Plutonium Biokinetics in Human Body A. Luciani - Kit-Bibliothek - FZK

3.1.3 MODIFICATION OF ICRP 67 MODEL
Part of the following study was already reported in recent publications [154, 156].
3.1.3.1 New concepts of skeletal remodelling
In order to achieve a better agreement with reference data set, particularly for the
urinary excretion of Plutonium, the ICRP 67 model was firstly analyzed pointing out the
leading transfer processes determining the biokinetics and so the excretion of Plutonium.
According to the purpose of developing a physiologically based model, the ICRP67-a model
previously described was the starting point.
The activity in the central transfer compartment represents the amount of activity
generally available to successive metabolising processes as urinary and fecal excretion.
Therefore the contribution to the amount of activity retained in blood from the organs directly
transferring activity to the blood compartment was calculated. This allows identifying which
organs or tissues are of main importance to the excretion processes. At this preliminary phase
of the study of the model such approach was preferred to a complete sensitivity analysis for
the urinary excretion performed on all the transfer rates of the compartments present in the
model. The main reasons of this approach are:
• it is not as much time-consuming as the calculation of sensitivity coefficients that should
be evaluated for a number of time points covering the whole time range of interest;
• it can easily and quickly provide the contribution of whole functional systems by
considering the single compartment directly connecting them to the blood compartment.
This is the case of the skeletal model where the whole skeletal system transfers its activity
to the blood through the marrow compartments. In a similar way the hepatic system clears
its activity just through the Liver 2 compartment.
The analysis was performed for all the organs and tissues contributing to the activity
content of the blood compartment: skeleton (trabecular marrow and cortical marrow), liver
(compartment Liver 2), ST0, ST1 and ST2 soft tissue compartments, other kidney tissue
compartment (OKT), gonads and small intestine. In Figure 3.1.8 the daily transfer of activity
from those organs and tissues that mainly contribute to the blood central compartment activity
is presented (daily transferred activity greater than 10 -5 d -1 ).
It can be pointed out that the activity transfer from the ST0 compartment almost
exclusively determines the activity content of the blood for the first 20 days after the
injection. The ST1 compartment has a significant contribution just in the time range 20 – 100
days post injection. More interesting are the contributions at long term, when the
disagreement between reference data set and modified version of ICRP 67 (ICRP67-a) was
observed. After 100 days the contribution due to the skeleton becomes predominant. The
hepatic system becomes significant at longer time: at around 8,000 days post injection it is the
80 and 66% of the contributions of ST0 soft tissue and skeleton compartments, respectively.
The small intestine contributes only marginally to the activity in the blood compartments: at
about 30 days its contribution is 50% of ST0 contribution and it vanishes soon from 100 days
post injection.
From the previous analysis it turns out that the skeleton is the main system in
determining the activity in the blood compartment at intermediate and long times. Therefore it
should be considered first if ICRP 67 model predictions for biokinetics of Plutonium in this
time range can be improved by considering the skeletal system. A new model for Plutonium
biokinetic in skeleton recently developed was considered [157]. This model is based on
available information on the microdistribution of transuranic elements in animals and humans
as obtained from autoradiographic analyses. It is also based on morphometric and
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