Br J Ind Med: first published as 10.1136/oem.3.4.207 on 1 October 1946. Downloaded from THE TOXICOLOGY OF THE NEWER METALS BY LAWRENCE T. FAIRHALL From the Industrial Hygiene Division, United States Public Health Service In the following discussion of the toxicology of resulted from chemical pneumonitis. A similar ' newer' it is more accurate to chemical pneumonitis developed in- an additional 33 the metals, perhaps workers at various occupations in these plants. While refer to them as metals which have only recently the hazard due to dust and fume that existed in the plants become of industrial importance. Most of the was undeniable, the term ' beryllium poisoning ' is a metals mentioned have long been known, and in misnomer, since no toxic action can be directly attributed some instances have actually been used in quantity. to the beryllium ion itself, and the beryllium in these cases merely acted as an adjuvant. However, many new types of use have developed, In connexion with the manufacture of fluorescent or unusual compounds have become important lamps, a number of cases designated as sarcoidosis were industrially and have aroused the interest of the reported in 1943 in the Massachusetts area. Since industrial hygiehist. beryllium oxide is one ofthe constituents ofthe fluorescent powder, and since very little was known concerning the It should be realized that the metals and their toxicity of beryllium, this substance was suspected as the compounds in general have distinctive character- aetiological factor in the production of sarcoidosis. istics, and that it is somewhat difficult to group their The inhalation of beryllium sulphate dust was shown physiological action in the same way as is possible to be injurious to guinea-pigs, 67 % mortality in one exposure, in experimental work reported by Hyslop with great groups of organic compounds. For et al. in 1943; but, when the more neutral potassium instance, the nitro or amino compounds, or the beryllium sulphate was substituted, the animals were able halogenated hydrocarbons, have many character- to tolerate much larger doses; there was no mortality in of large doses daily for seven days. Later experimental istics which permit some evaluation the toxic work, using rabbits, has confirmed this earlier finding. qualities of the individual members of the group Beryllium sulphate is so extensively hydrolysed that from what we know of the group in general. The hydrogen is evolved when zinc is placed in a solution of behaviour of the metals and their compounds is far the salt. It is understandable that the inhalation of less predictable from this point of view. Character- beryllium sulphate dust would prove strongly irritating, owing to the local production of sulphuric acid in contact istics which belong to the group as a whole may with the delicate tissue of the lung substance. The pro- vanish with one particular compound, or vice versa. duction a in victim to of pneumonitis the exposed such http://oem.bmj.com/ Thus, tin salts are quite harmless. Individuals irritating material is readily understood. Potassium daily consume quantities of tin that would be a beryllium sulphate, on the other hand, is soluble in cold water, is nearly neutral in reaction, and yields all the matter of concern if tin were as toxic as many other reactions characteristic of the beryllium ion. It is not metals generally regarded as harmless. Yet tin bound as a complex, which might be expected to have tetrahydride is stated to be one of the most toxic different properties from other beryllium salt solutions. substances, being more poisonous than arsine. The If beryllium were a protoplasmic poison, both beryllium sulphate and potassium beryllium sulphate should show following discussion, therefore, tries to evaluate the similar effects. With reference to the ulceration pro- known facts about the physiological action of the duced by beryllium sulphate entering cracks in the skin- on September 23, 2021 by guest. Protected copyright. metals and their compounds as separate entities. a condition which occasionally occurs with employees Very little is known of some of these substances, handling this material-it would be of interest to try the effects of beryllium salts of more inert acids, such as either because they have been of no great commercial beryllium citrate or beryllium malate. importance, or because heretofore they have not displayed properties which are distinctive in a Cadmium physiological sense. In spite of the increased attention which has been devoted to the hygienic significance of cadmiumr, cases of poisoning-usually resulting from unsuspected origin- Beryllium appear with sufficient frequency to re-emphasize the fact A few articles have been added to the recent literature that cadmium is a potentially dangerous substance. The concerning the industrial hazards associated with the extensive report of Spolyar and his associates on cases of production of beryllium, but during the past three years cadmium poisoning resulting from flanging operations no work has been reported on the physiological action on cadmium-plated pipe gives a particularly clear insight of beryllium itself. Shilen, Galloway, and Mellor (1944) into the type of danger resulting from exposure to reported the health hazards incident to the extraction of cadmium oxide fumes. Five cases, including one death, beryllium. Kress and Crispell have reported cases of are summarized. On the basis of the 59 cases reported chemical pneumonitis in men working with fluorescent in the literature, the mortality rate of industrial cadmium powder containing beryllium. Van Ordstrand, Hughes, poisoning appears to be 15 °/0. De Nardi and Carmody have recently reported the As a result of cases of cadmium poisoning arising from dermatological and other effects which they have observed the heating ofcadmium-coated metal-with the attendant in the beryllium industry during the past four years, and formation and volatilization of dangerous quantities which were reported under the heading of ' beryllium of cadmium oxide-the labelling of cadmium-coated poisoning.' The fatal cases described in this report metals has been urged. While this measure is effective Q 207 208 BRITISH JOURNAL OF INDUSTRIAL MEDICINE Br J Ind Med: first published as 10.1136/oem.3.4.207 on 1 October 1946. Downloaded from for large pieces, it is somewhat difficult to ensure that the rapid growth of the cemented tungsten carbide small objects so coated are labelled. A very con- industry-has drawn attention to possible injurious venient test that can be directly applied to the cadmium- action, both on the skin, and after inhalation of this coated surface depends upon the formation of a yellow finely-divided material. There is a substantial amount cadmium sulphide stain on the metal surface. of experimental work on the physiological action of Cases of cadmium poisoning from careless use of cobalt reported in the literature, and it would appear that vessels as beverage containers continue to be reported. the toxicity of cobalt by mouth is low. Antal (1894) In 1944 Lufkin and Hodges reported twelve men as found that a gramme of cobalt nitrate in 1 °0 solution having been affected by artificial lemonade prepared in had no perceptible effect on rabbits, although the same metal containers which were later shown to be cadmium- quantity in 5 %Y solution' was occasionally lethal. coated. The significant feature of cadmium poisoning Chittenden and Norris (1889) also observed that the by mouth is the rapidity of physiological response. The poisonous action of cobalt on rabbits is slow, and effects usually occur within 15 to 30 minutes after inges- apparent only after the administration of relatively large tion of food or drink containing toxic quantities of doses. Intravenously, cobalt has been observed to cause cadmium. This in itself should be suggestive in cases paralysis of the extremities, enteritis and death. Le Goff of so-called food poisoning. Occasionally, however, (1930) found that cobalt given intravenously in man symptoms may be delayed as long as four or five hours. produced a marked dilatation of the blood vessels of the Although cases of extensive cadmium poisoning have face, with a slight fall of blood pressure. been reported from the use of cadmium-coated ice-cube A well-recognized effect. of the administration of containers in refrigerators, an unusual source of cadmium cobalt salts to animals is polycythaemia, and most of the contamination was reported by Shiftner and Mahler in investigations relating to the physiological activity of 1943 as having affected seven persons: cadmium plating cobalt have revolved around this phenomenon. Orten of the refrigerating unit itself was responsible. Flakes (1936) concluded that the haematopoietic activity of of cadmium had dropped into the ice-cube compart- cobalt is the result of an increase in rate of formation of ment. A sample of ice cubes from the trays contained haemoglobin and erythrocytes, rather than of a passive 769 parts per million of cadmium. A survey of apart- accumulation of red cells resulting from a diminished ment houses showed that 25 % of the refrigerators tested rate of cell destruction. Frequent reference has been had cadmium-coated parts. made to the work of Barron and Barron (1936), who state Ross has recently cited a case of mass poisoning due that small amounts of cobalt inhibit the respiration in to cadmium oxide fumes, in which 23 individuals were vitro of various tissues-notably reticulocytes and bone affected. Finely divided cadmium dust from a cadmium- marrow. However, in recent experiments Warren et al. recovery chamber became ignited owing to red-hot have been unable to confirm this finding. Frost et al. cigarette ash carelessly dropped by one of the workers. found haematopoietic response at a minimum level of In a few minutes the cadmium dust became incandescent, 1 mg. per kg. of body weight per day when cobalt was emitting clouds of cadmium-oxide fumes.