UDC 613.632+613.62]: 66

Major Problems of Occupational Pathology in the Chemical Industry

Prof. S. I. Ashbel

Gorky Research Institute of Occupational Hygiene and Occupational Diseases, Ministry of Health of the RSFSR

For many years, extensive work has been carried out at chemical plants to improve the working environment, organize work processes rationally, and introduce effective measures to protect workers’ health. This has led to a sharp reduction in the frequency and severity of occupational poisoning and to the elimination of some forms altogether. In particular, severe poisoning by such “old” industrial toxicants as lead, tetraethyl lead, mercury, manganese, phosphorus, and solvents has almost completely disappeared, while cases of acute poisoning by irritant gases, carbon monoxide, and other occupational toxicants have become relatively rare.

The progress made in reducing occupational disease among chemical industry workers should not, however, give rise to complacency. The rapid growth of this industry, the widespread introduction of the latest scientific and technological advances, and the adoption of numerous new chemical substances may all contribute to the emergence of new forms of occupational disease requiring specialized, in-depth study.

The production of pesticides with pronounced toxic properties poses a major danger to workers’ health. The danger is particularly great when production of new pesticides is being established or when their output is sharply increased within the same facilities. During this period, acute, subacute, and chronic poisoning may occur. Such cases have been observed among workers producing the organomercury fungicide Granosan (S. I. Ashbel); organophosphate insecticides—metaphos, mercaptophos, methylmercaptophos, chlorophos, thiophos, and others (Yu. S. Kagan; M. A. Kazakevich; I. Ya. Sosnovik; S. L. Tribukh and coauthors; I. S. Faerman and E. M. Bongardt, and others); and organochlorine pesticides—DDT,

hexachlorane, lindane, chlordane, heptachlor, and others (P. I. Kalyaganov; V. A. Kayanovich and coauthors, 1956; E. P. Krasnyuk¹ and others).

A characteristic feature of the production of many pesticides is that not only the final products but also the starting materials and intermediates used in their synthesis possess pronounced toxic properties. Thus, in the production of granosan, the starting materials are mercury and mercuric chloride, and the intermediate is ethylmercuric chloride (the active ingredient of granosan). All these products are highly toxic. In the production of chlorophos, workers have occupational contact not only with the final product but also with the intermediates—phosphorus trichloride and dimethyl phosphite—which are likewise toxic in nature. In the production of the pesticides heptachlor and chlordane, the intermediate hexachloropentadiene is more hazardous than the final products.

The risk of occupational pesticide poisoning threatens not only those engaged in preparing them but also those who come into contact with them during transport and warehouse storage, as well as when using them to treat grain or destroy insects, rodents, weeds, and so forth.

The rapid increase in the production of synthetic resins, plastics, artificial fibers, and rubber necessitates a manyfold expansion in the output of the corresponding raw materials. The chemical products ordinarily encountered in their production often lack pronounced toxic properties, and workers handling them do not develop significant occupational disease. In some cases, however, prolonged exposure to starting materials, intermediates, or final products, or a change in the technological process involving the use of a new substance, may give rise to severe forms of occupational poisoning.

For example, in the manufacture of ethylene hydrocarbons (olefins) and an ethylene derivative (vinyl chloride), which serve as starting materials for the synthesis of organic compounds—primarily plastics, synthetic resins such as vinylite, rubber via butadiene, artificial fibers, and so forth—the health of workers gave no cause for concern for many years. After some time, however, changes in the nature of production were followed by cases of occupational poisoning resembling angioneurosis and seriously affecting the workers’ health and ability to work (V. A. Antonyuzhenko and coauthors; N. A. Smirnova²). Prolonged observation over more than 10 years of the health of workers engaged in the manufacture of caprolactam, the raw material for kapron fiber, revealed no pathological changes that could be attributed to exposure to the chemicals encountered in this production process. But when the technological process was changed and trichloroethylene began to be used as a solvent for extracting caprolactam, cases of subacute and chronic poisoning appeared, with a distinctive clinical picture of nervous system damage (V. A. Antonyuzhenko and coauthors).

Thus, workers in some new chemical production processes may develop occupational poisoning. Timely study of occupational pathology at the many new enterprises of the large-scale chemical industry is therefore highly important, particularly during the commissioning of pilot chemical plants.

When studying the effects of new chemical products on workers, it should be borne in mind that many of them, upon entering—

¹ Candidate’s dissertation. Kyiv, 1961.
² Candidate’s dissertation. Moscow, 1959.

…upon entering the body (for example, through the skin), can alter its reactivity, that is, sharply increase its sensitivity. This can lead to the development of occupational allergic diseases of the bronchopulmonary system—asthmatic bronchitis and bronchial asthma—as well as skin diseases, including dermatitis and eczema (S. I. Ashbel and Z. V. Sharonova). Cases of occupational bronchial asthma have been described among workers exposed to polyisocyanates (Schürmann; Svensson et al.), trichloroethylene (Gilbert-Dreyfus), persulfates (N. T. Sverdlina and Z. V. Lukina), complex chloroplatinates (Hunter et al., Marshall, A. Roberts), beryllium fluoride (B. E. Izrael), chromium and its compounds (M. M. Batsheva and V. G. Skripnichenko, S. M. Genkin), antibiotics—penicillin, streptomycin, and biomycin (A. M. Ranevskaya and L. P. Zorina, A. Roberts)—and many other substances. An even larger number of chemicals, including most of those listed above, can cause allergic skin diseases.

When chemicals are suspected of having allergenic properties, particularly those newly introduced into industry, efforts should be made not only to identify features in the clinical course of the occupational diseases they cause that confirm their allergic origin, but also to use the diagnostic methods of modern allergology. These include specific skin tests with the relevant potential occupational allergens, the Prausnitz–Küstner skin test, the antiglobulin agglutination test using tanned erythrocytes, controlled expiratory allergy tests, and others.

Early diagnosis of occupational allergic diseases is of great importance. It makes it possible to take the necessary preventive measures promptly, begin treating affected workers, and arrange suitable employment for them.

According to statistical data, cases of occupational cancer at various sites have recently become more frequent (P. P. Dvizhkov). This is largely attributable to the pronounced carcinogenic effects of certain substances manufactured and used in various industries. Thus, cancer of the lung and nasal passages has been found to occur more frequently than in the general population among workers with prolonged exposure to nickel compounds (Amor; Hueper; Teleky). Lung cancer has also been found among workers with prolonged occupational contact with chromates (Abwens et al., Baetja, Bidstrup, Gregorius), arsenic compounds (Currie, Perry et al.), asbestos (Gloyens, Stoll et al.), vapors or mists of mineral oils and emulsions (Huguenin et al.), and isopropyl alcohol (Well et al.). Acute and chronic leukemias have been associated with chronic benzene poisoning (Bousser et al., Galanotsi et al.). Lung cancer occurs more often in patients with pneumosclerosis of toxicochemical origin than in patients with nonoccupational pneumosclerosis (S. I. Ashbel, 1959).

More than 300 substances are now known to have caused tumors in experimental animals.¹ However, the number of chemical carcinogens whose effects are more or less strong and unequivocally established is considerably smaller and does not exceed 30 (L. M. Shabad). Since some new chemicals may have carcinogenic properties, experimental studies of their toxicity must also pay particular attention to the possibility that they may promote…

¹ According to Hartwell, approximately 25% of the 2,113 chemical substances studied proved to be carcinogenic.

…develop cancer. Experimental studies have revealed pronounced blastomogenic properties in a number of chemical substances, including compounds of beryllium and selenium, dicyclohexylamine and its nitrite, metallic cobalt, certain chlorinated hydrocarbons, polyvinyl chloride, Silastic, and others.

However, fully reliable information is not yet available on the frequency of malignant neoplasms among workers who regularly handle these and similar substances. One pressing task, therefore, is a comparative clinical and statistical study of the incidence of malignant neoplasms among people occupationally exposed to chemicals that are potential carcinogens and among other population groups without such exposure. Hygienists, occupational disease specialists, oncologists, and pathologists must also jointly investigate the conditions that predispose individuals to occupational cancer. Great progress has been made in studying the pathogenesis of many occupational poisonings. A new theory has emerged according to which the toxic action of many poisons can be regarded as a consequence of their damaging effects on enzymatic processes. Thus, the toxicity of a number of enzyme poisons—arsenic, mercury, chromium, bismuth, nickel, and others—has been found to depend on their action on the sulfhydryl (thiol) groups of cellular proteins (M. L. Belenky, V. I. Rosengart). This discovery led to the synthesis of highly active antidotes (BAL and the Soviet drug Unithiol) which, because of the thiol groups in their structure, can help free enzyme systems from the blocking effects of thiol poisons.

The discovery of the anticholinesterase mechanism underlying the toxic action of organophosphorus compounds, which are widely used as highly effective insecticides, provided the basis for treating poisoning by these compounds with anticholinergic drugs (atropine, tropacin, pentaphen, merpanit, and others). These drugs can block the cholinoceptive systems selectively affected by the poison, thereby helping to cure the poisoning.

Over the past decade, complexing agents have come into use as antidotes. The most commonly used is the calcium disodium salt of ethylenediaminetetraacetic acid (CaNa₂ EDTA), which can bind ions of lead, uranium, yttrium, cerium, and other elements (D. I. Semenov and I. P. Tregubenko; Seven). Work is now under way to develop new, effective complexing agents.

It is thus evident that the study of underlying biochemical processes is of enormous importance for elucidating the pathogenesis of occupational poisonings and developing highly effective antidotal therapies. One of the important tasks of modern occupational pathology and industrial toxicology is to make extensive use of biochemical, and particularly enzymological, approaches in studying the toxic properties of industrial poisons. This will equip physicians with new, more effective methods for the early diagnosis, treatment, and prevention of occupational poisonings caused by various substances, including those newly introduced into industry.

Large numbers of women work in many chemical plants. It is therefore essential to clarify the particular effects of chemical products, especially new ones, on the female body and, in particular, on its specific maternal functions. Unfortunately, very few reports have been published on this subject (S. M. Kanevskaya; V. A. Kayanovich and co-authors, M. A. Petrov-Mas-

…varnishes). Obstetrician-gynecologists, working together with occupational disease specialists, need to study the effects of various industrial poisons on reproductive function and the course of pregnancy in women employed in chemical manufacturing, as well as on their offspring.

With the rapid growth of the chemical industry, many young people will join its new enterprises in the coming years; a very large number of adolescents will prepare for work in chemical manufacturing at specialized vocational schools and technical colleges. It should also be borne in mind that senior secondary-school pupils may work in various chemical production shops as part of their practical training, for no more than three hours a day. All this makes it necessary not only to intensify experimental work in age-related toxicology, but also to investigate the effects of various chemicals on adolescents and young adults, taking sex differences into account.

A legally binding list should be established of chemical manufacturing operations in which adolescents are prohibited from working, even for short periods of several hours a day. This list should include enterprises or production shops where occupational poisoning still occurs or where the potential risk of poisoning is high—for example, facilities manufacturing many toxic pesticides—as well as operations in which young workers may be exposed even to low concentrations of poisons that affect the nervous system, particularly organic solvent vapors (narcotics), since young people are more sensitive to the latter (N. V. Lazarev).

Thus, the development of large-scale chemical production poses a wide range of challenges for medical science, and especially for occupational pathology. Meeting these challenges requires a well-organized occupational pathology service that fully satisfies the needs and demands of the chemical industry; thorough training in occupational pathology, particularly clinical industrial toxicology, for physicians caring for workers in this industry; and a substantial expansion of the facilities available for studying occupational pathology through the establishment of occupational disease clinics not only within institutes of occupational hygiene but also within medical institutes. These clinics should not only train future physicians to combat occupational diseases, but also engage researchers from the various theoretical and clinical departments of medical institutes in studying regional patterns of occupational disease, including diseases of toxicochemical origin. In this way, they would help substantially improve the effectiveness of efforts to combat occupational diseases and occupational poisoning in many territories and regions of our country.

References

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Russkikh A. A. In: Proceedings on Occupational Hygiene and the Clinical Study of Occupational Diseases. Gorky, 1956, issue 5, p. 52. — Kayanovich V. A., Kozhevnikova Z. I., Miropolskaya I. L., et al. Gigiena truda, 1958, no. 1, p. 26. — Lazarev N. V. General Principles of Industrial Toxicology. Moscow–Leningrad, 1938. — Petrov-Maslakov M. A. Vestn. AMN SSSR, 1960, no. 7, p. 53. — Sverdlina N. T., Lukina Z. V. In: Proceedings of the Scientific Session of the Leningrad Institute of Occupational Hygiene and Occupational Diseases, Devoted to the Results of the Institute’s Work in 1959–1960. Leningrad, 1961, p. 58. — Sosnovik I. Ya. Clinical Features and Prevention of Pesticide Poisoning. Moscow, 1959, p. 26. — Tribukh S. L., Kazakevich M. A., Tsivileva E. A. Gig. i san., 1954, no. 4, p. 16. — Faerman I. S., Bongardt E. M. In: Industrial Toxicology and the Clinical Study of Occupational Diseases of Chemical Etiology. Moscow, 1962, p. 260. — Shabad L. M. Ibid., 1960, no. 3, p. 8. — Hueper W. C., Texas Rep. Biol. Med., 1952, vol. 10, p. 167. — Hunter D., Milton R., Perry K. M. A., Brit. J. industr. Med., 1945, vol. 2, p. 92. — Marshall J., S. Afr. med. J., 1952, vol. 26, p. 8. — Schürmann D., Dtsch. med. Wschr., 1955, vol. 80, p. 1661. — Svensson A., Holmquist C. E., Lundgren K. D., Brit. J. industr. Med., 1955, vol. 12, p. 50. — Teleky L., Die Gewerbliche Vergiftungen. Berlin, 1955, p. 106.

Received August 7, 1964.