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Abstract
Introduction In a previous analysis of a case–control study of testicular cancer nested in a cohort of automobile workers, we observed an increased risk for testicular cancer among workers who had ever been involved in occupational metal-cutting tasks. We investigated whether this risk increase was due to exposure to metal-working fluids (MWF).
Methods Occupational exposure to MWF was assessed in detail using a job-specific questionnaire for metal-cutting work. We calculated ORs and associated 95% CIs individually matched for age (±2 years) and adjusted for a history of cryptorchidism by conditional logistic regression.
Results The prevalence of exposure to MWF was 39.8% among cases and 40.1% among controls. For total germ cell tumours and seminomas we did not observe risk increases for metal-cutting tasks or occupational exposure to MWF (OR 0.95; 95% CI 0.69 to 1.32 and OR 0.88; 95% CI 0.58 to 1.35, respectively). However, dermal exposure to oil-based MWF was associated with an increased risk for non-seminomatous testicular cancer. Dermal exposure to oil-based MWF for more than 5000 h showed particularly high risk estimates (OR 4.72; 95% CI 1.48 to 15.09).
Discussion Long-term dermal exposure to oil-based MWF was a risk factor for the development of non-seminomatous testicular germ cell cancer. Possible measures to reduce exposure include the introduction of engineering control measures such as venting or enclosing of machines, and enforcing the use of personal protective equipment during metal cutting.
- Job-exposure-matrix
- metal industry
- metal-cutting fluids
- solvents
- testicular cancer
- epidemiology
- hygiene/occupational hygiene
- asthma
- cancer
- exposure assessment
- statistics
- mortality studies
- radiation
- biological monitoring
- public health
- psychology
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- Job-exposure-matrix
- metal industry
- metal-cutting fluids
- solvents
- testicular cancer
- epidemiology
- hygiene/occupational hygiene
- asthma
- cancer
- exposure assessment
- statistics
- mortality studies
- radiation
- biological monitoring
- public health
- psychology
What this paper adds
Working in the metal industry has been frequently associated with an increased risk for testicular cancer, but most analyses have been based only on job titles.
Experimental studies showed that metal-working fluids (MWF) had toxic effects on testicular cells.
To study a cluster of testicular germ cell tumours in a cohort of automobile workers, we employed a detailed job-specific questionnaire which solicited exposure to various types of MWF among metal cutters.
Long-term dermal exposure and dermal exposure to oil-based MWF were associated with an increased risk for non-seminoma.
New engineering control measures (ventilation, enclosing of machines) should be introduced and the use of personal protective equipment enforced among workers to reduce occupational exposure to MWF during metal cutting.
Introduction
In an incidence cohort study of nearly 170 000 workers in the automobile industry, we observed a cluster of testicular germ cell tumours, which was most pronounced among men above 50 years of age and in a plant in a rural area of Germany.1 In a subsequent case–control study nested into this cohort, the workers' detailed job biographies and occupational tasks were studied, with a focus on exposure to industrial endocrine disrupting chemicals. The spectrum of possible endocrine disrupting chemicals in the metal-working industry is wide, and includes glues, paints, softeners or plasticisers, metal dusts and epoxy resins. In previous analyses from our nested case–control study, we detected increased testicular cancer risks for metal workers who were involved in metal-cutting tasks. In contrast, no risk increase was observed for workers not involved in metal cutting.2
Metal-working fluids (MWF) are used for cooling and lubricating a work piece, and include oil–water emulsions, pastes, gels or oil-based chemicals which are a major cause of occupational skin disease.3 Exposure mainly occurs from inhalation of aerosols and dermal exposure from machine spray or contact with the wetted work piece. Since MWF are suspected risk factors for cancers at various sites4 and caused increased oxidative testicular stress in experimental mice,5 we investigated whether occupational exposure to these substances was a risk factor for testicular cancer in this industrial cohort.
Methods
The study methods are described in detail elsewhere.2 6 Briefly, the study included 205 incident cases of testicular germ cell cancer diagnosed between January 1989 and December 2006 and 1105 control subjects. We identified cases by systematically screening hospitals, hospital registers and outpatient cancer clinics in the study area. A reference pathologist reviewed tumour material and pathology reports to confirm diagnoses.
Control subjects were cohort members without a diagnosis of testicular cancer up to the diagnosis date of the matched case. Controls were individually matched to cases by age (±2 years) using incidence density sampling. Two to eight control subjects were matched to each case. After exclusion of next-of-kin and other surrogate interviews, 186 cases and 988 control subjects were included in the final analyses. One hundred and nine cases were seminomas and sixty non-seminomas. Fifteen tumours were diagnosed as combined germ cell tumours with seminomatous and non-seminomatous components, which we excluded from the analysis stratified by histological subtype. No pathological differentiation was available for two cases. All subjects had to have worked in the studied automobile company for at least 6 months between 1989 and 2002.
Study subjects were interviewed by trained personnel using computer-assisted personal or telephone interviews. The interview consisted of questions regarding medical conditions, family history of cancer and lifestyle, and a detailed job history. All jobs held during a subject's lifetime were coded according to the International Standard Classification of Occupations (ISCO). As part of the interview, we also employed 37 job-specific questionnaires (JSQ) to solicit detailed information on occupational exposures and occupational activities. We used a maximum of six JSQs per study subject. One JSQ addressed exposure to metal-cutting tasks and MWF. Subjects were asked whether they had performed metal cutting (drilling, forming, or grinding and polishing of metals), whether they had used aqueous or oil-based MWF, and whether regular dermal contact had occurred during the application.
Duration of exposure was estimated from the number of years, days per week, and daily hours a subject had performed metal-cutting tasks.
We calculated conditional logistic regression analyses and associated 95% CIs individually matched for age, adjusted for a history of cryptorchidism, and stratified by histological subtype (seminoma, non-seminoma). To test whether more toxic cutting fluids had been used in the past, we conducted analyses with respect to time of first contact with MWF (≤1980 and >1980).
The study was approved by the University of Bremen Ethics Committee. Study subjects gave written informed consent to participate in the study.
Results
Ninety-three cases and 463 controls completed a JSQ for metal-cutting work in the automobile industry. The prevalence of exposure to MWF was 39.8% among cases and 40.1% among controls.
Metal cutting was not associated with an increased risk for overall or seminomatous testicular cancer, although a positive trend was implied for overall testicular cancer risk with increasing duration of metal-cutting tasks (table 1; p test for trend=0.29).
Risk estimates for testicular germ cell cancer and exposure to metal-working fluids, stratified by histological subgroup
Neither exposure to aqueous or oil-based MWF, nor dermal exposure showed an association with total germ cell tumour or seminoma risk. However, dermal exposure and exposure to oil-based MWF were associated with an increased risk for non-seminomatous testicular cancer. Risks were most pronounced among subjects who were dermally exposed to oil-based MWF for >5000 h (OR 4.72; 95% CI 1.48 to 15.09) (table 1).
Analyses stratified by year of first exposure to MWF (≤1980 or >1980) did not indicate an increased risk for testicular cancer (results not shown).
Discussion
Working in the metal industry has been frequently associated with an increased risk for testicular cancer. However, these analyses were based on job titles without detailed information regarding exposure to occupational agents in the metal industry.7 8 Previous analyses from our nested case–control study also revealed increased risks for metal-working jobs: the job groups of machinery fitters and assemblers as well as plumbers, welders, and sheet and structural metal workers showed increased risks for testicular cancer, which were restricted to workers performing metal-cutting tasks (OR 1.87; 95% CI 1.31 to 2.67 and OR 1.57; 95% CI 1.06 to 2.34, respectively).2
MWF are suspected risk factors for cancers at various sites.4 No association with testicular cancer has been reported yet, but MWF demonstrated toxic effects on testicular cells in previous in vitro studies.5 In accordance with these results, we observed an increased risk for non-seminomas, but not for seminomatous testicular cancer. In contrast to our findings, a previous German case–control study only identified increased seminoma risks among metal workers. However, these authors did not distinguish between metal-cutting and non-metal-cutting jobs and did not report detailed chemical exposure, such as exposure to MWF.7
Whether seminoma and non-seminoma are separate diseases with differing disease aetiologies is debated. It has been proposed that non-seminoma develops as a result of the reprogramming of a seminomatous tumour cell to a pluripotent embryonal carcinoma cell, which should be considered as one disease entity at different developmental stages.9 Risk factors should therefore not differ between seminomas and non-seminomas. Accordingly, a recent systematic review did not identify different aetiologies with respect to medical, lifestyle, socio-economic, pregnancy-related or genetic risk factors for the two histological subgroups.10 If the proposed pathway is true, MWF should therefore primarily initiate the transformation of an existing seminomatous tumour cell, which may have originated as the result of prenatal exposures or influences in early life.
Previous studies observed that exposure period was a significant determinant affecting aerosol exposure levels. Exposure to MWF after the 1970s was associated with a significant reduction in exposure levels as compared to the 1970s, which was probably due to changes in machining operations or fluid types, or increased engineering control measures.11 To test whether workers had experienced more hazardous exposures in the past, we stratified analyses by year of first exposure to MWF. However, stratification did not reveal exposure differences with respect to time period of exposure in this study.
An advantage of this study is that we examined a cluster of pathologically confirmed testicular germ cell tumours in one particular industry. Limitations include the fact that we cannot rule out that a few subjects who were actually exposed to metal-cutting work did not answer the corresponding JSQ. Due to the multitude of possible job-specific modules in this study, we solicited a maximum of six JSQs from each study subject. Underestimation of the prevalence of metal-cutting work would rather be non-differential and could have biased the ORs towards unity. The difficulty of recalling exposures over several years is also a serious concern. However, since exposure to MWF is not an established risk factor for testicular cancer, incorrect assessment of exposure would rather tend to be non-differential with respect to case status and lead to attenuation of risk estimates towards unity. A final limitation is that we did not solicit information about the use of personal protective equipment, and consequently, intensity of exposure to MWF could not be assessed. However, lack of protective equipment appears to be common among metal-cutting workers.11 Dermal contact results in substantial exposure for a worker,11 and MWF are known to damage skin integrity,3 which may further facilitate penetration of MWF, resulting in increased systemic exposure.
In summary, dermal exposure and particularly dermal exposure to oil-based MWF were associated with an increased risk for non-seminoma in this industrial cohort. Measures to reduce exposure to MWF include introducing engineering control measures such as venting or enclosing of machines. Since the latter may require cleaning of machines or still involve exposure from machine spray, strict rules requiring the use of personal protective equipment (gloves, long sleeves, overalls, goggles, etc) need to be enforced in order to prevent dermal exposure.
Acknowledgments
We are grateful to the study subjects who agreed to report their occupational history and other lifestyle factors in a detailed interview. We also acknowledge the continuous effort and support of the members of the Exposure Assessment Panel which far exceeded that which could be expected.
References
Footnotes
Funding This work was funded by the ‘Vereinigung der Metall-Berufsgenossenschaften’ and the German Social Accident Insurance association (DGUV). We received supplementary funding from the company where the study was performed.
Competing interests We received supplementary funding from the company where the study was performed. We are independent of the company regarding study design, access to the collected data, responsibility for data analysis and interpretation, and the right to publish. The views expressed in this paper are those of the authors and not necessarily those of the sponsors.
Ethics approval Ethics approval was provided by the University of Bremen Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.