posure to Sr-90, Sr-89, and Sr-85. Health
Phys., 10:171, 1964.
13. Rivera, J.: Stable strontium concentration in three bones of the human skeleton. HASL
Report 140, p. 303, U. S. Atomic Energy
Commission, Health and Safety Laboratory,
New York, October 1, 1963.
14. International Commission on Radiological Pro-tection, ICRP Report 6, New York:
Per-gamon Press, 1964.
15. Beninson, D., Ramos, E., and Touzet, R.:
Strontium in children. HASL Report 165,
U. S. Atomic Energy Commission, Health
and Safety Laboratory, New York, January
1, 1966.
16. Marcus, C. S., and Wasserman, R. H.:
Com-pariscm of intestinal discrimination between
calcium-47, strontium-85, and barium-133.
Amer. J. Physiol., 209:5, 1965.
17. Della Rosa, R. J., Wolf, H., and Calvert, S.:
Discrimination in beagle puppies: The
effect of extended ‘nursing’ on the
deposi-tion and retention of strontium in bone and
teeth. UCD 472-112, AEC Research and
Development Report, Biology and
Medi-in bone tissue of the population of the
So-viet Union in 1959-1963. UDC 612.014.482:
546.42, State Committee on the Use of
Atomic Energy USSR, Atomizdat, Moscow,
1964.
19. Federal Radiation Council Staff Report No. 7,
May, 1965. Available at the Superintendent
of Documents, U. S. Government Printing
Office, Washington, D.C.
20. Hallden, N. A., Fisenne, I. M., and Harley,
J. H., Radium-226 in human diet and bone.
Science, 140:1327, 1963.
21. Hailden, N. A., and Harley, J. H.:
Radium-226 in diet and human bone from San Juan,
Puerto Rico. Nature, 4955:240, 1964.
22. Harley, N. H., Fisenne, I. M., and Harley,
J. H.: Radium-226 in infant diet and bone.
Presented at the Eleventh Meeting on
Bio-assay and Analytical Chemistry,
Albuquer-que, New Mexico, October 8-9, 1965.
23. Mitchell, H. H., Hamilton, T. S., Steggerda,
F. R., and Bean, H. \V.: The chemical
com-position of the adult human body and its
bearing on the biochemistry of growth.
J. Biol. Chem., 158:625, 1945.
DISCUSSION
DR. KORNBERC: When Doctor Rivera said
that the principal objective of these
mea-surements was to verify a model of
strontium9#{176} metabolism and not primarily to document bone strontium9#{176} levels, he im-plied that there is no pediatric significance of peacetime radioactive fallout, at least as far as strontium9#{176} is concerned, and I am
inclined to agree. But, before examining
whether such is the case, it may be
inter-esting to compare the results the Health
and Safety Laboratory obtained from
hu-mans with some we obtained from the
mini-ature pig. We chose this animal because of
the many physiological characteristics it
shares with humans.
Seven years ago we began a long-term
experiment designed to find what quantity of strontium9#{176} ingested daily would not
pro-duce demonstrable damage.
One of the early findings by McClellan
was that the “observed ratio” used in the
model Dr. Rivera tested varied with age of
the animals. The ability of the bone to discriminate against dietary strontium9#{176}
changed over a sixfold range-from a
bone-diet K of 1.2 at 15 days old to 0.2 at 250
days old. It appears that a correction of
nearly this magnitude was applied to the
model Dr. Rivera tested.
The changing nature of discrimination is
exemplified in strontium to calcium ratios
in sow’s milk as compared to their diet.
Figure 23 shows how the factor changed
significantly with time post-partum,
per-haps reflecting the effects of increased
strontium and calcium turnover from diet
to milk.
Despite such variations with age and
diet, the accuracy with which strontium9#{176} to
calcium levels in food can be used to
pre-dict strontium9#{176} to calcium levels in human
bone is excellent, and Dr. Rivera and the
Health and Safety Laboratory are to be
complimented.
-J
0
0) .0 U)O
5
I-w 0
0 as
(,c-) 0
24
0.30
- (Mo ANIMALS 4, 5,6,7, 8, AND 9
(B). ANIMALS 1,2, AND 3
0.20
(B)y0.079+O.0024X
0.10
o #{176} (A)y=O.085+O.0008X
0 10 20 30
DAYS POST-PARTUM
40
SUPPLEMENT 237
FIG. 23. Changes in discrimination of strontium relative to calcium with time post-partum in sows’
milk compared to sows’ diet.
we found the average concentration of
strontium#{176}#{176}in vertebrae of our
experimen-tal pigs higher than the average for the
skeleton by a factor of about two. Figure 24 illustrates the variation in strontium9#{176}
deposition and the corresponding dose rate
in a vertebrae taken from one of these ani-mals. At certain stages of growth of teeth,
the strontium was even higher in the
man-dible.
But, perhaps the finding of most
rele-vance is that after feeding pigs 5 Ci
strontium9#{176} per day for 6 years (starting
pre-conception in sows), we have seen no
biological effect. This is something more
than 100,000 times the peak mean daily
in-take of strontium#{176}#{176}Dr. Rivera reported for
the New York diet in 1963. Whether a
life-time of exposure to 5 iCi per day will also
be without effect remains to be seen. It
probably won’t be, since we have noted
leu-kemia induced in a few animals fed 25 Ci
per day for 4 years. But what, in fact, pro-duces the biological effect is the radiation dose from strontium#{176}#{176},which is about 2,000
rads or more. To accumulate such a dose
from the peak dietary levels noted by Dr.
Rivera would take from one-half to one
million years. I doubt there are many other toxic substances in the biosphere that have such a margin of safety.
DR. RIVERA: The variations are a
prob-lem. I meant to mention that the way this
diet is constructed is rather strange and I
am frequently asked for whom the diet is
intended. I hesitate to say that itis a diet of
an average adult person. We took diet
sta-tistics compiled by the Department of
Agri-culture on the consumption of something
like 219 separate items. We grouped these
into categories (19) which could be
ana-lyzed and, from the statistics obtained,
computed the consumption per week per
family. We divided this by the number of
persons per family, which happened to be
3.3, and took this as per capita intake. We assume our data refers to adult intakes and
indeed this seems to be so because we can
fit the model very accurately for adults. The variability is great and one of the chief
problems we have is trying to learn how
well our model fits in ages where we don’t
have lots of bone samples, that is, for ages
140
100
60
20
0
FIG. 24. Autoradiograph and radiation dose rate projection of lumbar vertebrae
of animal fed 3.1 tCi Sr per day for 3 months starting at 9 months of age.
> CD
vu
. CD
there iS no problem. We have many
sam-ples and we can verify our model very vel1;
but, for younger groups we have few
sam-ples and it is ilard to tell whether we are agreeing with the model or not. Certainly, we are not off by more than a factor of two. One of the things that is needed, and I
am trying to do, is to find some way to
use other people’s data, such as that from
Poland, the United Kingdom and Japan.
They all have bone data and diet data, but
not enough, and our problem is to normal-ize the data so that we can put it together
and see whether it fits a single model or
not. This is hard to do, but hopefully, we
should be able to do it. We should then be
able to see if there are variations that can be statistically observed in turnover rates
and discrimination factors as a function of age.
DR. EISENBUD: I am not sure that this is
exactly relevant to the current discussion,
but it is a question that bothers me and I
don’t see another place to bring it up. As I
look at the mathematics of the dose
re-sponse curve and tile fact that a linear non-threshold dose response curve is an inher-ent assumption in the calculations
estimat-ing population damage, it seems to me
sim-ply to be an algebraic basis and derives
from the mathematics of the curves. What
is of interest is the mean dose to the popu-lation. In calculating tile damage to a
pop-ulation, deviations from the mean have to
cancel out because the dose response curve
SUPPLEMENT 239 resolution of significance of the deviations
from the mean in estimates of dose to the
bone, to the thyroid, etc.
Dn. CHARLES: I shall follow through with
what Dr. Eisenbud has to say-this
devia-tion from the mean is a little disturbing be-cause it does not take into consideration from the practical standpoint of clinical
practicing physicians the wide gamut of
human sensitivities. Dr. Kornberg, on your
bone sample data, could you project just
what the mean dose is to the bone? I think
that in all bone the concentration of the
strontium9#{176} is at the highly active growth centers. In these highly active growth cen-ters the cells are more active and more sen-sitive. How do you predict with any
mathe-matical formula how these cells will
re-spond to the concentration of the radioac-tivity in this area
One other question to Dr. Rivera. I don’t
think he meant to suggest that because a
youngster consumes a lot of milk with a
fa-vorable strontium to calcium ratio, the
extra calcium will protect that youngster.
DR. PIcERmNG: Our studies of the
de-veloping skeleton in the monkey fetus have
involved, among other things, the investiga-tion of calcium5 and strontium9#{176} uptake,
distribution, and turnover. They have
re-vealed many points pertinent to this discus-sion. By way of introduction, the young
de-veloping monkey fetus (conception age 50
days) has only 2 mg of calcium in its
skele-ton. Its subsequent phenomenal rate of
growth is reflected by the fact that the fetal
skeleton at term (conception age 167 ± 7
days) has nearly 2,000 times that amount of
calcium. I should like to present a few of
the observed features of calcium
metabo-lism in this rapidly developing skeleton. The ratio of calcium to strontium#{176}#{176}uptake
by the skeleton remained constant during
fetal life, indicating that placental transport
mechanisms did not vary with advancing
gestation. However, the nature of bone
crystal did change remarkably. As fetal life
advanced bone crystal progressively
ma-tured and the crystal maturation was
reflected strikingly by a changing calcium to phosphorus ratio. In earliest fetal life the ratio was less than 1.0 and as term was ap-proached it approximated 1.5. The calcium tite is 1.67. The crystal population in various
to phosphorus ratio of mature hydroxy
apa-areas of the skeleton thus increasingly
ma-tured with advancing gestation. Various
areas were of a different degree of maturity at any given time.
We have found that the calcium and
strontium#{176}#{176}uptake in any area of bone at
any time bore a direct relationship to the
calcium to phosphorus ratio of the crystal population and thus to crystal maturity. In
fact, essentially all uptake of those
ele-ments at any given time by any single area
was due to this process of continuing
matu-ration. Such uptake did not reflect new
bone formation as characterized by, and
re-lated to, the laying down of new organic
elements and their mineralization. The
proximity and metabolic activity of the
many and varied cellular constituents of
bone to the crystal elements changed
dra-matically as fetal life advanced. On the
basis of these and related studies in the
skeletons of many primate fetuses of exact-ly known gestation, I would like to caution physical scientists against quantitatively predicting likely effects of specific amounts of isotopes (calcium and strontium#{176}#{176},etc.) in various areas of the fetal skeleton at any given age or as age advances.
DR. SPENCER: For the interpretation of
strontium9#{176} to calcium ratios of bone, it
would be important to know the dietary
calcium intake of the infants and children. In our studies in adults we have found that the intestinal calcium to strontium
discrimi-nation is greatly decreased when the
di-etary calcium intake is high while the renal
strontium to calcium discrimination
re-mains unchanged. In view of these changes
in calcium to strontium absorption, the
