EMSL-LV-0539-23
BIOLOGICAL TRANSPORT OF CURIUM-243 IN DAIRY ANIMALS
Environmental Monitoring and Support Laboratory
U.S. ENVIRONMENTAL PROTECTION AGENCY
Las Vegas, Nevada 89114
April 1979
This work was performed under
Memorandum of Understanding No. EY-76-A-08-0539
for the
U.S. DEPARTMENT OF ENERGY
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EMSL-LV-0539-23
BIOLOGICAL TRANSPORT OF CURIUM-243 IN DAIRY ANIMALS
by
W. W. Button, R. G. Patzer,
P- B. Hahn and G. D. Potter
Environmental Monitoring and Support Laboratory
U.S. ENVIRONMENTAL PROTECTION AGENCY
Las Vegas, Nevada 89114
April 1979
This work was performed under Memorandum of Understanding
No. EY-76-A-08-0539 for the
U.S. DEPARTMENT OF ENERGY
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ABSTRACT
Lactating cows and goats were used to examine the biological transport
of curium-243 in dairy animals. After either single oral or intravenous
nuclide doses were administered, samples of milk, urine, blood, and feces
were taken over a l44-hour collection period, and the curium concentrations
were determined by gamma counting.
Gastrointestinal uptake of curium was
estimated to be 0.02 and 0.006 percent of the oral dose for cows and goats.
respectively. The cumulative percentage of oral dose transported to milk
and urine was 4.6 x 10-4 and 1.9 x 10-3. respectively. for a cow and
2.7 x 10-4 andl.6 x 10-~ respectively, for goats. Plasma concentrations
of curium decreased rapidly following all intravenous injections.
The average percentage of injected curium transferred to milk. urine.
and feces was 2.8. and 1 percent. respectively, for a cow' and 2, 5. and
5 percen4 respectively, for goats.
All animals were sacrificed one week
after dosing.
Bovine bone retained the greatest fraction of the administered
dose and the next highest was the liver:
However. in all three intravenously
dosed goats the liver contained the greatest amount of curium.
Nuclide
deposition in bone and liver was essentially equal for two of the three
orally dosed goats while the skeleton contained the most curium in the
other animal.
Comparisons are presented between curium-243 and americium-24l
transport in dairy cows.
ii
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INTRODUCTION
In assessing the potential transport of curium in a terrestrial ecosystem,
it is particularly important to establish the metabolic retention of curium in
those domestic animals maintained as a source of food for the human population.
Milk and milk products form a direct link in man's food supply and a signifi-
cant percentage of beef comes from cows and bulls discarded from dairy herds.
Low gastrointestinal absorption values, e.g., <0.05 percent of dose
(Hamilton, 1947) and 0.04 percent of dose (Sullivan and Crosby, 1975) have
been reported following the administration of curium to laboratory rats.
Sev-
eral studies have also been reported on curium transport following intravenous
doses.
In the case of beagle dogs, Lloyd et al., (1974) have shown that intra-
venously injected curium was excreted primarily in the urine.
These investi-
gators injected five beagles with approximately 2.6 microcuries (~Ci) curium
citrate per kilogram (kg) and noted that the average urinary curium excretion
1 day after injection was about 5 times as great as the average nuclide loss
in the feces.
Tissue concentrations 1 week after injection revealed that
approximately 39 and 37 percent of the curium dose had been retained in the
canine liver and bone, respectively.
Following intravenous nuclide doses to
lactating Suffolk sheep, McClellan et a1., (1962) noted that while p1utonium-
239 and americium-24l both reached peak concentrations in the milk 7 hours
after injection, the peak milk concentrations for curium-244 occurred slightly
earlier at the 4- to 7-hour period.
Both americium and curium were cleared
more rapidly from the plasma, and their subsequent transfer to milk was greater
than was observed for plutonium.
Results on curium metabolism in dairy animals have been reported at the
Nevada Applied Ecology Group meetings (Sutton et a1., 1977; Patzer et al.,
1977) .
Information from these two reports, as well as some additional data
1
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from the same experiments~ has been incorporated into this summary document.
The overall objectives of this investigation were (1) to establish the gastro-
intestinal uptake of curium~ (2) to determine the amount of activity trans-
ported to milk~ (3) to examine the plasma clearance rate of curium, (4) to
quantify the excretion characteristics of curium in urine and feces, and (5)
to establish the tissue deposition pattern of curium in dairy animals.
In
pursuing the objectives, samples of blood, milk, urine and feces were taken
from groups of cows and goats after the animals had received either oral or
intravenous doses.
Tissue collections were made at time of sacrifice.
METHODS AND MATERIALS
The study was conducted in two phases at the Nevada Test Site farm.
lactating goats~ between 1 and 3 years of age and confined to individual
metabolism stalls, were used in the initial phase. Three of these goats
Six
received acute oral doses of curium-243 (200 ~Ci per animal), and the other
three goats received single intravenous curium-243 doses of 20.8 ~Ci per
animal.
Both intravenous and oral doses were in the chloride form.
Intra-
venous doses were citrate-buffered and were administered by jugular veni-
puncture.
Oral doses were placed in gelatin capsules containing cellulose
fiber and administered using a balling gun. No intravenous or oral dose
adjustments were made for individual variations in animal weight. Composite
daily collections of milk, urine and feces were sampled from each goat
over a l44-hour period after dosing.
this period.
Blood samples were also taken during
The animals were catheterized with in-dwelling, inflatable urinary
catheters and the urine was allowed to drain through polyethylene tubing
into plastic bottles at the rear of each stall. Fecal pellets were collected
in a modified tray. The goats were milked by hand twice daily and single
blood samples were taken by jugular venipuncture. All urine, milk and fecal
collections were weighed and then combined (a.m. + p.m.) into respective
24-hour composites for each animal. Fecal collections were manually mixed.
Respective composites of milk and urine were shaken thoroughly in plastic
containers. Weighed subsamples were then taken from the respective composites
2
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and placed in individual 200-ml aluminum cans with formaldehyde added as
preservative. Blood samples were centrifuged and the plasma and cells
separated using disposable pipettes. The packed cells were washed two times
with physiological saline. Samples of plasma and cells were then individually
diluted with distilled water and formaldehyde was added as a preservative.
in the second phase of this study, two Holstein dairy cows, average
weight 666 kg, were used,and the same procedures as the caprine experiment
were followed.
The first animal was given a single oral dose (39.6 mCi) of
curium-243 chloride,and the second animal received 1.12 millicuries (mCi) of
citrate-buffered curium-243 chloride in a single intravenous injection.
As
before, the oral dose was placed in a gelatin capsule and administered using
a balling gun.
The intravenous dose was administered by jugular venipuncture.
The cows were each catheterized for urine collection~ and a grid-covered pan,
lined with polyethylene sheeting, was used to collect the feces.
Milk was
collected with individual bucket milkers twice daily,and the 24-hour composite
sampling was conducted for milk, urine and feces. A Hobart mixer was used to
mix the large fecal collections.
both cows.
Daily blood samples were also taken from
Cows and goats were sacrificed 7 days after dosing (Table I) using intra-
venously administered euthanasia solutiop.
Extensive precautions were taken
in the sacrifice area (Nevada Test Site farm) to reduce any possibility of
cross-contamination during tissue collection.
Organs and tissues were
removed from the partially exsanguinated animals within approximately 60
minutes of sacrifice.
Extraneous tissue (adipose tissue or muscle associated
with bone samples) was discarde~ and the required sample, plus formaldehyde,
was sealed in 200-ml aluminum cans.
Total weights were taken on most organs
so that the percentage of administered dose retained by a specific tissue
or organ could be calculated.
When total weight was not practical (for muscle,
bone, blood, etc.), total curium-243 content was based on extrapolated organ
weights using the respective percentage of body weight reported by Davis
et al., (1975), Smith and Baldwin (1974) and Matthews ~ al., (1975). Curium
concentrations from the femur (diaphysis and epiphysis) and sternum were
averaged to estimate the osseous retention values.
3
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Table I
BACKGROUND INFORMATION ON THE EIGHT DAIRY ANIMALS DOSED WITH CURIUM
Animal
Sacrifice Time
Average Daily Output
( )
~
Animal Weight Post-treatment During Experiment kg
Number Curium Dose (kg) (days) Milk Urine Feces
singl~ oral dose
Cow 256 (39.6 mCi) of curium-243 596 7 8.7 7.6 10.7
chloride
single intravenous dose
Cow 344 (1.12 mCi) of citrate- 736 7 12.7 17.8 2.0.2
buffered curium-243 chloride
single oral dose
Goat 1 (200 ~Ci) of curium-243 37.5 7 1.3 1.0 0.8
chloride
single oral dose
Goat 2 (200 ~Ci) of curium-243 35.5 7 1.2 0.9 0.7
chloride
single oral dose
Goat 3 (200 ~Ci) of curium-243 49.5 7 1.5 1.3 0.8
chloride
single intravenous dose
Goat 4 (20.8 flCi) of citrate- 52.0 7 1.5 1.4 0.9
buffered curium-243 chloride
single intravenous dose
Goat 5 (20. 8 ~Ci) of citrate-buffered 39.0 7 0.9 0.8 0.3
curium-243 chloride
,
single intravenous dose
Goat 6 (20. 8 ~Ci) of citrate-buffered 33.0 7 1.1 1.0 0.6
curium-243 chloride
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Gamma counting was considered the most feasible analytical technique for
use in conjunction with these experiments.
Curium-243 concentrations in the
sample material were determined by counting the 228 and 278 KeV gamma rays
that occur, respectively, in 7.3 and 11,2 percent oŁ the disintegratiQns.
Samples were counted in 200~mil1i1iter aluminum cans using a NaI(Tl) detector
and pulse height analyzer. For samples with low (1 picocurie per gram)
curium-243 concentrations, 400-minute counting times were used. Checks were
made for gain shifts and changes in efficiency with an aliquot of the dosing
solution. Backgrounds were taken before, during and after each series of
counts to confirm that contamination of the counting chamber had not occurred.
Various spiked standards (feces, milk, urine, plasma, blood cells, distilled
water and agar) were also prepared. The amount of curium added (spike) was
based on (1) the supplier's value for the stock solution and on (2) the
calculated concentration range (percentage of dose per gram) likely to occur
in milk, urine, etc., throughout the project.
The curium-243 stock material
was obtained from Oak Ridge National Laboratory and contained curium-244 as
a major impurity (as of May 1975; 55.9 atom % curium-243 and 42.1 atom %
curium-244).
After assaying the samples by direct counting methods, radiochemical
analyses (LFE Corporation, Richmond, California) were performed (1) on a
portion of the quality assurance samples, (2) on sets of samples that demon-
strated considerable between-animal or within-animal variability and (3) on
samples that contained less than 500 femtocuries (fCi) of curium-243 per gram
of material.
These radiochemical assays were conducted for total curium
concentration (curium-243 plus curium-244) using alpha spectrometry.
Curium-
242 was used as a tracer.
In order to extract values for curium-243 from the
total curium concentrations, i.e., radiochemical assays, it was assumed that
both isotopes had been metabolized in the same way.
The decay-corrected
isotopic ratio present in the dosing solution was therefore assumed to be
the same (decay-corrected) isotopic ratio encountered in the sample material.
5
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RESULTS AND DISCUSSION
Approximately 0.02 percent of the oral curium dose was absorbed from the
bovine gastrointestinal tract.
Of this relatively small amount, approximately
9 percent and 2 percent were subsequently transported to bovine urine and milk,
respectively.
Curium uptake in orally dosed goats was estimated to be 0.006
percent of the administered nuclide.
Five percent of this absorbed amount
was then transported to caprine urine and less than 4 percent was recovered
in the milk.
At time of sacrifice (160 hours after dosing), 89 percent of
the absorbed nuclide was recovered in the bovine carcass and approximately
88 percent of the absorbed curium was retained in the caprine carcass.
Th~
abovementioned findings for the orally dosed animals are summarized in Table
II.
Carcass retention values used in this table were derived by summing the
curium recovered in bone, liver, kidney- lung, spleen, heart, gonads, thyroid,
muscle and plasma for the individual animals.
The percentages of dose contained in plasma, milk, urine and feces for
the orally dosed animals are shown in Tables III and IV.
Values are given
for each collection interval and for the total transport to milk, urine and
feces during the l44-hour collection period.
For the orally dosed cow (Table
III), peak curium output in the feces occurred between the 48- and 96-hour
collection periods.
Plasma values were highest at 24 hours and remained
elevated through the 48-hour period.
Nuclide transport to milk and urine
reflected these plasma values and, in the case of milk, a peak plateau was
noted between 48 and 72 hours.
The nuclide transport to urine increased to
a peak at 48 hours and then gradually declined throughout the remainder of
the collection period. Total nuclide transport to bovine milk and urine was
0.0005 and 0.002 percent of the administered oral dose, resp8ctively. The
.mean peak curium transport to caprine milk (Table IV) occurred at the 72-hour
collection period.
However, two of the three goats had a distinctive peak
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--.J
Table II
GROSS ESTIMATE OF CURIUM TRANSPORT IN DAIRY ANIMALS FOLLOWING A SINGLE ORAL CURIUM-243 DOSE
Cow 256 Goat 1 Goat 2 Goat 3
% of % of % of % of % of % of % of % of
Oral Absorbed Oral Absorbed Oral Absorbed Oral Absorbed
Dose Dose Dose Dose Dose Dose Dose Dose
Milk 4.6 x 10-4 2.0 6.2 x 10-4 6.1 x 10-5 1. 1 x 10-4 1.8
(144 h) 8.4 1.3
Urine 1. 9.x 10-3 8.5 2.7 x 10-4 3.7 3.4 x 10-4 7.0 3.5 x 10-4 5.6
(144 h)
Feces* 88.9 1.0 116 2.9 111 2.9 100 2.9
(144 h)
Carcass 2.0 x 10-2 88.9 6.1 x 10-3 84.7 4.3 x 10-3 88.7 5.5 x 10-3 89.4
(160 h)
Estimated** 2.3 x 10-2 7.2 x 10-3 4.9 x 10-3 6.2 x 10-3 -
- - -
G.1. Uptake
*Curium excretion in feces should eventually approach 100 percent of dose following nuclide
ingestion. Calculations for goats 1 and 2 (% of oral dose) exceed 100 percent due to
inaccuracies associated with fecal determinations. Values for % of absorbed dose are
based on observed nuclide transport to feces for intravenously dosed animals.
**Gross summation composed of (1) the total transport (144 h) to milk and urine, (2)
recovered activity estimate for each carcass (160 h) and (3) the extrapolated amount of
absorbed curium-243 returned to the gastrointestinal tract.
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Table III
PERCENTAGE OF ORAL CURIUM-243 DOSE NOTED IN BLOOD PLASMA, MILK, URINE AND
FECES FOR ONE DAIRY COW DURING THE 144-HOUR SAMPLING PERIOD
Time After P1asma* Milk Urine Feces
Dosing
8 h - 1. 38 x 10-6 1. 06 x 10-5 -
15 h 3.00 x 10-4 - - -
24 h 4.15 x 10-4 2.19 x 10-5 2.17 x 10-4 4.43
48 h 3.66 x 10-4 1. 32 x 10-4 7.11 x 10-4 16.3
72h 1. 53 x 10-4 1. 41 x 10-4 3.93 x 10-4 32.6
96 h 7.84 x 10-5 7.42 x 10-5 2.84 x 10-4 27.4
120 h 4.31 x 10-5 5.33 x 10-5 1. 91 x 10-4 8.04
144 h 3.81 x 10-5 3.51 x 10-5 1. 36 x 10-4 4.14 x 10-3
Total - 4.60 x 10-4 1. 94 x 10-3 88.8
*Extrapo1ated values
Table IV
MEAN PERCENTAGE OF ORAL CURIUM-243 DOSE NOTED IN BLOOD PLASMA, MILK, URINE AND
FECES FOR THREE DAIRY GOATS DURING THE 144-HOUR SAMPLING PERIOD
Time After P1asrna* Milk Urine Feces
Dosing
8 h 3.64 x 10-5 1. 69 x 10-6 2.08 x 10-5 -
24 h - 2.01 x 10-5 1. 59 x 10-4 13.8
48 h - 5.06 x 10-5 7.03 x 10-5 84.0
72h - 1. 73 x 10_4 2.06 x 10-5 10.1
96 h - 8.66 x 10-6 1. 84 x 10-5 1. 20
120 h - 5.77 x 10-6 1. 37 x 10-5 1. 12 x 10-1
144 h - 5.96 x 10-6 1. 33 x 10-5 1. 00 x 10-2
160 h** 6.34 x 10-6 - - -
Total - 2.66 x 10-4 1. 59 x 10-4 109.2
*Extrapo1ated values, limited data available.
**Approxirnate time of sacrifice.
8
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curium transport to milk by the 48-hour period. In all three goats the peak
nuclide transport to urine and feces occurred 24 and 48 hours after dosing,
respectively.
Limited information on the amount of curium present in caprine
plasma is also shown in Table IV.
Curium concentrations decreased rapidly in the plasma of all intravenously
dosed animals (Table V).
Approximately 1 percent of the injected nuclide was
present in the plasma 8 hours after dosing.
While further declines were not
as dramatic, analysis of the l44-hour collections from the cow and goats
revealed that 0.09 percent of the respective doses remained in the plasma.
A rapid plasma clearance rate for curium has also been reported in sheep
(McClellan ~ al., 1962).
Bovine plasma extrapolations (to percentage of dose per total plasma)
were based on the assumption that whole blood would be 8 percent of the body
weight and subsequently that plasma represented 60 percent of the whole blood.
Caprine plasma was calculated at 55.9 ml per kg of body weight (Klement ~ al.,
1955).
Multiple samples of bovine and caprine blood
analyzed by both the
direct counting and radiochemistry techniques indicated that the major fraction
of whole blood curium was occurring in the plasma.
In spite of some fluctua-
tion in the percentage distribution, approximately 90 percent of the whole
blood curium was noted in the plasma fraction and approximately 10 percent
of the whole blood nuclide content was recovered in the cellular portion.
Tables VI through XI present a comparison of the mean curium transport
to milk, urine and feces for all treatment groups.
Values are expressed as
both a percentage of the dose recovered per total collection and as the
percentage of dose per gram of milk, urine or feces.
Where the respective
tables show a blank at an early post-dosing time (8 hours through 24 hours),
it indicates a slight alteration in the sampling schedule.
Nuclide transport to milk, urine and feces was basically similar between
the orally dosed cow and the orally dosed goats.
Curium concentrations
reached a peak in bovine milk 48 hours after dosing and at 72 hours after
dosing in caprine milk. Without the one unexplainably high milk value
9
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Time post
injection
8 h
16 h
24 h
48 h
72h
96 h
120 h
144 h
Table V
MEAN PERCENTAGE OF CURIUM DOSE REMAINING IN BOVINE AND
CAPRINE PLASMA FOLLOWING ACUTE INTRAVENOUS INJECTIONS
OF CITRATE-BUFFERED CURIUM-243 CHLORIDE
% of Dose per Total P1asma* % of Dose per Gram of Plasma
Cow Goats Cow Goats
9.20 x 10-1 1. 23 2.61 x 10-5 4.68 x 10-4
1. 21 5.75 x 10-1 3.41 x 10-5 2.58 x 10-4
9.55 x 10-1 4.54 x 10-1 2.70 x 10-5 1. 91 x 10-4
7.41 x 10-1 3.18 x 10-1 2.09 x 10-5 1. 33 x 10-4
5.09 x 10-1 2.32 x 10-1 1. 45 x 10-5 9.76 x 10-5
2.23 x 10-1 6.11 x 10-2 6.23 x 10-6 2.40 x 10-5
1. 43 x 10-1 6.33 x 10-2 4.03 x 10-6 2.40 x 10-5
9.87 x 10-2 8.82 x 10-2 2.80 x 10-6 3.85 x 10-5
-.-
*Extrapo1ated values
'10
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(goat 1 at 72 hours), the mean peak concentration would have occurred in
caprine milk 48 hours after dosing (2.31 x 10-8 percent of dose per gram) with
a peak plateau from the 24-hour to 72-hour collection period. The mean total
curium transport to caprine milk would also have been reduced to 1.06 x 10-4
percent of oral dose (instead of 2.66 x 10-4 as shown in Table VI) if the high
72-hour value for goat 1 had not been included with values for goats 2 and 3.
However, multiple sampling and the results from two assay techniques produced
no direct evidence of contamination and Tables II, IV, VI and VII include the
higher-than-expected 72-hour milk value for goat 1. Total curium excretion
in the urine was somewhat greater for the orally dosed cow than for the orally
dosed goats (Table VIII).
Peak nuclide concentrations occurred at 48 hours
in bovine urine and at 24 hours in caprine urine (Table IX).
Curium excretion
in bovine feces was greatest between the 48-hour and 96-hour collection
periods and reached a distinct peak in caprine feces 48 hours after nuclide
ingestion (Table X and XI).
Similarities in curium transport to milk, urine and feces (between the
cow and the goats) were also noted after intravenous dosing.
The average
percentage of injected curium transferred to milk, urine and feces was 2, 8
and 1 percent, respectively, for the cow and 2, 5 and 5 percent, respectively,
for goats.
Peak curium concentrations were found in the milk and urine of
all intravenously dosed animals during the initial 8-hour collection period.
The peak nuclide concentration was found in bovine feces 24 hours after
nuclide injection, and the fecal concentrations subsequently declined through-
out the remainder of the collection periods.
In caprine feces the peak
nuclide concentration was not reached until the 120-hour period. Curium
excretion was mainly urinary for the cow, but in the case of intravenously
dosed goats the total nuclide excretion was equally divided between urine
and feces (Tables VIII, X and XII). The goats were excreting a somewhat
greater quantity of feces (increasing daily fecal weight) toward the end of
the collection period but, as shown in Table XI, the curium concentration
(percentage of dose per gram) maintained somewhat of a peak plateau from 48
hours to 144 hours after curium injection.
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Time After
Dosing
8 h
24 h
48 h
72h
96 h
120 h
144 h
Total
Time After
Dosing
8 h
24 h
48 h
72h
96 h
120 h
144 h
Table VI
MEAN PERCENTAGE OF CURIUM DOSE TRANSFERRED TO MILK
DURING THE 144-HOUR COLLECTION PERIOD
Oral Dose Intravenous Dose
Cow Goats Cow Goats
1. 38 x 10-6 1. 69 x 10-6 4.91 x 10-1 8.07 x 10-1
2.19 x 10-5 2.01 x 10-5 4.11 x 10-1 5.09 x 10-1
1. 32 x 10-4 5.06 x 10-5 4.29 x 10-1 3.29 x 10-1
1.41 x 10-4 1. 73 x 10-4 3.30 x 10-1 1.87 x 10-1
7.42 x 10-5 8.66 x 10-6 1. 79 x 10-1 1. 74 x 10-1
5.33 x 10-5 5.77 x 10-6 8.93 x 10-2 8.99 x 10-2
3.51 x 10-5 5.96 x 10-6 5.80 x 10-2 6.41 x 10-2
4.60 x 10-4 2.66 x 10-4 1.99 2.16
Table VII
MEAN PERCENTAGE OF CURIUM DOSE TRANSFERRED
PER GRAM OF MILK
Oral Dose Intravenous Dose
Cow Goats Cow Goats
7.25 x 10-10 2.73 x 10-9 7.46 x 10-5 1. 59 x 10-3
7.81 x 10-9 1.87 x 10-8 5.71 x 10-5 6.12 x 10-4
2.06 x 10-8 2.31 x 10-8 3.54 x 10-5 2.88 x 10-4
1.64 x 10-8 1. 29 x 10-7 2.44 x 10-5 1.81 x 10-4
7.65 x 10-9 5.45 x 10-9 1. 36 x 10-5 1.09 x 10-4
4.72 x 10-9 5.10 x 10-9 7.32 x 10-6 8.66 x 10-5
3.03 x 10-9 2.56 x 10-9 5.09 x 10-6 5.61 x 10-5
12
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Time After
Dosing
8 h
24 h
48 h
72h
96 h
120 h
144 h
Total
Time After
Dosing
8 h
24 h
48 h
72h
96 h
120 h
144 h
Table VIII
MEAN PERCENTAGE OF CURIUM DOSE TRANSFERRED TO URINE
DURING THE 144-HOUR COLLECTION PERIOD
Oral Dose Intravenous Dose
Cow Goats Cow Goats
1. 06 x 10-5 2.08 x 10-5 3.23 2.08
2.17 x 10-4 1. 59 x 10-4 1. 68 9.94 x 10-1
7.11 x 10-4 7.03 x 10-5 9.64 x 10-1 3.94 x 10-1
3.93 x 10-4 2.06 x 10-5 8.55 x 10-1 2.95 x 10-1
2.84 x 10-4 1. 84 x 10-5 6.46 x 10-1 2.92 x 10-1
1.91 x 10-4 1. 37 x 10-5 4.58 x 10-1 2.92 x 10-1
1. 36 x 10-4 1.33 x 10-5 3.50 x 10-1 2.07 x 10-1
1. 94 x 10-3 3.16 x 10-4 8.18 4.55
Table IX
MEAN PERCENTAGE OF CURIUM DOSE TRANSFERRED
PER GRAM OF URINE
Oral Dose Intravenous Dose
Cow Goats Cow Goats
7.50 x 10-9 4.62 x 10-8 8.28 x 10-4 6.86 x 10-3
6.77 x 10-8 2.10 x 10-7 1. 20 x 10-4 1. 32 x 10-3
1.29 x 10-7 6.74 x 10-8 5.81 x 10-5 5.00 x 10-4
6.34 x 10-8 3.07 x 10-8 5.81 x 10-5 3.56 x 10-4
3.46 x 10-8 1.71 x 10-8 3.73 x 10-5 2.84 x 10-4
1. 87 x 10-8 1. 03 x 10-8 2.30 x 10-5 2.29 x 10-4
1. 28 x 10-8 9.88 x 10-9 1. 74 x 10-5 1. 47 x 10-4
13
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Time After
Dosing
8 h
24 h
48 h
72h
96 h
120 h
144 h
Total
Time After
Dosing
8 h
24 h
48 h
72h
96 h
120 h
144 h
Table X
MEAN PERCENTAGE OF CURIUM DOSE TRANSFERRED TO FECES
DURING THE 144-HOUR COLLECTION PERIOD
Oral Dose Intravenous Dose
Cow Goats Cow Goats
- - 7.34 x 10-3 3.54 x 10-3
4.43 13.8 3.61 x 10-1 6.94 x 10-2
16.3 84.0 3.21 x 10-1 6.94 x 10-1
32.6 10.1 2.95 x 10-1 5.54 x 10-1
27.4 1.20 2.05 x 10-1 9.28 x 10-1
8.04 1.12 x 10-1 1. 43 x 10-1 1.13
4.14 x 10-3 1. 00 x 10-2 9.82 x 10-2 1.14
88.8 109.2 1.43 4.52
Table XI
MEAN PERCENTAGE OF CURIUM DOSE TRANSFERRED
PER GRAM OF FECES
Oral Dose Intravenous Dose
Cow Goats Cow Goats
- - 2.30 x 10-6 4.17 x 10-5
1. 58 x 10-3 2.61 x 10-2 2.30 x 10-5 3.01 x 10-4
3.79 x 10-3 1. 01 x 10-1 1.79 x 10-5 1. 60 x 10-3
3.11 x 10-3 1. 81 x 10-2 1.49 x 10-5 1.56 x 10-3
1.72 x 10-3 1. 45 x 10-3 9.55 x 10-6 1. 54 x 10-3
6.09 x 10-4 1.31 x 10-4 6.55 x 10-6 1.72 x 10-3
2.45 x 10-7 2.07 x 10-5 4.66 x 10-6 1. 70 x 10-3
14
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Table XII
RELATIVE EXCRETION OF CURIUM IN URINE AND FECES FOLLOWING SINGLE INTRAVENOUS DOSES
(Values Expressed as a Mean Percentage of the Total Curium-243 Transported
to both Urine and Feces over the l44-Hour Collection Period)
Time
Post-Injectio
24 h
48 h
72h
96 h
120 h
144 h
Total
Cow Goats
% of Total % of Total % of Total % of Total % of Total % of Total
Excretion Excretion Excretion Excretion Excretion Excretion
Recovered in Recovered Recovered Recovered in Recovered Recovered
n Urine & Feces in Urine in Feces Urine & Feces in Urine in Feces_-
55.0 51.1 3.8 35.4 34.5 0.9
13.4 10.0 3.3 12.1 4.3 7.8
12.0 8.9 3.1 9.5 3.3 6.1
8.8 6.7 2.1 13.1 3.2 9.9
6.2 4.7 1.5 14.9 3.1 11. 8
4.6 3.6 1.0 15.0 2.3 12.7
100 85.0 14.8 100 50.7 49.2
15
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There was some suggestion of a species difference in the relative nuclide
deposition between liver and bone. Bovine skeleton was the major deposition
site following both intravenous and oral curium doses (Table XIII). However,
in all three intravenously dosed goats, the liver contained the greatest
amount of curium. Nuclide deposition in bone and liver was essentially equal
for two of the three orally dosed goats while the skeleton contained the most
curium in the other animal. These comparisons refer to total organ content
only since the liver contained the greatest nuclide concentration (curium
per gram of tissue) in all groups (Table XIV). Initial deposition of curium
has been reported to occur primarily in the liver of laboratory rats (Hamilton,
1947). In the case of dogs, more curium was retained in the skeleton than in
the liver 2 weeks after nuclide inhalation (McClellan et al., 1972).
Intra-
venously dosed dogs (Lloyd et al., 1974) retained more curium in the liver 6
days post-injection but by the thirteenth day, bone had become the primary
retention site.
Tables XV, XVI, XVII and XVIII present some comparisons between the
metabolism of curium-243 and americium-24l in Holstein dairy cows.
Following
intravenous injections, nuclide transport to milk, urine and feces was quite
similar with a dramatic decline in urinary nuclide excretion after the first
24 hours (Table XV). Liver contained the greatest concentration of both
nuclides (Table XVI) approximately I week after the respective intravenous
doses.
Similarities were also noted in nuclide transport to edible bovine
products after oral dosing (Table XVII) and the relative nuclide deposition,
expressed as a percentage of absorbed dose, was nearly identical following
nuclide ingestion.
16
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Bone
Liver
Kidney
Lung
Muscle
Spleen
Heart
Diaphysis
Epiphysis
Sternum
Liver
Kidney
Lung
Muscle
Spleen
Heart
Thyroid
Adrenal
Mammary G1d.
Gonads
MEAN PERCENTAGE OF CURIUM DOSE RETAINED
IN DAIRY ANIMALS AT TIME OF SACRIFICE
Oral Dose Intravenous Dose
Cow Goats Cow Goats
1. 09 x 10-2 3.10 x 10-3 58.6 18.7
6.92 x 10-3 1. 73 x 10-3 29.1 37.2
5.23 x 10-4 1.13 x 10-4 2.95 1.57
3.33 x 10-4 8.70 x 10-5* 1. 38 7.31 x 10-]
1. 03 x 10-3 2.25 x 10-4 3.17 4.86
1.09 x 10-4 1. 78 x 10-5* 7.50 x 10-1 8.84 x 10-2
2.53 x 10-4 1. 90 x 10-4 7.50 x 10-1 3.13 x 10-1
*Based on two animals
Table XIV
MEAN PERCENTAGE OF CURIUM DOSE RETAINED
PER GRAM OF TISSUE
Oral Dose Intravenous Dose
Cow Goats Cow Goats
6.84 x 10-8 6.67 x 10-7 3.35 x 10-4 7.37 x 10-3
8.01 x 10-8 8.34 x 10-7 4.22 x 10-4 6.41 x 10-3
1. 61 x 10-7 1. 86 x 10-6 6.39 x 10-4 8.14 x 10-3
6.62 x 10-7 1. 89 x 10-6 2.54 x 10-3 4.23 x 10-2
3.13 x 10-7 6.33 x 10-7 9.91 x 10-4 1. 08 x 10-2
6.89 x 10-8 I 1. 36 x 10-7* 2.16 x 10-4 1.30 x 10-3
I
3.75 x 10-9 1.13 x 10-8 9.38 x 10-6 2.66 x 10-4
5. 76 x 10-8 1. 22 x 10- 7 * 2.92 x 10-4 9.54 x 10-4
7.96 x 10-8 2.50 x 10-7 2.09 x 10-4 1. 62 x 10-3
2.65 x 10-8 --** 1.04 x 10-4 1. 69 x 10-3
3.13 x 10-8 --** 2.49 x 10-4 9.04 x 10-4
1. 06 x 10-7 2.50 x 10-7 2.39 x 10-4 3.33 x 10-3
4.95 x 10-8 --** 1.43 x 10-4 1.46 x 10-3
*Based on two animals
**Limited data available
17
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Table x:v
COMPARISON OF CURIUM-243 AND AMERICIUM-24l TRANSPORT
TO MILK, URINE AND FECES IN HOLSTEIN DAIRY COWS.
(Values Expressed as a Percentage of the
Respective Intravenous Doses)
Time Curium-243* Americium-24l**
post-injection Milk Urine Feces 'Milk Urine Feces
24 h 0.902 4.91 0.368 1. 41 3.25 1. 09
48 h 0.429 0.964 0.321 0.470 0.887 0.454
72h 0.330 0.855 0.295 0.281 0.540 0.296
96 h 0.179 0.646 0.205 0.229 0.328 0.201
120 h 0.089 0.458 0.143 0.167 0.291 0.152
Total 1. 93 7.83 1. 33 2.56 5.30 2.19
*Values from one cow given an intravenous dose (1.12 mCi) of
citrate-buffered curium-243 chloride.
**Average values from two cows each given an intravenous dose
(0.96mCi) of citrate-buffered americium-24l chloride (Sutton
et al., 1978).
18
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Table XVI
COMPARISON OF CURIUM-243 AND AMERICIUM-24l RETENTION IN HOLSTEIN DAIRY COWS
APPROXIMATELY ONE WEEK AFTER RECEIVING SINGLE INTRAVENOUS DOSES.
(Values Expressed as a Percentage of Dose per kg of Tissue).
Tissue Curium-243* Americium-24l**
Diaphysis 3.35 x 10-1 3.05 x 10-1
Epiphysis 4.22 x 10-1 6.07 x 10-1
Sternum 6.39 x 10-1 6.79 x 10-1
Liver 2.54 3.82
Kidney 9.91 x 10-1 1.15
Muscle 9.38 x 10-3 1. 93 x 10-2
Lung 2.16 x 10-1 2.64 x 10-1
Spleen 2.92 x 10-1 2.71 x 10-1
Heart 2.09 x 10-1 2.88 x 10-1
*Values from one cow given an intravenous dose
(1.12mCi) of citrate-buffered curium-243 chloride.
**Average values from two cows each given an intra-
venous dose (0.96 mCi) of citrate-buffered ameri-
cium-24l chloride (Sutton et aZ.. 1978).
19
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Table XVII
TRANSPORT OF ORALLY ADMINISTERED AMERICIUM-241 AND
CURIUM-243 TO EDIBLE BOVINE PRODUCTS
N
o
Americium 2 animals
chloride sacrificed
41. 7 mCi/ animal 2 4.4 x 10-4 8.6 x 10-6 8 days 4.1 x 10-3 4.3 x 10-7 9.6 x 10-4 3.6 x 10-9
acute dose post-
(Sutton et aZ., 1978) treatment
Curium 1 animal
chloride sacrificed
39.6 mCi/anima1 1 4.6 x 10-4 2.0 x 10-5 7 days 6.9 x 10-3 6.6 x 10-7 1.0 x 10-3 3.8 x 10-9
acute dose post-
treatment
Nuclide
Dose
No. of
Animals
% of
% of-Dose Dos~/liter
Secreted in of Milk at
Milk Peak
(Cumulative) Concentration
Time of
Sacrifice
% of
Dose in
Liver
% of
Dose/g
of Liver
% of
Dose in
Muscle
(Skeletal)
% of Dose/g
of
Muscle
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Table XVIII
RELATIVE DEPOSITION OF CURIUM-243 AND AMERICIUM-241 IN HOLSTEIN DAIRY COWS
ONE WEEK AFTER RECEIVING SINGLE ORAL DOSES. (Values Expressed as a
Percentage of the Absorbed Dose*)
Bone
Liver
Muscle
Kidney
Spleen
Gonads
Thyroid
Curium-243 Americium-241
Cow 256 Cow 281 Cow 269
48.1 40.7 41.2
30.4 30.5 31.4
4.5 7.9 6.5
2.3 3.4 2.2
0.5 0.6 0.6
0.005 0.003 0.005
0.004- 0.005 0.003
*Gastrointestina1 uptake of curium in cow-256
was estimated to be 2.3 x 10-2 percent of the
oral dose; uptake of americium (Sutton et al.,
1978) was estimated to be 1.4 x 10-2 and
1.2 x 10-2 percent of the oral dose for cows
281 and 269 respectively. Both nuclides were
given as chlorides.
21
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REFERENCES
Davis, C. N., L. E. Davis and T. E. Powers. 1975. "Comparative Body Compo-
sitions of the Dog and Goat." Am.~. Vet. Res. ]2.: 309-311.
Hamilton, J. G.
Elements."
1947. "Metabolism of the Fission Products and the Heaviest
Radiol. 49:325-343.
Klement, A. W., Jr., D. E. Ayer and E. B. Rogers. 1955. "Simultaneous use
of CrS1 and T-1824 Dye in Blood Volume Studies in the Goat." !!!!. {.
Physiol., 181:15-18.
Lloyd, R. D., D. R. Atherton, C. W. Mays, S. S. McFarland and J. L. Williams.
1974. "Early Excretion, Retention and Distribution of Injected Curium
Citrate in Beagles." Health Phys. 11..:61-67.
Matthews, C. A., W. W. Swett and R. E. McDowell.
Internal Anatomy of Holsteins and Jerseys."
1975. "External Form and
~. Dairy Sc~. 58:1453-1475.
McClellan, R. 0., H. A. Boyd, A. F. Gallegos and R. G. Thomas. 1972. "Re-
tention and Distribution of 244Cm Following Inhalation of 244CmC13 and
244Cm01.73 by Beagle Dogs." Health Phys. ~:877-885.
McClellan, R. 0., H. W. Casey and L. K. Bustad. 1962. "Transfer of Some
Transuranic Elements to Milk." Health Phys. ~:689-694.
Patzer, R. G., W. W. Sutton, P. B. Hahn and G. D. Potter. 1977. "Comparisons
of Curium-243 and Plutonium-238 Biological Transport in Dairy Animals
Following Intravenous Injection." pp. 243-265. In Transuranics in
Desert Ecosystems. M. G. White, P. B. Dunaway and D. L. Wireman, Eds.
USDOE-NVO-18l.
Smith, N. E., and R. L. Baldwin. 1974. "Effects of Breed, Pregnancy and
Lactation on Weight of Organs and Tissues in Dairy Cattle." J. Dairy
Sci. 57:1055-1060.
--
Sullivan, M. F. and A. 1. Crosby. 1975. "Absorption of Uranium-233, Neptunium-
237, Plutonium-238, Americium-24l, Curium-244 and Einsteinium-253 from
the Gastrointestinal Tract of Newborn and Adult Rats." pp. 1.05-108. In
Pacific Northwest Laboratory Annual Report. BNWL-1950 (PT. 1).
22
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Sutton, W. Wo. R. G. Patzer, P. B. Hahn and G. D. Potter. 1977. "Biological
Transport of Curium-243 in Lactating Dairy Goats." pp. 167-178. In
Environmental Plutonium on the Nevada Test Site and Environs. M. G. White,
P. B. Dunaway and W. A. Howard, Eds. USERDA-NVO-17l.
Sutton, W. W., R. G. Patzer, A. A. Mullen, P. B. Hahn and G. D. Potter. 1978.
"Metabolism of Americium-24l in Dairy Animals." IN:NVO-192, in press.
USDOE-NVO'.
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