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ASSESSMENT OF OCCUPATIONAL EXPOSURE DUE TO INTAKE OF RADIONUCLIDES. Biokinetic Models. Biokinetic Models – Unit Objectives.

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biokinetic models unit objectives
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.

biokinetic models unit outline
Biokinetic Models - Unit Outline
  • Introduction
  • Inhalation
metabolic vs dosimetric models
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
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
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 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
slide9

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
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 w t
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
general model for radionuclides kinetics
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
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
description of biokinetic models 2
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
  • 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

Individual specific data may be obtained through special monitoring, i.e. repeated direct measurements of:

  • Whole body,
  • Specific sites and/or
  • Excretion measurements
definitions
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

definitions 2
Definitions /2
  • Aerodynamic equivalent diameter
definitions 3
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

respiratory tract model
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)

respiratory tract model 2
Respiratory tract model/2
  • Geometrical model
respiratory tract model 3
Respiratory tract model/3
  • Target and source tissue in bronchial epithelium
masses of respiratory tract target tissues
Masses of respiratory tract target tissues

Target tissue masses have been specified for 6 age classes. Adult tissue masses are:

physiological parameters
Physiological parameters

For Reference Man - 176 cm, 73 kg

what has changed
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).
respiratory tract model features
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
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
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
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
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
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

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
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.
particle transport 2
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
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
Absorption into blood/2

Deposition

Particles in initial state

Particles in transformed state

spt

st

sp

Body fluids

absorption into blood 3
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
absorption 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
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.
absorption rates references for material specific values
Absorption rates – References for material specific values
  • Material specific dissolution rates
    • Uranium : NRPB-W22
    • Plutonium: NRPB-W52
    • Caesium : NRPB-W51
    • Thorium : NRPB-W57
  • All available at http://www.hpa.org.uk/radiation/publications/w_series_reports/index.htm
deposition of gases and vapours
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
deposition of gases and vapours1
Deposition of gases and vapours
  • Guidance on the deposition and clearance of gases and vapours similar to particulates
  • Default SR classes and absorption types
    • Type F
    • Type V, very rapid absorption

recommended for elements for which inhalation of gas or vapor form is important

  • Only low mass concentrations of gases and vapours are considered.
dosimetric model
Correspondence between source regions and compartments in the clearance model.

Target regions

Dosimetric model

Source regions

dosimetric model 2
Evaluation of AF(T<-S) for the different regions.

For g radiations the AF calculated by Cristy and Eckerman are used.

For alpha , beta the functions of AF(x) in function of energy emission are fitted by means of exponential functions using 9 to 12 parameters.

All these parameters are reported in Annex H of ICRP 66.

Dosimetric model/2
dosimetric model 21
Dosimetric model/2
  • Tissue and cell at risk and dose
  • In the table are reported the target cells the mucous thickness the depth of the target organ and the assigned fraction related to sensitivity
workplace specific assessments
Workplace specific assessments
  • After accidental exposures, use individual and situation specific parameters to calculate equivalent doses and effective dose
  • In routine situations specific circumstances of exposure rather than using default parameters.
  • Respiratory tract model uses an AMAD of 5 m as a default particle size
workplace specific assessments 2
Workplace specific assessments/2
  • Deposition of airborne particles is subject to:
    • Sedimentation
    • Impaction
    • Diffusion
  • Deposition and inhalation dose coefficients depend on aerosol parameters, e.g. AMAD
  • Ingestion dose coefficients depend use of an appropriate f1 value
effect of particle size on aerosol deposition
Effect of particle size on aerosol deposition
  • Aerosol deposition of occupational concern is highest in the AI region of the thorax
  • AI deposition decreases with increasing particle size
  • Extent of deposition in each region, as well as the chemical form inhaled, has an appreciable influence on the effective dose
influence of particle size on deposition in various regions of the respiratory tract
Influence of particle size on deposition in various regions of the respiratory tract

100

ET2

ET1

10

Al

bb

Regional deposition (%)

1

BB

0.1

0.01

0.1

1

10

100

AMAD (m)

effect of particle size on aerosol deposition1
Effect of particle size on aerosol deposition
  • Committed effective dose for Type M and S 239Pu compounds decreases with increasing AMAD
  • Reflects decreasing deposition in the AI region and BB and bb with increasing AMAD
  • In this case, the assumption of Type M characteristics is more restrictive than Type S for the calculation of effective dose
  • Other aerosol characteristics have slight influence on the committed effective dose
influence of amad on the committed effective dose
Influence of AMAD on the committed effective dose

10-3

Adult male

Light work (5.5 h) + sitting (2.5 h)

10-4

Type M

Committed effective dose per unit intake (Sv/Bq)

Type S

10-5

10-6

0.1

1

10

100

AMAD (m)

239Pu

application of icrp 66
Application of ICRP 66
  • For the correct application of ICRP 66, two documents are available:
    • ICRP Guidance Document 3 : for choice of default parameter values
    • ICRP 71 : for the application of the model to the general population (age specific)
references
References

FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS, INTERNATIONAL ATOMIC ENERGY AGENCY, INTERNATIONAL LABOUR ORGANISATION, OECD NUCLEAR ENERGY AGENCY, PAN AMERICAN HEALTH ORGANIZATION, WORLD HEALTH ORGANIZATION, International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources, Safety Series No. 115, IAEA, Vienna (1996).

INTERNATIONAL ATOMIC ENERGY AGENCY, Occupational Radiation Protection, Safety Guide No. RS-G-1.1, ISBN 92-0-102299-9 (1999).

INTERNATIONAL ATOMIC ENERGY AGENCY, Assessment of Occupational Exposure Due to Intakes of Radionuclides, Safety Guide No. RS-G-1.2, ISBN 92-0-101999-8 (1999).

INTERNATIONAL ATOMIC ENERGY AGENCY, Indirect Methods for Assessing Intakes of Radionuclides Causing Occupational Exposure, Safety Guide, Safety Reports Series No. 18, ISBN 92-0-100600-4 (2002).

INTERNATIONAL ATOMIC ENERGY AGENCY, Intercomparison and Biokinetic Model Validation of Radionuclide Intake Assessment, Results of a Co-ordinated Research Programme, 1996-1998, TECDOC 1071, IAEA, Vienna (1999).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Report of the Task Group on Reference Man, ICRP Publication 23, Pergamon Press, Oxford (1975).

references1
References

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Limits for Intakes of Radionuclides by Workers, ICRP Publication 30, Part 1, Annals of the ICRP 2(3/4), Pergamon Press, Oxford (1979).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Limits for Intakes of Radionuclides by Workers, ICRP Publication 30, Part 2, Annals of the ICRP 4(3/4), Pergamon Press, Oxford (1980).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Limits for Intakes of Radionuclides by Workers, ICRP Publication 30, Part 3 (including addendum to Parts 1 and 2), Annals of the ICRP 6(2/3), Pergamon Press, Oxford (1981).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Individual Monitoring for Intakes of Radionuclides by Workers: Design and Interpretation, ICRP Publication 54, Annals of the ICRP 19(1-3), Pergamon Press, Oxford (1988).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Age-dependent Doses to Members of the Public from Intake of Radionuclides: Part 1, ICRP Publication 56, Annals of the ICRP, 20(2), Pergamon Press, Oxford (1989).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Human Respiratory Tract Model for Radiological Protection, ICRP Publication 66, Annals of the ICRP 24(1-3), Elsevier Science Ltd., Oxford (1994).

references2
References

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Age-dependent Doses to Members of the Public from Intake of Radionuclides: Part 2, Ingestion Dose Coefficients, ICRP Publication 67, Annals of the ICRP 23(3/4), Elsevier Science Ltd., Oxford (1993).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Dose Coefficients for Intakes of Radionuclides by Workers, ICRP Publication 68. Annals of the ICRP 24(4), Elsevier Science Ltd., Oxford (1994).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Age-dependent Doses to Members of the Public from Intake of Radionuclides: Part 3, Ingestion Dose Coefficients, ICRP Publication 69, Annals of the ICRP 25(1), Elsevier Science Ltd., Oxford (1995).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Age-dependent Doses to Members of the Public from Intake of Radionuclides: Part 4, Inhalation Dose Coefficients, ICRP Publication 71, Annals of the ICRP 25(34), Elsevier Science Ltd., Oxford (1995).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Age-dependent Doses to Members of the Public from Intake of Radionuclides: Part 5, Compilation of Ingestion and Inhalation Dose Coefficients, ICRP Publication 72, Annals of the ICRP 26 (1), Pergammon Press, Oxford (1996).

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Individual Monitoring for Internal Exposure of Workers: Replacement of ICRP Publication 54, ICRP Publication 78, Annals of the ICRP 27(3-4), Pergamon Press, Oxford (1997).

references3
References

INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Guide for the Practical Application of the ICRP Human Respiratory Tract Model, ICRP Supporting Guidance 3 (in press).

NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS, Deposition, Retention and Dosimetry of Inhaled Radioactive Substances, NCRP Report No.125, NCRP, Bethesda (1997).

NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS, Evaluating the Reliability of Biokinetic and Dosimetric Models and Parameters Used to Assess Individual Doses for Risk Assessment Purposes, NCRP Commentary No.15, NCRP, Bethesda (1998).