a Medical Institute for Environmental Hygiene at the Heinrich Heine University of Düsseldorf, Germany.
b Institute of Medical Epidemiology, Biometry and Medical Informatics at the Martin Luther University, Halle, Germany.
c Institute for Kidney and Hypertension Research, Berlin, Germany.
d Bremen Institute for Prevention Research and Social Medicine, Bremen, Germany.
e Collaborators of the Multicenter Urothelial and Renal Cancer Study (MURC Study Group): Wolfgang Barth, Uta Brettschneider, Elisabeth Bronder,
Reprint requests to: Beate Pesch, Unit of Environmental Epidemiology, Medical Institute for Environmental Hygiene, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods In a population-based multicentre study, 1035 incident urothelial cancer cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Exposure to the agents under study was self-assessed as well as expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR) and to control for study centre and age.
Results Urothelial cancer risk following exposure to aromatic amines was only slightly elevated. Among males, substantial exposures to PAH as well as to chlorinated solvents and their corresponding occupational settings were associated with significantly elevated risks after adjustment for smoking (PAH exposure, assessed with a job-exposure matrix: OR = 1.6, 95% CI : 1.12.3, exposure to chlorinated solvents, assessed with a job task-exposure matrix : OR = 1.8, 95% CI : 1.22.6). Metal degreasing showed an elevated urothelial cancer risk among males (OR = 2.3, 95% CI : 1.43.8). In females also, exposure to chlorinated solvents indicated a urothelial cancer risk. Because of small numbers the risk evaluation for females should be treated with caution.
Conclusions Occupational exposure to aromatic amines could not be shown to be as strong a risk factor for urothelial carcinomas as in the past. A possible explanation for this finding is the reduction in exposure over the last 50 years. Our results strengthen the evidence that PAH may have a carcinogenic potential for the urothelium. Furthermore, our results indicate a urothelial cancer risk for the use of chlorinated solvents.
Keywords Bladder cancer, urothelial cancer, case-control study, aromatic amines, polycyclic aromatic hydrocarbons (PAH), chlorinated solvents, job-exposure matrix
Accepted 29 September 1999
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Since the 1980s there has been epidemiological evidence that occupation-related agents other than aromatic amines can be causally linked to urothelial cancer.5 Coal gasification, and steel and aluminium production as well as exposure to tar or pitch are occupational settings with exposure to polycyclic aromatic hydrocarbons (PAH), and these are associated with an elevated bladder cancer risk.68
The International Agency for Research on Cancer has recently concluded that tetrachloroethylene and trichloroethylene are probably carcinogenic to humans.9 A review of epidemiological studies5 and recently a French case-control study10 reported an excess risk for cancer of the urothelium from occupational exposure to chlorinated solvents.
This multicentre population-based case-control study was conducted to estimate the urothelial cancer risk for occupational exposure to aromatic amines, PAH, and chlorinated hydrocarbons besides other suspected risk factors. Details of the study design and further results are reported elsewhere.11
![]() |
Material and Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The controls were frequency-matched to cases by region, sex (Table 1), and age (5-year interval). The matching procedure was such that for the two case series a 1:2 matching for urothelial cancer and a 1:4 matching for renal cell cancer to controls was planned. During the recruitment, an increase in the incidence rates of renal cell cancer was observed. Therefore, the recruitment period of renal cell cancer cases was expanded to clarify possible causes. Due to this extension and because of differences in the age distribution of urothelial and renal cell cancer cases, a group of 4298 randomly selected population controls from local residency registries was finally enrolled. This control group was used in the statistical analysis of both cancer sites.
|
|
So far, only the information provided by the interviewee was used for exposure assessment. For quantifying the exposure to specified agents, we additionally applied expert knowledge by means of job-exposure matrices (JEM) and a job task-exposure matrix (JTEM). For every job title and job task, respectively, the exposure matrix provided an expert rating in terms of the probability and the intensity of exposure to a specified agent using for both measures the categories none, low or medium, and high. For the job title-based assessment, we adapted two job-exposure matrices (the so-called British JEM;13 and the German JEM14). Experts within our study group developed a corresponding job task-exposure matrix (JTEM) where regional differences between East and West Germany and temporal changes concerning occupational exposure were taken into account. To obtain an agent-specific measure of a subject's lifetime exposure, the products of duration, probability, and intensity were summarized over all jobs held or job tasks operated, respectively. For this quantification, the ordinal categories none, low or medium and high for both probability and intensity of exposure were transformed into the scores 0, 1, and 3. We referred to these exposure variables as exposure indices.
Statistical analysis
Conditional logistic regression models15 were applied for risk estimation using the SAS procedure PHREG,16 separately for males and females because of gender differences in the anatomy of the urogenital tract and in the metabolism of xenobiotics.17 According to the frequency matching of cases and controls, the risk estimation was conditional on 45 strata resulting from nine age groups (<40, 4049, 5054,...,7579, 80+) and five study regions.
Considering possible highly non-linear associations between risk estimates and exposure measures, four exposure categories were defined for each exposure variable using the 30th, 60th and 90th percentiles of the distribution of the exposure variable among the exposed controls. Concerning exposure duration, we refer to these categories as short, medium, long and very long duration of exposure, and with respect to exposure indices, as low, medium, high and substantial exposure. The reference groups comprised the unexposed subjects and the subjects with short duration or low exposure.
Smoking was considered as a confounder because it is an established risk factor for urothelial cancer1 and has a higher prevalence among blue collar workers.18 Cumulative cigarette consumption was measured as log (packyears + 1). Additionally, quitting smoking (cutpoint 2 years before interview) and exclusive smoking of other tobacco products (yes/no; for males only) were included. Socioeconomic status (SES) was not used as a confounder for occupational risk analysis, since the definition of SES was based upon professional qualification and graduation at school.11 Table 3 shows the risk estimates for tobacco smoking and SES.
|
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Products and substances
Table 5 presents the regression results for the self-assessed and expert-rated exposure indices, adjusted for smoking. Occupation- related exposure to aromatic amines and to paints and pigments were not associated with urothelial cancer risk. But the production of paints, especially the use of benzene as a raw material and chlorophenols as intermediates of dyestuff production, may imply a possible cancer risk.
|
Chlorinated solvents were assessed as a further independent risk factor for the urothelium, especially if the job task metal degreasing is considered as an occupational setting with exposure to trichloroethylene.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Whereas the job history does not seem to be vulnerable to differential recall, the agent-specific information derived from job titles is limited. Job tasks can have a higher specificity.28 The use of chlorinated solvents in the job task metal cleaning is more likely than for the job title tool maker. On the other hand, data for selected job tasks can suffer from loss of sensitivity if interviewee knowledge about technological processes or materials is necessary to gain exposure information.29 The number of job tasks reported by retired people showed a decline with age, but the number of job titles did not.11
In bladder cancer epidemiology, the majority of case-control studies are hospital-based. This study was population-based, and a selection bias resulting from the lower response rate of the population controls cannot be excluded. On the other hand, the similar SES distribution of male controls and renal cell cancer cases, which were another independent outcome of this project, does not indicate a strong selection bias.11 Renal cell carcinoma is not considered to be an occupation-related cancer.
Exposure estimates based on duration of exposure only seemed not to be strongly affected by recall bias. Relatively high risks for a very long duration of exposure in specified occupational settings like metal cleaning or production of tar, pitch and bitumen could be identified. The low prevalence of subjects working for a very long time in some specified job tasks or occupations reduced the statistical power considerably. The next step towards an agent-specific exposure assessment by means of JEM and JTEM can introduce an additional misclassification of exposure or a loss in specificity and, hence, the corresponding risk estimates for exposure indices were for the most part closer to the null value. The evaluation of the probability and intensity of exposure for a large set of agents is only very crude and can differ considerably between experts due to subjective ratings and due to the outcome for which the exposure is rated. The German JEM was developed for a Morbis Parkinson study focused on the impact of solvents. Therefore, in the low dose range, more occupations were considered exposed than in the British JEM. Another misclassification of exposure can be introduced by unspecific exposure variables. The exposure variable lead and its compounds does not differentiate between organic and inorganic lead compounds which have a different carcinogenicity.
Dose-response relations
One of the postulates for epidemiological evidence is to show a dose-response relation for the agents under study. Clear dose-response relations are difficult to demonstrate for occupational exposures in a population-based case-control study. Besides the methodological problem of exposure misclassification both from self- or expert-assessed exposure to a chemical agent, the misspecification of the exposure metric can also contribute to a smoothing of the dose-response relation towards the null value. For this study, cumulative exposure indices were developed according to the 1986 US EPA guidelines for carcinogenic risk assessment.30 The underlying assumption of toxicological equivalence of exposure time and concentration for cumulative exposure indices may not hold for many agents, like chlorinated solvents. The 1996 revised guidelines of the US EPA refer to the growing toxicological data on defence mechanisms.31 Furthermore, cumulative exposure indices do not take into account age at exposure. Recent studies showed that people exposed at different ages can differ in cancer risk.32,33
An increase of effect with increasing dose can more easily be observed for a potent carcinogen like tobacco smoke with a high exposure prevalence (Table 3). For occupation-related carcinogens, only a very small fraction of the general population is exposed to high workplace concentrations. Therefore, our emphasis was on the category of substantial exposure. As a trade-off, the small numbers in this category caused large confidence intervals in the risk estimates.
The reference group comprised unexposed as well as little-exposed people to compensate for a possible recall bias or confounding by social status. This inclusion of people with low exposure was supported by the assumption that a complex set of defence mechanisms can detoxify low or even medium doses of several xenobiotics34 e.g. trichloroethylene.35
Occupations and job tasks
Coal gasification, iron and steel founding, aluminium production, the rubber industry, magenta and auramine production, and shoe and leather manufacture were rated as occupational circumstances with sufficient carcinogenic potential for the human urinary bladder,6 and this is still reflected in the German bladder cancer mortality pattern in men.36 In our study, leather manufacturers and workers in steel and iron foundries showed an excess risk of urothelial cancer. Aluminium and rubber production were not among the large industries in the study regions.
Many studies found a bladder cancer risk among chemical workers,10,20,3740 but negative findings have also been reported.21,4144 We found no excess risk among the chemical workers in our study. Chemical industry covers exposure to a wide range of chemical agents, and the job title chemical worker is unspecific for the agents under study.
The elevated risk for motor vehicle drivers reported in many studies2,10,19,4556 could be confirmed. Two other German case-control studies did not find an excess risk for drivers20 or for non-smoking drivers.21 Besides diesel exhaust,56 high concentrations of side stream components of tobacco smoke in the driver's cabin should also be taken into account as possible causal agents.
There is toxicological evidence that water-soluble azodyes can be metabolized into carcinogenic aromatic amines.5759 Dyers, painters, printers, barbers, and hairdressers are expected to show an excess risk. We could demonstrate a significantly elevated risk only for male printers with a very long duration of employment. Other studies are not conclusive with respect to an association for the commercial use of paints, with the exception of textile and leather dyers.5051,6061
Metal degreasing, manufacture of tar, pitch and bitumen, and dyeing and finishing of leather exhibited high risks for a very long duration of exposure, but statistical significance could only be shown for metal degreasing.
Products and substances
Selected aromatic amines have been known to be strong carcinogens since the end of the last century.6264 Both substitution and technological progress have reduced exposure in the German dyestuff production industry considerably. Our negative findings may reflect this reduction in exposure levels to aromatic amines. On the other hand, for benzene as a raw material and chlorophenols as intermediates in paint production, an excess risk for cancer of the urothelium cannot be excluded. This is also supported by the elevated bladder cancer mortality in German regions with a benzene processing industry.36,65
Hitherto, no consensus exists to acknowledge other agents as causally linked with bladder cancer. Reviews of epidemiological studies5,8 suggested increased risks with exposure to combustion gases, and more recent studies7,22,24 also found evidence for a bladder cancer risk from PAH. We could confirm the cancer risk for exposure to PAH as well as to tar and pitch. The elevated risks found for exposure to heat and for the use of asbestos for heat protection also support the possible cancer risk of combustion gases.
Epidemiological studies and long-term carcinogenicity studies in animals suggest that some chlorinated hydrocarbons are probably or possibly carcinogenic.6 Trichloroethylene is a vapour degreaser for the cold cleaning of metal parts, a chemical intermediate and a solvent for fats, rubber, inks, and paints. Tetrachloroethylene is also a standard solvent for dry cleaning. Rubber workers, dyers and printers may have contact with chlorinated solvents among many other agents. An excess bladder cancer risk for occupational exposure to chlorinated solvents was reported in a French study.10 Our data indicate an excess risk among substantially exposed males in occupational settings which are likely exposed to chlorinated solvents, especially in metal degreasing. For the majority of the corresponding exposure indices, elevated risks for highly or substantially exposed males could be shown and, with limited evidence, for some indices in females. There was a significant excess risk for substantially exposed males for both trichloroethylene and tetrachloroethylene (JTEM) and for highly exposed males to tetrachloroethylene (German JEM).
![]() |
Acknowledgments |
---|
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Silverman DT, Levin LI, Hoover RN, Hartge P. Occupational risks of bladder cancer in the United States. I. White men. J Natl Cancer Inst 1989;81:147280.[Abstract]
3 Vineis P, Simonato L. Proportion of lung and bladder cancers in males resulting from occupation: a systematic approach. Arch Environ Health 1991;46:615.[ISI][Medline]
4 Arbeitsgemeinschaft Bevölkerungsbezogener Krebsregister in Deutschland (ed.). Krebs in Deutschland. Häufigkeiten und Trends. Saarbrücken, 1997.
5 Steineck G, Plato N, Norell S, Hogstedt C. Urothelial cancer and some industry-related chemicals: An evaluation of the epidemiologic literature. Am J Ind Med 1990;17:37191.[ISI][Medline]
6 International Agency for Research on Cancer (IARC). IARC Monographs on the evaluation of carcinogenic risks to humans. Supplement No. 7. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Vols. 142. IARC Lyon, France, 1987.
7 Bonassi S, Merlo F, Pearce N, Puntoni R. Bladder cancer and occupational exposure to polycyclic aromatic hydrocarbons. Int J Cancer 1989;44:64851.[ISI][Medline]
8 Mastrangelo G, Fadda E, Marzia V. Polycyclic aromatic hydrocarbons and cancer in man. Environ Health Perspect 1996;104:116670.[ISI][Medline]
9 International Agency for Research on Cancer (IARC): IARC Monographs on the evaluation of carcinogenic risks to humans. Vol. 63. Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals. IARC Lyon, France, 1995.
10 Cordier S, Clavel J, Limasset JC et al. Occupational risks of bladder cancer in France: A multicentre case-control study. Int J Epidemiol 1993;22:40311.[Abstract]
11 Greiser E, Molzahn M (eds). (Multicenter Urothelial and Renal Cancer Study.) Multizentrische Nieren- und Urothel-Carcinom-Studie (Abschlussbericht). Schriftenreihe der Bundesanstalt für Arbeitsschutz und Arbeitsmedizin. Bremerhaven: Wirtschaftsverlag NW, 1997, pp.1464.
12 International Labour Office (ILO). International Standard Classifications of Occupations. Geneva: ILO, Revised edition 1968.
13 Pannett B, Coggon D, Acheson ED. A job-exposure matrix for use in population based studies in England and Wales. Br J Ind Med 1985;42: 77783.[ISI][Medline]
14 Robra BP, Seidler A. A job-exposure matrix for exposure to solvents and other industry-related agents. Personal communication (1994).
15 Breslow NE, Day NE. Statistical Methods in Cancer Research. Vol. I: The Analysis of Case Control Studies. Lyon: IARC 1980;7:24879.
16 SAS/STAT Software. Changes and Enhancements Through Release 6.11. Cary, NC: SAS Institute pp.80784, 1996.
17 Calabrese EJ. Sex differences in susceptibility to toxic industrial chemicals. Br J Ind Med 1986;43:57779.[ISI][Medline]
18 Helmert U, Borgers D. Rauchen und Beruf. Bundesgesundheitsblatt 1998;3:10206.
19 Claude JC, Frentzel-Beyme RR, Kunze E. Occupation and risk of cancer of the lower urinary tract among men. A case-control study. Int J Cancer 1988;41:37179.[ISI][Medline]
20 Bolm-Audorff U, Jöckel KH, Kilguss B, Pohlablen H, Siepenkothen T. Bösartige Tumoren der ableitenden Harnwege und Risiken am Arbeitsplatz. Schriftenreihe der Bundesanstalt für Arbeitsschutz. Bremerhaven: Wirtschaftsverlag NW, 199, pp.1179.
21 Golka K, Schläfke S, Dickhut S, Reich SE, Urfer W, Bolt HM. Anwendung Statistischer Methoden zur Identifikation beruflicher Risiken für maligne Tumoren der Harnblase und der Prostata. Egelsbach, Frankfurt, St. Peter Port: Hänsel-Hohenhausen, 1996, pp.1172.
22 Clavel J, Mandereau L, Limasset JC, Hemon D, Cordier S. Occupational exposure to polycyclic aromatic hydrocarbons and the risk of bladder cancer: A French case-control study. Int J Epidemiol 1994;23:114553.[Abstract]
23 Hours M, Dananche B, Fevotte J et al. Bladder cancer and occupational exposures. Scand J Work Environ Health 1994;20: 32230.[ISI][Medline]
24 Siemiatycki J, Dewar R, Nadon L, Gerin M. Occupational risk factors for bladder cancer: Results from a case-control study in Montreal, Quebec, Canada. Am J Epidemiol 1994;140:106180.[Abstract]
25 Bond GG, Bodner KM, Olsen GW, Burchfield CM, Cook RR. Validation of work histories for the purpose of epidemiological studies. Appl Occup Environ Hyg 1991;6:52127.
26 Calvert GM, Mueller CA, O'Neill VL, Fajen JM, Briggle T, Fleming LE. Agreement between company-recorded and self-reported estimates of duration and frequency of occupational fumingant exposure. Am J Ind Med 1997;32:36468.[ISI][Medline]
27 Fritschi L, Siematycki J, Richardson L. Self-assessed versus expert-assessed occupational exposures. Am J Epidemiol 1996;144:52127.[Abstract]
28 Orlowski E, Pohlabeln H, Berrino F et al. Retrospective Assessment of Asbestos ExposureII. At the job level: complementarity of job-specific questionnaires and job exposure matrices. Int J Epidemiol 1993;22(Suppl.2):96105.[Abstract]
29 Basso O, Olsen J, Bisanti L, Karmaus W, European Study Group of Infertility and Subfecundity. The performance of several indicators in detecting recall bias. Epidemiology 1997;8:26974.[ISI][Medline]
30 US Environmental Protection Agency (EPA). Guidelines for carcinogenic risk assessment. Fed Reg 1986;51:339924003.
31 US Environmental Protection Agency (EPA). Guidelines for carcinogenic risk assessment. Fed Reg 1996;61:179608011.
32 Stewart AM, Kneale GW. Relations between age at occupational exposure to ionizing radiation and cancer risk. Occup Environ Med 1996;53:22530.[Abstract]
33 Ritz B, Morgenstern H, Moncau J. Age at exposure modifies the effects of low-level ionizing radiation on cancer mortality in an occupational cohort. Epidemiology 1999;10:13540.[ISI][Medline]
34 Wilson JD. So carcinogens have thresholds: How do we decide what exposure levels should be considered safe? Risk Analysis 1997;17:13.[ISI][Medline]
35 Henschler D, Birner G, Dekant W. Karzinogene chlorierte aliphatische Kohlenwasserstoffe: Möglichkeiten des Biomonitorings und Risikobewertung. In: Horst A, Norpoth K, Verkoyen C (eds). Krebsrisiken am Arbeitsplatz. Berlin Heidelberg New York: Springer Press, 1992, pp.199207.
36 Becker N, Wahrendorf J. Atlas of Cancer Mortality in the Federal Republic of Germany 19811990. 3rd Edn. Berlin Heidelberg New York: Springer, 1998, pp.472500.
37 Steenland K, Burnett C, Osorio AM. A case-control study of bladder cancer using city directories as a source of occupational data. Am J Epidemiol 1987;126:24757.[Abstract]
38 Dubrow R, Wegman DH. Cancer and occupation in Massachusetts: a death certificate study. Am J Ind Med 1984;6:20730.[ISI][Medline]
39 Malker HSR, McLaughlin JK, Silverman DT et al. Occupational risks for bladder cancer among men in Sweden. Cancer Res 1987;47: 676366.[Abstract]
40 Howe GR, Burch JD, Miller AB et al. Tobacco use, occupation, coffee, various nutrients, and bladder cancer. J Natl Cancer Inst 1980;64: 70113.[ISI][Medline]
41 Burns PB, Swanson GM. Risk of urinary bladder cancer among blacks and whites: the role of cigarette use and occupation. Cancer Causes Control 1991;2:37179.[ISI][Medline]
42 Silverman DT, Hoover RN, Albert S, Graff K. Occupation and cancer of the lower urinary tract in Detroit. J Natl Cancer Inst 1983;70:23745.[ISI][Medline]
43 Dolin PJ, Cookmozaffari P. Occupation and bladder cancer: a death-certificate study. Br J Cancer 1992;66:56878.[ISI][Medline]
44 Zahm SH, Hartge P, Hoover R. The National Bladder Cancer Study: employment in the chemical industry. J Natl Cancer Inst 1987;79:21722.[ISI][Medline]
45 Hoar SK, Hoover R. Truck driving and bladder cancer mortality in rural New England. J Natl Cancer Inst 1985;74:77174.[ISI][Medline]
46 Coggon D, Pannett B, Osmond C, Acheson AD. A survey of cancer and occupation in young and middle aged men. II. Non-respiratory cancers. Br J Ind Med 1986;43:38186.[ISI][Medline]
47 Baxter PJ, McDowall ME. Occupation and cancer in London: an investigation into nasal and bladder cancer using the cancer atlas. Br J Ind Med 1986;43:4449.[ISI][Medline]
48 Kabat GC, Dieck GS, Wynder EL. Bladder cancer in non-smokers. Cancer 1986;57:36267.[ISI][Medline]
49 Jensen OM, Wahrendorf J, Knudsen JB, Sörensen BL. The Copenhagen case-referent study on bladder cancer: risks among drivers, painters and certain other occupations. Scand J Work Environ Health 1987;13:12934.[ISI][Medline]
50 Risch HA, Burch JD, Miller AB, Hill GB, Steele R, Howe GR. Occupational factors and the incidence of cancer of the bladder in Canada. Br J Ind Med 1988;45:36167.[ISI][Medline]
51 González CA, López-Abente G, Errezola M et al. Occupation and bladder cancer in Spain: a multi-centre case-control study. Int J Epidemiol 1989;18:56977.[Abstract]
52 Silverman DT, Levin LI, Hoover RN. Occupational risks of bladder cancer among white women in the United States. Am J Epidemiol 1990;132:45361.[Abstract]
53 Lynge E, Thygesen L. Occupational cancer in Denmark: cancer incidence in the 1970 census population. Scand J Work Environ Health 1990;16(Suppl.2):335.[ISI][Medline]
54 Michaels D, Zoloth SR. Mortality among urban bus drivers. Int J Epdemiol 1991;20:399404.
55 Minder CE, Beerporizek V. Cancer mortality of Swiss men by occupation, 19791982. Scand J Work Environ Health 1992;18:127.[ISI][Medline]
56 Silverman DT, Hoover RN, Mason TJ, Swanson GM. Motor exhaust-related occupations and bladder cancer. Cancer Res 1986;46:211316.[Abstract]
57 Genin VA. Formation of blastomogenic diphenyl aminoderivatives as a result of direct azo dyes metabolism. Vop Onkol 1977;23:5052.
58 Gregory AR. The carcinogenic potential of benzidine-based dyes. J Environ Pathol Toxikol Onkol 1984;5:24359.
59 Myslak ZW, Bolt HM. Berufliche Exposition gegenüber Azofarbstoffen und Harnblasenkarzinom-Risiko. Zbl Arbeitsmed 1988;38:31021.
60 Anthony HM, Thomas GM. Tumours of the urinary bladder: an analysis of the occupations of 1,030 patients in Leeds, England. J Natl Cancer Inst 1970;45:87995.[ISI]
61 Zheng W, McLaughlin JK, Gao YT, Silverman DT, Gao RN, Blot W. Bladder cancer and occupation in Shanghai, 19801984. Am J Ind Med 1992;21:87785.[ISI][Medline]
62 Rehn L. Blasengeschwülste bei Fuchsin-Arbeitern. Arch Klin Chir 1895;50:588600.
63 Case RAM, Hosker ME. Tumour of the urinary bladder as an occupational disease in the rubber industry in England and Wales. Brit J Prev Soc Med 1954;8:3950.
64 Case RAM, Hosker ME, McDonald DB, Pearson JT. Tumours of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. Part I: The role of anilin, benzidine, alpha-naphthylamine and beta-naphthylamine. Brit J Ind Med 1954;11:75104.[ISI]
65 Pesch B, Halekoh U, Ranft U, Richter M, Pott F. Krebsatlas Nordrhein-Westfalen. Ministerium für Arbeit, Gesundheit und Soziales des Landes Nordrhein-Westfalen, Germany, Düsseldorf 1994.