1
132 PROCESSING AND PACKAGING CONTAMINANTS [The finding on potassium chromate is particu- larly interesting in connection with the Lehman article on stainless steels in cooking (Lehman, Quart. Bull. Ass. Food Drug Off. U.S. 1961, 25, 123). Lehman dealt with the toxicity of trivalent chromium and not the hexavalent form as compounds of the latter are not formed during cooking. Here the hexa- valent form is also shown not to exercise chronic toxic effects under the experimental conditions employed.] Anwar, R. A., Langham, R. F., Hoppert, C. A., Alfredson, B. V. & Byerrum, R. U. (1961). Chronic toxicity studies. III. Chronic toxicity studies of cadmium and chromium in dogs. Arch. environ. Hlth. 3, 456. 117. CADMIUM: OCCURRENCE IN HUMAN TISSUES, FOOD AND WATER In man, the highest level of cadmium occurs in the kidneys and increases with age. The authors set out to answer two important questions: What are the sources of this cadmium; and are these sources natural, or has cadmium been introduced into foods and beverages as an industrial contaminant ? A straight-line relation exists between dosage and the amount found. Cadmium forms a stable complex with protein and is not removed from the tissues by chelating agents. It may be an essential trace element but mostly its action on enzyme and other biological systems is inhibitory or toxic. The authors give the amounts of this element found in over 100 analyses of foodstuffs and water. It is possible that some cadmium was introduced during processing and canning but the amount was inconstant. The general conclusion reached was that no consistent difference in cadmium content was seen between fresh foods and the processed products. Highest amounts were found in sea foods, kidneys and grains. Rock phosphate fertilisers contained high amounts of cadmium and crops grown with their aid showed a higher level than those grown without such fertilisers. Kidneys and livers of domestic animals contained cadmium derived from their food. Tests suggested that water pipes were not a signifi- cant source of environmental cadmium. Schroeder, H. A. & Balassa, J. J. (1961). Abnormal trace metals in man: cadmium. J. chron. Dis. 14, 236. 118. ABSORBED CADMIUM ACCUMU- LATES IN THE BODY Experiments with isotopically labelled cadmium compounds have demonstrated that this element is not excreted but accumulates in the body. Elements of physiological importance are maintained at a constant level by various mechanisms but there appears to be no mechanism to regulate cadmium levels in the body. These findings are supported by the fact that cadmium levels in the tissues show a steady increase with age. Cotzias, G. C., Borg, D. C. & Selleck, B. (1961). Vir- tual absence of turnover in cadmium metabolism: Cd 1*9studies in the mouse. Amer. J. Physiol. 201,927. 119. TUMOURS INDUCED BY CADMIUM Cobalt metal powder is a potent carcinogen when injected intramuscularly (in suspension in fowl serum) into rats. Zinc and tungsten metal powders do not have this effect (Heath, Brit. J. Cancer 1960, 14, 478). One action of cobalt is to inhibit the oxi- dation of ketoacids. Cadmium is known to share this property and on these grounds it was tested in the above manner for carcinogenic effect. Ten rats received injections into the thigh muscle of 0.028 g cadmium metal powder in 0.4 ml fowl serum and a further 10 were given half that amount of cadmium. Two tumours were seen in the former group after 23 and 24 weeks respectively and a 3rd turnover in the latter group at 28 weeks. Subsequently 10 more rats developed malignant tumours. Heath, J. C., Daniel, M. R., Dingle, J. T. & Webb, M. (1962). Cadmium as a carcinogen. Nature, Lond. 193, 592. 120. CADMIUM UNCOUPLES OXIDA- TIVE PHOSPHORYLATION In this paper the effect is described of cadmium ion (I) and arsenite (II) on oxidative phosphorylation by mitochondrial particles prepared from rat liver and beef heart. Both I and II serve to uncouple or disrupt the conversion of inorganic phosphate ion to energy-rich phosphate esters, a process which nor- mally accompanies the uptake of oxygen by the cell. This effect was similar to that exerted by I and II upon whole mitochondria. The heart mitochondrial particles were less sensitive than the liver particles to the uncoupling action of I, II and 2, 4-dinitrophenol. [This is an important finding as the phosphate esters normally formed during oxidative phosphory- lation associated with the uptake of oxygen by living cells are of crucial importance to cell metabolism, for which they supply energy.] Fletcher, M. J. (1962). Uncoupling of oxidative phosphorylation by cadmium ion and by arsenite in submitochondrial fragments. Fed. Proc. 21, 53. 121. CADMIUM INFLUENCES SODIUM EXCRETION Kagi & Vallee (J. biol. Chem. 1960, 235, 3460; ibm 1961, 236, 2435) found that cadmium accumu- lated in the renal cortex in the form of a complex with protein, metallothionein; the physiological role of this compound is not known. In the present investigation the effect of cadmium chloride (I) on renal function was studied. Intravenous infusions of 0.35-4.46 laM I/kg were made in anaesthetized dogs together with cysteine in order to prevent or minimize changes caused by I upon blood pressure, or the amount of blood passing through the kidneys and glomeruli. A decreased excretion of sodium resulted in all cases; the dose-response curve for this

120. Cadmium uncouples oxidative phosphorylation

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132 PROCESSING AND PACKAGING CONTAMINANTS

[The finding on potassium chromate is particu- larly interesting in connection with the Lehman article on stainless steels in cooking (Lehman, Quart. Bull. Ass. Food Drug Off. U.S. 1961, 25, 123). Lehman dealt with the toxicity of trivalent chromium and not the hexavalent form as compounds of the latter are not formed during cooking. Here the hexa- valent form is also shown not to exercise chronic toxic effects under the experimental conditions employed.] Anwar, R. A., Langham, R. F., Hoppert, C. A., Alfredson, B. V. & Byerrum, R. U. (1961). Chronic toxicity studies. III. Chronic toxicity studies of cadmium and chromium in dogs. Arch. environ. Hlth. 3, 456.

117. CADMIUM: OCCURRENCE IN HUMAN TISSUES, FOOD AND WATER

In man, the highest level of cadmium occurs in the kidneys and increases with age. The authors set out to answer two important questions: What are the sources of this cadmium; and are these sources natural, or has cadmium been introduced into foods and beverages as an industrial contaminant ? A straight-line relation exists between dosage and the amount found. Cadmium forms a stable complex with protein and is not removed from the tissues by chelating agents. It may be an essential trace element but mostly its action on enzyme and other biological systems is inhibitory or toxic.

The authors give the amounts of this element found in over 100 analyses of foodstuffs and water. It is possible that some cadmium was introduced during processing and canning but the amount was inconstant. The general conclusion reached was that no consistent difference in cadmium content was seen between fresh foods and the processed products. Highest amounts were found in sea foods, kidneys and grains. Rock phosphate fertilisers contained high amounts of cadmium and crops grown with their aid showed a higher level than those grown without such fertilisers. Kidneys and livers of domestic animals contained cadmium derived from their food.

Tests suggested that water pipes were not a signifi- cant source of environmental cadmium. Schroeder, H. A. & Balassa, J. J. (1961). Abnormal trace metals in man: cadmium. J. chron. Dis. 14, 236.

118. ABSORBED CADMIUM ACCUMU- LATES IN THE BODY

Experiments with isotopically labelled cadmium compounds have demonstrated that this element is not excreted but accumulates in the body. Elements of physiological importance are maintained at a constant level by various mechanisms but there appears to be no mechanism to regulate cadmium levels in the body. These findings are supported by the fact that cadmium levels in the tissues show a steady increase with age.

Cotzias, G. C., Borg, D. C. & Selleck, B. (1961). Vir- tual absence of turnover in cadmium metabolism: Cd 1*9 studies in the mouse. Amer. J. Physiol. 201,927.

119. TUMOURS INDUCED BY CADMIUM

Cobalt metal powder is a potent carcinogen when injected intramuscularly (in suspension in fowl serum) into rats. Zinc and tungsten metal powders do not have this effect (Heath, Brit. J. Cancer 1960, 14, 478). One action of cobalt is to inhibit the oxi- dation of ketoacids. Cadmium is known to share this property and on these grounds it was tested in the above manner for carcinogenic effect. Ten rats received injections into the thigh muscle of 0.028 g cadmium metal powder in 0.4 ml fowl serum and a further 10 were given half that amount of cadmium. Two tumours were seen in the former group after 23 and 24 weeks respectively and a 3rd turnover in the latter group at 28 weeks. Subsequently 10 more rats developed malignant tumours. Heath, J. C., Daniel, M. R., Dingle, J. T. & Webb, M. (1962). Cadmium as a carcinogen. Nature, Lond. 193, 592.

120. CADMIUM UNCOUPLES OXIDA- TIVE PHOSPHORYLATION

In this paper the effect is described of cadmium ion (I) and arsenite (II) on oxidative phosphorylation by mitochondrial particles prepared from rat liver and beef heart. Both I and II serve to uncouple or disrupt the conversion of inorganic phosphate ion to energy-rich phosphate esters, a process which nor- mally accompanies the uptake of oxygen by the cell. This effect was similar to that exerted by I and II upon whole mitochondria. The heart mitochondrial particles were less sensitive than the liver particles to the uncoupling action of I, II and 2, 4-dinitrophenol.

[This is an important finding as the phosphate esters normally formed during oxidative phosphory- lation associated with the uptake of oxygen by living cells are of crucial importance to cell metabolism, for which they supply energy.]

Fletcher, M. J. (1962). Uncoupling of oxidative phosphorylation by cadmium ion and by arsenite in submitochondrial fragments. Fed. Proc. 21, 53.

121. CADMIUM INFLUENCES SODIUM EXCRETION

Kagi & Vallee (J. biol. Chem. 1960, 235, 3460; ibm 1961, 236, 2435) found that cadmium accumu- lated in the renal cortex in the form of a complex with protein, metallothionein; the physiological role of this compound is not known. In the present investigation the effect of cadmium chloride (I) on renal function was studied. Intravenous infusions of 0.35-4.46 laM I/kg were made in anaesthetized dogs together with cysteine in order to prevent or minimize changes caused by I upon blood pressure, or the amount of blood passing through the kidneys and glomeruli. A decreased excretion of sodium resulted in all cases; the dose-response curve for this