Geochemistry and the Environment: Volume I: The Relation of Selected Trace Elements to Health and Disease (1974)

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2 THE RELATION OF SELECTED TRACE ELEMENTS TO HEALTH AND DISEASE of element distribution should be compared with patterns of animal and human disease. One fruitful approach for judging whether causal rela- tionships do exist is to compare maps of geochemical provinces, soil types, climatic conditions, plant chemis- try, and water chemistry with similar patterns of animal or human disease incidence. Against this natural back- ground, man's effect on the environment can be measured and evaluated. Inorganic ions migrate from rocks to soils and waters, and thence into plants, animals, and fmally into man. Many factors affect the availability or transport of mineral sub- stances along the food chain and their influence on the ultimate well-being of animals, including man. These ele- ments may be utilized or stored in a different manner by different plant and animal species. Small excesses or de- ficiencies of any one ion in the food chain, when present over a long period of time, may have a measurable effect on the life of an individual. Clues to the extent of this effect may be provided by large, but short-term, changes in the release of metals into the environment by man's activities. The levels of concentration in the environment of sev- eral of the trace elements considered at the Workshop- fluorine, cadmium, zinc, lead, and chromium-appear to be rising because of man's activity. The essential, optimum, and critical levels of these metals, their known .beneficial or deleterious effects on plants and animals, and the increases in concentration that are likely to occur with time were considered. Increases that can be tolerated depend largely on the natural background levels in the particular environ- ment in which the contamination occurs. Maximum limits of tolerance set by legislation should, therefore, vary from place to place, depending on a careful consideration of local background values. The need for reliable baseline data for monitoring the environment requires increased use of standard samples to obtain chemical analyses that can be compared and vali- dated. Analytical methods should be sufficiently sensitive to detect low levels of trace substances in plant and animal tissue or in the physical environment. Methods of sampling. types and long-term storage of standard samples, data storage and retrieval, and data plotting were all considered, and the basic steps needed to ensure reliability and uni- formity of data discussed. The participants agreed that a similar multidisciplinary workshop should be held to consider another group of ele- ments and their possible relationship to disease. Following this second overview, investigations of pertinent interfaces would be of considerable value. The answers can only be obtained by multidisciplinary teamwork in uninterrupted, long-term studies. The ultimate achievement may be con- structive regulation of the chemical environment; the im- mediate concern is the formulation of appropriate recom- mendations for high-priority research and positive action. The following sections specify concepts of the various Work Groups regarding the present state of the art and how best to approach specific problems. HELEN L. CANNON Workshop Chainnan

I Overview HOWARD C. HOPPS, Chairman Emest E. Angino, James E. Banta, Kenneth C Beeson, Donald J. Horvath, Richard Janda, Everett A. Jenne, Robert Tardiff, E. J. Underwood Close examination can teach us much about the detalls of problems, but universal truths often emerge from a general survey. The survey approach was used in this examination of the relations between geochemical environment and health and disease. Such questions were asked as the follow- ing: Where and under what conditions does the geochemical environment relate to health and disease? How and under what conditions are chemical data on rocks and waters re- lated to soils, soil data to plants, plant data to subhuman animals, and animal data to human health and disease? Given present knowledge, is it possible to infer that a direct relation exists between geochemical environment and hu- man health?lf not, what kind of indirect relationships exist, and how can they be determined? Mechanisms for relating geochemical environment and human health are indicated in Figure I. From these mech· anisms, it is evident that determination of the levels of trace elements in the environment, and of the geochemical and other factors that influence these levels, is essential. However, the value and meaning of these determinations are limited without satisfactory data on the minimum and maximum intakes compatible with the long-term health and weD-being of man. The amounts of trace elements responsible for severe deficiency or acute intoxication are, for the most part, weD established, but the biological con· sequences of continuous exposure to the lesser amounts present in the modem environments are largely unknown. 3 This knowledge is particularly pertinent in dealing with harmful elements such as arsenic, cadmium, lead, and mercury, and with marginally deficient elements such as zinc and chromium. Long-term studies in man are there· fore urgently needed to assess the minimum adequate and maximum safe levels of intake of the trace elements from food, the water supply, and the atmosphere. Of these sources, food should receive highest priority in studies con· cemed with deficiency because the major portion of trace elements ingested comes from food, rather than water. Food provides roughly 4-times the quantity of trace elements that water does (Underwood, 1971 ). Every organism responds in a unique manner to its total environment, influenced by genetic traits it possesses, its age, sex, and state of health. Moreover, there is a difference between "normal" requirements for trace elements and re· quirements for larger-than-usual amounts to meet particular stresses or to treat specific diseases: For example, the amount of zinc required to support optimal wound healing, or of fluorine required as prophylaxis against osteoporosis, will be very much higher than otherwise. Such requirements will be in the toxic range for some individuals. With fluorine, for example, the amount taken by an adult woman to help prevent postmenopausal osteoporosis would almost certainly cause mottling of tooth enamel, and perhaps other effects among young children. Table I lists the concentrations of some elements in vari-

TABLE 1 Concentrations of Some Elements in Various Natural Materials (Michael Fleischer) Type of Concentrations by Elements, ppm Material Cadmium Ouomium Copper Fluorine Iodine Lead Lithium Molybdenum Selenium Zinc Ultramafic 0-0.2 IOOo-3400 2-100 0.06-().3 igneous"•b o.os (?) 1800 15 0.1 o.s 0.3 o.os 40 Basaltic 0.006-().6 4o-600 3o-160 2o-1060 2-18 3-SO 0.9-7 48-240 igneous"•b 0.2 220 90 360 o.s 6 20 l.S o.os 110 Granitic 0.003-().18 2-90 4-30 2o-2700 6-30 1o-120 1-6 S-140 igneous"•b 0.15 20 IS 870 o.s 18 3S 1.4 o.os 40 Shales and o-n 3o-S90 18-120 1o-7600 212-380 16-SO 4-400 18-180 clays"•b,c 1.4 120 so 800 s (?) 20 80 2.6 0.6 90 Black shales 0.3-8.4 26-1000 2o-200 1- ISO 1-300 34-1500 (highqd 1.0 100 70 20 10 100 (?) Deep sea clays"•b 0.1-1 11-SO o.s 90 250 1300 3S (?) 80 57 27 0.17 165 Limestones"•b,c,e o-1200 0.4-29 S-10 o.os 10 4 220 s 9 7 0.4 0.08 20 Sandstones"•b,c 1o-880 1-31 7-90 2-41 o.os 3S 2 180 1.7 7 30 0.2 o.os 16 Phosphorites f o-170 3o-3000 1Q-100 24,000-41,500 Io-30 3-300 1-100 2o-300 30 300 30 31,000 10 30 18 so Coals (ash)4 1o-IOOO 2-40 40-480 1-11 2-SO 2-300 0.2-16 0.4-3.9 7-108 2 20 1S 80 4 IS so s 21 so 4 Turekian and Wedepohl (1961}. dvine, J. D., and E. B. Tourtelot, Econ. Geol., 65, fGulbrandaen, R. A., Geochim. Cosmochim. Acta, 30, bParker (1967). 223 (1970). 769 (1966). CBecker et al. (1972). ewedepohl (1970). KU.S. Geoloaical Survey (1972). NOTE: The upper r~gure Is the range usually reported, the lower figure the average.

Overview S ~ Radioactive Materials TRACE ------ _ ELEME' ., Ar lomaatnu·rmaladsoeurces] . ' t lc ---------~ HEALTH/DISEASE WATER [ind~strial contamination J santtary wastes treatment methods I quantity importation ~FOODS [processing J ROCKS AND --------1.,_ CROPS AND ~ storage SOILS [:~::~:;:i~es] ANIMALS [:i~::~sharvest] preparation fungicides herbicides storage FIGURE 1 Schema showing mecllanisms by which trace elements find their way to man, influencing the quality of his health or producing disease (Kenneth C. Beeson). ous natural materials. These data can serve as guidelines for comparing the average concentration of the various elements in different types of geologic materials. Although the ranges of concentrations are often very wide, the average may be useful in defming geographic areas where, because of a pre- dominance of one or two rock types, high or low levels may be expected in the substrate. Table 2 extends the information listed in Table 1 to in- clude provisional data on soils, water, grasses, legumes, vege- tables, and fruits. The median values in Table 2 probably represent ordinary adequate levels of these elements in wa- ters, soils, and foods. In some instances, it was necessary to take weighted averages of several medians. In general, two kinds of information concerning effects of trace elements on human health should be explored. First, much more comprehensive disease maps are needed, showing morbidity and mortality at a level of resolution involving areas as small as counties, with reliable trace ele- ment data on natural materials indigenous to those areas. Where anomalous amounts (demonstrating either deficiency or excess) are present, it should be determined whether this situation can be correlated with actual intake by plants and animals and, if so, whether such exposure can be related to diseases in animal and human populations of the region. To do this would require, at the very least, more extensive anal- yses of soils, plants, and waters together with an indication of the approximate amounts actually ingested. More detailed information from the subgroups, is presented below by individual authors. BASELINE DATA (Everett A. Jenne) The term baseline data has caused much confusion because it is used to describe quite different sorts of data. For exam- ple, it is applied to determinations of the median and the range of concentrations of some constituent in the material of interest before significant man-induced pollution. • The term baseline data is also applied in other ways. It is applied, for example, to present values of the trace element content of stream waters to assess time changes-particularly to learn if pollution of the waterways is increasing or decreasing. Reference is also often made to baseline samples. This term implies that the particular sample is representative of some particular population and has been preserved in such a way that the desired information can be extracted. "AVAILABILITY" OF TRACE METALS (Everett A. Jenne) The trace element content of silicate minerals generally con- tributes very little to the biological-geochemical cycling of trace metals at any one time. Thus, although total analysis- i.e., alkali fusion or hydrofluoric acid (HF) decomposition- may provide informative data, those nonsilicate mineral *These values are also referred to as background data. However, the term background values implies, in addition, that natural excesses are ordinarily minimal.

TABLE 2 Predicted Concentrations of Trace Elements in Unrnineralized and Uncontaminated Areas (Helen L. Cannon) Predicted Concentrations Finished Municipal Water,IA8fl Plants, ppm (dry wt) Soils,ppm"-e (approx. ppb)f-1 Foraae Grassese.i-q Forqe Legumesf,/,m,o,r Vegetables and Fruitse.l.r-u No. No. No. No. No. Element Samples Median Ranp Samples Median Ranae Samples Median Ranae Samples Median Ranae Samples Median Ranae Cadmium 0.06 0.01...().7 726 -1.0 <l.G-10 47 0.37 0.03-2.4 4 0.04 0.04...().05 14 0.10 0.01-G.96 (riven) Ouomium 104 40 7-300 100 0.43 ND-35 48 0.61 0.42...().95 10 0.35 0.13-2.2 157 <0.06 <0.06-10 Copper 54 30 7-150 100 8.3 <0.61-250 1196 4.4 0.29~0 455 10 l.S-40 157 4.0 <1-30 Auorine 311 270 1G-7070 100 400 SG-7000 14 0.69 0.2G-3.0 3 i.2 2.1-7.3 128 3.4 0.028-134 Iodine 32 5.85 l.S-13.5 14 4.0 l.G-16 124 0.1 0.002...().77 177 0.18 0.04-1.3 885 0.2 0.002-95 0\ (rainwater) Lead 54 20 1G-SO 100 3.7 ND-62 31 1.7 <0.8-4.0 4 2.5 ND-3.6 101 1.S <l.S-18 lithium 421 10 S-200 100 2.0 ND-170 48 <0.4 0.01-4.4 13 0.20 0.01...().40 21 0.40 0.01-650 Molybdenum 2.0 0.2-S 100 1.4 ND-68 79 0.91 <0.06-28 101 1.3 ND-13.8 157 0.4 <0.2-10 Selenium 0.1-2 <0.04-100 43 0.2 0.1-400 205 0.26 <0.01-9 4 0.2 0.075...().7 20 0.05 0.01-G.20 (surface) Zinc 36 so 25-190 7U 20 <l.G-400 300 24 2.G-80 305 38 11.4-210 157 27 2.5-200 (riven) "Swaine (1955). 11 Reeden, W. W., B. Hitchon, and A. A. Levinson, Geoclllm. 11 Allaway (l968b ). bMitchell eut. ( 1957). Comtoclllm. Acta, J6, 815 (l97l). 0 Hodpon et at. ( 1971 ). cRobinson and Edpngton ( 1946). IMiller, D. F.,Natl. Aclld. Set. Publ. No. 285 (1958). PErdman et al. (1973). dMitchell, J. H., SoU ScL, 52, 365 (1941). IWUiiams, R. Darrington, Commonw. Agrlc. Bur. MlmeOfr. qFletcher and Brink ( 1969). eChllean Iodine Educational Bureau (1956). Publ. No. I (1959). 'Beeson ( 1941 ). fourfor and Becker ( 1964 ). kL. E. Washburn, written communication (1960). .rFleischer and Robinson (1963). .fDurum and Haffty (1961). tu.s. Geological Survey, unpubllalted data . 'McClure, F. J., U.S. Public Health Sen. Publ. No. 825 (1962). mPrice et at. (1955). "Morris, V. C., and 0. A. Levander,/. Nutr., 100, 1383 (1970). NOTE: NO = not detected.

trace element fractions with much higher mobilities or avail- ability are considerably more significant with respect to pos- sible deficient or toxic levels in plants, and consequent po- tentially deleterious effects in animals, including man. Measurements of the available fraction of a given trace metal for a given plant crop have met with limited success. One of the several important reasons for this is that plant roots draw from many microenvironments within their rooting depth, and these may vary considerably in pH, Eh (oxidation-reduction potential), microbiological popula- tion, and soluble organic complex formers. In addition, there is great species variation and considerable varietal variation among plants with regard to their ability to ex- tract trace metals from soils and the minimum quantity of trace metals they require for maximum production. More- over, the relative efficiency of the extractant for the various trace element fractions or reservoirs (e.g., organics, carbon- ates, manganese and iron oxides, and clays) may differ greatly from that of plants. Much effort has been expended to improve methodology in this area. Literally dozens of methods exist for the esti- mation of available trace elements from soils and stream sediments. Typically, these methods differ either in choice of acid or acid strength, or in the choice of other complex- ing agents and their concentrations. Future work in this general area might profitably be di- rected toward (I) estimation of the total biodiagenetically available trace element fraction (i.e., the nonsllicate frac- tion); and (2) development of methods for the selective extraction of that trace element fraction present in organics, carbonates, iron and manganese oxides, and in silicates (clays). GROUNDWATER GEOCHEMISTRY (Ernest E. Angino) One of the most difficult problems that has to be faced in a study of the relation between trace element geochemistry and health and disease is the inability to isolate subjects from the immense complexities caused by the nomadic character of people and the fact that most consume food that is derived from many different places-such as orange juice from Florida,lettuce from Texas, beef from Kansas, and potatoes from Idaho. For this and other reasons, trace element intake from local water supplies has received in- creased attention in scholarly investigations. Rural areas, where populations tend to be more geographically stable and water supplies less complex, seem to offer an ideal locale for such studies. Here, however, there is a major deficiency of data; little, if any, trace element data are available for the major groundwater aquifers of the United States. This dearth of chemical data is a problem of fust priority and warrants a major research effort. ACCUMULATOR PLANTS (Kenneth C. Beeson) Overview 7 There are many plants that accumulate mineral elements to an anomalous degree: These are the so-called accumullltor plants. Some of these plants are feed or food crops; others are consumed occasionally by animals, including man. Thus, accumulator plants may represent major sources of trace element intake. Among these accumulator plants, the ability of the As- tragalus (locoweed) species to concentrate selenium has long been recognized (Death et al., 1934); certain tree spe- cies of the Ny1111 (black gum) and the C/ethra (alder) genera are accumulators of cobalt on soils where other species con- tain concentrations well below normal; 1/e:x glllbra (a holly) is an accumulator of zinc (Beeson et al., 1955). The musk- melon, zinnia, and sweet clover are reported to be accumu- lators of boron. One of the more striking examples has been reported by Robinson (Robinson and Edgington, 1945) who states that the brazil nut may accumulate as much as 4,000 ppm of barium. He also reported that the hickory and pecan trees (Carya genus) can accumulate large quantities of the rare elements in the leaves; no data for hickory nuts are available. Cannon ( 1969) has listed a number of unusual ele- ments found in plant tissue, sometimes in high concentra- tions. Data compiled by Helen L. Cannon are presented in Table 3. (See also Table 2.) In solution culture work, Beeson and Lyon (1948) found up to 8,000 ppm of manganese, 4,000 ppm of molybdenum, · 1,500 ppm of zinc, and 1,000 ppm of boron in apparently edible turnip leaves. Only iron and copper in high concen- trations were rejected by the plant. Even greater quantities TABLE3 Quantities of Rare Elements Found in Certain Accumulator Plants (Helen L. Cannon) Accumulations by Plant, ppm Hickory Pecan Brazil Leavesb Element Nutt' Nutt' (6 samples) Beryllium <1 <1 S-20 Yttrium <10 <10 1SO-SOO Scandium <10 <10 <10 Lanthanum <SO <SO 100-SOO Barium 1,000 >10,000 100-S,OOO TOTAL (rare elements) ND ND 981 Ash, percent 2.0 3.S 7.1-10.7 0 U .S. Geological Survey, unpublished data. bRoblnson and Edslnaton. (1945) reported 981 ppm (dry wt) of rare elements In the leaves of hickory but only 5 ppm In the nut meats. NOTE: ND = not detected.

8 THE RELATION OF SELECTED TRACE ELEMENTS TO HEALTH AND DISEASE of these micronutrients were taken up by the tomato plant and stored in the leaflets. Identification of additional accumulator plants used as food and feed should be determined by worldwide surveys, together with quantitative data on the amounts actually consumed (showing where, when, and under what circumstances). Since few crops grow everywhere, the work should be concentrated in certain climatic zones, and soil differences considered within each zone. The corn survey of the Agricultural Board of the National Re- search Council would be a useful model for such a study (Schneider et al., 195 3). The results of an investigation of this sort could be used to diVide food crops into three classes: (1) those that reject a specific element or elements present in an available form in the nutrient media; (2) those that absorb an element in excess when it is present in high concentrations in the media; and (3) those that are able to absorb excessive quan- tities of an element present in low concentrations or in rela- tively insoluble forms from the nutrient media. In general, those food crops in class (2) are probably in the majority; however, those in class (3) are likely to pose special prob- lems with respect to animal or human disease, and are therefore of greater importance to this study. EFFECTS OF AGRICULTURAL TECHNOLOGY ON TRACE ELEMENT ENTRY INTO THE FOOD CHAIN (Donald J. Horvath and Ernest E. Angino) The effects of agricultural technology on trace element con- tent of plants can be profound under certain conditions, and Allaway ( 1968a) has discussed some of these condi- tions. Important variables are listed in the outline below. 1. Choice of Soil 2. Choice of Crop a. Species b. Variety 3. Choice of Harvesting Date (plant maturity) 4. Choice of Plant Portion to Be Harvested 5. Application of Soil pH-regulating Material (usually lime) This factor has a major influence on metal uptake in grasses, for example. In general, the plant level of molybde- num rises, and levels of copper, zinc, manganese and iron decline, as pH is raised from the acid range toward neu- trality. 6. Application of Plant Macronutrients (nitrogen, phos- phorus, and potassium) Although there is no clear instance of frank animal disease related to trace elements of major interest to the Workshop occurring from intensive nitrogen-phosphorus- potassium (NPK) applications, a reasonable case can now be made for (1) an inverse relationship between NPK appli- cations and an animal's intake of the essential elements sodium and magnesium, and (2) a direct relationship for phosphorus. Evidence suggesting altered trace metal and element status is discussed in the paragraphs below. a. Nitrogen Nitrogen, at intensive levels {>150 kg/ha), was associated with an increased incidence of goiter in sheep (Reid et aL, 1969) and rats (Lee et aL, 1970) in the absence of supplemental iodine. Forage level of iodine may be lowered with intensive nitrogen fertilization (Alder- man and Jones, 1967). On the other hand, the levels of iodine may be raised substantially if Chilean nitrate is the source of nitrogen. The short-term effect of intensive nitrogen may be an increase in plant copper (Raymond and Spedding, 1966) and liver copper of weanling Iambs (Bubar and Reid, un- published data, 1972). There may be some effect of most nitrogen fertilizers on soil acidity that could increase plant copper. However, in trials of 6- (Kreil et aL, 1966) and 16- years' (Bosch, 1954) duration, there was an opposite trend, perhaps caused by reduction of available soil copper through increased crop removal. (In the 16-year study, the response measured was serum copper of grazing cattle.) There is a trend toward increased zinc levels in plants following intensive nitrogen applications in some instances(Raymond and Spedding, 1966), but little change is likely if pH does not decline appreciably. Reports of consistent effects of nitrogen on other elements of interest to the Workshop have not been located. b. Phosphorus Overfertilization with phosphorus is less likely than with nitrogen because there is less immediate payoff in crop yield. Intensive phosphorus applications are most likely to reduce crop zinc level, though treatment in· teractions in soil may occur (Keefer and Singh, 1971 ). Re- ports of effects on other elements of interest to the Work· shop have not been found. c. Potassium Intensive potassium applications appear to have little effect on the elements of interest to the Work- shop. d. Other The trend to higher analysis fertilizers (those with a greater N P K concentration) has been accom- panied by increasing purity of the sources of nitrogen, phosphorus, and potassium used. The result is that fewer contaminant trace elements are applied, some of which might be beneficial. A recent report (Pope, 1971) sug- gests that this practice has led to a deficiency of sulfur in crops. An extensive compilation of trace element analyses offertilizers was prepared by Swaine ( 1962). It includes values for sewage used as fertilizer, as well as more conven- tional chemical fertilizers and liming materials. The follow- ing data are adapted from this source:

Iodine: up to a few hundred parts per million in phosphate rocks and Chilean nitrate; otherwise <20 ppm. Fluorine: up to 40,000 ppm in some rock phosphates; a few hundred parts per million in some liming materials. Lithium: up to 100 ppm in various fertilizers; a few liming materials somewhat higher. Approximately 2,000 ppm has been found in some dried sewage sludge. Chromium: up to a few hundred parts per million, with higher values in some phosphate and basic slags. More recent analyses show ~9,100 ppm chromium in sewage sludges. Cadmium: about 100 ppm in some phosphate rocks and superphosphate&, including Florida materials. Recent analyses show <50-2,850 ppm cadmium in sewage sludges. Zinc: up to a few hundred parts per million in phosphates; little in potassium salts. Dry-sewage sludge content as high as 10,000 ppm has been reported. Lead: little present in nitrogen sources; several hundred parts per million in some phosphates; somewhat less in some liming materials; up to 3,500 ppm in dried sewage sludge. Selenium: very little selenium in U.S.-manufactured super· phosphates (<2 ppm, generally). Idaho and Wyoming phosphate rock has higher values. Tellurium: no data other than one fly-ash sample at 10 ppm. Copper: generally <10 ppm in nitrogen sources; somewhat higher in phosphates. Recent analyses show 200-10,300 ppm copper in sewage sludges. Molybdenum: up to a few parts per million in many sources; liming materials are also low. Recent analyses show 2-30 ppm molybdenum in sewage sludges. 7. Application of Plant Micronutrient& Direct application of a number of elements to soil has been used to alter food-chain components-especially co- balt, copper, and selenium. Underwood (1966) notes that copper may be minimally effective in this regard on highly Overview 9 calcareous soil, and Jenne (1968) extends this concept to include other trace minerals and s.Jme acid soil conditions. Plants may also respond favorably to molybdenum. Simi- larly, zinc application will increase zinc content of deficient corn. However, in general, micronutrient fertilizer is applied to increase crop yield rather than to increase its nutritive quality. 8. Application of Water (irrigation) From studies of the effects of water on the uptake of nutrients, it is evident that irrigation may also affect plant content of trace elements: For example, in one series of lysimeter studies in California (Pratt and Blair, 1964), irri· gation with cropping led to soil depletion of zinc and copper but accumulation of molybdenum and boron. 9. Heavy-Metal Pesticides The continuing decline in use of chlorinated hydro- carbon pesticides has been accompanied by an increase in heavy-metal pollution. (Other metals, such as aluminum and tellurium, are also common components of heavy- metal pesticides.) When this summary was being prepared, precise produc- tion figures were not available. Table 4 provides minimal data on metal-based pesticides commercially available as of 1970 Farm Chemicals Handbook, focusing on the elements of primary concern to the Workshop. Knowledge of toxicity levels at relatively low-level long-term dosages for many of these pesticides are completely lacking. Furthermore, the ultimate depository in nature for many of these elements is at present unknown. It can be safely assumed, however, that some of the metals, and fluorine and chlorine, will fmd their way by means of water or other pathways into the food chain and, ultimately, into man. A concerted effort is required to provide data on the amount and use pattern of the metal-based pesticides, the depository sinks of these nondegradable elements, their toxicity levels, and the pathways for each of the lesser- studied elements (e.g., tellurium) into the food chain. TABLE4 Minimal Data on Metal-based Pesticides Commercially Available in 1970° Type of Number of Metal-based Pesticides Available Pesticide Lithium Chromium Lead Cadmium Zinc Selenium Copper Fluorine Iodine Fungicide 3 s 11 24 2 Insecticide 2 4 1 3 24 Preservative 3 2 3 2 Seed treatment 1 Disinfectant Rodenticide Herbicide TOTAL 1 6 2 6 19 30 30 a Based on 19 70 Farm Chemicals Handbook, Meister Publishing Company, Willoughby, Ohio. pp. D I 52-D 310.

10 THE RELATION OF SELECTED TRACE ELEMENTS TO HEALTH AND DISEASE EFFECTS OF URBAN AND INDUSTRIAL ACTIVITY ON TRACE ELEMENT ENTRY INTO THE FOOD CHAIN THROUGH AGRICULTURE (Donald J. Horvath) Atmospheric Inputs The atmosphere may be a major transfer route for sulfur and zinc in a beneficial context, as it may be for fluorine, lead, and cadmium in the opposite context. The conse- quences of excess fluorine deposition on plants consumed by grazing animals have been recognized for several decades. There are additional, largely local effects from other metals occurring in the vicinity of smelters and other industries. Some metals, such as lead, are more widely dispersed. On a still wider geographic scale, combustion of fossil fuel may be a significant source of many trace elements. Recycled Solids Livestock Recycling of animal wastes to the land was once a diffuse, low-intensity practice. With concentrations of ani- mals in smaller areas, such as feed lots, the pattern has changed. The consequences vary from element to element; at one extreme are elements, such as manganese for which little change in the amount and intensity due to recycling is expected (Horvath, 1972a). At the other are elements such as copper. The addition of 250 ppm copper to swine diets, for example, may upset plant growth if the manure from animals so treated is heavily applied as fertilizer. This is not likely to have a widespread effect on entry of copper into the food chain, but tonnage consumption data should be monitored, particularly if feeding of antibiotics is banned by U.S. Food and Drug Administration action. Mean levels of 21 ppm copper. reported by Batey et al. ( 1972) would be toxic to sheep. Human Waste Ecologists concerned with water quality and conservation of nutrients (particularly phosphorus) have urged that in urban areas, human (metabolic) waste products be recycled through the land. The consequences of this pro- cedure are potentially serious, however, because sewage can be very high in metals-e.g., containing as much as 1,000 ppm of zinc, and 400-500 ppm each of lead and copper (Horvath, 1972b ). At 25 tons dried sludge per acre, the following amounts of metals would be added. West VirginiD Uni11enity dllt11 Ob) Illinois dlltll* (lb) zinc 65 lead 25 copper 20 chromium 5 cadmium 0.5 500 115 150 250 30 •calculated from data in King (1971). Rhode ( 1962) has reported apparent copper toxicity in plants on sewage-irrigated soils in Europe. Le Riche (1968) and Schafer and Kick (1970) have reported increased metal content in vegetables that were grown on sewage-irrigated land, and which entered man's food chain directly. This problem requires more study. Table 5 gives known or suspected effects of trace element deficiencies or excesses on plants and animals, including hu- mans. Table 6 presents data relating regional patterns of mineral-related syndromes in animals. A DISEASE CLASSIFICATION EMPHASIZING TIME RELATIONS BETWEEN CAUSE AND EFFECT (Howard C. Hopps) The two major problems in determining the relationship (if any) between a particular case of trace element de- ficiency or low-level excess (cause) and the health or dis- ease of the animal (effect) are the multifactorial causation of disease (Hopps, 1971, 1972; Hopps and Cuffey, 1969) and the enormous variation in the time between cause and effect. The following classification of animal diseases according to the time between trace element cause and disease effect considers the directness of the cause-and-effect process. 1. Acute-Reaction Diseases. These diseases have a single major cause and a quick effect; e.g., streptococcal pharyn- gitis. 2. Diseases with a Long Incubation Period. Although the critical causal step has been taken, considerable time elapses before these diseases are manifest. In certain in· fectious diseases, this period may be the time during which the agent is adapting to its new environment or producing toxin that must accumulate to a particular threshold level, or it may be the time required before the body develops a state of hypersensitivity to the organism or its products. Leprosy has an incubation period of 3 or 4 years more or less; the so-called slow viruses may require 10 or more years; cancer in human beings ordinarily requires a time interval of 10-20 years between carcinogenic stimulus and overt cancer. 3. Diseases That Merge Imperceptibly with Health (de- pending upon the amount of the agent and/or resistance of the individual). Examples in this category include iron- deficiency anemia, some kinds of cirrhosis of the liver, and hookworm disease. 4. Diseases Caused by a Multiplicity of Factors Acting in Sequence (the effects of one or more being necessary before effective action of another). Hypertensive disease frequently produces cerebral hemorrhage, but usually only in conjunc- tion with the cerebrovascular lesion/defect, associated with atherosclerosis. 5. Diseases That Require Multiple Exposures. Examples

include most hypersensitivity conditions, also certain infec- tious diseases-especially parasitic ones. The multiple expo- sures achieve much more than just a simple summation of the effects of the individual "doses"; many times there are important qualitative changes in the effect-complex. CONCLUSIONS Relationships between geochemical environment and human health certainly do exist: A classic example is iodine defi- ciency and endemic goiter. The members of the Overview Work Group, however, found that it is very difficult to make meaningful general comparisons between the geochemical environment and health and disease, especially of human beings. One of the many reasons for this is that the appro- priate geochemical data have not been accumulated. How- ever, the Overview Work Group questioned the value of establishing geochemical data on trace elements with poten- tial significance to health or disease for the whole United States. Instead, it proposes as more productive alternatives, approaches based either on reconnaissance surveys of a dis- ease problem area or on more detailed studies of defmable physiographic units: Reconnaissance Surveys-In an area where a specific disease is prevalent and an environmental connection is suspected, reconnaissance surveys should be conducted to collect air and water samples, as weD as soil samples, strati- fied by soil category, in cultivated crop areas. The total number of samples may be greatly reduced by focusing on higher taxonomic categories. Studies of Physiographic Regions-Where the disease problem is less acute, selected physiographic units-such as drainage basins of smaU rivers-may be selected for more detailed study. These areas should be reasonably distant from the concentrations of heavy industry and dense pop- ulation found around large cities, but they might include small towns or cities of not more than 30,000 people. The areas should be largely agricultural and populations fairly stable. Obviously, it would be advantageous to select areas where some basic data of the kind described here have al- ready been collected. However, one of the great problems in dealing with data in hand for the kind of multidiscipli- nary studies proposed by the Overview Work Group is that observations made several years ago may not reflect the current situation. Moreover, the old data will probably be incompatible with the overall objectives because of inap- propriate sample selection or preparation, wrong times of sampling, and analytic procedures that are incompatible or less than adequate for a variety of reasons. Basin units of two sizes would be desirable: a small basin unit of 100-1,000 mi2 to serve as a pilot study area; and a Overview ll larger basin unit of 1,000-10,000 mi2 , selected according to disease data (perhaps focusing on a specific disease, such as hypertension or coronary atherosclerosis). The pilot study would focus on the movement of trace elements through the ecosystem of the related larger units from the rock up through the food chain, to indicate what parts of that system should be sampled and how to provide information bearing on the relationship of the geochemical environment and disease patterns. The larger basin studies would concentrate on interrelationships between the geo- chemical environment and health and disease. Among the variables to be considered would be climate, native plants and animals, slope, configUration of groundwater table, and soil parent material (rock, where available). Chemical anal· yses should be made of bulk precipitation (dry fallout and rains), water, rock, soil, colluvium, alluvium, plants, tissues of indigenous animals, including man if possible (Bormarm and Likens, 1967). SPECIFIC RECOMMENDATIONS These studies should extend over at least 2 years, with cer- tain observations being repeated perhaps 5 and 10 years later. The Overview Work Group concluded the following: 1. A multidisciplinary approach is essential to determine those important causal relationships between environmental geochemistry and health and disease. Moreover, there is need for uninterrupted long-term studies that are not dependent on year-to-year grant support. 2. Better mapping of human and other animal disease (as described) is highly desirable and should be correlated with appropriate biochemical and clinical data. 3. More data are needed on the normal ranges of values of trace elements in plants because average values or means are very inadequate descriptions of trace element content in either biological or earth-material systems. There is great merit in publishing frequency-distribution data, or at least in making them available in histograms or in other forms in a data repository. 4. It is critically important that compatible methods of sampling, analysis, and reporting be used by different groups to provide a basis for useful exchange of information and to support effective multidisciplinary efforts to determine causal relationships between geochemical environment and health and disease. Methods must be sufficiently sensitive, accurate, and reproducible to assure valid comparisons of results among various groups, and they must be standard- ized to permit use of automatic storage and retrieval mech· anisms. This is the only way to avoid production of mis- information in multidisciplinary studies. 5. Many more chemical data are needed to characterize the major groundwater aquifers in the United States. 6. More data are needed to evaluate potentially serious

TABLE 5 Known or Suspected Effects of Anomalous Levels of Trace Elements on Plants and Animals, Including Humans Effects of Anomalous Levels Environ- Trace Element mental On Plants On Animals Other Than Man° OnMan° (Atomic No.) Level Established Conjectured Established Conjectured Established Conjectured Lithium (3) low Increased inci- dence of mania. hign Some ability to sub- Control mania in some stitute forK when patients. K is limiting. Fluorine (9) low ~ower rowth rate Greater incidence of Greater incidence m rats. dental caries, espe- of osteoporosis in pecially in young. postmenopausal female; greater in- cidence of x-ray opaque aortae in male. N high Necrosis of tissue Sparing effect upon Mottled enamel. Bone with F air pollution. Mg-deficient animals abnormalities. re calcinosis; mottled enamel and bone ab- normalities, etc. in fluorosis. Vanadium (23) low Growth stimulation Stimulates growth and Deficient 0 2 trans- in one species of development in chicks. port pigment in some green algae. Lowers serum triglyce- invertebrates. ride levels. high Partial substitute for Depresses cholesterol Affmity for mito- Lower cholesterol Mo in N03 reductase, synthesis in rat liver chondrial, nuclear synthesis, pos- but not interpreted as and serum level in fractions of cell. sibly age de- essential. young rats. Reduces Possible role in pendent. tuberculous lesions. bone and enamel Toxic, growth depres- mineralization. Nega- sion in rats and chicks. tive interaction with Mn re cholesterol synthesis. Chromium (24) low Lower yield and Altered carbohydrate Slower growth rate, im- Trivalent form in or- Impaired glucose tol- Trivalent form in sugar content;'" but metabolism. paired glucose tolerance ganic molecule with erance in some human organic molecule function not de- and eye lesions in rats. vitamin-like function. beings responds to with vitamin-like termined. Insulin adjuvant. Cr3+ function. Insulin adjuvant. Progres· sive depletion in Wc~tcrn ~ncicty .

high Toxic; yellow branch Experirnen tally, toxic disease of citrus and especially in 6+ valence, witch's broom of but no regional patterns tea.d known or expected. Nickel (28) low Sorbed by plants but Olick legs show some no evidence of essen- enlargement of bocks, tiality. thickening of bone and abnormal color. Can ac- tivate arginase, etc. Con- centrates in RNA and possible function there. high Toxic.d Moderately toxic. Ni dust may in- duce respiratory neoplasia and dermatitis. Copper (29) low Impaired growth; Regional differences Anemia with milk diets. dieback (exanthema) known. Anemia, im- No regional deficiencies of citrus shootsf paired growth, pigment known. essential. defects (achromotrichia in cattle, rabbits), con- nective tissue defects (aneurysm of chicks and pigs), central nervous system amyelination and vacuolization (neo--w natal ataxia in sheep). high Toxic; may interfere 250 ppm may improve Interaction with Zn Wilson's disease pa- Role in aging with K metabolism.e swine growth yet sheep and Fe. tients accumulate Cu through increas- very susceptible to tox- due to metabolic ing free radical icity; liver damage and "enor." formation.! hemolytic episodes par- ticularly if Mo low. Zinc (30) low Stunted growth Poor growth, skeletal Role in insulin pro- Hypogonadal dwarfs. Impaired healing (rosetting), etiola- defects, dermatitis, tes- duction or action. and vascular func- tion,poorseed ticular atrophy, altered tions including "set" in maize; maternal behavior; ex- vasospastic dis- essential. acerbated by Ca and orders. Impaired pbytate. taste. high Toxic at available soil Interferes with Cu levels beyond approx- utilization. imately 20 ppm. Arsenic (33) low No evidence of es- Skin and hair ap- sentiality known. pearance less favor- able than with As supplement.

TABLE 5 (continued) Effects of Anomalous Levels Environ- Trace Element mental On Plants On Animals Other Than Mana On Mana (Atomic No.) Level Established Conjectured Established Conjectured Established Conjectured Arsenic (33) high Plant uptake of As Toxic at high doses, but Ameliorates selenosis. Toxic at high doses. (continued) from soils with above S ppm in drinking water averqe As levels is bad no adverse effects in very limited; but may lifetime studies with rats interfere with phos- and mice. Marine animals phorus metabolism. tend to have higher As levels than terrestial ani- mals. Selenium (34) low No evidence of es- liver necrosis in rats, Enhanced by As. Exacerbates sentiality. muscle degeneration in kwashiorkor. Pos- ~ calves, lambs, sterility in sible relation to rats. dental caries, cn"b deaths,l and can- cer. high May suppress growth Poorgrowtb,dougbed Progressive myo- of some plants, but a hooves in cattle, de- cardia! failure. few species are Se formed chick embryos, accumulaton. etc. Molybdenum (42) low Poor growth, failure Xanthine oxidase co- lmpainnent of Possible influence of N fixation by legume factor; poor growth; cellulose di3estion on dental caries. root nodule bacteria Cu toxicity more by rumen flora; in- (N03 reductase). likely in sheep. creased renal xan- thine calculi in sheep. high Weight loss, "teart" Complex of Mo and scoun in cattle. Con- Cu. ditioned Cu deficiency (regional differences partly due to soil drain- age and soil reaction rather than Mo level of parent geochemical rna- terial alone). Cadmium (48) low Absorbed through plant roots but no evidence of euen- U.J.Uv .

Vo Rf811 IUAJ\;, l'l\.U,~· '""""'._.,._. u""ua ···"""''""'"'"' .......... _ orrhage, male sterility. tion of Zn, Fe, and Cu. Competes with Zn Ouonic: hypertension. (Se prevents Cd-induced at metaUothionein Little transfer to cow's pregnancy toxemia.) binding site in kid· milk from oral dose. ney. Regional dif· ferences in human kidney (Japan and the United States have hisher levels). Tellurium (52) low high Iodine (53) low Not considered es· Endemic goiter, still· Endemic goiter, stunted Natural goitrogens sential, yet some births, hairless new· physical and mental de- in some human plant growth born pigs. Deficiency velopment (cretinism). problems, e.g., wal· response.d may be enhanced by nut in Spain.h In· natural goitrogens such teraction with Co. as from Brtlssictl species and water supplies. high Toxic (maize)d Experimentally im· Toxic. Possible problem in solution culture. paired reproduction. in one area of Japan. Lead(82) low high Toxic in sand culture; Toxic, shortens life of Impaired protein syn· Toxic, accumulates in limited translocation mice, accumulates in thesis. Exacerbates bone, central nervous from roots during bone. swayback in sheep in system damage in chil· growing season, low Cu regions.i dren, anemia; increased though air pollution urinary delta amino- fallout may deposit levulinic acid is an on above ground early sign. portions of plants. Mitochondrial effects in sand culture.i DUnderwood ( 1971 ), except as otherwise noted. bSchwarz and Milne (1972). cBertrand (1967). dChapman, H. D. I ed I DtqnNtic Criterillfor Plan~ and SoU (University of California, Berkeley, 1966). !Harman, D.,J. Gerontol., 20, lSI (1965). KMoney (1970). hLinazasoro, J. M., J . A. Sanchez-Martin, and C. Jimenez-Diaz, Endocrinology, 86, 696 (1970). IMiller and Koeppe (1971). eChllders, N. F. I ed I Mlnertlh Nutrition of Fruit Crop1 (Rutaers University Press, New Brunawlck, N.J. 1954). i Alloway , B. J ., Ph D Theala (University of Wales, Aberystwyth, Sept. 1969). NOTE: Thla table was compiled primarily for aeochemlats by D. J. Horvath at the suaestlon of the Workshop participants. The objective Ia to provide a synopsla, alvin& probable bio- lopcal consequences of anomalous levels or those trace elements belna considered at the Workshop. Conaequently, aeveral bloloalcally important trace elements are not lilted. The values "low" and "hl&h" are defined on the basla of bloiOJical effects. Absolute levela are not readily available nor easily established because of the multiple Interactions amana various elements and the effects of many other variables. An Important advantaae of Its matrix form Ia that thla table hl&hllahts areas in which Information Ia seriously deficient or abient.

TABLE 6 Minerals in Pastures in Relation to the Health of Grazing Animals as of 1956 (with subsequent modifications by Donald J. Horvath) Dl.tt•as~ SIN*ci~s ufft:cll·d Country Principal ar~as lnrt'sli6atfil Principal 5oils Churactr:r of p4JSturc -· - Bush·s.ick ness Sheep and caule New Zealand Central plat~au of Nonh VolcaniG soils and soils stronaly Less thon 0·07 p.p.m . Co Island; leached from basalt; aranite unhealthy for sheep, I«S th.an Nelson. South Island soils 0 ·04 p.p.m. unhcahhy for C.J.ttl Morton Mains disease Lambs New Zealand Southland Locssic Mairoa dop~- ··---- · --- l'iew Zealand -- ----Sheep ~orth hland, Mairoa Volcanic and sandy soil!, L:.ckina h:aumc!.. Lo-. in Co, 111 "'· Ca and P - Enzootic marumus Sheep and callle Wesl and South Dc!nmark distnct: south· Coarse sands and sandy loanu; Littt: natural pasture. Australia eastern South Australia clay o\·cr limestone Mixed sp:ci.es sown. Co 0·;)~ to 0 ·07 p.p.m .• Cu 2·2 to 6·3 p.p.m . - ------- Nakuruitis Cank antJ ~hup Kcny.11. Nakuru Volcanic ---- -- ---- - Pi nina Sheep and cattle Great Britain anu Widespread Volcanic, andcsitic soils; blown Of1en low in Co; crit ical l.e·u:l nt> lr'eland shell sand; aranite ; Old Red demonstrated. &>dmin MOor Sheep Devon and Cornwall sandstone Low Co conlt.:nt. 0·01 to sickness 0·20 p.p.m. Grand Traverse Callie United States Michipn, Wisconsin, --- Commonly liaht and undy Hay low in Co tl disease and others New Hampshire, New York State, MassachuK"tts Yosk or Yoskhed Callie. sheep Denmark Jutland Podsolised undy soils n:c:laimed from moor Hinsch Cattle Germany Black Forest, Bavuria Granite Hay low in Co and Cu - · · Likzucht Calli<, sheep and Netherlands Eastern provinces Sand and sandy moor soils Pasture and hay low in Co or C.., aoau reclaimed from heath and Cu Sukhotka, mos&juka Caul:, sheep, rarely U.S.S.R . Lat"·ia, Estonia, Baltic coasts Podwlised sandy soils; r..:claim.:J Hay low in Co pip, hones peaty wils Lickin& disease Cattle, sheep Norway Mainly on cout, but alw Shell sands and aravcl; peat - ·- Hay low in Cu or Co or P or~ rc inland than one of these PhaLuis staucn Sheer, cattle Australia, South~astern South Black soil ftats; sandy soils; lush n4:w growth of PhcJluri.~o Auslralia ; New South Wales: aranite tub~ro1a. Barely sufficient Co. New Zealand South Island Cu somewhat low Coast diJeasc Cattle, sheep Australia Couts of South ani.l West lllown shell sand and allied ---- - Pasture low in Cu and Co Austrillia: offshore islanLI1 calcareous soils Salt sick Cattle, sheep, aoats, United StatO$ Florida coast and coastal Fine white sands; peat Predominantly wirearass; lo'-'- in pia• plains Ca. Ma. P, Fe, not low in Cu; no Co found. but method S\bl '«:I Enzootic 1111axia c Lambs West and South Mainl)· near coasts Blown shell sand; cal..:~ucous - Hi.ii. in ·c;;. and P . Low in Cu. Australia; New soils; aranite; peat usually less than 3 p.p.m. Zealand Swayback,. Lambs Great Britain Widespread Cretaceous orivin, lima;tonn - Hiah inCa, wmctimcs in Pb- or Zn; not low in Cu or hish i n Mo ------ Fallina disease Cattl< South and West Coastal areu; liinain Heavy loam; ara .. ·cl; arcy sands, Mainly Trifolium urnuum, wllh Australia usually on yellow clay subsoil other species. Low Cu content, usually leu than 3 p.p.m. Pasture diarrhoea Cattle Nethcrla~ Widespread Sandy soils reclaimed from sea; Now low in Cu. Low in Mn.- low moor peat Some hi&h Mo values Scour ina on •• teart" Cattle GrcatBri~ Somerset and nearby Lo.wcr Lias oriain, stiff cl.l)'S High Mo content, 10 to I 00 pastures 1 counti('s p.p.m. Not low in Cu Peat scour~ Cattle New Zealand Mostly in North Island ReclaimcJ pea-t; pumice Fairly low in Cu, 1·7 to 11·3 p .p . m. Hiah Mo conlcnt. May to October, up to 16·3 p.p .m. ------ Ch1onic copptr Sheep Austu.Ha Lachlan Rh·cr Valley Copper-bearina andesite High Cu content, up to 61 ·6 p.p.- poisonina K in Curthamu$ Cattle, sheep --- ·--- Often with lush n.:w sro~u:h Grass tetany, arau Netherlands, \\ idesprcad No connection foun..J in mo)\ staaacn, lactation Norway, German)·, c:ountnes. Pumice in l'lew in protein and K . Not usual)) tetany t Great Britain, Zealand low in Ma i New Zealand, etc. Bone-dlcwina and Cattle, sheep, hones \\orld-wide South Africa l'tot established Low in P wutina diseuc5 ---- ---- Simple aoitre All domestic animals \\-orld-wiuc Mountain urcas c~pccially m Low I content~ ha .. -e been rip:;;tc but not wii.Sel)' ---- Alkali disease, Cattle, horoe>, United State~, Great Plaint of U.S. Cretaceous ~hafe or limc)tonc. Jn Amcaica c~pt."Ciall)· rich in- blind •taaaen sheep, pias Canada, usually with I to 6 p.p.m. Sc. but As1ragulu1 spp., which conc:n- Colombia, up to 324 p.p.m. in Ireland Irate Sc. 4 p.p.m. Sc appcan Ireland Count)' Limerick to be lower toxic limit SOURCE: Adapted from fold-out table In Mineral$ In Puture: Deficlencle:~llnd Exceuu In Rellltlon to Anintlll Helllth, Tech. Commun. No. I 5 (Common· wealth Agricultural Bureaux, Farnham Royal, Bucks, England. 1956). 16

Topdressina v.:ith Co controls di~asc: Linte .,. superphosphate + Co control disease Co drcssin¥ controls disease h Co dressing controls discaooe in Easter ROS5 Topdr~sing ~ith Co ghcs healthy fodders Prc .... cmtt:d by t.lres~ing with miJ~.lure of Cu, Co, Mn, Zn and 8 Prcn:ntcd by topdrcssinv ":ith Cu ~ Co Prc .... entc:t.J by dr'-"$~ina with Cu Drt:S5in& with Cu improu~s heo.ahh of cattle ~o content reduced by sulphate: of ammonia Drcssina with Cu gi"'·"-s spce~acular - impro ... ·ement Maint:sium fcrtili~rs may th:--- bt:nefic::ial. Hca"Y N drcssin& may be harmful k Phosphates beneficial /ncidf*ltC~ of dis~us~ In some areas all year round. in others worst from Nov. to Fc:b. Dec. to Jan. ·-------·- ·--- -- Commonest in spring and early summer Seasonal, cspcci~lly after rains Anaemia common Lh·er Co low Bon~.:s. low in ash Anaemia common Hacmo~iderosis . Liver low in Co \Vor~t from '-'\ardt to August Anaemia common Winter Anaemia common WiOlcr Usually appt.:ars in winter, but may be all)"e~r roumJ Mostly towards end of winter l:sJ'k,'Ciall)' in winter Wht:n rotins brinv on new vrowth Not seasonal Anaemia common Anaemia common Anaemia con1mon Haemosidc:rosis common Central nervous lesions Li\c:r Jow in Co and Cu Anacmht common Haemos.idcrosis. Liver. spleen, kidneys low in Cu Anaemia common HaemosiUc::roJi~ Cobalt-rich limonile and cobalt salts prevent and cure Co salts prevent and cure Local earths and Co salts cure Conclusions Simple deficiency due to lack of Co in pasture Mild deficiency of Co "'ith lack of Ca and P and under- nutrition Simpk deficiency of Co Probably- sinlPi.: d.:ticicncy of Co Co salt5. pr.:vent and~-- Simple dcticicnc)' of Co Co sahs cure Simple dcticicnC)· of Co Co salts cure _C_o_sa-hs-or mo·l,-,-asscs..,--cu_rc_;_o_n_c -- report of cure with Mn Co salts cur~ O~Co and~- Co cures or prc\·ents Co, Cu and P each some&imcs cure, esJ>«ially Co Simple deficiency of Co Prob~bly simple deficiency of Co Simple deficiency of Co, some- time$ complicated by low intake ofCu Simple <leficien<:y of Co Chiedy deficiency of Co, but complicated by low intakes of Cu or P Probably a toxic effect manifest only when Co intake is low Cured by Cu and Co toaeth<r Dual deficiency of Co and Cu Cured by Cu .,.. Fe salts, or Co, or Probably dual deficiency of <;o all three and Cu EsJ>«ially lambs born in June and July. Favoured by lush pa>turc growth Anaemia common Cu pre ... ·.ents and arrest.s disc~ Simple deficiency of Cu due to Varies from )'ear to year August 10 October. -.·hen pasture is lush Pasture season, worse after rain Worst in autumn Worst when Mo content of past~;; hiahest All year round Commonl)·-in spnn.: aaa autumn I - - - ---- \\' orst in dry $Casons Some ~asonal \'ariatlon, ditTerin& from place to place Ha.:mosidc:rosis. Li\'er low Cu intake of ewn and ewe's milk low in Cu J Anacmhi-COmmon. Li't'cr and blood low in Cu J Anaemia common Hacmosidero~is. li\ cr low in Cu Anaemia common. Fe dc:positr:d in tissues Liver low in Cu ---- Anaemia Lh·er low in Cu T crminal haemol)·tic anaemia. Hi1h lh·er Cu Low serum M&. often also low serum Ca Low serum inorgamc P Thyroit.l low in I Anaemia. Sc in bl"od and tissues 17 ~C~u--p-re-,-.c-nt~.------------------ Cu prevents Cu alon< or with Co cures Cu cures anJ pre\'c:nu -i'o-la)-bc-cu_r<_d_ by "Cin.,..i<""ct'"=io-::-n-:o::-f ;M~-::-~~-.,.­ Ca. Ma)· be pr<\'cnted by MaO or NaCI J cures und pr~\c:nts Compounds of As may protect •• Conditioned '" deficiency of <.:u. cause unknown ,. Simple dc:uciency ot Cu ·• Conditioned •• deficiency of Cu, cause unknown •• Conditioned " deficiency of cU, due to e:~tcess of Mo Deficiency of Cu and excess of Mo Poisonina due to excess Cu in pasture lr Still undec::idea Simple deficiency of P Simple or •• conditioned ., de- ficiency of 1, causes not well understood Poisonina due to excess Sc in pasture

TABLE 6-Addendum (Compiled by Donald J. Horvath) m.- Specilr A/flcttd Country PrlltdptJI A,.., Jnrat,.ttd l'rlltclptd Soib Molybdenouf Cattle United Stateo Nenda, Orep>n, Wet, panltlc aUuYill California, IJid IOib and peats other -tem rtatea Muerte rubita Cattle Cuba (sudden death)0 MIHeoponsiYe Cattle Holland, ryndromeol' Britain liHetpOIIIIYe .st.- Cattle, lheep, Aurtralla. New Continental United ;; Forap crops low In Se - bo.-a Zelland, Statea-prlndpally White murcle United States acldaoDueas .u-.e, Iliff tamba, m thrift, lowered fertU. ity, DOODatal mortality, pero- dontaldllale ofeweaq Enteque oec:o' Cattle Alpnlinl Lowlands, near Buenos Airel Urinary calcull, Male lbeep, Wntom A,.trolla, llllc:aurolithluls, male cattle Wutom Conoda, "water belly"' ondWntom United States 0Add: -clally .,_ (Underwood, 1971). bAdd: Cobllt f_..Oiaotlon effective (Uad.wood, 1971). cE,..ootic oiUiot ond .-yboc/1: .. virtually synoaymouo with rnpect to patholopcol monlfortatlons: aloo known u "lamkruil," ''r...,uora," ond "Giqla ricuta" (Underwood, 1971). Cl'IINcfer of,...,_ Mo toxk:lty, I 0 to 400 ppm Solorlfum llflll«oJtyltHt ,._..I Silk:a lnel nla!Miy ltilb In IOIIIC plants, ruc:b U Bt..sy pall (/,_.,,. cylbttlllal), In one report from Aurtnlla dLowcoppert ... lln brain t-..e (Underwood, t971). 'Aloo almplo copper deficiency (Underwood, t971). IScourllll 011 t#ort ,__ doocribM dlarrhoa In cattle from pMiurn wltb excoaolve molybdenum. Soo olso moly_,..,.,. (above) or molybdenum toxicity In Ia cattle, w111c11 ealatlla tho United Statoa, -lilly In poorly drained IOIIo of Nnado, Callfomia, ond Ores- (Nnado Aplc. Exp. Stn., Bul. 108, 1959; Kubota nlll., 1967). IAtoo roforrod to u "Yellows" (toxic jaundice) In Now South WIIM and VIctoria, A,.tnlla (Underwood, t971). lls..-ptlbtuty to copper toxicity on puturo illncroMod by bopatotoxlc horbo sueb u bollotrope ond rqworta (SoMclo apecloo). A wldo copperfmolybdo· num rotlo occun In subtorronoon ct.,... in ootly powih. Curlq of plants for boy opparontly incroMM tho tilt of cbtonlc copper toxicity u Ia bo- -P In Nortbom lnlud. Hay hod 30 ppm copper In ono teatonco (Todd, J . R., he>c. N11tr. Soc. , 2/1, 189 (t969)( . 18 .

Elf,et of Fmfllznr llfdd'*" of DJM.• Blood •ltd ~, Rapotl# to F'«<illr Tm1 Cia f.-tillzatloD Cia 111pplomeotatloo ofloilaaot elfectm Jocreuecl by mea. lllcb Edema of hql, 101110 120 1111 CuS04 ID I01llle t.V • .. drlvlaa; raiDy - burt defects but DOt moDtbly did DOt preoeot peak; you,. uJma1a ........ lYe f1brools oppueady more 111• of "faiJIDa .U..." ceptlble lofertlllty ID female, bone Reporta of reopo1111 to MD ID defect repor!Aid ID Dorth- field triala; DOt CODflrmecliD -m Unl!Aid Statea mtudy ID Hollud MIUCie patboloQ -D ID EIIMIAid •nam a1u- Se effectt.e ID New Zeolaod YOIIJIIulmala tamlc OxaiOICitlc tr.....w.a. (SGO'I) (iafertlity exceptloo ID most areu other thiD New Zeolaod) Blood Ca and p .. PIIDt extnct toxic n!Aid; Ca depooill ID ....U; blood and lim' Cia IUIWiy ... low oormal Principally notric!Aid to male, ..... wetben and 11-.; more common In willter wben Yitamln A and aniJ. able water may be lllb- OPtimal loan.: lactation tataoy (D. J . Homoth). llfllbnlftlttt: "o-ay" for ".....Uy." Add: Sprlna and autumo tetany duriDa luah new powtll of- rlciiiD proteiD, pot-.lum, and In..,_ 1Attanc11, \WPIIk ackla sucll • dtrlc aod ,_acoolllc (D. J. Homoth). "Add: Nltropo ph• pot-.lum b ... a clelrlaaeotallne.nctloa (D. J. H""atb). I Add: Winter t.W.y oo small po paiiDaiD the Uolled Sta ... aod Arpolloa. aod oo- bay lo Appobclollo (D. J. Horntb). "'Add: Prlodpally ecld toO .. u (D. J. Hornlb). "Add: Cootnry effecto ofoltropo (Aiclerman and J-. 1967; Leo er.rl., 1970; Rold.ra, 1969). 0~, Vida, and T. N. Suthorluulln TN«B-IIttM,,._ lilA,., C. F. NUio (ed( (E lo. S Lloloptooe, Edlob ...... , l970), p. 114. I'Jtcinatll (1971&). qUo--.1 (1971). 'Cam ........ H. R., G. K. Daril, and N. I. Djaferlo TN« Eirlfl111t M•- Ill A,., op. cit., p. 369 . ._,..., K. F., and H. M-. Alfl. I . V.,. Ra., 14, 16 (1953). 19 Co..elu'*"'• McMaduced Cu deflcleocy NotCudeflc:leiiC)' Not lll<ely to be dmple MD deficiency Se defkieDey. thOUib other focton operate ID IODIOCUOI MlnenJ cllatwbance ...., ... daty to pbytotoxill Other catlo111, pyco- proteinl, and urine >Olume ue ili>Olwcl

20 THE RELATION OF SELECTED TRACE ELEMENTS TO HEALTH AND DISEASE consequences from extensive recycling of human waste products through the land. 7. More attention should be directed to effects of food processing on availability of trace elements in such food. 8. More studies should be directed toward wild animals as a source of health or disease data because these animals live in intimate contact with their geochemical environ- ments, reflecting the experiments of nature. 9. There are still opportunities in the world to study primitive groups that live on foods derived from their im- mediate geochemical environment. Moreover, many of these groups are still relatively unaffected by man-made pollution. Now is the time to study these isolated popula- tions because they are rapidly being exposed to the "bene- fits" of civilization, which include drastic changes in their surroundings. REFERENCES Alderman, G., and D. I. H. Jones. 1967. The iodine content of pas- tures. J. Sci. Food Agric. 18:197-199. Allaway, W. H. 1968a. Agronomic controls over the environmental cycling of trace elements. Adv. Agron. 20:235-274. Allaway, W. H. 1968b. Control of the environmental levels of se- lenium. In Proceedings of the Second Annual Conference on Trace Substances in Environmental Health, July 16-18, 1968, D. D. Hemphill (ed). University of Missouri, Columbia. pp. 181-206. Batey, T., C. Berryman, and C. Line. 1972. The disposal of copper- enriched pig-manure slurry on grassland. J. Br. Grassl. Soc. 27:139-143. Beath, 0. A., J . H. Draize, and C. S. Gilbert. 1934. Plants poisonous to livestock. Wyo. Agric. Exp. Stn. Bull. 200:1-84. Becker, V. J., J. H. Bennett, and 0. K. Manuel. 1972.1odine and uranium in sedimentary rocks. Chern. Geol. 9 :133-136. Beeson, K. C. 1941. The mineral composition of crops with par- ticular reference to the soils in which they were grown. U.S. Dept. Agric. Misc. Publ. No. 369. U.S. Government Printing Office, Washington, D.C. 164 pp. Beeson, K. C., V. A. Lazar, and S. B. Boyce. 1955. Some plant ac- cumulators of the micronutrient elements. Ecology 36: lSS-156. Beeson, K. C., and C. B. Lyon. 1948. Influence of toxic concentra- tions of micronutrients in the nutrient medium on the vitamin content of turnips and tomatoes. Bot. Gaz. 109:506-520. Bertrand, M. D. 196 7. Should chromium be added to the trace ele- ments used as supplementary fertilizers? In Proceedings of the Conference of the Academie d'Agriculture de France, Jan. 25, 1967. C. R. pp. 113-117. Bormann, F. H., and G. E. Likens. 1967. Nutrient cycling. Science 155:424-429. Bosch, S. 1954. Overdruk 260 van bet Centraallnstituut voor Landbouwk. Ondenoek 13 7. Cited in The biology of the trace elements by K. H. Schutte. J. B. Lippincott Co., Philadelphia, Pa., 1964. p. 183. Cannon, H. L. 1969. Trace element excesses and deficiencies in some geochemical provinces of the United States. In Proceedings of the Third Annual Conference on Trace Substances in Environ- mental Health, June 24-26, 1969, D. D. Hemphill) ed). Univer- sity of Missouri, Columbia. pp. 21-42. Chilean Iodine Educational Bureau. 1956. Geochemistry of iodine. Shenval Press, London. 1 SO pp. 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. 1961. Occurrence of minor elements in water. U.S. Geol. Surv. Circ. No. 445. U.S. Government Print- ing Office, Washington, D.C. 10 pp. Erdman, J. A., H. T. Shacklette, and J. R. Keith. 1973. Geochemical survey of vegetations. In Geochemical survey of Missouri, June- December 1972. U.S. Geol. Surv. Open-File Rept. U.S. Geologi- cal Survey, Denver, Colo. Fleischer, Michael, and W. 0. Robinson. 1963. Some problems of the geochemistry of fluorine, R. Soc. Can. Spec. Publ. 6:58-75. Fletcher, K., and V. C. Brink. 1969. Content of certain trace ele- ments in rqe forages from south central British Columbia. Can. J. Plant Sci. 49:517-520. Hodgson, J. F., W. H. Allaway, and R. B. Lockman. 1971. Regional plant chemistry as a reflection of environment. In Environmental geochemistry in health and disease, H. L. Cannon and H. C. Hopps (eds). Geol. Soc. Am. Mem. No. 123. Geological Society of America, Boulder, Colo. pp. 57-72. Hopps, H. C. 1971. Geographic pathology and the medical implica- tions of environmental geochemistry. In Environmental geo- chemistry in health and disease, H. L. Cannon and H. C. Hopps (eds). Geol. Soc. Am. Mem. No. 123. Geological Society of America, Boulder, Colo. pp. 1-11. Hopps, H. C. 1972. Ecology of disease in relation to environmental trace elements-particularly iron.ln Geochemical environment in relation to health and disease, H. L. Cannon and H. C. Hopps [ eds) . Geol. Soc. Am. Spec. Pap. No. 140. Geological Society of America, Boulder, Colo. pp. 1-8. Hopps, H. C., and R. J. Cuffey. 1969. Cause/effect relationships in disease. lot. Pathol. (journal of the International Academy of Pathology) 10:23-25. Horvath, D. J. 1972a. Availability ofmqanese and iron to plants and animals. Geol. Soc. Am. Bull. 83:451-461. Horvath, D. J. 1972b. An overview of soil/plant/animal relationships with respect to utilization of trace elements. Ann. N.Y. Acad. Sci. 199:82-94. Jenne, E. A. 1968. Controls on Mn, Fe, Co, Ni, Cu and Zn concen- trations in soils and water: the significant role of hydrous Mn and Fe oxides. Adv. Chern. Ser. 73:337-387. Keefer, R. F., and R. A. Singh. 1971. Zinc-phosphate interaction in roots, stems and leaves of soybeans and corn grown in solu- tion culture. Proc. W. Va. Acad. Sci. 42:35-47. King, S.M. 1971. Fluid wastes for more fertile farms. Fert. Solu- tions 15 :24-28. , Kreil, W ., G. Wacker, H. Kaltofen, and E. Hay. 1966. Paper in Nitro- gen and grassland, P. F. J. VanBurg and G. H. Arnold [eds) . Pro- ceedings of the First General European Meeting of the European Grassland Federation, Wageningen. Centre for Agricultural Pu~ lications and Documentation, Wageningen, Netherlands. pp. 127-132. Kubota, J., V. A. Lazar, G. H. Simonson, and W. W. Hill. 1967. The relationship of soils to molybdenum toxicity in grazing animals in Oregon. Proc. Soil Sci. Soc. Am. 31 :667-671. Lee, C., R. Weiss, and D. J. Horvath. 1970. Effects of nitrogen ferti- lization on the thyroid function of rats fed 40% orchardgrass diets. J. Nutr. 100:1121-1126. Le Riche, H. H. 1968. Metal contamination of soil in the Woburn Market-Garden experiment resulting from the application of sewage sludge. J. Agric. Sci. (Cambridge) 71 :205-207. Miller, R. J., and D. E. Koeppe. 1971. Accumulation and physio- logical effects of lead in corn. In Proceedings of the Fourth