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Knowledge Web(r) Document Display Page 1 of 3 Document #8 of 200 from MEDLINE previous returnto show new summaries selected search next Organic solvents and cancer. Cancer Causes Control 1997 May;8(3):406-19 (ISSN: 09575243) Relevanceto Query: 71 Maximum Relevance: 1 1 Lynge E; Anttila A; Hemminki K Danish Cancer Society, Kobenhavn. Epidemiologic evidence on the relationship between organic solvents and cancer is reviewed. In the 1980s,more than a million persons were potentially exposed to some specific solvents in the United States; in Canada, 40 percent of male cancer patients in Montreal had experienced exposure to solvents; in the Finnish population, one percent was regularly exposed. There is evidence for increased risks of cancer following exposure to: trichloroethylene (for the liver and biliary tract and for non-Hodgkin's lymphomas); tetrachloroethylene (for the esophagus and cervix--although confounding by smoking, alcohol, and sexual habits cannot be excluded--and non-Hodgkin's lymphoma); and carbon tetrachloride (lymphohematopoietic malignancies). An excess risk of liver and biliary tract cancers was suggested in the cohort with the high exposure to methylene chloride, but not found in the other cohorts where an excess risk of pancreatic cancer was suggested. 1,1,1-trichloroethane has been used widely, but only a few studies have been done suggesting a risk of multiple myeloma. A causal association between exposure to benzene and an increased risk of leukemia is well-established, as well as a suggested risk of lung and nasopharynx cancer in a Chinese cohort. Increased risks of various gastrointestinal cancers have been suggested following exposure to toluene. Two informative studies indicated an increased risk of lung cancer, not supported by other studies. Increased risks of lymphohematopoietic malignancies have been reported in some studies of persons exposed to toluene or xylene, but not in the two most informative studies on toluene. Occupation as a painter has consistently been associated with a 40 percent increased risk of lung cancer. (With the mixed exposures, however, it is not possible to identify the specific causative agent[s].) A large number of studies of workers exposed to styrene have evidenced no consistent excess risk of all lymphohematopoietic malignancies, although the most sensitive study suggested an excess risk of leukemia among workers with a high exposure. r Include in Selection List? Related Searches Titles In: [ M E D L I N E l n Authors In: [ M E D L I N E l u Subjects In: JMEDLINEI Major Subject Minor Subject Heading(s) Heading@) 0 Alcohol Drinking [adverse effects] [epidemiology] 0 Benzene [adverse effects] CAS Registry / EC Numbers file://C:\WINDOWS\TEMP\KnowleWdgeeb(r) Document Display.htm t 3/16/01 Cancer Causes and Control,1997,8, pp. 406-419 Organic solvents and cancer Elsebeth Lynge, Ahti Anttila, and Kari Hemminki (Received 16 May 1996; accepted in revised form 25 July 1996) Epidemiologic evidence on the relationship between organic solvents and cancer is reviewed. In the 1980s, more than a million persons were potentially exposed to some specificsolventsin the United States; in Canada, 40 percent of male cancer patients in Montreal had experienced exposure to solvents; in the Finnish population, one percent was regularly exposed. There is evidence for increased risks of cancer following exposure to: trichloroethylene(for the liver and biliary tract and for non-Hodgkin's lymphomas); tetrachloroetlylene (for the esophagus and cervix- although confounding by smoking, alcohol,and sexualhabits cannot be excluded - and non-Hodgkin's lymphoma); and carbon tetrachloride (lymphohematopoieticmalignancies). An excess risk of liver and biliary tract cancers was suggested in the cohort with the high exposure to methylene chloride, but not found in the other cohorts where an excess risk of pancreatic cancer was suggested. l,l,l-trichloroethane has been used widely, but only a few studies have been done suggesting a risk of multiple myeloma. A causal association between exposure to benzene and an increased risk of leukemiais well-established,as well as a suggested risk of lung and nasopharynx cancer in a Chinese cohort. Increased risks of various gastrointestinal cancers have been suggested following exposure to toluene. Two informative studies indicated an increased risk of lung cancer, not supported by other studies. Increased risks of lymphohematopoieticmalignancies have been reported in some studies of persons exposed to toluene or xylene, but not in the two most informative studies on toluene. Occupation as a painter has consistently been associated with a 40 percent increased risk of lung cancer. p i t h the mixed exposures, however, it is not possible to identify the specific causative agent[s].) A large number of studies of workers exposed to styrene have evidenced no consistent excess risk of all lymphohematopoieticmalignancies, although the most sensitive study suggested an excess risk of leukemia among workers with a high exposure. Cancer Causes and Control 1997,8,406-419 Key words: Malignant neoplasms, organic solvents. Introduction Solvents are used to dissolve or suspend material to make the application easier. Organic solvents denote those composed of carbon in their structure. Aliphatic solvents are composed of chained carbon structures while aromatic solvents contain carbon atoms arranged in rings. In some cases, such as styrene, reactive ingredients are also called solvents. Organic solvents represent an important occupational health problem. Numbers of exposed persons are known from the National Occupational Exposure Survey in the United States in 1981-83,' from a multi-site case-control study of cancer patients in Montreal, Canada, in 1979-85,' and from surveys in Finland in 1989.` Forty percent of the men in Montreal had been exposed occupationallyto at least one solvent: and 50,000 persons were exposed regularly in Finland-' (Table 1). In Finland, levels of exposure estimated from the industrial hygiene surveys varied from 0.5 mg/m-' for benzene to 100 mg/m' for styrene. As these solvents are well absorbed by inhalation, the uptake can be estimated by assuming a daily inhalation at work of 10 m-'. D r Lynge is with the Danish Cancer Society, Kflbenhavn, Denmark. D r Antilla is with the Finnish Institute of Occupational Health, Helsinki, Finland. D r Hemminki is with the Center for Nutrition and Toxicology, Karolinska Institute, Huddinge, Sweden. Address correspondence to Dr Lynge, Danish Cancer Society, Strandboulevarden 49, DK-2100 Knbenhavn 0,Denmark. 406 Cancer Causes and Control. Vol 8. 1997 01997 Rapid Science Publishers Organic solvents Table 1. Occupational exposures to solvents. Estimates of potentially exposed persons from United States, 1981-83,percent of exposed male cancer patients, Montreal, Canada, 1979-85,and regularly exposed persons in Finland, 1989 Compound Use United States Montreal, Canada 1981-83' 1979-85b Finland 1989' Number of potentially exposed Percent of Number of Estimated exposed male regularly concentration cancer patientsd exposedd mg/m3 Trichloroethylene Degreasing Tetrachloroethylene Dry cleaning, degreasing Carbon tetrachloride Production of fluorocarbons, solvent Methylene chloride Pharmaceuticals, paint removal 1 ,I ,1-Trichloroethane Metal cleaning solvent Chloroform Pharmaceuticals Benzene Oil refining, gasoline distribution Toluene Paint, printing, shoe industry Xylene Paint Styrene Lamination All solvents Various a United States 1982:Total population 232 million.' Montreal, Canada, 1979-85:Total population 2.7 million.2 Finland 1989:Total population 5 m i l l i ~ n . ~ Aged 35-70 years. 401,000 566,000 104,200 1,440,000 2,528,000 96,000 272,000 1,278,000 1,106,800 333,000 NR 2% 1Yo 4% 2% 1 Yo 0.7% 17% 14% 11% 1% 40% 1,000 2,000 NR 2,000 NR 1,000 5,000 10,000 10,000 3,000 50,000 1 1 NR 10 NR 1 0.5 40 10 100 NR Few measurements are available from occupational exposures in prior decades. In general, the use of organic solvents has increased over time, but this does not necessarily correlate with exposure, as the selection of solvents may have changed for particular work tasks and industrial hygiene measures may have reduced the exposure level. In air measurements from Denmark, the exposure to styrene in 1955-70 was four times the level in 1981-88.' In biological-monitoring data from Finland, the exposure to trichloroethylene in 1965 was three times the level in 1987, whereas the exposure to tetrachloroethylene and styrene changed little from the mid-1970s to 1987.' Past exposures often are poorly recorded and also may have been to a number of solvents. It is difficult to assess the potential cancer risk following such exposures, and, therefore, we have focused on data related to specific solvents or to occupational groups heavily exposed to solvents. Animal carcinogenicity and genotoxicity Organic solvents as single agents have been studied extensively for induction of cancer in experimental animals. By contrast, few studies are available on solvent mixtures. Among the aliphatic chlorinated compounds, there is sufficient evidence in experimental animals for the carcinogenicity of trichloroethylene, tetrachloroethylene, carbon tetrachloride, methylene chloride, and chloroform according to the International Agency for Research on Cancer (IARC)5-6(Table 2). The liver has been a target site for all compounds; for trichloroethylene and chloroform, also the kidney; for trichloroethylene and methylene chloride, also the lung; and for trichloroethane, also the hematopoetic tissue. Studies on 1,1,1-trichloroethane have been negative, apart from one where leukemia was observed.' Among the aromatic compounds, benzene has induced malignancies at many sites, including liver and mammary cancers and l e ~ k e m i a s .S~tyrene has increased the frequency of lung and other cancers in studies considered limited by IARC,' and studies on toluene and xylene were inadequate.' None of the solvents discussed here are overtly geno- toxic. With the exception of methylene chloride, none are mutagenic in bacteria. Yet, all the animal carcinogens, except tetrachloroethylene, have shown some genetic activity in yeast and fungi. Benzene has caused chromosomal aberrations in exposed humans, and styrene has induced adducts in hemoglobin and white blood-cell D N A of lamination workers.*Most of the solvents display organ toxicity which may be related to induction of cell proliferation and most are hepatotoxic; benzene is toxic to bone marrow; as are I,I,I-trichloroethane, styrene, toluene, xylene, and benzene in high concentrations to the central nervous tissue. The occupational exposure levels often have been high enough to induce organ toxicity. Thus, cytotoxicity cannot be excluded as a possible mechanism of carcinogenicity for these solvents. Cancer Causes and Control. Vol 8. 1997 407 E. Lynge et a1 a sC C Le a: sL > C :- -m .c0- -m E -0) c a, 5 -a21 U 0 -m3 >m Q mv) 2 -JC 0 0 c 0 .3.0- C Qcn .0c- 0 5 C 0 0CW Q 9 5 W 5 c 0 zF 5 '0 ::(I) Ca cri 9) B F E '0" 1 (I) nz 408 :lancer Causes and Control. Vol 8. 1997 (I)(I)-(I)m zn zn zn zn ug + + #+ + 5 -- (I zn nz :; a *im '0 0 C II zn Umc ai 0 C 0) 0> 0) a, Im 3 W a, -m0 .c- -II d .ca-, .-E- -II 1 C .Q- 50 v) II (I) . Organic solvents Trichloroethylene The epidemiology on trichloroethylene and cancer has been reviewed Two cohort studies have been undertaken of workers biologically monitored for expo- Sure to trichloroethylene. The first study" included 1,670 workers monitored in Sweden 1955-75. Seventy-eight percent of the person-years (PY) for men were accumu- lated in the category with mean concentration 0-49 mg/L, 14 percent with 50-99 mg/L, and eight percent with category > 100 mg/L. A total of 253 deaths were observed (standardized mortality ratio [SMR] = 1.0), and 129 incident cancer cases (SIR = I.O)." The second cohort included 3,974 persons monitored in Finland 1965-83for exposure to three halogenated hydrocarbons (trichlo- roethylene = 3,089; tetrachloroethylene = 849; and l,l,l-trichloroethane = 271 with some persons monitored for exposure to more than one solvent). The median urinary concentration of trichloroacetic acid was 7.8 mg/L for men and 10.3 mg/L for women. There were 208 cancer cases among individuals monitored for trichloro- ethylene (SIR = l.l)."-" Three cohort studies investigated workers exposed to trichloroethylene in cleaning of metal parts in the aircraft industry. The most informative of thesei4included 14,457 civilians employed at an Air Force base in Utah (US)from 1952-56. In the early years, 1939-54, cold solvents were used to clean metal parts -primarily Stoddard solvent, but also carbon tetrachloride, trichloroethylene, and alcohols. In 1955, trichloroethylene replaced Stoddard solvent, and in 1968, 1,1,1-trichloroethane replaced trichloroethylene. Trichloroethylene was the primary solvent used in vapor drgreasing from 1939-79, when it was replaced by I,I,I-trichloroethane. Of the 14,467 cohort members, 10,256 had been exposed to mixed solvents, 7,282 to trichloroethylene, 6,977 to Stoddard solvent, and 6,737 to carbon tetrach10ride.l~Combining data for men and women exposed to trichloroethylene, there were 1,694 deaths from all causes (SMR = 0.9), and 281 cancer deaths (SMR = 0.9).15 Of the less informative studies, onel` included 20,535 employees from the Tucson, Arizona (US) facility of Hughes Aircraft Company. All employees were poten- tially exposed to trichloroethylene through the drinking water, but 4,733 also were potentially occupationally exposed. Among these employees, 484 cancer deaths occurred (SMR = 0.7). The last study" covered 14,067 persons who had worked in aircraft manufacturing in San Diego County, California (US), 1958-82. Data from a relatively small, nested case-control study indicated that 37 percent of the jobs held in the plant entailed exposure to trichloroethylene. A total of 1,804 deaths was observed (SMR = 0.8), and 453 deaths from cancer (SMR = 0.8). A study of renal cancer and exposure to trichloro- ethylene" included 169 men employed for at least one year (during 1956-75) in a cardboard-manufacturing factory in Germany, and 190 unexposed workers. Assessment of cancer occurrence was based on abdominal sonography, various health records, and interviews with relatives. Four renal-cell carcinomas and one urothelial cancer of the renal pelvis were seen in the exposed group, and none in the controls. There are a number of, less informative studies on trichloroethylene which will not be reviewed here.''.'' The three most informative cohorts consistently indicated an excess relative risk (RR) for cancer of the liver and biliary tract with 23 observed (Obs) cases cf 12.9 expected (Exp) (Table 3). The risk for these cancers also was elevated in one of the two less informative studies. The results for liver ~ a n c e r ' ~w- 'e~re reported separately in the studies from Finland and the Utah Air Force base. Seven cases were observed cf4.0 expected. Three casecontrol studies of primary liver cancer indicated elevated risks for people exposed to solvents, but only a few subjects in each study reported exposure to trichloroethylene. The results for non-Hodgkin's lymphoma were con- sistent across the three most informative studies indicating a modest excess RR, with 27 O b s cf 18.9 Exp cases. The risk of non-Hodgkin's lymphoma was not increased in the two less informative studies. In a case-control study of malignant lymphomas,27 an elevated odds ratio (OR) for exposure to trichloroethylene was indicated on the basis of seven exposed cases." The risk for non-Hodgkin's lymphoma was not increased among people exposed to trichloroethylene in the Canadian multi-site case-control study.' Tetrachloroethylene and occupation as dry cleaner The epidemiology of tetrachloroethylene and cancer has been recently As indicated earlier, the Finnish study' included 849 persons biologically monitored for exposure to tetrachloroethylene. The median level of tetrachloroethylene in the blood during 1974-83 was 116 pg/L in men and 66 pg/L in women. Thirty-one cancer cases were observed (SIR = 0.9)." To date, we are aware of only two cohort studies of dry cleaning workers primarily exposed to tetrachloro- ethylene. The first studyZ9included 1,701 workers in four labor unions from California, Illinois, Michigan, and New York (US), employed for at least one year before 1960 in a shop where tetrachloroethylene was the primary solvent used and where there was no known exposure to carbon tetrachloride. A survey in 1977-79 showed geometric mean, time-weighted average concentrations of tetrachlo- roethylene in the range of 20.3 to 149 mg/m'. There were 769 deaths (SMR = 1.0), of which 209 were cancer deaths Cancer Causes and Control. Vol 8. 1997 409 Organic solvents (SMR = 1.2, 95 percent confidence interval [CI] = 1.1- the median exposure level was 490 to 2,600 mg/m3in the 1.4). The cohort was divided into people employed in main areas. The reported mean exposure in a study of shops using only tetrachloroethylene, and other d r y film production workers was 91 mg/m'.'j The cohort with cleaners. the highest exposure suggested an excess risk of liver and A union study of dry cleaning w o r k e f r o m Missouri biliary tract cancers, not found in the two other cohorts (US)" included 5,365 identifiable members with member- (Table 5). The two latter studies suggested an excess risk ship for more than a year during 1945-78. There were of pancreatic cancer not found among the cellulose fiber 1,129 deaths (SMR = 0.9), of which 249 were cancer workers. The Canadian multi-site case-control study' deaths (SMR = 1.2, C I = 1.0-1.3). The authors stated that reported small increases in the risk of rectal and lung the RRs were similar for workers first employed before cancers following exposure to methylene chloride. Other 1960 and those employed after that date, when use of tetrachloroethylene became predominant. studies, for which the use of methylene chloride has been documented, have not suggested consistent finding^.'^.^"^' A study was undertaken of 2,610 White men employed Despite the common use of l,I,l-trichloroethane as a for one o r more years, during 1956-80, in a chemical metal cleaning solvent, there are only three studies on company in Louisiana (US)," where tetrachloroethylene cancer risk'"'.'' of which ~ W O ' ' . ' ~found increased risks of was one of many chemicals produced. There were 48 multiple myeloma based on small numbers. deaths (SMR = Oh), of which 11were cancer deaths (SMR To date, there is no study on cancer following occupa- = O . 8 ) , including t h r e e deaths f r o m leukemia and tional exposure to chloroform. Several studies''." have aleukemia (SMR = 4.9, C I = 1.01-1.4). Among civilians at attempted 'to assess the potential carcinogenic effect of the Utah Air Force base exposed to tetra~hloroethylene,~~ chlorination byproduc ts, including chloroform, in drink- there were two deaths from multiple myeloma (SMR = ing water. Excess risks of rectal and bladder cancer have 17, CI = 2.1-61.6) and four deaths from non-Hodgkin's been suggested,+' but it is not possible to evaluate the lymphoma (SMR = 3.2, C I = 1.2-7.1)." effect of chloroform alone. Results for esophageal cancer were reported from the t w o subgroups of the four-state US study and the Missouri study, and elevated risks were found in all of Benzene them with a total of 23 observed cases cf 10.8 expected (Table 4). Results for cervical cancer were reported from these studies and from the cohort of biologically monitored women from Finland. Elevated risks were found in all studies with a total of 43 observed cases cf 28.4 expected. Although these associations appear unlikely to be due to chance, confounding by strong risk factors such as smoking, alcohol, and sexual habits cannot be excluded. Elevated risks for non-Hodgkin's lymphoma were observed both in the Finnish study, in the Missouri cohort, and among the civilians exposed to tetrachloroethylene at the Air Force base in Utah. The association between occupational exposure to benzene and an increased risk of leukemia is well-do~umented.~' The two largest cohort studies have been recently updated. They have provided further data o n the risk of leukemia subtypes and improved the basis for assessment of the leukemia risk following low-dose exposure. O n e cohort" consisted of 1,212 white men employed from 1936-75 in the production of Pliofilm, a covering material made from rubber hydrochloride whose production involved the use of large volumes of benzene as a solvent. Various estimates have been made of the exposure levels in this cohort with the proportion of person-years accumulated by men exposed to less than 50 ppm-years Carbon tetrachloride, methylene chloride, l,l,l-trichloroethane, and chloroform varying from 78 percent to 56 percent. The latest followu p showed 481 deaths (SMR = 1.0), 111 cancer deaths (SMR = l.l), 14 leukemia deaths (SMR = 3.6, CI = 2.0- Two cohort studies, thus far, have assessed exposure to 6.0)" of which six were from acute myeloid leukemia carbon tetra~h1oride.l~A"~study from the 'lasting' and (SMR = 5.0, CI = 1.8-1l.O), and showing a strong asso- 'making' departments of boot and shoe manufacture listed ciation with cumulative exposure.'' use of carbon tetrachloride along with benzene and A cohort of 74,828 workers were recruited from 1,427 trichloroethylene." The cancer risk following exposure benzene-exposed work units in 672 factories in 12 cities to carbon tetrachloride also has been assessed in the in China. There were 1,369 deaths which gave a low Canadian multi-site case-control study.' Some of these overall mortality compared with the general population studies suggest an increased risk of lymphohematopoietic (SMR = 0.5). However, a cohort of 35,805 unexposed malignancies following exposure to carbon tetrachloride. workers had the same overall mortality (RR = 1.1). The Three cohort studies have studied workers heavily exposed cohort had 42 incident leukemia cases (RR = 2.6 exposed to methylene ~ h l o r i d e . ~ 'I'n~ ~a study among compared with unexposed, C I = 1.3-5.7).The largest group employees in the production of cellulose triacetate fiber^,'^ was acute myelogenous leukemia (Obs = 23, RR = 3.1, C I Cancer Causes and Control. Vol 8. 1997 411 E. Lynge e t a] U mC U Cm 2 5 a, 0* 0 i 0 0 c s! 3 u) 0nx -a, 2 .0- cma 3 L al 00 -0 8m c0 a, a, 3 a c na, I Uz I zU I zU s ! ) 1 c ?: c 5 Jl XNI N a, 5 c 0 4 c\I a0 I Uz I zU I za I Z I zU '9 7 -al m 0 N I za [r Z n za: k m - CD w mm I u-? 0 m az Lo II Uz Uz 4 7 z7 U l az m0 (ND U0J cj u? 0 m zU Uz zU Uz Uz c9 0 0m m -m b (u az 9m I za: Ic9 .0- 0 c 2 u) 73 zaml U U 0 0 N % 412 Cancer Causes and Control. Vol 8. 1997 Organic solvents Cancer Causes and Control. Vol 8. 1997 413 E. Lynge et a1 = 1.2-10.7), but risk estimates of the same size were seen (SMR = 1.0), and 68 incident cancers (SIR = 1.3). The for chronic myelogenous leukemia (Obs = 2, RR = 2.6) other included 7,814 workers from two shoe- and acute lymphocytic leukemia (Obs = 5, RR = 2.8)" manufacturing plants with toluene levels from 83 to 188 Significantly elevated risks for other types of cancer were not found in the relatively small Pliofilm cohort. mg/m', where exposure to hexane and some other solvents was also documented. There were 1,540 deaths (SMR = However, the large Chinese cohort had a borderline sig- 1.0), and 353 cancer deaths (SMR = 1.0). nificant excess risk of lung cancer (RR = 1.4) and an excess In addition, there are four minor studies reporting risks risk of nasopharynx cancer compared with the unexposed for t o l ~ e n e . ' ~ ~In' ~a ~st'u*d~y ~of~ 5,653 persons with sus- workers. pected solvent-related disorders from S ~ e d e n ,e~x'posure Low level exposure to benzene is widespread as gaso- information was obtained only for a subsample of the line contains benzene in up to five percent on cent ration.^^ cohort, showing that most of the workers were exposed Based on data from the Pliofilm cohort, it has been esti- to mixtures of solvents including white spirits, xylene, mated that a worker occupationally exposed to benzene and toluene. There were 182 deaths (SMR = 0.9), and 118 at an average exposure level of 1 ppm for 40 years would incident cancer cases (SIR = 1.2). have an increased risk of death from leukemia of 1.7.47 Five of the cohort-based studies on toluene have indi- Estimates based on the updated cohort data show a life- cated some elevated risks for cancers of digestive organs time leukemia risk following 45 years of exposure to 1 such as stomach, intestine, or rectum (Table 6). Among ppm to vary between 0.3 and 1.3 per 1,000.+8In order to Swedish rotogravure printers: the risk of gastrointestinal overcome the uncertainty inherent in extrapolation of cancers was slightly higher for a longer duration of results from high exposures to low exposures, studies also exposure (five or more years, latency of more than IO have been undertaken of the cancer risk among gasoline years). The risks of rectal cancer were elevated among distribution workers. persons with substantial exposure to toluene and xylene in the Canadian multi-site case-control study.' Toluene, xylene, and solvents in mixtures Both of the most informative cohort studies on toluene have shown an increased risk of lung although Use of toluene, xylene, Stoddard solvent, white spirits, and other solvents in mixtures have prevailed in industries considered to entail carcinogenic risks, such as furniture this finding was not repeated in the less informative studies. Increased risks of lymphohematopoietic malignancies have been reported in many studies of persons exposed and cabinet making, paint manufacture and painting, boot and shoe manufacture, graphics industry, petrochemical to toluene or xylene, but the results from the two most informative cohorts on toluene do not support this find- and other chemical industrie~."~.~D.`u~e~t"o exposure to concurrent agents, no evaluation of solvent-specific risks ing. Two studies have suggested an association between exposure to toluene or xylene and brain turn or^.'^^^^ A can be made from these studies. significantly elevated risk of cervical cancer was found in A meta-analysis of 55 cohort studies of mortality the cohort of solvent-exposed workers." among workers exposed to organic solvents showed a significantly elevated mortality from leukemia (SMR = 1.1, CI = 1.0-1.5) and from cancer of the liver and biliary tract (SMR = 1.2, C I = 1.0-1.4). No other cause of death Occupation as a painter, Stoddard solvent, white spirits was significantly e l e ~ a i e d . ~S'e~eraI,"~~b'-u~t 'not all,'.M Occupation as a painter was evaluated for carcinogenicity case-control studies have reported a risk of non- by IARC in 1989.' A consistent increase was found of Hodgkin's lymphoma following occupational exposure about 20 percent in the risk of overall cancer and of about to organic Four case-control ~ t u d i e s ' ~ . ~ha~v.e~ ' , ~4~0 percent in the risk of lung cancer.' The risks of cancers indicated a risk of Hodgkin's disease following solvent of the esophagus, stomach, rectum, liver, pancreas, buccal exposure, and one studyGi7ndicated a risk of acute myeloid cavity, larynx, prostate, bladder, and lymphomas and leukemia. Only one small study of Hodgkin's diseaseh5 leukemias were raised in some studies. As painters in had a detailed description of the solvents; all exposed cases general have been exposed to a multitude of carcinogens had handled several solvents/mixtures, including xylene - such as asbestos, metals, pigments, solvents, gasoline, and toluene. and polycyclic aromatic hydrocarbons (PAH), there is no Of two cohort studies of workers heavily exposed to firm evidence concerning specific causative agents. toluene, one" followed-up 1,020 rotogravure printers employed 1925-85 and exposed to average air levels of Seven studies have been published on the carcinogellic afArisk of painters 1989,2.7"' in which the risks of cancers toluene from 110 to 1690 mg/m'. Benzene also may have of the lung and urinary organs have been consistently been used in the earlier years, and contact with carcino- elevated. The studies provide further evidence that genic dyestuffs was common. The cohort had 129 deaths there may be increased risks of cancer in the l i ~ e r , ' ~ ' ~ ' . ~ ~ c 414 Cancer Causes and Control. Vol 8. 1997 4 ~ 0 e0) n8 0 d a, a .vL-o) c .0- .cW- 0 (I 0 em E, c c0n -5 s0 c 0 v) -Ea, n 0 0 C c Cm .-Cc-n 2 2 m W C F 21 iv) 0 c Fa" -n0z m .C0taij a 0 0 C al s0) c n0 .C0.cm- 0 0 v) m .mE, Y Sa A K 5 afn 0 -9 N N I I n! v a0 xm b 9 v rT) u) 0 If! 5 .9- c 0 W 2 2 e E =-vWi 2 c0 s0 ~~ mI I T- 7 00 IlI az: az 0 III az: [zr 0 22 I 7m 0 I II az: az: 0 0 N T(D (D 0 u) (D N- u) bi- eL c f0 80 -.W>- c 0 " =.5:0 .W>- e 0 an, vi .W- c i 0 2 e F 2 e E ed -5 0 0 ;c 0 E P 0 c 0m c 8 Organic solvents E . Lynge et a1 gallbladder,"^" colorectum,2'7Z pancreas,76m o u t h a n d pharynx," prostate: lymphoma^,^' m y e l ~ m a ,a~n"d leukemias.'` There is also a consistent but marginal increased risk of brain tumors. Good data on the cancer risk following exposure to Stoddard solvent or white spirits are not yet available. The study by Siemiatycki et a1 showed small increased risks of pancreatic, lung, and prostatic cancers. In Swedish case-control studies, exposure to white spirit and thinners has been suggested to be associated with an increased risk of malignant lymphomas,bl'b'primary liver cancer: and acute leukemia." Styrene Studies in the rubber industry raised suspicion about a risk of lymphohematopoietic malignancies among workers employed in manufacture of styrene-butadiene rubber." This suspicion was confirmed in the first study which focused on this industry." Further studies in both the styrene-butadiene rubber industry and in the manufacture of styrene monomers and polymonomers showed inconsistent Exposure to styrene has been high in the reinforced plastics industry where boats and similar products have been produced, and exposures to known carcinogens are limited. In a study from two reinforced-plastics boatbuilding facilities in the US: no case of lymphatic or hematopoietic malignancies was found. A study from eight British facilitiesub included 7,949 persons employed during 1947-84. Exposure for hand laminators was estimated to 170-426 mg/m'. There were 693 deaths (SMR = O.8), and 181 cancer deaths (SMR = 0.8). A cohort of 15,826 persons from 30 reinforced plastics plants in the US`'who had worked from 1948-77showed 1,628 deaths ( S M R = 1.1), of which 425 were cancer deaths (SMR= 1.2, C I = 1.0-1.3). An international cohort studyX8included 35,443 workers from 660 plants of the reinforced plastics industry from Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. Exposure to styrene was reconstructed from job and production records, environmental measurements, and, in Italy, biological monitoring. An exposure database was based o n 16,500 personal air samples and 18,500 measurements of styrene metabolites in urine. Styrene exposure levels decreased considerably during the study period. Data from Denmark, considered to be representative of all six countries, showed exposures of about 852 mg/m' in the 1950s and 85 mg/m' in the 1980s. The cohort had 2,196 deaths (SMR = 1.0) and 550 cancer deaths (SMR = 0.9). A cancer incidence study from Denmarkx' included 36,525 men employed 1964-89 in 386 facilities having produced reinforced plastics. Of these men, 12,800 also 416 Cancer Causes and Control Vol 8. 1997 were included in the international cancer mortality study." Exposures were assessed from national air samples going back to 1955. The cohort had 3,031 deaths (SMR = 1.1) and 1,246 incident cancer cases (SIR = l.O).xy~yo The data on lymphohematopoietic malignancies are summarized in Table 7, together with a `pooled estimate' where account is taken of the overlap among studies." Overall, there is no excess risk of all lymphohematopoietic malignancies, nor of any of the diagnostic subgroups. An increasing risk by average exposure was suggested for all lymphohematopoietic malignancies and for lymphomas in the international study, but not for leukemia.u8In the Danish cancer-incidence study? which is the most sensi- tive, an excess risk of leukemia (Obs = 30, SMR = 1.5, CI = 1.0-2.2) was found among persons employed in the early production phase, 1964-70, where an average exposure level of 767 mg/m' was measured. A risk of pancreas cancer was suggested in the high exposure group. Conclusion Organic solvents are widely used. Several of these solvents are carcinogenic in experimental animals, and it is therefore important to assess thoroughly their carcinogenicity in humans. Trichloroethylene is used as a degreasing agent. There is some evidence for increased risks of cancer of the liver and biliary tract and for non-Hodgkin's lymphomas following exposure. Tetrachloroethylene is used for dry cleaning and degreasing. There is some evidence for increased risks of cancer of the esophagus and cervix following exposure, but confounding by smoking, alcohol, and sexual habits cannot be excluded. There is also some evidence for an increased risk of non-Hodgkin's lymphomas. Carbon tetrachloride is used in the production of fluorocarbons, etc. Some excess risk of lyrnphohematopoietic malignancies has been suggested following exposure. Methylene chloride is used widely in paint removal and pharmaceuticals. An excess risk of liver and biliary tract cancers was suggested in the cohort with the highest exposure, but not found in the other cohorts where a risk of pancreatic cancer was suggested. 1,1,1trichloroethane has been used widely as a metal cleaning solvent, but only a few epidemiologic studies have been made suggesting a risk of multiple myeloma. Benzene previously was used widely as a solvent in glues, etc. Low level exposure to benzene is widespread as gasoline contains benzene in up to a five percent concentration. There is convincing evidence that exposure to benzene is associaPted with an increased risk of leukemia. A study of a large Chinese cohort also suggested a risk of lung and nasopharynx cancer. Toluene is used widely in paint, printing, and in shoe ~ Organic solvents manufacture. Increased risks of various gastrointestinal cancers have been suggested following exposure. Both of the most informative cohort-studies showed an increased risk of lung cancer, not supported by the other studies. Increased risks of some lymphohematopoietic malignancies have been found for persons e x w e d to toluene or xylene, but not in the two most informative studies on toluene. Occupation as a painter has been shown consistently t o be associated with a 40 percent increased risk of lung cancer. 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