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MICROCOPY RESOLUTION TEST CHART
NATIONAL BUREAU OF STANDARDS - 1963
MICROCOPAL BUREAU OF
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ORNE P. 3541
8
JAN 19
MASTER
THE VARIATION WITH AGE OF ELEMENTAL CONCENTRATIONS IN HUMAN TISSUE
*Isabel H. Tipton **
· Judy 0. Johns***
and
Monica Boyd ****
LEGAL NOTICE
This report mo propared us an account of Government sponsored work. Noither the United
States, nor the Commission, nor any person acting on behalf of the Commissions
A. Makes Lay warranty or roprosentation, expressed or implied, with respoct to the acou-
racy, complotoneDI, or unofulness of the information contained in this roport, or that the use
of any information, apparatu, mathod, or procesu disclosed in this roport may not Infringe
privately owod richta; or
B. Assumos any liabiliuos with respect to the wo of, or for damages rosuldag from the
uos of any information, appuratw, method, or procos, disclosed in Wale report.
As used in the above, "pornon acting on behalf of the Commission" includes any om- :
picyo or contractor of the Comiatsslon, or employou of such contractor, to the extent that
such employo. or contractor of the commalusion, or employee of much contractor proparas,
diorominates, or provides accou to, any information pursuant to his employment or contract
with the Commission, or hin employment with such contractor.
**Department of Physics, The University of Tennessee, Knoxville, Tennessee and
Health Physics Division, Oak Ridge National Laboratory. (operated by Union Carbide
Corporation for the United States: Atomic Energy Comm 1881on).
***ath Panel, Oak Ridge National Laboratory, .Oak Ridge, Tennessee.
****Health Phys106' Division, .Oak Ridge National Laboratory, Oak Ridge, Tennessee.
*This work was supported by subcontraot 2351 under: W7405 eng 26 between Union Carbide
Nuclear Corporation and The University of' Tennossoo..
Pre-publication Copy
July 1966

DISTRIBUTION OF THIS DOAMNE IS UNLIMITED
Tipton
July 1966
Abstract
To determine MPC values for var:.ous segments of the population it is desirable to
take into account the possible variation with age of the concentration or an element in
.a tissue. Studies carried out on data for 173 subjects from the United States indicate
a significant (p <0.001) correlation with age of: aluminum in lung: calcium in aorta,
COI
11
rib, kidney, and testis; copper in cartilage and liver; magnesium in aorta, rib and
vertebra; manganese in rib; phosphorus in aorta and testis; tin. in lung. Since the values
ror the concentrations of these elements are found to be distributed log-normally (except
those for calcium .in rib which were normally distributed), equations for regression lines
of the log or concentration on age (concentrations on age for calcium in rib) have been
.
determined and lines drawn with a 95% conridence interval.
The concentracions of calcium,
magnesium, and manganese in bone,, and .oopper and manganeso in. liver are found to decrease;
and the concentrations of caloium, magnesium, and. phosphorus in. aorta, .0110ium in kidney,
and aluminum and tin in lung to increase with age...
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TRE
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Tipton
July 1966
To determine whether or not the concentrations of elements in human tissue vary with
age, studies of the correlation between uge and elemental concentration have been carried
out using the data on 150 adult subjects (1,2,3,4) plus 23 ohildren 15) from the United
States. Rank correlation coefficients have been computed for each element in each tissue
and the difference from zero tested as described previously 67.
•
To take age dependence into consideration when attempting to determine MPC values
for various segments of the population : 1t is desirable to estimate the quantitative
relation between age and concentration. It is userul to calculate intercept and slope or
a regression line relating age and concentration and to make a plot of the line for quick
visval reference.
ence
Before a meaningful regression line can be plotted,. it is necessary to establish the
fact that the quantities can be expected to have a linear relation. If, for every fixed
value of the independent variable (in this case age), the values for the dependent variable
(in this case concentratior) show a normal statistical distribution about a mean value, then
the regression line may be determined by the method of least squares and confidence intervals
determined by ordinary statistical procedures. However, in this study most of the values
for concentration of a trace element in human tissue prove not to be distributed normally.
KA
Therefore before plotting regression lines for an element, the data have been tested for
normality and for log normality Mon.
Since caloium.. in bone showed a normal distribution,
a regressivio line of concentration on age has been plotted for valoium;. for all other
elements the 10g of the concentration has been used instead of concentration in oaloulating
and plotting the regression line.
Table 1 includes those correlation coefficients of magnitude 0.32 and above and
significantly (p <0.001) dirferent from zero for elements which were observed in concentrations
above the limit of detection in 90% of the samples of a t18sue. In this table the column
**
*
"Number of Individuals" shows the number of samples for which both a value for the concen.
tration of the element in wet tissue and the age of the individual were known. The last
.
.C
L
Tipton
July 1966
column in this table contains the equation of the regression line of concentration or los
concentration on age.
In the figures age 16 plotted as absoissa, and concentration or log of concentration
o an element in wet tissue is plotted as ordinata. The equation of the line, the value
of the correlation coefficient and the probability what the value could have ocourred by
small circles. The 95% confidence interval 18 indicated by triangular points on each side
or the regression line. This interval 18 not bounded by straight lines, because there were
different variabilities and different numbers of observations for different age groups.
The increase in aorta of the concentrations of caloium (Fig. la), magnesium (F18. 10),
and phosphorus (718. 10) reflects the commonly observed changes in blood vessels with age.
The analyses which provided the values for the elements in bone (rib) were made on ·
ashed samples or wet rib from which the marrow had not been removed. The ash fraction of
' wet weight of these samples deoreased significantly, whereas the dry fruction of wat did not
change significantly with age. The decrease in the concentration of calcium (P18. 2a),
magnesium (Fig. 26).. and manganese (Fig. 20) in the wet sample (concentration in wet . concen-
..tration in ash x ash fraction of wet) 18 thus a refleotion not only of the actual decrease
of the inorganic matrix of the bone with age but also of an increase of the low-ashing rat
component of marrow.
Calcirication acoompanying pathologic 1081ons in the kidney apparently has no specifio
correlation with age 19). Since the kidneys which were analyzed for the present study were :
taken from grossly normal individuals, the inorease in the concentration of calcium in
kidney (F18. 3) probably reflects an increase with age in the deposition of plagues in the
blood vessels within the kidney rather than an increase in the concentration or caloium in
the tissue of the kidney itself. The increase of oalolum in tostis can probably be!
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:
attributed to the same cause. (818. 6)
Tipton
July 1966
The decrease of copper (F18. 4a), manganese (P18. 45), and molybdenum (Fig. 4c) in
ease
pes
liver is slight but significant.
The individual variation of aluminum (Fig. 5a) and tin (Fig. 50) in lung 16 wide but
the general increase from birth to old age 18 more than tenrold.
The compounds of these
elements which enter the lung by inhalation as dust are for the most part insoluble and so
are not absorbed.
.
*
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Tipton .
July 1966
References
1.
I. H. Tipton', M. J. Cook, R. L. Steiner, H. M. Perry, Jr., and H. A. Schroeder,
Health Physics 9, 89 (1963).
2. I. H. Tipton and M. J. Cook, Health Phys108 9. 103 (1963).
3. S. R. Koirtyohann and C. Peldman, Health Physics, Annual Report, ORNL-3492, D. 178 (1963).
4. I. . Tipton and J. J. Shafer, Health Phy8108 Annual Report, ORNL-3697, p. 179 (1964).
5.
Unpublished data.
.6. I. H. Tipton and J. J. Sharer, Archives of Environmental Health 8, 58 (1964).
7. "gests of Non-Normality
Memorandum from D. A. Gardiner to W. S. Snyder, June 20, 1963.
8. Biometrika Tables for statisticians, ed. by 8. S. Pearson and H. O. Hartley, Cambridge
Press (1954).
9.
J. 0. Salik and B. S. Abeshouse, Radium Therapy, and Nuclear Medicine, Am. J. Roentgenology:
88,.125 (1962).
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Tipton
July 1966
· TABLE I
Correlation or Concentration of Trace Element in Wet Tissue with Age
(Correlation coefficients different from zero p <0.001).
(Concentrations in micrograms per gram or wet t188ue)
Number of
Individuals
Correlation
Doerficient.
Element
Tissue
Equation of Regression Line
· Aluminum
Lung
153
0.34
log conc Al - 0.654 + 0.014 (Age)
Calcium
Aorta
Bone - Rib
Kidney
Testis
och har
0.53
-0.47
0.39
0.37
log conc Ca - 2.337 + 0.012 (Age)
cono Ca. 113,500 - 608 (Age )
10g cong Ca - 1.717 * 0.005 (Age)
log oonc Ca - 1.784 + 0.003 lage)
Copper
Liver
.
-0.35
log cono cu - 1.033 - 0.004 (Age)
Magnesium
Aorta
Bone • Rib
mä
0.47
-0.64
:
log oonc Mg - 1.962 * 0.008 (Age)
10g çono Mg = 3.173 - 0.004 (Age)
Manganese
Bone - R1b.
· Liver
oo b
-0.41
. -0,33
log cong Mn - -0.142 - 0.003 (Age)
10g cono Mn = 0.226 - 0.002 (Age)
Molybdenum
Liver
-0.33
108 cono Mo - 0.039 - 0.002 (Age )
Phosphorus
Aorta
0.46
log oond p = 2.700 + 0.007 (Age )
Tin
Lung
0.42
log cono sn - -0.958 + 0.013 (Age).
ves
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ST
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ORNL DWG 66-45:

VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
CALCIUM IN AORTA
102a842ad99940404040404
144984444444444444
4444444444484
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
ooooooooooo
LOG CONCENTRATION Co=2,337 +0,012 (AGE)
r-0.53 p=0.000001
0
10
20
30
60
70
80
90
100
40 50
AGE -YEARS
.
.
ORNL DWG 66-4557
VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
MAGNESIUM IN AORTA
· 10%
mo
2498448808900 manns odda44444444444
aaaaaaAAAAAAAAAAAAAA
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
40 42 44444440 2888084444404448
90 90 89 8804°4444444444
LOG CONCENTRATION Mg* 1.962 +0.008(AGE)
p.0.47 p. 0.000002
10
20
30
40
50
60
70
80
90
100

AGE-YEARS
ORNL DWG 66-4563

VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
PHOSPHORUS IN AORTA
4°444048 20444444444444444
A48444444444
ه ه ه ه ه ه ه ه ه
ه ه
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CONCENTRATION • MICROGRAMS PER GRAM WET TISSUE
1.0.46
pe 0.000001
LLLLLLLLL
10 20 30 40 50 60 70 80 90
AGE-YEARS
100
ORNL-DWG. 66-4567
VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
CALCIUM IN BONE (RIB)
187,125.00
170,6!6.50
CONCENTRATION Co=113,500-608 (AGE)
r= -0.47 p=0,000003
154,108.00
137,599.50
121,091.00f ºg
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
104,582.50
bocoon
AMD Dad
88,074.00%
ه ه ه ه ه ه ه ه ه ه ه ه
71,565.50
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55,057.00
DDDDD.CONDDDDDDDDDDDDDDDD
38,548.50
o
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LLLLLLL
10 20 30 40 50 60 70
AGE-YEARS
80
90
-
100
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ORNL-DWG. 66-4564
VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
MAGNESIUM IN BONE (RIB)
-
109
AAAAA
o Yo
PER GRAM WET TISSUE
ه ه ه ه ه ه ه ه ه ه ه
AAAAAAAAAA SAA
QORBA
CONCENTRATION - MICROGR
LOG CONCENTRATION Mg= 3.173 -0.004(AGE)
r=-0.64 p=0.00001
O'
LILILLLLL
0 10 20 30 40 50 60 70 80 90
AGE-YEARS
100
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Fig. 2c
ORNL-DWG. 66-4566

VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
MANGANESE IN BONE (RIB)
PAAAAAL
ه ه ه ه ه ه ه ه ه ه ه ه ه ه ه ه ه ه هه
0% DABASARABA AAGADDDDDS
همه خدمه ه
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
DADA
LOG CONCENTRATION Mn=-0.141 -0.003 (AGE)
r=-0.41 p=0.000005
0
10
20
30
70
70
80
90
100
40 50 60
AGE-YEARS
ORNL DWG 66-4559
VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
CALCIUM IN KIDNEY
Ao9404444 65A AS 184 DADA 402 400000000000's 14444
PRAA80404 4434 AA 42 203 204 800MAAAAAAAAA
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
LOG CONCENTRATION CO= 1.717 +0.005(AGE)
p=0.39 po 0.000003
10
20
30
40
50
60
70
80
90
100
AGE-YEARS
.
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-
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ORNL DWG 66-4561
VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
COPPER IN LIVER
10
o
---DADADAA GAA 18S & AARDOSADA ASANDRA
Frönssson BA BA BA BA B 4A AASA DE
88
oC
هه هه
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
LOG CONCENTRATION Cu = 1.033 -0.004 (AGE)
p=-0.35 p= 0.000002
0
LIIIII
10 20 30 40 50 60 70
AGE-YEARS
80
90
100

ORNL DWG 66-4568

VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
MANGANESE IN LIVER
AAAAAAAAAA°
AAAAAAAAA Sciasco S AA
Addo AAAAAAAA 84A AA 41AA, A
LA
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CONCENTRATION- MICROGRAMS PER GRAM WET TISSUE
LOG CONCENTRATION Mn=0.226 -0.002(AGE)
på-0.33 p=0.000003
02
LLLLLLL
10 20 30 40 50 60 70 80 90
100
AGE -YEARS
ORNL. DWG 66 - 4565

VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
MOLYBDENUM IN LIVER
هههه ههمهمه حمهه هه هه ه ه ه ه ه ه ه ه م
ه ه ه ه ه ه ه ه ه همه
ܬܬܬܬܬ ܬ8ܬ8ܬܬܬܬܬܬܬܬܬܬ ܘܘܬܬܬ
ه ه ه ه د
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
دة
LOG CONCENTRATION Mo=0.039 -0.002(AGE)
0 -0.33 p=0.000003
___
0
10
__
20
______ ______ ________ ____
30 40 50
__ _____
60
70
60
90
100
AGE-YEARS
ORNL DWG 66-4556

VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
ALUMINUM IN LUNG
&044444444444
CONCENTRATION MICROGRAMS PER GRAM WET TISSUE
09
$98494990% 4 8.0
$444444444444490%
Bg64884200044
LOG CONCENTRATION AI=0.654 +0.014(AGE)
r=0.34 p=0.000005
0
10
20
30
70
80
90
100
40 50 60
AGE -YEARS
ORNL-DWG. 66-4558
VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
CALCIUM IN TESTIS
sansada pemenanannadasanda
80 9
88
AGA AO 40044 ADAAAAA
ebo od 220
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
1
11
LOG CONCENTRATION Ca= 1.784 +0.003(AGE)
p=0.37 p=0.00001
0
IIIIIIII
10 20 30 40 50 60 70 80 90
100

AGE -YEARS
ES
Sabay
UL
SA
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55
ORNL-DWG. 66-4562R
VARIATION OF CONCENTRATION IN WET TISSUE WITH AGE
TIN IN LUNG

LOG CONCENTRATION Sns-0.958 + 0.013(AGE)
p=0.42 p=0.000005
CONCENTRATION - MICROGRAMS PER GRAM WET TISSUE
OOO
0908 4 8 448 484 444 44 8 44444444
644444444444
/
O
0 vois094886400 of 848448 ada
10
20
30
40 50 60
AGE-YEARS
70
80
90
100

TEL
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