doses, • From monitoring data. • For occupationally workers, a suite of models to represent radionuclide behaviour after entry by: • Inhalation or • Ingestion
Routes of intake, transfers and excretion Extrinsic removal Ingestion Inhalation Exhalation Respiratory Tract Model Lymph nodes Skin Direct absorption Gastro Intest. Tract model Liver Transfer compartment Sweat Subcutaneous tissue Wound Kidney Other organs Skin Urinary bladder Urine Faeces
Other routes of intake • For other routes of exposure, intakes are only likely to occur as a result of accidents • Almost no internationally accepted models for: • Entry through intact skin or • Wounds • Exception - HTO • Readily absorbed through intact skin. • Assumed to give additional tritium intake • Equal to 50% of the inhaled tritium
Tissue weighting factors, wT • wT introduced to calculate committed effective dose equivalent from individual tissue dose equivalents • Provided a common way of expressing external and internal doses • ICRP used wT in biokinetic models for dose equivalents to organs and tissues from: • Inhalation and • Ingestion • Earlier models didn’t fully describe biokinetics
ICRP defined tissue weighting factors ’90 recommendation 0.08 ’07 recommendation 0.04 0.12 0.04 0.04 0.04 0.12 Salivary gland 0.01 Brain 0.01
General model for radionuclides kinetics Respiratory tract model Gastrointestinal tract model Ingestion Inhalation Faecal excretion Transfer compartment a1 a2 a3 ai Tissue compartment 1 Tissue compartment 2 Tissue compartment 3 Tissue compartment i fu ff Excretion Urinary bladder Gastrointestinal tract model Urinary excretion Systemic faecal excretion
Description of biokinetic models Uptake factors and biological half time: • If the biological half time within compartment i , Ti, and a fraction aij of the activity in compartment i to be transferred to compartment j are given, the transfer rate lij from i to j is calculate by ln 2=0.693
Description of biokinetic models/2 Transfer rates • On the other hand, if activity is transferred from compartment i to compartments 1, … ,n with transfer rates li1, li2,… ……., linthen the overall biological half-time Ti in compartment i is calculated by • and the uptake factor aij to compartment j by
ICRP Biokinetic models • ICRP biokinetic models are to be used in normal situations, e.g. doses from routine monitoring measurements. • Evaluation of accident doses needs specific information: • Time and pattern of intake, • Physicochemical form of the radionuclides, • Individual characteristics (e.g. body mass).
Individual specific data Individual specific data may be obtained through special monitoring, i.e. repeated direct measurements of: • Whole body, • Specific sites and/or • Excretion measurements
Definitions • Aerodynamic diameter The diameter of the unit density sphere that has the same terminal settling velocity in air as the particle of interest • AMAD - Activity median aerodynamic diameter 50% of the activity (aerodynamically classified) in the aerosol is associated with particles of aerodynamic diameter (dae) greater than the AMAD. A log-normal distribution is usually assumed
Definitions /2 • Aerodynamic equivalent diameter
Definitions/3 • Thermodynamic diameter The diameter of a spherical particle that has the same diffusion coefficient in air as the particle of interest (practically equal to the geometric diameter) • AMTD - Activity median thermodynamic diameter 50% of the activity (thermodynamically classified) in the aerosol is associated with particles of thermodynamic diameter (dth) greater than the AMTD
Respiratory tract model Anterior nasal passage ET1 Posterior nasal passage Nasal part Extrathoracic Pharynx Oral part ET2 Larynx Thoracic BB Trachea Bronchial Main bronchi Bronchi Bronchioles Bronchiolar bb Alveolar - interstitial Al bb Bronchioles Terminal bronchioles Respiratory bronchioles Al Alveolar duct + alveoli Extrathoracic (ET) • ET1, anterior nasal passage, • ET2, posterior nasal and oral passages, the pharynx and larynx Thoracic • Bronchial (BB: trachea, and main bronchi), • Bronchiolar (bb: bronchioles) • Alveolar-interstitial (AI: the gas exchange region). Lymphatic tissue (for ET and TH) Average lung dose
Respiratory tract model/2 Epithelium tissue structure to show source & target • Geometrical model If cut in this section……
Respiratory tract model/3 • Target and source tissue in bronchial epithelium
Physiological parameters/2 Lung volume to estimate respiration rate
Respiratory tract model features Deposition of inhaled particulates: • Calculated for each RT region • Both inhalation and exhalation are considered, as a function of: • Particle size, • Breathing parameters and/or • Work load, • Assumed independent of chemical form
Respiratory tract model features/2 Default deposition parameters: • Age dependent • Range of particle sizes: • 0.6 nm activity median thermodynamic diameter (AMTD) to • 100 m activity median aerodynamic diameter (AMAD). • For occupationally exposed individuals, based on average daily patterns of activity
Respiratory tract model features/3 Inhalation dose coefficients: • AMAD of 5 m - Now considered most likely for the workplace • AMAD of 1 m - Previous workplace default value (ICRP 30) • AMAD of 1 m - Default for the public
Inhalation - Deposition model • Evaluates fractional deposition in each region • Aerosol sizes of practical interest - 0.6 nm to 100 μm • ET regions • Measured deposition efficiencies related to: • Particle size • Airflow • Scaled by anatomical dimensions
Inhalation - Deposition model/2 • Thoracic airways - theoretical model for gas transport and particle deposition is used • Calculates particle deposition in BB, bb, and AI regions • Quantifies effects of lung size & breathing rate • Regions treated as a series of filters • Efficiency is evaluated considering both: • Aerodynamic processes (gravitational settling, inertial impaction) • Thermodynamic processes (diffusion)
Inhalation - Deposition model/3 • Regional deposition fractions calculated for lognormal particle size distributions • Geometric standard deviations (g) - a function of the median particle diameter • From 1.0 at 0.6 nm to 2.5 above ~ 1 μm • Deposition parameters are given for three reference levels of exertion for workers • Sitting • Light exercise • Heavy exercise
Clearance from the respiratory tract Clearance from the respiratory tract is treated as two competing processes: • Particle transport (by mucociliary clearance or translocation to lymph nodes), and • Absorption to blood
Particle transport • Treated as a function of deposition site • Independent of particle size and material • Modeled using several regional compartments with different clearance half-times, e.g. • AI region given 3 compartments, • Clearing to bb with biological half-lives of about 35, 700 and 7000 days.
Full compartment model for Clearance Whole Compartment Model
Simultaneous differential equation for Clearance model based on whole compartment model
Particle transport/1 Clearance Deposition
Particle transport/2 • Similarly, bb and BB have fast and slow clearance compartments • Clearance from the AI region also involves transfer to lymphatic tissue • For bb, BB and ET; • Compartments to represent material sequestered in tissue and transported to lymphatic tissue
Absorption into blood • Depends on the physicochemical form of the radionuclide • Independent of deposition site - Except ET1 (no absorption is assumed). • Changes in dissolution and absorption with time are allowed
Absorption into blood/2 Deposition Particles in initial state Particles in transformed state spt st sp Body fluids
Absorption into blood/3 • Material specific dissolution rates preferred • Use default absorption parameters if no specific information is available: F (fast) -100% absorbed with a half-time of 10min M (moderate) -90% absorbed with a half-time of 140days S (slow) -99.9% absorbed with a half-time of 7000days • Broadly correspond to lung classes D (days), W (weeks) and Y (years), but lung classes referred to overall lung clearance rates
Absorption rates • Expressed as: • Approximate biological half-lives, and • Corresponding amounts of material deposited in each region that reach body fluids • All the material deposited in ET1 is removed by extrinsic means, such as nose blows
Absorption rates/2 • In other regions, most material not absorbed is cleared to the gastrointestinal tract by particle transport. • Small amounts transferred to lymph nodes are absorbed into body fluids at the same rate as in the respiratory tract.
Deposition of gases and vapours • Respiratory tract deposition is material specific • Inhaled gas molecules contact airway surfaces • Return to the air unless they dissolve in, or react with, the surface lining • Fraction of an inhaled gas or vapor deposited depends on its solubility and reactivity • Regional deposition of a gas or vapor obtained from in-vivo experimental studies