60
Медицинская радиология и радиационная безопасность, 2015, Том 60, № 2
V.F. Demin
1,2
, A.A. Antsiferova
2
, Yu.P. Buzulukov
2
, V.A. Demin
2,1
,
V.Yu. Soloviev
1
NUCLEAR PHYSICAL METHOD FOR THE DETECTION OF CHEMICAL
ELEMENTS IN BIOLOGICAL AND OTHER SAMPLES USING ACTIVATION
BY CHARGED PARTICLES*
В.Ф. Демин
1,2
, А.А. Анцифирова
2
, Ю.П. Бузулуков
2
, В.А. Демин
2,1
,
В.Ю. Соловьев
1
Ядерно-физический метод детектирования химических элементов
в биологических и других образцах на основе активации заряженными
частицами*
ABSTRACT
Purpose: To develop a method of radioactive tracers by the
activation by charged particles for the studying quantitative content of
chemical elements and nanoparticles in biological samples and in the
environment.
Material and methods: Theoretical analysis and test experiment
were carried out to study the possibility of using various nuclear
methods for detection of chemical elements and nanoparticles in
biological and other samples, using the activation of different isotopes
by a charged particles flux. The characteristics of the products and the
various nuclear reactions, taken from the IAEA’s nuclear databases,
have been considered. The irradiation of natural isotopes of titanium
by fast neutron flux produces radioactive isotopes
46
Sc and
47
Sc
(with half-life T
1/2
, respectively, equal to 83.8 and 3.35 days), by fast
protons flux
48
V (T
1/2
= 16 days) and by alpha-particles flux
51
Cr
(T
1/2
= 27.7 days). The flux of fast protons after interaction with the
natural isotopes of platinum mixture generates radioactive isotope
195
Au (T
1/2
= 186 days), with the isotopes of iron
56
Co (T
1/2
= 77.7
days), with the isotopes of manganese
54
Mn
(T
1/2
= 312 days), with
europium isotopes
151
Gd (T
1/2
= 124 days) and
153
Gd (T
1/2
= 241.6
days). We also consider the possibility of exposure to iron isotopes by
fast deuterons flux with the formation of isotope
56
Co. All radioactive
isotopes are gamma-emitters and are suitable for the measuring on
gamma-spectrometers. Particular attention is paid to the detection of
nanoparticles of titanium dioxide, which takes one of the first places in
the list of priority nanomaterials. For estimate the proportion of silver
nanoparticles or another nanoparticles passing through the blood-brain
barrier, evaluation of the content of iron in the blood can give a key
information.
Results: The use of such methods in addition to the traditional
neutron activation analysis expands the list of chemical elements, which
can be successfully detected by the nuclear activation. This expansion
includes such elements as titanium, iron, platinum, manganese,
europium and some others.
РЕФЕРАТ
Цель: Разработка метода радиоактивных индикаторов на ос-
нове активации заряженными частицами для исследования био-
кинетики химических элементов и наночастиц в биологических
образцах и окружающей среде.
Материал и методы: Проведен теоретический анализ и те-
стовый эксперимент по исследованию возможности применения
различных ядерно-физических методов детектирования химиче-
ских элементов в биологических и других образцах, в том числе в
составе наночастиц, с использованием активации различных изо-
топов потоком заряженных частиц. Проанализированы продукты
различных ядерных реакций. При облучении природных изотопов
титана потоком быстрых нейтронов образуются радиоактивные
изотопы
46
Sc и
47
Sc периодами полураспада T
1/2
равными со-
ответственно 83,8 и 3,35 дня), потоком быстрых протонов
48
V
(T
1/2
= 15,98 дня), а альфа-частицами —
51
Cr (T
1/2
= 27,7 дня). При
облучении быстрыми протонами природной смеси изотопов пла-
тины образуется радиоактивный изотоп
195
Au (T
1/2
= 186,12 дня),
изотопов железа
56
Co (T
1/2
= 77,7 дня), изотопов марганца с об-
разованием изотопа
55
Mn (T
1/2
= 312,1 дня), изотопов европия
изотопы гадолиния
151
Gd и
153
Gd (T
1/2
составляет, соответствен-
но, 124 и 241,6 дня). Рассмотрена также возможность облучения
изотопов железа быстрыми дейтронами с образованием того же
изотопа
56
Co. Все образующиеся радиоактивные изоптопы явля-
ются гамма-излучателями и имеют удобные для целей измерения
на гамма-спектрометре энергетические линии. Особое внимание
уделяется детектированию наночастиц из двуокиси титана, зани-
мающими одно из первых мест в списке приоритетных наномате-
риалов. При количественной оценке доли наночастиц серебра или
других наночастиц, проходящих через гематоэнцефалический ба-
рьер, оценка содержания железа в крови может дать недостающую
ключевую информацию. При выборе оптимальной процедуры
проведения эксперимента получаемые радиоактивные продукты
будут иметь активность ниже минимально значимой активности.
Результаты: Применение рассмотренных ядерно-физических
методов в дополнение к традиционному нейтронно-активацион-
ному анализу существенно расширяет список химических элемен-
тов, на такие как титан, железо, платина, магний, европий и др.,
для детектирования которых они могут быть успешно применены.
Key words: nuclear-physical methods, radioactive tracer, charged
particles, biokinetics, laboratory animals, the environment, nanoparticles
Ключевые слова: ядерно-физические методы, радиоактивный
индикатор, заряженные частицы, биокинетика, лабораторные
животные, окружающая среда, наночастицы
1
Федеральный медицинский биофизический центр им. А.И.Бур-
на зяна ФМБА России, Москва. E-mail: vfdemin_kiae@mail.ru
2
Национальный исследовательский центр «Курчатовский
институт», Москва
1
A.I. Burnasyan Federal Medical Biophysical Center of FMBA,
Moscow, Russia. E-mail: vfdemin_kiae@mail.ru
2
National Research Center “Kurchatov Institute”, Moscow, Russia
ЯДЕРНАЯ МЕДИЦИНА NUCLEAR MEDICINE
*Applied research is carried out with financial support from the state on behalf of the Russian Ministry of Education and Science
(RFMEFI60414X0114)
* Прикладные научные исследования проводятся при финансовой поддержке государства в лице Минобрнауки России
(RFMEFI60414X0114)
61
Introduction
Accelerated development of nanotechnology
increases the amount of products containing nanoparticles
(NPs). Only in the food industry currently more than 200
products with nanomaterials are used. Exponential growth
of the amount of products with nanomaterials requires
an assessing not only their useful properties, but also the
degree of risk to humans and the environment that creates
the problem of ensuring their safety for human health and
the environment.
A key way in solving this problem is to study biokinetics
(absorption, biodistribution, metabolism and excretion)
of nanoproducts in animals and humans. The basis of this
research is a quantitative measurement of the NPs mass
content in biological samples.
Quantitative measurement of NPs content in living
organisms and material / waste of nanotechnology presents
considerable difficulties because of the high demands for
sensitivity and accuracy. These difficulties in the most
concentrated form manifest in quantitative measurements
of NPs content in complex, multi-component and
polydisperse systems, such as tissues of living organisms.
One of the most promising methods for measuring the
mass of inorganic NPs is a method of radioactive tracers,
based on neutron activation of the atomic nuclei. In previous
years, NRC “Kurchatov Institute” in collaboration with
the Moscow Institute of Nutrition performed a significant
amount of work on the development of the method and its
application to the study of biokinetics of NPs, such as silver,
zinc dioxide, gold and selenium. For the first two types of
NPs the techniques were developed and certified in GOST
R system [1]. These techniques are recommended for use
in Rospotrebnadzor’ document MR 1.2.0048-11 [2].
Method of detecting chemical elements contained in
the NPs based on thermal neutron activation is applicable
to a limited number of such elements. They include silver
(Ag), zinc (Zn), selenium (Se), cerium (Ce), lanthanum
(La), iron (Fe), gold (Au), iridium (Ir). The most serious
limitation is imposed on the number of elements in
the biokinetics’ study in the experiments on laboratory
animals due to possible requirements on their duration. In
studies of trace elements and hazardous pollutants in the
environment, agricultural and food products, this list may
be expanded considerably. Practical needs in quantifying
the content of trace elements in the various materials
demands significant expansion of this list.
In different practical fields (scientific research,
medicine, nanotechnology) there is a need for methods of
detecting other elements such as titanium (Ti), platinum
(Pt), europium (Eu) and some others. In addition, not for
all elements, listed in the first list, and not in all options
of research the high sensitivity of the measurement in
the application of the neutron activation method can
be ensured. For example, such situation may occur in
measuring the iron content in the samples due to the low
content of isotope
58
Fe (0.28 %) in the natural isotope
mixture. The measurement sensitivity may fall due to long
time isotope activation with relatively short half-life, for
example,
195
Pt
78
with T
1/2
= 4 days. In connection with
this, we started the study of the possibility of using the
elements’ activation in nanomaterials by irradiation with
fast charged particles (p, d,
3
He,
4
He) paying particular
attention to proton irradiation. Preliminary theoretical
analysis and experimental research using beams of fast
charged particles of the cyclotron in NRC “Kurchatov
Institute” promises the hope of the viability of this method
of activation as applied to biological and environmental
research.
Material and methods
The method of radioactive tracers based on neutron
activation was developed many decades ago for the purpose
of biochemical and physico-chemical analysis.
Radiotracer method based on the neutron activation
was developed several decades ago to conduct biochemical
and physico-chemical analysis. This method is unique in
its features of sensitivity and accuracy (see review paper
[3]). It is one of the widely used technologies from the
standpoint of its sensitivity [1, 3–7].
Originality and features of modern development of the
radiotracer method are as follows:
the scope of the application nanoparticles / nanomaterials
with specific chemical elements, support research on
their bio- and toxico-kinetics;
the application of modern highly sensitive gamma-
spectrometric equipment;
development of standardized measurement techniques
to ensure the reliability and accuracy of measurement;
one embodiment of this method (the method of
comparison with a standard sample) allows to receive
the result of measurement with a high precision (with a
relative error less than 15 %);
• it is possible to determine the mass content of biophilic
elements (e.g., zinc, selenium) in biological tissues and
organs, in contrast to many other methods;
it is possible to measure directly the mass content in
solid samples, while many other methods require prior
sample transformation into a liquid or gaseous state;
• determination of the mass content of nanomaterials can
be produced both in micro- and macro-samples up to
several centimeters in all three dimensions;
if the activated isotope has a sufficiently long half-life
(a few ten-day periods), this method can be applied
to biological and other experiments lasting for tens
hundreds of days, commensurate with the time of
process of transport of nanomaterials in experimental
animals or objects of the environment;
62
the possibility of using not only thermal neutrons flow
but also charged particles flow for the isotope activation
significantly expands the scope of the nuclear-physical
methods.
NRC “Kurchatov Institute” has a certified equipment
necessary for the application of nuclear-physical
methods of measuring the mass of chemical elements
(research nuclear reactor IR-8 with a thermal neutron
flux of at least 10
12
neutrons/s×cm
2
, cyclotron, modern
multichannel analyzers of gamma-spectra, etc.).
Activation analysis options
As in the embodiment of neutron activation analysis
two modifications of the method are used: the absolute
and relative measurements [1, 4, 7]. In absolute method,
the mass content of the investigated element in the sample
is calculated by the known nuclear properties of the target
and activated radioactive isotope and the value of the flux
density of charged particles during irradiation and others.
In this case, the measurements can contribute significantly
to systematic and random components of uncertainty into
the results.
The absolute method is used for the preliminary
assessment of activity of the samples. Using the results
of this evaluation, a scenario of the experiment using
nuclear-physical methods of detection of nanomaterials
in the samples is determined. In particular, the exposure
time of the sample by neutrons or charged particles, the
holding time after the exposure and the time of measuring
the activity on a gamma-spectrometer are determined.
In the relative method of measuring, the content of
the element in the sample is determined by comparison
of the radiation activity of the test sample and the
standard sample with a known content of an element after
simultaneous exposure of test and standard samples to the
activating particles’ flow. In this case, the measurement’
result does not depend on the variation of the value of the
particle flux density. Thus, the measurement uncertainty
in the relative activation analysis method is much smaller.
To use it, the standard samples with known content of the
element must be prepared.
Depending on the goals and objectives of the
study, as well as on the biological properties of the sought-
for element (whether it is a biophil element, i.e., is it
contained in the body in a natural amount, or it is not
biophil) one of two experiment’ variants on laboratory
animals is chosen:
1) co-activating irradiation of the test and standard samples
with subsequent gamma-spectrometric analysis;
2) preliminary preparation of the radiolabeled material
containing a tested chemical element in a particular
physico-chemical form by irradiation of primary non-
radioactive material; administration of radioactively
labeled material in the test medium (animal’ organism
or some other sample); gamma-spectrometric analysis
of the sample with the tested radiolabeled element.
For such elements as Pb, Ag, Au, As, etc. one may use
both types of the experiments. For biophilic elements (Fe,
Zn, Se, Ti, etc.), when a varying amount of the element
is contained in the animal organs, in the biological
studies only the second type of the experiment may be
recommended — with the radiolabel material.
When studying the penetrability of the blood-brain
barrier by investigated NPs it is necessary also to determine
the iron content in the blood and brain samples. Knowing
the NPs concentration in the peripheral blood one can
estimate the NPs content in the blood veins of the brain
of laboratory animals. And then the NPs fraction passing
through the blood-brain barrier can be determined.
Determination of iron in the blood is carried out by the
same method of radioactive tracers: activation of iron
isotopes.
Theoretical analysis of the activation method with
charged particles
This analysis was performed for a number of elements
relevant from scientific and practical points of view.
Titanium. One of the first places in the list of priority
nanomaterials is taken by titanium Ti, used usually in
the form of titanium dioxide TiO
2
[8]. For this element
there are no radioactive isotopes, activated by the thermal
neutron flux, with the required properties. Because of
the special needs in developing a method of detecting
nanomaterials with this element the method of activation
of titanium in fast neutrons flux was investigated.
Upon irradiating natural isotopes of titanium with fast
neutrons, radioisotopes
46
Sc and
47
Sc are produced in the
reaction (n, p) with the necessary properties for gamma-
spectrometry measurements (T
1/2
are 83.8 and 3.35 days
respectively). In this study the secondary beam of fast
neutrons, generated in the cyclotron of NRC “Kurchatov
Institute”, was used. The study has shown that it was
impossible to obtain high detection sensitivity with a
titanium content of nanomaterials due to the relatively
small cross section of the (n, p) reaction and insufficient
power of the secondary beam of fast neutrons.
In this regard, the development of another method
of detecting the content of titanium nanomaterials was
initiated. That method is based on the activation of titanium
by fast protons to form radioactive isotope
48
V in reactions
(p; n, 2n, ..) on natural titanium isotopes. Radioisotope
48
V has a sufficiently long half-life (T
1/2
= 16 days) and two
gamma-lines 1.31 and 0.98 MeV with a single output for
each decay. Preliminary theoretical analysis of this method
showed its satisfactory characteristics.
Both methods of analysis absolute and relative
ones — are equally applicable to activation of the target by
fast protons.
63
The evaluation of the titanium activation with the
absolute method has demonstrated the possibility of the
radioactive label
48
V formation with sufficient activity. In
this evaluation the characteristics of the proton beam of
the cyclotron and the available literature’ nuclear data on
the target nuclei and radioisotope
48
V were considered.
Nuclear data were taken from the IAEA’s nuclear
databases, see fig. 1 with the data on the cross section of
proton activation of natural titanium isotopes. Thus, the
possibility to achieve a sufficient sensitivity of detection of
nanomaterials with titanium can be real.
We also considered the option of activating titanium
with fast alpha particles. Fig. 2 shows the cross section
of the reaction
nat
Ti(α,x)
51
Cr with the release of the
radioactive isotope
51
Cr (T
1/2
= 27.7 days, E
g
= 0.32 MeV).
The cross section for this reaction is higher than for the
activation by protons and
51
Cr radiolabel has almost two
times longer half-life, than
48
V.
Platinum. When irradiating natural platinum isotope
mixture in the fast protons beam, reactions (p; n, 2n, ..)
form radioisotope
195
Au, having a half-life T
1/2
= 186.1
days and gamma-line with energy 0.099 MeV. For a
sufficiently long time’ experiments (tens hundreds of
days), this activation option can give the desired results in
the terms of sensitivity and accuracy.
Iron. The irradiation of a natural mixture of iron
isotopes by fast protons produces radioactive isotopes of
cobalt in the reactions
nat
Fe(p,x)
56,57,58
Co. Radioisotope
56
Co presents the greatest interest. It is formed from the
main natural isotope
56
Fe (91.75 % content in the natural
isotope mixture), has a half-life T
1/2
= 77.7 days and
gamma ray line of energy 0.847 and 1.24 MeV (respectively
with the quantum yields per unit of radioisotope decay
n
g
= 1; 0.67).
The option of activating iron isotopes by fast deuterons
is also of interest. In reactions
nat
Fe(d,x)
56
Co radioisotope
56
Co is generated. Fig. 3 shows the dependence of the
reaction cross section on the energy of the deuterons. In
these options with the existing technical characteristics
of the cyclotron one can achieve better results than with
irradiation by thermal neutrons.
Europium. Upon irradiation of natural europium
with fast protons, reactions
151
Eu(p,n)
151
Gd and
153
Eu(p,n)
153
Gd generate radioactive isotopes of
gadolinium
151
Gd and
153
Gd with half-life, respectively,
124 and 241.6 days and gamma ray lines 0.154; 0.243 and
0.097, 0.103 MeV respectively. This option is suitable for
the detection of europium in various nanomaterials.
Manganese. Manganese has the single natural isotope,
55
Mn. Its irradiation by fast protons creates in the reaction
55
Mn(p;p,n)
54
Mn radioisotope
54
Mn with a half-life T
1/2
=
312.1 days and gamma line with energy 0.835 MeV.
Description of the experiment. Test experiment was
performed with irradiation of TiO
2
NPs in the form of
powder rutile (Sigma-Aldrich, USA Germany) by the
proton beam of the cyclotron. According to the study on
the transmission electron microscope TEM, the rutile was
presented partially by aggregated nanorods with a diameter
of 5–10 nm and a length of 40–50 nm [6].
Fig. 1. Сross section of reaction Ti(p,x)
48
V on the natural
mixture of isotopes of titanium depending on the energy of the
protons (IAEA, Nuclear Databases)
Fig. 2. Сross section of reaction Ti
.
(α,x)
51
Cr on the natural
mixture of isotopes of titanium depending on the energy of the
alpha-particles (IAEA, Nuclear Databases)
Fig. 3. Сross section of reaction Fe(d,x)
56
Co on the natural
mixture of isotopes of iron depending on the energy of the
deuterons (IAEA, Nuclear Databases)
500
Cross section (mb)
400
300
200
100
450
350
250
150
50
0
0 5
5
5
10
10
10
15
15
15
20
20
20
25
25
25
30
30
30
35
35
40
40 5045
900
Cross section (mb)
Cross section (mb)
700
500
400
400
200
200
800
600
300
300
100
100
0
0
0
0
Particle energy (MeV)
Particle energy (MeV)
Particle energy (MeV)
64
For planning the experiment, the theoretical
calculations were made with the absolute method.
Taking into account the rather high cross section of
natural titanium isotopes’ activation by fast protons and
characteristics of the proton beam of the cyclotron, the
following parameters were chosen for the irradiation of
ampoules with TiO
2
: proton beam power with an energy
of 32 MeV 0.1 mA, exposure time 28 minutes. For
the irradiation the sample was prepared containing 0.6 g
of titanium dioxide powder (0.36 g of titanium) in a sealed
tube, made of quartz glass.
Fig. 4 shows the spectrum of gamma-lines after proton
activation of the sample with TiO
2
obtained on gamma-
spectrometer in NRC “Kurchatov Institute”.
After opening the ampoule 0.58 g of powder were
dissolved in 25 cm
3
of water and, after vigorous stirring,
the solution was aliquoted in the tubes in amount of 1
cm
3
. Thus, each tube contained 23.2 mg of rutile NPs.
Measurements on gamma-spectrometer have shown that
activity of radioisotope
48
V in tubes corresponded to 4.4
kBq, which gives a specific activity about 190 Bq / mg.
One should take into consideration a nonuniformity of
irradiation of rutile mass in the tube due to relatively short
free path of the protons and the narrowness of the proton
beam. Homogeneity of samples was provided by dissolving
them in water and stirring.
Two tubes were subjected to centrifugation at 18.000
rpm for deposition of particles and nanoparticles and
evaluation of the possible content of
48
V ions in solution.
After merging the liquid of the two tubes in one other tube,
its activity was measured.
Results and discussion
In the reaction with the fast protons radionuclides
48
V produced possess high recoil energy. It was necessary
to determine the
48
V amount which can be outside the
nanoparticles volume. Behavior of radioisotopes
48
V and
NPs themselves are different in the body of the animal.
Measured activity of the test tube with liquid from
the two initial test tubes after centrifugation was equal to
7.1 Bq. Its initial activity was 8.8 kBq. Thus, the activity
of the isotope ions did not exceed 0.8·10
–3
of initial NPs
activity. This testifies to the low yield of radioisotope
48
V
outside NPs after proton irradiation.
The main purpose of developing MRI on the basis of
the activation by charged particles is to provide a reliable
and sensitive method for measuring the content of NPs
with TiO
2
and other substances in the studies of NPs
distribution kinetics in experimental animals. For NPs
loaded with silver, zinc and selenium, these experiments
were carried out using thermal neutron activation [1, 5, 6].
Previous experience in this part of the experimental work
with animals and of gamma-spectrometry analysis is fully
applicable in experiments with activation by the charged
particles.
Fig. 3. Сross section of reaction Fe(d,x)
56
Co on the natural mixture of isotopes of iron depending on the energy of the deuterons
(IAEA, Nuclear Databases)
65
The main attention of past and planned experiments
on NPs biokinetics was given to per oral way of NPs
administration. It is appropriate to note that the earlier
MRI method, based on the activation by accelerated
protons, was applied in Germany to determination of
titanium oxide distribution after its inhalation by rats [8].
During the session with the optimal proton irradiation
of test samples and gamma-spectrometry analysis one can
expect that the detection limit of titanium in the sample
can be reduced to a few — tens of nanograms.
The sensitivity of the detection method of titanium
in various samples 2–3 orders of magnitude higher with
activation by cyclotron’ fast protons than by fast neutrons
generated in the same cyclotron.
Titanium is not biophilic element. Nevertheless, it
is present in small amounts in some animal tissues [9].
For this reason, the biological experiments with titan
containing materials should be made using the 2nd
option (see above): pre-production of radioactive-labeled
material containing the desired chemical element.
Conclusion
Summing up, it can be noted that the theoretical
analysis and test experiments have shown the possibility
of effective application of nuclear physics methods to
measure the NPs content in biological, environmental
and other samples containing a number of scientifically
and practically significant elements, using the activation
of source isotope by fast charged particles. Application of
this method of activation, in addition to the method of
thermal neutron activation extends the list of the NPs and
the chemical elements, to which nuclear physical method
of detection can be successfully applied.
Experimental verification of the possible release of the
radioisotope
48
V beyond the NPs volume because of the
relatively high energy recoil in the reaction (p, x) shows
that this output is negligible, and its impact on the accuracy
of measurement of the NPs with TiO
2
is insignificant. A
similar result can be expected for other elements using
activation by accelerated charged particles. Such test
was carried out only for the activation of the elements by
fast protons. According to available data, some of which
is shown above, the reaction cross sections with other
charged particles (d,
3
He,
4
He) have the same order of
magnitude as the reactions with protons. This means that,
if it is necessary for activation of the studied elements,
these charged particles may also be used.
Nuclear-physical methods of detecting the trace
elements in different samples based on neutron activation
has continuously been used in various research institutes,
see e.g. [3, 7]. But ecological and hygienic control of these
micronutrients is still comprise an actual scientific and
practical problem.
LIST OF REFERENCES
1. Demin V.A., Demin V.F., Buzulukov Yu.P. et. al.
Formation of certified reference materials and
standard measurement guides for development of
traceable measurements of mass fractions and sizes of
nanoparticles in different media and biological matrixes
on the basis of gamma ray and optical spectroscopy. //
Nanotechnologies in Russia, 2013, 8, No. 5–6, P. 347–
356.
2. Methodological recommendations MR 1.2.0048-
11 “Procedures and methods for determining
organotropona and toxicokinetic parameters of
engineered nanomaterials in tests on laboratory
animals”. M.: Federal Center of Hygiene and
Epidemiology of Rospotrebnadzor, 2011, 33 pp.
3. Frontasyeva M.V. Neutron activation analysis for the
life sciences. A Review. // Phys. Part. Nucl., 2011, 42,
No. 2. P. 332–378.
4. Kuznetsov R.A. Activation analysis. M.: Atomizdat,
1974, 343 pp.
5. Buzulukov Yu.P., Arianova E.A., Demin V.F. et al.
Bioaccumulation of silver and gold nanoparticles in
organs and tissues of rats studied by neutron activation
analysis. // Biol. Bulletin, 2014, 41, No. 3, P. 255–263.
6. Gmoshinski I.V., Khotimchenko S.A., Popov V.O. et al.
Nanomaterials and nanotechnologies: methods of
analysis and control. // Russian Chem. Rev., 2013, 82,
No. 1, P. 48–76.
7. Gorbunov A.V., Lyapunov S.M., Okina O.I. et al.
Assessment of human organism’s intake of trace
elements from staple foodstuffs in central region of
Russia. Preprint of the Joint Institute for Nuclear
Research. Dubna, 2004.
8. Kreyling W.G., Wenk A., Semmler-Behnke M.
Quantitative biokinetic analysis of radioactively
labelled, inhaled titanium dioxide nanoparticles in a rat
model. http:. //www.uba.de/uba-info-medien-e/4022.
html.
9. Sigubayashi K., Todo H., Kimura E. Safety evaluation
of titanium dioxide nanoparticles by their absorption
and elimination profiles. // J. Toxicol. Sci. 2008, 33,
No. 3. P. 293–298.
Поступила: 11.12.2015
Принята к публикации: 04.02.2015