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MODELLING THE DYNAMIC TRITIUM TRANSFER TO
FARM ANIMALS. EXTENSION TO WILD MAMMALS AND
BIRDS
Anca Melintescu PhD
“Horia Hulubei” National Institute for Physics and Nuclear Engineering, Bucharest-
Magurele, ROMANIA
ancameli@ifin.nipne.ro, melianca@yahoo.com
2nd Meeting of the EMRAS II Working Group 7, “Tritium”, Chatou, France, 28–29, September
2009
MODELLING OF TRITIUM TRANSFER IN ANIMALS
Simplified models and experimental data base
• Models in use are schematic and non-validated or are empirically derived
and cannot be used out of initial data set;
• Use one compartment for OBT with halftime given by total organic carbon
one;
• Animal products contribute significantly to the diet - reliable dynamical
models are needed;
• Sparse experimental data - old experiments insufficiently reported;
• BUT very good experimental data and model for rat (experiments done by H.
Takeda, NIRS, Japan);
• Need a different approach based on comparative metabolism and OBT-C
links;
Animals bioenergetics
• Review of past results of 3H and 14C transfer modelling
in mammals → necessity to have a common approach E=mc2 →
based on energy needs and on the relation between
energy and matter (well established in Atomic and
Quantum Physics)
• Knowledge on animal metabolism and nutrition GE in food
• Metabolism = countless chemical processes going on
continuously inside the body that allow life and normal GEf
functioning
• These processes require energy from food DE
• Energy is derived from the digestion of several
compounds, including carbohydrates and fats. Excess GEug
dietary protein can also be used as an energy source,
ME
but it is a costly practice.
• Gross energy, Digestible energy, Metabolisable Basal Met.
Energy, Net energy Maint. Met.
• Maintenance metabolism (basal+heat of digestion), Heat of Dig.
lost as heat
Cold Therm.
• Heat needed for cold thermogenesis, activity and
losses in processes of growth, production and
Used for work,
reproduction Growth, re-prod
• Energy stored (deposited, retained) in the products of
growth, lactation (egg) and reproduction NE
• Daily Energy Expenditure (Field Metabolic Rate)
• Food must include maintenance protein
• Field Metabolic Rate (FMR, MJ kg -1 d-1) = the net daily energy expenditure of
animals
- depends on the level of nutrition, taxon, diet, environment
FMR= a*BWb ? b ~0.75 or 0.67 or ?
BW – body weight (kg)
a, b – scaling coefficients
• Specific Metabolic Rate (SMR, MJ kg -1 d-1) = the daily energy expenditure per unit
fresh body mass
• Relative Metabolic Rate or the energy turnover rate (ReMR, d -1) = ratio of SMR
and the energy content of the body, determined by the body composition (protein,
lipids, and carbohydrates):
ReMR - used also for loss rate of organic matter (as in ontogenetic growth)
EBW - the empty body mass (kg) defined as the live-weight less the mass of the
gastrointestinal contents;
BED - the body energy density (MJ kg -1 fw)
- depends on body composition
BED=flipid*39.6+fprotein*23.7+fcarbohydrate*17.7
Body Size : Surface Area Ratio and Energy Demand Comparison of
Endotherms
8
(B/M)=aM1/4
Allometric relation
7
Mass-specific metabolic rate (ml O2/gram/hour)
Shrew
6
5
4
3
Harvest mouse
2
Mouse
Flying squirrel
1 Bat Cat Dog Human Horse Elephant
0
0.01 0.1 1 10 100 1000 10,000
Mass (kg)
Derivation of a generic model based on energy
metabolism tested with experiments
MAGENTC - MAmmal GENeral Tritium and Carbon transfer
• Complex dynamic model developed by us in the last four years in an
international collaboration for H-3 and C-14 in mammals
• full description given in:
D. Galeriu, A. Melintescu, N. A. Beresford, H. Takeda, N.M.J. Crout,
“The Dynamic transfer of 3H and 14C in mammals – a proposed
generic model”, Radiation and Environmental Biophysics, (2009)
48:29–45
• A key element in any model of radionuclide transfer in animals is the
loss rate (half-time) from the body or organs;
• There are too few experimental data for 14C and 3H from which one
could derive these values, and we therefore advance the working
hypothesis that the loss rate of organic compounds (organic carbon,
OBH or OBT) from the body or organs can be linked with the energy
turnover rate.
• The model has 6 organic compartments and
distinguishes between organs with high transfer
and metabolic rate (viscera), storage and very
low metabolic rate (adipose tissue), and
„muscle‟ with intermediate metabolic and
transfer rates.
• Some organs have high metabolic activities
and will therefore have high 3H and 14C transfer
rates.
• Liver, kidney, heart, and the gastrointestinal
tract use about 50 % of the basal metabolic
requirements whilst typically contributing less
than 10 % of the body mass; these organs are
included as a combined “viscera” compartment.
• Blood is separated into red blood cells (RBC)
and plasma as plasma is the vector of
metabolites in the body (and also as a
convenient bioassay media).
• The remaining tissues are bulked into one
model compartment („remainder‟) in order to
achieve mass balance.
• The organic compounds of 3H and 14C enter
the body via the stomach and they are mostly
absorbed from the small intestine and a
simplified transfer through gastrointestinal tract
is used to reproduce the delay between intake
and absorption.
• The stomach and small intestine compartment
refers to the content, as an input pathway,
whilst the stomach and small intestine walls are
included in the viscera, having high metabolic
rate.
Modelling approaches
• The metabolisable fraction of dietary intakes of organic tritium and carbon are transferred
to systemic body compartments; the remainder is excreted. In the case of dietary tritium,
the exchangeable fraction is transferred directly to body water and only the non-
exchangeable fraction enters blood plasma;
• Ingested HTO is assumed to be immediately mixed in the body water compartment
• The transfer rates between compartment and blood plasma are given by RMR. The
transfer rates from blood plasma to model compartments are assessed using the mass
balance of the stable analogues (include net growth);
• Transfers include the net flux after the digestion and transformation of dietary compounds
in protein, lipids or carbohydrates;
• Transfer rate to urine (organic) given by mass balance (urine dry matter production,
plasma organic content);
• Transfer rate between body HTO and plasma OBT given by hydrogen metabolism
(equilibrium value of OBH derived from free H);
• Transfer rate for respiration (or body HTO) by mass balance of stable nuclide: intake
assumed correlated with energy needs;
• Organ composition assumed similar to humans (cf. Geigy tables and other models)
• Plasma composition (OBC,OBT) same for all mammals (cf. Baldwin 1995);
• All model compartments have a single component (no fast-slow distinction)
Model tests with experimental data on rats
• Complete database for 3H and 14C transfer, obtained from
experiments with Wistar strain rats thanks to H. Takeda (NIRS,
Japan)
• Studies included:
– continuous 98 days intakes of 14C and OBT contaminated food
or HTO;
- acute intakes of HTO or 14C and 3H labelled glucose, leucine,
glycine, lysine, and oleic and palmitic acids.
• Available data include 14C, OBT and HTO measurements in visceral
organs, muscle, adipose tissue, brain, blood and urine.
• For the acute studies data on labelled organic compounds in
proportions typical of normal rat food were combined.
• Model parameters not obtained from the study were estimated from
the literature:
- organ mass,
- whole body and
- organ energy expenditure.
• The intakes of OBT (metabolisable and non-exchangeable fractions)
and organic 14C were estimated from the known food composition.
Results of model test with rat data (no calibration)
Average and standard deviation of predicted to observed ratios in rat viscera,
muscle, blood, adipose tissue and whole body (except bone and skin) for the six
forms of intake
14 14
Organ C chronic C acute OBT OBT HTO HTO acute
chronic acute chronic
Viscera 1.12 ± 0.15 0.51 ± 0.4 1.06 ± 0.15 0.67 ± 0.43 ± 0.07 0.87 ± 0.34
0.56
Muscle 1.25 ± 0.14 0.81 ± 1.23 ± 0.21 0.90 ± 0.40 ± 0.09 1.02 ± 0.38
0.29 0.37
Adipose 1.11 ± 0.15 0.61 ± 0.97 ± 0.2 0.75 ± 0.3 ± 0.1 1.33 ± 0.3
0.12 0.13
Whole 1.12 ± 0.27 0.4 ± 0.1 0.88 ± 0.12 0.38 ± 0.37 ± 0.09 0.62 ± 0.18
blood 0.03
Whole-body 1.18 ± 0.08 0.7 ± 0.1 1.08 ± 0.11 0.8 ± 0.1 0.36 ± 0.08 1.09 ± 0.18
Data error ?!
Representative results, no calibration
Model predictions and experimental observations for rat muscle
following acute intakes of food labelled with 14C or OBT
Model tests with cow data (no
calibration)
• Several exposures
– Single HTO intake
– Continuous HTO intake
– Continuous OBT intake
• Cow mass, feed and water intake, milk
and urine production taken from
experiments
• All other model parameters taken from
literature – no calibration with tritium data
Results of model test with cow data (no calibration)
Model performance for dairy cow; NA: not calculated/available
Experiment R2 Milk total 3H Milk OBT Urine HTO
Mean standard deviation P/O
(range presented in parenthesis)
Cow_P 0.97 2.60 ± 1.7 1.68 ± 0.8 2.90 ± 2.34
(0.8 -1.9) (0.5 - 2)
Cow_C 0.89 0.97 ± 0.08 0.73 ± 0.17 0.97 ± 0.06
(0.9 -1.4) (0.65 - 1.7)
Cow_H3 0.67 1.02 ± 0.15 0.49 ± 0.12 1.36 ± 0.42
(0.9 - 1.5) (0.4 - 0.9)
Cow_H 0.88 1.45 ± 0.59 1.86 ± 0.38 NA
(0.6 - 2.3) (0.55 - 2.12)
Representative results, no calibration
Experimental data and model predictions for OBT in milk after OBT fed
for 26 days. Experimental data were reported only after stop dosing
Model tests on sheep data (no calibration)
• Scottish Blackface female sheep – acute intake of 14C- and 3H-
labelled glucose and acetate
• The experiment provides approximate information on the transfer
from feed to organs.
• We added a sub-model for growth (from 27 kg at the beginning of
exposure to 47 kg after one year)
- Organs‟ masses growth were taken from experiment and
literature
• The model considered normal marked food intake: protein + fat +
carbohydrates (not only carbohydrates as in experiment);
• The study did not include labelled protein, although production of
protein by rumen bacteria may have led to some labelled protein
being present
• Model results are sensitive to the growth rate in the day of intake
Representative results, no calibration
Dynamics of organic 14C (left) and OBT (right) in sheep muscle
after an intake of labelled glucose and acetate.
Model tests with pig data (no calibration)
• Data on organ OBT concentrations are available for a gestating sow
fed OBT for 84 days and who died before delivery.
Results of model test with pig data (no calibration)
Organ P/O
blood 1.17
muscle 1.7
viscera 1.4
• Initial body composition was adjusted to be close to
lean or fat genotype considering the lipid content of muscle
according with experimental information on inter-muscular
fat for the contrasting genotype PP, SL and MS.
• The results show a clear distinction between meat
concentrations of genotypes at the time of killing,
the fat MS genotype having the highest value and PP the
lowest.
Conclusions for MAGENTC
• Despite simplifications, the model tests are encouraging for tissues and milk
for a range of animals.
• Without parameter optimization, the model predictions are within a factor of
3 of the reported values in all cases.
• Some improvements could be made to the model in the future, in order to
increase the predictive power:
1. Incorporation of an understanding of ruminant digestion to clarify the
exchangeable fraction of net organic intake;
2. Incorporation of fast and slow compartments for each organ/organs
group, if a general rule can be obtained from animal science and physiology
research;
3. Inclusion of up-to-date knowledge on organ specific metabolic rate (in
vivo) for animals; there has been considerable progress in the use of
modern noninvasive techniques such as Positron Emission Tomography
(PET) and Magnetic Resonance Imaging (MRI) for metabolic studies.
Extension of the current model to wild mammals and
birds
• Full description is given in:
A. Melintescu, D. Galeriu, “Using energy metabolism as a tool for modelling the transfer of 14C and
3
H in animals”, submitted to Radiation and Environmental Biophysics
Extension to wild mammals
• Clear need to explicitly consider non-human biota within radiological
assessments (ICRP 2007);
• ICRP proposes the use of Reference Animals and Plants;
• We have past experience to assess the concentration ratio for specific
animals for tritium and 14C in the frame of European projects (EPIC,
FASSET) for routine emissions; full details are given in:
D. Galeriu, N.A. Beresford, A. Melintescu, R. Avila, N.M.J. Crout, “Predicting tritium and
radiocarbon in wild animals”, International Conference on the Protection of the Environment on the
Effects of Ionising Radiation, Stockholm, Sweden, 6 –10 Oct. 2003, P. 186-189, IAEA-CN-109/85
• Data for radionuclides in wild animals are sparse and a number of
approaches including allometry have been proposed to address this issue
• Unlike to laboratory or housed farm animals, wild mammals and birds are
subjected to large environmental and dietary variability for which they must
adapt.
• Our definition of biological halftime has been used in order to explore the
range for wild mammals; full details given in:
D. Galeriu, A. Melintescu, N.A. Beresford, N.M.J. Crout, H. Takeda, “14C and tritium dynamics in
wild mammals: a metabolic model”, Radioprotection, Suppl. 1, Vol. 40 (2005), S351-S357, May
2005
• There are many studies demonstrating allometric (mass dependent) relations for basal
metabolic rate, daily energy expenditure and organs‟ masses.
• For DEE there is considerable evidence of taxon specific allometric relationships, but
dietary habits can still have a large influence for rodents with herbivorous, omnivorous or
granivorous diets.
• DEE depends on environmental temperature (small mammals in the Arctic have a 2 fold
higher DEE for the same body mass compared with animals in Mediterranean climates).
Variation with body mass in the mass of DEE (kJ d-1) for granivorous, carnivorous,
visceral organs expressed as a percentage of and herbivorous diets, compared with an allometric
whole body mass. relationship for rodents.
• The biological halftime does not only depend on animal mass but also on taxon either.
• For the same body mass, taxon and diet may affect the biological half time
with a factor 2.
Biological half times for Carbon (and OBT) units days
Mass (kg) 0.03 0.1 1 5 10 30 300
Animal Biological half-times
Terrestrial 3.1 4.8 11.1 19.8 25.4 37.8 -
mammals
Mesic rodents 2.8 4.1 8.4 13.7 - - -
Carnivores 5.5 6.7 9.4 12.0 13.3 15.7
Granivores 4.9 10.0 - - - - -
Herbivores 3.1 4.8 10.8 19.2 24.5 36.2 81.8
Insectivores 3.8 6.1 14.6 26.8 - - -
Omnivores 3.7 5.4 11.4 19.2 - - -
• Our model needs as input the Basal Metabolic Rate (BMR), the field energy expenditure
(FMR), organ mass and organ Specific Metabolic Rate (SMR).
• Body mass is not the only predictor of BMR, but body temperature, taxon, diet and
climate are also important;
• A gap in the database for wild animals is the assessment of maintenance energy needed
per kg tissue and time unit, the so called specific metabolic rate (SMR) for organs in
basal and active states.
• Due to adaptation to various environmental constraints it is possible that the organ
metabolism of wild mammals to differ from domesticated ones.
• The organ mass for wild mammals also is less documented than for farm animals and
the intraspecific variability can be higher. This explains why our predicted BMR values
are sometimes close to observed values, but there are cases of 50 % discrepancies.
• In practice we have considered the relative contribution of organs to whole body BMR
and use the experimental BMR in the model input values.
Species Mass (kg fw) Measured BMR (MJ d -1) Estimated BMR (MJ d-1)
Hare (Lepus carpensis) 2.9 0.78 0.79
Jackal (Canis mesomelas) 2.8 0.7 1.05
Racoon (Procyon lotor) 2.2 0.5 0.76
Puma (Felis capensis) 9.6 1.9 1.5
Wild cat (Felis ocreata) 2.7 0.5 0.52
Chipmunk (Tamias 0.0075 0.045 0.07
striatus)
We reassessed all input data and also select red deer as a large herbivore.
We include two rodents (lemming and chipmunk), a small herbivore - rabbit and a carnivore –
red fox.
The lemming from Arctic regions is modelled with enhanced energy needs.
As much as possible input data correspond to same habitat, diet, temperature and subspecies
for each considered mammal.
The effect of a coherent selection of model parameters is exemplified for chipmunk, for which
we considered mixed literature data but also measured BMR and FMR of the same population
(Quebec - personal data from Careau).
Model inputs
Animal Latin name Mass (kg) BMR Mass fractions BMR FMR
(MJ day-1 ) (MJ day-1 ) (MJ day-1 )
adipose muscle viscera
lemming Lemmus 0.06 0.045 0.35 0.28 0.15 0.042 0.19
trimucronatus
chipmunk Tamias 0.096 0.052 0.15 0.4 0.22 0.081 0.12
striatus
chipmunk Tamias 0.0915 0.0675 0.15 0.4 0.22 0.078 0.17
C striatus
rabbit Lepus 1.8 0.57 0.1 0.43 0.13 0.573 1.3
californicus
red fox Vulpes vulpes 6 1.1 0.15 0.45 0.13 1.43 4.5
red deer Cervus 107 11.7 0.1 0.43 0.12 12.4 24.5
(elk) elaphus
Model results
Animal Mass Fast half- Slow half- Fast Effective half- Transfer factor
(kg) time time (day) contribution in time (day) (day kg -1)
(day) retention
lemming 0.06 4.2 52 0.8 5.2 36.88
chipmunk 0.096 4.4 69.3 0.91 4.76 47.75
chipmunk 0.0915 3.1 55.4 0.926 3.32 34.6
C
rabbit 1.8 7.4 79.8 0.87 8.44 3.35
red fox 6 8.1 147.6 0.91 8.76 1.51
red deer 107 25.2 227.2 0.83 29.6 0.21
Concentration ratios in different model compartments
Animal whole body adipose muscle viscera remainder
lemming 0.70 1.38 0.32 0.28 0.79
chipmunk 0.48 1.26 0.32 0.28 0.76
chipmunkC 0.49 1.34 0.32 0.28 0.76
rabbit 0.44 1.19 0.32 0.28 0.57
red fox 0.38 1.03 0.24 0.21 0.50
red deer 0.45 1.28 0.32 0.28 0.55
Short term dynamics of 14C in whole body (generalised coordinates)
Generalised coordinates:
Normalised concentration=Whole body conc *Mature mass
T*RMR – non-dimensional time = time * mature RMR
Despite these shortcomings, the results presented above are less uncertain than
for many other radionuclides and can provide useful results for biota radioprotection.
Extension of the current model to birds
• The model developed for mammals is based on energy metabolism and
body composition with the assumption that the turnover rate of organics is
linked to energy turnover rate.
• There are not reasons to restrict the model to mammals, if the assumptions
are qualitatively correct.
• The allometry of basal metabolic rate of birds has close mass exponent to
mammals.
• After a selection of good data and correction for phylogenetic bias, we
found:
BMR = 303*M-0.33 (mass in kg and metabolic rate in kJ day-1).
• There is no difference between passerine and non passerine and the higher
values for birds comparing to mammals are explained by higher body
temperatures.
• The scaling exponent of BMR in captive birds (0.670) is significantly lower
than in wild-caught birds (0.744) due to phenotypic plasticity.
• The scaling exponents of FMR for birds and mammals were not significantly
different:
birds: FMR = 1.02 M0.68,
mammals: FMR = 0.68 M0.72
Disregarding the effect of increased body temperature we compare our model BMR to
experimental data
Comparison between BMR model and experimental data for birds
For small birds we under predict with 20-40 %.
With one exception (Arenaria interpres) all are passerine with higher body temperature than
other birds.
We conclude that our mammals SMR, corrected for body temperature, can help as a first attempt
to expand the model to birds.
For food chain modelling, laying hens and broilers are of special concern and there are
not experimental data for eggs or meat contamination with 3H and 14C.
We considered a tritium intake (1 Bq day -1) for 60 days in both forms (HTO or OBT).
Dynamics of tritium in eggs after HTO or OBT intake
OBT concentration in eggs is predicted to increase rapidly in the first 7 days corresponding to the
duration of egg formation, and slowly thereafter, due to contribution of recycled body OBT.
We observe that the OBT concentration in egg, after stop dosing decreases in the first days with
a half-time of about 5 days and slower later (halftime of about 40 days), due to contribution of
body reserves.
Total tritium in eggs is 2 times higher when the intake is OBT, but share of OBT is about 75 % for
OBT intake and only 9 % for HTO intake.
In order to obtain directly the transfer factor, intake has been fixed at 1 Bq day -1, while for
concentration ratio, intake was 1 Bq kg -1 dry matter or 1 Bq L -1 of water.
Transfer factor for tritium in broiler Concentration ratio for tritium in broiler
In the case of fast growing broiler, at the market weight of about 2 kg (42 days old) the model
predicts lower transfer factors (TF) than for the equilibrium case
The predicted concentration ratios (CR) for our fast growing broiler are close to those
obtained for “equilibrium” .
In absence of any experimental data or previous modelling assessments, our results give
a first view on the transfer of 3H and 14C in birds.
CONCLUSIONS
• We developed research grade model for plants and
animals based on process level, pointing out that model
inputs can be obtained using Life Science research in
connection with National Research on plant physiology
and growth, soil physics, and plant atmosphere
interaction, as well as animal physiology, nutrition and
metabolism;
• We re-use these knowledge with a very low cost, but
spending time to learn basics from these fields →
Interdisciplinary Research;
• Classical compartmental models can be derived and
appropriate parameters for each case can be obtained in
this way.
Thank you!
