Accepted Manuscript

Internal dose assessments – Concepts, models and uncertainties

Bastian Breustedt, Augusto Giussani, Dietmar Noßke

PII: S1350-4487(18)30014-3
DOI: 10.1016/j.radmeas.2018.06.013
Reference: RM 5935

To appear in: Radiation Measurements

Received Date: 12 January 2018

Revised Date: 25 May 2018
Accepted Date: 10 June 2018

Please cite this article as: Breustedt, B., Giussani, A., Noßke, D., Internal dose assessments
– Concepts, models and uncertainties, Radiation Measurements (2018), doi: 10.1016/
j.radmeas.2018.06.013.

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 ACCEPTED MANUSCRIPT
Internal Dose Assessments – Concepts, Models and
Uncertainties
Bastian Breustedt1, Augusto Giussani2, Dietmar Noßke3

1 KIT - Karlsruher Institut für Technologie, Karlsruhe, Germany

2 BfS - Bundesamt für Strahlenschutz, Oberschleißheim, Germany
3 BfS - Bundesamt für Strahlenschutz, Oberschleißheim, Germany - retired

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Abstract
In contrast to external dosimetry, which can be based on measurement of operational

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quantities directly related to the effective dose (mSv), the assessment of doses due
to intakes of radionuclides relies on the measurement of activities (Bq) and
subsequent modelling. The methodology and the models are published by the

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International Commission on Radiological Protection (ICRP) and are later
implemented in national regulations. This paper describes the general concepts for
assessment of internal occupational exposure and diagnostic nuclear medicine

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applications using biokinetic and dosimetric models. The current changes in the
models which are presented in the OIR series (Occupational Intakes of Radionucldes)
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of ICRP are outlined and information on the uncertainties in internal dose
assessment are presented.

Internal Dosimetry – Concepts

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Doses due to intakes of radionuclides cannot be assessed using measurements of

dose quantities (mSv) because the source of the radiation is inside the body.
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Information about the exposure can be obtained by measuring activities (Bq) in the
material entering the body (intake), in the body itself (or parts thereof) or in the
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excreta (urine, feces). The measured values must then be converted to doses using
models. These models must be able to describe:
• The time-dependent distribution of the radionuclide (being the source of
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radiation) in the body and

• The energy deposition in the organs and tissues (being the target) following
the emission of radiation associated to the decay of the nuclei.
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One peculiarity of internal exposures is that in general radionuclides are

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inhomogeneously distributed between (and within) different organs and regions of the
body, and this distribution changes with time due to the physiological processes
governing their biokinetic behaviour and excretion. In addition to that, the activity in
the whole body decreases over time as a consequence of the nuclear decay. As a
result of this, intakes of radionuclides are characterized by a chronic irradiation with
changing geometry and dose rate.
To account for the chronic irradiation, the dose quantities used in internal dosimetry
are expressed in terms of committed doses, which are the dose accumulated over a
given commitment period τ. In radiological protection this period is set to 50 years for
workers and adults of the population and up to the age of 70 years for children. In
 ACCEPTED MANUSCRIPT
diagnostic medical applications using short-lived radioisotopes the commitment
period is conventionally considered to be infinite.
The methodology and the models used in radiation protection are published by the
International Commission on Radiological Protection (ICRP) and are subsequently
implemented to national regulations.
Biokinetic Models – Retention and Excretion Functions
The radionuclide distribution is described using biokinetic models. The reference

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models of ICRP describe the behaviour of the radionuclides in a reference person.
The models are using a compartmental approach which divides the body in several
pools of activity between which the activity is exchanged. Each pool is characterised

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by a uniform kinetic behaviour. Depending on the radionuclides, these pools can be
interpreted as organs, tissues or group of organs and linked to anatomical structures.
A set of first order differential equations describing the activity content of the pools

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can be derived considering the total mass balance of the system.
The behaviour of the radionuclide depends on many factors, such as element,
chemical form, pathway of intake, aerosol size (for inhalation). These dependencies

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need to be taken into account by the model. The solutions of the models provide
predictions of the activity of the nuclide over time in the organs, in body regions and
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in the whole body (retention functions) or the excretion rate of the activity for urine
and feces (excretion functions) for the different parameters and scenarios. By
integration of the retention functions the number of decays (in ICRP terminology:
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nuclear transformations) over a given time after the intake can be calculated. The
retention and excretion functions are used to interpret the monitoring measurement,
i.e. to estimate the original amount of activity that entered the body (intake) from
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measured values.
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In medical applications of radionuclides, biokinetic models for the reference patient

have been developed. In therapeutic applications individual dose assessments are
required both for the region to be treated (in order to ensure that it receives the
required therapeutic dose) and for the surrounding healthy tissues (in order to ensure
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that their doses are minimized); therefore generic models cannot be applied and the
individual biokinetic behaviour needs to be determined.
Dosimetric Models – Dose Coefficients
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The physical properties of the nucleus determine type, energy and emission
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probability of each radiation emitted following a decay of the nucleus. Using

reference computational phantoms of the human body (ICRP 2009) and Monte Carlo
methods for radiation transport simulation, the deposition of energy in a target tissue
per decay in a source region can be calculated taking into account the weighting
factors for the different types of radiation. (ICRP 2016a). These numbers are called
radiation weighted S-coefficients (formerly known as specific effective energy). The
number of decays that will occur in a source region is given by the biokinetic models
and, by multiplication with the S-coefficient for the appropriate source-target pair, can
be used to estimate the energy deposition in any target organ. The total energy
deposited in a target organ and thus the dose (committed equivalent dose to an
organ) is calculated by summing the contributions of all source regions. Finally, the
committed effective dose is calculated by summing the sex-averaged committed
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equivalent doses for all target organs of the reference male and female multiplied by
the respective tissue weighting factors.
The assessment of doses can be simplified by calculating the dose values due to the
intake of 1 Bq of the radionuclide. This quantity (dose per unit intake) is referred to as
dose coefficient and has units of Sv/Bq. The committed equivalent doses to the
organs and the committed effective dose are then simply calculated multiplying the
dose coefficient by the estimated intake. Figure 1 summarizes the steps in the
calculation of reference dose coefficients.

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Figure 1: Calculation of dose coefficients using biokinetic models (retention functions) and dosimetric
models (radiation weighted S-coefficients). For workers the commitment period τ is 50 years, for
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children the commitment period is up to the age of 70 years.

In diagnostic nuclear medicine dose coefficients are calculated using biokinetic and
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dosimetric models for a reference patient. In therapeutic nuclear medicine patient-

specific dosimetric models can be generated from tomographic data acquired to
provide individual phantoms. However, Monte Carlo calculations for the
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determination of individual S-coefficients are time consuming even on modern

computers, therefore tabulated Voxel-S-values are provided to facilitate a fast
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calculation.
Dose assessment – occupational exposure
The evaluation of internal doses from data gathered in a monitoring programme in
occupational radiation protection is a two-step procedure. First the intake is estimated
comparing the result of the monitoring measurement with the corresponding
prediction (retention or excretion function) obtained with the biokinetic models. In the
second step of the assessment, the dose is calculated multiplying the estimated
intake by the corresponding dose coefficient.
The model predictions used for the intake estimation depend on the assumptions
made about time and pathway of intake as well as about the characteristic of the
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incorporated material (e.g. aerosol size - AMAD1 - and solubility). These assumptions
can be reference assumptions or based on information gathered at the workplace,
and should be specified in the monitoring programme.
After a manifest or supposed accidental intake special monitoring programmes,
consisting in repeated in vivo and/or in vitro measurements, need to be initiated. In
this case more effort is required for the estimation of the intake. Reference
procedures for estimating intakes using the ICRP methodology and guidance for their
application are described in the literature [ISO 2011, Castellani et al. 2013,

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Etherington et al. 2016]. The availability of multiple measurements enables to refine
the assumptions on the scenario (e.g. by fitting the model predictions to the data),
and consequently to improve the dose estimate. Figure 2 summarizes the workflow in

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the dose assessment for occupational exposures.

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Figure 2: Workflow of occupational dose assessment. In the first step the reference biokinetic model
are applied to estimate the intake from the monitoring data. In the second step the dose coefficients
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are applied to calculate the committed dose resulting from the assessed intake. In both steps the
same biokinetic models have to be applied.
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Dose assessment – medical exposure

In medical applications the intake is known. For diagnostic procedures models
describing the reference patient can be used to estimate doses using the MIRD
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approach, which mathematically is equivalent to ICRP’s methodology using a slightly

different terminology (Bolch et al. 2009). In therapeutic applications the individual
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biokinetic behaviour must be observed using multiple measurements. Using the set
of data either individual biokinetic models can be developed or the number of decay
in the source regions can be estimated by numerical integration (interpolation) of the
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observed values. Figure 3 summarizes the steps in the dose assessment for nuclear
medicine diagnostic (a) and therapeutic (b) applications.
a)
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b)

1
AMAD: Activity Median Aerodynamic Diameter is a measure of the size of aerosols used in modeling
the biokinetic behavior of the inhaled materials.
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Figure 3:
a) In diagnostic applications of radionuclides dose can be calculated directly from the known intake by
using the dose coefficients derived from biokinetic and dosimetric models of the reference patient
b) In therapeutic applications of radionuclides the data on the individual biokinetic and anatomy of the
patient need to be used in the direct dose assessment, which can be done using e.g. quantitative
Imaging techniques and Voxel S-Coefficients.

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Revision and update of internal dosimetry data

Present national and international legislation in internal dosimetry is largely based on

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dose coefficients and bioassay data for workers (ICRP 1994b, ICRP 1997) and
members of the public (ICRP 1995) which were published by ICRP more than 20
years ago.

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Since that time, ICRP has published new standards for radiation protection including
a new approach for calculating the effective dose (ICRP 2007) and has developed
several new models:
•
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a new model for the human alimentary tract (HATM) (ICRP 2006),
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• new nuclear decay data (ICRP 2008),
• new voxel phantoms for the calculation of dosimetric parameters (ICRP 2009)
based on new reference person data (ICRP 2002).
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Therefore, there is a need to update the present dose coefficients and bioassay
functions according to these new data and to other new information. ICRP started
this task with the preparation of a series of Publications for occupational intakes of
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radionuclides (OIR) aimed to update its Publications 68, 78 and 119 (ICRP 1994b,
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1997, 2012).
Revised biokinetic models in the OIR Report series
The gastro-intestinal model presented in ICRP Publication 30 (ICRP 1979) was used
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for the calculation of the current internal dosimetry data. In the OIR Reports the
Human Alimentary Tract Model (HATM) of ICRP Publication 100 (ICRP 2006) is used.
The former model is a four-compartment structure (stomach, small intestine, upper
and lower large intestine) allowing absorption to blood from the small intestine
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contents. The transfer rates within the tract are considered to be independent of age,
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sex, and the ingested material. The HATM has more compartments, starting with the
oral cavity followed by two oesophagus compartments (fast and slow). The colon is
subdivided into three compartments (right, left, and rectosigmoid colon). Absorption
to the systemic circulation is possible from almost all sites of the tract with a possible
retention within the walls. Transfer rate values depend on age and sex of the person
considered as well as on the type of ingested material.
The Human Respiratory Tract Model (HRTM) of ICRP Publication 66 (ICRP 1994a),
which was used for the calculation of the present internal dosimetry data, describes
• the deposition in different regions of the respiratory tract,
• the mechanical clearance of the deposited material to the upper part of the
tract (followed by transfer to the alimentary tract) and the lymph nodes, and
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• the absorption to blood.
The HRTM was slightly revised for the OIR reports (ICRP 2015b). The number of
compartments representing the different transfer rates for the mechanical clearance
to the upper part of the tract by mucociliar clearance has been reduced, and activity
in the anterior nose compartment is also allowed to be transferred to the naso-
oropharynx/larynx region. The default fast absorption type now is element-specific
with the tendency to be a little bit slower than in the original model. Besides the
default absorption types there are partly much more compound-specific absorption

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rates. Additionally, in some cases now also the bound state, a retention within the
airway walls during the absorption process, is considered.
Changes have been introduced also for the systemic models, i.e. the models

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describing the behaviour of radionuclides which have entered the systemic circulation.
Whereas the systemic behaviour was described insofar for most radionuclides by

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simple structures with unidirectional material flow, the models adopted in the OIR
Report Series are physiologically based structures allowing recycling between
compartments. For example, the systemic behaviour of caesium in the present model
was described by two whole body compartments, while the new OIR model is a

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complex recycling structure based on a blood-flow model with 16 systemic
compartments besides the two blood compartments. Moreover, daughter nuclides
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produced within the body as a consequence of the decay of incorporated parent
nuclides are now assumed to follow independent kinetics, and no longer to follow the
kinetics of the parent nuclides, as it was assumed in most cases in the previous
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publications.
Revised dosimetric models in the OIR Report series
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The main step forward in dosimetric models is the move from the use of stylized
mathematical phantoms, which approximate the anatomy of the reference persons
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representing their organs with geometric shapes, to the use of voxel phantoms.
These are based on medical images of actual subjects and are adjusted to the
dimensions and organ masses of the reference persons defined by ICRP Publication
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89 (ICRP 2002). Voxel phantoms for the male and female adult have been published
in ICRP Publication 110 (ICRP 2009). Another improvement in the dosimetric
approach of the OIR reports is that the dosimetric calculations for β radiation are now
performed using the voxel phantoms and the complete β spectra as given in ICRP
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Publication 107 (ICRP 2008), and not assuming complete absorption in the source
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region, as in general made before.

There are also refinements in the dosimetry for the skeleton and the HAT walls.
While for the HAT walls, similarly to the HRT airway walls, the dose to special
radiation sensitive cells lying in a depth between 60-100 µm (stomach wall) and 280-
300 µm (colon walls) is calculated, for the skeleton fluence-to-dose response
functions are coupled with the particle fluence inside specific bone regions obtained
by micro-CT images of the skeleton structures.
The effective dose is calculated using sex-averaged organ equivalent doses and the
updated tissue weighting factors given in ICRP Publication 103 (ICRP 2007).
Present and forthcoming ICRP Publications in internal dosimetry
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Parts 1, 2 and 3 of the OIR series already have been published as ICRP Publications
130, 134 and 137 (ICRP 2015b, 2016b, 2017), respectively. Part 1 describes the
general methodology used within this series. Part 2 contains models and data for 14
elements from hydrogen to technetium. Part 3 presents models and data for 14 other
elements from ruthenium to uranium. This part also includes biokinetic models for
radon and its short-lived progenies and will give radon dose coefficients calculated
with the dosimetric approach. Part 4 with 15 lanthanides and 10 actinides and Part 5
with the remaining elements will be published later.

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For each element, OIR Parts 2-5 contain its radioisotopes with the most relevant
decay characteristics and chemical forms in the workplace, the lung and alimentary
tract absorption parameters for several compounds, the description of the biokinetic

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systemic model including daughter kinetics, and, for the most relevant radioisotopes,
individual monitoring data, effective dose coefficients and bioassay data (Tables of
dose per activity content in body, organs, or excreta, and graphs of retention and

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excretion functions).
In the near future it is planned to update also ICRP Publication 72 (ICRP 1995) which
compiles age-dependent dose coefficients for members of the public and ICRP

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Publication 119 (ICRP 2012) by a series of reports for environmental intakes of
radionuclides (EIR) accordingly. Within this series, also updates of ICRP Publication
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88 on doses to embryo and foetus (ICRP 2001) and ICRP Publication 95 on doses to
infants by ingestion of mother's milk after radionuclide intake by the mother (ICRP
2004) are planned. To this purpose new voxel phantoms for reference children,
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pregnant women and foetuses are being developed.

Another update is needed for doses to patients from radiopharmaceuticals
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administered in diagnostic nuclear medicine. The recent ICRP Publication 128 (ICRP
2015a) is a compilation of doses calculated with the former models and definitions.
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Therefore, a revision of this publication is planned, which will bring a harmonisation

with the OIR and EIR documents. It will use the same dosimetric models, the HATM
and the revised HRTM of Publication 130 (ICRP 2015b). More complex biokinetic
model structures will also be considered for the description of the systemic activities.
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Internal Dosimetry - Uncertainties

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Internal dosimetry relies on models. Particularly biokinetic models are a rough

mathematical approximation of complex biological and physiological processes. Inter-
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and intra-individual biological variability contributes to the uncertainty on the model

outputs. Another primary source of uncertainty is the limited knowledge of the
processes and the lack of data for identifying the models and quantifying their
characteristic parameters. It must be stressed here that the reference models of
ICRP are characterized by reference parameter values, which are established and
selected from a range of human and animal studies through judgements. For
regulatory purposes, these models and parameters are fixed by convention and are
not subject to uncertainty (ICRP 2007; 2015b).
Uncertainties should anyway be taken into account when shifting from reference
assessment to a more individualized assessment, for instance for retrospective
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assessment of doses for risk assessment in individual cases and/or in the frame of
epidemiological studies.
Main sources for uncertainty in the biokinetic models are related to the adequacy of
the model structure and to the reliability of the source data used for assessing the
model parameters: human studies are more reliable than animal ones, and studies
with chemical analogues less reliable than studies performed with the compound of
interest. Main sources of uncertainty in the dosimetric models can be associated with
inhomogeneous activity distributions and simplifying assumptions on the location of

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radiosensitive cells (particularly important for high LET radiation and for walled hollow
organs). On the other hand, the physical properties of the radionuclides (energy and
spectra of the emitted radiation) are known to a very good degree of precision, and a

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number of different voxel phantoms are currently available than enable to assess and
quantify intraindividual variabilities.
All variables affected by uncertainty, specifically the transfer coefficients of the

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biokinetic models and the anatomical characteristics of the dosimetric models, may
be represented as random variables following probability distributions. This
uncertainty can be propagated onto the dose or other outputs of relevance for

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internal dosimetry (e.g., the retention or excretion functions) by randomly sampling
with Monte Carlo methods a representative number of values for all uncertain
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variables. The challenge in this process lies in the choice of probability distributions,
conditional probabilities and correlations for the model parameters. Knowledge of
these quantities is rarely available, so that one often relies on expert judgment, which
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however is a subjective judgment and therefore itself prone to be an additional

source of uncertainty. The resulting probability distributions of the model outputs is
therefore strongly affected by the assumptions on the input probability distributions.
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When reliable information is missing, different assumptions can be made for the
probability distribution functions (normal, lognormal, flat, triangular…) to evaluate how
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the results depend on the assumed distribution.

In the case of monitoring potential intakes of radionuclides and assessment of doses
based on bioassay data, uncertainties are associated, among others:
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• with the measurements of the activity of a radionuclide in the body (in vivo) or
in a biological sample (in vitro),
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• with the choice of the exposure scenario (for instance, route and pattern of
intake) used to interpret the bioassay results,
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• with the chemical and physical form of the deposited radionuclide(s).

Two types of measurement errors can be identified. Type A uncertainties are of
statistical nature, generally related to counting statistics, and decrease with
increasing activity or with increasing counting time. Type B uncertainties are of non-
statistical nature and may largely be independent of the activity or the counting time.
Examples of Type B components for in vivo monitoring include counting geometry
errors; positioning of the individual in relation to the detector; interference from
radioactive material deposits in adjacent body regions, including natural radionuclide.
Examples of Type B components for in vitro measurements include the quantification
of the sample volume or weight; errors in dilution and pipetting; source positioning for
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counting; impurities and contaminations (ISO 2011, Castellani et al. 2013,
Etherington et al. 2016).
In epidemiological studies, uncertainty sources may be characterized in different
ways and accordingly used in the risk evaluation process. Errors that are correlated,
or even the same, for many individuals or among cohorts are indicated as "shared
errors". In general little is known about this source of uncertainty, and methods for
modelling these errors and then accounting for them in dose and risk estimates are
only in the early stages of development. "Unshared errors" (i.e., those which are

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independent between individuals) may also exist but, contrary to “shared errors”, their
effect on risk estimates is well understood and methods for dealing with the resulting
effects are available (Land et al., 2015; Simon et al., 2015; Stram et al, 2015).

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In the recent years, the Bayesian approach has been gaining a central position in the
treatment of uncertainty in internal dosimetry. In the Bayesian framework, all
uncertain quantities are modelled by random variables with possible values weighted

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by their degree of belief in the form of a probability density function (PDF). For a
more specific discussion the reader is referred to the relevant literature (e.g.,
Hoffmann et al., 2017; Land et al., 2015; Puncher, 2014; Puncher and Birchall, 2008;

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Kwon et al., 2016).
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Conclusion

The basic principles and the methodology of internal dose assessment, which is still
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used today, have been originally developed and published by ICRP in the 1970s and
revised and refined over time. The biokinetic and the dosimetric models have been
constantly improved. The recent OIR Series of ICRP (ICRP 2015b, 2016, 2016b,
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2017) will present the latest developments and provide models and data to be used
in future dose calculations for occupational exposures. The reference models for
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diagnostic nuclear medicine applications are presented in the recent ICRP

Publication 128 (ICRP 2015a), for which a revision is planned. For situations which
cannot be described using the reference models and scenarios (e.g. radionuclide
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therapy, or application of decorporation agents) the methodology of internal dose

assessment can be applied, but individual models need to be used.
The reference biokinetic models published by ICRP are per definition free of
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uncertainties, when they are applied to assess effective dose and equivalent dose to
the organs of reference individuals. The description and quantification of
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uncertainties in the models and thus the dose estimates now has become a field of
research in internal dosimetry. Further research and developments in internal
dosimetry, which will lead to improved models is continuously being conducted e.g.
on the development of new reference computational phantoms based on the mesh
structures instead of voxel models (Kim et al. 2016, Yeom et al. 2013).

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 ACCEPTED MANUSCRIPT
Internal Dose Assessments – Concepts, Models and
Uncertainties
Bastian Breustedt1, Augusto Giussani2, Dietmar Noßke3

1 KIT - Karlsruher Institut für Technologie, Karlsruhe, Germany

2 BfS - Bundesamt für Strahlenschutz, Oberschleißheim, Germany
3 BfS - Bundesamt für Strahlenschutz, Oberschleißheim, Germany - retired

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Highlights
• Models and Methodology for dose assessment after intakes of radionuclides

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are presented.
• Recent developments in internal dosimetry (e.g. OIR series of ICRP) are
summarized.

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• Uncertainties in internal dose assessments are presented.

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