PROTEINURIA DUE TO INHALATION OF CADMIUM STEARATE DUST

Transcription

1 Ind. Health, 1965, 3, 73. PROTEINURIA DUE TO INHALATION OF CADMIUM STEARATE DUST Shosuke SUZUKI, Tsuguyoshi SUZUKI and Masami ASHIZAWA Department of Public Health, Faculty of Medicine, University of Tokyo, Motofujicho, Bunkyo-ku, Tokyo and Department of Public Health, School of Health Care Sciences, Faculty of Medicine, University of Tokyo, Motofujicho, Bunkyo-ku, Tokyo (Received September 18, 1965) The workers, who had been exposed to dusts of stabilizers including lead stearate, lead orthosilicate, cadmium stearate and others in a vinyl chloride film manufacturing factory, were examind in 1963 and A high occurrence of proteinuria was observed without any change in the function of the respiratory organs. Their urinary excretion of cadmium was found to increase, though slight, but no increase in urinary lead excretion. From the results, the proteinuria was supposed to be due to the absorption of cadmium stearate. This is a study of health conditions in workers employed in a vinyl chloride film plant. In this factory, polymers of vinyl chloride are blended with plasticizers and stabilizers, and are laminated to a film. Dioctyl phthalate, dioctyl adipate and dibutyl phthalate used as plasticizers are all in the liquid state, but cadmium stearate, lead stearate, lead orthosilicate, calcium stearate and dibutyl tin laurate used as stabilizers are treated in the form of powder. Consequently, workers are exposed to the dust of these stabilizers during the weighing, casting into a blender and blending of them. The present study is mainly concerned with lead compounds and cadmium stearate, because, the toxicity of these compounds are considered to be much preponderant than others. The paper is divided into two parts; part 1 reports on the concentrations of these materials in air during the various work processes and part 2 deals with the health conditions of workers who have been exposed to these dusts. PART 1 Methods Standard impingers were used as air samling devices and operated with 75 73

2 S. SUZUKI, T. SUZUKI AND M. ASHIZAWA ml of 10% nitric acid and at sampling rate of 20 1pm. After sampling, the impinger samples were extracted with adequate volume of ether to exclude free organic acid. Lead in the samples was determined colorimetrically with a dithizone method of Tada 1) and cadmium with a dithizone method of Saltzman. 2) A cascade impactor was used for the determination of particle size distribution of dusts in air and the number of particles on each slide was counted by the optical microscopy in the dark field illumination. Results Table 1 shows the results of the determination of lead and cadmium concentrations in air. High concentrations of lead were found to be caused by the casting and weighing of its compounds. The concentration of cadmium was usually lower than that of lead in each work process except in a case of the sampling several minutes after the casting. Between the first and second surveys, local exhaust hoods was equipped at the sites of weighing and casting. The concentrations of these metal dusts decreased considerably, though not satisfactorily at the second survey. Table 1. Concentrations of lead and cadmium in the air during various work processes. Table 2 shows the results of the determination of particle size distributions. It is noteworthy that the particles larger than 6ƒÊ were found only in the casting process of the mixture including lead stearate, cadmium stearate and stabinex, and the most particles were found to belong to the smallest group in the case of cadmium stearate only. It took twenty minutes to complete a series of work processes including 74

3 PROTEINURIA BY CADMIUM STEARATE the weighing, casting and blending of the stabilizers. The workers usually repeated these processes three or four times in each work shift of eight hours. Table 2. Particle size distribution of metallic soap dusts. (The percentage in the table shows that of the number of particles on each slide to the total number of dusts.) PART 2 Methods of Investigation Health examinations on workers were carried out twice in 1963 and In 1963, 34 workers were examined, in whom 27 men were exposed to stabilizers and other 7 men were not and served as control. In 1964, 19 exposed workers, including 17 men examined 1963, and 24 non-exposed were examined. The nonexposed workers in 1964 were not examined in An interview and clinical examination was made. The occupational history, past medical history and family history were obtained, and a specific inquiry was made about cough, dyspnea, watery discharge from the nose, anosmia and yellow discoloration of the teeth. Olfactory acuity was measured by the method described by R. G. Adams and N. Crabtree. 3) At the clinical examination, height, weight, circumference of the chest and blood pressure were measured. The hemoglobin concentration was estimated by cyan-methemoglobin method 4) and the specific gravity of the whole blood by copper sulphate method. 5) Giemsa staining was used for estimation of the basophilic stippled erythrocyte. Thymol reaction of the serum was observed. The concentration of serum cholesterol was determined by Zak and Henly's method 6) only in All the men discharged the urine for examination when they attended for clinical examination. The urine were tested for specific gravity, sugar, blood and protein. The methods used for the test of protein were the boiling test, 25 % trichloracetic acid test and sulfosalicylic acid test. The urinary coproporphyrin concentration was determined by Askevold's method. 7) The concentration of lead and cadmium in the urine were determined with the same dithizone method as in the air, after oxidation of the urine with the mixture of conc. nitric acid, 75

4 S. SUZUKI, T. SUZUKI AND M. ASHIZAWA sulphuric acid and perchloric acid. In 1964, the urinary zinc concentration was determined by Kato and Takei's dithizone method. 8) Following respiratory function tests were performed on all the men attended for the examination in 1964 ; the vital capacity, one second vital capacity and its rate to the vital capacity, and the maximal expiratory flow rate, which were measured from three curves of fast vital capacity of each subject obtained by an instrument made by Mckesson Appliance Co., vitalor. Peak flow rate was determined with a Wright's peak flow meter. Results 1) Assessment of the Extent of Lead Exposure in 1963 In 1963, the major purpose of survey was to evaluate the extent of risk due to lead compounds. As is shown in Figs. 1 and 2, no increase of urinary lead and coproporphyrin concentrations were found in the exposed workers. They Fig. 1. Distribution of lead concentration in exposed & control. Fig. 2. Urinary coproporphyrin concentration in exposed and control. 76

5 PROTEINURIA BY CADMIUM STEARATE did not tend to be anemic and the rates of the basophilic stippled cell were all below 0.05% (Table 3). From these results, the risk due to lead was assumed to be negligible. Table 3. Results of blood examinations in ) Proteinuria and Glycosuria The most prominent finding in 1963 was a high frequency of proteinuria and glycosuria in the exposed workers (Table 4). It was noteworthy that the rate of urine reacted positively for protein was higher in case of trichloracetic acid test than in sulfosalicylic acid test. Table 4. Results of urine examiantions in ) Cadmium Concentration in the Urine in 1963 Urinary cadmium concentrations ranged from 0 to 10.0 Đg/1 (Table 5), and Table 5. Cadmium concentratoins in the urine (Đg/1) in

6 S. SUZUKI, T. SUZUKI AND M. ASHIZAWA they had not significant correlations with urinary lead concentrations (Fig. 3) and urinary protein concentrations (Fig. 4). Fig. 3. Lead and cadmium concentrations in urine. Fig. 4. Proteinuria and cadmium concentration in urine. 4) Evaluation of Effects of Cadmium in 1964 In 1964, 24 workers, not exposed to stabilizers and being similar to the exposed workers in terms of their age, years of employment and physique, 78

7 PROTEINURIA BY CADMIUM STEARATE were selected as control (Table 6). No hypertensive man was included in both groups. Table 6. Age, years of employment and results of physical measurements in the exposed and control groups in ) Subjective complaints and olfactory acuity. The specific inquiry revealed that there was no difference on the frequencies of subjective complaints, such as fatigue, cough, shortness of breath, watery discharge from the nose, loss of appetite, nausea, epigastralgia, dizziness, sleeplessness and headache, between the two groups (Table 7). Yellow discoloration of the teeth was not found. Two anosmic men in the exposed group and three in the control were found by the olfactory acuity test. Table 7. Subjective complaints of workers in ) Laboratory findings on the blood. Table 8 shows the results of the examination on the blood. No difference was found on the specific gravity of the blood, 79

8 S. SUZUKI, T. SUZUKI AND M. ASHIZAWA hemoglobin concentration, serum cholesterol concentration and value of Thymol reaction of the serum between the two groups. Table 8. Results of blood examinations in ) Urinary cadmium and zinc concentration. The results of cadmium and zinc Fig. 5. Cadmium and zinc concentrations in urine. 80

9 PROTEINURIA BY CADMIUM STEARATE determination in the urine are shown in Table 9 and Fig. 5. The corrected cadmium and zinc concentration was calculated by the following equation : Table 9. Frequency distributions of exposed and control groups for cadmium and zinc concentrations in the urine in corrected conc. = original conc. ~ (1.024/ specific gravity of the original urine) The mean cadmium concentration, original and corrected, was slightly higher in the exposed than in the control, but the difference was not statistically significant. However, there was seen a significant difference between the values of variance of both groups (Fs=4.40, Fo (0.05) =2.07). In the zinc concentration, no particular finding was obtained. An interesting finding was obtained on the relation of urinary cadmium and zinc concentrations. As is shown in Fig. 6, workers, whose urinary cadmium concentrations are high (above 6.0 Đg/1), have low urinary zinc concentrations irrespective of the exposure to stabilizers. Fig. 6. Relationship of urinary zinc and cadmium concentrations. 4-4) Proteinuria. A high frequency of proteinuria in the exposed workers was 81

10 S. SUZUKI. T. SUZUKI AND M. ASHIZAWA observed also in Fig. 7 shows the results of three tests of trichloracetic acid, sulfosalicylic acid and boiling, and it is seen that the exposed group has a significantly high frequency of proteinuria in all three tests comparing to the control group. In the reexamined workers, the frequency and severity of proteinuria increased (Fig. 8). No definite correlation was found between urinary cadmium and protein concentrations (Fig. 9). Fig. 7. Proteinuria in Fig. 8. Change in urinary protein excretion of the exposed workers. By TCA test. Fig. 9. Cadmium and protein in urine. 4-5) Other laboratory findings on the urine. Results of sugar and occulted blood tests on the urine are shown in Table 10. Six out of 19 exposed workers had positive reactions of glucose, but no workers with occulted blood were found. 4-6) Respiratory functions. As for the maximal expiratory flow rate, vital capacity, one second vital capacity and the rate of one second vital capacity to vital 82

11 PROTEINURIA BY CADMIUM STEARATE capacity, no difference was found between the exposed and control groups. (Table 11). Table 10. Laboratory findings on the urine. Table 11. Results of respiratory function tests in Comment Since the first description by Stephens in 1921,9) many reports have been accumulated on chronic cadmium poisoning. As the symptoms characterizing chronic cadmium poisoning, the presumably irreversible renal failure with proteinuria, on which protein is said to be of low molecular weight, and the bronchectasia with the respiratory hypofunction, have been depicted by many authors. 10 `13) Besides these two symptoms, yellow rings at the neck of incisors,14) inflammatory lesion of the upper respiratory tract or ulcer of the nasal mucous membrane, 15) anosmia.3,16) anemia of slight extent, 17) hypofunction of the liver,18) degeneration of the bone 19) and others have been reported occasionally in chronic cadmium poisoning. Hitherto, most of the reports have been concerned with cadmium fume and cadmium oxide in alkaline battery works, cadmium alloy factories, metal soldering factories and so on. As far as the authors know, the report on poisoning due to cadmium stearate was first described by Sakabe and Ushio in ) and it represented some cases of acutely intoxicated worker, whose symptoms were nausea, vomiting, loss of appetite and epigastralgia and these symptoms began to occur several hours after the start of work with cadmium 83

12 S. SUZUKI, T. SUZUKI AND M. ASHIZAWA stearate. Now, the present authors should discuss the results of survey. Summing up the results : The workers had been exposed to the dusts of lead compounds of large particle size and cadmium stearate of small size. Although the concentrations of lead in air were higher than those of cadmium, workers were assumed not to receive the influence of lead compounds. They had a frequent occurrence of proteinuria with a slight increase of urinary cadmium concentration. Glycosuria was also found to a somewhat high frequency. It is an important and interesting fact that no respiratory hypofunction has been found, even though the concentrations of cadmium in the air have not been so high as in the literal cases and the workers have had relatively short years of exposure in the present case. Concerning the effects of cadmium oxide to the respiratory organs, Hardy, 21) Friberg, 18) and Bonnel 13) described that the respiratory symptoms could be found already in the concentrations from several tens to several hundreds microgram of cadmium per cubic meter of air. Cadmium stearate may have a less severe local action to the lung than cadmium metal or cadmium oxide. From the results on the determinations of urinary cadmium and lead concentrations, it might be supposed that the absorption of cadmium was not so much but distinct in the exposed workers, but that of lead was negligible. Then, the cadmium stearate was assumed to play a leading role in manifesting a high occurrence of proteinuria. The fact that the frequency of proteinuria was found to be the highest by trichloracetic acid test, may partly support the probability of the role of cadmium. Although most of the studies indicate that cadmium is rather poorly excreted in the urine, 22) the increase of urinary cadmium excretion in the present cases is not so large as in the literature. There may be a tendency of slow excretion of cadmium stearate in the urine as seen in the suggestive result by Yoshikawa et al., 23) by whom cadmium stearate injected intraperitoneally was more slowly excreted in mice than cadmium chloride. As for glycosuria in chronic cadmium poisoning, only Bonnel 12) reported its occurrence and it was said by Yoshikawa 24) that glycosuria was found in an experimental poisoning by cadmium stearate. As far as the present knowledge, any precise discussion is impossible on the origin of this glycosuria. Finally, the items to be discussed is the relationship of zinc and cadmium in the living body. Recently, an administration of cadmium salts is reported to occur the change of the normal metabolism of zinc 25) and it was already reported that a large dose of zinc could protect the lesion of the testicles resulted from cadmium injection in experimental animal. 26) The present findings on urinary zinc and cadmium concentrations may be an expression of homeostatic 84

13 PROTEINURIA BY CADMIUM STEARATE mechanism for zinc in the living body. Anyway, a further investigation is necessary to clarify the relationship of zinc and cadmium in their urinary excretion. ACKNOWLEDGEMENT This survey was supported by the able guidance of Prof. H. Katsunuma and the cooperation of Mr. S. Nishii, Dr. H. Toyokawa, Mrs. K. Tsuda and Miss T. Miyama. The authors wish to say the heartfelt thanks to them. REFERENCES 1) Tada, O. (1957). J. Sci. Labor, 35, 669. (in Japanese) 2) Saltzman, B. E. (1953). Anal. Chem., 25, ) Adams, R. G. & Crabtree, N. (1961). Brit. J. Ind. Med.,18, ) Drabkin, D.L. (1950). Med. Phys., 2, ) Phyllips et al. (1950). J. Biol. Chem., 183, ) Zak, B. (1957). Am. J. Clin. Pathol., 27, ) Askevold, R. (1951). Scand. J. Clin. Lab. Invest., 3, ) Kato, T. & Takei, N. (1953). Jap. J. Anal. Chem., 2, 208. (in Japanese) 9) Stephens, G.A. (1920). J. Ind. Hyg., 2, ) Friberg, L. (1952). A. M. A. Arch. Ind. Hyg. Occupational. Med., 5, ) Friberg, L. (1959). A. M. A. Arch. Ind. Health, 20, ) Bonnel, J. A. (1955). Brit. J. Ind. Med., 12, ) Bonnel, J. A. (1959). Brit. J. Ind. Med., 16, ) Princi, F. & Geever, E. F. (1950). A. M. A. Arch. Ind. Hyg. Occupational Med., 1, ) Baader, E. W. (1951). Deut. Med. Wochschr., 76, ) Friberg, L. (1948). J. Ind. Hyg. Toxicol., 30, ) Hunter, D. (1954). Arch. Hig. Rada, 5, 221. (abstracted in Ind. Hyg. Digest, 1954,18, 15.) 18) Friberg, L. (1950). A. M. A. Arch. Ind. Hyg. Occupational Med., 1, ) Nicaud, P. et al. (1942). Arch. Maladies Profess., 4, 192. (cited in Bonnel, J. A. (1955) Ref. No. 12) 20) Sakabe, H. & Ushio, K. (1960). Bull. Nat. Inst. Ind. Health,, 3, ) Hardy, H. L. & Skinner, J. B. (1947). J. Ind. Hyg., 29, ) Elkins, H. B. (1959). The Chemistry of Industrial Toxicology, 2nd ed., p. 38. John Wiley & Sons, Inc., New York. 23) Yoshikawa, H. (1960). Jap. J. Ind. Health, 2, 342. (in Japanese) 24) Yoshikawa, H. (1965). Private communication. 25) Cotzias, G. C. & Papavasilion, P. S. (1964). Am J. Physiol., 206, ) Parizek, J. (1956). J. Endocrinol., 15,