PRODUCED BY DCC & DCW
In an earlier
report issued from these Laboratories (No. 86199B dated December 15, 1967)
the results of 2 year toxicologic studies in dogs receiving three injection regimens and one group on test for only one year
were described. The latter group consisted of three dogs that received one subcutaneous
injection of 1 ml of C14 randomly labeled DC 360 fluid. The test material
was reported to be labeled in the end blocking methyl groups and in the methyl groups along the polymer chain. The toxicological findings including tissue morphology at the end of a 1 year period were described. The present supplement to the report covers the result of the C14 analyses
of tissues from one dog sacrificed at each of three intervals up to one year.
The injection material, DC 360 Fluid cs,
was described by Dow Corning Corporation as containing a specific activity of 1 mc per g.
Samples of injection fluid were received via Railway Express and bore the following labels
__________________________________________________________________
Date
Label
Received
__________________________________________________________________
6/4/65
Yellow label: “Caution
Radioactive material: Isotope; Carbon 14
…Source Strength: 5.0 mc..Serial Number: A-1494-131…Assay
Date: 5-21-65..Investigator:
G. Vogel”
White Label: “Uniformly Carbon-14 labeled 360 Fluid…350 centistokes..1.0
mc/g..5.0 grams”
6/16/66
“Caution Radioactive Material; Isotope:
Carbon-14; Source strength: 0.50 mc; Serial Number: A-1640-41; Assay Date: June 3, 1966; Investigator: G. Vogel”
Shipping ticket identification: “Dow Corning 360 fluid, 350 ca.
cont’g. c-14, 1mc/g
__________________________________________________________________
Identification of the sample received on June 16, 1996
was inadvertently omitted from our report: (Laboratory No. 86199B issued on December
15, 1967).
The protocols employed are described in the report referred to above which included
the findings with respect to the growth, food intake, hematological and clinical chemical findings as well as organ weights,
gross and microscopic postmortem findings after sacrifice at 3,6, and 12 months.
Procedure
At autopsy, following selection of tissues
for histological sectioning, the organs were prepared in separate labeled plastic bags and frozen liver, spleen, stomach,
small and large intestines, pancreas, kidneys, urinary bladder, gonads, thyroid, thymus and salivary glands, lymph nodes,
heart including aorta, lungs, skin, muscle, spinal cord, and brain. They were
stored and held in a frozen state until all samples were available after completion of the 1-year sacrifice. They were shipped in the frozen state to our collaborating laboratory (New England Nuclear Corporation)
for radioactive counting. Portions of the tissues were weighed in sealed tubes,
combusted, diluted with priming fluid, and counted in a scintillation counter.
The distribution of animals, their body weights and time of initiation are shown
below:
_________________________________________________________________________
Animal No. Body Weight
Total Dose Time
of Sacrifice
_________________________________________________________________________
kg
ml
mc
months
9913M
6.2
1 1
3
9914M
8.3
1 1
6
9915M
8.9
1 1 12
_________________________________________________________________________
Inasmuch as the experiment was not designed as a balance study, organ weights were recorded only
for the eight major organs of the dogs.
Results
The appended tables include the individual radioactive counts together with organ
weights and total activity on an organ basis of the liver, spleen, kidneys, gonads, thyroid, heart, lungs and brain.
The date are summarized for the 3-, 6-, and 12
month intervals in Tables 1, 2 and 3, respectively, and in each instance the specific C14 activity is shown for
the individual organs. The data are indicative of an ubiquitous distribution
among all the organs and tissues without evidence of tissue concentration. Although
the total counts in several of the larger organs may be somewhat elevated (e.g., in the liver and brain at 3 months, liver,
spleen, heart, lungs, and brain at 6 months, and the liver and kidneys at 12 months), they are not indicative of selective
concentration based on specific activity counts but rather a function of organ weight.
The broad distribution can be followed by an examination of the patterns in the organs of excretion, i.e., the kidneys
and bladder, in which significant activity may be noted. This was most marked
at 6 months, the gladder and kidney counts approaching the nanocurie level.
It is of interest that despite parenteral route
of administration, C14 was present in the gastrointestinal tract, in the aorta and apparently in the lymphatic
pathways as evidenced by the lymph nodes, and salivary glands, thus suggesting that transport and distribution in these animals
was via the vascular system, the lymphatics, and recirculation via the biliary tract.
Summary and Conclusions
Counts
for radioactivity of tissue samples taken from dogs 3, 6, and 12 months, respectively, after a single subcutaneous dose of
C14 – labeled DC 360 Fluid, 350 cs provides indication of generalized distribution throughout all the organs
and tissues. Transport via the vascular network (i.e., the lymphatics) and biliary
recirculation is suggested by the presence of C14 in these organs
and suggests that the material was being excreted via normal pathways in the urinary and gastrointestinal tracts. The generalized distribution is without pattern of tissue concentration and is further indication of its
broad, non-specific distribution at low levels of concentration.
The results of radioactive studies following
parenteral administration of a single 1 cc dose of DC 360 Fluid suggests that
distribution occurs throughout the entire body with no apparent concentration in any specific organ. Examination of organs at 3, 6, and 12 month intervals warrants the conclusion that the material is mobilized
from the injection site as evidenced by the decreased volume of the injection site by palpation and is excreted via normal
urinary and gastrointestinal pathways. The latter observation is indicative of
biliary recirculation since the material was not administered orally.
The ubiquitous distribution throughout the organism indicates that the material or
its metabolic products are mobilized from the injection site and are handled via normal excretory patterns. Because this was not designed as a balance study initially, conclusions as to rate of mobilization and
clearance are unwarranted. These findings are confirmatory of the passive role
played by the parenterally administered materials as tentatively concluded in the report of the 2 year study.
Although there are quantitive differences in
distribution between the findings at 6 months and at the 3 and 12 months, there is no explanation for these. In view of the limited numbers of animals (1 per time interval), and their qualitative similarity, indicative
of lack of specific organ concentration, the variation between the 3 and 6 month
counts is believed to be essentially the same at each of the periods and is illustrative of a continuous slow process.
