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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 ... – PowerPoint PPT presentation

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  • Anca Melintescu PhD
  • Horia Hulubei National Institute for Physics
    and Nuclear Engineering, Bucharest-Magurele,

2nd Meeting of the EMRAS II Working Group 7,
Tritium, Chatou, France, 2829, September 2009
  • 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 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
  • Metabolism countless chemical processes going
    on continuously inside the body that allow life
    and normal functioning
  • These processes require energy from food
  • Energy is derived from the digestion of several
    compounds, including carbohydrates and fats.
    Excess dietary protein can also be used as an
    energy source, but it is a costly practice.
  • Gross energy, Digestible energy, Metabolisable
    Energy, Net energy
  • Maintenance metabolism (basalheat of digestion),
    lost as heat
  • Heat needed for cold thermogenesis, activity and
    losses in processes of growth, production and
  • Energy stored (deposited, retained) in the
    products of growth, lactation (egg) and
  • Daily Energy Expenditure (Field Metabolic Rate)
  • Food must include maintenance protein

Emc2 ?
GE in food
Basal Met.
Maint. Met.
Heat of Dig.
Cold Therm.
Used for work, Growth, re-prod
  • 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 aBWb ? 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
  • BED - the body energy density (MJ kg-1 fw)
  • - depends on body composition
  • BEDflipid39.6fprotein23.7fcarbohydrate17.7

Body Size Surface Area Ratio and Energy Demand
Comparison of Endotherms
(B/M)aM1/4 Allometric relation
Mass-specific metabolic rate (ml O2/gram/hour)
Harvest mouse
Flying squirrel
Mass (kg)
Derivation of a generic model based on energy
metabolism tested with experiments
  • MAGENTC - MAmmal GENeral Tritium and Carbon
  • 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)
  • 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
  • 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
  • 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
  • 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

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
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
Organ 14C chronic 14C acute OBT chronic OBT acute HTO chronic HTO acute
Viscera 1.12 0.15 0.51 0.4 1.06 0.15 0.67 0.56 0.43 0.07 0.87 0.34
Muscle 1.25 0.14 0.81 0.29 1.23 0.21 0.90 0.37 0.40 0.09 1.02 0.38
Adipose 1.11 0.15 0.61 0.12 0.97 0.2 0.75 0.13 0.3 0.1 1.33 0.3
Whole blood 1.12 0.27 0.4 0.1 0.88 0.12 0.38 0.03 0.37 0.09 0.62 0.18
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
Model performance for dairy cow NA not
Experiment R2 Milk total 3H Milk OBT Urine HTO Urine HTO
Experiment R2 Mean ? standard deviation P/O (range presented in parenthesis) Mean ? standard deviation P/O (range presented in parenthesis) Mean ? standard deviation P/O (range presented in parenthesis) Mean ? standard deviation P/O (range presented in parenthesis)
Cow_P 0.97 2.60 1.7 (0.8 -1.9) 1.68 0.8 (0.5 - 2) 1.68 0.8 (0.5 - 2) 2.90 2.34
Cow_C 0.89 0.97 0.08 (0.9 -1.4) 0.73 0.17 (0.65 - 1.7) 0.73 0.17 (0.65 - 1.7) 0.97 0.06
Cow_H3 0.67 1.02 0.15 (0.9 - 1.5) 0.49 0.12 (0.4 - 0.9) 0.49 0.12 (0.4 - 0.9) 1.36 0.42
Cow_H 0.88 1.45 0.59 (0.6 - 2.3) 1.86 0.38 (0.55 - 2.12) 1.86 0.38 (0.55 - 2.12) NA
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
  • - 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
  • 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

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
  • fat for the contrasting genotype PP, SL and MS.
  • The results show a clear distinction between
  • concentrations of genotypes at the time of
  • 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
  • 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
  • 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
  • 3H 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
  • 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,
  • 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).

DEE (kJ d-1) for granivorous, carnivorous, and
herbivorous diets, compared with an
allometric relationship for rodents.
Variation with body mass in the mass of visceral
organs expressed as a percentage of whole body
  • 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
Mass (kg) 0.03 0.1 1 5 10 30 300
Animal Biological half-times Biological half-times Biological half-times Biological half-times Biological half-times Biological half-times Biological half-times
Terrestrial mammals 3.1 4.8 11.1 19.8 25.4 37.8 -
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

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 striatus) 0.0075 0.045 0.07
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 (MJ day-1) Mass fractions Mass fractions Mass fractions BMR (MJ day-1) FMR (MJ day-1)
Animal Latin name Mass (kg) BMR (MJ day-1) adipose muscle viscera BMR (MJ day-1) FMR (MJ day-1)
lemming Lemmus trimucronatus 0.06 0.045 0.35 0.28 0.15 0.042 0.19
chipmunk Tamias striatus 0.096 0.052 0.15 0.4 0.22 0.081 0.12
chipmunkC Tamias striatus 0.0915 0.0675 0.15 0.4 0.22 0.078 0.17
rabbit Lepus californicus 1.8 0.57 0.1 0.43 0.13 0.573 1.3
red fox Vulpes vulpes 6 1.1 0.15 0.45 0.13 1.43 4.5
red deer (elk) Cervus elaphus 107 11.7 0.1 0.43 0.12 12.4 24.5
Model results
Animal Mass (kg) Fast half-time (day) Slow half-time (day) Fast contribution in retention Effective half-time (day) Transfer factor (day kg-1)
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
chipmunkC 0.0915 3.1 55.4 0.926 3.32 34.6
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
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
concentrationWhole body conc Mature mass TRMR
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
  • 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 303M-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
  • The scaling exponent of BMR in captive birds
    (0.670) is significantly lower than in
    wild-caught birds (0.744) due to phenotypic
  • 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
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.
Concentration ratio for tritium in broiler
Transfer factor 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.
  • 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!
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