Document Ra2vM172RwJdRmxV1M2ZYy6wX

#0-11018911 26003A Am: PHONE: FXf: (304) 234-8771 304 234-8330 SwlMll'XD: 2000-03-23 9:55:08 AM DE&-: 2000-03-24 8 : 0 7 : 5 4 AM REQUEST ND: RBG-11058911 S m T V I A : OOcLeJg wvc-0003231106 TI=: vOL/ISsm: DATE: AU!t!HOR OF ARTICLE: TITLE OF ARTICLE: PAGgS: OTHgff N O S / L m m R s : somcg: M U COST: CADBRWS DE SACYDE m I C A / M Z I U S m O RA SAUDE, FUNDACAO -0 CRUZ, ESCOLA XACICKUU DE SAUDE PUBLICA. 1998 1 4 Suppl 3 ( ) : 4 1 - 6 6 1998 Rego MA N W - H o d g k i n ' S lymphoma risk d e r i v e d from e x p o s m e 41-66 DoCLzm SR0060929 99051486 HEVLJXE T U s document contains 26 p a g e s . m:!l?iIS M A W MAY BE PROTECTKD BY COPYRIGHT LAW (TITLE 17, U.S. CODE) ARTIGO ARTICLE 41 Marc0 Antbnio V R6go 1.2 Non-Hodgkin's lymphoma risk derived from exposure to organic solvents: a review of epidemiologic studies Risco d e linfoma nSo-Hodgkin resultante da exposicdo a solventes orgiinicos: revisio d e estudos epidemiologicos 1 Crnrro dr E S I I ~ UdSu Saude -do liabalhador CESAT: Rtra Pedro Lersa 123. Canela. Salvador. Bahia 401 IO-IJSO. Rrasil. 2 Insritrrro de Saude Coleriva. Unrvcrsidude Federal da flaitia. R i m Padre Feijd 29. Canela. Saltador. Bahia 401 I I . I io. Rrflsil. mngo@logner.com.hr Abstract The rate of non-Hodgkini lymphomas ( N H L ) has increased around the world during the last decades. Apart from the role of the h u m a n immunodeficiency virus (HIV) infection in the development of NHL. exposure to chemical agents like phenoxyacetic pesticides, hair dyes, metal fumes and organic solvents are suspected to be involved. The present review evaluates the results of studies that directly or indirectly searched for an association between solvent exposure and NHL. The selected studies comprised those published from 1979 to 1997, designed to investigate risk factors for NHL, whether specifically looking for solvent exposure or for general risks in which solvent exposure could be included. In 25 of the 45 reviewed studies (55.5%)f.ifty-four statistically significant associations between NHL and solvent exposure related occupations or industries were reported. Statistical significance was more frequently shown in studies where solvent exposure was more accurately defined. I n eighteen of such studies, 13 (72.2%)defined or suggested organic solvents as possible risk factors for Y H L . Key w o r d s iVon-Hodgkin4 Lymphoma: Occupational Exposure; Solvents: Epideni iology Resumo A taxa de incidPncia de linfomas ndo-Hodgkin ( L N H ) tern aitmentado mundialrnente durante as iiltimas decadas. A l k m do papel da infecqdo pel0 virus da imunodeficitkcia humana (HIV).suspeita-se que a exposiqao a agentes quimicos. como os pesticidas fenoxiaceticos. tinturas de cabelo.fiimos metalicos e so1ven;es organicos. esteja envolvida. A presence reuisao avalia os resitltados de estrrdos que direta ou indiretamenre procuraram por uma associaqao entre exposiqao a solventes orgdnicos e LIVH.Os estudos selecionados compreendem aqueles pitblicados entre 1979 e 1997, que investigam fatores de risco para LNH, sejam os qiie especificarnente analisam solvenres organicos, sejurn os que analisam riscos e m geral. entre os quais a exposiqdo a solventes pudessse estar incluida. Em 25 dos 45 esriidos rerlisados (55,576)f.orarn citadas 54 ussociaqdes estatisticamente significatiuas entre L,VH e ocupaqbes relacionadas d exposiqdo a solventes. A presenqa de significancia estatistica foi evidenciada mais freqiientemente e m estudos nos quais a exposiqdo a solventes foi definida de forma mais aciuada. Em 18 destes estudos, 13 (72.2%)definiram ou sicgrriram ser os soluentes organicos possiveis fatores de risco para os LNH. Palavras-chave Linfoma Nrio-Hodgkin; Exposipio Ocupacional; Solventes; Epiderniologia Cad Saude Publica. Rio de Janeiro. 1 4 ( S u ~3'41-66. 1998 $2 REGO. M.A. V. Introduction The increasing rate of non-Hodgkin lymphomas (NHL) around the world during the last decades has been exhaustively demonstrated (Linos et al.. 1986; Zheng et al., 1992; Devesa & Fears, 1992; Holford et al., 1992; Hartge & Devesa, 1992; Costantini et al.. 1992; Rabkin et at., 1993;Hartge et al.. 1994; Palackdharry, 1994; Scherr & Mueller, 1996; Seow et al., 1996;Vineis, 1996).On the one hand. some research shows that the increase is mainly a result of viral infection, primarily the human immunodeficiency virus (HIV)infection (Hardy et al., 1988). On the other hand. it has been discussed that this virus had little impact on the NHI, incidence trends (Hartge & Dcvesa. 1992), and that the increase in NHL was apparent before the arrival of the acquired immunodeficiency syndrome (AIDS) (Holford et ai.. 1992; Carti et ai., 1994).Therefore, this suggests other unknown environmental causes, including chemical exposures (Longo, 1994). Other studies have presented the role of changes in the criteria disease classification and of improvement in diagnosis technology to explain part of the rate growth (Devesa & Fears, 1992).mainly for the marked increase in extra-nodal NHL in older people (Cozen & Bernstein. 1994).This explanation does not agree with the findings of Lutz & Coleman (1994) for primary cerebral lymphoma. This diagnostic bias has been denied (Banks, 1992) and a real annual increase in NHL rates of 4v0 in recent years in Britain (Cartwright, 1992) and a recent increase in Uenmark (Hjalgrim et al.. 1996) have been demonstrated. Among the chemical exposures, there are several agents suspected of being involved in the development of NHL (Blair et al.. lW2: Pearce & Bethwaitc, 1992; Vineis. 1996). 'ionie examples are the phenoxyacetic pesticides. hair dyes. metal fumes and organic solvents. The goal of the present review is to evaluate the results of these studies which directly or indirectly looked for an association between organic solvent exposures and NHL. Methods The selected studies included those designed to investigate risk factors for NHL. whether the main objective was specifically to look for solvent and N H L relationship or to find general risks. from which solvent exposure could appear (Table I ) . I n the latter ones. exposure to organic solvents was derived from the information of the occupation or the industry in which the study subjects were enrolled. Therefore, studics whose main objectives were to study general mortality patterns, conducted within particular workers' cohorts. like mechanics, painters, printers, dry cleaners, refinery, petrochemical. chemical and rubber workers were not selected, even though some of them could have investigated the relationship of interest in this review. In the same way, the studies linking all occupations a n d all causes of disease or death. those focusing on N H L a n d the role of other specific exposures such as pesticides, smoking, sun light, etc., and those involving children also were not reviewed. Studies that had a further re-analysis, and released a new publication were evaluated again. It is also important to nore that most selected studies were written in English language a n d were published from 1979 to January11997. The method of selection was based on the linkage of the words lymphoma and occupational, environmental or solvent exposure using MEDLlNE data from 1966 to 199;. The search was cornplemented by looking for other studies cited by the authors of the previously selected investigations. Results An observation based on a clinical case series was d o n e in a community composed of 117 Caucasian individuals, from 1968 to 1974 (Capurro, 1979). in that area. where a chemical plant was located, solvent exposure was measured in the environment and detected in 20% of the visits. Also, some solvents like methyl isobutyl ketone, benzene. chloroform and trichloroethylene were detected in the blood of t h e residents. W e n t y three cases of cancer were listed, eight of rhem were lymphoma. Considering specifically the three deaths d u e to lymphosarcoma in this six year period. the relation between observed and expected cases was 3/0.0187 = 160 fold. The first epidemiologic study relating NHL and occupations with potential exposure to solvents was conducted using death certificates of NewYork State from 1950 to 1969. excluding NewYork City (Vianna & Polan, 1979). I t was a cohort mortality study in which all male deaths with age 20 and over, among individuals within 14 benzene-related occupations were analyzed. The authors found 116 reticu- lum cell sarcomas (RCS) and 353 lymphosarcomas (LS),compared them with the same dis- eases in the general population and had the following findings: RCS, relative risk ( R R ) = 1.6: Cad. Saude Publica. Roo de Janewo, 14(Sup 31 41 64, 1O W 43NON-HOOGKIN'S LYMPHOMA RISK A N 0 ORGANIC SOLVENTS LS, R R = 2.1. Among subjects 45 years old and over, within the seven occupations for which age distributions were available, the number of deaths observed was significantly higher than the n u m b e r of deaths expected for the two types of lymphoma: RCS,observed/expected (OIE) = 1.7 (p<O.Ol)and LS. OIE = 2.1 (peO.01). These findings were discussed and criticized for the way Vianna & Polan (1979) had gotten the information about occupations from both death certificates and the U.S. decennial census. It was said that these sources are incomparable with each other and that they should have calculated proportionate mortality ratios, based only on occupation as defined on the death certificates (Enterline, 1979). The age-adjusted mortality rates of N H L in 3,056 counties of the Ilnited States between 1950 and 1975 were verified utilizing an ecological design (Cantor & Fraumeni Ir., 19801. It showed suggestive associations in a multiple regression analysis between NHL rates among white males and five industrial groups, including printing and publishing (significant at p< 0.0251, petrochemicals a n d rubber products. They did not find an association for other potential solvent-related industries such as Furniture, machinery and electrical. The first srudy which directly looked for the relationship between lyniphoma and exposure to solvents (among other exposures) was performed in Sweden (flardell et al., 1981).They studied all 169 men admitted to the Department of Oncology in Umea with 109 diagnosed NHL a n d 60 Hodgkin's disease (IID).and eight controls matched by age, sex and residence for each living case and I O for each deceased case matched also by year of death, from the National Population Registry. Analysis of high grade and low grade exposure produced an odds ratio (OR) = 2.8 (1.6-4.8)and a n OR = 1.2 (0.5-2.6). respectively. Exposure to styrene. trichloroethylene, perchloroethylene and benzene among the high grade exposed individuals gave greater risk than exposure to other organic solvents. OR = 4.6 (1.9-11.4).A modifying effect was found when combined exposure tv organic soivents and phenoxy acids, OR = 11.2 (3.2-39.7)and chlorophenols (eight exposed and n o exposed controls) were analyzed. These data were reanalyzed (Hardell et al.. 1994) and the authors found the following results: carpenter: 13 exposed cases/36 exposed controls. OR = 1.1 (0.6-2.4):mechanic: .i/7, OR = 2.5 (0.7-9.6):motor mechanic: 7/20, OR = 1.3 (0.5-3.41:all organic solvents: 45/88, O R = 2.4 (1.4-3.9):high grade exposure: 3 1/ 5 0 . OR = 2.9 ( I .6-5.6):low grade: 14/38. OR = 1.8 (0.8-3.8); benzine: 31 1 , OR = 2.8 (1.8-730);thinner: 1 I / 14, OR = 3.4 (1.4-10);trichloroethylene: 41.1. OR = 7.2 (1.3-42);turpentine: 517. OR = 3.3 (0.9-17); white spirit: 12/20, OR = 3.2 (1.3-8.3);degreas- er: 7/4, OR = 1 1 (2.9-72);multivariate analysis - high grade OR = 3.5 (1.7-7.1 ): low grade, OR = 1.1 (0.5-2.7);organic solvents :for lymphocytic and well differentiated NHL), OR = 2.9 (1.3-6.6). The mortality patterns of workers were defined in two styrene-butadiene rubber (SBR) plants with specific focus on hematopoietic and lymphatic malignancies (Meinhardt et al.. 1982). It was a retrospective cohort mortality study that received information from 1,662 individuals (34,187p/y) in plant A. 1,094 individuals in plant B (19,742p/y) that gathered information about butadiene, styrene and benzene levels in the workplaces. Only white males with at least six months of non-management and non-administrative employment were included in their analysis. They found standard mortality ratio (SMR) = 155 (plant A) and 78 (plant 6 ) for lymphatic and hematopoietic tissues in general (International Classification of Dis- eases - ICD 220-205) and S M R = 181 (plant A ) and 132 (plant 8)for lympho and rericulosarcoma (ICD 200). These excesses in mortality were not statistically significant. The authors concluded that their findings continue to suggest that the production o r manufacturing of SBR may be associated with an excess of lymphatic and hematopoietic neoplasms. A hospital-based case-control study conducted in ltaly did not find positive results for industries (Franco & Ponte, 1983). In the chemical and pharmaceutical industry there were four exposed cases (EC). OR = 0.16; textiles, shocs and leather, 21 EC, OR = 0.50; paper and printing, three EC, OR = 0.90 and rubber and plastics. three EC, OR = 0.33. An important association was seen for woodworkers, with 14 EC and OR = 5.55 (2.39-12.85).The authors discussed the role of some agents used during the manufacture and treatment of wood. like benzene. chlorophenols, phenoxyacids and coal tar derivatives. In this study, cases were 282 NHL and 387 HD (347 male and 322 female patients of both sexes admitted to the Clinica Medica A. Ferrata - University of Pavia. from 1969 to 1980. diagnosed as malignant lymphoma. Controls w,ere 757 male and 588 female patients admitted to an internal medicine unit in Pavia from 1975 to 1980. Occupations were defined as proposed by the Annuario Sraristico Itdinno. The analysis did not consider the N t I L and the HD separately. Hased o n the National Cancer Registry in England and Wales, a case-control study was Cad Saude Publica Rio de Janeiro 14(Sup 3) 41-66, 1998 4 REGO, M.A. V. conducted with malignant lymphomas in male road transport workers aged 15 and over, diagnosed from 1973 to 1977. Control individuals were randomly chosen from other cancer patients, matched 1:l by age. sex and region of residence. Among all lymphomas (426). 256 were recognized as NHL (ICD200 and 202). The results did not reach statistical significance, and the authors implied some positive findings to possible exposure to exhaust fumes. Thus, the following results were reported: ICD 200: drivers of buses a n d coaches. OR = 1.16 (0.60-2.26):drivers of other road passenger vehicles, OR = 0.95 (0.48-1.88);drivers of road goods vehicles, OR = 0.93 (0.71-1.22);bus conductors, OR = 0.57 (0.12-2.25);lorry drivers` mates, etc.: no cases: ICD 202: drivers of buses and coaches, OR = 1.63 (0.62-4.52);drivers of other road passenger vehicles, OR = 1.67 (0.684.32);drivers of road goods vehicles. OR = 0.90 (0.63-1.28); bus conductors, OR = 2.67 (0.6415.6);lorry drivers' mates, etc.: no cases (Balarajan, 1983; Balarajan & McDowall, 1983). All new cases of lymphoid malignancies diagnosed between October/ 1979 and December/ 1981 were selected among adult residents in six health districts in Yorkshire Health Region. There were 81 male and 77 female NHL, 48 HD, 66 chronic lymphocytic leukemia a n d 13 acute lymphoblastic leukemia cases. It was a hospital-based case-control study where the control group was performed by non-cancer hospital patients (162 male and 154 female for NHL cases), matched for age, sex and geographic area in a ratio of 1:l. Past occupations and selected exposures were analyzed and the following results were observed: occupational exposure to solvents (excluding benzene), OR = 1.52 (0.70-3.26)male a n d OR = 7 . 7 1 (1.2447.93) female; petroleum industries. OR = 4.21 (0.54-32.79)male; solvent use as hobby. OR = 1.39 (0.30-6.46)male: benzene. OR = 0.49 (0.212.0) male; petrol products. OR = 0.59 (0.251.39) both sexes: hair sprays. OR = 1.49 (0.752.95) female; hair sprays. OR = 4.67 (1.50-13.63) female >65 years old. The number of exposed cases was not referred, nevertheless it can be inferred that they were small by looking at the large confidence intervals. including those statisticaly significant associations were seen among women (Bernard et al.. 19841. A new paper with the complete Yorkshire study data set was published including cases diagnosed until December/R4 (Cartwright et al.. 1988).The final rate between controls and cases was 1.7. At thar time. 337 cases (244 males and 193 females) and 724 controls were studied. N H L cases were confirmed by the Regional Histopathology Lymphoma Panel. The new analysis showed the following results: solvents, OR = 1.2 (0.9-1.5);glues, OR = 1.8 (1.2-2.6);and other non-significant associations in solvent related occupations. however with no rnentioned OR value: chemical workers, printers, painters and decorators. A population-based case-control study with all incident cases of myeloproliferative and lymphoproliferative diseases was done in Tasmania, Australia, with data from 1972 to 1980. Within that population there were 798 total cases, including 241 NHL (125 male and 116 female).The control group was selected. based on a I:1 ratio. lndividuals were mainly asked for both occupational and familial histories. Based on a few cases, it was seen a strong association between male foundry workers and NHL, OR = 8.0 (1.07-356.0).There were five exposed cases and no exposed controls among female hairdressers (Smith & Lickiss, 1980; Giles et al.. 1984). A population-based case-control study evaluated environmental chemical exposures as risk factors for leukemia a n d N H L (Everett et al.. 1985).The selected subjects were 1,200 men with rhese diseases and controls by random diaiing and from social security files. Exposure evaluation included a series of chemicals which are seen in [he workplace or home. For NHL, the following odds ratio were noted for soIven t- reIa ted exposures : 1acqu ers/ var- nishes, OR = 1.24 ( p < 0.1); engine exhaust, OR = 1.26 (pc0.05):hydrocarbon coats. OR = 1.67 ( ~ ~ 0 . 1h)y:drocarbon cleaners, OR = 2.13 (pc0.001);paint aerosols, OR = 1.28 ( p < 0.1) a n d gasoline as a cleaning agent. OR = 1.29 (P<O.05). information was recorded from patients admitted to the Hospital ofvarese, Italy to treat NHL and HD during 1984 a n d from non-cancer patients who were admitted to the same hospital. The eligibility criteria included living in that city for at least 15 years. There were 43 NHL ( 1 4 male a n d 28 female) a n d 46 HD cases and 89 controls. Some occupations were considered "exposed occupations": professors, farmers. metal-mechanics, chemists and textile workers. Their results showed an increased risk for metal-mechanics, RR = 1.98 (0.75-5.20)based o n 13 exposed cases and for chemists, RR = 1.Ol (0.27-3.74)based in four exposed cases. In this hospital-based case-control study the selected cases were neither prevalent nor incident cases in a defined period of time, and it does not seem that those cases have been representative of either general population or hospital population (Binaschi et al., 1985). Cad.Saude Rjblica. Ria de Janwro 14(Sup 31 11 66.1998 NON-HOOGKIN'SLYWWOMA RISK AND ORGANIC SOLVENTS 45 A death certificate-based case-control study posed of 435,425rnen13.704.864 personlyears of NHL and occupations with 501 and 569 male from 80 U.S.Navy occupations. The P!HL cases cases a n d controls. respectively. was carried were reviewed by a board of specialists and out in North Carolina (Schumacher & Delzell. classified according to the ICD 8th: (200.0. 1988).They observed a n increased risk for oc- 200.1.202.0-202.9):ICD 9th: 200.0,200.1, 202.1, cupations in rubber, plastics a n d synthetics' 202.8.202.9.Sixty eight N H L cases were found industries only for whites, based on four ex- in the exposed group. There were five cases posed cases and no exposed controls. Associa- among aviation structural mechanics. standard tions were neither seen for occupations with incidence ratio (SIR) = 1.5 (0.5-3.5)and 1 case potential benzene exposure nor for chemical among machinery repairmen. SIR = 1.8 (0.0- drugs and paint industries. 10.0). Two hundred and two male cases (ICD 200- A nested case-control study was conducted 2021.age 20 a n d over a n d 666 age matched within a cohort of 29.139employed men from male controls, excluding smoke-reIated can- two chemical plants between I940 and 1978 cers a n d prostate cancer were selected from (Ott et ai.. 1989).The authors were looking for Missouri Cancer Registry between 1984 and lymphatic and hematopoietic tissue cancers. 1985.Risk excess was found only among print- and among all cases (129),52 were identified as ers, OR = 2.72(0.96-7.69)N.o associations were NHL from both underlying and contributory observed with other solvent-related occupa- causes of death. Controls were selected from tions (Brownson & Reif. 1988). the total employee cohort according to a Another Swedish study was specifically de- group-matched incidence density sampling in signed to investigate the risk of NHL among a 5:l ratio. Elevated odds ratios were seen in men occupationally exposed to organic sol- the ethanoi unit, OR = 5.4(1.5-19.5)based in vents. It was a hospital-based case-control five cases. and in two maintenance and con- study, where the case group was performed by struction groups, foremen and others, 11 cases, a consecutive series of 167 men admitted be- OR = 3.2 (1.4-7.2)and instrument men, OR = tween 1978-1981,in the Department of Oncol- 5.2(1-26.71t,hree cases. The authors discussed ogy, University Hospital of Lund (Sweden)and the role of the carcinogenic action of alkyl sul- the control group by 130 healthy men selected fates which originated from the reaction be- from the population registry. Exposure was de- tween alkenes and sulfuric acid to produce fined by "handling organic solvents for at least ethanol and isopropanol. They also discussed o n e year daily". Categorization in five year age the difficulties in explaining the findings groups showed a n ORM-H = 3.3 (1.9-5.8)f;or among foremen and others because of their supra-diaphragmatic tumors, OR = 6.5 (3.2- heterogeneity and the lack of trends with em- 13.3)a n d for other lymphoma presentations. ployment duration. The authors found an O R = OR = 2.3 11.3-4.3)(Olsson & Brandt, 1988). 1.2(two exposed cases) for less than five years In Hancock County. Ohio, all white male and an OR = 1.6 (three exposed cases) for more residents aged 15 o r more who died during than five years of exposure. 1958-1983with malignanr lymphoma were en- The epidemiology of N H L i n north-east rolled in a case-control study. There were 61 Italy was evaluated through a hospital-based N H L and 15 HD. who were matched with other case-control study. There were 110 men and 98 deceased individuals, chosen through a strati- women be!ow age 80 with NHL.admitted from fied random sample by age at death and year of June 1983 to March 1988 at the Aviano Cancer death, in a proportion of 4 : l . N o associations Center and in all general hospitals in the were found with solvent-related occupations or province of Pordenone. Controls were 215 men industries. in addition, with the small number and 186 women ages 17-79 with acute disor- of subjects and despite t h e rush to complete ders. who were from the same hospitals and study. the authors discussed the limitations of same catchment area. Exposures to 20 poten- such a death certificate-based case-control tially carcinogenic chemical or physical agents study. mainly because of the inaccuracies in the were evaluated. For those activities with prob- cause of death and the lack of occupational and able solvent exposure, they found an increased industrial information (Dubrow et ai., 1988). risk for chemical. OR = 1.64(0.88-3.06)and All white U.S. Navy enlisted men during petrochemical workers, OR = 1.83(0.87-3.84) 1974-1983 were the subjects of a large cohort and suggested that employment in these in- study (Garland et ai.. 1988). The unexposed dustries may increase the probability of the on- group was performed by the U.S.population set of the disease. On the other hand, they had provided by SEER (Surveillance. Epidemiology, the following negative findings: dye and paint. and End Results). The exposed group was com- OR = 0.72 (0.36-1.44); plastic resinlglue, OR = Cad Saude Publica 910 de Janciro. 14Sup. 3):41-66. 1998 REGO. M. A. v 1.01 (0.46-2.23): benzene/solvents. OR = 1.14 (0.57-2.28) a n d woodlfurniture, OR = 0.66 (0.37-1.19) (Franceschi et al., 1989). Another Italian study did not show any as- sociation between NHL a n d a group of selected solvent related occupations and agents (chem- ical, petrochemical plastic resins/glues, solventdbenzene, oil, dyes/paints. rubber, printing and furniture). It was a hospital-based case-control study which included 153 incident cases of NHL (93 males and 60 females), 69 Hodgkin`s disease a n d 110 multiple myeloma diagnosed in patients aged 15-74. admitted to a network of teaching a n d general hospitals in the greater Milan area, from 1983 to 1988. Controls were 396 patients admitted to the same hospitals with acute conditions (LaVecchia et al., 1989). Data from a previously selected control group for two other studies, from the population registry, were utilized in a new case-control study (Persson et ai., 1989).Cases were 106 NHL (66 men and 40 women) and 54 HD cases, obtained from the Department oi Oncology at Orebo Medical Centre Hospital, Sweden. They were diagnosed between 1964 a n d 1986, and were still alive in 1986. ranging in age from 2080 years. Both groups answered posted questionnaires. In this hospital-based case-control study, solvent exposure was classified by five levels of intensity, for at least one year, taking into consideration a latency time of five to 45 years before diagnosis a n d time of selection for controls. There were seen some important increased risks: solvents, OR = 2.0 (33l50exposed caseslcontrols); thinner, OR = 2.7 (15/ 16);white spirit, O R = 3.1 (13/12);trichloroethylene, OR = 1.5 (8114);styrene, OR = 8.0 (311);painters, OR = (3/0);plasticlrubber chemicals, OR = 2.5 (9/101: carpenter/cabinet makers. OR = 3.1 (1019).The confidence intervals were not cited. The logistic OR = 1.9 (90% 1.1-3.2)and OR = 2.8 (90% 1.1-7.1) apply to solvent exposure to car- penters and cabinet makers, respectively. A new study was conducted (Persson et al., 1993) with the same planning. Cases were 93 NHL and 31 HD occurred in men living in Ostergotland. Jonkoping and Kalmar counties, obtained from the Regional Cancer Registry at the University Ilospital in Linkoping, diagnosed between 1975 a n d 1984, alive in 1986, and aged 20-80.At this time, only men were studied. Two hundred a n d four referent individuals were drawn from the population registry. In that study, occupational exposure to solvents revealed a n OR = 1.2 (28/53exposed caseslexposed controls) and an OR = 1.7 a n d an ORlog = 1.1 (0.6-2.2) (24/34)w,hen intensity category levels 2-5 X 0- 1 were analyzed: white spirit, OR = 1.6 (14/20);aviation gasoline, OR = 3.0 (4/3).For non-occupational exposure was seen an OR = 3.4 ( 3 1 2 ) .Carpenters and cabinet makers had an OR = 1.0 a n d a n ORlog = 0.9 (0.4-2.1) (11/25),which means a conflicting result in regards to the former investigation. A population-based case-control study was primarily designed for looking for associations between NHL occurrence and specific agents in farm practices. Cases were 20 1 men aged 2 1 or older in 66 counties of eastern Nebraska, diagnosed with NHL from 1983 to 1986. They were identified through the Nebraska Lymphoma Study Group Registry and area hospitals and physicians, and reviewed by a pathologist. Controls were 725 subjects selected from residents of the s a m e area, matched by age, race and vital status. Both groups were interviewed by telephone. For exposure to chlorinated hydrocarbons a n OR = 1.9 (0.8-2.3) was observed (Weisenburger et a1..1990). The relationship of occupational risks a n d hematological malignancies development were evaluated through a hospital-based case-control study (Pasqualetti et al.. 1991).They selected 108 NHL within 620 neoplasm hospital patients aged 24-85, and 2:l sex and age matched hospital controls with "medicaldiseases", except cancer and congenital diseases, from the same area as the cases, On o n e hand, the authors found statistically significant dssociations between hematological malignancies in general and industrial activities, OR = 2.97 (1.98-4.46). exposure to aromatic hydrocarbons, OR = 2.15 (1.39-3.32). dyes and inks, OR = 1.28 (1.11-1.99),mineral oils, OR = 2.59 (1.753.84) and paints a n d related products, OR = 1.55 (1.06-2.26). On the other hand. when they analyzed specifically the NHL subset, only an association with mineral oils was seen, OR = 3.4 (1.65-7.38).They have found a lack of asso- ciation between NHL and other potential expo- sures to solvents such as auto mechanics, railroad workers. or specific exposures to cetonas, aliphatic hydrocarbons, chlorinated hydrocarbons. and dye. paints and inks. With the Danish Cancer Registry data. individuals aged 20-64 from 1970 (census data on industry and occupations) were followed up for cancer incidence until 1980 (Skov & Lynge, 1991). NHL cases were 1,167in men and 849 in women during that period, distributed among 492 male and 447 female occuparional groups. Statistically significant associations were not obtained, however it was suggested that potential exposure to chemical agents may be implicated in the increased risk for N H L based Cad. Saude Publica, Rio d8 Janeiro. 14(Sup. 3).41db. 1998 47NON-HOOGKINS LYMPUOMA RISK AND ORGANIC SOLVENTS mainly in the findings of wood working (male). Questionnaires were directly applied to cases RR = 1.15 (0.87-1.52);chemists (female), R R = (67%). to cases' proxies (31%)and to cases' 2.32 (0.85-5.04) and hairdressers (female),RR = guardians (2%).No information was mentioned 2.01 (0.81-4.14). regarding distribution of these interviews with- Incident cases of NHL (572) a n d leukemia in the control group. The main results, related (520)a m o n g white men diagnosed between to solvent exposures were: gasoline or kerosene. 1980 and 1983 in Iowa a n d IMinnesota were se- OR = 1.0 (0.6-1.7): benzene, OR = 1.2 (0.5-2.6); lected for a population-based case-control chorinated solvents. OR = 1.2 (0.8-1.R):metal study in the USA (Linos et al., 1991). Diagnoses industry, OR = 1.2 (0.6-2.5):machinery. OR = were reviewed by a panel of pathologists. Con- 0.8 (0.4-1.4): shipbuilding. auto, OR = 1.0 (0.6- trols were frequency-matched by year of birth. 1.7);chemicals, drugs and paints. O R = 0.3 (0.1- vital status, state of residence a n d year of 0.9); leather, OR = 2.1 (0.9-4.8);dry cleaning, death. by a two-stage random digit dialing ( ~ 6 5 OR = 1.6 (0.6-4.0);painter and plasterer, OR = years) and from Health Care Finance Adminis- 6.0 (0.9-38):carpenter, brick and stone mason. tration (65 years). Questionnaires were applied plumber and roofer, OR = 12.0 (2.0-72):air- to study subjects or their next-of-kin, and ex- plane or auto mechanic, gas station attendant, posure was defined as the location of residence OR = 1.1 (0.6-3.6). within 3.2 a n d within 0.8 Km from a factory. Cancer incidence from 1971 to 1984 was Among the first ones, were factories where or- defined using the Swedish Cancer- Environ- ganic solvents are handled. In the chemical ment Registry, with occupational information plant there were 18 EC, RR = 1.0 ( 0 . 6 - 1 . 9 ) .in from the 1970 census (Eriksson et al.. 1992).At the petroleum industry, 14 EC, R R = 1.5 (0.7- rhe end of the follow up the authors got 1,082 3.2) a n d in the rubber plant, 1 1 EC. R R = 0.6 NHI, cases (030 men 252 womenl, 317 HD and (0.3-1.3). 684 MM classified according the ICD 7th 200- In a n ecological study, information about 203. Among all occupational groups with po- lympho-hematopoietic neoplasm incidence in tential exposure to solvents, carpenters (149 22 counties in the UK (1984/1988) was crossed OC) yielded ;ISIR = 1.2 (1.0-1.5). to car ownership by county (1981) from Great A nesrcd case-control study was carried Britain Population Census and Transport Sta- our with fatal lymphatic and hematopoietic tistics data. There were 2,115 low grade a n d malignancies which occurred in male workers 2.550 high grade NHL within a total of 21.072 of eight North American styrene-butadiene neoplasms. The Spearman rank correlation co- plants between 1943- 1982. The original cohort efficients showed a statistically significant as- had 13,686 workers and yielded 15 NHI. cases sociation between low grade N H L incidence among 59 lymphohematopoietic cancers. The and cars per household (0.66 p e 0.001) and control group was performed by 193 individu- cars per thousands (0.68 p<O.OOl).No associa- als. matched by year of hire, date of death. age tion was seen for high grade NHL. The author and duration of work. selected from the same called for reservation about these preliminary cohort with causes of death other than neo- outcomes from data based on geographical plasms. A job exposure matrix (JEM)was con- correlation, but implied that if these are true. structed by a panel of four chemical engineers the non-occupational low exposure to benzene who classified the exposure to styrene and to from petrol combustion and petrol evapora- butadiene using data from personal records. tion may be playing a n important role (Wolff. For styrene exposure a n OR = 1.39 (0.13-3.92) 1992). was seen for lymphosarcoma and an OR = 2.42 A hospital-based case-control study, where (0.50-11.6) for other lymphomas, which in- cases were all newly N H L diagnosed patients, clude myeloma (Santos-Burgoa et al.. 1992). from 1980 to 1982 was carried out among resi- Epidemiologic studies pertaining to the possi- dents of the Boston Metropolitan Area who ble relation between exposure to 1.3-butadi- were treated in one of nine participating hospi- e n e and the occurrence of lymphatic and tals (Scherr et al., 1992).The control group was hematopoietic cancer among styrene-butadi- composed of individuals matched by age. sex. ene rubber and butadiene production workers town a n d precinct of residence, randomly se- were reviewed. In the aggregate data. there lected from the town residence list. Cases were were 20 observed us. 17.9 expected deaths from made u p of 152 males a n d 1 5 1 females. with lymphosarcoma cases. In general, it was con- controls for the 303 individuals. Diagnoses cluded that there is no support for a causal re- were reviewed by a panel of pathologists, who lationship for such exposures (Coleet al., 1993). utilized Rappaport (modified)and Internation- An industry-based case-control study al Working Formulation N H L classifications. was carried out in Finland (Partanen et al., Cad. Saude Publica. RIO de Janeim. lO(Sup. 3l:41-66.1998 48 REGO. M. A. V 1993). Cases were malignant lymphomas and leukemias notified to the Finnish Cancer Registry, diagnosed in male woodworkers of 35 plants, within a cohort of 7.307 workers, between 1957-1982. Controls (52 for the NHL cases) were matched by year of birth and survivailnon-survival status in 1983, selected from the s a m e cohort. Only eight NHL cases were found (ICD 200. 202). Individual exposures to solvents and to other agents were reconstructed using a plant/period-specific JEM (cases and controls). Also interviews of persons at the plants were performed and questionnaires were applied (only to cases or their next-ofkin). For unidentified solvents. leukemias and lymphomas pooled (four exposed cases) produced an OR = 5.62 (0.99-32.0)and adjustment for formaldehyde exposure showed an OR = 5.07 (0.40-63.5).Two exposed cases and no exposed controls were seen when NHL were analyzed separately. White men with NHL reported to the Iowa State Health Registry, between 1981 to 1983 and between 1980 to 1982 at a network of hospitals in Minnesota were included in a population-based case-control study (Blair et al., 1993).The 1.245 control individuals were frequency matched with the 622 N H L cases by age, year of death for deceased cases, and state, from random digit dialing, medicare files and listings of death. Questionnaires were directly applied to cases and controls or their surrogates and included information about job titles and industries, which were further evaluated by a n industrial hygienist. who decided the probability of exposure (four levels) and intensity of exposure (three levels).The authors concluded that industrial exposures are not a major contributor to the etiology of NHL. Some important findings were: pain tingjpaper hanging, OR = 1.9 ( 0 . 9 - 3 . 8 ) ;petroleum refining, OR = 1.6 (0.5-5.8);printing, OR = 1.5 (0.4-5.1); paints. OR = 1 . 1 (0.9-1.5);asphalt and creosote, OR = 1.0 (0.7-1.6);gasoline and diesel exhausts. OR = 1.0 (0.8-1.3).This study tried to find a relationship between low and high exposures and sub-types of the disease. classified as follicular or diffuse. It was seen that the risk of NHL rose slightly with increasing levels of exposure to benzene and other solvents. The main results were: benzene, OR = 1 . 1 (0.9-1.4);OR = 1.3 (0.91.9) for low levellfollicular; OR = 1.9 (0.7-5.3) for high/follicular; OR = 1.2 (0.8-1.8)for low/diffuse: OR = 1.8 (0.6-5.4) for highldiffuse; solvents other than benzene OR = 0.9 (0.9-1.4)O; R = 1.4 (0.9-2.0) for lowlfollicular: O R = 1 . 1 (0.4-2.7)For highlfollicular; OR = 1.0 (0.7-1.5)for low/diffuse and OR = 2.4 (1.2-5.0)for highldiffuse. A large cohort study linked information about cancer incidence from 1961 to 1979 using the Swedish Cancer-Environment Registry with occupational information from the 1960 census (Linet et al.. 1993).There were 4,496 observed cases among employed Swedish men distributed among industrial and occupational categories, which derived from international standards. The most important associations regarding solvent exposure were seen in the shoe repair industry: 23 cases, SIR = 1.8 p<0.05; shoemakers: 23 cases, SIR = 1.7 (p<O.OS);porcelain and earthenware: 14 cases, SIR = 1.9 (pc0.05); furniture maker: 44 cases, SIR = 1.3 (p<O.Ol) and lorry drivers: 12 cases, SIR = 1.4 (pcO.01). Other well known solvent related industries and occupations failed to show associations. The same strategy was applied to study the female workers (Linet et al., 1994). They observed 1,174 cases of NHL in employed Swedish women. At that time, the following results were verified: furniture and finishing industry: four cases. SIR = 1.5;graphics industry and pubiishing business: 15 cases, SIR = 0.7;rubber industry: five cases, SIR = 1 . 1 ; chemical industry: nine cases, SIR = 0.8; machine and electronics industry: 26 cases, SIR = 0.8; shoe and leather workers: 10 cases, SIR = 1.4. A death certificate-based case-control study (Massoudi. 1994; Massoudi et ai.. 1997) was done in Kanawha County (West Virginia). Cases were 435 lymphatic and hematopoietic neoplasms in white male aged 23-96 who had died between 1965-1990. Among them there were 106 NHL (ICD9th 200, 202) reviewed by a pathologist. Industries and occupations were obtained from death certificates and validated by interviewing next-of-kin. Three categories of exposure were defined: chemical manufacturing workers, those exposed to chemicals at other jobs. and those not exposed. The association between NJJL and work in chemical industries was analyzed (chemical workers versus not exposed): crude analysis. OR = 1.52 (0.82.8);age c65 OR = 3.11 ( 1 . 1 - 8 . 8 ) ;age 65 OR = 0.97 (0.5-2.1). Another large cohort study was developed in Denmark (Kolstad et al., 1994). The exposed group consisted of 53,720 male workers (584,556 persons/year) employed any time from 1964 to 1988 in 386 reinforced plastic industry and resident in Denmark after 01101170. followed up until 12/31/89.The non-exposed group was composed of individuals from t h e general population. Exposure to styrene was evaluated using 2,473 personal air samples from work sites during 1964-1970. 1971-1975 and 1976- 1988 with rhe mean styrene levels of Cad Saude Publica. R m de Janewo. Icl(Suo 3) A1 4 6 1998 ... 49UON.HODGK~N'SLYMPHOMA 5K AND ORGANIC SOLVENTS 180,88 and 43 ppm (1.814 were sampled from companies included in the study).Among the companies with 1-49 % of workers in reinforced plastics production the following results were seen: c IO years since 1st employment: 19 observed cases (OC).SIR = 2.35 (1.42-3.67):10 years: 17 OC, SIR = 1.23 (0.71-1.98).Among those conlpanies with 50-100 70of workers in reinforced plastics production different results were found: e10 years since 1st employment: 2 OC, SIR = 0.43 (0.05-1.57);10 years: four OC. SIR = 0.79 (0.22-2.02).When all companies were evaluated together, SIR was 1.33 (0.96- 1.80) with 42 OC. The analysis per year of the 1st employment did not show significant findings: 1964-1970, 21 OC, SIR = 1.28 (0.79-1.96): 1971-1975, 10 SIR = 1.19 (0.57-2.18):1976-1988. 11 OC. SIR = 1.64 (0.82-2.94). Based on death certificates. a case-control study where cases were 23,890 NI 11. deaths was done among residents from 24 American states berween 1984-1989 (Figgs et al., 1995).There were five non-cancer death controls per case, totaling 119,450 individuals. Cases were classified according to the ICD 9th, categories 200 and 202 (except 202.3 and 202.6). Exposure was defined as industries and occupations obtained from death certificates. Occupations with certain or potential exposure to solvents were stratified for race. For white men, aircraft mechanics had a n OR = 2.5 (1.1-6.0) with eight exposed cases: farm equipment mechanics. seven exposed cases, OR = 2. I (0.9-5.3);electronic repairs, 12 exposed cases, OR = 2.1 ( 1 . 1 4.1):miscellaneous electronic and electrical repairs. 10 exposed cases. OR = 2.0 (1.0-4.3): painters, 65 exposed cases, OR = 0.6(0.5-0.8). For black men, only ship/boat building a n d repair industry was important in relarion to solvent exposure and had seven exposed cases and an O R = 2.9 (1.1-7.9). A case-control study in Lyon. France. evaluated cases of hematological malignancies. which included 52 NHL of both sexcs. aged 3074 and diagnosed between January/1981 and December/ 1987 in two hospitals (Hours et al.. 19951. Control subjects were non-cancer a n d non-occupationally diseased patients, 1:1 matched by sex, age a n d nationality, from t h e same hospitals. Occupational exposure to 320 conipounds was verified using questionnaires plus evaluation by experts in chemistry and occupational medicine. An OR = 2.1 ( p = 0.23) based on 13 exposed cases was seen For exposure to mononuclear aromatic hydrocarbons which include benzene. An OR = 14.86 ( p c 0.01) was found for exposure to a mixture of b e n zene. toluene and xylene (BTW based in six ex- posed cases. Polynuclear aromatic hydrocarbon had (30 EC), OR = 0.76. Exposure to inks (20 E(:) yielded an OR = 2.47 (p = 0.02) and varnish and paints exposure (six EC). OR = 2.55 ( p = 0.08). In a small cohort mortality study, 338 male employees (3.813 p/y) of the fleet maintenance division of the DC's Department of Public Works (DPW),employed for at least o n e year between 1977-1991 were followed up (Hunting et a].. 1995). Nine cancers and three lymphatic and hematopoietic deaths (one NHL death) were found. Potential exposure to fuels and solvents was classified as low, medium or high. according to personal records data and DPW and union representatives discussion. The three lymphatic and hematopoietic cancers showed a SMR = 4.22 (0.87-12.34)and the NHL case. a SMR = 2.57 (0.06-14-27). A very large multicenter retrospective study was conducted within a cohort of Chinese workers (Dosetneci et al., 1994: Travis et al.. 1994;Yin et al.. 1996).The exposed group was composed of 74,828 workers employed from 1972 to 1987 in 672 factories in 12 Chinese cities and the unexposed were 35.805 workers from 109 factories in the same period and places. They analyzed all available data: work units; job titles; monitoring data: list of row material and Factory products: engineering control; personal protective equipment and with them, benzene exposure in parts per million was estimated. Seventeen exposed deaths. RR = 4.5 (1.3-28.4)and 20 exposed cases. R R = 3.5 (1.3-14.91were found. In this study, the limitation was the lack of homogeneity of the data from too many different plants. In a nested case-control study in Canada, cases were all male NHL deaths from a cohort of petroleum workers and controls were selecre d from the same cohort matched by a decade of birth in a proportion of 4:l (Schnatter et a\.. 1996). Of a total o f 3 1 lympho-haematopoietic cancers. eight were NHI.. Personal records plus evaluation by experts in industrial hygiene were utilized to estimate benzene and the total hydrocarbon exposures in ppm. No association was found between the low level exposures and mortality by NHL. The size and consequentialty the power of this study were seen as important limitations. Also in Canada, a large registrv-based casecontrol study was developed. Lymphoma plus 18 other types of neoplasia were studied to generate a hypothesis about the occupational causes of cancer (Fritschi & Sierniatycki, 1996). Subjects were 215 men aged 35-70. with a new histologically confirmed NHL diagnosed be- Cad Saude Public2 Rjo de Janeiro. lO(Sup. 31:41-66, 1998 ) RGO.M A V tween 1979-1985 and residing in Montreal. The ing results were found: all NHL subtypes, OR = control group consisted of 2.357 other cancer 1.10 (0.90-1.30); small cell diffuse, OR = 1.60 patients, excluding lung cancer, and by 533 in- (1.10-2.20); small cell diffuse. 9 years o f e x p o - dividuals selected from a n electoral list or by sure, OR = 1.50 (0.99-2.20):small cell diffuse. > random digit dialing. A structured question- 9 years of exposure, OR = I .70 (1.10-2.60);small naire plus evaluation by a team of chemists cell diffuse. IO years since first exposure, OR = and industrial hygienists were used to define 3.00 (1.60-5.80);small cell diffuse, > 10 years exposure. Exposure was categorized as possi- since first exposure. OR = 1.SO ( 1.OO-2.IO);fol- ble, probable a n d definite, and the frequency licular, OR = 1.0 (0.79-1.40): large cell diffuse, of exposure defined as c5%, 5-30970and ~ 3 0 % . OR = 0.97 (0.79-1.20). 'The concentration of the agent at the work- place was also analyzed. These three measures were combined, producing three groups: unex- Oiscussion posed, non-substantial and substantially ex- posed. Occupations and industries were also In rotal. 45 studies were rcvierved. Twenty o n e classified. No association was found. There (46.7?/,)were conducted in Europe. This issue were 20 cases exposed to benzene and classi- was a colicern mainly i n Sweden where eight of fied as the non-substantial exposed group. OR these studies were done, in Italy five studies = 0.7 (0.4-1.1) and six in the substantial ex- and four in the United Kingdom. In North posed group, OR = 0.8 (0.3-2.1).For solvents in America, 20 studies (44.4%)were d o n e in the general, classified a s low levcl, there were 2fi llnited States and two (4.4%)in Canada. The EC. OR = 0.6 (0.4-1.0) and for high level expo- remaining two studies came from Australia and sure, 48 EC. OR = 0.9 (0.6- 1.3).Among carpen- China. Only one study focused exclusively on ters, there was no case with 1-9 years of expo- women. In 25 studies ( 5 5 . 5 % ) only m e n were sure a n d four EC. OR = 0.8 (0.3-2.2) for those selected a n d 19 (12.2%)included both sexes. with 10years or more in that occupation. In the This difference could be partially explained by furniture indusrry: 1-9 years, one EC, O R = 0.4 t h e fact that more male workers have an o p - (0.1-3.4); 10 years or more: three EC, O R = I.fi portunity to be exposed to organic solvents. (0.4-6.1). Finally, among the rubber and piastic Nevertheless. most occupational cancer epi- workers: 1-9years: four EC. OR = 3.6 (0.9-150); demiologic research has focused on white IO+ years: one EC. OR = 9.0 (0.6-148.0). men. The reasons for excluding women a n d Holly et al. ( 1997) developed a case-control minorities from consideration in this kind of study. Cases were 312 N H L among homosexual study are numerous and often legitimate. Small men. a n d controls were also homosexual men, numbers of subjects or events. lower exposures marched by age within five years and county of and difficulty in tracing were the reasons most residence. Chemical and occupational expo- commonly given. However, a general lack of in- sures were evaluated using questionnaires. The terest or lack of consideration are also possible authors concluded that among t h e H I V posi- reasons (Zahm et al.. 1994). tive men. occupational exposures were of brief Since the outcome of these studies is a rare duration and did not account for the develop- disease, it was not a surprise that the case-con- ment of the N H L cases. trol design had been chosen in 32 studies One of the most important studies was de- ( i I . l % ] . Among them, hospital based case- veloped by Tatham et al. (1997) using data control srudies were most often conducred, 12 from eight cancer registries in t h e United (37.5%). followed by the populational case- States between 1984 and 1988. I t was a popu- control design, nine (28.1'801. death certificate- lation-based case-control study, where the based. four ( 12.5%)- nested case-control. four 1,048 NHL cases in men were grouped by sub- ( 1 2.5%) and registry-based case-control. three types defined by a panel of pathologists. There (9.Jo/,).Other designs were 10 ( 2 2 . 2 v 0 )cohort were 185 small cell diffuse lymphomas; 268 studies, two ecologic (4.4%) and o n e clinical follicular lymphomas and 526 large cell diffuse case series (2.2%).The number of cases ranged lymphomas. Conrrols were 1.659 individuals from one to 23,890 individuals. matched by date of birth (within five years) In 20 studies (44.4%),cases of N H L were re- through random digit dialing. All individuals viewed by a pathologist or by a panel of pathol- were interviewed by telephone. Time of expo- ogists and in 25 (55.6%) this review was not sure for all jobs with known dates were defined done. The objective of most studies was to within 10 vears and more than 10 years. An OR eval11 ate lym pha ric and he ma to poietic rnali g- = 0.9 1 (0.75- 1.10) was seen for chlorinated hy- nancies. including leukemia. mycloma. HD drocarbons. For solvent exposure. the follow- and NHL.NHL was mostly classilied as a whole Cad Saude Publica. Rio d e Janoiro. 14ISuo 3) A 1 66, 1998 disease which included all sub-types. Three studies differentiated reticulurn cell sarcomas and lymphosarcomas, one study classified it according to the severity of the disease as low or high grade. Two studies made the distinction between low and high grades. and/or differentiated between diffuse and follicular patterns of the tumor. In comparing studies where pathologists reviewed slides with studies having n o slide review, there was no difference between the results. This issue was the target point of a review of 668 slides of NHL, a n d a n agreement of 93% was observed between reported diagnosis and the panel review. I t was concluded that depending on the degree of potential bias allowable in the study being undertaken, panel review to confirm diagnoses of NHL may not be necessary and panel review to develop subtypes of N H L may not be useful in epidemiologic studies, especially relative to the time and cost involved (Dick et al., 1987). As mentioned, most studies did not use the current classification systems to differentiate various histologies of NHL. One reason for not using a detailed classification scheme may be the size of the study that would be required to have a sufficient number of cases or even a few of the various histologies that would achieve statistical significance for a twofold relative risk or less (Scherr & Mueller, 1996). 7Lvenry seven (60.0%)studies had informatiun about exposure to specific agents. but only five (11.1%) were based on environmental measurements. Most studies used job titles (62.2%1 and/or industries (46.6%1as the measure of the exposure. Twenty two studies (48.9%) got information from questionnaires and five (11.1T0) used chemistry or industrial hygiene expert judgments to complete the available information. This latter procedure has been generally recognized as the reference merhod for exposure evaluation, at least for population-based case-control studies (Bouyer & Hemon, 1993; Stiicker et ai.. 1993). In 34 studies of a total of 41 (82.9%), 68 non-statistically significant associatiom were found. Two studies published only statistically significant associations. NO associations were seen in 29 of 39 studies (74.3%)which referred to negative results. It is impossible to enumerate all of them. because some of these associations were not pointed out by the authors. Fifty four statistically significant associations between solvent exposure or related occupations or industries were reported in 25 studies (55.5%).For each study, these associa- tions were seen: ( 1) lymphosarcoma and proximity with chemical industry; (2) benzene and related occupations; (3)printing: (4) styrene. trichloroethylene, perchloroethylene. benzene. other solvents and solvents plus chlorophenols and phenoxi acids; (5) solvents (female); (6) wood industry; (7) lacquers and varnish. engine exhaust. hydrocarbon coats and cleaners. paint aerosols and gasoline as a cleaning agent; ( 8 ) glues; (9)rubber, plastics and synthetics: (10) solvents; ( 1 1) ethanol unit, foremen and instrument men: (12) solvents and carpenters: (13) mineral oil; (14) car per household and car per thousands; (15)carpenters and other similar; (16) carpenters: (17) high exposure to solvents and diffuse NHL; (18) shoe workers. porcelain workers, furniture workers and lorry drivers; (19) organic solvents; (20) chemical workers less than 65 years: (21) styrene less than 10 years of exposure with 1-4970of workers in production section; (22) mechanics. electronic and electrical repairs and ship building; (23) mixture of benzene, toluene and xylene and inks: (24)benzene: (25) solvents and small cell diffuse. I n a review of the epidemiology of the OCCUpational factors of chemically induced lymphoid and hemopoietic cancers. the difficulties associated with such a review are recognized. They are mainly related to both disease and exposure definitions. However, consistent findings were reported for occupations with benzene exposure [Tsongas. 1985). h o t h e r review about leukemia and lymphoma risks derived from solvenrs pointed out that a relation between solvent exposure and malignant lymphomas has been called into question (Brandt, 1987).The author referred the contradictory results from specific studies and mentioned that the reasons are obscure. It was explained that, apparently, the studies which failed to find an association were based on register data or occupational titles. suggesting the need for further investigations in this field. Some occupations were shown to be relate d with N H L as in the cases of the rubber industry (Monson & Nakano. 1976: Wilcosky e l al.. 1981; Delzel & Monson. 1984); petroleum refining workers (Thomas et al.. 1982: Wen et al.. 1983; Uelzell et al.. 1988); chemists (Li et al., 1Y69: Searlc et al., 1978; Olin, 1978; Olin & Ahlbom. 1980; Rinsky et al.. 1988): printers (Zoloth et al., 1986); highway workers (Maizlish et ai.. 1988); dry cleaners (Blair et al., 1990) and heavy machinery production workers (Mallin et ai., 1986). The etiologic agents responsible for these excess have not been identified definitively, but all occupations have ex- posure to organic solvents in common (Zahm. 1996). Cad 'jauae Publica. Rio de Janefro 14(Sup 31 4 1 46.1998 ' REGO. M A V Beyond the millions of industrial workers with potential exposure to solvents. the general population is also potentially exposed through contact with commercial products and contaminated drinkink water. Because exposures have increased over the same time period as the increase in NHL, it is plausible that solvents may have contributed to rising incidence (Ries et a1..1994). Besides, a low risk was observed for all lympho-hematopoietic cancers, including N H L in Circumpolar Inuit, which suggested that it may reflect protective environment or genetic factors (Lanier & Alberts. 1996). ` b e n t y three studies (51.1%) concluded either that there was no association, or that there was no need for future investigations. even if there was the possibility of relationship. Some studies suggested that organic solvents can act as a risk factor for NHL dcvelopment. It was noticed in this review that statistical significance was more frequently shown in studies where solvent exposure was more accurately defined, OR = 5.2 (1.11-26.19) - exposure to or- ganics solvents was specifically evaluated: yes/ nu; results with statistically significance: yes/ no. Eighteen such studies, 13 172.2%)defined or suggested organic solvents as possible risk factors for NHL. Tablet - Studies on non-Hodgkin`s lymphoma in relation to potential occupational organic solvents exposure. ~ ~~~ Authorslyearl country 1- Capurro. 1979. USA 2- Vianna & Polan, 1979, USA Dosign Sourco population Study Subjects Disrase Exposure Classification Results Clinical case series Cohort mortality A community of Caucasian 117 individuals Lymphoma people from 1968 to 1974 All deaths male 2 age 20 146 RCS, 353 RCS,LS with RCS. LS or H D from LS and 267 HD and HD death certificates of New York State, excluding New York City, from 1950 to 1969 Solvent exposure measured in the environment and in the blood of the residents --- Benzene related occupations 23 cases of cancer 8 of them were lymphoma, considering specifically the 3 deaths due to lymphosarcoma in a 6 year period. OtE, =. 310 0187, 160 fold RCS =RR1.1 1 6. LS RR = 2 1, HD RR = 1 6 For 45 years old and over -RCS O/E = 1 7 p<O 01 LS O/E = 2 1 p 4 01 H D O/E 1 9 p<o 01 3- Cantor & Ecological Fraumeni. 1980. USA 4- Hardell et ai.. 1981 Sweden Hospitalbased casecontrol Age adjusted mortality rares for NHC!' in counties of the contiguous US. 3.056 counties ICDI. 200. 202 and 205 Proportion of printing, chemical. petroleum, furniture. iectncal, machinery and rubber industries per each county Cases all men assisted m Cases 109 the Dep Of Oncology in NHL and Umea (catchment area), 60 HD. 25-85 years old. controls controls.338 8 matched (age, sex. residence) controls for each living case and 10 matched (age, sex, residence and year of death) from the National Population Registry -- - Lukes-Collins Self administered (modified) questionnaires. supplemented by telephone, high and low grade solvent exposure Associations in a multiple regression analysis for white males and printing (p significant a t p<O 025) petrochemrcals and rubber products low grade RR = 1 2 (0 5-2 6).high grade (Styrene. trichloroethylene. perchloroetnylene. benzene) RR = 4 6 (1 9-1 1 4). other RR = 2 8 (1 6-4 8). high t. IOW RR 3 2 4 (1 5-3 8). solvents + chlorophenols and phenoxy acids RR 8 5 (4 4-17 2) 5- Meinhardt et al , Cohort 1982, USA mortality Workers in 2 styrenebutadiene rubber plants Plant A 1662 indiv. 34,187 ply Plant 8. 1094 indiv 19.742 p l y Hematopoi- Butadiene. styrene etic and and benzene lymphatic environmentai malignancies measures IC0 200-205 Lymphatic and hematopoietic tissues (220-205) SMR*'c -155 (plant A) and 78 (plant B), lympho and reticulosarcoma (200). SMR= 181 (plant A) and 132 (plantB1. Excess mortality not statistically significant Cad. Satid* Publica. Rio de Jamiro. 14(Sup 3):41-66. 1998 53NON-HOOGKINS LYMPHOMA RISK A N 0 ORGANIC SOLVENTS Authordye8d country 6- Balaralan. 1983. UK 7- Franco 81 Ponte. 1983. Italy 8- Bernard et ai., 1984. U K 9- Giles et al.. 1984, Australia Design Source population Study Subjects Diurse Exporuro Uassifiution Rorults Registrybased case control Cases: malignant Cases. 426 lymphomas in men lymphomas aged 15 and over, from (256 NHL). 1973 to 1977 collected controls: 256 -at the National Cancer Registry; controls: randomly chosen from other cancers, matched 1.1 by age, sex and region of restdence ICD 8 h : 200 and 202 Road transport workers ICD 200: drivers of buses and coaches. ORg**= 1.16 (0.60-2.26); driven of orher road passenger vehicles: OR 0.95 (0.48-1.88): drivers of road goods vehicles: OR = 0.93(0.71 1.22); bus conductors: OR 0.57 (O.lZ-2.2SI; lorry drivers' mates, etc.. no cases; IC0 202. drivers -of buses and coaches: OR 1.63 (0.62-4.52); drivers of other road -passenger vehicles: OR 1.67 (0.68-4 32): drivers of -road goods vehicles: OR 0.90 (0 63-1.28); bus conductors: OR- 2.67 (0.64- t S 6); lorry drivers' mates, etc.. no cases Hospitalbased case-control Cases: patients of both sexes aomitted to the Ctinica Medica A. Ferrata - University of Pavia. from 1969 to 1980, diagnosed as malignanr lymphoma; controls: patients admined to an internal medicine unit in Pavia from 1975 to 1980 Cases: 282 NHL ana 387 HO (347 male and 322 female; controls: 757 male and 588 female NHL Occupations as proposed by the Annuario Statistic0 Italian0 Chemical and pharmaceutical: 4 EC,li, OR = 0.16; Textiles, shoes and leather 21 EC, -OR 0.50; Paper and -printing: 3EC. OR 0.90; rubber and plastics: 3 EC. OR = 0 33; wood: 14EC. OR 5.55(2.39-12.85) Hospitalbased case-control Cases: all new cases diagnosed between Octobed1979 and December/l981 in adult residents in six health districts in Yorkshire Health Region; controls: 1:l hospital patients, matched for age, sex and geographic area Cases: 81 male N H L and 77 female NHL; 48 HD; 66 CLL,,; 1 3 ALL controls: 162 male and 154 female patients for NHL cases Questionnaires applied by one interviewer; past occupations and selected exposures Occupational solvents -(excluding benzene): OR 1.52 (0.70-3.26) male; OR = 7 71 (1.2447.93) fernale: petroleum industries: OR = 4.21 (0.54-32.79) male; solvent use as hobby: OR 1 39 (0.30-6.46) male: benzene: OR = 0.49 (0.21-2.0) male; petrol -products: OR 0.59 (0.25- 1 39) both sex; hair -sprays: OR 1.49 (0.75- 2.95) female; hair sprays: OR * 4.67 (1.50-13.63) female >65 years old Populationbased casecontrol Cases. all incident Cases: 798 cases of total cases, myeloproliferative 241 NHL (125 and lymphoproliferative male and 116 diseases in Tasmania female): from 1972 to 1980: controls: 241 controls: 1:1age and sex matched from electorai rolls and Child and School Health Services All cases Personal interview; reviewed by occupations an oncologist. a hematologist and a pathologist Male foundry workers: OR * 8.0 (1.07-356.0); female hairdressers: 5 exposed cases and no exposed controis Cad. Sauda Publica. Ria de Janciro, 14610 31 41-66, 1998 ?EGO. M. A. '4 Tablet (cont.) Authordyed country 10- Everen et al.. 1985. USA ? 1- Binaschi et al., 1985, Italy 12- Schumacher & Deltell, 1988, USA Dorign Sourco population Populationbased casecontrol Cases: men with NHL and leukemia; controls: selected by random dialing and from:sociai securny files Study Subjoctr Cases: 1200 controls: not cited Diseau Exporuro Classification NHL Personal interview: exposure evaluation to a series of chemicals in the workplace or home Hospitalbased case- control Cases: patients admitted Cases: 43 NHC NHL (Kiel) to the Hospital of Varese (14 male and to treat NHL and HD 28 female) and during 1984. living in that 46 HD; city for a t least 15 years; controls: 89 controls: patients admitted to the same hospital to treat other non-cancer diseases Personal interview; occupations ~ Death certificatebased case- control Cases: men who died from Cases: SO1 age 35 to 75. between controls: 569 1968-1970; 1975- 1977; 1980-1982: controls: other non-cancer deaths, frequency matched b y age, year of death and race, 1:1 whites and 2:l blacks ICD 200-202 Occupations Results - Lacquerslvarnishes: OR = 1.24 p< 0.1; engine exhaust: OR = 1 26 p<O.OS. hydrocarbon coats. OR = 1.67 p<O.l; -hydrocarbon cleaners: OR = 2 13 p<O.OOl, paint aerosols: OR 1.28 -p < 0 1: gasoline as a cleaning agent: OR 1.29 p<o.os - -Metai-mechanics: RR 1 98 (0 75-5 20) 13 EC. chemists: RR 1.01 (0.27-3.74) J EC Benzene. 'unites OR = 0.77 (0.56-: $7); blacks OR 9 0.94 (0.47-1.87) chemicals. drugs and paints: whites OR = 0.67 (0.3-1.51); blacks 1 exposed case, no exposed control (32 1- ) rubber, plastics and synthetics: whites 4 exposed cases. no exposed controls (1.29-) fuel. whites OR = 0.97 (0.19-5.02) blacks no cases and no controls furniture whites OR * 0.71(0.43-1.26) 13- Brownson & Reif, 1988, USA 14- Olsson & Brandt, 1988, Sweden t 5- Dubrow et ai.. 1988, USA Cancer registrybased case- control Cases: males, age 20 and Cases. 222 over from Missouri Cancer controls: 666 Registry (1984-198s); controls: 3 age matched white males to each case from the same source excluding smoke-related cancers and prostate cancer ICD 200-202 Usual occupation and industries collected by Missouri Center Registry Hospitalbased casecontrol Cases: a consecutive series of men admitted in 1978-1981, in the Department of Oncology, University Hospital. Cund; controls: two groups of healthy men selected from population registry Cases: 167 controls: 130 Rappaport Questionnaires applied by Interviewers; Exposure: handling organic solvents for at teasc one year daily Death cettificatebased casecontrol Cases: all white male residents of Hancock County, aged 1S or more, died during 1958- 83; controls: 4.1 chosen as a stratified random sample by age at death and year of death Cases: 61 NHL and 15 HD; controls: 304 ICD 7th (200. 202 and 205). 8* (200 and 202) and 9th (200 and 202 except 202.2 and 202.6) Occupation and usual industry or business Printers. OR 1 2.72 (0.96-7 69): no associations were found with atner solvent-related occupatlcns -Categorization in five year age group: ORWH 3.3 (1.9-5.8); supradiaphragmatic tumors: OR = 6.5 (3.2-13.3); other tumor presentations: OR = 2 3 (1.3-4.3) No associations were found with solventrelated occupations or rndustries Cad. Saude Publica, Ria de Jannro. 14(Sup.31:41-66. 1998 55NON-HODGKIN'S LYMPHOMA RISK AND ORGANIC SOLVENTS Tablet (cont.) Authorsfyear/ country Design Source population Study Subjects 16- Camright et ai.. 1988. UK Hospital- based casecontrol Cases: all new cases Cases: 437 diagnosed between 1979 and 1984 in adult residents in all districts (244 males and 193 females); in Yorkshire Health Region. controls: 724 controls: 2: 1 non-cancer hospital inpatients. matched for age. sex and residential health district Disoaso Exporuro Cladcation NHL Questionnaires applied confirmed by by interviewers: past the Regional occupations and solected Histopathol- exposures ogy Lymphoma Panel Results -Solvents: OR 1.2 (0.9-1.5); glues: OR = 1.8 (1.2-2.6); other nomsignificant associations without referring OR value. chemical workers; printers; painters and decorators 17- Garland e t al.. 1988. USA Cohon 18- Ott et al., 1989, USA Nested casecontrol Exposed group. all white U.S. Navy enlisted men during 1974-1983; unexposed group: U.S. population provided by SEER. Exposed group: 435,425 men/ 3,704.864 personlyears; NHL reviewed by a board 80 US. Navy occupations of specialists ICD 8th (200.0, 200.1, 202.0202.9); IC0 ?Ih: 200.0. 200.1. 202.1, 202.8, 202.9 Cases: selected from a Cases: 52; cohort of 29,139 men in controls: 260 two chemical plants; controls: selected from rhe total employee cohon according to a group- matched incidence density sampling In a S:: ratio NHL 111 work areas, 52 chemical activity groups and 21 specific chemicals 68 NHL cases in the exposed group; aviation structural mechanic: 5 cases. SIR = 1.S (0.5-3.5); machinery repairman: 1 case, SIR = 1 8 (0.0-10.0); -Ethanol unit OR 5.4 (1.5-19 5); foremen and -others OR 3.2 (1.4-7.2); InstrJrrent men OR = 5.2 (1-26.7) 19- Franceschi et al., 1989, Italy Hospitalbased casecontrol Cases: men ana women below age 80,admitted from June 1983 to March 1988 at Avlano Cancer Cases: 208 IC0 200-202;Questionnaires applied (110 males and Rappaport: by interviewers; 20 98 females); International potentially carcinogenic controls: 401 Working chemical or physical Center and all general hospitals in province of (215 males and Formulation agents 186 females) Pordenone; controls: men and women age 17-79 with acute disorders. from the same hospitals and catchment area Chemlcal workers: OR * 1 64 (0.88-3.06) petrochemtcal: OR * 1.83 (0.87-3.84) dye and paint: OR = 0.72 (0.36-1 44) -plastic resin/glue: OR 1.01(0.46-2.23) benzene/solvents: OR = 1.14(0.57-2.28) wood/furniture: OR = 0.66 (0.37-1.19) 20- La Vecchia et al., 1989, Italy Hospitalbased casecontrol Cases: patients aged 15-74. admitted in to a network of teaching and general hospitals in the greater Milan area, from June 1983 to October 1988; controls patients admitted In the same hospitals with acute conditions Cases: 153 NHL (93 NHL Quesaonnaires applied histologically by interviewers; males and 60 females); 69 HD and 1 10 multiple myeloma; confirmed Exposure: 16 industries or occupations and 13 selected occupational agents or group of agents controls: 396 (269 males and 127 females) N o associations were found between NHL and solvent-related OCCupatlOnS (chemical, petrochemical plastic resindglues. solvents/benrene, oil, dyes/paints. rubber, printing and furniture) 21- Penson et al.. 1989, Sweden Hospitalbased casecontrol Cases: NHL and HD obtained from the Department of Oncology at Orebo Medical Centre Hosoital. Cases: 106 NHL NHL (66 men and 40 women) and 54 HD: controls: 275 diagnosed between 1964 and 1986, alive in 1986. aged 20-80;controls: from the population registry. resident in the same catchment area of the cases Posted questionnaires; Five levels of solvent exposure, at least for 1 year Solvents: OR = 2.0 (33150 exposed cases/controls); -thinner OR = 2.7 (15116); white spirit: OR 3.1 (13112); trichloroethylene: - -OR = 1 5 (8/14). styrene: OR .I8.0 (3/1); painters: OR = (310); plastidrubber chemicals: OR 2.5 (9/10); carpenterlcabinet makers: OR = 3.1 (10/9) Cad. Swde Publica. Rio de Janeim. !d(Sup. 3):41-66. 1998 5 REGO. M. A. V Tablet (cont ) Author./ yosr/ country 22- Weisenburger et al.. 1990. USA 23- Pasqualetti et al , 1991, Italy 24- Skov & Lynge. 1991, Denmark 25- Linos e t a l , 1991, USA 26- Wolff, 1992. UK 27- Eriksson et a1 , 1992, Sweden Dorign Sourco population Study Subjuts Disoaw Exposuro U.rrifk.tion Rosults Population- based casecontrol Cases NHL in men aged Cases 201, 21 or older in 66 counties controls.725 of eastern Nebraska, from 198 to 1986. identified through the Nebraska Lymphoma Study Group Registry and area hospitals and physicians. controls selected from residents of the same area. matched by age. race and vital status cases Telephone interviews, reviewed by specific agonts in farm pathologist practices -Chlorinatea hydrocarbons. OR 1 9 (08 2 3) Hospitalbased casecontrol Cases hospital patients Cases 108 aged 24-85 with NHL within hematological 620 total malignancies. controls neoplasms, sex and age matched controls 276 hospital controls with within 1 240 "medical diseases". from total the same area as the cases NHL Questionnaires applied by interviewers in 59% of the cases and 85% of the controls, remaining informarion obtained from relatives Exposure 21 risk categories Cohort Populationbased casecontrol ~ Persons aged 20-64 in 1.167 ICD 1970 (census data on observed industry and occupations) cases in men followed up for cancer and 849 in incidence until 1980 women linked with Danish Cancer -Registry data Cases new cases of NHL Cases 572 Diagnoses and leukemia among NHC and 520 reviewed by white men diagnosed leukemia a panel of between 1980 and 1983 cases, pathologists in Iowa and Minnesota, controls 1,130 controls frequency matched by year of birth, vital status, stare of residence and year of death, from RDD.8 (e65 years) and from Health Care Finance Administration (265 years) ~ Detailed occupational classification with 492 male groups and 447 female groups Questionnaires applied to study subjects or their next-of-kin, exposure location of residence within 3 2 and within 0 8 Km from a factory Hematological malignancies industrial activities OR = 2 97 (1 98-4 46) exoosure to aromatic hydrocarbons OR * 2 15 (1 39-3 32). dyes and nks OR= 1 28 (1 11-1 99). mineral oils -OR = 2 59 ( 1 75-3 841, paints and related products OR 1 55 -(1 06-2 26) UHL mineral oils OR 3 4 (1 65-7 38) No association between NHL and auto-mechanics. railroad workers and specific exposures to cetonas, alipharic hydrocarbons, chlorinated hydrocarbons and dye paints and inks Wood working (male) RR = 1 15 IO 87-1 52). chemists (female) RR = 2 32 (0 85-5 04). hairdressers (female) RR = i 01 10 81-4 14) Factory within 3.2 Km chemical: 18 EC, RR = 1.0 (0.6-1.9); petroleum: 14 EC. RR = 1.5 (0.7-3.2); rubber. 11 EC. RR 0.6 (0.3-1 3) Ecological Lympho-hematopoietic neoplasm incidence in 22 counties in the UK. 198411988 2.41 5 low grade and 2,550 high grade NHL, 21,072 total neoplasms NHL Cohort People followed u p for cancer incidence from 1971 to 1984 (Swedish Cancer-Environment Registry) with occupational information from 1970 census 1.082 NHL (830 men 252 women), 317 H D and 684 Mmll ICD 7ih 200-203 Car ownership by county, 1981 (Great Britain Population Census and Transport Statistics) ~~ Occupational groups Spearman rank correlation coefficients low grade NHL 0 66 p<O001 (cars per household), 0 68 p<O.OOl (cars per thousands) high grade NHL 0 21 and 0 08 p>O 05 respectively 'Carpenter 49 observed cases, SIRlja- 1 2 (1 0-1 5) Cad. Saude Publics. Ria de Janetro, 14(Sup. 3):41.66. 1998 5 7NON-HODGKIN'S LYMPHOMA RISK A N 0 ORGANIC SOLVENTS 9 Table1 (cont.) Authordyoar/ country ~~ 28- Santos-Burgoa et al.. 1992, US Dorign Source population Study Subjoctr Diuau Exposure Chuifiution Nested Cases: fatal lymphatic Cases: 59 care-control and hematopoietic lymphohe- malignancies in male matopoietic workers of 8 North cancers and American styrene- 15 NHL; butadiene plants. controls: 193 within a cohort of (total) 13.606 workers, between 1943-1982; controls: marched by year of hire. date of death, age and duration of work, selected from the same cohorr among causes of death other than neoplasms ICD 8* 200 and 202 Personal records + panel of 4 chemical engineers to form JEM.81: y d n o exposure, exposure rank from 0 to 10 and continuos/discontinuous exposure Results Everinever exposure to styrene: lymphossarcoma: OR = 1.39 IO.13-3.92); other lymphoma -(includes myeloma): OR 2.42 (0.50-11.6) 29- Scherr et al., 1992, USA Hospitalbased casecontrol Cases: a l l new cases of Cases: 303 NHL Questionnaires directly NHL diagnosed from (152 males and reviewed applied to cases (67%). January/l980 to May/ 151 females; by a panel of to cases' proxies (31%) 1982 among residents of controls: 303 pathologists; and to cases' guardians Boston Metropolitan Area Rappaport (2%); no information who were treated in one of (modifiedland regard distribution the nine participating hospitals; International of the mterviews in controls: matched by age, Working control group; sex, town and precmct of Formulation occupations and agents residence. randomly selected from town residence iist -gasoline or kerosene: OR 1 0 (0.6-1.7); benzene: OR = 1.2 (0.5-2.6).chorinated solvents: OR = 1 Z (0.8-1 8);metal industry: -OR = 1 2 (0.6-2 5); machinery: OR 0.8 (0 4-1.a); shipbuilding, auto: OR 1.O (0.6-1.7), -chemicals. drugs and paints: OR 0.3(0.1-0.9); leather: OR 2.1 (0.9-4.8); dry cleaning. OR = 1.6 -(0.6-4 0): painter and plasterer. OR 6.0 (0.9-38).carpenter. brick and stone mason, plumber and roofer. OR = 12.0 (2.0-72); airplane or auto mechanic. gas station attendant: SR = 1 4 (0.6-3.6) 30- Partanen et al., 1993. Finland 31- Persson et a l , 1993, Sweden Nested case-control Cases: malignant lymphomas and leukemias notified to the Finnish Cancer Registry. diagnosed in wood male workers of 35 plants, within a cohort of 7,307 workers, between 1957.1962; controls matched by year of birth and suTvival/non-suTvival status in 1983. selected from the same cohort Cases: 8 NHL. ICD. 200. 4 HDand 12 202 leukemia cases; controls: 152 (52 for the NHL cases) Hospltalbased casecontrol Cases NHL and HD Cases 93 NHL occurred in men living and 31 HD, In dstergotland, controls. 204 Jonkoping and Kaimar counties. obtained From the Regional Cancer Registry at the University Hospital in Linkoping. diagnosed between 1975/ 1984. alive In 1986. aged 20-80 controls from the population registry. resident in the same catchment area of the cases I C 0 8th 200 0.200.1 and 200 Z Individual exposure to solvents and to other agents reconstructed using a plantlperiodspecific JEM (cases and controls). interviews of persons a t the plants + questionnaires (only cases or their next-of-kin) Unidentified solvents: -leukemias and lymphomas pooled 4 EC. OR 5 62 (0 99-32 0). adjustment for formaldehyde exposure OR 9 5 07 (0 40-635). NHL Z E C a n d n o exposed controls Posted questionnaires. Five levels of solvent exposure, a t least for 1 year -- - Solvents occupational OR * 7 2 (28153 exposed cases/controls) and Intensity categoriy 2-5 X 0-1 (24134) OR = 1 7 OR,,, = 1 1 -(0 6-2 2). white spirit OR = 1 6 (14/20). aviation gasoline OR 3 0 (413). solvents non-occupational OR 9 3 4 (312). carpenter/ cabinet makers OR- 1 0. ORi, * 0 9 (0 4-2 1) (11/25) Cad Saude Publeca. Rio de Jancwo. 146up 3) 41-66. 1998 3 REGo.M.A. J Table1 (cont.) Authodyerrl country 32- Blair et al., 1993, USA 33- Linet et al.. 1993, Sweden 34- Linet e t al.. 1994. Sweden Dosign Sourco population Study Subjects Dirorso Exposuro Classification Results Population- based casecontrol Cases: NHL in white men, Cases: 622; reported to the Iowa State controls: 1,245 Health Registry. 1981 to 1983; NHL in white men diagnosed between 1980 to 1982 at a network of hospitals in Minnesota; controls: frequency matched by age, year of death for deceased cases and state, from ROO. medicare fdes and listings of death Cases Questionnaires directly reviewed applied to cases and b y a panel of controls or their surrogates; pathologists job titles, industries and and classified industrial hygienist according to the ludgrnent; probability of exposure (4 levels) and International intensity of exposure Working (3 levels) Formulation -Paintinglpaper hanging: OR 1.9(0.9-3 8); -petroleum refining: OR 1.6 10.5-5 8); printing: OR = 1 5 (0.4-5.1); benzene: OR- 1 1 (0.9-1.41; -benzene (low/foilicular): OR 1.3 (0.9-1.9); benzene (low/diffure): OR * 1.2 (0.8-1 8); -benzene (high/follicular): OR 1.9 (0.7-5.3); benzene (high/diffuse): OR = 1.8 (06-5.4; solvents other than benzene: -OR 9 0.9 (0.9- 1 .A); OR low/follicular 1.4 (0.9-2.0); OR low/ diffuse = 1.0 (0.7-1.5); OR high/follicular = 1.1 (0.4-2.7): OR high1 diffuse = 2.4 (1 2-5 0); paints: OR= 7 1 j0.9-:.S); asphalt and creosote' OR = 1 0 (0.7-1 6); gasoline and diesel exhausts: OR = 1 0 (0.8-1.3) Cohort People followed u p for 4.496 NHL cancer incidence from observed cases microscop- 1961 to 1979 (Swedish in employed ically Cancer-Environment Swedish men verified Registry) with occupational information from 1960 census Industrial and occupational Shoe repair industry: categories derived from international standards 23 cases. SIR = 1.8 p<0.05 shoemakers: 23 cases. SIR- 1.7 p<O.OS ' porcelain and earthenware: 14 cases, SIR = 1 9 p<O.O5 -furniture maker- 44 cases. SIR 1.3 ~ ~ 0 . 0 1 -lorry drivers. 42 cases, SIR 1.4 p<O.Ol Cohort People followed up for cancer incidence from 1961 to 1979 (Swedish Cancer-Environment 1,174 NHL observed cases microscop- in employed ically Swedish verified Registry) with occuparional women information from 1960 census -Industrial and occupational Furniture and finishing categories derived from Industry. 4 cases. international standards SIR t.5; graphics industry and publishing business: 15 cases, SIR = 0.7, rubber industry: -5 cases. SIR = 1.1: chemical industry: 9 cases, SIR 0 8; machine and electronics industry: 26 cases, SIR = 0.8;shoe and leather workers: 10 cases. SiR = 1 4 Cod. Saude Publica. Rio de Janeim. lP(Sup 3) 41-66. 1998 NON-HOOGKINSLYMPHOMA RISK AND ORGANIC SOLVENTS 59 Table1 (cant.) Authordyoad counvy 35- Kolstad et at.. 1994. Denmark 36- Hardell et al.. 1994. Sweden 37- Figgs et al , 1995. USA Dosign Cohort Source population Study Subjects Exposed group: male Exposed workers employed any group: time from 1964 to 1988 53.720 (584. in 386 reinforced plastic 556 p/y) Tdustry and resident in Denmark after 01/01/70. followed up until 12/31/89; non-exposed group general population Disoau Eaposuro Chuifiution Rosults I C 0 7m 200-205 Styrene exposure in Companies with 1.49% reinforced plastic industry: of workers in reinforced 2.473 personal air samples plastics production from work sites during ~ 1ye0ars since 1st 1964-1970. 1971-1975 and employment 19 OC. 1976-1988 with the mean SIR = 2 35 (1 42-3 67). styrene levels: 180, 88 2 10 years 17 OC. and 43 ppm (1814 were SIR = 1 23 (0 71-1 98). sampled from companies companies with 50.1 00% included in the study) of workers in reinforced plastics production c 10 years since 1st employment 2 OC, SIR 0 43 (005-1 57). 2 10 years 4 OC. SIR = 0 79 10 22-2 02). All compantes 42 OC. SIR = 1 33 (0 96-1 80)151 year of employment 1964-1970 21 OC, SIR * 1 28 (079-1 96) 197101975 SIR = 1 19 f0 57 2 18). 1976-1988 I 1 CC. SiR = 1 54 f0 82 2 94) Hospitalbased casecontrol Cases all men admitted Cases: 105, to the Depanment of controls: 335 Oncology in Umea (catchment area). 25-85 years old; controls: 8 matched (age, sex. residence) controls for each living case and 10 matched (age. sex, residence and year of death) from the Nanonal Population Registry Rappapon Death certificarc based casecontrol Cases. YHL deaths among residents from 24 American states between 1984-1989: controls. 5 matched non-cancer deaths Cases: 23.890: controls 119.450 -NtiL (IC0 9th 200 and 202, except 202.3 and 202.6) Self administered questionnaires, supplemented by telephone. Low (less than 1 week continuously or less than 1 month in total); high (more than that) Carpenter 13 exposed -cases/36 exposed controls. OR 1 . 1 (0.6-2.4):mechanic: 517. OR * 2 5 (0.7-96); motor mechanic: 7/20. OR = 1.3 (05-3 4;all organic solvents: 45/88. OR = 2.4 (1 4-3.9);high grade. 3llSO.OR = 2.9 (1 6-5 61. low grade: 14/38. OR = 1.8 (0.8-3 8); benzine: 3;l. OR = 2.8 (1.3-730);thinner: 11/14. OR = 3 4 (1 4-10); rrichlorcethyiene: 414. -OR = 7 2 (1 3-42); turpentine: 5/7. OR 3.3 (0.9-17). white spirit. 12/20, OR * 3.2 (1.3-8.3); degreaser 714. OR = 1 1 (2.9-72);multivariate -analysis high grade. -OR = 3.5 (1 7-7 1); low grade: OR 1 1 (0.5-27); organic solvents (lymphocytic. well differentiated NHL): OR = 2.3 il 3-6.6) Industries and occupations obtained from death certificates -White men. aircraft mechanics: 8 EC. OR 2.5 -(1.1-6.0).farm equipment mechanics. 7 EC. OR 2.1 (0.9-5.3).electronic repairs: 12 EC, OR = 2.1 ( 1 1 4 1 ) ; miscellaneous electronic -and electrical repairs: 10 EC. OR 2.0 (1.0-4.3); painters: 65 EC.OR= 0.6 (05-08).black men: ship/ boat building and repair: 7 EC. OR = 2.9\(1 1-7.9) Cdd Saude Publica. Ria de Jancrro. 1 PISup 31 4 1-66. 1998 REGO. M. A V Table1 (cont.) Authorslyerr/ county 38- Hours et al., 1995, France 39- Hunting et al., 1995, USA 40- Yin et al. 1996. China 41- Schnatter, 1996, Canada Design Source population study Subjects Disease Exposure aauifiution Results Hospital- based casecontrol Cases: hematological malignancies diagnosed in both sexes, aged 30-74. between 01/01/81- 12/31/87 in 2 hospitals in Lyon; controls: 1:1 matched non-cancer and non- occupationally diseased patients by sex, age and nationality from the same hospitals Cases: 52 NHL; 48 AML* leukemia and 18 orher leukemias Occupational exposures to 320 compounds; -questionnaires + evaluation by experts in chemistry and occupational medicine: -Mononuclear aromatic hydrocarbon: 13 EC. OR = 2.10 p 0.23; - -polynuclear aromatic hydrocarbon. 30 EC. OR 0.76 p 7; ETX mix: 6 EC, OR * 14.86 ~ ~ 0 . 0 1 ; -inks: 20 EC. OR = 2 47 P 0.02; varnish and paints: 6 EC. OR = 2.55 p - 0.08 Cohort mortality 338 male employees (3,813 p/y) of the fleet maintenante division of the DC's Department of Public Works (DPW). employed for at least 1 year between 1/1/7 - 12/31/91 9 cancer and IC0 9th 3 lymphatic and hematopoletic deaths (1 NHL death) Low, medium or high potential exposure to fuels and solvents according to personal records data and DPW and union representatives discussion Lymphatic and -hematopoletic cancers: 3 cases 5 M R 4.22 -(0.87-12.34) NHL. 1 case SMR 2 57 (0.06-14-27) Multicenter Exposed group: retrospective benzene-exposed cohort workers employed from 1/1/72 to lti31187 in Exposed group: 74.828 workers; 672 factories in 12 Chinese unexposed cities; unexposed group: group: 35.805 workers from 109 factories workers in the same period and places International Working Formulation Work units. lob titles; monitoring data; l i s t of row material and factory products: engineering control; personal protective equip.. estimated exposures In PPm Mortality. 17 EC; RR = J 5 (1.3-28.4); incidence 20 EC. R R = 3 5 (1.3-14 9) Nested case- Cases: all male NHL control deaths from a cohort of petroleum workers; controls: 4:1 from the same cohort.matched by decade of birth Cases: 31 lympho- haematopoietic including 8 NHL; controls: 124, 32 for NHL cases IC0 8* ; 200, 202.0, 202.1, 202.2 and 202.9 Benzene and total hydrocarbon exposures; personal records + evaluation by experts in industrial hygiene; estimated exposures in p p m Totai hydrocarbons, cumulative exposure in pmm-y. 0-11.6 OR = 1; 11 7-29.9 OR = 1.73 (0.02-137), 30-549 OR = 0; 550-6721 OR = 1.22 (0.01-137); benzene: 0-0.49 OR 1; 0 50-7.99 OR = 1 21 (0.16-a 37); 8-19 .99 OR = 1 14 (0.02-27 6); 20-219 8 -OR .I0: benzene (mean ppm): 0-0.01 OR 1; ->0.01-0.19 OR = 1 25 (0.10-11 31; 0.20-0.49 OR 0.97 (0.08-7 58); 0.50-6.16 OR .I0; benzene (maximum intensity in -ppm): ~ 0 . 5OR = 1, 0.51-O.99OR 5.85 (0.30-354); 21 0 OR- 0.54 (0.01-5.94) Cad. Saude Publica. Ria do Jmoira. 14(Sup. 3131-66. 1998 NON-HOOCKIN'SLYMPHOMA RISK A N 0 ORGANIC SOLVENTS 61 Table1 (cont.) Authodyoarf country 42- Friachi & Siemiatycki, 1996. Canada 43- Massoudi et al., 1997, USA 44- Holly et al.. 1997. USA Dosign Source population Study Subjocts Disoaso Exposuro Classification Registrybased casecontrol Cases: all new male cases Cases: 258 NHL diagnosed berween 1979- eligible and 1985. aged 35-70. resident 215 interviewed; in Montreal; controls: from controls: 2,357 other cancer patients. from the cancer except lung cancer and registry and from electoral list or 740 from by ROD population with 533 interviewed Questionnaires + evaluation by a team of chemists and industrial hygienists; confidence of exposure: possible. probable and definite; frequency of exposure. <5%, 5 3 0 % and >30%; and the level of the agent at the workplace; classification of occupations and Industries Rosultr -Benzene: low level. 20 EC. OR 0 7 (0 4- 1 1); high level: 6 EC. OR = 0.8 (0.3-2.1); solvents: low -level. 26 EC. OR 0.6 (0.4-1 0);high level, 48 EC -OR 0.9 (0.6-1.3). carpenters: 1-9 years: no cases; 10+ years: 4 EC. OR = 0.8 (0.3-2.2); furniture: 1-9 years. 1 EC, OR = 0.4(0.1-3 4);10+ years. 3 EC. OR= 1.6 (0.5-6.1);rubber and plastic workers: 1-9 years: 4 EC, OR = 3.6 (0.9-15.0); 10+ years: 1 EC. OR = 9.0 10.6-148.0) Death certificatebased casecontrol Cases: lymphatic and Cases: 309 hematopoietic cancer lymphatic and in white male, aged 23-96 hematopoietic who had died between cancers (106 1965-1990 and lived In NHL); Kanawha County (West controls: 106 Virginia); controls: matched 1:1 cardiovascular disease patients with rhe same characteristics NHL (IC0 9th 200. 202) reviewed by a pathologist Industries and occupations obtained from death certificates and validated by interviewing next of kin; 3 categories of exposure: chemical manufacturing workers; those exposed to chemicals at other jobs; those not exposed Chemical ,workers X not exposed: unstratified: OR = 1.52 (0 8-2.9). p = 0.168. ~ 6 550 MP, OR = 3.11 (1 :-e 9). p= 0.03. 5 65. 56 MP. -OR = 0 97 (0.5-2.1). p 0.94 Populationbased casecontrol Cases: NHL in homosexual Cases: 312 men; controls: homosexual NHL; men, matched by age controls: 420 within five years and county of residencs NHL Chemical and occupational exposures from questionnaires Petroleum products. HIV+ men: OR = 0.37 (0.18-0.72), 10-499 hours: -OR 0.61 (0.34-1.1). >SO0 h; HIV- men: -OR 1 6 (0.69-3.6). -10-499 h; CR 0 94 -(0.37-2.41, gasoline, HIV+ men. OR 0.65 (036-1.2). >10 h; HIV. men: OR = 1.7 (0.72-4.0); Kerosene and other oils. H I V t men OR = 0.72 -(0.36-1,s). >lo0 h; HIV - men. OR 1.3 (0 52-3 1). > 100 h; aldehydes, cleaning solvents and adhesives, HIV + men: OR = 0.60 -(032-1 1). 10-249 h; OR 0.52 (0.29-0.93). ->250 h; HIV men: OR 1 0 (047-2 2 ) . 10-249 h, OR = 1.5 (0.69-3.1). >250 h; benzene. all men: OR = 1 2 (0.62-2 4), >10 h; chlorinated solvents, all __men' OR = 0 73 (0.41-1 3) .. . . .- Cad. Saudo Publica. Rio do Janciro. 1~ ( S U P3).41.66. 1998 62 RPGO.M A v Table1 (cont.) Authordyoarl country 45- Tatham et al., 1997. USA Dosign Sourco population study Subjocts Diroaso Exposuro Clauifiution Populationbased casecontrol Cases: NHL in men from Cases: 1.048 Subtypes eight cancer registries NHL (185 small of NHL between Decemberll984- cell diffuse defined by November/l980; controls: lymphomas; a panel of matched by date of birth 268 follicular pathologists (five yearslthrough random and lymphomas digit dialing 526 large cell diffuse lymphomas); controls. 1,659 individuals Telephone interview. Tim. of exposuro for all jobs with Known dates; exposuros were defined as within 10 years and more than 10 y o m ~ ~~ * Observedlexpected - - -11 RCS reticulum cell sarcoma, LS lymphosarcoma, HD Hodgkin's disease. NHL = non-Hodgkin's lymphoma, ALL = acute lymphocitic leukemia. -CLL = chronic lymphocitic leukemia. MM multiple myeoma. AML = acute myeloid leukemia 111 RR = relative risk, OR = odds ratio, EC = exposed case, SMR = standard mortality ratio, SIR = standard incidence ratio 1" International Classification of Diseases -v Surveillance, Epidemiology and End Results Program, at National Cancer Institute USA VI RDD = random digit dialing "11 JEM = lob exposure matrix Rorults Chlorinated hydrocarbons: OR = 0.91 (0.75-1.10); -solvents (all NHL subtypes): OR 1.10 (0.90-1.30); solvents (small cell diffuse): OR = 1.60(1.10-2.20); solvents (small cell diffuse), 5 9 years of exposure: OR = 1.SO (099-2.20); solvents (smallcell diffuse). > 9 years of exposure. OR 1.70 (1.10-2.60); solvents (small cell diffuse), -s 10 years since first exposure. 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