Document Zn8eL5bEp7DzawGzZeBqz201Z

R&S 002800 3 OCCUPATIONAL HAZARDS IN PRODUCTION AND PROCESSING OF STYRENE POLYMERS - EPIDEMIOLOGIC FINDINGS William J. Nicholson and Diane Tarr Environmental Sciences Laboratory, Mount Sinai School of Medicine of CUNY, New York 10029 INTRODUCTION Of the major plastic monomers, styrene is exceeded only by ethylene, propylene and vinyl chlorid| in terms of produc tion. In 1977, approximately 3 x 10^ metric tons were produced in the United States and 7 x 10 metric tons world wide (IARC, 1979). Approximately 60% of the monomer pro duced was used in homopolymers, largely for the packaging industry. Other important uses of styrene are in the pro duction of copolymers with acrylonitrile (SAN) and acryloni trile and butadiene (AES). Styrene also finds widespread use as a copolymer with butadiene in the production of the synthetic elastomer, styrene-butadiene rubber (SBR), which forms the basis of approximately 80% of U.S. rubber products. Finally, it is extensively used as a solvent and cross-link ing agent for polyester resins in the fiber reinforced plastic (FRP) industry. Estimates of the number of workers employed in the various industries using styrene-based polymers are given in Table 1 along with typical exposure levels (Tossavainen, 1978). In addition to occupational exposure, low-level environmental contamination can occur from combustion of styrene-based products, as the thermal decomposition of polystyrene leads to evolution of the monomer, in contrast to other polymer materials. MORTALITY STUDIES OF STYRENE-EXPOSED WORKERS Studies on the mortality of populations exposed to styrene are fraught with difficulty because of confound- R&S 002801 Tabic 1 Occupational exposures to scyrctit Process Percent of stym* production Humber of worker* involved Monomer production Polymer production (PS.ABS.SBR) Reinforced plastics production (FRP) Polymer processing (PS.ABS.SBR) 100 60 - 70 10,000 50,000 20 - 30 200,000 5-10 1, 000,000 Typical Axposure (ppm) 1-20 1-20 20 - 300 0.01 - 1 From Tosaavalnco, 1978 iag exposures to other known carcinogenic materials. Benzene exposures can occur in the production of styrene monomer, as the principal production process utilizes benzene to produce ethylbenzene, which, in turn, is dehydrogenated to form styrene. Copolymerization invol ves exposures to acrylonitrile and/or butadiene, which are carcinogenic in animals (Huff, 1983). Finally, some of the additives used in styrene products may be carcino genic, as well as other chemicals used in facilities producing styrene or polystyrene. Only three studies provide data on possible human carcinogenicity of styrene, each having some of the confounding exposures mentioned above. All were of groups of individuals employed in monomer production, polymerization or polymer fabrication, where exposures were relatively limited. No data exist on the mortality of individuals employed in the FRP industry, where sty rene concentrations were (and are) commonly ten times higher. Table 2 lists the cohorts observed and some of the characteristics of the three studies. As can be seen from Table 2, the large number of indivi duals lost to follow-up in the study by Frentzel-Beyme et al (1978) severely limits its usefulness. Of those exposed, 7% of the German workers and 71% of foreign "guest workers" were untraced. Of those traced, 74 had died, 12 from cancer. Only 37 deaths occurred in those with five or more years of exposure. The overall result did not demonstrate excess mortality for any cause of death. However, the limitations of the study are clear. Table 2 Population and follow-up characteristic* of three studies of styrene exposed worker* Study Country Ott et al. 1980 Nlebolaon et al. 1978 Frentzel-Beviae et al* 1978 OSA DSA CEB Analysis cohort Jize 2904 560 1960 Number of Percent Percent death* of traced analyzed total 97.4 100.0 93.0Ger 29.0For 303 83 73 10.4 14.8 3.7 Minimua Minimum exposure latency (year*) (year*) Tears follow-uo Ott et al. 1980 Nicholson et el. 1978 Frentzel-Beyme et al. 1978 1 5 1 so. 1 1940-1975 10 1960-1975 1 no. 1956-1976 Exnosure* <10 ppn (3)* <20 ppn (5) < 1 ppttfe * C ) Estimated average exposure Current measurement after Installation of controls R&S 002802 The study of Nicholson et al (1978) successfully traced all of 563men employed in styrene production, polymerization and polymer processing who had 5 years of employment on May 1, 1960 and were 10 years from onset of work in a large U.S. production facility. The basic mortality data are shown in Table 3 and demonstrate no excess mortality from any cause of death. Analyses according to years from onset of exposure and calendar years of observation did not reveal any pattern of excess mortality. However, because of the limited number of deaths, the data can be used only to establish upper limits of risk. For example, the data are only suffici ent to indicate that the SMR for lymphoma or leukemia is less than 280 at the 0.05 level of significance and that of lung cancer, less than 220. While no excess mortality was identified in the cohortobserved, the above publica tion mentioned the existence of 7 deaths from leukemia and 5 of malignancy of the lymphatic system among 444 deaths known to have occurred in the plant workforce. While the ages of death were not available for exact proportionate mortality calculations, the number of lymphomas is in line with expectations, while leukemia appears to be in excess by as much as a factor of two. However, the possibility of high exposures to benzene in the facility during earlier years weakens the likelihood Table 3 Expected and observed mortality experiences of 360 Individuals employed in styrene production and polymerisation prior to 1 May 1955, followed ten years after onset of exposure (1 May 1960 -- 31 December 1975) Cause of Death Expected Observed SMS. All causes Cancer Cancer of the lung Leukemia Lymphomas Other cancer Reart and circulatory dls. Respiratory disuse* Other causes of death 106.41 21.01 6.99 0.79 1.25 11.98 56.35 6.64 22.41 83 17 6 1 1 9 52 1 13 78 81 117 126 80 75 92 13 38 From Nicholson ct al. 1978 R&S 002803 of association of any possible excess of leukemia with styrene exposure. The final study of styrene mortality is that of Ott et al (1980) who described the experience of 2,904 individuals with potential exposure to styrene prior to January 1, 1976. Three hundred three deaths occurred, 292 among production and nonprofessional research employees. The mortality experience for this latter group is shown in Table 4 and is compared to the' expected deaths calculated from U.S. white male rates and rates from observations on other company employees. As can be seen, the mortality of styrene-exposed individuals compares favorably with each group; the only excess of note being six leukemias compared to 2.9 expected using U.S. rates and 1.6 from company rates. Lymphomas were also elevated, but not at an 0.05 level of significance. The excess leukemia was further investigated in an analyis of cancer incidence in the styrene-exposed population com pared to that expected from rates of the Third National Cancer Survey. In this analysis, it was found that a signi ficant number of lymphatic leukemias (5 observed vs. 0.26 expected) occurred in individuals who were exposed to sty rene (< 5 ppm), ethylbenzene (< 5 ppm), polystyrene extru sion fumes, and colorants. Indeed, four of the five cases worked in the same general area during the period of time, 1947-1948, although their dates of death and other exposures varied widely. Interestingly, there were no deaths of lymphocytic leukemia among 442 individuals exposed to higher Table i Observed and expected deaths by cause for total production and non-professional research employees (2310 men), 1940-1976 Causes All causes Malignant neoplasms Respiratory system Digestive system Lymphatic and hematopoietic system except leukemia Leukemia Other sites Cardiovascular disease Nonmalignant respiratory dis. All ocher causes Observed deaths 282 55 14 16 6 6 13 143 12 72 Expected deaths US vhite males 357.8 64.2 20.8 18.0 4.5 2.9 18.0 172.4 14.3 106.9 SMR 79 87 67 89 133 207 72 83 84 67 Expected deaths, Company comotrlson 287.6 65.0 23.9 21.2 2.6 SMR 98 85 59 67 230 1.6 15.7 141.5 10.0 71.1 375 83 101 120 101 From Oct et al. I960 concentrations of styrene (5-9 ppm). Because of a lack of a definitive exposure-response-relationship and the presence of possible confounding exposures, the authors refrained from drawing any conclusions on an etiological relationship. In 1976, nine cases of various types of leukemia were identified in two SBR plants and reported to the U.S. National Institute for Occupational Safety and Health (Meinhardt et al, 1978). All occurred after 1971 in a population of 5,600 workers. No data were presented on the expected numbers of deaths from leukemia in the group. Concern generated by the findings in the two plants led to reports on the leukemias present in two large ongoing studies of rubber workers. McMichael et al (1976) reported a relative risk of 6.2 for lymphatic and hematopoietic malignancies among employees producing elastomers, including SBR. However, this was based upon only 6 cases, 3 leukemias and 3 lymphomas. In a subsequent case control study of the same plant, a relative risk of 2.4 was found for the same exposure group (Spirtas et al, 1976). The difference in the two values reflect the uncertainties associated with small numbers of cases. A similar investigation by Monson et al (1978) showed an excess of leukemia to be present in calendering, extrusion, tire building and rubberized fabrics. However, the excess was associated with exposure to solvents and not to styrene. R&S 002804 Since 1976, considerable interest has existed in poten tial carcinogenicity of styrene. This has been heightened by the data on mutagenicity and possible carcinogenicity of styrene and styrene oxide (Huff, 1983). Some suggestive human data are available from studies of polymerization workers and SBR production facilities. The irony of the situation is that no studies have been conducted of groups exposed to the enormously higher concentrations found in the FRP industry. The data available on styrene carcinogenicity are such that they can provide no assurance of safety at these higher exposures. CARCINOGENIC RISK FROM COMONOMERS USED WITH STYRENE The two principal comonomers used in styrene-based copolymers have each been shown to be carcinogenic in ani mals. Of these, acrylonitrile has also been associated with lung cancer in humans. In a group of 1,365 male employees, with potential exposure to acrylonitrile and followed from 1956 through 1976, 8 cases of lung cancer occurred compared with 4.4 expected from company rates (O'Berg, 1980). Fur ther, there was a correlation of increased risk with inten sity and duration of exposure. Among production workers employed between 1950 and 1952, 6 lung cancer deaths were observed vs. 1.5 expected (p < 0.01). A second study of 327 employees of a rubber chemicals plant with potential expo sure to acrylonitrile identified 9 deaths of lung cancer compared to 5.9 expected, based on mortality rates for U.S. white males (4.7 based on mortality rates for other rubber workers from the same city) (Delzell and Monson, 1982). The excess was greatest among those who had worked for more than 5 years in the facility. These data, while limited by the small numbers, strongly suggest that acrylonitrile is carci nogenic for humans. While butadiene has been demonstrably carcinogenic in animals (Huff, 1983), no data are available from human exposures. CLINICAL FINDINGS AMONG STYRENE-EXPOSED WORKERS A variety of symptoms have been reported from styrene exposure, dating from the rapid increase in production during World War II. Eye, nose and throat irritation. R&S 002805 R&S 002806 various respiratory symptoms, and gastrointestinal dis turbances, such as nausea, vomiting and loss of appetite, are commonly reported by styrene-exposed workers. Other abnormalities reported include headaches, tiredness and sleep disturbance. After a period of exposure, adaptation may occur and there can be a decrease in the various symp toms. Nevertheless, significant alterations still exist among currently employed workers. Several systematic studies of the various clinical ef fects from styrene exposure have been conducted in recent years. Many of these focused on possible neurological alterations and clearly demonstrated adverse findings at moderate styrene exposures (less than most national stand ards). The most extensive of these is that by investigators from the Institute of Occupational Health of Finland (Seppalainen and Harkonen, 1976; Lindstrom et al, 1976; Harkonen, 1977; Harkonen et al, 1978). They examined 98 workers employed at 24 plants manufacturing FRF products. Air concentrations were sampled and ranged from 5 to 300 ppm. The means of five post-workday urine mandalic acid (MA) concentrations ranged from 7 to 4,700 mg/1 with a lin ear relationship existing between the log of the MA concen tration and the log of the styrene concentration. The mean value of MA in the population was 808 mg/1 and corresponded to an exposure of about 40 ppm of styrene. Abnormal EEG's were found in 30% of those with MA in excess of 700 mg/1, compared to about 10% for those with lower MA values and normal controls (Seppalainen and Harkonen, 1976). Lindstrom et al (1976) noted increased visuomotor inaccuracy (symmetry drawing and Bourdon-Wiersma tests) and lowered psychomotor performance (Mira test) for various MA concentrations rang ing from 800-2,000 mg/1 (See also: Harkonen et al, 1978). Fatigue, irritation, difficulty in concentration, nausea, dizziness, and lightheadedness were more frequently reported by the styrene-exposed workers than by unexposed controls (Harkonen, 1977). A deteriorating EEG among styrene workers has also been described by Klimkova-Deutschova et al (1973). Alterations of nerve conduction have been documented by Rosen et al (1978) who observed an increased duration and decreased amplitude of sensory action potentials. Lilis et al (1978) suggested the possibility of a decrease in peroneal nerve conduction velocity. The decrease, however, was only asso ciated with length of employment and not intensity of expo R&S 002807 sure. Subjective symptoms of physical and mental tiredness after styrene exposure have been reported by Klimkova-Deutschova et al (1973) and Cherry et al (1980), among others. The reported neurological findings among styrene-exposed workers are less serious than those reported in some other groups occupationally exposed to solvents, such as as paint ers (Lindstrom, 1980; Hane et al, 1977). However, the continued exposure to concentrations causing the observed abnormalities may lead to more serious central nervous system impairment. In addition to neurological disturbances, alterations of pulmonary function have been noted among styrene-exposed workers. Lorimer et al (1977), in an examination of 494 polymerization workers, found a reduction in FEV^ to be associated with intensity of exposure and with urine MA concentration. Further, the workers in the higher exposed group reported a greater percentage of acute and recurrent lower respiratory symptoms. Harkonen (1977) reported an increase in incidence of chronic bronchitis which correlated with intensity of exposure. On the other hand, Axelson et al (1978) did not find any abnormalities of pulmonary func tion among 27 FRF boat manufacturing workers. Laboratory test results have been rather unremarkable. Lorimer et al (1977) suggested the possibility of increased lymphocytosis among polymerization workers and Checkoway (1982) found a correlation between decreased red blood cell count and increased basophil count with styrene/ butadiene exposure. Increased blood enzyme concentrations, charac teristic of abnormal liver function, occasionally have been reported. Lorimer et al (1977) found a significant increase in concentrations of GGTP (gamma glutamyl transpeptidase) and Hotz (1980), noted increased concentrations of OCT (orinthine carbamoyl transferase) and ALAT (alanine amino transferase) among polymerization workers. SUMMARY OF HUMAN MORTALITY AND MORBIDITY The limited epidemiological studies of mortality asso ciated with styrene exposure do not demonstrate any excess cancer risk that can be attributed to styrene, although elevated risks for leukemia have been noted in exposed groups. However, these excesses may be related to exposures 44 to other chemicals, such as benzene. The studies are se verely limited because of the relatively low styrene expo sure of the groups studied. They provide no guidance on carcinogenic risk in populations much more heavily exposed as in the FRP industry. The significant clinical findings among styrene-exposed workers are largely limited to abnor malities of the central nervous system, where a variety of objective and subjective symptoms have been reported in the FRP industry. Concern for long-term degnerative neurologi cal disease exists for continued long-term exposure in this industry. The possibility of pulmonary effects from styrene exposure has also been noted. REFERENCES Axelson 0, Gustavson J (1978). Some hygienic and clini cal observations on styrene exposure. Scand J Work Environ Health 4:215-219 (suppl 2). Checkoway H, Williams TM (1982). A hematology survey of workers at a styrene-butadiene synthetic rubber manu facturing plant. Am Ind Hyg Assoc 43:164-169. Cherry N, Waldron HA, Wells GG, Wilkinson RT, Wilson HK, Jones S (1980). An investigation of the acute behavioral effects of styrene on factory workers. Brit J Ind Med 37:234-240. Delzell E, Monson RR (1982). Mortality among rubber workers: VI. Men with potential exposure to acrylonitrile. J Occ Med 24:767-769. Frentzel-Beyme R, Thiess AM, Wieland R (1978). Survey of mortality among employees engaged in the manufacture of styrene and polystyrene at the BASF Ludwigshafen works. Scand J Work Environ Health 4:231-239 (suppl 2). Hane M, Axelson 0, Blume J, Hogstedt C, Sundell L, Ydreborg B (1977). Psychological function changes among house painters. Scand J Work Environ Health 3:91-99. Harkonen H (1977). Relationship of symptoms to occupa tional styrene exposure and to the findings of electroencephalographic and psychological examinations. Int Arch Occ Environ Health 40:231-239. Harkonen H, Lindstrom K, Seppalainen AM, Asp S, Hernberg S (1978). Exposure-response relationship between styrene exposure and central nervous functions. Scand J Work Environ Health 4:53-59. Hotz P, Guillemin MP, Lob M (1980). Study of some hepa tic effects (induction and toxicity) caused by occupa tional exposure to styrene in the polyester industry. Scand J Work Environ Health 6:206-215. R&S 002808 Huff JE (1983). National toxicology program and carci nogen bioassays of the United States. This volume. XARC (1979). Evaluation of the carcinogenic risk of chemi cals to humans; some monomers, plastics and synthetic elastomers, and acrolein. Vol 19. Klimkova-Deutschova , Jandova D, Salamanova Z, Schwartzova K, Titman 0 (1973). Recent advances concerning the clini cal picture of professional styrene exposure. Cs Neurol 36:20-25. Lilis R, Lorimer WV, Diamond S, Selikoff IJ (1978). Neuro toxicity of styrene in production and polymerization workers. Environ Resh 15:133-138. Lindstrom K, Harkonen H, Hernberg S (1976). Disturbances in psychological functions of workers occupationally exposed to styrene. Scand J Work Environ Health 3:129-139. Lindstrom K (1980). Changes in psychological performances of solvent-poisoned and solvent-exposed workers. Am J Ind Med 1:69-84. Lorimer WV, Lilis R, Nicholson WJ, Anderson H, Fischbein A, Daum S, Rom W, Rice C, Selikoff IJ (1976). Clinical studies of styrene workers: Initial findings. Environ Health Persp 17:171-181. McMichael AJ, Spirtas R, Gamble JF, Tousey PM (1976). Mor tality among rubber workers: Relationship to specific jobs. J Occ Med 18:178-185Meinhardt TJ, Young RJ, Hartle RW (1978). Epidemiologic investigations of styrene-butadiene rubber production and reinforced plastics production. Scand J Work Environ Health 4:240-246 (suppl 2). Monson RR, Fine U (1978). Cancer mortality and morbidity among rubber workers. J Natl Cancer Inst 61:1047-1053. Nicholson WJ, Selikoff IJ, Seidman H (1978). Mortality experience of styrene-polystyrene polymerization workers. Scand J Work Environ Health 4:247-252 (suppl 2). O'Berg MT (1980). Epidemiologic study of workers exposed to acrylonitrile. J Occ Med 22:245-252. Ott MG, Kolesar RC, Schamweber HC, Schneider EJ, Venable JR (1980). A mortality survey of employees engaged in the development or manufacture of styrene-based products. J Occ Med 22:445-460. Rosen I, Haeger-Aronsen B, Rehnstrom S, Welinder H (1978). Neurophysiological observations after chronic styrene exposure. Scand J Work Environ Health 4:184-194 (suppl 2). Seppalainen AM, Harkonen H (1976). Neurophysiological findings among workers occupationally exposed to styrene. Scand J Work Environ Health 3:140-146. R&S 002809 f 46 Spirtas R( Van Ert M, Gamble J, Wolf P, McMichael AJ (1976). Toxicologic, industrial hygiene and epidemiologic conside rations in the possible association between SBR manufac turing and neoplasms of lymphatic and hematopoietic tissues. In: Proceedings of NlGSH Styrene-Butadiene Briefing. US Department of Health, Education and Welfare Publication (NIOSH) 77-129. Tossavainen A (1978). Styrene use and occupational exposure in the plastics industry. Scand J Work Environ Health A:7-13 (suppl 2). X & CO oo IO 00 o