1

Internal Dosimetryfrom Radionuclides Intakes

Christian Hurtgen

6 June 2005

Content I

• Dose (some definitions)• Biokinetics (Compartment model)• HRTM• HAT• Wound model• Monitoring Internal contamination• From measurements to Intake

2

Content II

• General Guidelines for the Assessment of Internal Dose from monitoring Data. (project IDEAS)

• ExamplesAcute Inhalation of 60CoAcute Inhalation of fission products: 90SrAcute Inhalation of Plutonium

Absorbed Dose

• The physical dose quantity given by

• dε = mean energy imparted by ionisation radiation to the matter in a volume element

• dm = the mass of the matter in this volume element

• SI unit is joule per kilogram (J kg-1) = gray (Gy)

mddD ε

=

3

EquivalentRadiation weighted Dose ( HT,R )

• Equivalent Radiation weighted Dose in tissue or organ T due to radiation R

• DT,R = the average absorbed dose from radiation R in tissue T

• wR = the radiation weighting factor based on the quality of the radiation emitted by the source.

• SI unit = J kg-1 = sievert (Sv)

RTRRT DwH ,, •=

Radiation weighting factors ( wR )ICRP 60

20Alpha particles, fission fragments, heavy nuclei

5 2Protons5 - 20

Neutrons, energy from< 10 keV to > 20 MeV

1Electrons, Beta1Photons, gamma

Radiationweighting factor (wR)

Type and energy range

4

Total equivalent Radiation weighted Dose (HT)

• The sum of HT,R over all radiation types

∑=R

RTT HH ,

Effective Dose ( E )

• The sum of the weighted radiation weightedequivalent doses in all tissues and organs of the body.

• wT = tissue weighting factor• HT = equivalent radiation weighted dose for tissue

or organ T

∑ •=T

TT HwE

5

Tissue weighting factor

0.05 0.10Remainder

0.01Skin, Bone surface, Brain, Kidney, Salivary glands

0.05Bladder, Breast, Liver, Oesophagus, Thyroid

0.12Bone marrow (red), Colon, Lung, Stomach, Breast

0.20 0.05Gonads

Tissue weighting factor ( wT )Organ or Tissue (T)

Committed equivalent dose ( HT(τ) )

• The time integral of the equivalent dose rate in a particular tissue or organ that will be received by an individual following intake of radioactive material into the body, where t is the integration time in years following the intake.

• For adults, the integration time is 50 year

∫+

=τ

τ 0

0

)()(t

t TT dttHH

6

Committed equivalent dose (HT(50))

• US(50) = number of nuclear transformations (Bq s) in 50 y in source S following acute intake

• = Specific Effective Energy, equivalent dose in T per transformation in S expressed as (Sv(Bq s)-1)

∑ ←•=S

ST STSEEUH )()50()50(

)( STSEE ←

Specific Effective Energy

• YR = yield of radiation R per nuclear transformation • ER = energy of radiation R (J)• wR = radiation weighting factor for radiation R• = absorbed fraction in T per transformation in

S for radiation R• mT = mass of the target tissue, T (kg)

∑ ←=←

R T

RRRR

mSTAFwEYSTSEE )()(

RSTAF )( ←

7

• The sum of the product of the committed equivalent doses in organs or tissues and the appropriate organ or tissues weighing factor ( wT) where τ is the integration time in time following the intake.

•

• For adults, the integration time is 50 year

Committed Effective Dose

∑ •=T

TT HwE )()( ττ

Dose coefficient

• hT(τ) = committed tissue equivalent dose per unit acute intake

• e(τ) = committed effective dose per unit acute intake

• Where τ is the time period in years over which the dose is calculated

• Example : 239Pu Type S, e(50) = 8.3 10-6 Sv Bq-1

8

Dose limits

• The occupational exposure of any worker shall be so controlled that the following limits be not exceeded:

an effective dose of 20 mSv per year averaged over five consecutive years;an effective dose of 50 mSv in any single year;an equivalent dose to the lens of the eye of 150 mSv in a year;an equivalent dose to the extremities (hands and feet) or the skin of 500 mSv in a year.

BiokineticsIntroduction to compartment models

9

Biokinetic behaviour

• Route of intake (ingestion, inhalation, injection …)• Accumulation of activity in specific organs• Retention of radionuclides in those organs• Transport of radionuclides between organs• Removal, by excretion and radioactive decay, of

activity from the body

Transport out of a compartment

LIVER

A(t)

teAtA α−= 0)(

10

Uptake

• Material which is absorbed from the respiratory tract or the gastro-intestinal tract first enter the blood or lymph (body fluids) and is then available for uptake by organs.

Compartment model for uptake

• From the transfer compartment with half-time 6 hours (for most radionuclides)

• 30 % to Organ 1, 70 % to Organ 2

)(941.1

)(832.0

)(25.0

)2ln(73

12

11

121

2

1

−

−

−

=

=

=+

=

d

d

d

α

α

αα

αα

11

Compartment model for uptake

TRANSFER COMPARTMENT

ORGAN1 ORGAN2

α1= 0.832 d-1

α2 = 1.941 d-1

From respiratory tract

30% 70%

Compartment model for retention

TRANSFER COMPARTMENT

From respiratory tract

ORGAN1 ORGAN2 ORGANn

x1% x2% xn%

α1 α2 α

αΕ

n

xE%

DIRECT EXCRETION

β β β 1 2 n

teA

tAtR α−==0

)()(

12

Model for caesium retention

TRANSFER COMPARTMENT

From gastro-intestinaltract

α1 α2

β2= (ln2)/110 d−1

β1 = (ln2)/2 d−1

EXCRETION

10% 90%

WHOLE BODY 1

WHOLE BODY 2

Model for transport between organs

AL(t) AGI(t)

t t

A(t)A(t)

αL αGI

A0 A0

13

Model for excretion

TRANSFER COMPARTMENT

From respiratory tract

ORGAN1 ORGAN2 ORGANn

x1% x2% xn%

α1 α2 α

αΕ

n

xE%

ACCUMULATED EXCRETION

β β β 1 2 n

Model for an excretion function

TRANSFER COMPARTMENT

From gastro-intestinal tract

αn= kan/λn

α1= ka1/λ1

α2= ka2/λ2 αIR

ACCUMULATED EXCRETION

λ λ λ 1 2 n INFINITE RETENTION

U1 U2 Un

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Multiple path compartment model

A2

A1 A4A3ka

kb

kc

Recycling compartment model

A1 A2

15

Human Respiratory Tract Model

ICRP Publication 66

Human Respiratory Tract

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Human Respiratory Tract

EXTRATHORACIC

BRONCHIAL

BRONCHIOLAR

ALVEOLAR INTERSTITIAL

ET1

ET2

BB

bbAI

Posterior noseNasal partOral part

Larynx

Trachea

Main bronchi

Bronchi

Bronchioles

RespiratoryAlveolar ductsAlveoli

Pharynx

Anterior nose

THORACIC

Particle transport in the human respiratory tract

17

Deposition (I)

• Deposition model evaluates fractional deposition of the aerosol in each region for all particle sizes of practical interest ( 0.0006 – 100 µm)

• Aerosols:Activity Median Aerodynamic Diameter = AMAD

Lognormal particle size distributionGeometric standard deviation ( σg ) function of the median particle size

⋅ = 1.0 at 0.0006 µm⋅ = 2.5 at 1 µm and above

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Deposition (II)

• Exposure : Occupational or environmental• Male or Female, adult or child or infant or baby• Activities

SleepSittingLight exercisesHeavy exercises

• Nose and/or mouth breather

Deposition (III)

• Standard worker (ventilation rate = 1.200 m³/h)Sleep 0 %Sitting 31.3 %Light exercises 68.8 %Heavy exercises 0 %

• Heavy worker (ventilation rate = 1.688 m³/h)Sleep 0 %Sitting 0 %Light exercises 87.5 %Heavy exercises 12.5 %

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Deposition of inhaled aerosols

82.051.2Total

5.310.7AI

1.101.65bb

1.781.24BB

39.921.1ET2

33.916.5ET1

AMAD 5 µmAMAD 1 µmRegion

Regional deposition % in function of AMAD

20

Compartmental representation of absorption to blood (I)

Compartmental representation of absorption to blood (II)

21

Absorption rate

• If known used absorption rate for specific coumpound

• Default values for three materialType F (fast)Type M (moderate)Type S (slow)

Type F (fast)

• 100 % absorbed with a half-time of 10 minutes.• There is rapid absorption of almost all material

deposited in BB, bb, and AI, • and 50% of material deposited in ET2 is clear to

the GI tract by particle transport.

• Example: all compounds of Cs and I

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Type M (moderate)

• 10% aborbed with a half-life of 10 minutes and 90% with a half-life of 140 d.

• There is rapid absorption of about 10% of the deposit in BB and bb; and 5% of material deposited in ET2.

• About 70% of the deposit in AI eventually reaches the body fluids.

• Example: all compounds of Ra and Am

Type S (slow)

• 0.1% absorbed with a half-life of 10 minutes and 99.9% with a half-life of 7000 d.

• There is little absorption from ET, BB, or bb;• about 10% of the deposit in AI eventually reaches

the body fluids.

• Examples: all insoluble compounds of U and Pu

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Compartmental representation of absorption to blood (II)

Default absorption parameters

0.00010.005-St

100900Spt

0.110100Sp

Type SType MType FModel parameters (d-1)

24

Absorption parametersfor gas and vapour

• Absorptions Type F or V (Very rapid absorption)• Class SR-0: Insoluble and non-reactive

negligible deposition41Ar, 85Kr, 133Xe

• Class SR-1: Soluble or reactivedeposition may occur

Tritium (g), 14CO, 131I vapour, 195Hg vapour

• Class SR-2: Highly soluble or reactivecomplete deposition in ET2for calculation = directly injected in blood

3H organic compounds and tritiated water

Full compartmental representation of absorption to blood

25

Gastro-Intestinal Tract Model

ICRP Publication 30

26

GI Tract (ICRP 30)

GI Tract compartments

• StomachMean residence time = 1 hour

• Small IntestineMean residence time = 4 hoursAbsorption to bloodFraction of material reaching body fluidsSI is alkaline

• Upper large intestineMean residence time = 13 hours

• Lower large intestineMean residence time = 24 hours

SIB

Bfλλ

λ+

=1

27

Human Alimentary Tract Model

ICRP Publication ?? 2005

HATHuman Alimentary Tract

28

Some biokinetic models

29

Biokinetic model for the ActinidesICRP 67

Biokinetic model forAlkaline earth, Pb & U

ICRP 67

30

Biokinetic model for IronICRP 69

31

Biokinetic model for IodineICRP 30

Wound model (I)

Local and regional diffusion

Deposited in WoundQ

Non-metabolizedstay in situ

Blood

Rapid transferT = 0.01 d

Soft tissue

LymphNodes

Slow transfer

Q1 Q2 Q3

32

Wound model (II)

• Q1 = metabolically inert, it remains where it was deposited

• Q2 = enters the bloodstream quickly via the vascular breaches

• Q3 = diffuse slowly in the soft tissue (conjunctive tissue, muscles ..) from where it is finally transferred to the blood, either directly or indirectly via the lymph nodes.

33

Monitoring Internal contamination

34

Routes of entry

Ingestion Inhalation Wound Skin Absorption

Respiratory tract Site of Entry

ScabExhalation

GI Tract

Pulmonary Lymph nodes

Regional Lymph nodes

Transfer Compartment

Bile Liver Bone Kidneys Skin Others

Sweat HairUrineFaeces

Gastro Intestinal

Tract

Monitoring type (I)

• Air samplingStatic air sampler

♣localisePortable air samplerPersonal air sampler PAS

♣Low sampling rate♣Trigger biological

monitoring

35

Monitoring type (II)

• Direct measurements - in vivo monitoringPossible when the incorporated radionuclide emit penetrating radiation of sufficient energy and yield to be detectable outside the body (X ray or gamma photon)

• Indirect measurements – excreta measurements organs & tissues concerned are not sampledKnowledge of relationships betweenbioassay samples organ burdens of interest

Monitoring type

• Direct measurementsWhole body counting Thyroid measurementLung countingWound counting

• Indirect measurementsNose-blowUrineFaecesBlood, hair, sweat, saliva …

36

In vivo monitoring

Jean-Louis Genicot

Bioassay measurements

37

Types of Bioassay samples (I)

• Chemical element involved• Physical & chemical form• Magnitude of the internal deposition• Biological & Physical half-lives of radionuclides

involved• Elapsed time since the deposition• Sensitivity of analytical method

Types of Bioassay samples (II)

• Urinemost used24 hours samplingat SCK-CEN 3 consecutive days (36h)3H2O: a voidingrepetitive sampling

38

Types of Bioassay samples (III)

• Faecesnot often used for routineaccidental inhalation

• Nose-blow, Nose-swapα emitterstriggers complementary analysis

Types of Bioassay samples (IV)

• blood• sweat• saliva• hair• teeth• breath

14CO2, 3H2O, 222Rn, 220Rn

• tissueremove for medical purpose, post mortem

39

Radiochemical Procedure (I)

• Sample preparation & Pre-concentration• Urine

wet ashingco-precipitation

• FaecesashingdissolutionHF treatment

Radiochemical Procedure (II)

• Chemical separationion-exchange resinsolvent extractioncombination ...

40

Radiochemical Procedure (III)

• Source preparationα emitters

direct evaporationco-precipitation with LnFElectro-deposition

• ß emittersprecipitation & filtration of insoluble saltMgNH4PO4, SrCO3, Y2(C2O4)3, PdI2

Measuring Techniques

α spectrometry• ß counting• Liquid Scintillation Counting - LSC

γ spectrometry• Fluorimetry• Neutron Activation Analysis - NAA• Delay Neutron Assay - DNA• Mass spectrometry - ICPMS, SIMS• Fission Track Analysis

41

α spectrometry

• Th, U, Pu, Am, Cm...• radiochemical procedure• source preparation

co-precipitation LnFelectro-deposition

• Yield determinant229Th, 232U, 242Pu, 243Am

• MDA = 0.1 mBq/l

ß Counting

• strong ß emitters32P, 89Sr, 90Sr, 90Y, 131I

• radiochemical procedure• source: insoluble salt• gas proportional counter - low background• MDA = 0.08 Bq/l

for 90Sr, urine sample of 250cc

42

Liquid Scintillation Counting LSC

• weak energy ß emitters - 3H, 14C, 63Ni, 241Pudirect measurementuse of internal standardMDA = 5 Bq/l for 3H in urine (Vol. = 9 cc)

• pure ß emitters - 32P, 89Sr, 90Srradiochemical procedureMDA = 0.12 Bq/l (Vol. = 600 cc)

γ Spectrometry

• direct measurement• 250 cc sample• MDA = 0.2 Bq/l• in-vivo measurement

Whole-bodyThyroid

43

From measurements to Intake

Lung Model

44

Lung Retention

• Calculate the retention of a radionuclide at times after inhalation

• NeededAMADSolubility classLung Model (new) from ICRP 66

• Σ all the compartments• Then…

Lung Retention 239Pu Class Yacute inhalation 1 µm AMAD

0

0.05

0.1

0.15

0.2

0.25

Lung

rete

ntio

n (B

q)

1E0 1E1 1E2 1E3 1E4Time since intake (d)

ICRP 30 ICRP 66

Lung retention following intake of Pu(1 Bq acute intake of Pu-239)

45

Whole body retention

• Total amount of activity in the body• Includes activity retained

Respiratory tractAlimentary tract (f1)BloodBody organs

• Activity in body organs (excluding HAT & HRT) = systemic activity

Simple biokinetic models

46

Systemic retention function

• Organ or tissue represented by a sum of exponential terms

• Whole body = sum of each organ = sum of exponential terms

• Systemic retention function. In ICRP Publication 54 given for 22 elements

∑=

−=5

1)(

i

ti

ieatR λ

Lead biokinetic modelICRP Publication 67

47

Comparison of ICRP 67 model with exponential approximation

0.01

0.1

1

Ret

entio

n

1E0 1E1 1E2 1E3 1E4Time (d)

exponential approximation exact model solution

Whole body retention of lead (following unit uptake to blood)

Lead systemic retention function

tt

ttt

eeeeetR

00617.00000767.0

000491.00337.04.5

288.00895.0122.0452.00485.0)(

−−

−−−

++

++=

48

Lead compartment system

Systemic retention of Caesium

49

Urinary excretion (ICRP 30)

• Retention function R(t) = sum of exponential• Instantaneous excretion rate obtained by

differentiation of systemic retention function• fu = fraction of excreted activity to urine

∑=

−=−=5

1

)(i

tiiuu

ieafdt

tdRfdt

dU λλ

Caesium excretion

• Caesium retention

• fu = 80 %• Urinary excretion

110)2ln(

2)2ln(

9.01.0)(tt

eetR−−

+=

110)2ln(

2)2ln(

110)2ln(72.0

2)2ln(08.0

tt

eedt

dU −−+=

50

Excretion compartmentalrepresentation

Excretion compartmentalrepresentation (II)

• K is very fast• Dummy compartments start with ai/λi amounts• Instantaneous excretion rate = sum of exponential

terms aiexp(-λit)• Integration, total amount excreted at t=∞, Σ(ai/λi)• If all material in blood is excreted, Σ(ai/λi)=1• If material goes to tissue or organ indefinitely retained

excreted via a different route• => an other compartment where [1- Σ(ai/λi)] not

available for excretion

51

Excretion compartmentalrepresentation (III)

Faecal excretion

• Faecal excretion comprises 2 componentsActivity cleared from the lungs by mechanical transport through the HATActivity in blood extracted by the liver= systemic faecal excretion

• Caesium example: systemic faecal excretion

110)2ln(

2)2ln(

110)2ln(18.0

2)2ln(02.0

tt

eedtdF −−

+=

52

Urinary excretion rates

• By differentiation of the retention function• Not simple with the new models• Urinary excretion is explicitly in the model• Calculation of instantaneous urinary excretion rate by:

Solving the amount in the urine compartment at times t and t-δt and dividing by (t-δt) = instantaneous rate as δt tends to 0Solving for the amount in the urinary bladder contents (CONT) at time t and multiplying by the rate constant from CONT to URINE

Lead biokinetic modelICRP Publication 67

53

Comparison of instantaneous urinary excretion of lead

1E-06

1E-05

0.0001

0.001

0.01

0.1

Exc

retio

n ra

te (/

d)

1E0 1E1 1E2 1E3 1E4Time (d)

exponential approximation exact solution

Instantaneous urinary excretion rate(following unit uptake of lead)

Lead urinary excretion

• Calculate this for 1 to 104 days• Can fitted a function with sum of exponential• At t=0, CONT = 0 => Σai = 0

ttt

ttt

ttt

eeeeee

eeedt

dU

221.000205.00000761.0

000431.000901.011

7.730411.021.4

00166.00000707.000000378.0000026.000145.0242.0

327.000915.007264.0

−−−

−−−

−−−

+++

+++

−+=

54

Instantaneous urinary excretion rate of lead

Daily urinary excretion rates

• Can be calculated by either:Integrating the instantaneous excretion rate function from t-1 to tCalculating the amount in the excretion compartment at times t-1 and t and subtracting one from he other

• To calculate daily excretion rates following inhalation (or ingestion) the respiratory tract and GI tract must be added to the compartment representation and the second calculation option used

55

Systemic instantaneous faecal excretion rate

• Non-systemic component of faecal excretion from material in the GI tract must be added when convoluting with respiratory and GI tract

tt

ttt

ttt

eeeee

eeedtdF

4.4400732.0

000075.0000412.00277.0

00154.026.123.1

00046.0000595.000000216.00000139.000457.0

0000262.0613.006073.0

−−

−−−

−−−

++

+++

+−=

Suggestion

• Thank you and …• What about filling up

the Human Alimentary tract.

• “Bon appétit”