ASSESSMENT OF OCCUPATIONAL EXPOSURE DUE TO INTAKE OF RADIONUCLIDES

1. ASSESSMENT OF OCCUPATIONAL EXPOSURE DUE TO INTAKE OF RADIONUCLIDES Biokinetic Models

2. Biokinetic Models – Unit Objectives The objective of this unit is to provide an overview of principles for development and use of biokinetic and dosimetric models for internal dose assessment. The unit describes intake, transfer and excretion, and outlines the features of the respiratory tract and gastrointestinal tract models. At the completion of this unit, the student should understand the principles involved in development and use of biokinetic models, as well as the need for individual specific models when intakes approach relevant limits.

3. Biokinetic Models - Unit Outline • Introduction • Inhalation

4. Introduction

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. ICRP defined tissue weighting factors

13. 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

14. 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

15. 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

16. 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).

17. 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

18. Inhalation

19. 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 that the AMAD. A log-normal distribution is usually assumed

20. Definitions /2 • Aerodynamic equivalent diameter

21. Figures of aerosols

22. Lognormal Distribution

23. 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 that the AMTD

24. 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)

25. Respiratory tract model/2 • Geometrical model

26. Respiratory tract model/3 • Target and source tissue in bronchial epithelium

27. Masses of respiratory tract target tissues Target tissue masses have been specified for 6 age classes. Adult tissue masses are:

28. Physiological parameters For Reference Man - 176 cm, 73 kg

29. Physiological parameters/2

30. Physiological parameters/3

31. What has changed? • ICRP Pub. 30 treats only average lung dose • ICRP Publication 66: • Calculates doses to specific RT tissues, and • Includes differences in radiosensitivity • RT is represented by five regions • Extrathoracic (ET) airways are divided into ET1, and ET2 • Thoracic regions are bronchial (BB), bronchiolar (bb) and alveolar–interstitial (AI), the gas exchange region. • Lymphatic tissue is associated with the extrathoracic and thoracic respectively (LNET and LNTH).

32. 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

33. 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

34. 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

35. 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

36. 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)

37. 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

38. Respiratory tract - Deposition

39. Respiratory tract - Clearance

40. 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

41. 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.

42. Particle transport/1

43. 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

44. 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

45. Absorption into blood/2 Deposition Particles in initial state Particles in transformed state spt st sp Body fluids

46. Alternative mode of indication of absorption

47. Absorption into blood/3 • Material specific dissolution rates preferred • Use default absorption parameters if no specific information is available: F (fast) M (moderate) S (slow). • Broadly correspond to lung classes D (days), W (weeks) and Y (years), but lung classes referred to overall lung clearance rates

48. 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

49. 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.

50. Absorption rates - Default values