assessment of occupational exposure due to intake of radionuclides

1

International Atomic Energy Agency

ASSESSMENT OF OCCUPATIONAL EXPOSURE DUE TO INTAKE OF

RADIONUCLIDES

Biokinetic Models

2 International Atomic Energy Agency

Introduction


Trough Wound

Trough SkinInhalation

Ingestion

From ICRP 30 to ICRP 100

ICRP 66

NCRP Report No. 156

No model but some ICRP’s…..

Biokinetic Models First of all, the entrance of intake

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

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 BIntake

C

Urine

Faeces

a

b


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

Transfercompartment

Respiratory Tract Model

Liver

Kidney

Urinary bladderOtherorgans

Subcutaneoustissue

LymphnodesS

kin

Ski

n

GastroIntest.Tract model

UrineUrine FaecesFaeces

IngestionIngestionExhalationExhalationInhalationInhalation

Extrinsic removalExtrinsic removal

WoundWound

SweatSweat

Direct absorptionDirect absorption


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


Tissue or organ Tissue weighting factor (wT)

Gonads 0.20 Bone marrow (red) 0.12 Colon (c) 0.12 Lung (d) 0.12 Stomach 0.12 Bladder 0.05 Breast 0.05 Liver 0.05 Oesophagus 0.05 Thyroid 0.05 Skin 0.01 Bone surface 0.01 Remainder (e) 0.05

ICRP defined tissue weighting factors

’90 recommendation

’07 recommendation

0.08

0.040.120.040.040.04

0.12

Salivary gland

Brain0.01

0.01


InhalationRespiratory

tractmodel

Gastrointestinaltract

model

Ingestion

Faecal excretion

Transfer compartment

Tissuecompartment

1

Tissuecompartment

2

Tissuecompartment

3

Tissuecompartment

i

a1 a2 a3 ai

Excretion

Urinarybladder

Urinary excretion Systemic faecal excretion

Gastrointestinaltract model

fu ff

General model for radionuclides kinetics


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 ij from i to j is calculate by

i

ijij T

a

693.0

ln 2=0.693


Description of biokinetic models/2

• On the other hand, if activity is transferred from compartment i to compartments 1, … ,n with transfer rates li1, li2,… ……., lin then

the overall biological half-time Ti

in compartment i is calculated by

• and the uptake factor aij to

compartment j by

n

kik

iT

1

2ln

n

kik

ijija

1

Transfer rates


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


Inhalation


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


Figures of aerosols


Lognormal Distribution


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

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)

Extrathoracic

ThoracicBB

Bronchial

ET2

ET1

Larynx

Trachea

Oral partNasal part

Main bronchi

Bronchi

Bronchioles bb

Al

Anterior nasal passage

Posterior nasal passage

Pharynx

bb

Al

Alveolar duct + alveoli

Respiratory bronchioles

Terminal bronchiolesBronchioles

Bronchiolar

Alveolar -interstitial

Average lung dose


Respiratory tract model/2

• Geometrical model

If cut in this section……

Epithelium tissue structure to show source & target


Respiratory tract model/3

• Target and source tissue in bronchial epithelium


Physiological parameters/2Lung volume to estimate respiration rate


Physiological parameters/3

Volumes related to light work Activity Air breathed during 1 day

(m3) Sleep (8 h) 3.6

Occupational (5.5h light exercise + 2.5h rest sitting)

9.6

Non-occupational (4h rest + 3h light exercise+1h heavy

exercise)

9.7

Total 23

Ventilation rates

Activity Tidal

Volume (L)

Ventilation rate (m3/h)

Respiration frequency

(min-1) Sleep 0.625 0.45 12

Rest (sitting awake) 0.75 0.54 12 Light exercise 1.25 1.5 20 Heavy exercise 1.923 3 26


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


Region Deposition (%) of 5 m AMAD

ET1 34

ET2 40

BB 1.8

bb 1.1

AI 5.3

Total 82

Respiratory tract - Deposition


Respiratory tract - Clearance


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

Particles in initial

state

Particles in transformed

state

Body fluids

Deposition

spt

spst


Alternative mode of indication of absorption

st

srrpt

srrsp

ss

ssfs

ssfss

1


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.


Absorption rates - Default values

Model parameters

(d-1) F (Fast) M (moderate) S (slow)

sp 100 10 0.1

spt 0 90 100

st - 0.005 0.0001


Absorption rates – Alternative presentation

Model parameters F (Fast) M (moderate) S (slow)

fr 1 0.1 0.001

Sr (d-1) 100 100 100

Ss (d-1) - 0.005 0.0001


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


Solubility/Reactivity (SR) classes Description Examples Class SR-0 Insoluble and non-reactive:

negligible deposition in the respiratory tract.

41Ar, 85Kr, 133Xe

Class SR-1 Soluble or reactive: deposition may occur throughout the respiratory tract.

Tritium gas, 14CO, 131I vapour, 195Hg vapour

Class SR-2 Highly soluble or reactive: total deposition in the extrathoracic airways (ET2). For the purpose of calculation they are treated as they were injected directly into the blood.

3H in organic compounds and tritiated water

SR0

Insoluble and nonreactive

Soluble and reactive

Deposition ET : 100% Instantaneous transfer to blood : type "V"

SR1

SR2

Rn Xe N2 H2 He SF6

Soluble or reactive gas

Reactivity ->

Solubility

->

Deposition : ET1 : 10% ET2 : 20 % BB : 10 % bb : 20 % AI : 40 %

Transfer to blood : Type "V' or "F"

CO2 O3 HF HTO SO2

Elemental I CO Hg vapour Ni carbonyl


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 modelCorrespondence between source regions and

compartments in the clearance model.

Target regions Source regions Source Compartments in clearance

model ET1-sur ET1 ET2-sur ET2+TET2 ET2-seq ETseq+TETseq LN-ET LNET+TLNET BB-gel BB1+TBB1 BB-sol BB2+TBB2 BB-seq BBseq+TBBseq bb-gel bb1+Tbb1 bb-sol bb2+Tbb2 bb-seq bbseq+Tbbseq AI AI1+AI2+AI3+TAI1+TAI2+TAI3 LN-TH LNTH+TLNTH

TargettissuesET1-basET2-basLN-ETBB-basBB-secbb-secAILN-TH


BB

bb

Al

ET2

0.1 1 10 100AMAD (m)

100

10

1

0.1

0.01

Reg

ion

al d

epo

siti

on

(%

)

ET1

Influence of particle size on deposition in various regions of the respiratory tract


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


Adult male

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

Type M

Type S

0.1 1 10 100AMAD (m)

10-3

10-4

10-5

10-6

Co

mm

itte

d e

ffe

cti

ve

do

se

pe

r u

nit

in

tak

e (

Sv

/Bq

)

Influence of AMAD on the committed effective dose

239Pu


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)

assessment of occupational exposure due to intake of radionuclides

Documents