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Journal ArticleDOI

30-Y follow-up of a PU/AM inhalation case

01 Apr 2015-Radiation Protection Dosimetry (Oxford University Press)-Vol. 164, pp 57-64

TL;DR: The undisturbed metabolism of Pu and Am can be derived from the data since no decorporation measures had been taken, and the estimated committed effective dose is in the order of 1 Sv.

AbstractIn 1983, a young man inhaled accidentally a large amount of plutonium and americium. This case was carefully followed until 2013. Since no decorporation measures had been taken, the undisturbed metabolism of Pu and Am can be derived from the data. First objective was to determine the amount of inhaled radionuclides and to estimate committed effective dose. In vivo and excretion measurements started immediately after the inhalation, and for quality assurance, all types of measurements were performed by different labs in Europe and the USA. After dose assessment by various international groups were completed, the measurements were continued to produce scientific data for model validation. The data have been analysed here to estimate lung absorption parameter values for the inhaled plutonium and americium oxide using the proposed new ICRP Human Respiratory Tract Model. As supplement to the biokinetic modelling, biological data from three different cytogenetic markers have been added. The estimated committed effective dose is in the order of 1 Sv. The subject is 30 y after the inhalation, of good health, according to a recent medical check-up.

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Introduction

  • An estimate of the isotopic composition of the inhaled material is necessary to determine the initial amount of americium and plutonium deposited in the lungs.
  • Note that this effect is achieved even if liver and skeleton data are not included in the fitting because it is mainly driven by the urine data.
  • Figures 1–4 show measurements and best-fit model predictions for a subset of the datasets.
  • In summary, the significant increase of symmetrical aberrations, while no enhancement of dicentric chromosomes is observed, provides evidence for a past radiation exposure of the blood forming tissue and/or ongoing chronic low dose exposure.

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30-Y FOLLOW-UP OF A PU/AM INHALATION CASE
Christian Wernli
1,
*, Jost Eikenberg
1
, Olaf Marzocchi
2
, Bastian Breustedt
2
, Ursula Oestreicher
3
, Horst Romm
3
,
Demetrio Gregoratto
4
and James Marsh
4
1
Paul Scherrer Institute (PSI), Villigen, Switzerland
2
Karlsruhe Institute for Technology (KIT), Karlsruhe, Germany
3
Federal Office for Radiation Protection (BfS), Oberschleissheim, Germany
4
Public Health England (PHE), Harwell Science and Innovation Campus, UK
*Corresponding author: christian.wernli@alumni.ethz.ch
In 1983, a young man inhaled accidentally a large amount of plutonium and americium. This case was carefully followed until
2013. Since no decorporation measures had been taken, the undisturbed metabolism of Pu and Am can be derived from the data.
First objective was to determine the amount of inhaled radionuclides and to estimate committed effective dose. In vivo and excre-
tion measurements started immediately after the inhalation, and for quality assurance, all types of measurements were performed
by different labs in Europe and the USA. After dose assessment by various international groups were completed, the measure-
ments were continued to produce scientific data for model validation. The data have been analysed here to estimate lung absorp-
tion parameter values for the inhaled plutonium and americium oxide using the proposed new ICRP Human Respiratory Tract
Model. As supplement to the biokinetic modelling, biological data from three different cytogenetic markers have been added.
The estimated committed effective dose is in the order of 1 Sv. The subject is 30 y after the inhalation, of good health, according
to a recent medical check-up.
HISTORY OF THE INHALATION CASE
A first paper describing the details of the accident, the
early measurements and dose estimates of the Pu/Am
inhalation case of 1983 at the former Federal Institute
for Reactor Research in Switzerland has been pub-
lished in 2007
(1)
. Immediately after accidental inhal-
ation by a 26-y-old male technician, dose estimates
were of primary interest. The results of measurements
perf ormed in various la bs w er e used by sever al organisa-
tions for testing their internal dosimetry pr ogr ammes for
actinides. La ter on, this case became mainl y of scientific
interes t since no chela ting agent w as used and, ev en
after 30 y, in vivo and excretion measur ements wer e still
possible. Fortunatel y, the person concerned accepted
all these measurement procedur es. Over the last fe w
years, organ measurements were performed with
highly specialised instruments at Karlsruhe Institute
for Technology (KIT)
(2)
and the excretion measure-
ments were done again at Paul Scherrer Institute
(PSI)
(1)
.Inadditiontoallthephysicalmeasure-
ments, current cytogenetic analyses were performed
at Federal Office for Radiation Protection
(3)
to com-
plete scientific data by biological studies.
RECENT IN VIVO MEASUREMENTS
Instruments and method
Recent in vivo measurements have been performed at
KIT Karlsruhe using a system of four HPGe detec-
tors
(2)
. Two detector configurations were used: a
mixed one to monitor four organs (left lung, right
lung, liver and knee), and a configuration specific for
the skeleton (two detectors around the skull and two
detectors for the knees). The measurement time was
4000 s per configuration. The net area of the peaks
was estimated according to ISO 28 218. The calcula-
tion of the activity for
241
Am in each organ was per-
formed using both ICRP Man and ICRP Female as
calibration phantoms, and the calibration data were
obtained using MCNPX
(4)
after a validation of the
method
(2)
. The analysis of the data was performed first
for the mixed configuration; the results were used to
correct the calculations for the skeleton configuration.
The calculation of the activities in the mixed con-
figuration was not performed using each detector in-
dependently, because it is known that a measurable
part of the counts is generated by the crosstalk
between neighbouring organs and detectors. Instead,
the direct and the indirect contributions and the four
peak areas were used to write a system of linear equa-
tions. The solution of the system consisted of the ac-
tivity in each organ.
DISCUSSION
The solution of the system of equations applied to the
mixed measurement configuration produced a negative
value of
241
Am activity in the liver, independently from
the calibr ation phantom used, suggesting the la ck of
241
Am in the organ. The system was therefore rewritten
to exclude the liver and the solution calculated again.
The final data are shown in Table 1.
The activity in the lungs calculated using the mixed
configuration was used to correct the peaks recorded
in the detectors around the skull. This was performed
# The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.per missions@oup.com
Radiation Protection Dosimetry (2015), Vol. 164, No. 12, pp. 5764 doi:10.1093/rpd/ncu342
Advance Access publication 19 December 2014

by simulating with MCNPX the counting efficiency
for photons originated in the lungs and reaching the
detectors around the skull. The number of counts ori-
ginated by the skeleton was therefore lowered: the net
value was 3 5 % lower when using ICRP Male as
calibration phantom and 810 % lower for ICRP
Female. The different results can be explained by the
higher amount of muscles in ICRP Male that acts as
shield and lowers the cross-counting efficiency for the
detectors around the skull. The corrected activities
are listed in Table 2.
By comparing the results for the mixed detector con-
figur ation with the resul ts f or the skeleton configur ation,
it appears that the acti vity value f or the skeleton is co-
her ent only when using ICRP F emale: the calibration
with ICRP Man produces a discrepa ncy of 30 %.
A partial explanation for the issue is related to the
MCNPX simulations and the quality of the models
used to reproduce the detectors: currently, they are
optimised only for the front face, not for the photons
impinging on the sides of the crystal. More accurate
models will be available in the future.
The placement of the detectors relative to the
subject affects the results heavily, and it is the most
probable cause of the discrepancy between skull and
knees measurements. Additional simulations found
the efficiency for the skull to decrease by 50 % for a
2-cm slide of the subject down the reclined stretcher
[see the pictures in (2)]. The placement of the detec-
tors was checked at the beginning, but not at the end
of the measurement sessions; therefore, an accurate
correction factor for the measurements around the
skull is not possible. A similar issue may affect the
data for the knees, but the effect is an order of magni-
tude smaller: the simulations showed a decrease in the
counting efficiency of at most 7 % for a slide of 2 cm.
INTERPRETATION OF MEASUREMENTS
This inhalation case has been analysed in the past by
different authors and has been used in an internal
dosimetry inter-comparison exercise
(5)
. The analysis
did show a very long lung retention, which could only
in part be accounted for by assuming that the inhaled
material was very insoluble. A significantly slower
particle transport clearance mechanism in the lungs
had also to be assumed in order for the model predic-
tions to agree with the measurements.
The data have been analysed here, by using the fol-
lowing models:
for deposition, particle transport and absorption
to blood in the respiratory tract, a revision of
the Human Respiratory Tract Model (HRTM)
(6)
.
In the revised particle transport model, the mater-
ial deposited in the alveolar compartment clears
to the bronchial tree at a rate of m
T
¼ 0.002 d
21
and to the interstitial compartment at a rate of
m
I
¼ 0.001 d
21
. The interstitial compartment
clears very slowly to the regional lymph nodes at
a rate of 0.00003 d
21
;
for transit through the alimentary tract the ICRP-
30 model
(7)
;
for systemic biokinetics, the Leggett model f or plu-
tonium
(8)
and the ICRP model for americium
(9)
.
The isotopic composition of the inhaled aerosol was
estimated from measurements in January 1983 (4
months before the accident) on the fuel samples used
in the solution that was overheated and spread out in
the accident. The alpha activity composition is
recorded as 10 %
241
Am, 9 %
238
Pu, 55 %
239
Pu and
26 %
240
Pu. The
241
Pu (beta) activity is 750 % of the
total alpha activity. The uncertainty on these mea-
surements is not known. The above isotopic compos-
ition is consistent with the activity ratio (
238
Pu þ
241
Am)/(
239
Pu þ
240
Pu) ¼ 0.24 + 0.05 calculated
from the early faecal samples. There are no faecal
measurements for
241
Pu, but a previous laboratory
record gives the
241
Pu activity as 655 % of the total
alpha activity whereas all the alpha activities are
within a few per cent from the values given above. The
reason of the discrepancy for
241
Pu is not known.
As in the previous analysis, an effective AMAD
(10)
(Activity Median Aerodynamic Diameter) of 5 mm
has been estimated from early lung and early faecal
excretion data (including the activity that would have
appeared in the faeces if it had not been not removed
with a nasal swab and a bronchial slime before the
first chest measurement was done
(1)
). This value has
been used to calculate the fractions of material
Table 1. Activities calculated for the mixed configuration,
according to the calibration phantom used.
Organ ICRP Female [Bq] ICRP Man [Bq]
Skeleton
a
152 288
Lung left
b
60 73
Lung right
b
59 77
Liver 0 0
a
Based on knee measurements.
b
The calibration phantom did not distinguish between lung
and thoracic lymph nodes.
Table 2. Activities calculated for the skeleton-specific
configuration, according to the calibration phantom used.
Organ measured ICRP Female [Bq] ICRP Man [Bq]
Knee 103 216
Knee 141 270
Average knees 122 243
Skull left 176 556
Skull right 184 449
Average skull 180 503
C. WERNLI ETAL.
58

deposited in each of the lung regions. The calculated
activity deposited in the nasal region has been
adjusted by subtracting the amount that was removed
immediately after the intake by nose swab. This cor-
rection does not affect the estimate of the effective
dose but only the fit to the very early faecal data.
Particles deposited in the lungs are cleared by two
competing mechanisms, by particle transport (to the
gut and to the l ymph nodes) and b y absorption to
blood of the dissolving ma terial. For the latter, f
r
indi-
cates the fraction dissolved rapidly at the rate s
r
,
whereas the complementary fraction (1 2 f
r
)isdis-
solv ed slowly at the rate s
s
. A fra ction f
b
of the dissolved
material may not be absorbed directly into blood and
could bind temporaril y (s
b
. 0) or permanentl y (s
b
¼
0) to lung tissues. As mentioned, the fra ction (1 2 f
b
)is
availabletobeabsorbedtobloodattheratess
r
and s
s
.
Absorption of material fr om the respiratory tra ct to
blood wa s shown to be slo w in pre vious analy sis. The
inhaled material was initiall y assumed to be ‘type S’
solubility
(11)
, with absorption parameter values: f
r
¼
0.001, s
r
¼ 1d
21
, s
s
¼ 0.001 d
21
, and a bound state
was assumed with f
b
¼ 0.002 and s
b
¼ 0d
21(6, 12)
.
Note that the bound state does not play a significant
role in the long-term retention in the lungs because
the material is relatively insoluble. The gut uptake
fraction was kept fixed to its default value of f
1
¼ 5
10
24
for type S material.
Measurement err ors wer e assumed to be log-normally
distrib uted. The geometric standard devia tions, or sca tter -
ing factors , for the differ ent da tasets wer e either estima ted
from the data, as described by Marsh et al.
(13)
,or
based on the default values given in the IDEAS
guidelines
(10)
. The values for the scattering factors were
1.2, 1.6 and 2.4 for chest, urine and faecal measure-
ments and 2 for liver and skeleton.
The agreement between measurements and model
predictions was poor when using default parameter
values, and the following changes to the models were
introduced to improve the fit to the data:
the particle transport in the alveolarinterstitial
region was reduced;
the absorption parameter values of the inhaled
material were optimised, either assuming that
they were the same for Am and Pu (i.e. shared
values) or that they were different (i.e. independ-
ent);
the isotopic activity composition was allowed to
vary;
the transfer rates from blood to urinary bladder
were varied in order to improve the fit to the skel-
eton and liver measurements.
The changes were applied by finding optimal model
parameter values using the maximum-likelihood
method. To address first the issue of activity balance,
only chest and excretion data were used. Liver and
skeleton data were included only in the last stage of
the optimisation. The agreement between model pre-
diction and measurements improved significantly, in
terms of chi-squared, for each of the above changes
(Table 3).
The adoption of the revised HRTM model
(6)
improves the fit to lung and faecal excretion data,
compared with the previous HRTM
(11)
, but a further
reduction of the particle transport rate from the al-
veolar region to the bronchiolar needs to be applied,
from m
T
¼ 2
`
10
23
d
21
to m
T
¼ 3
`
10
24
d
21
. The
optimal value for the rate to the interstitial regions
(m
I
¼ 8.5
`
10
24
d
21
) differs only slightly from the
default value (m
I
¼ 1
`
10
23
d
21
). The changes may
also be expressed as an increase of the so-called
sequestered fraction in the alveolar interstitial
region, m
I
/(m
I
þ m
T
) from 0.33 to 0.74 and in the
slowdown of the clearance to the gut. This value is
relatively high but close to the upper limit of the 68 %
probability range for the inter-subject variation: (0.2,
0.7)
(14)
. Assuming that americium is more soluble
than plutonium in the lungs improves the overall pre-
diction for urine excretion, although the very late
americium excretion remains slightly overestimated.
The rapid and slow absorption rates s
r
and s
s
for plu-
tonium are not well determined by the data, and it
would be possible to assume the same values of s
r
and
s
s
(shared values) for both Am and Pu without affect-
ing significantly the fit to the data. However, a much
better fit is obtained when the values for the rapid
fraction f
r
are optimised independently. The optimal
shared values are s
r
¼ 0.2 d
21
and s
s
¼ 5
`
10
25
d
21
,
and f
r
¼ 0.0014 for Pu and f
r
¼ 0.05 for Am. The
result might be interpreted as an indication that
Table 3. Lung absorption parameters, committed effective
dose (CED) and organ doses (equivalent doses and per cent
contribution to the effective dose) for each added changes in
the optimisation.
PT þ
AbsP
þ isotopic
composition
þ Blood
UB
f
r
(Pu) 0.0014 0.0017 0.004
f
r
(Am) 0.05 0.04 0.08
s
r
(d
21
) 0.21 0.19 0.32
s
s
(10
25
d
21
)5 5 7
CED (Sv) 1.3 1.1 1.2
Lung
[Sv (%)]
8.3 (77) 6.8 (74) 6.3 (67)
Liver 2.3 (7) 2 (7) 3 (10)
Bone surface 10 (8) 9 (8) 14 (12)
R.B.M. 0.5 (5) 0.5 (5) 0.7 (7)
x
2
TOT
(236 data)
261 232 212
a
x
2
LUNG
(17 data)
38 16 12
a
242 data, including skeleton (3) and liver (3) data.
30-Y FOLLOW-UP OF A P
U/AM INHALATION CASE
59

initially americium dissolves faster. Americium oxide
is generally more soluble than plutonium oxide
(15)
,
but it is usually also considered that the rate at which
a particle dissociates is determined by the particle
matrix and therefore the dissolution parameter values
for americium and plutonium should be similar if
they belong to the same matrix. An interpretation of
the above result could possibly be provided by a better
knowledge of the physicochemical properties of the
inhaled material.
The overall fit is not sufficiently good, and this is
mainly due to the model prediction being ‘pulled’ in
opposite directions by chest and urine data.
An estimate of the isotopic composition of the
inhaled material is necessary to determine the initial
amount of americium and plutonium (isotopes)
deposited in the lungs. The values given above have
been considered as fixed in previous analysis. Based
on the available information, the authors assumed
here a relative error of 10 % and used it for a con-
strained optimisation. This would be equivalent to
introduce a prior distribution for the isotopic frac-
tions within a Bayesian framework.
The result of the optimisation, 13 %
241
Am, 9 %
238
Pu, 53 %
239
Pu, 25 %
240
Pu and 660 %
241
Pu,
shows that the complete set of data and the models
used might be more consistent with a different isotop-
ic composition. However, the ratio (
238
Pu þ
241
Am)/
(
239
Pu þ
240
Pu) ¼ 0.25 is still compatible with the es-
timate 0.24+0.05 based on the early faecal measure-
ments. The lower beta activity (
241
Pu) also cannot be
completely excluded because of the two different
values given in the laboratory records.
The previous adjustments to the models improve
significantly the overall agreement between model
prediction and experimental data, except for liver and
skeleton. The reasons for the discrepancy could be
various, but to improve the fit to the liver and skeleton
data, it is necessary to modify systemic parameter
values. A sensitivity analysis shows that reducing the
amount transferred from blood to bladder is the most
effective in ensuring a good fit to the two systemic
organ datasets and improving further the agreement
with the urine data. The main effect is an increase of
the dose to internal organs, because more activity is
retained in the body instead of being excreted through
urine, and an adjustment of the lung absorption para-
meters. Note that this effect is achieved even if liver
and skeleton data are not included in the fitting
because it is mainly driven by the urine data. The rates
from blood to urinary bladder have been changed by
keeping constant the removal half-time from blood. A
constraint equivalent to a lognormal prior distribution
with geometric standard deviation equal to log(1.7)
(16)
has been applied in the optimisation.
Table 3 shows how the optimal parameter values,
doses and chi-squared did vary when the changes [ par-
ticle transport (PT) plus absorption parameters (AbsP),
isotopic composition, blood to urinary bladder] w e r e
app lied sequentially.
LUNG ABSORPTION PARAMETERS
The maximum-likelihood procedure used for the
parameters estimation indicates that the shared par-
ameter s
r
and f
r
for Pu are less well defined by the
data than the other parameters. The estimates of f
r
, s
r
and s
s
are not significantly correlated between them
(j
r
j , 0.15) but show higher correlation with the esti-
mate of the blood-to-urinary bladder rate.
The uncertainty on the estimates of the lung ab-
sorption parameters has been further investigated by
using Bayesian Markov chain Monte Carlo sam-
pling
(17)
. Lognormal prior distributions have been
assumed for the parameters, which were constraint in
the optimisation. ‘Non-informative’ priors (normal
distribution for the log-transformed variable with
s
¼ 2 and centred on the best-fit result) have been
used for all the other parameters. Most of the absorp-
tion parameters were well defined (Table 4) as the pos-
terior distribution was relatively narrow (compared
with the prior distribution) and approximately
centred on the best-fit value. The exceptions are the
fast-absorbed fraction f
r
for plutonium, for which
only an upper limit ( f
r
, 0.015) is clearly defined,
and for the shared parameter s
r
for which the lower
limit is better defined than the upper limit (s
r
. 0.2
d
21
). All set of measurements used in the analysis are
given in the Annex (Tables A1 A5). Figures 14
show measurements and best-fit model predictions for
a subset of the datasets. As shown in Figure 1,mostof
the
241
Am activity predicted in chest at later times is
due to in-growth from
241
Pu.
CYTOGENETIC ANALYSIS
In addition to the biokinetic modelling, three differ-
ent cytogenetic assays have been performed to analyse
diverse biomarkers of exposure in blood lymphocytes.
Dicentric assay
Up to now, the conventional analysis of dicentric
chromosomes (dicentric assay) is the most appropriate
Table 4. MCMC results for lung absorption parameters
and CED.
Mean value 95 % probability interval
f
r
(Am) 0.08 0.040.12
f
r
(Pu) 0.003 ,0.015
s
r
(d
21
) 0.4 0.175
s
s
(d
21
)8
`
10
25
6
`
10
25
–1
`
10
24
CED (Sv) 1.2 1.01.35
C. WERNLI ETAL.
60

assay to estimate a dose in case of an acute irradi-
ation
(18, 19)
. This assay was also used in a previous
examination of the same person years ago
(1)
. In the
present study, a total of 1000 cells from Giemsa
stained slides were analysed. The observed frequency
of 2 dicentric chromosomes per 1000 cells was not sig-
nificantly different ( p . 0.05) in comparison with the
authors’ control value of 1.15 dicentric chromosomes
per 1000 cells. This result was to be expected because
of the 30-y time period between the first accidental
exposure and the current blood sampling. The bio-
logical half-life of lymphocytes with dicentric chro-
mosomes is assumed to be 3 y. Due to a detriment of
dicentric chromosomes during cell division, the yield
of lymphocytes in the circulating blood bearing this
biomarker will decrease in the course of time.
FISH assay (symmetrical translocations)
The yield of symmetrical translocations in 3017 cells
scored was significantly increased (23.8+5.0/1000
cells, FG (Genome equivalents) values) in compari-
son with an age-adjusted control group including 35
persons and 88 934 cells scored [7.5+0.51/1000 cells,
FG (Genome equivalent) values]. This aberration
type has the advantage to pass cell division without
major detriment and thus is more persistent. In conse-
quence , s ymmetrical a berra tions ar e the indica tor of
choice f or past and chronic radiation conditions
(20)
.In
the curr ent case, the significantincreaseofsymmetrical
translo cations indica tes an irradiation incident. Because
of the la ck of an appropriate doseef fect curve f or this
radiation quality (alpha particles) and the extreme long
time period since the exposur e, a dose r econs truction
wa s consider ed to be not feasible.
Figure 4.
239
Pu þ
240
Pu in 24-h faecal excretion.
Figure 1.
241
Am in chest. The dash-dotted curve shows the
predicted
241
Am activity without taking into account of
in-growth from
241
Pu.
Figure 2.
241
Am þ
238
Pu in 24-h urine excretion.
Figure 3.
239
Pu þ
240
Pu in 24-h urine excretion.
30-Y FOLLOW-UP OF A P
U/AM INHALATION CASE
61

Citations
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Journal ArticleDOI
TL;DR: The 2007 Recommendations introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series and Publications 54, 68, and 78.
Abstract: The 2007 Recommendations (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979a,b, 1980a, 1981, 1988) and Publication 68 (ICRP, 1994b). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1989a, 1997) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2 and its task groups. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. OIR Part 1 (ICRP, 2015) describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016), OIR Part 3 (ICRP, 2017), this current publication, and the final publication in the OIR series (OIR Part 5) provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic models; and data on monitoring techniques for the radioisotopes most commonly encountered in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv per Bq intake) for inhalation and ingestion, tables of committed effective dose per content (Sv per Bq measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The online electronic files that accompany the OIR series of publications contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. This fourth publication in the OIR series provides the above data for the following elements: lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), promethium (Pm), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), lutetium (Lu), actinium (Ac), protactinium (Pa), neptunium (Np), plutonium (Pu), americium (Am), curium (Cm), berkelium (Bk), californium (Cf), einsteinium (Es), and fermium (Fm).

25 citations


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Journal ArticleDOI
TL;DR: These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO2 inhalation, as a prophylaxis against lung cancer.
Abstract: Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO2 inhalation, as a prophylaxis against lung cancer.

19 citations


Cites background from "30-Y follow-up of a PU/AM inhalatio..."

  • ...Furthermore, the 30-year follow-up of a plutonium-americium inhalation exposure, with a committed effective dose of the order of 100 cSv, shows no evidence of lung cancer; the subject is in good health (Wernli et al. 2015)....

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01 Jan 2011
Abstract: The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements.

8 citations


Book ChapterDOI
01 Jan 2017
Abstract: Single large radioactive particles are not carcinogenic in the lung. Plutonium dioxide is not the most toxic chemical compound known. About a million grams of plutonium have been initially entrained in the air from nuclear weapon testing. An initial inhaled concentration of >100,000 submicron diameter 239-plutonium dioxide particles per gram lung are associated with formation of large particle aggregates in the lung, giving a threshold dose to the lung of about 1 Gy for lung tumor development in rats, dogs and humans. Evidence of radiation hormesis has been found in animals and plutonium workers. A nuclear technician accidentally exposed to americium, delivering enormous radiation doses to the lung, liver and skeleton, died eleven years later at the age of 75 without any evidence of cancer. USTUR participants lived ten years longer than those not exposed to high levels of transuranics.

1 citations


Journal ArticleDOI
Abstract: PURPOSE Biological and/or physical assays for retrospective dosimetry are valuable tools to recover the exposure situation and to aid medical decision making. To further validate and improve such biological and physical assays, in 2019, EURADOS Working Group 10 and RENEB performed a field exercise in Lund, Sweden, to simulate various real-life exposure scenarios. MATERIALS AND METHODS For the dicentric chromosome assay (DCA), blood tubes were located at anthropomorphic phantoms positioned in different geometries and were irradiated with a 1.36 TBq 192Ir-source. For each exposure condition, dose estimates were provided by at least one laboratory and for four conditions by 17 participating RENEB laboratories. Three radio-photoluminescence glass dosimeters were placed at each tube to assess reference doses. RESULTS The DCA results were homogeneous between participants and matched well with the reference doses (≥95% of estimates within ±0.5 Gy of the reference). For samples close to the source systematic underestimation could be corrected by accounting for exposure time. Heterogeneity within and between tubes was detected for reference doses as well as for DCA doses estimates. CONCLUSIONS The participants were able to successfully estimate the doses and to provide important information on the exposure scenarios under conditions closely resembling a real-life situation.

1 citations


References
More filters

Journal ArticleDOI
TL;DR: The versatility and simplicity of the CBMN assay together with new developments in automation should ensure its successful application in monitoring exposed populations as well as in identifying mutagen-sensitive individuals within a population.
Abstract: The development of the cytokinesis-block (CB) technique has transformed the human-lymphocyte micronucleus assay (MN) into a reliable and precise method for assessing chromosome damage. Recent studies in our laboratory have confirmed that this method is a sensitive indicator of in vivo radiation exposure in (a) patients undergoing fractionated partial-body radiotherapy and (b) rodents exposed to uniform whole-body irradiation, thus supporting the application of the cytokinesis-block micronucleus (CBMN) assay for biological dosimetry. To further define the use of this assay in biomonitoring we performed extensive studies to determine the spontaneous level of MN in normal human populations and its relationship to various life-style factors. We have also developed a new variation to the CBMN assay that permits the conversion of excision-repairable lesions to MN within one cell-cycle using cytosine arabinoside. With this method the slope of the in vitro dose-response curves was increased by a factor of 1.8 for X-rays, 10.3 for ultraviolet (UV, 254 nm) radiation and approximately 40-fold for methylnitrosourea. Consequently the CBMN assay can now be used to measure not only whole chromosome loss or chromosome breaks but also excision-repair events. The versatility and simplicity of the CBMN assay together with new developments in automation should ensure its successful application in monitoring exposed populations as well as in identifying mutagen-sensitive individuals within a population.

936 citations


"30-Y follow-up of a PU/AM inhalatio..." refers background in this paper

  • ...The reason is the relatively high and variable spontaneous frequency of micronuclei in control cells, which tends to increase with age and also shows gender dependency((21))....

    [...]



Journal ArticleDOI
Abstract: The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements.

204 citations


Journal ArticleDOI
TL;DR: Concerns with implementation should not deter the biostatistician from using MCMC methods, but rather help to ensure wise use of these powerful techniques.
Abstract: Appropriate models in biostatistics are often quite complicated. Such models are typically most easily fit using Bayesian methods, which can often be implemented using simulation techniques. Markov chain Monte Carlo (MCMC) methods are an important set of tools for such simulations. We give an overview and references of this rapidly emerging technology along with a relatively simple example. MCMC techniques can be viewed as extensions of iterative maximization techniques, but with random jumps rather than maximizations at each step. Special care is needed when implementing iterative maximization procedures rather than closed-form methods, and even more care is needed with iterative simulation procedures: it is substantially more difficult to monitor convergence to a distribution than to a point. The most reliable implementations of MCMC build upon results from simpler models fit using combinations of maximization algorithms and noniterative simulations, so that the user has a rough idea of the location and scale of the posterior distribution of the quantities of interest under the more complicated model. These concerns with implementation, however, should not deter the biostatistician from using MCMC methods, but rather help to ensure wise use of these powerful techniques.

184 citations


"30-Y follow-up of a PU/AM inhalatio..." refers methods in this paper

  • ...The uncertainty on the estimates of the lung absorption parameters has been further investigated by using Bayesian Markov chain Monte Carlo sampling((17))....

    [...]


Journal ArticleDOI
TL;DR: The systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information.
Abstract: Leggett, R. W., Eckerman, K. F., Khokhryakov, V. F., Suslova, K. G., Krahenbuhl, M. P. and Miller, S. C. Mayak Worker Study: An Improved Biokinetic Model for Reconstructing Doses from Internally Deposited Plutonium. Radiat. Res. 164, 111–122 (2005). The plutonium production facility known as the Mayak Production Association was put into operation in June 1948. A high incidence of cancer in the Mayak workers has been related to the level of exposure to plutonium, but uncertainties in tissue doses have hampered development of dose–risk relationships. As part of an effort to improve dose estimates for these workers, the systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information. This paper describes the proposed model and discusses its implications for dose reconstruction for the Mayak workers.

120 citations


"30-Y follow-up of a PU/AM inhalatio..." refers background in this paper

  • ...00003 d(21); † for transit through the alimentary tract the ICRP30 model((7)); † for systemic biokinetics, the Leggett model for plutonium((8)) and the ICRP model for americium((9))....

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  • ...3 (7) 2 (7) 3 (10) Bone surface 10 (8) 9 (8) 14 (12)...

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Frequently Asked Questions (1)
Q1. What contributions have the authors mentioned in the paper "30-y follow-up of a pu/am inhalation case" ?

Wernli et al. this paper, Jost Eikenberg, Olaf Marzocchi, Bastian Breustedt, Ursula Oestreicher, Horst Romm, Demetrio Gregoratto and James Marsh.