Trace metals in man: Strontium and barium

J Chron Dis 1972, Vol. 25, pp. 491-517. Pergamon Press. Printed in Great Britain

TRACE METALS IN MAN: STRONTIUM AND BARIUM* HENRYA. ScHRoEDER,t ISABELH. TIPTONand ALEXISP. NA~ON Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire, the Brattleboro Memorial Hospital, Brattleboro, Vermont, and the Department of Physics, The University of Tennessee, Knoxville, Tennessee, U.S.A. (Received 17 May 1971; in final form 11 May 1972)

INTRODUCTION

IN 1808, Sir Humphrey Davy added two$ elements to an expanding list. One he named strontium, after Strontian, a town in Scotland, and the other barium, after the Greek word barys (heavy) [l]. Both occur in relatively high concentrations on the earth’s crust, at 400 and 450 ppm, respectively, and both are constituents of sea water, at 8.1 ppm for strontium and 0.03 ppm for barium [2]. Therefore, living things have grown and evolved in the presence of these two alkaline earths, and have incorporated them in their tissues. Aside from natural occurrences, man has exposed himself to increasing concentrations of barium. Barite (barium sulfate) is used as a lubricating agent in drilling oil wells, 564,000 tons being consumed in the United States in 1968. Barium compounds are employed in making glass, ceramics, television picture tubes, as a pigment in paint (lithopone), in brick and tile refractories, for paper coating, steel hardening, vinyl stabilizers, lubricating oil additives, permanent magnets, railroad flares, fireworks and sugar refining. About 208,000 tons of barium compounds were sold in the United States in 1968. Some 2,172,OOOtons of barium were consumed in the world in that year [3,4]. Uses of strontium are fewer, there being only 12,500 tons produced in the free world in 1968 [3]. Major uses were as getters to remove traces of gas from vacuum tubes and as colors for tracer bullets, signal rockets, flares and fireworks. Strontium compounds also have a place in ceramics, medicines, greases, plastics, purifying zinc, permanent magnets and iron castings [3]. Although the actual amounts of exposures of the population were small, the greatest health hazard to the population at large came from atmospheric testing of atomic bombs, O”Srbeing a fission product. *Supported by grants in aid from the National Heart Institute, U.S. Public Health Service (HE 05076), General Foods Corporation, CIBA Pharmaceutical Products Inc., and Subcontract 2351 under W7405 of the Union Carbide Nuclear Corporation. tRequests for reprints should be sent to 9 Belmont Avenue, Brattleboro, *Davy also discovered calcium in that year [l]. 491

Vt. 05301, U.S.A.

492

HENRYA. SCHROEDER, ISABELH. TIPTONand ALEXISP. NA~~N

In order to learn more about these two metals, we have examined human contents and concentrations of stable strontium and barium in subjects from around the world, have analyzed human exposures to stable strontium and have attempted to calculate amounts of both metals in food, water and air. This report concerns the 20th and 21st elements so studied. It is not within its province to discuss radioactive strontium. METHODS

Strontium in foods and water was measured by atomic absorption spectrophotometry (Perkin-Elmer 303), using a Boling burner and an air-acetylene flame. Water and beverages were analyzed directly; other samples were ashed in silica crucibles at 400°C in muffle furnaces after drying to constant weight at 110°C dissolved in nitric acid and diluted to constant volume. Lanthanum was added to all solutions of samples and standards to a concentration of 1 per cent, to minimize chemical interferences. Analyses were made by the method of standard additions. The limit of detection was 0.02 pg/ml solution, the sensitivity was 0.1 ug for 1 per cent absorption, and the coefficient of variation was f 10-20 per cent. Eight consecutive analyses of a sample containing 0.25 pg/ml strontium gave a coefficient of variation of 10.24 per cent. Barium in sample diets was measured on the same spectrophotometer in the flame-emission mode, using nitrous oxide-acetylene flame. All standards and samples contained 2000 pg/g potassium. In general, a single sample of each substance was analyzed, in order to provide a broad survey of environmental strontium, without attempting to find ranges of values in a given species. When analytical results appeared inconsistent, the analysis was repeated on another sample of the same substance. Samples were obtained from local chain stores or gardens; water usually from taps in houses, and diets from a hospital menu. Strontium and barium in human tissues and in collected diets were measured by emission spectrography [5]. The individual data on 31 tissues of 168 American subjects came from the analyses of Tipton and Cook [6], and on tissues of Asians, African and Swiss subjects from Tipton et al [7]. The limits of detection were 1.0 ppm for strontium and 0.3 ppm for barium, in terms of ash, or about 0.01 and 0.003 ppm respectively, wet weight [8], depending on ash content of the sample. Coefficients of variation of the method were 8 per cent in both cases. For Reference Man, data were based on 150 accidental deaths of United States subjects [9]. For changes with age, data on nine tissues from each of about 400 domestic and overseas subjects were used. A majority of Americans died accidentally and a majority of the others from various diseases. RESULTS

Strontium and barium in human tissue The contents of strontium and barium in the major organs and tissues of Reference Man (a 70 kg American adult) are given in Table 1. The whole body contained 320 and 22 mg respectively, of which 99 per cent of the strontium and 93 per cent of the barium was in bone and connective tissues. Otherwise, the largest, but still small amounts of strontium were in muscle, fat and skin, and the largest amounts of barium were in fat, skin and lungs. There was more barium than strontium in fat, blood, connective tissue and lungs.

493

Trace Metals in Man: Strontium and Barium TABLE 1.

CONTENTOF STRONTIUM AND BARIUMIN REFERENCE MAN, WET WEIGHT

Organ Organ

Muscle Fat Bone Blood Skin Connective tissue Liver Brain G.I. tract Lungs Heart Kidneys Spleen Pancreas Other Total Soft tissues

weight g

Median mg

28,000 12,500 10,000 5,500 4,900 2,000 1,800 1,400 1,200 1,000 330 310 180

0.42 0.32 320.0 0.18 0.34 1.0 0.032 0.034 0.19 0.057 0.008 0.018 0.005 0.004 0.80* 323.0 3.3

:: 70,000 60,000

Barium

Strontium 80% range mg

Median mg

80% range mg

0.092-l .5 0.18-0.90 170-560

0.14 0.45 20.0
< 0.06-0.90 0.16-1.7 0.96-1.8 < 0.004-0.05 < 0.004-0.041 0.025-0.17 < 0.0007-0.011 < 0.001-0.014 < 0.0005-0.008 < 0.0002-0.005 -

0.14-0.53 0.016-0.094 0.028-0.18 0.052-0.48 0.028-0.11 0.004-0.023 0.009-0.04 0.003-0.014 0.002-0.010 -

Data from Tipton [9]. Values rounded to two significant figures. Ranges for some tissues not calculated. *Estimated

The major components of soft tissue ash are potassium (8-25 per cent), phosphorus (5-20 per cent), magnesium (0.8-1.8 per cent), calcium (0.4-7.0 per cent) and iron (0.3-2.5 per cent). The remainder is probably oxygen, carbon, hydrogen, nitrogen, sulfur, sodium, chlorine and silicon. As the Group IIA elements may go together in tissues, all being bone-seekers and presumably correlated with calcium, we can examine the concentrations of strontium and barium in 3 1 human tissues in this light (Table 2). Values of strontium above 20 ppm ash were found in aorta, which has a high calcium content (5.5 per cent), in larynx and trachea, which are also high in calcium, and in the lower gastrointestinal tract, probably from ingestion. Lowest values occurred in adrenal, brain, heart, liver, pancreas and spleen; these organs had less than 0.8 per cent calcium in ash. In bone and trachea the ratio of strontium x 1000 to calcium was 0.5; it varied from 0.4 to 0.61 in 1I other tissues. Ratios of 1.1 to 1.8 were found in the ovary and gastrointestinal tract, with 3.3 in muscle. It was very low in fat. The ratio in the whole body was 0.32. Thus, the relationship of calcium and strontium was not invariable. There were higher concentrations of barium than strontium in adrenal, muscle, fat and lung. Levels above 10 ppm were found in muscle, lung, the lower gastrointestinal tract, skin and fat. Lowest levels were in brain, heart, kidney, liver, pancreas, spleen and testes. Thus, barium was not entirely correlated with strontium. There were marked geographical differences in human tissue concentrations of barium from five areas of the world, in males aged 20-59 yr (Table 3). There was significantly more barium in aorta, brain, heart, kidney, liver and spleen of all foreign subjects than in these tissues of Americans, more in all tissues of Near Easterners, and more in all but lung of Orientals. Swiss had more than Americans in five organs. The number of differences significant at the 0.001 level of confidence was 28 of a

494

HENRY A. SCHROEDER,ISABELH. TIPTON and AL~xrs P. NA~~N TABLE 2.

BARIUMAND STRONTIUM IN HUMAN Barium No. found per no. samples

Adrenal Aorta Brain Diaphragm Muscle

Uterus Bladder Trachea Lung Esophagus Stomach Duodenum Jejunum Ileum Cecum Sigmoid Colon RectWll Omentum Heart Kidney Liver Pancreas Spleen Thyroid Prostate Testis Ovary Skin Fat Bone, rib Bone, vertebra

13/13 103/105 661129 76191 139/140 27132 106/110 50150

60;60

139/140 66166 126/130 65167 99/101 84184 31/31 108/108 41/42 74175 93/l& 121/142 68/146 108/139 89/143 20/21 44140 54172 14/16 2i/22 28128 91191 57157

TISS~F..S,PPM

ASH AND

Strontium

Median ppm

MeanfSEM ppm

Median ppm

MeanfSEM

6.0 7.0 0.2 1.8 14 2.0 3.4 5.3 5.0 14 3.0 3.2 3.7 4.0 9.2 18 6.1 7.2 7.0 0.7 1.3 <0.2

34*2-l -

3.5 33 1.4 3.3 8.2 9.5 12 25 18 8.2 8.2 9.9 11

4.5*1.0 41.0*2.9 2.3*0.23 4.5 +0.45 9.8zO.52 11*1.7 14*1.1 32k3.7 23f2.4 9.8IO.52 9.6*0.69 13+0.93 1311.2 15k1.3 32*4.1 52k8.9 33-12.8 28&2.9 12hl.2 3.5 to.24 6.5zO.35 2.1&0.19 4.9kO.41 3.4+0.45 1321.3 1652.3 5.8hO.54 15+3.7 1313.5 3.5+0.32 12Ok5.1 11014.7

-

6.6*0.69 6.2hO.72 8.1f2.7 -

:::

12Tl.O 18rt2.1 14k2.3 -

y2 2 2

17k3.9 26.4*4.0 -

A:: 5.8 2.1

:: 42 23 26 9.5 2.6 5.2 1.6 3.3 2.1 :: 4.3 11 8.6 1.28 110 100

ppm

CALCIUM,% ASH

Ash median % of wet wt. 0.46 1.4 1.5 0.96 1.2 0.98 0.80 3.0 1.6 1.1 0.9 0.8 0.8 0.9 0.76 0.6 0.7 0.7 0.2 1.1 1.1 1.3 1.2 1.4 1.1 1.1 1.1 0.97 0.7 0.18 28.0 28.0

Calcium median %

0.76 5.5 0.52 0.58 0.25 0.92 1.3 7.0 3.6 1.0 1.1 0.90 0.83 0.82 1.4 2.4 1.4 1.7 1.1 0.38 0.85 0.38 0.78 0.50 ;.: 0:86 0.98 2.1 11.2 20.0 20.0

Data from Tipton and Cook [6]. Strontium and calcium were present in every sample.

possible 36. Strontium did not follow the same pattern, significant differences occurring in only ten instances. These differences in barium suggest that exposures are higher, probably from dust, in the Near and Far East and Africa; similar differences were found for aluminium and titanium in these areas [7], both being dust-borne natural ‘pollutants’ of air. Barium was found in every foreign tissue but liver, where it was lacking in 11 of 145 samples, and spleen, where it was not detected in one of 136 samples from subjects of both sexes and all ages. In bone, however, where most of the strontium is stored, more strontium appeared in Far Eastern samples than in Near Eastern or American samples (Table 4). Children from the Far East also appeared to have increased amounts in bone, although numbers were few. Barium was not evaluated in foreign bones. These differences may represent lower intakes of dietary calcium in Orientals than in people from other areas. Female ribs had more strontium than male (P < 0.04).

Trace Metals in Man: Strontium and Barium

495

TABLE 3. COM~ARWN OF CONCENTRATIONS OF FORUM AND BARIUM IN HUMAN TISSUES,FROM L~VEGEOGRAPHICALAREAS,MEDUNVALUES,ASHWEIGHTS(MALEAGED 20-59~~)

Tissue Aorta Brain Heart Kidney Liver Lung Pancreas Spleen Testis

Far East

Switzerland

Sr ug/g

Ba ug/g

Sr uglg

Ba fig/g

Near East Sr Ba ugig pglg

Sr uglg

Ba uglg

Sr ug/g

Ba uglg

34 1.2 2.5 4.9 1.5 2:1 !.!

7 -Co.2 0.7 1.2 -Co.2 13 0:s 15

4.2

1.0

34 2.5 3.6 6.6 3.0* 9.9 9.4 3.9 6.3

14* 2.9* 5.0* 5.0* 3.6* 22 7.2 4.2* 20

35 3.5 3.1 1.8 4.91 12* 7.4 5.1* 5.7

22 1.5 3.0 6.8* 3.1* 8.7 3.9 1.9 4.4

19* 3.6* 3.5* 6.4* 4.0* 15 5.31 2.9* 4.V

10 1.8 5.1; 6.0* 2.0 11 14 3.5 10,

15 2.9* 3.6 4.0* 1x* 38* 5.3 4.4 21*

United States

Africa

19* 11* 7.4* 15*t 6.5* 28* 17* 11* 13*

*Differs from United States values, P< 0.001 tDiffers from African values, PC 0.001 There were 88 subjects from the United States, 34 from Africa, 24 from the Near East, 39 from the Far East and 8 from Switzerland. All were males in this age group. Barium was found in every tissue of foreign subjects. Data from Tipton, Schroeder et al [7]. TABLET.

STRON~UMINHUMANBONE,PPMA~H(RIB)

U.S. adults Near East adults Far East adults U.S. children Near East children Far East children

No. cases 91 19 52 21 4 3

Median

95% confidence interval

Mean jSEM

110 130 19o*t 96 210 3m*

110-120 110-200 180-230 71-210 120-280 250-430

120zt5.1 150&16 210*9.2t 120f10.7 210639 330*53t

*Differs by student’s t from Near East, PC 0.025 tDiffers from U.S., PC 0.001 *Differs from U.S. P-x 0.05, by confidence interval. Note: U.S. females had more strontium in rib than did males (P=O.O4) but did not differ in calcium levels.

Correlations of strontium and barium with other trace elements in human tissues There were only three highly significant coefficients of correlation of the concentrations of strontium with other trace elements in human tissues (Table 5). Barium, on the other hand, was associated with magnesium nine times, chromium 14 times, manganese 15 times, and copper eight times. Except for lung, there were few correlations with abnormal trace elements. The concentrations of most essential trace elements in human tissues are related to each other; magnesium with manganese, copper, zinc and phosphorus [lo], chromium with manganese, copper and zinc [l 11, manganese with copper, magnesium, phosphorus, chromium and iron [12], copper with iron, manganese, zinc, phosphorus, magnesium, chromium [13], and zinc with magnesium, phosphorus, manganese and copper [14]. These relationships apply to 30-76 per cent of 28 tissues. Therefore, it was surprising to find barium, a supposedly abnormal element, as intimately related to essential elements as it was, with strontium being unremarkable in this respect.

496

HENRYA.SCHROEDER,ISABELH.TIPTON~~~ALEXI~P.NASON TABLE%

SIGNIFICANTPAIREDRANKCORRELATIONSOFCONCENTRATIONSOFSTRONTIUM AND BARIUMWITH OTHER ELEMENTS IN HUMAN TISSUES, P-C o.c@l Strontium

Tissue Aorta Brain Heart Kidney Liver Lung Muscle Diaphragm Esophagus Stomach Jejunum IIeum Cecum Sigmoid Colon Rectum Omentum Pancreas Spleen Bladder Uterus Testis Prostate Skin Trachea

Essential

-

Mg

-

Cr, Mg -

Mg Cr, ‘3 Mg -

Barium Essential

Abnormal

-

Mg Mn, Mg Mn, Cu, Zn, Cr Cr, Mn Cr, Mn Cr, Mn, Cu, Cr, Mn, Cu Mn, Cu Mg Cr, Mg Cr, Mn, Cu, Mn Cr, Mn, Cu, Cr, Mn, Cu, Cr Cu, Zn, Mg Cr, Mn, Zn Cr, Mn Cr Cr, Zn Zn Mn Mn

Mg

Al, B, Ni, Sn, Ti, V

-

Zn Pb

Mg Mg Mg

Sn

-

Pb

Note: Coefficients of correlation were all positive. At this level of significance, they were not found in adrenal, hxynx and duodenum, nor with strontium and any abnormai trace element.

Interrelationships of strontium, barium and calcium in 21 human tissues are shown in Table 6. Strontium and calcium were related in 19 tissues. Barium was related to strontium in 13 tissues, and to calcium in only seven. Thus, it appears that barium goes along with many essential trace elements and with few abnormal ones, whereas strontium goes with calcium and with few other elements. Changes of barium and strontium in human tissues with age There is a tendency for barium to accumulate in certain American human tissues with age (Figs. l-3). Lung especially collected barium, probably from dust, and increases in aorta, kidney and spleen were found. Barium was present in every stillborn infant, and in every infant up to 1 yr of age. Although it occurred in every body, not all tissues contained it. Levels in infants were higher in aorta, heart, kidney, liver, spleen and muscle than in older persons, producing curves characteristic of essential trace elements. Foreign tissues behaved in most cases in an opposite direction with age (Figs. l-3). Levels were generally higher than in Americans, declining in kidney, liver, spleen, aorta, pancreas, and brain and rising with age in lung, and in heart through the sixth decade. Concentrations of strontium were fairly consistent throughout life in liver, spleen and muscle of both American and foreign subjects (Figs. 4-6), showing the usual

497

Trace Metals in Man: Strontium and Barium TABLE 6. INTERRELA~ONS OF CALCIUM, STRONTIUM AND BARIUM IN HUMAN TISSUES, PAIRED RANK CORRELATION COEFFICIENTS (r)OF SIGNIFICANCE,P< 0.001

Tissue Aorta Heart Kidney Larynx Trachea Lung Diaphragm Stomach Duodenum Jejunum Ileum Cecum Signoid Colon Rectum Omentum Pancreas Thyroid Bladder Uterus Testis Prostate

Calcium and strontium

Calcium and barium

Strontium and barium

0.28 0.35 0.49 0.44 0.62 0.38 -

-

0.43 0.39 0.50 0.42 0.40 0.53 0.37 0.44 0.40 0.51 0.49 0.57 0.50 0.51 0.32 0.12 0.59 0.40 0.50

0.28 -

0.24 0.36 0.39 0.27 0.36 0.48 0.67 0.48 0.47 0.43 0.35 0.34 0.54

Note: At this level of significance, coefficients of correlation for all these pairs were not found in adrenal, brain, liver, muscle, esophagus, spleen, skin and ovary. When a dash is shown the coefficient was not significant at this level of confidence.

high neonatal and infantile levels characteristic of essential trace metals, which were also seen in kidney, aorta, heart and lung. In these last four organs strontium accumulated with age, especially in aorta and lung, but did not accumulate in pancreas. In most cases there was more strontium in foreign than in American tissues, but agelinked changes were roughly parallel in kidney, liver, spleen, lung and muscle, declining with age in brain and pancreas. Human exposures to strontium and barium Foods. The concentrations of strontium

in various human foods are shown in Table 7. Amounts over 100 ppm were found in a fish flour made of whole fish including bones, a reference sample of dry kale from H.J.M. Bowen, brazil nuts, cinnamon, and 20 per cent superphosphate fertilizer. Amounts over 50 ppm occurred in two spices and kelp. Amounts of more than 10 ppm were present in clams, anchovies, Bengal gram, brown sugar, molasses, pecan nuts, spices, and dry tea and cocoa. There was no clear-cut correlation of strontium and ash per cent in foods. There were large apparent losses of strontium in refined sugar, most of it going to the molasses. Refined white cane sugar contained only 4.25 per cent of the amount in a semi-refined ‘raw’ sugar and 1.8 per cent of that in brown sugar. Beet sugar likewise had very little, 0.05 ppm, although beets contained 2.4 ppm. The contents of strontium and barium in 2-day hospital diets are shown in Table 8. They contained 2.1-2.4 mg strontium and 0.75 mg barium. In both diets the midday meal contributed the largest amounts, possibly partly from chocolate. Water. Concentrations of strontium in a number of waters are given in Table 9. Variations were wide, from 6 to 375 ppb. n

498

I-WRY A. SCHROEDER,~SABEL H.TIFTON

and ALEXBP.NA.WN

.

14

I

12

Ba ---

10.

pm

Kidney

ash 6..

.

\ . ‘\

‘\

‘\ l

‘\

0

sb

10

O-l

l-9 lo-19M-29 30-3940-4950-5960-6970-P)60+

--Ba

I

Liver

b

8-

Age,Years 12-

.

Ba

10.

-.-.-..

B-

.

pm

Spleen

. A.

1. .

ash

6.

‘a 1. \'

4,j

'\ '\ 0 -O-.

2.\\0 -0 sb

0-r

-T--O 0

9 O-l

l-9

lO-19 20-29 30-39 Agc,Years

40-49

0 50-59 60-69 'IO-79 80-w

FIG. 1. Mean concentrations of barium in kidney, liver and spleen, according to age, ppm ash. Open circles and dashes, American subjects; dots and dash-dots, foreign subjects. There were 215 kidneys, 220 livers and 174 spleens of American subjects, and 171 kidneys, 169 livers and 167 spleens of foreign subjects. Note declines in older foreign subjects and in American children. There was more barium in older foreign subjects and in American children. There was more barium in foreign than in American samples. SB denotes stillborn.

499

Trace Metals in Man: Strontium and Barium

l\ l

‘\ -Aorta

- 80

A.,

'\

Agc.Vcars

.

10

.I

&a .

0. 0

/"

PPm ash

o

.*": .

I,,,

, .#.-•

\ 2

0

_9_-D-T-

\ ~--o---~-o

0 sb

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lo-19 20-29 30-39 40-49 50-59 60-69

70-79

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Age,Veors

50 40 wm ash

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30.

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20.

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sb

l

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x_,

_40

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l-9

M-19

20-29 30-39 Age. Years

40-49

50-59

60-69

70-79

609

FIO. 2. Mean concentrations of barium in aorta, heart and lung according to age, ppm ash. Open circles and dashes, American subjects; dots and dash-dots, foreign subjects. There were 118 aortas, 174 hearts and 182 lungs of American subjects, and 110, 152 and 165 respectively of foreign subjects. Note increase in American aortas and decline in foreign, increase in foreign hearts up through sixth decade, and increase in all lungs. There was more barium in foreign than in American samples. Unlike other tissues, stillborn (SB) lungs had little.

500

HENRY A. SCHROEDER,ISABELH.TIPTON andA~msP.N~so~

.

Ba -~

20r 16

Pancreas

. 1.

wm

1.

ash

\. .

12

'.\'

cl

8.

'\ '\' .

4-

'\

0 __>~--O

00-o sb

0

-0 0

_-o-o--

P O-1

1-9

IO-19 20-29 30-39 Age, Years

LO-49

50-59

60-69

Ba -__

12

70-79

80-e

Brain

PPm ash B/ 40

l-.\.

. \

Osb

l-9

\.

A.0 --e-

l

cg--o-_o,_rJO-l

1.

--O-P10-19 20-29 Age,

30-39

40-49

50-59

60-69

m-79

0 ao*

Years

Ba Muscie

. .

. .

I

-o--_,L--a-0

0 sb

0

o-1

l-9

lo-19 20-29 30-39 Agc.Vears

LO-49 50-59

60-69

70-79 BOaa

Fro. 3. Mean concentrations of barium in pancreas, brain and muscle according to age, ppm ash. Open circles and dashes, American subjects, dots and dash-dots, foreign subjects. There were 165 pancreases, 130 brains and 171 muscles of American subjects, and 107, 100, 12, respectively of foreign subjects. Note declines in pancreas and brain of foreign subjects. Values of foreign muscle were scattered; there was more barium in foreign than in American samples.

501

Trace Metals in Man: Strontium and Barium

--Kidney

Sr

20

0t

\’

. ‘\

%?,

\ 12-\o

L,

’

.2*_.>_.-.-‘-.

8‘A 4’

0

0

sb

o-1

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10-19 20-29

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30-39

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609

Age.Vears

16. PPm

.-.-.v_ .

,p--o---e-,_ 1-S

10-19 M-29

8

l

30-39 LO-&S 60-59 60-69 m-79

B(k

Agc,Vears

7D PPm 16 ash 12 \

\

*- \

.

40 0 sb

o-1

l-9

lo-19 m-29

30-39

,,O-49 60-59

60-69

TO-79 BO-,

Agc.Vears

FIG. 4. Mean concentrations of strontium in kidney, liver and spleen according to age, ppm ash. Open circles and dashes, American subjects, dots and dashdots, foreign subjects. There were 214 kidneys, 218 livers, and 191 spleens of American subjects, and 175 kidneys, 171 livers and 161 spleens of foreign subjects. Note the parallel behavior according to age, and the declines from stillborn (SB) values characteristic of essential trace metals. There. was usually more strontium in foreign than in American samples.

502

HENRY

sb

A.

SCHROEDER,ISABELH. TIPTON and

o-1

1-S

IO-19 20-29

30-39

40-49

NASON

ALEXISP.

50-5s

60-69

m-79

60+

Age. Years

Sr

Heart

pm

ash

01 sb

O-l

1-S

4

IO-19 20-29 30-3s 40-4s 50-5s 60-69 70-7s 60-w Age, Yiars

Lung sr. -_ .

.

20 t

\

16 PPm ash

'\ 12t 0

dsb

l

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Age,Years

of strontium in aorta, heart and lung according to age, FIG. 5. Mean concentrations ppm ash. Open circles and dashes, American subjects; dots and dash-dots, foreign subjects. There were 128 aortas, 187 hearts, and 192 lungs of American subjects and 104, 152, 174, respectively in foreign subjects. Note the fall from stillborn (SB) levels, and the subsequent rise in aorta and lung of Americans, and the age-hnked rise in foreign aortas, hearts and lungs. Fkept in aorta, there was more in foreign than in American samples. Strontium in aorta does not follow the steady increase in calcium found with age in Americans.

503

Trace Metals in Man: Strontium and Barium .

32

1

30

\ ‘\

10

&r

Pancreas

‘Y,

PPm ash 8-

%. cl --9

l

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l

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.A?_

0 01

sb

o-1

L

0

.

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l-9

VI-19 20-29 30-39 40-49

50-59

60-69

70-79 80+

Ag*.V*.m

&r PPm "1 ash 6.

Brain

.

‘.\

4-

‘1 .

2,

0

c-OLO--

,_

01 0 sb o-1

l-9

lo-19

.i.

l

l

0

l*L.

-._.-

“_--_-0*

-o-

20-29 30-39

40-49

-0

.

70-79

50-59

60-69

-Sr

Muscle

SO+

Age,Yews

26 d 24

wm (

ash

\

6-\ 4-

'\

0 .

2-

0, sb

'0 \

O-l

*_----0 0 1-9

o*

-: l

7-0 o

lo-19 20-29 30-39 40-49

-0

l

SO-59 60-69

70-73 BOe

Agc,Ycars

FIG. 6. Mean concentrations of strontium in pancreas, brain and muscle according to age, ppm ash. Open circles and dashes, American subjects; closed circle and dash-dots, foreign subjects. There were 160 pancreases, 149 brains and 169 muscles of American subjects and 106, 99, 11, respectively, of foreign subjects. Note age-linked declines in pancreas and brain of foreigners, similar to the declines of barium in the same subjects. Differences between American and foreign strontium concentrations were not apparent at older ages.

504

HENRYA. SCHROEDER, ISABELH. TABLE7.

TIPTON

and ALEXISP. NA~~N

STRON~WMIN FOODS Ash per cent of wet weight

Strontium uglg

3.50 2.22 2.24 4.32 26.96 2.22 2.70 21.70 21.50

25.93 6.18 16.46 5.77 3.42 4.00 5.14 280.38 231.38

2.87

9.56

1.79 1.28 1.28 1.15 3.44 3.09 1.53 2.87 1.65

1.44 1.89 1.82 1.09 0.76 0.76 1.25 0.52 1.24

2.01

1.20

0.0 6.50 1.25 0.51 0.85 0.86 0.92 -

0.80

Mean, cow’s milk

0.86

0.50

Grains and cereals Wheat Oats Millet Buckwheat Barley Bengal gram All-Bran, Kellogg’s corn, sweet

3.03 2.54 2.66 2.11 2.33 5.78 5.00 0.71

3.46 3.01 1.29 3.84 0.98 18.62 8.56 0.52

3.05

5.04

1.73 1.68 1.16 2.69 1.13 1.10

1.08 1.09 2.38 3.34 2.65 1.98

Fish and sea food Clam Shrimp Anchovy, canned Sardine, canned Cod, salt Halibut Haddock Fish flour, No. 1 Fish flour, No. 2 Mean, excluding fish flour Meat Beef and fat Round steak, ground Iamb chops Pork loin Beef liver Pork liver Beef kidney Chicken breast Chicken leg Mean Dairy products Butter, unsalted Cheese, American Milk, whole dairy Milk, instant, non-fat dry A&P Milk, non-fat, dry Starlac Milk, non-fat, dry Carnation Milk, non-fat, dry Breadlac Milk, human breast, fluid

Mean Vegetables, roots Potato, skin Potato, sweet Beet Beet, greens Carrot Turnip

5.03 0.50 0.51 0.47 0.52 0.51 6.04

505

Trace Metals in Man: Strontium and Barium TABLE 7. STRONTIUMIN

Vegetables, roots (continued) Parsnip Onion Garlic Mean Vegetables, legumes Lima bean, seeds Lentils, dry Beans, red kidney Beans, shell, dry Beans, green Mean Vegetables, leafy Lettuce, ruby Escarole Celery Kale, dry (Bowen) Kale, same Parsley Chicory Brussels sprouts Broccoli Cauliflower Mean, excluding kale Vegetables, fleshy Green pepper Squash, butternut Tomato Cucumber Squash, summer Mushroom Mean Fruits, fresh Grape Banana Strawberry Plum Blueberry Mean Sugars and syrups Sugar, relined white Sugar, raw Sugar, brown Sugar, beet Sugar, Demerara Sugar, Maple Molasses, beet

FooDs-continued Ash per cent of wet weight

Strontium uglg

1.55 0.76 3.82

4.21 0.65 3.48

1.81

2.12

6.25 17.40 0.97 2.00 -

4.38 5.07 0.65 1.10 1.09

6.66

2.46

1.98 1.12 16.43 16.43 4.27 1.06 1.51 1.os 0.71

3.39 2.84 1.72 109.13 117.28 6.20 1.65 0.59 1.04 0.52

1.67

2.24

0.54 0.84 0.72 0.50 0.49 -

0.29 0.94 0.48 0.50 0.77 0.54

0.62

0.59

0.53 1.02 0.55 0.50 0.82

1.72 0.88 2.29 0.74 0.59

0.68

0.89

0.16 1.28 2.24 0.06 0.53 1.60 -

0.19 4.56 10.50 0.05 1.30 2.77 12.03

506

HENRYA. SCHROEDER, ISABELH. TIPT~N and ALEXISP. NA~~N TABLE7.

STRONTIUM IN FooDs-continued

Nuts Brazil nut Pecan Fats and oils Beef, tallow Pork fat Corn oil, Mazola, No. 1 Corn oil, Mazola, No. 2 Soy bean, Crisco, No. 1 Soy bean, Crisco, No. 2 Cottonseed oil, Wesson Safflower oil, Betty Cracker Cod liver oil, Penslar Meall Condiments and spices Nutmeg, dry Cinnamon, dry Allspice, dry Thyme, ground dry Salt, iodized Cocoa, dry Tea, Red Rose, dry Tea, instant Tetley, dry

Ash per cent of wet weight

Strontium bg/g

4.04 2.80

107.43 13.63

-

1.56 0.14 < 0.07 0.08 0.15 0.07 0.11 0.05 0.10

-

0.26

2.22 6.36 8.23 6.48 97.00 5.49 7.58 20.45

13.90 118.75 79.17 90.30 4.51 29.88 35.09 11.58

5.82

75.04

1.50 1.16

0.97 1.17

1.33

1.07

Animalfood Rat diet (rye, milk, corn oil) Rat diet (white sugar, torula yeast, lard) same, with raw sugar same, with brown sugar Hay

4.83 4.15 9.19 5.48 3.52

2.67 4.58 5.91 7.71 9.40

Miscellaneous Doric, yeast, dry Kelp, dry Lecithin, soy Superphosphate fertilizer, 20 per cent

1.00 42.50 8.55 -

4.09 98.58

Mean of spices Frozen dinners Scallops Fillet of Sole Mean

5.80 386.13

Note: When ash per cent is not shown, sample was wet-ashed. Values of dry milk are on the basis of reconstituted milk.

507

Trace Metals in Man: Strontium and Barium TABLE 8.

STRONTIUMANDBARIUMINZ-DAYHOSPITALDJETS,WETWEIGHT

Wet weight

Barium

Strontium

Meal

g

Ash per cent of wet

1965 Breakfast Lunch Dinner

518 519 660

1.06 1.46 1.45

0.93 2.41 0.98

0.48 1.25 0.65

1697

1.33

1.40

2.38

645 848 647

1.15 1.25 1.13

0.55 1.22 1.06

0.35 1.03 0.69

0.31 0.47 0.24

0.20 0.39 0.16

2140

1.18

0.97

2.08

0.35

0.75

Total and mean 1969 Breakfast Lunch Dinner Total and mean Compositions

uglg

Total, mg

Total, mg

c/g

of these diets have been reported, [14, 681. TABLET.

STRONTIUMMWATER IM.

Source

Sea water, Virgin Islands Brattleboro, Vt., Connecticut River Reservoir, feeder and stream Hospital tap, fresh Hospital tap, stagnant Spring, W. Brattleboro Well, Dummerston Spring, mineral, Guilford New Hampshire, Lake Spofford Municipal waters, tap: Bridgeport, COM. White Plains, N.Y. Bangor, Pa. Pipe&em, Va. Gibsonville, 0. Peterboro, N.H. La Grange, Ga. Santa Fe, N.M. Alexandria, La. Cisco, Tex. Dauphin Island, Ala.

8000 106 43 50 63 3% 250 200

58 29 14 1:: 43 43 50 1: 308

Hot Springs, Ark., bottled

6

DISCUSSION

Metals of Group IIA of the Periodic Table are bone-seekers. Of the total amounts in the human body, bone contains 25 per cent of the beryllium, 57.9 per cent of the magnesium, 98.6 per cent of the calcium, 99.1 per cent of the strontium, 91 per cent of the barium and 87.1 per cent of the radium. Lead is the onIy other common metalhc bone-seeker, with 91.6 per cent stored there [15] ; fluorine is in bone to the extent of 96.2 per cent of the total bodily content, and phosphorus to the extent of 97.2 per

508

HENRY

A.

SCHROEDER,ISABELH. TIPTON and ALEXIS P. NAS~N

cent [9]. Lead and beryllium are known contaminants, coming from industrial uses; the remainder are of natural occurrence, and four are essential elements for bone: magnesium, calcium, phosphorus and fluorine. In order to evaluate the possibility that strontium and barium may have some biological function, it is rewarding to examine the geochemistry and biochemistry of these two prevalent metals. 1. Geochemistry In the geosphere, Mason ranks strontium 15th at 450 ppm and barium 16th at 400 ppm in the order of elemental crustal abundance [ 161; Vinogradov reverses the order, placing barium 13th and strontium 15th [17]. Abundances of these two metals are greater than those of carbon, chlorine and chromium, and slightly less than those of sulfur and fluorine. Of the trace elements, they rank fifth and sixth in abundance [16]. Barium tends to be more abundant than strontium in most rock types with the exception of limestones and in most soils and coal ashes. Although the bulk of the earth’s barium and strontium are to be found concealed as impurities in the common rock-forming minerals, they are also major components of a number of discrete minerals such as barite (BaS03 and celestite (SrSO,). In sea water, where life began, strontium at 8 ppm is greatly enriched relative to barium at 0.006 ppm [16]. This follows in part as a result of the greater solubility of strontium salts in sea water relative to barium and also of the preferential absorption of barium salts by argillaseous sediments. Strontium is the most abundant trace element in sea water. In fresh water rivers, barium averages 0.05 ppm with a range of 0.007-15 ppm [18]. Municipal waters of the United States had a median value of 110 ppb strontium (range 2.2-1200 ppb) and a median of 43 ppb barium (range 1.7-380 ppb) [19]. Water at 2 1. per day would provide a person about 0.22 mg strontium and 0.086 mg barium, on the average, or about 11 (0.2-55) and 9 (0.3-30) per cent of the total intakes, respectively, with these wide variations. Hard water in two Texas cities could contribute 2.4 mg strontium and 0.4 mg barium to the daily intake, an amount of strontium exceeding the daily intake from food. Air. Strontium and barium are not routinely measured in air, as they are natural pollutants from dust. Tabor and Warren [20] measured barium levels in the air of 18 cities and four suburban areas in the United States in 1956. Of 754 samples, the highest were in Houston and its suburbs, where 76 per cent of samples contained 0.005-1.5 ug per m3. In nearby Fort Worth, 66 per cent had low values. No pattern related to industrialization appeared; low values O-0.005 pg per m3 occurred in Jersey City, New York City and Philadelphia. At 20 ma inspired air per day, of which half of the particulates are retained in lung, human intake from this source would amount to O-5 pg per day, depending on area.

2.

In living organisms

Barium and strontium are found in all living things, where measured [2]. Marine plants concentrate both metals from sea water, strontium 32-185 times and barium 1000 times. Marine animals also concentrate strontium about 2.5-62 times and barium 7-100 times. Land plants, on the other hand, partly exclude both metals from

Trace Metals

in Man: Strontium and Barium

509

soil. Only fungi have concentrations of strontium in the range of that in soil, at the same time partly excluding calcium. Three plants accumulate strontium: Curex humilis, a sedge, Arabis stricta, of the cabbage family, and brown marine algae. Barium has been found in Brazil nuts at 300@-4000 ppm, and plants of the genus Astragalus are known to accumulate barium [17], as do an oak, Douglas fir, walnut and green ash [21]. Crustacea contain high concentrations of strontium but little barium. Hard tissues of marine plants and animals, as would be expected, are rich in strontium, with some barium [2]. The exoskeleton of the rhizopod Xenophyofera is made up largely of barium sulfate. Barium and strontium both occur in insects [22]. Fish undoubtedly contain both of these metals. A radiolarian Acanthuriu has an exoskeleton made up largely of strontium sulfate. Therefore, in at least two species, these trace metals are essential for skeletal structure. In mammals, there is a concentration of strontium and barium in the pigmented parts of the eye [23]. In the iris of the cow concentrations of barium up to 206 pg/g and in the choroid up to 1100 vg/g wet weight have been found, but barium was not concentrated in the tapetum lucidum [24]. Lesser amounts were detected in these parts of the eyes of rabbits and man. Strontium was concentrated to much less extent but followed the same distribution in iris and choroid, with lower values in cornea, lens, vitrous body, retina and sclera [23]. There is a high concentration of zinc, 16-19 per cent of dry weight, in the tapetum lucidum of mammals [25, 261. Strontium in human bone has been found to increase regularly with age, rising from 79.1 f20 (S.D.) ppm ash in infancy to 114+28 pg/g in adult life [27]. Our results (Table 4) suggest the same trend. Barium, on the other hand, did not increase with age, infants having 7.0+4.0 ppm and adults 8.5+4 ppm [27]. 3.

Atomic structure and biochemical functions

It is likely that some ligands in bone do not discriminate too sharply between small amounts of the elements of Group IIA. In large amounts (2% Sr(CO,),), strontium can produce rickets in experimental animals [28], probably by displacing calcium. Beryllium also causes rickets, but the mechanism is unclear [29]. Strontium can substitute for calcium in the apatite of tooth enamel [30], but the tooth structure becomes abnormal [31]. Nothing is known about the biochemical functions, if any, of strontium and barium in bone or in soft tissues [32, 331. No catalytic or electrochemical functions have been discovered, although structural ones have been postulated [2]. In general, the experimental evidence suggests deleterious effects of strontium on calcified structures [32]. Strontium can replace calcium in some bacteria and fungi [34] insofar as growth and reproduction are concerned. Rygh [35, 361 believed that strontium and barium were both essential for mammalian bony structure. He showed that strontium increased mineralization of bone and teeth of rats and guinea pigs, whereas barium retarded deposition of calcium. There is evidence that strontium increases dentine aposition of rat’s teeth [37], there is more strontium reported in sound than in carious human teeth [387, and there is epidemiological data relating absence of caries with strontium and molybdenum in water [39]. Shorr and Carter fed to human patients with post-menopausal osteoporosis strontium at 1.75 g daily for several years [40]. They believed that bone remineralized as a result of this treatment. Therefore there is some evidence both for the adverse and beneficial effects of strontium on bone and teeth.

510

4.

HENRYA. SCHROEDER, ISABELH. TIPTONand &ms

P. NASON

Metabolism

Because of contamination of the globe with radioactive strontium from nuclear fission explosions in the atmosphere, there has been much interest in the metabolism of strontium [41]. In brief, (a) there is an invariable association of strontium with calcium in the food chain, from soil to plants to animals to man. (b) There is a differential absorption of calcium in preference to strontium. (c) There is a preferential utilization of calcium over strontium for bone and milk production [25, 321, and (d) there is a preferential urinary excretion of strontium over calcium. The renal plasma clearance of strontium in eight adults was measured at 9.7 1. per day (range 7.4-12.7 I.), with concomitant calcium clearance of 3.2 1. per day (range 1.8-5.8 1.) [42]. Respective clearances in 12 children aged 4-14 yr were 4.0 and 1.3 1. per day. Thus, the clearance of strontium was three times that of calcium. Plasma mean concentration of strontium was 29 ug per 1. (range 16-43 ug) in eight adults and in about the same range in children. Similar values were calculated from the long-term balance studies of Tipton et al [43, 441, clearances of strontium being 6.8 1. per day and of calcium being 1.7 1. per day. Means of 11.0 per cent of the dietary intake of strontium and 12.6 per cent of calcium appeared in the urine. Little is known of the metabolism of barium in man. Three subjects excreted 1.8, 1.9 and 5.7 per cent of the dietary intake in urine [44] ; little natural barium is absorbed by the gastrointestinal tract from foods and water. In rats fed barium, 24 hr urinary excretion was 7 per cent of the amount ingested [45], but when it was injected, the renal clearance considerably exceeded that of calcium [33]. Human blood plasma contains 79 ug per 1. barium. At 1200 ml urine per day containing 26 pg of barium, the mean urinary excretion of three of Tipton’s subjects [44], renal plasma clearance would be about 330 ml per day. On this basis the clearance of barium was about 9 per cent of that of calcium and 4.8 per cent of that of strontium, indicating preferential excretion of strontium. These figures are only approximate. Retention of strontium in the body after oral doses of 5-250 mg has amounted to 10-12 per cent in a month and 16.3-22.7 per cent in two weeks [42,46]. More strontium is absorbed by persons on a low calcium intake than on a high calcium intake [47]. In adults with bone disorders, strontium did not invariably behave like calcium [48]. It is clear from Figs. l-6 that barium and strontium cross the placental barrier, for both metals are found in all infants and children in the first decade of life, including the stillborn. In later life, barium may disappear from some organs, but strontium does not. Infants retain strontium regularly with age [49]. 5.

Toxicity

By the oral route, calcium, strontium and barium have low orders of toxicity. The order of toxicity to living organisms of Group IIA metals is Be >Ba > Sr > Mg=Ca. It is possible that the slight toxicity of barium depends on its ability to form stable and insoluble sulfates with essential metabolites [2]. Oral toxicity of barium depends upon the form administered. Lethal doses of barium carbonate were (mg per kg body weight): 200 in mice, 1480 in rats, 418-557 in rabbits, 104-139 in guinea pigs [4] and 800 in chickens [50] ; for barium chloride, lethal doses were 7-14 in mice, 355-533 in rats, 170 in rabbits, 90 in dogs, 800-1200 in horses and 100 in man [4]. Insoluble barium sulfate is tolerated by all species, and a barium meal or enema may amount to 0.5 per cent of the body weight. Barium carbonate is used as a rat poison and

Trace Metalsin Man: Strontium and Barium

511

barium hydroxide and hexafluoracetate as pesticides. The principal physiological effect of barium is to stimulate all types of muscle. 6. Possible essentiality of barium and strontium According to hypotheses we have made, to be suspected of being biologically essential for mammals an element must fulfill the following criteria: (a) The element must be ubiquitous on the earth’s crust in large enough amounts to supply fairly uniform exposures and must be present in all living organisms. This criterion applies to barium and strontium. (b) The chemical nature of the element must be compatible with some physiological or structural function. Barium and strontium interact with calcium, although not always to the integrity of calcium structures. (c) The atomic number of the element should fall within those now known to be essential for life or health, i.e. l-53. The atomic number of barium is 56, which does not entirely exclude it. (d) The element must pass both the placental and mammary barriers, in order to supply the new-born animal with adequate amounts during the neonatal period. Concentration of the element, therefore, should be high in the tissues of infants, Barium and strontium fulfill this criterion. (e) Concentration of the element in human tissues should be quite constant throughout life, or perhaps decline in later life because of dietary deficiencies. Strontium fulfills this criterion, and all of the data are compatible with the presence of mammalian homeostatic mechanisms, Moderately excessive exposures should not lead to accumulation. The data on barium suggest that homeostasis is only fair, for it accumulated in some human tissues with age and was lost from others. (f) The element must have a low order of toxicity for all forms of life. Strontium is virtually non-toxic; barium has only slight toxicity. (g) Biological activities in mammals must be demonstrated. There is some evidence that strontium could harden bone and teeth. It has been considered among the anticariogenic agents in man [39]. No demonstrable effects on growth of a mammal have been found. There is little evidence that barium has specific activity for optimal formation of bone, and the small concentrations in bone are probably inert. From these considerations the hypothesis that strontium is an essential trace metal is suggestive but unproven. Barium does not entirely meet the requirements, and it is probably not essential for mammalian biological function. 7.

Balances of strontium and barium in man

Tipton et al [43, 441 have measured dietary intakes and excretions of 17 elements by five adult subjects for 30-347 days. Mean intake of strontium was about 1.8 mg and of barium about 1.2 mg daily with individual variations of 1.2-2.3 mg strontium and 0.65-1.77 mg barium. Excreted in urine were 11.0 per cent of the strontium, 3.1 per cent of the barium and 12.6 per cent of the calcium ingested. Feldman and Jones [51] analyzed teenage diets from ten United States cities; concentrations were 0.73 ppm strontium (range 0.52-1.23 ppm) and 0.44 ppm barium (range 0.25-1.24 ppm). Our concentrations for strontium were higher than theirs (table 8).

512

HENRYA. SCHROEDER, ISABELH. T~PT~Nand ALEXISP. NAS~N

Murphy et al [52] analyzed 20 Type A school lunches from 300 schools in 19 states for trace minerals. They found means of 0.33 mg strontium (range
Barium, strontium and chronic disease

Barium miners breathing barite dusts, and workers making lithopone, a white pigment composed of 30 per cent barium sulfate and 70 per cent zinc sulfide, may exhibit baritosis. X-rays of the lungs show fine nodules with a reticulated background evenly distributed, which usually disappear when exposure is discontinued for long periods. This disorder is associated with few or no symptoms [4]. Exposure of guinea pigs to barite dust produced nodular granulation of the lungs characteristic of baritosis [45]. Except for baritosis, there is no suspicion that barium in deficient or excess amounts causes any chronic disease. There is no evidence that excess strontium causes a chronic disease. On the other hand, it is possible that the intake of strontium in some persons could be marginal, for several reasons.

513

Trace Metals in Man: Strontium and Barium TABLE 10. ESTIMATEDMEAN DAILY BALANCES OF CALCIUM, STRONTIUM AND BARIUM IN MAN

Calcium mg

Strontium mg

Barium mg

Intake

Food Water* Airt Total output Urine Feces* Sweat 5 Hair, nails 11 Total Soft tissues, total7 Per cent soft tissues in diet Per cent of intake in urine Per cent of excreta in urine

800 52 < 0.04 852

140 667 45 0.003 852 14.000 6.1 16.5 21.0

2.0 0.22 0.00006 2.22

0.2 1.78 0.24 0.0001 2.22 3.3 67.3 9.1 10.1

1.24 0.086 0.001 1.33

0.03 1.215 0.085 < 0.0001 1.33 1.8 74.0 2.3 2.4

*Median value x 2 from Durfor and Becker [19] tMedian value x 10 from Tabor and Warren [20] $By difference, calculated for equal balance $Total mean +4 from Consolazio et al [55] and from Howell [54] /Calculations of Howell [54] BFrom Tipton [9]. Strontium in water provides the largest increment, compared to the intake from food, of any other bulk or trace element found in water. It is absorbed by vegetables from cooking water, unlike most other water-borne elements [39, 561. Because the intake of strontium from municipal water can vary so widely, and because strontium and hardness of water are directly associated, this variation may be large enough to make the difference between marginal and high intakes in various geographical areas with hard or soft waters. Low intakes of strontium are possible when the major sources of calories are refined white flour, polished rice, refined white sugar and refined fats (Table 7) and

when little milk is consumed. Wheat loses 60 per cent of the calcium, 89 per cent of the barium and most of the strontium when it is refined into white flour [57, 581. The measured contents of strontium in diets from ten cities varied widely, by two-fold or more, which was not the case for calcium or most trace elements [51]. Strontium deposited in human rib varied (Table 2) from 38 to 360 ppm ash and in vertebra from 58 to 200 ppm ash, whereas calcium was quite constant, 29-39 g per 100 g ash in rib and 32-37 g per 100 g in vertebra. These findings suggest variations in exposure. Relatively more strontium is absorbed by older people on low calcium intakes than on high calcium intakes [47]. There was significantly more strontium in bone in the ribs of Oriental subjects who have low calcium intakes, than in ribs of subjects from other areas of the world. Strontium in bone increased considerably with age [27]. Therefore, deficiency of strontium in older persons is unlikely, unless it should occur as a result of abnormal calcium metabolism. Injected labeled strontium was rapidly C

514

HENRY A. SCHROEDER, ISABELH. TIPTON and ALEXB P. NAS~N

excreted by a patient with senile osteoporosis and slowly by a patient with Paget’s disease [60]. The role of strontium, if any, in common bone diseases remains unproven. The evidence for strontium being anti-cariogenic in man is most indirect. A number of trace metals have been implicated: vanadium [61, 621, molybdenum [63-651, boron, lithium [66] and strontium [35, 36, 39, 561. Excess selenium was cariogenic [62, 671. Caries was absent in Navy recruits exposed to high concentrations of strontium in local water from northwest Ohio, northeast South Carolina and west central Florida, compared to high incidences of caries in recruits from other areas with little strontium in water [39]. The Ohio water was also high in boron, lithium and molybdenum, but the increment provided by water to the total intake of these elements was low. At present, strontium cannot be implicated positively in any disorder of bones or teeth, although such involvement is possible. SUMMARY

AND

CONCLUSIONS

Analyses of strontium and barium in about 400 human subjects from many areas of the world were made by emission spectrography. Strontium was omnipresent in human tissues, 99 per cent being stored in bone. In soft tissues, highest concentrations were found in aorta, larynx, trachea and the lower gastrointestinal tract. Barium was found in all tissues, with 93 per cent in bone, but not all samples contained it. There was more barium in most tissues of foreign subjects than of Americans, and more strontium in kidney and liver. Adults and children from the Far East had more strontium in bone than did Americans. Barium tended to accumulate in or to be lost from some tissues with age; strontium accumulated only in lung and aorta. Infants had higher concentrations of both metals than adults and children. Barium in human soft tissues was significantly correlated with most essential trace metals; strontium was not. Concentrations of strontium were highly correlated with calcium; both metals were found in newborn infants, usually in high concentrations. Human exposures to strontium were evaluated by analyses of 100 foods and 21 waters and of whole diets. Largest concentrations were found in spices, sea foods, grains and cereals, root and leafy vegetables and legumes. There were major losses of barium and strontium when wheat was refined, and of strontium when sugar was refined. There was much more barium than strontium in wheat. Water supplied on the average 10 per cent of the dietary intake of strontium, range 0.2-55 per cent, and barium 6 per cent, range 0.3-30 per cent. Hospital diets contained 2.2 mg strontium per day, and long-term diets contained 1.8 mg strontium (1.2-2.3 mg) and 1.2 mg barium (0.65-l .8 mg). Urinary excretion of ingested strontium was 11 per cent and of barium 3 per cent. Considerable strontium can be excreted in sweat. The diets contained more than two-thirds of the strontium and nearly three-quarters of the barium present in soft tissues. Barium and strontium are ubiquitous in relatively high concentrations in the geosphere and are found in all living organisms analyzed. There is more barium than strontium in soils, most rocks and some coals. Marine organisms concentrate both metals from sea water, from 3 to 1000 times. Plankton, brown algae and fungi concentrate strontium; bryophytes concentrate barium. Hard tissues of marine animals contain much strontium and some barium. All group IIA metals are bone-seekers.

Trace Metals in Man: Strontium and Barium Strontium sphere and strontium in it is possible the evidence

behaves largely but in mammals. Data small amounts acts that strontium is is unconvincing.

515

not completely as an essential trace metal in the bioon barium are less convincing. It is possible that to harden the structures of bones and teeth. Whereas concerned in dental caries and senile osteoporosis,

REFERENCES Handbook of Chemistry and Physics, 47th Ed. The Chemical Rubber Co., Cleveland, Ohio, 1966-67 Bowea HJM: Trace Elements in Biochemistry, New York, Academic Press, 1966 Mineral Facts and Problems, US Department of the Interior, Bureau of Mines, US Government

Printing Office, Washington, 1970 Miner S : Air Pollution Aspects of Barium and Its Compounds (prepared for National Air Pollution 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

19.

20. 21. 22. 23. 24. 25. 26. 27.

Control Administration) Litton Systems Inc. Environmental Systems Division, Bethesda, Md 1969 Tiptoa IH, Cook MJ, Steiner RL et al: Trace elements in human tissue I. Methods. Health Phys 9: 89, 1963 Tiptoa IH, Cook MJ: Trace elements in human tissues-IT. Adult subjects from the United States. Health Phys 9: 103, 1963 Tiptoa TH, Schroeder HA, Perry HM et al: Trace elements in human tissue-III. Subjects from Africa, the Near and Far East and Europe. Health Phys 11: 403, 1965 Tipton IH, Stewart PL: Spectrographic analysis of biological materials. Dev Appl Spectrosc 5: 343, 1966 Tiptoa IH: Chapter II Gross and Elemental Content of Reference Man. ICRP Report of Subcommittee II on Permissible Dose for Internal Radiation. Oxford, England, Pergamoa Press (in press) Schroeder HA, Nasoa AP, Tiptoa IH: Essential metals in man: Magnesium. J Chron Dis 21: 815, 1968 Schroeder HA, Nasoa AP, Tiptoa IH: Chromium deficiency as a factor in atherosclerosis. J Chron Dis 23: 123, 1970 Schroeder HA, Balassa JJ, Tiptoa IH: Essential trace metals in man: Manganese. A study in homeostasis. J Chron Dis 19: 545, 1966 Schroeder HA, Nasoa AP, Tipton IH et al: Essential trace metals in maa: Copper. J Cluon Dis 19: 1007, 1966 Schroeder HA, Nason AP, Tiptoa IH et al: Essential trace metals in man: Zinc. Relation to environmental cadmium. J Chron Dis 20: 179, 1967 Schroeder HA, Tiptoa IH : The human body burden of lead. Arch Environ Health 17 : 965, 1968 Mason B: Principles of Geochemistry, 2nd Ed. New York, Wiley, 1958 Vinogradov AP: The Geochemistry of Rare and Dispersed Chemical Elements in Soils, 2nd Ed. Consultants Bureau, New York, 1959 Skougstad M, Horr CA: Occurrence and Distribution of Strontium in Natural Water, Geol Survey Water-Supply Paper 14%-D, US Dept of Interior, US Government Printing Office, Washington 1963 Durfor CM, Becker E: Public Water Supplies of the 100 largest Cities ia the United States: 1962, Geological Survey Water-Supply Paper, 1812, U.S. Dept of the Interior, U.S. Govt Printing Office, Washington, 1964 Tabor EC, Warren WV: Distribution of certain metals in the atmosphere of some American cities. Arch Indust Health 17: 145, 1958 Carlisle D, Cleveland GB: Plants as a Guide to Mineralization. State of California Division of Mines, San Francisco, 1958 Waterhouse DF: Occurrence of barium and strontium in insects. Au&al J Sci Res B4: la,1961 Sowdea E, Pirie A: Barium and strontium concentrations in eye tissue. Bin&em J 70: 716,1958 Kostial-Simoaovic K, Pirie A: Barium content of different parts of the choroid of the bovine eye. Nature, Lond 199: 1007, 1963 Underwood EJ: Trace Elements in Human and Animal Nutrition 2nd Ed. Academic Press, New York, 1962 Vallee BL: Zinc, in Mineral Metabolism, Vol. 2B (Comar CL, Broaaer F, Eds) Academic Press New York, 1962 Sowdea EM, Stitch SR: Trace elements in human tissue. Estimation of the concentrations of stable strontium and barium in human bone. B&hem J 67: 104, 1957

516 28. 29. 30. 31. 32. 33. 34. 35. 36. 37.

38. 39. 40. 41.

42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52.

53. 54. 55. 56. 57.

HENRYA. SCHROEDER, ISABELH. T~PT~Nand AL_EXIS P. NA~~N Follis RH: Bone changes resulting from parenteral strontium administration. Fed Proc 14: 403, 1955 Irving RF: Dynamics and Function of Phosphorus, in Mineral Metabolism, Vol2B (Comar CL, Bronner F, Eds) Academic Press, New York, 1962 Johnson AR, Armstrong WD, Singer L: Strontium incorporation into dental enamel Science 153, 1396, 1966 Sognnaes RF: Dental Aspects of the Structure and Metabolism of Mineralized Tissues, in Mineral Metabolism Vol2B (Comar CL, Bronner F, Eds) Academic Press, New York, 1962 Comar CL, Wasserman RH: Strontium, in Mineral Metabolism, Vol2A (Comar CL, Bronner F, Eds) Academic Press, New York, 1962 Bauer GCH, Carlsson A, Lindquist B: Metabolism and Homeostatic Function of Bone, in Mineral Metabolism, Vol 1B (Comar CL, Bronner F, Eds) New York, Academic Press, 1961 Lewin SZ, Lucchesi PJ, Vance JE: Significance of fungus growths in analytical and radiochemical work with strontium-containing solutions. J Am Chem Sot 75: 6058, 1953 Rygh 0: R6cherchBs sur les oligo Blkments-I. Des l’importance du strontium, du baryum et du zinc. Bull Sot Chim Bio131: 1052, 1949 Rygh 0: R&herchBs sur les oligo BlBments-III. Sur l’importance du strontium, du vanadium, du baryum. du thallium et du zinc dans les scorbuts. Bull Sot Chim Biol 31: 1408. 1949 Wei&ann’JP: Effect of strontium on the incisor of the rat-I. Injections of small doses of strontium chloride as a means of measuring the rate of incremental dentine apposition. J Dent Res 21: 497, 1942 Piercuccini R, Zotti R: Biological function of strontium and manganese in teeth. Atti della Sot Toscana di Sci Nat (Pisa) Mem (Ser A) 56: 119, 1949 Losee FL, Adkins BL: A study of the mineral environment of caries-resistant Navy recruits. Caries Res 3: 23, 1969 Shorr E, Carter AC: Usefulness of strontium as an adjuvant to calcium in the remineralization of the skeleton of man. Hospt Joint Dis Bul 13: 59, 1952 Wasserman RH, Comar CL: Annotated Bibliography of Strontium and Calcium Metabolism in Man and Animals. Miscellaneous Publication 821, Agriculture Research Service, U.S. Dept of Agriculture, U.S. Government Printing Office, Washington, 1961 Sutton A, Shepherd H, Harrison GE et al: Excretion and retention of stable strontium in children. Nature, Lond 230: 396, 1971 Tipton IH, Stewart PL, Martin PG: Trace elements in diets and excreta. Health Phys 12: 1683, 1966 Tipton IH, Stewart PL, Dickson J: Patterns of elemental excretion in longterm balance studies. Health Phys 16: 455, 1969 Browning E: Toxicity of Industrial Metals 2nd Ed. London, Butterworth’s, 1969 Harrison GE, Raymond WHA, Tretheway HC: The metabolism of strontium in man. Clin Sci 14: 681, 1955 Spencer-Lazlo H, Samachson J, Hardy EP et al: 90-Strontium balances in man. Clin Sci 24: 405, 1963 Bronner F, Aubert JP, Richelle J et al: Strontium and its relation to calcium metabolism. J Clin Invest 42: 1095, 1963 Kahn B, Straub CP, Robbins PJ et al: Retention of radiostrontium, strontium, calcium and phosphorus by infants. Supplement to Pediatrics 43 (4) (Part II): 651, 1969 Johnson D, Jr, Mehring AL, Jr, Titus HW: Tolerance of chickens for barium. Proe See Exp Biol Med 104: 436, 1960 Feldman C, Jones FS: Tissue Analyses, Laboratory Progress Report. Ann Prog Report, Internal Dosimetry ORNL 3697, 31 July, 1964 Murphy EW, Page L, Watt BK: Trace minerals in type A school lunches. J Amer Diet Assoc 115, 1971 Gormican A: Inorganic elements in foods used in hospital menus. J Amer Diet Assoc 58: 391, 1970 Howell GP: Chapter III. Elemental Intake, Output and Balances of Reference Man. ICRP Report of Subcommittee II on Permissible Dose for Internal Radiation. Oxford, England, Pergamon Press (in press) Consolazio CF, Nelson RA, Matoush LO et al: The trace mineral losses in sweat. US Army Mod Rcs & Nutr Lab Report 283 : 1, 1964 Losee FL, Adkins BL: Anti-cariogenic effect of minerals in food and water. Nature, Lond 219: 630. 1968 Czerniejewski CP, Shank CW, Bechtel WG et al: The minerals of wheat flour and bread. Cereal Chem 41: 65, 1964

Trace Metals in Man: Strontium and Barium 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68.

517

The Millfeed Manual, The Millers’ Federation, Chicago, Ill 1967 Shorr E, Carter EC: Strontium as an adjuvant in the treatment of post-menopausal osteoporosis in Conference on Metabolic Aspects of Convalescences, 16th Meeting Transactions, Josiah Macy Jr Foundation, 1947 Spencer H: Strontium-85 metabolism in man and effects of calcium on strontium excretion. Sot Exp Biol Med Proc 91: 155, 1956 Geyer CF: Vanadium, a caries-inhibiting trace element in the Syrian hamster. J Dent Res 32: 590, 1953 Tank G, Storvick CA: Effect of naturally occurring selenium and vanadium on dental caries. J Dent Res 39: 473, 1960 Ludwig TG, Cadell PB, Malthus RS: Soils and the prevalence of dental caries. Int Dent J 14: 433, 1964 Anderson RJ: Dental caries prevention in relation to trace elements. Br Dent J 120: 271, 1966 Stookey GK, Roberts RA, Muhler JC: Synergistic effect of molybdenum and fluoride on dental caries in rats. Pree Sot Exp Biol Med 109: 702, 1962 Malthus RS, Ludwig TG, Healy WB: Effect of trace elements on dental caries in rats. New Zealand Dent J 60: 291, 1964 Hadjimarkos DM: Effect of selenium on dental caries. Arch Environ Health 10: 893, 1965 Schroeder HA, Balassa JJ, Tipton IH: Essential trace metals in man: Molybdenum. J Chron Dis 23: 481, 1970