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28 THE RELATION OF SELECTED TRACE ELEMENTS TO HEALTH AND DISEASE RECOMMENDATIONS FOR RESEARCH 1. The chemistry of iodine in soils, and mechanisms of uptake and translocation by terrestrial plants, are important areas for investigation. It is particularly important that io- dine levels in plants be established for areas of high occur- rence of goiter. 2. The chemical speciation of iodine in water is of great importance in any effort to elucidate uptake and metabolic pathways of this element in marine organisms. Improved analytical methods are required for the determination of iodide, iodate, and total iodine. 3. The biochemical pathways and function of iodine in marine animals, especially in those that concentrate it, need investigation. 4. In view of the successful reduction of the incidence of goiter in various parts of the world by increased consump- tion of dietary iodine, it would seem to be highly desirable for public health officials and the medical profession to undertake cooperative efforts to ensure that those suffer- ing from goiter in their areas be informed of proper dietary measures. 5. The distribution of particulate iodine in the atmo- sphere is fairly well documented. However, although a considerable percentage of atmospheric iodine is known to occur in the gaseous form, knowledge of the factors controlling the concentration of gaseous iodine is very limited because of difficulties in quantitative collection. Sources and sinks of gaseous iodine need to be identified. 6. The release of 1311 from nuclear power facilities, hospitals, and other sources should be monitored inten- sively. REFERENCES Becker, V. J., J. H. Bennett, and 0. K. Manuel. 1972. Iodine and uranium in sedimentary rocks. Chern. Geol. 9:133-136. <llilean Iodine Educational Bureau. 1956. Geochemistry of iodine. Shenval Press, London. 1 SO pp. Gaitan, E., R. MacLennan, D. P.lsland, and G. W. Liddle. 1972. Identification of water-borne goitrogens in the Cauca Valley of Colombia. In Proceedings of the Fifth Annual Conference on Trace Substances in Environmental Health, June 29-July 1, 1971, D. D. Hemphill (ed). University of Missouri, Columbia. pp. 55~1. Oddie, T. H., D. A. Fisher, W. M. McConakey, and C. S. Thompson. 1970. Iodine intake in the United States: A reassessment. J. Clin. Endocrin. Metab. 30:659~65. Scrimshaw, N. S. 1964. The geographic pathology of thyroid disease. In The thyroid, J. B. Hazard and D. E. Smith (eds). Int. Acad. Pathol. Monogr. No. S. Williams and Wilkins Co., Baltimore, Md. pp. 100-122. Shacklette, H. T., and M. E. Cuthbert. 1967. Iodine content of plant groups as influenced by variation in rock and soil type. Geol. Soc. Am. Spec. Pap. 90:30-46. Underwood, E. J. 1971. Trace elements in human and animal nutri- tion (3rd ed.). Academic Press, New York. 543 pp. Vought, R. L. 1972. Upward trend of iodide consumption in the United States. In Proceedings of the Fifth Annual Conference on Trace Substances in EnvironmentalHealth, June 29-July 1, 1971, D. D. Hemphill [ ed I. University of Missouri, Columbia. pp. 303-312. Vought, R. L., F. A. Brown, and W. T. London. 1970. Iodine in the environment. Arch. Environ. Health 20:516-522. Wood, F. 0. 1970. Present usage of iodized salt in the United States: Geographic differences. In Iodine nutriture in the United States: summary of a conference of the Food and Nutrition Board, Oc- tober 31,1970. National Academy of Sciences-National Re- search Council, Washington, D.C. World Health Organization. 1960. Endemic goitre. WHO Monogr. Ser. No. 44. World Health Organization, Geneva. p. 33.
IV Chromium WALTER MERTZ, Chairman Ernest E. Angina, Helen L. Cannon, K. Michael Hambidge, A. Wouter Voors Chromium is one of the trace elements known to be essen- tial to animal and human health. Trivalent chromium was identified in 1959 as the active ingredient of the glucose tolerance factor, a dietary agent required for optimal glu- cose utilization in experimental animals and man (Schwarz and Mertz, 1959). It potentiates the effect of the hormone insulin, probably through formation of a ternary complex involving chromium, insulin, and the thiol receptor sites of cell membranes (Christian et al., 1963). Chromium defi- ciency can be produced in a variety of species; it results in impaired glucose tolerance and a reduction of insulin sensi- tivity in peripheral tissues. Under special conditions, chro- mium deficiency can result in growth retardation, fasting hyperglycemia, and glycosuria (Schroeder, 1966). Chro- mium deficient rats have been shown to develop lipid plaques in their aortas, as well as elevated serum choles- terol levels. Whether the effects of chromium on lipid metabolism are direct or mediated through changes in carbohydrate metabolism is not known at present (Schroe- der, 1966). Mild deficiency symptoms occur when diets contain less than 100 ppb; addition of a variety of chro- mium compounds at a level of 1-5 ppm prevents the de- ficiency in rats, mice, and monkeys. Impaired glucose tolerance can also be cured by a single oral dose of 20-40 1-tg of a suitable chromium complex. Toxicity from trivalent chromium fed to experimental animals as part of the normal diet appears to be minimal. 29 Animals have tolerated levels of 100 ppm without adverse effects (Romoser et al., 1961). The hexavalent form of chromium is more easily absorbed and is toxic at high levels. Inhalation of chromium in industrial environments that re- sults in cancer of the lung has been recognized for many years, and less severe exposure results in ulceration of the respiratory mucosa (Baetjer, 1956). Industry has taken ef- fective measures to prevent such exposure. CHARACTERISTIC GEOCHEMISTRY AND SOURCES Chromium has atomic number 24 and an atomic weight of 51.996; it forms naturally occurring compounds with va- lences of 3+ and 6+. In the more common trivalent state, its ionic radius is 0.63 A, and it is isomorphous with All+ and Fe3 +. The only commercial source of chromium is the mineral chromite (Mg, Fe) (Cr, AI, Fe)204 ⢠Rocks Average chromium content is given for different rock types in Table 10. Chromium in igneous rocks decreases sharply as the silica content decreases and shows strong positive correlation with magnesium and nickel content. This chro- mium is present mainly in chromite. Argillaceous sedimen- tary rocks also tend to contain large quantities of chromium;
30 THE RELATION OF SELECTED TRACE ELEMENTS TO HEALTH AND DISEASE TABLE 10 Chromium Content of Various Materials Type of Material Ultramafic and serpentine Basalts and gabbros Andesites, diorites Granitic rocks Limestones and dolomites Sandstones Cays and shales Soils Phosphorites Coal Usual Range Reported, ppm 11()()-3400 6()-420 to-200 2-60 1-200 to-150 3o-3000 Average, ppm 1800 200 so s 11 35 90 40 30cf 10 SOURCES: Turekian and Wedepohl (1961); Bowen (1966); Tureklan and Carr (1960). 4 Phosphorites from Idaho, Wyoming, and Utah average close to 1000 ppm Cr. here chromium is concentrated in phosphorites (and there- fore in phosphate fertilizers), and in bauxite and lateritic iron ores formed by the alteration of ultrabasic rocks (Goldschmidt, 1945). The Phosphoria Formation has an average content of 1 ,000 ppm chromium, with a positive correlation between chromium and phosphate in shale mem- bers of the formation. Chromium deposits in the United States occur as chromite in ultrabasic rocks in Maryland, Montana, North Carolina, Pennsylvania, Texas, Wyoming, Washington, Oregon, and California; in beach-sand deposits in Oregon and California; and in lateritic iron ores in Wash- ington. Chromium is recovered from laterite developed in ultrabasic rocks in Cuba, Brazil, Puerto Rico, Haiti, New Caledonia, Samoa, the Philippines, and French Africa. Chro- mite is also found in the ultrabasic rocks of Turkey, Yugo- slavia, Greece, Rhodesia, the Philippines, Union of South Africa, and U.S.S.R. Soils During weathering, chromium tends to be easily oxidized to soluble complex anions (Goldschmidt, 1945), except in un- usual cases where residual concentrations are formed. Shack- lette and colleagues collected 863 soil samples throughout the United States that averaged 53 ppm chromium and ranged from 1 to 1,500 ppm (Shacklette et al., 1971). The geographic distribution of high and low values suggests a low chromium content in soils of the coastal plain, New York, and Michigan, and relatively high levels in Kentucky, the Rocky Mountain area, and on the West Coast. An aver- age of 100 ppm chromium in soils (5-3,000 ppm) has been reported by Bowen (1966), who found that the largest con- centrations occur in soils derived from basalt or serpentine. Robinson and Edgington (1935) reported that the chro- mium concentration in serpentine soils of Maryland is as much as 2.74 percent Cr2 0 3 and occurs both as an insolu- ble chromite and in a soluble form. A soil traverse run across a contact between serpentine and sedimentary rocks showed a steady decrease from 7,600 to 500 ppm chro- mium in an area of New Zealand (Lyon et al., 1970). Swaine and Mitchell ( 1960) have reported the following distribution of chromium in soils derived from till. chromium extl'rlctt~ble total chromium in with acetic acid in till derived 10il horizon, ppm: 10il horizon, ppm: from: A B c A B c granite and granite gneiss 20 40 20 .15 .10 .11 sandstone 20 25 10 .25 .51 .19 ultra basic serpentine 3500 2000 3000 .31 .24 .63 andesite 80 so 150 .40 .12 .24 mica schist 150 ISO 175 slate 250 250 200 olivine gabbro 300 150 300 gneiss 200 ISO 173 Total chromium ranged from 10-25 ppm in soils on sand- stones to 2,000-3,500 ppm in soils on serpentines, but the differences in acid-extractable chromium were much less. Swaine (1955) reports values of several parts per million in soil profiles derived from rocks high in nickel and chromium in Cuba and Puerto Rico. Soils developed on phosphatic shales of the Phosphoria Formation in eastern Idaho con- tain as much as 1 ,000 ppm chromium (Lotspeich and Mark· ward, 1963). Mertz ( 1969) has expressed the view that chromium de- ficiency in crops is indicated when suboptimal plant growth is raised to normal by the application of chromium to the soil. Areas of low soil chromium might be expected in re- gions underlain by carbonate rocks, or in relatively pure sand as reported in Florida. Some soils in Europe may also contain areas of low chromium (Dobrolyubskii, 1959; Bertrand and DeWolf, 1968). Water Seawater contains less than 1 ppb chromium because a large percentage of the chromium being contributed by rivers is being deposited on the ocean floor. A study of chromium in rivers of the United States showed a range of 0.7-84 pt,/1, the latter amount being found in the Mississippi River (Durum and Haffty, 1963). In a study of surface water by Kopp and Kroner ( 1968), chromium was present in 25 per· cent of the samples with a mean value of 9. 7 pg/1 and a range of 1-112 p.g/1. Durfor and Becker (1964) report a median value of only 0.43pg/l in municipal water supplies with a range of from not detected (N D) to 35 p.g/1. The geo- graphic distribution of chromium levels in waters of the
United States suggests that the higher values are caused by industrial pollution. Chromium is amphoteric and can exist in water in more than one valence state. However, in the weathering pro- cess, chromium as Cr3 + behaves like iron, and little chro- mium would be expected to go into solution under normal pH conditions. With few exceptions, natural waters contain only trace amounts of this element. Little is known of the aqueous species of chromium present in natural brines. The possibility that chromium might be present in the form of ion pairs or complexes, or tied up with organic material has not been adequately in· vestigated. On the basis of standards set in 1968, water with a Cr6 + concentration in excess of 0.05 ppm is rejected for domestic use. Trivalent chromium is not usually encountered in fresh waters, although it is believed to constitute almost 50 per· cent of the chromium present in seawater. One of the major problems in developing reliable data on the regional distribution of chromium in water for concen- trations from 0.5 to 10 ppb has been the lack of a simple, rapid, economic method of analysis yielding accurate repro- ducible results. In recent years this problem has been largely resolved by the introduction of refined techniques. P/Jmts Chromium is present in measurable amounts in all soils and plants, but except in soils formed from serpentine and other ferromagnesian rocks the quantities are very small. Plants grown on the latter must also tolerate high levels of nickel, low levels of molybdenum, and soils that retain water poorly. To obtain background information on chromium in vege- tation, Cannon et aL (1972) sampled four trees growing on unmineralized schist in Colorado in a remote area more than a half mile from the nearest road. First-year leaves, older twigs and wood from two coniferous trees, Pinus ponderosa (Ponderosa pine) and Pseudotsuga taxifolia (Douglas ftr), and two deciduous trees, Populus tremu- loides (aspen) and Acer glabrum (mountain maple) were sampled in May, July, and October. A single collection of roots and fruits was also obtained. The results are shown in Table 11. Chromium, along with iron, appear to be concentrated in maple leaves and in pine and ftr cones. The amounts in leaves are high in the spring but decrease during midsummer. The values average less than 1 ppm, comparable to values reported by Mitchell ( 1954). Schroeder et aJ. (1962) studied samples of vegetation in a Vermont forest and found the average chromium content to be 0.140 ppm (wet wt) and 0.390 ppm (dry wt). Vege- table products for human consumption contained much less chromium-from 0.030-0.050 ppm; fruit averaged 0.020, and grains and cereals 0.040 ppm. In contrast, values Chromium 31 TABLE 11 Variations in Chromium Distribution with Season and Plant Part Chromium Concentration, ppm (dry wt) Douglas Plant Part/Season Aspen Maple Pine Fir Young lea11e1 or needles Sprins <0.15 1.4 0.20 1.3 Summer 0.08 0.62 0.05 0.15 Fall 0.34 1.0 <0.05 0.23 1968 Twigs Sprins 0.15 0.60 0.66 1.7 Summer 0.11 0.11 0.13 0.15 Fall 0.14 0.14 0.63 0.23 Older twigs Sprins 0.31 0.60 0.77 0.50 Summer 0.14 0.31 0.55 0.36 Fall 0.18 0.24 0.96 0.52 &eds or cones <0.06 1.4 1.6 Wood 0.35 0.66 0.30 SOURCE: Cannon et tiL (1972). as high as 200 ± 20 ppm (dry wt) were obtained in the ash of twigs from an Engelman spruce growing on Phosphoria Formation (Lotspeich and Markward, 1963). Plants col- lected from serpentine areas of New Zealand contained from 10 to 34,000 ppm in ash, or 1 to about 3,400 ppm (dry wt), with the highest value in a specimen of lichen (Lyon et al., 1970). Reporting on the accumulation of chromium in AUysum markgrafi growing on chromium deposits in Yugo- slavia, Karamata (1967) said that the plant contained from 10 ppm chromium in background areas to 3,000 ppm in the ash in three areas of chromium deposits. Whittaker (1954) has characterized serpentine areas as being sterile and unproductive, with unusual floras of nar- rowly endemic species and strikingly physiognomic vegeta· tion. Such areas are commonly populated by dwarf pine, dwarf shrubs, mosses, lichens, ferns, and certain genera of the laurel, pink, chickweed, and borage families. Serpentine vegetation is not a seral stage in the vegetation of other soils, but a distinct climax of its own particular successions. Walker ( 1954) has pointed out that only plants with the ability to extract enough calcium from the low level of ad· sorbed calcium in acid clay soil can grow on serpentine be· cause the magnesium/calcium ratio is high. Evidence that total chromium content may not be re- sponsible for the poor growth on some serpentines was obtained from a forest maintenance project in Czechoslo- vakia. Nemec (1954) reported that fertilization of growth- stagnated hardwood plantations (alder, basswood, hazelnut) with ground limestone and diabasic dust resulted in a con- siderable decrease in nickel and cobalt content in the leaves and reduced plant failure in spite of the fact that the addi· tion of lime increased the chromium content. On the other
32 THE RELATION OF SELECTED TRACE ELEMENTS TO HEALTH AND DISEASE hand, unpublished work by R. L. Chaney of the U.S. De- partment of Agriculture suggests that nickel and chromium in the serpentines of Maryland are indirectly responsible for the infected soils. Biologic effects of naturally high levels of chromium in soil (I ,370-2,740 ppm) have been reported (Monier-Williams, 1950) in South Africa, where chlorosis has been observed in citrus. Pot experiments show toxic effects on barley from 50 ppm chromium as chromate or potassium dichromate, but amounts of less than 50 ppm stimulated growth (Voelcker, 1924). Hunter and Vergnano (1953), who studied the effects of potassium dichromate on oats, found that at 5 ppm the plants were generally normal; at 10 ppm the plants were small and most of the leaves were slightly chlorotic; at 25-50 ppm the plants were stunted, with nar- row reddish brown leaves and small necrotic spots. In water experiments (Scharrer and Schropp, 1935) with corn seed- lings, chromium concentrations in Richter's solution [chro· mium as Cr2(S04 h] of 1 mg/kg stimulated growth;>l-10 mg/kg reduced growth; and 100 mg/kg almost completely inhibited growth, nearly destroying the plants. Experiments repeated with Na2 Cr04 ⢠1 OH2 0 showed a similar stimula- tion at 0.1-1 mg chromium per kilogram, but larger amounts were harmful. Top growth was damaged more than were the roots. In consideration of the essentiality of chromium to plant life, Mertz (1969) has reviewed the effects of chromium ap- plied to crops in Germany, France, Poland, and Russia. Both the weight of grapes and enzyme activity were increased in Russia by adding 5 ppm to the soil (Dobrolyubskii, 1959). Addition of 0.5 ppm or less of chromous acetate to soil in Germany had a very beneficial effect on carrots, barley, lupines, and cucumbers, as well as on wheat. These results were conftrmed and extended in water and sand cultures in which trivalent, but not hexavalent, chromium increased yields of wheat, rye, oats, com, and peas, and particularly stimulated root growth. Bertrand (Bertrand and DeWolf, 1968) has recently studied the effect on potato growth of chromium added to a low-chromium soil in France. Ap· plication of 40 g of chromium (as the alum) per hectare in- creased the potato yield by 42 percent or from 32.7 tons in the control areas to 46.5 tons/ha in the treated areas. The soil in which these experiments were performed orig- inally contained only 65 ppb of extractable chromium, and this amount had been further depleted by subsequent crops. These data suggest that chromium is essential to plants and point to the possible existence of areas of chromium deficiency. One-hundred and eighteen vegetable samples collected from the coastal plain in Georgia averaged <0.02 ppm (dry wt) (Shacklette eta/., 1970). Experiments de- signed to establish the requirement for chromium in plants are in progress at the Soil, Plant, and Nutrition Laboratory at Ithaca, New York, of the U.S. Department of Agriculture. Animals and Man Available data are insufficient for ftrm conclusions on how the geochemical environment may influence the chromium status of our population. High chromium concentrations have been detected in the soils of the northwestern states, and very low concentrations are known to occur in the southern part of Florida. So far these data do not support a connection between the variation of chromium in the environment and variation in disease incidence. Of major importance to the understanding of chromium metabolism in man is the fact that the biological effect of chromium depends very much on the compound in which the element is present. The optimal form is the glucose- tolerance factor, a yet unidentified, water-soluble chro- mium complex of low molecular weight (Mertz and Rogin- ski, 1971 ). Only in this form does chromium behave like an essential element with regard to homeostatic regulation, placental transport, and physiological responses (e.g., to an insulin challenge). Animals, as well as man, have a limited capacity to synthesize inorganic chromium into the glu- cose tolerance factor; the rate of this synthesis, which probably occurs in the intestinal flora, may be a very im- portant determinant of the chromium nutrition of indi- viduals. Most animal products contain much of their total chromium in this efficient form. Seeds have moderate con- centrations of glucose-tolerance factor, whereas leafy plants do not (Toepfer et aL, 1973); these data indicate that de- termination of total chromium in any material gives little information about its biological value. EFFECTS ON HEALTH With chromium, the major concern with respect to human health is deficiency rather than excess. Chromium defi- ciency results in impaired glucose tolerance (Mertz, 1969). Glucose tolerance in man declines with age, and a large proportion of elderly Americans have a somewhat abnormal glucose-tolerance test. Streeten et al. ( 1965) have shown that as many as two thirds of the elderly population of those sampled in the United States have abnormal glucose- tolerance tests, and tissue chromium levels in the United States also decline with age (Schroeder et aL, 1962). Re- peated pregnancies, as well as diabetes, are associated with decreased tissue chromium levels (Hambidge et aL, 1968; Hambidge and Rodgerson, 1969). High intakes of refmed sugars, which furnish almost no chromium, result in a sig- nificantly increased urinary chromium excretion and can lead to overall negative chromium balance (Schroeder, 1968). All these facts suggest that part of our population may be in a state of marginal chromium deficiency. Trivalent chromium, when administered in the form of simple compounds (i.e., hexaaquo, acetato, etc., com-
plexes) is poorly absorbed from the intestines (Mertz, 1969). Regardless of dietary history or amount adminis- tered, only O.S-3 percent of a given dose is available to the organism. Excretion of the absorbed chromium is almost entirely urinary. Circulating chromium is not in equilibrium with tissue stores; therefore, blood concen- tration of chromium is of little value as an indicator of the chromium nutritional state, except in certain special conditions (Glinsmann eta/., 1966). Chromium concentrations in animals range from several hundred parts per billion in liver, spleen, and kidney, to only 0.5-5 ppb in blood serum. Hair is a good indicator of pre- vious history of chromium nutrition; urinary level repre- sents a reasonable picture of recent dietary intake. A valid criterion for the diagnosis of chromium defi- ciency is the positive response of subjects with impaired glucose tolerance to physiological amounts of chromium. Glinsmann and Mertz (1966) demonstrated that ingestion of 150 p.g of chromium restored impaired glucose tolerance to normal in approximately half of the subjects tested un- der the strict control of a metabolic ward. Hopkins and Price ( 1968) showed the same pattern in middle-aged sub- jects, and Levine et al. (1968) found this to be true for aged people. A double-blind study on the effect of chro- mium on geriatric subjects is now under way. Pronounced chromium deficiency resulting in glucose intolerance occurs in children with protein-calorie mal· nutrition, but not in all areas studied. Chromium-responsive impairment of glucose tolerance was present in children from the Jerusalem area of Jordan (Hopkins et al., 1968), but not in children from the Jordan River Valley; this was true for Turkey (Gurson and Saner, 1971) and Nigeria (Hopkins et aL, 1968), but not for Egypt (Carteret a/., 1968). POLLUTION Chromium content in water, air, soil, and plants is probably increasing as a result of industrial and motor pollution in populated areas. A cursory look at the geographic distri- bution of chromium levels in municipal water supplies (Lieber and Welsch, 1954) suggests industrial pollution as a source. Waste from many types of industry is adding chromium to our rivers today. During World War II, large areas of groundwater in two counties of Long Island (Cannon and Anderson, 1971) were contaminated with chromium from aircraft plants and remained polluted for many years. It is possible that the additions of chromium to en- vironmental materials of naturally low chromium may be beneficial rather than harmful. Recent studies of the ef- fluent from the Four Corners Electrical Power Plant in Fruitland, New Mexico, show increased levels of chro- Chromium 33 mium and other metals for a radius of a few miles around the plant. As pointed out by Hem (1959), natural chromates are rare. Chromium under strongly oxidizing conditions can be converted to the Cr6+ state and in water can occur as the chromate (Cr04 2 -) anion. When high values of Cr04 2 - are present in water, this is usually assumed to be the result of industrial-waste pollution. Under these conditions, high values of chromate anions can occur in water of ordinary pH. Contaminated groundwater with a hexavalent chromium level of 25 ppm has been reported in one well in Long Is- land, which was the sole source of water for one farm family. Surprisingly, no adverse reaction was noted. RECOMMENDATIONS FOR RESEARCH In view of the evidence that suboptimal human chromium nutrition may be widespread in this country, it is recom- mended that the possible contribution of the geochemical environment to human deficiency of this element be de- termined. The following actions are therefore proposed: 1. Recently developed analytical techniques for the measurement of nanogram or subnanogram quantities of chromium should be perfected and utilized for the determination of chromium in soils, water, plants, ani- mals, and man. 2. A determination should be made as to whether the plant content of chromium varies with the type of soil on which the plant grows. In particular, chromium content should be compared in crops grown in areas where rocks and soils have high, medium, and low chromium concen- trations. If a positive correlation is found, these studies should be extended to a comparison of chromium levels in livestock and humans in the same areas. 3. Studies of human chromium nutrition should be greatly intensified; specifically, populations that have a high incidence of diabetes mellitus should be examined, and in particular those that subsist largely on local pro- duce and drink local water. If evidence of an etiological role of chromium deficiency results from these investi- gations, a detailed study of the geochemical environment in these specific areas should be undertaken. REFERENCES Baetjer, A.M. 1956. Relation of chromium to health. In Chromium, J. J. Ucly (eel). Reinhold PubL Corp., New York. pp. 76-104. Bertrand, D., and A. DeWolf. 1968. Requirement for the trace ele- ment chromium in the growth of potatoes. C.R. (Acad. Sci., Paris) Ser. D. 266:1494-1495. (In French.) Bowen, H. J. M. 1966. Trace elements in biochemistry. Academic Press, New York. 241 pp. Cannon, H. L., and B. M. Anderson. 1971. The geochemist's involve-
34 THE RELATION OF SELECTED TRACE ELEMENTS TO HEALTH AND DISEASE ment with the pollution problem. In Environmental geochemistry in health and diseue, H. L. Cannon and H. C. Hopps (eds). Geol. Soc. Am. Mem. No. 123. Geological Society of America, Boulder, Colo. pp. 155-177. Cannon, H. L., C. S. E. Papp, and B. M. Anderson. 1972. Problems of sampling and analysis in trace element investigations of vege- tation. Ann. N.Y. Acad. Sci. 199:124-126. Carter, J.P., A. Kattab, K. Abd~l-Hadi, J . T. Davis, A. El Gholmy, and V. N. Patwardhan. 1968. Chromium (Ill) in hypoglycemia and in impaired glucose utilization in kwashiorkor. Am. J. Clin. Nutr. 21:195-202. Cuistian, G. D., E. C. Knoblock, W. C. Purdy, and W. Mertz. 1963. A polarographic study of chromium-insulin-mitochondrial inter· action. Biochim. Biophys. Acta 66 :420-423. Dobrolyubskii, 0. K. 1959. The effect of chromium trace fertilizer on the biochemical processes of the grape. Biochem. J. 24:577- 582. (Transl. from the Russian.) Durfor, C. N., and E. Becker. 1964. Public water supplies of the 100 largest cities in the United States, 1962. U.S. Geol. Surv. Water Supply Pap. No. 1812. U.S. Government Printing Office, Washington, D.C. 364 pp. Durum, W. H., and J. Haffty. 1963. Implications of the minor- element content of some major streams of the world. Geochim. Cosmochim. Acta 27:1-11. Glinsmann, W. H., F. J. Feldman, and W. Mertz. 1966. Plasma chro- mium after glucose administration. Science 15 2: 124 3-1245. Glinsmann, W. H., and W. Mertz. 1966. Effect of trivalent chromium on glucose tolerance. Metabolism 15:510-519. Goldschmidt, V. M. 1945. The geochemical background of minor element distribution. Soil Sci. 60: 1-17. Giirson, C., and G. Saner. 1971. Effect of chromium on glucose utilization in marasmic protein-<:alorie malnutrition. Am. J. Clin. Nutr. 24:1313-1319. Hambidge, K. M., and D. 0. Rodgerson. 1969. A comparison of the hair chromium levels of nulliparous and parous women. Am. J . Obstet. Gynecol. 103:320-321. Hambidge, K. M., D. 0. Rodgerson, and D. O'Brien. 1968. The con- centration of chromium in the hair of normal children and chil· dren with juvenile diabetes mellitus. Diabetes 17:517-519. Hem, J . D. 1959. Study and interpretation of the chemical charac- teristics of natural water. U.S. GeoL Surv. Water Supply Pap. No. 1473. U.S. Government Printing Office, Washington, D.C. 269pp. Hopkins, L. L., Jr., and M.G. Price. 1968. Effectiveness of chro- mium (III) in improving the impaired glucose tolerance of mid- dle aged Americans (Abstr.)./n Western Hemisphere Nutrition Congress, Puerto Rico. American Medical Association, Chicago, IlL p. 235. Hopkins, L. L., Jr., 0. Ransome-Kuti, and A. S. Majaj. 1968. Im- provement of impaired carbohydrate metabolism by chromium (Ill) in malnourished infants. Am. J. Clin. Nutr. 21:203-211. Hunter, J. G., and 0. Vergnano. 1953. Trace element toxicities in oat plants. Ann. Appl. Bioi. 40(4):761-777. Karamata, S. 196 7. 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