Biokinetics of ruthenium isotopes in humans and its dependence on
chemical speciation.
Augusto Giussania, Marie Claire Cantoneb, Udo Gerstmanna, Matthias Greitera,
Ralf Hertenbergerc, Vera Höllriegla, Karsten Leopolda, Ivan Veroneseb, Uwe Oeha*
a
Helmholtz Zentrum München, German Research Center for Environmental Health,
Institute of Radiation Protection, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
b
Università degli Studi di Milano, Department of Physics, and INFN, via Celoria 16,
20133 Milano, Italy.
c
University of Munich, Am Coulombwall 1, 85748 Garching, Germany.
Abstract. Tracer studies in healthy volunteers using stable isotopes of ruthenium were performed with the
objective of extending the limited knowledge about the biokinetics of the radionuclides of this element. Tracer
solutions were prepared starting from metallic ruthenium powders enriched in either 99Ru or 101Ru (isotopic
enrichment ca. 98%). Tracer administration was followed by the collection of blood and urine samples at fixed
times. Some investigations were conducted by means of the double tracer technique, consisting in the
simultaneous administration of two tracers, one orally and the other intravenously. Tracer concentrations in
biological samples were determined by means of proton activation analysis. Blood clearance and urinary excretion
were noticeably affected by the degree of complexation of ruthenium in the administered solution. After injection
of solutions characterized by a high degree of complexation between ruthenium and citrate, the disappearance
from plasma was faster than with poorly complexed ruthenium. Accordingly, the percentage promptly eliminated
into urine was about 50% for highly complexed ruthenium and 20% in the case of low complexation. The fraction
absorbed from the intestine into the circulation was lower than the current ICRP estimate of 0.05 for nearly all
chemical forms investigated. Only in the case of high complexation degree the absorbed fraction was significantly
higher (0.108±0.022) than the ICRP value.
KEYWORDS: internal dosimetry, ruthenium, biokinetics, systemic model.
1. Introduction
The radionuclides of ruthenium 103Ru (T1/2=39 d) and 106Ru (T1/2=374 d) are produced in appreciable
amounts during fission processes, and in case of accidents they may be released in the environment in
amounts which are comparable to those of 131I and 137Cs [1-7]. These radionuclides were emitted in
particulate form at the time of the explosion of the Chernobyl reactor, and in volatile form during the
successive burning phase [8]. Particles with very high specific activity ("hot particles"), containing a
relevant proportion of 103Ru and 106Ru, were found also at very large distances from the site of the
accident [4, 8-11]. The activities of these nuclides, traced back to the time of the accident, were as high
as 140 kBq per particle, i.e. approx. 100 Bq⋅μm-3. The shape and size of these "hot particles" (up to 20
µm diameter, and even larger in the vicinity of the reactor) were typical of fused material, indicating the
high temperature reached inside the reactor core (melting point of ruthenium: 2583 K) [12]. The
radiological hazard of these highly active particles is related mainly to skin deposition and ingestion;
inhalation doesn't seem to be a relevant incorporation pathway due to the dimensions of the particles
[13].
Radioisotopes of ruthenium have been reported to contribute up to 60% of the beta activity released into
the environment from aqueous wastes [14]. They were also major contributors to the contamination of
the Techa River waters (Muslyumovo region, former Soviet Union) in the period when the Mayak
plutonium production facility intentionally discharged its wastewaters into the river [15]. Additionally,
the release of 103Ru and 106Ru into the environment following atmospheric nuclear tests conducted
between 1945 and 1980 should also be considered. According to the calculations performed by
*
Presenting author, E-mail: [email protected]
1
UNSCEAR (United Nation Scientific Committee on the Effects of Atomic Radiation), the contribution
of 103Ru and 106Ru amounts to 7.5 % of the dose due to external exposure and to 24% of the dose due to
inhalation exposure [16].
In spite of this broad evidence on the release of ruthenium radionuclides and on the radiological risks
connected to their potential incorporation, information on the biokinetics of ruthenium is mainly limited
to experimental animals. The only human data refer to a work by Yamagata et al. [17], in which
intestinal absorption, whole body retention and excretion patterns were investigated after successive
oral administrations of 103Ru to one subject. In the three studies the tracer was administered in the form
of metabolized ruthenium in shellfish, of unmetabolized chloro complexes of nitrosylruthenium(III),
and of ruthenium(III-IV) chloride complexes, respectively. No other data from controlled studies on
humans are available to our knowledge. Consequently, the International Commission on Radiological
Protection ICRP [18] describes internal distribution and retention of ruthenium with a systemic model
which is based mainly on data from animal experiments. The model assumes that ruthenium is cleared
from the circulation with a biological half-life of 0.3 d and is homogeneously distributed in the
organism where it is retained with half-lives of 8 d (35%), 35 d (30%) and 1000 d (20%). The remaining
15% is promptly eliminated into the excreta. Of the ruthenium that entered the systemic circulation,
80% is eliminated into the urine and 20% into the feces.
More human information would be desirable for the correct set-up of the model, in order to provide
reliable estimates of the dose coefficients and solid interpretation of bioassay measurements in possibly
contaminated subjects. The use of isotopically enriched stable tracers represents an ethically acceptable
methodology for performing biokinetic investigations in healthy human volunteers. Through the
administration of the tracers to the volunteers and the determination of their concentrations in biological
samples, like blood plasma and urine, it is possible to obtain information about absorption into the
systemic circulation, clearance from blood, and urinary elimination. The comparison between model
predictions and actual human data can indicate if and to what extent the model can be improved.
A methodology for conducting ruthenium biokinetic studies based on stable tracer administration and
activation analysis with charged particles was presented previously, together with preliminary results on
the kinetics in blood of animals and humans [19-22]. In this work, the whole set of human tracer studies
is presented, and the effect of chemical speciation on intestinal absorption, blood clearance and urinary
excretion is discussed on the basis of the results achieved.
2. Materials and Methods
2.1 Stable isotopes
Stock solutions were prepared starting from metal powders enriched in 99Ru (Campro Scientific,
Veneendal, The Netherlands) and 101Ru (Chemotrade, Düsseldorf, Germany). The isotopic
compositions of the two tracers, which were selected on the basis of the preliminary optimization
studies, are shown in Table 1 and compared to the naturally occurring abundances. In order to bring
ruthenium into solution, 10 mg of metal powder was weighed in a nickel crucible with an oxidizing
alkaline mixture of about 1.4 g potassium hydroxide and 0.14 g potassium nitrate and heated for 45
min at 520 °C in a muffle furnace. The cooled melt was then dissolved at room temperature in 40 ml
of HCl/HNO3 mixture and evaporated to dryness. Finally, the residue was diluted in deionized water to
the desired concentration.
Table 1: Isotopic composition (atom %) of natural ruthenium [23] and of the stable isotopes (as
certified by the producers).
96
natural
99
Ru tracer
101
Ru tracer
2
Ru
5.54
0.12
0.07
98
Ru
1.87
0.12
0.07
99
Ru
12.76
97.69
0.15
100
Ru
12.60
0.74
0.32
101
Ru
17.06
0.48
97.82
102
Ru
31.55
0.58
1.35
104
Ru
18.62
0.27
0.21
The injection solutions were made isotonic by adding adequate amounts of sodium chloride and
sodium citrate, which correlates to a ratio of 1 mmol Na-citrate for 10 µmol ruthenium. Sterility of the
solutions was checked according to German and European Pharmacopeia [24]. The injection solutions
had a pH value of ca. 3.
2.2 Tracer kinetic studies
2.2.1 Amount and form of administration
A total of 16 studies in 5 volunteers (4 males and one female, ages 23-60 years) were conducted over a
period of 7 years. In particular, repeated investigations on the same subject were performed to check
the reproducibility of the observed biokinetic profiles and to examine how they are influenced by the
chemical form of administration. Table 2 summarizes the main features of the studies.
Table 2: Tracer studies of ruthenium biokinetics.
Volunteer
Study
code
Oral tracer
0100
0101
0102
0103
Amount
0.84 mg 101Ru
1.78 mg 101Ru
-
0104
2.90 mg 99Ru
0105
-
0112
2.97 mg 99Ru
0206
0207
0300
0308
0309
0310
0311
0.58 mg 99Ru
2.85 mg 99Ru
0.84 mg 101Ru
1.77 mg 101Ru
1.11 mg 101Ru
04
0413
1.06 mg 99Ru
05
0514
1.07 mg 99Ru
01
02
03
Form*
citrate (L)
ascorbate
inorganic, with baby
formula
inorganic, dissolved
in black tea
ascorbate
ascorbate
ascorbate
citrate (L)
citrate (H)
citrate (L), with
salad
citrate (L), with
salad
Intravenous tracer
Amount
Form*
101
0.21 mg Ru
citrate (L)
101
0.24 mg Ru
citrate (H)
0.24 mg 101Ru
citrate (H)
0.26 mg 101Ru
citrate (M)
0.23 mg 101Ru
citrate (H)
0.23 mg 101Ru
0.24 mg 101Ru
0.25 mg 101Ru
0.25 mg 101Ru
-
citrate (H)
citrate (H)
citrate (H)
citrate (H)
-
0.23 mg 101Ru
citrate (H)
0.26 mg 101Ru
citrate (H)
* Complexation degree: L = low, M = moderate, H = high (see text for more details)
In two studies (0102 and 0105) the injection solution was sterilized just before administration through
single sterile filter membranes (Millipore, 0.22 µm pore diameter). In all other investigations the
injection solution was taken from sealed glass ampoules which had been additionally autoclaved at
120°C for 20 min. Chemical analysis presented in [22] demonstrated that the degree of complexation
of ruthenium and citrate increased with time after preparation and with heating. So, in experiment
0102 the injected solution contained mainly ruthenium in inorganic form, with only a low fraction
bound to citrate, since the unheated solution was administered to the volunteer on the day of
preparation. In study 0105 the complexation degree was moderate, since this experiment was
performed one day after the preparation of the solution for injection. In all other investigations the
injection solution, taken from the sealed ampoules, contained primarily stable ruthenium-citrate
complexes.
3
Different chemical forms were used also for the oral administration, adding Na-citrate or ascorbic acid
to the stock solution. In most of the studies, citrate solution was added shortly before the
administration, so that the complexation degree can be considered low. An exception is study 0311,
where the volunteer ingested an aliquot of the highly-complexed solution for injection. Also ascorbic
acid was added shortly before the administration; differently from citrate, however, the chemical
reaction of ascorbate and ruthenium proceeded very rapidly, as it was evident also by the rapid change
of colour of the solution. Therefore it can be speculated that in studies 0101, 0206, 0207, 0300
ruthenium was mainly present in form of Ru-ascorbate-complexes. Finally, an aliquot of the stock
solution, containing inorganic ruthenium, was administered in two additional tests: together with a
baby formula (0104) and dissolved in black tea (0112).
2.2.2 Study design
The investigations were performed according to the protocol approved by the Ethical Committee of
the Technical University Munich. Informed consent was obtained from the volunteers before each
investigation. All investigations started in the morning with the subject fasting from the evening
before. Six investigations were conducted according to the double tracer technique, by simultaneous
administration of the two tracers (one given orally, the other injected) to the volunteers. In the
remaining ten experiments only one tracer was administered, either via ingestion or intravenously.
One blood sample (blank) was taken few minutes before the start of each investigation. Also one total
24-h blank urine sample was collected prior to the experiment. Blood samples of 10 ml volume each
were collected at fixed times post-administration. In the experiments with intravenous administration,
the blood samples were withdrawn via an in-dwelling catheter from a vein of the arm opposite to that
used for injection. By withdrawal of the blank value, the first few ml of blood were discarded in order
to eliminate a possible contamination of metal traces through the catheter needle. Complete urinary
excretion was collected up to 6 d post-administration, pooled in 24-h samples (two 12-h samples in the
first day). Two hours after administration of the tracers, the subjects consumed a standard continental
breakfast consisting of black coffee with sugar and 2 rolls with butter and jam.
2.3 Sample measurements
2.3.1 Sample processing
Blood plasma was separated from whole blood by centrifugation and then stored frozen until analysis.
An aliquot of plasma equal to 0.8-1.0 ml was withdrawn with a micropipette from each test tube,
weighed and placed in a polyethylene dish. After addition of a known amount of 51V, used as an
internal reference isotope, the samples were dried, powdered in an agate mortar and compressed to
form self-supporting tablets. The technique for the preparation of the tablets from the urine samples,
described in a previous work [25], was more complicated, requiring several chemical steps of acid
dissolution and extraction starting from about 10 ml urine. In the course of the studies, a simpler
procedure was developed consisting of the following steps:
(a) mixing of urine with a 100 µl of 51V standard solution, followed by incubation for 8 h at
37°C;
(b) pressure digestion of urine samples with a mixture of 4.8 ml HNO3 and 0.8 ml of H2O2 at
increasing temperature from 50°C to 180°C, during a period of 5h;
(c) evaporation of the digested samples to dryness on a hot plate (∼ 30 h at 120 °C).
For each experiment, standard samples were prepared using the same procedures and adding known
amounts of the reference isotope 51V and of the tracer(s) of interest, taken from the solution(s) used for
the corresponding investigation. The biological material for the plasma standard samples was
extracted from a pool consisting of mixed blood plasma of healthy subjects. The urine blank sample
collected before the investigation provided enough material also for the preparation of the standard
samples.
4
2.3.2 Activation experiments
Activation analysis with protons was used for the quantitative determination of the tracers in the
biological samples. Previous experiments had been performed using the cyclotrons at the Laboratories
of JRC-IHPC in Ispra, Italy (Scanditronix MC-40) and at the Paul Scherrer Institut in Villigen,
Switzerland (Philips Cyclotron). Since autumn 2005 the irradiation chamber has been transferred to
the Maier-Leibnitz-Laboratorium (MLL) in Garching (Germany) and connected to the beam-line of
the Tandem accelerator. With this chamber it is possible to irradiate simultaneously and in the same
experimental conditions up to 39 tablets, mounted into appropriate aluminium frames. On the basis of
preliminary studies, (p,n) reactions were chosen for the activation of the two tracers in blood plasma
and urine (Table 3).
Table 3: The reactions used in the activation experiments and the physical characteristics of the
radioactive products.
Ru(p,n)99Rh
Product
half-life
16.1 d
Ru(p,n)101mRh
V(p,n)51Cr
4.34 d
27.7 d
Reaction
99
101
51
Production cross section*
σmax (b)
Emax (MeV)
0.8
10.4
1.0
0.7
9.5
11.4
main γ-emissions
energy (keV)
intensity
528 keV
38.0 %
353 keV
34.6 %
90 keV
33.4 %
307 keV
81 %
320 keV
10 %
* Emax is the proton beam for which the production cross section reaches its maximum σmax
2.3.3 Gamma spectrometry
After the irradiation, the tablets were transferred into inactive supports and their gamma spectra were
acquired at the Radioanalytical Laboratory of the Helmholtz Zentrum München using two high purity
germanium detectors. The detectors' relative efficiencies (response towards 60Co) were 35.9% and
40.2%; the resolution (full width half maximum at 1332.5 keV line) were 1.79 keV and 1.80 keV,
respectively. For each sample the unknown tracer amounts were determined by comparing the
intensities of the gamma lines emitted by the corresponding reaction products and by the activated
reference isotope with those measured in the standard samples, after appropriate corrections for the
different cooling and measurement times.
3. Results and discussion
3.1 Optimization of the experimental conditions
As already mentioned, the irradiation facility was recently moved to the MLL laboratories in
Garching. Therefore, the experimental conditions had to be optimized and adjusted to the beam
characteristics of the Tandem accelerator (beam energy 20 MeV, beam intensity max. 2.5 µA).
Linearity and reproducibility tests were performed using biological samples artificially doped with
increasing amounts of the tracers of interest (from approximately 8.5 ng·ml-1 up to 170 ng·ml-1). Tests
were also performed in order to determine the optimal thickness of the aluminum cover encasing the
samples. As an example, Figure 1 shows the ratios between the intensity of the gamma lines of 99Rh
and the gamma emission of 51Cr as a function of cover thickness. The highest ratios, indicating the
most favorable conditions for the activation of 99Ru, were achieved with the thinner Al cover of 0.76
mm thickness; the higher signals were measured in correspondence to the line at 90 keV, due to the
higher detector efficiency in the low-energy portion of the spectrum. However, this line was disturbed
by interfering signals (x-rays emitted by the lead shielding). Further interferences were detected also
near the emission at 353 keV. On the basis of these analyses, the line at 528 keV proved to be the most
reliable for the detection of 99Rh in the biological samples, although the corresponding signal is lower
than those measured at lower energies. A similar analysis conducted on the samples doped with 101Ru
5
showed that the most favorable conditions for the activation of this second isotope could be achieved
when the two thicker covers (0.93 and 1.13 mm Al, respectively) were used. Taking all results into
account, it was therefore concluded that aluminum covers with thickness of 0.93 mm are the most
appropriate for the simultaneous determination of the two tracers.
Figure 1: Signal intensities in 99Ru-doped samples as a function of cover thickness.
0.04
90 keV
353 keV
528 keV
0.02
99
Rh/51Cr
0.03
0.01
0.00
0.7
0.8
0.9
1.0
1.1
1.2
Cover thickness (mm Al)
Figure 2 shows that the technique is linear over a broad range of concentration values.
Figure 2: Linearity test for the emission of 99Rh at 528 keV.
0.016
Line at 528 keV
0.014
0.012
0.008
99
Rh/51Cr
0.010
0.006
0.004
0.002
0.000
0
50
100
150
200
Amount of 99Ru added (ng ml-1)
The minimum detectable concentrations were evaluated as the concentrations that correspond to a
signal equal to 4.65 times the square root of the underlying background signal [26]. They amount to
7.5 ng·ml-1 for 99Ru and to 2 ng·ml-1 for 101Ru in blood plasma under typical experimental conditions
(irradiation time > 48 hours, measurement time ~ 3 d). In urine samples, the minimum detectable
concentrations were definitely lower (0.7 ng·ml-1 for 99Ru and 0.2 ng·ml-1 for 101Ru) as more material
was used for the preparation of the tablets. A specific optimization of the measurement conditions
enabled to improve the sensibility of the technique for selected samples. It should be mentioned that
measurements of blood plasma samples should start after a cooling time of at least 8 d in order to let
decay the interference at 306.5 keV emitted by 79Kr (half-life 35 h, produced by activation of 79Br
naturally present in blood).
6
3.2 Biokinetic studies
Until now blood plasma samples from 11 experiments and urine samples from 5 experiments have
been analyzed, covering 12 of the 16 experiments. In some cases, concentration of the oral tracer in
blood plasma and urine samples were near or below the detection limits, therefore only upper limits of
the amount transferred into the circulation and of the amount excreted in the urine could be estimated.
3.2.1 Plasma clearance and urinary excretion
The kinetics of ruthenium in the systemic circulation was strongly dependent on the chemical form of
administration. As already described in [22], inorganic ruthenium remained in the circulation with a
retention time of 23±2 h, whereas ruthenium complexed with citrate was rapidly eliminated (biological
half life 17±2 min). These results were confirmed by the analysis of the urine samples, shown in Fig.
3. It can be seen that urinary excretion of highly complexed ruthenium was rapid, with more than 40%
excreted in the first 12 h after administration and up to 70% over 2 d. On the contrary, after
administration of the poorly complexed solution the 48-h cumulated excretion amounted to less than
25%. For comparison, also the prediction of the ICRP is shown in Figure 3. It can be seen that the
current model underestimates the urinary excretion for all chemical forms considered.
Figure 3: Urinary excretion of the injected tracer. Green symbols: Ru-citrate, high complexation
degree; blue symbols: Ru-citrate, low complexation degree.
Percentage excreted in the urine
80
60
ICRP Model
0102
0103
0206
0514
40
20
0
0
12
24
36
48
Time after administration (h)
3.2.2 Intestinal absorption
The fraction of oral tracer which is absorbed into blood (named fA in ICRP Publication 100 [27],
previously indicated with the symbol f1) was estimated:
(i)
comparing the amounts of oral tracer and of injected tracer excreted in the urine over a certain
period (24-h or 48-h cumulated excretion),
7
(ii)
analyzing the concentration curves of the two tracers in blood plasma by means of the
convolution integral technique and/or by implementation of simple linear compartmental
models.
In order to achieve reliable values of the absorbed fractions, biokinetic differences due to speciation
should be taken into account. The analyses were therefore performed coupling sets of data related to
similar chemical forms for the oral and for the injected tracers. It should be however kept in mind that
some properties of the gastrointestinal environment, like its pH or the presence of other binding
ligands, might have affected the chemical form of the oral tracer before its transfer into the blood
system.
On the basis of these assumptions, it was possible to calculate an absorbed fraction of 0.0070±0.0018
for the solution containing ruthenium poorly complexed with citrate, and of 0.108±0.022 for the
solution with high degree of complexation. In three other cases (administration of inorganic
ruthenium, of Ru-ascorbate and of the poorly complexed solution together with salad) only upper
values of the absorbed fractions could be evaluated.
Figure 4: Fraction of ingested ruthenium absorbed to blood for different chemical forms of
administration (± SD). Bars have been used to indicate those cases for which it was possible to
estimate only the upper limit of the absorbed fraction. The dashed red line corresponds to the current
value of 0.05 recommended by ICRP for workers and adult members of the public.
Citrate, low complexation degree
Citrate, high complexation degree
Anorganic, with baby formula
Citrate, low complexation degree,
with salad
Ascorbate
Fraction absorbed into blood
0.12
0.10
0.08
0.06
0.04
0.02
0.00
0
The results of the fractional absorption of ruthenium for different chemical forms are presented in
Figure 4. The studies for which only an upper limit was evaluated are shown as bars. All estimates fall
below the current ICRP recommendation of 0.05 (dashed red line), with the exception of the one after
administration of the solution containing predominantly Ru-citrate complexes.
The human study of Yamagata et al. [17] indicated an absorbed fraction of 0.01 for ruthenium
metabolized in shellfish (clams). For the two other investigations reported in the same paper
(administration of chlorocomplexes of nitrosylruthenium(III) and of ruthenium(III, IV)), only values
for the urinary excretion were given. By comparison with the corresponding data from the experiment
8
with clams, absorbed fractions of 0.04 and 0.015 can be extrapolated for nitrosylruthenium(III) and
ruthenium(III, IV) respectively. The current value of 0.05 recommended by ICRP can be therefore
seen as a conservative upper estimate of the experimental findings for nearly all chemical forms
investigated. It should be pointed out that the value obtained for the highly complexed solution is the
result of one single investigation, and therefore it should be considered with caution and possibly
confirmed in new studies.
4. Conclusion
The effects of chemical speciation on intestinal absorption and biokinetics of ruthenium in humans
were studied in a series of investigations with stable isotopes. It was observed that the degree of
complexation of ruthenium strongly affected plasma retention and elimination into the urine. Intestinal
absorption for inorganic ruthenium, Ru-ascorbate, and poorly complexed Ru-citrate was lower than
the current value of 0.05 recommended by ICRP. The results presented give indications for possible
modifications to the current ICRP biokinetic model for ruthenium radioisotopes and specifically
underline the need of recommending separate sets of parameters depending on the chemical form.
Acknowledgements
The study was partially supported by the European Commission in the frame of EURATOM research
programmes (contracts FI4P-CT95-0011 and FIGD-CT2000-00053) and by the German Federal
Office for Radiation Protection BfS (contract StSch-4471). The authors would like to thank Prof. Dr.
Thomas Zilker and Dr. Norbert Felgenhauer of Technische Universität München, Department of
Clinical Toxicology, for the supervision of the tracer kinetic studies, Dr. Ludwig Beck, Walter Carli
and the whole staff at the Tandem Laboratory in Garching for their valuable assistance during the
activation experiments, and Prof. Luigi Garlaschelli from the Università degli Studi di Milano,
Department of Inorganic, Metallorganic and Analytical Chemistry, for interesting and fruitful
discussions.
REFERENCES
[1]
FRY, F.A, et al., Early estimates of UK radiation doses from the Chernobyl reactor, Nature 321
(1986) 193-195.
[2] BUSUOLI G., Radiological consequences of the Chernobyl accident for Italy, Radiat. Prot.
Dosim. 19 (1987) 247-251.
[3] GALASSINI, S., et al. Radioattività indotta dal fall-out della nube di Chernobyl, Il nuovo
saggiatore 4 (1986) 71-78 (in Italian).
[4] DENSCHLAG, H.O., et al., Fallout in the Mainz area from the Chernobyl reactor accident,
Radiochimica Acta 41 (1987) 163-72.
[5] HOFFMANN, P., et al., Radionuclides from the Chernobyl accident in the environment of
Chattia, a region of the FRG, Radiochim. Acta 41 (1987) 173-179.
[6] SHERSHAKOV, V. M., et al. Analysis and prognosis of radiation exposure following the
accident at the siberian chemical combine TOMSK-7, Radiat. Prot. Dosim. 59 (1995) 93-126.
[7] TOIVONEN, H., et al., A nuclear incident at a power plant in Sosnovyy Bor, Russia, Health
Phys. 63 (1992) 571-573.
[8] ARVELA, H., et al. Mobile survey of environmental gamma radiation and fall-out levels in
Finland after the Chernobyl accident, Radiat. Prot. Dosim. 32 (1990) 177-184.
[9] SCHUBERT, P., BEHREND, U., Investigations of radioactive particles from the Chernobyl
fall-out, Radiochimica Acta 41 (1987) 149-155.
[10] PÖLLÄNEN, R., Highly radioactive ruthenium particles released from the Chernobyl accident:
particle characteristics and radiological hazard, Radiat. Prot. Dosim. 71 (1997) 23-32.
[11] KASHPAROV, V.A., et al., Formation of hot particles during the Chernobyl nuclear power
plant accident, Nucl. Technol. 114 (1996) 246-253.
[12] DEVELL, L., et al., Initial observations of fallout from the reactor accident at Chernobyl,
Nature 321 (1986) 192-193.
9
[13] HOFMANN, W., et al., The radiological significance of beta emitting hot particles released
from the Chernobyl nuclear power plant, Radiat. Prot. Dosim. 22 (1988) 149-157.
[14] LONGLEY, H., TEMPLETON, W.L., "Marine environmental monitoring in the vicinity of
Windscale", Radiological monitoring of the environment (GODBOLD, B.C., JONES, J.K., Ed.)
Pergamon Press, Oxford (1965) 219-247.
[15] MOKROV, Y., et al., Reconstruction of radionuclide contamination of the Techa river caused
by liquid waste discharge from radiochemical production at the Mayak production association,
Health Phys. 79 (2000) 15-23.
[16] UNITED NATION SCIENTIFIC COMMITTEE ON THE EFFECTS OF ATOMIC
RADIATION, Sources and effects of ionizing radiations, UNSCEAR 2000 Report to the
General Assembly, Vol. I (2000) 213-230.
[17] YAMAGATA, N., et al., Uptake and retention experiments of radioruthenium in man – I,
Health Phys. 16 (1969) 159-66.
[18] INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Age-dependent
doses to members of the public from intake of radionuclides: Part 1. Publication 56, Pergamon
Press, Oxford (1989).
[19] CANTONE, M.C., et al., Proton nuclear activation in stable tracer technique for ruthenium
metabolism studies, Nucl. Instrum. Meth. A353 (1994) 440-443.
[20] CANTONE, M.C., et al., Stable and radioactive tracers in Ru biokinetic studies, J. Radioanal.
Nucl. Chem. 178 (1994) 407-415.
[21] VERONESE, I., et al., Kinetics of systemic ruthenium in human blood using a stable tracer, J.
Radiol. Prot. 21 (2001) 31-38.
[22] VERONESE, I., et al., Influence of the chemical form on the plasma clearance of ruthenium in
humans, Appl. Radiat. Isotopes 60 (2004) 7-13.
[23] MAGILL, J., et al., Chart of the nuclides, 7th edition. European Communities, Karlsruhe (2006).
[24] ARZNEIBUCH KOMMENTAR, Wissenschaftliche Erläuterungen zum Europäischen
Arzneibuch und zum Deutschen Arzneibuch, Wissenschaftliche Verlagsgesellschaft GmbH,
Stuttgart (1999) (in German).
[25] VERONESE, I., et al., A technique for the determination of ruthenium stable isotopes in urine
samples, J. Radioanal. Nucl. Chem. 271 (2007) 497-501.
[26] CURRIE, L.A., Limits for qualitative detection and quantitative determination. Application to
radiochemistry, Anal. Chem. 40 (1968) 586–593.
[27] INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION, Human
Alimentary Tract Model for Radiological Protection, Publication 100, Elsevier, Oxford (2007).
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