Mortality studies of machining fluid exposure in the automobile industry I: A standardized mortality ratio analysis.

Machining fluids are widely used in a variety of common industrial metalworking operations to lubricate and cool both the tool and the working surfaces. Previous studies have suggested elevated respiratory, digestive, and skin cancers in exposed populations. This cohort study was initiated to assess whether long-term exposure to machining fluids in the course of machining, grinding, and other cutting operations is associated with excess cancer mortality. The cohort includes more than 45,000 automobile production workers from 3 plants, almost 1 million years of follow-up, over 10,000 deaths, and an extensive exposure assessment component. Standardized mortality ratios (SMRs) have been estimated for each of the 3 plants, using both U.S. as well as local populations as reference. Relative risks of 1.2-3.1 have been observed for several specific respiratory and digestive cancers of a priori interest, including cancer of the stomach, large intestine, pancreas, lung, and larynx. In addition, elevated risks for leukemia and asthma were noted. Future exposure-response analyses will provide the opportunity to identify relatively modest excesses in cause-specific mortality risk associated with exposure to specific types (straight, soluble, or synthetic), additives, or components of machining fluids.     

Respiratory health of automobile workers and exposures to metal-working fluid aerosols: lung spirometry

BACKGROUND: Despite substantial evidence that workers exposed to metal-working fluids (MWF) have increased respiratory morbidity, the few studies of chronic effects on lung function have not been conclusive. METHODS: Lung spirometry was measured and both current and past exposures to metal-working fluid (MWF) aerosols were estimated in this cross-sectional cohort of 1,811 male automobile workers. Satisfactory exposure data were available for 1,745 (96%): 239 assemblers (never-exposed to MWF), 487 assemblers (previously exposed), 352 machinists currently exposed to straight oils, 441 to soluble oils, and 226 to synthetic fluids. Operations were classified as either grinding or non-grinding machining. RESULTS: Current exposure was not found to be associated with either forced expiratory volume in 1 second (FEV(1)) or forced ventilatory capacity (FVC). Nor was past exposure to water-based fluids (soluble or synthetic MWF) related to pulmonary function. Past exposure to straight oils, however, was significantly associated with FVC. This association was more obvious among older workers and among workers who had never transferred from MWF exposed jobs to assembly. CONCLUSIONS: The magnitude of the association between FVC and lifetime exposure to straight MWF was slightly larger than the estimated cigarette effect, suggesting that the impact of an additional year of exposure to 1 mg/m(3) of mineral oil particulate in the thoracic particle size range, has the same impact on FVC as smoking one pack per day for one more year.     

Mortality studies of machining fluid exposure in the automobile industry IV; a case-control study of lung cancer

Machining fluids are diverse products that contain numerous additives and contaminants, including polycyclic aromatic hydrocarbons. Studies treating machining fluids as an aggregate exposure have found both positive and negative associations with lung cancer. In this nested case-control study of automotive workers (667 cases and 3,041 matched controls), individual estimates of exposure quantity and duration for specific classes of machining fluids were derived. An inverse dose-response relationship was found between synthetic machining fluids and lung cancer mortality, with an odds ratio of 0.6 (95%Cl = 0.4, 0.8) for the highest level of lifetime exposure. The relationship was strongest for recent exposures. There was little evidence of an association with soluble or straight oil machining fluids. Risks were inconsistently elevated in workers exposed to aluminum. Results from this study provide strong evidence that exposure to machining fluids is not associated with an increased risk of lung cancer mortality in automotive workers. Am. J. Ind. Med. 31:525–533, 1997. © 1997 Wiley-Liss, Inc.     

Rectal cancer and exposure to metalworking fluids in the automobile manufacturing industry

Background

Rectal cancer has been previously associated with exposure to metalworking fluids in a cohort mortality study of autoworkers.

Objective

To better specify the exposure–response relationship with straight metalworking fluids (mineral oils) by applying non‐parametric regression methods that avoid linearity constraints and arbitrary exposure cut points and by lagging exposure to account for cancer latency, in a nested case–control analysis.

Methods

In addition to the classical Poisson regression with categorical exposure, survival models with penalised splines were used to estimate the exposure–response relationship between cumulative exposure to straight metalworking fluid and mortality from rectal cancer. Exposures to water‐based metalworking fluids were treated as potential confounders, and all exposures were lagged by 5, 10, 15 and 20 years to account for cancer latency. The influence of the highest exposures was dealt with by a log transformation and outlier removal. The sensitivity of the penalised splines to alternative criteria for model selection and to the placement of knots was also examined.

Results

The hazard ratio for mortality from rectal cancer increased essentially linearly with cumulative exposure to straight metalworking fluid (with narrow confidence bands) up to a maximum of 2.2 at the 99th centile of exposure and then decreased (with wide confidence bands). Lagging exposure up to 15 years increased the initial steepness of the curve and raised the maximum hazard ratio to 3.2.

Conclusions

Non‐parametric smoothing of lagged exposures has shown stronger evidence for a causal association between straight metalworking fluid and rectal cancer than was previously described using standard analytical methods. This analysis suggests an exposure–response trend that is close to linear and statistically significant over most of the exposure range and that increases further with lagged exposures. Smoothing should be regularly applied to environmental studies with quantitative exposure estimates to refine characterisation of the dose–response relationship.Metalworking fluids are complex mixtures of oils and chemicals used to cool and lubricate metal machining operations in many industrial settings. Automobile manufacturing is the largest sector with widespread metalworking fluid exposure. More than 1.2 million workers are exposed to metalworking fluids in the US,¹ and their use is increasing internationally as developing countries industrialise. This growth is occurring despite the presence of known carcinogens, such as chlorinated compounds and polycyclic aromatic hydrocarbons in oil‐based fluids, and ethanolamines and nitrosamines in water‐based fluids.²Metalworking fluids are generally classified into four types in two overlapping groups, according to base composition as oil based (straight and soluble mineral oil) or water based (soluble, semisynthetic and synthetic). All types include some oil (except for synthetics or “chemical fluids”), as well as a variety of additional compounds. The earliest report of cancer among workers exposed specifically to oils used in metalworking appeared in 1950.³ Between 1950 and 1967, two thirds of the 187 cases of scrotal cancer in the West Midlands area of England were attributed to exposure to machining fluid.⁴ With the introduction of high‐speed machining and grinding, concern has shifted from dermal exposures to inhalation of aerosolised metalworking fluids and possible respiratory and gastrointestinal cancers.The cancer mortality study of a United Autoworkers‐General Motors cohort is the largest study with quantitative estimates of lifetime exposure to specific types of metalworking fluid.⁵ In the extended follow‐up of this cohort, results were presented from exposure–response models for 12 cancers, including colon and rectal cancers, using a uniform set of exposure categories.⁶ Although most epidemiological studies examine rectal and colon cancer as a single outcome, they were considered separately because there is growing evidence that they are distinct diseases.⁷ Results of that study suggested the increasing risk of rectal cancer, but not of colon cancer, in relation to increasing exposure to straight metalworking fluids. In light of widespread industrial exposure and poor survival rates for rectal cancer, we have taken this opportunity to re‐examine the data more closely by refining the measures of exposure to account for latency and applying more informative non‐parametric exposure–response models with fewer statistical assumptions.     

Health effects of oil mists: a brief review

Metal cutting/grinding fluids are of three basic types: straight oil (insoluble), oil-in-water emulsions (soluble) and synthetic/semisynthetic. All contain a variety of additives to improve performance. Human exposure occurs primarily by direct skin contact with the liquid or by skin and respiratory contact after fluid misting. Dermatitis caused by primary or direct skin irritation is the most prevalent health effect of exposure to cutting fluids. Occasionally allergic dermatitis is seen which is related to the development of sensitization to one or more of the additive components. Recent studies indicate that long-term exposure to cutting fluids does not result in increased incidences of lung cancer, urinary bladder cancer, gastrointestinal cancer, or death from non-malignant respiratory diseases. Long-term exposure to certain cutting fluids, however, is believed to have resulted in certain types of skin cancer, especially scrotal cancer. It is likely that these carcinogenic responses were caused by contact with polycyclic aromatic compounds (PCA) of 3-7 rings. Modern base oils which are severely refined have very low levels of PCA, are not carcinogenic in animal bioassays, and are unlikely to be carcinogenic in man. This is not necessarily true for re-refined oils which may contain significant levels of PCA and polychlorinated biphenyls derived from comingling used cutting oils with used engine oils and transformer oils. Cutting oils, themselves, generally do not accumulate significant levels of carcinogenic PCA during use. Additives, in theory, can cause a variety of health effects either directly or through the generation of reaction products such as nitrosamines. In actual use, adverse health effects appear to be limited to occasional instances of allergic contact dermatitis. Nitrosamines are extremely carcinogenic in test animals; although no human cancer cases directly attributable to nitrosamine contamination have been observed, nitrosating agents and amines should not be combined in cutting fluid formulations. It is difficult to anticipate or predict the potential toxicity of a particular cutting fluid formulation because of the presence of variable amounts of proprietary additives which, themselves, are often complex reaction mixtures. Thus, each additive and final formulation must be evaluated on a case by case basis to appropriately assess potential health hazards.     

Mortality studies of metalworking fluid exposure in the automobile industry: VI. A case-control study of esophageal cancer

Background Results are reported from a nested case-control study of 60 esophageal cancer deaths among 46,384 automobile manufacturing workers potentially exposed to metalworking fluids (MWF) in machining and grinding operations. Methods By using incidence-density sampling, controls were selected with a sampling ratio of 20:1 from among co-workers who remained at risk by the age of death of the case, matched on race, gender, plant, and year of birth. Conditional logistic regression was used to evaluate the risk associated with cumulative exposure (mg/m³-years) to each of three types of metalworking fluid (straight, soluble, and synthetic MWF), as well as with years of exposure to selected components of MWF, including nitrosamines, sulfur, biocides, and several metals. Results Esophageal cancer was found to be significantly associated with exposure to both soluble and synthetic MWF in grinding operations. The odds ratios (ORs) for grinding with soluble MWF were elevated at 2.5 or greater in all categories of cumulative exposure, although the exposure-response trend was statistically significant only when exposure was measured as duration. Those with 12 or more years exposure to soluble MWF in grinding operations experienced a 9.3-fold relative risk of esophageal cancer mortality (95% CI = 2.1–42.1). The OR for ever grinding with synthetic MWF was 4.1 (95% CI = 1.1–15.0). Elevated risk was also associated with two agents found in both synthetic and soluble fluids, nitrosamines, and biocides. For exposure to nitrosamines, the OR was 5.4 (95% CI = 1.5–19.9); for biocides the OR was 3.8 (95% CI = 0.8–18.9). However, because the same workers were exposed to grinding with synthetics, nitrosamines and biocides, it was not possible to separate the specific risks associated with these components. Am. J. Ind. Med. 34:36–48, 1998. © 1998 Wiley-Liss, Inc.     

Mortality studies of machining fluid exposure in the automobile industry V: A case-control study of pancreatic cancer

Results are presented from a case-control study of 97 cases of pancreatic cancer nested in a cohort of workers from three automobile manufacturing plants. Risk was examined for lifetime exposure to straight, soluble, and synthetic metalworking fluids, as used in specific machining or grinding operations, as well as for constituents of the fluids. Pancreatic cancer was associated with exposure to synthetic fluids in grinding operations, with an odds ratio of 3.0 (95% CI: 1.2–7.5) among those with more than 1.4 mg/m³-years of exposure. We were unable to examine synthetic exposure in the absence of grinding because there was virtually no exposure to synthetics in machining operations in this study population. Although a disproportionately high percent of the cases were black, no black workers had any exposure to synthetic fluids, and no other measured exposure was found to be related to risk. Thus, the previously documented excess risk of pancreatic cancer among blacks in this cohort remains unexplained. Am. J. Ind. Med. 32:240-247, 1997. © 1997 Wiley-Liss, Inc.     

A nested case-control study of stomach cancer mortality among automobile machinists exposed to metalworking fluid

PURPOSE: In a nested case-control study of 140 stomach cancer deaths (1941-1984) among 46,384 automobile workers, we examined risk in relation to lifetime exposure to metalworking fluid (MWF) in machining and grinding operations.METHODS: Exposure was defined during varying windows of biologic time (<10 years before death, 10-20 years before death, and > 20 years before death) and evaluated using a nonparametric smoothing technique and conditional logistic regression. Exposure was measured by duration, intensity (mg/m(3)), and cumulative exposure (mg/m(3)-years) to each MWF type (straight, soluble, or synthetic), as well as by duration of exposure to selected metals, additives, and components of the fluids.RESULTS: When data from three plants were combined, grinding with water-based synthetic or soluble MWF increased the risk of stomach cancer mortality. Those grinding with synthetic MWF with more than 1.3 mg/m(3)-years exposure during the 10 years just prior to death experienced a 4.4-fold risk of stomach cancer (95% CI 1.5-13.1). Increased risk was also observed among those in the highest category of soluble grinding grading exposure (OR 1.9; 85% CI 1.0-3.6). In plant-specific analysis, there was evidence of increased risk of stomach cancer associated with exposure to straight MWF and iron, as well as the water-based fluids.CONCLUSIONS: Study findings suggest that stomach cancer mortality was associated with exposure to each MWF type. Results suggesting that synthetic MWF may act as a stomach cancer promoter are of particular concern because this MWF is widely used in today's high speed grinding operations.     

Mortality studies of machining fluid exposure in the automobile industry III: A case-control study of larynx cancer

A case-control study of larynx cancer was conducted within a cohort of automobile workers exposed to metal working fluids, commonly referred to as machining fluids (MF). Results are based on 108 cases of larynx cancer and 5:1 matched controls. Risks associated with specific types of MF, as well as specific components of the fluids were evaluated. Based on a retrospective exposure assessment, lifetime exposures to straight and soluble fluids, grinding particulate, biocides, selected metals, sulfur, and chlorine were examined. Exposure to asbestos and acid mists at two of the three study sites was also characterized. Results suggest that straight mineral oils are associated with almost a two-fold excess in larynx cancer risk. There was also evidence of an association with elemental sulfur, commonly added to straight MF to improve the integrity of the materials under extreme pressure and heat. It is not clear whether sulfur is causally related to an excess relative risk of larynx cancer or whether the observed association is the result of unmeasured confounding by another contaminant or process feature. For example, the high stress operations that require MF enriched with sulfur are also more likely to produce polycyclic aromatic hydrocarbons (PAHs) during the process. Thus, the observed association with sulfur may be due to an association with PAH. The finding of excess risk of laryngeal cancer associated with MF is consistent with several previous reports in the literature. This is the first study, however, to distinguish straight mineral oils from other types of MF. Based on these findings, a general reduction in concentrations of straight mineral oil particulate in occupational environments would be prudent.     

Exposure-response models based on extended follow-up of a cohort mortality study in the automobile industry

OBJECTIVE: This report describes the extended follow-up of a cohort of 46 399 automobile manufacturing workers with potential exposure to metalworking fluids (MWF). The outcomes of interest were cancers of the esophagus, stomach, colon, rectum, liver, pancreas, larynx, skin, prostate, and brain, as well as leukemia. Additional follow-up increased the power to detect modest elevations in mortality rates in association with specific types of MWF, including synthetic fluids not in widespread use until the 1970s. METHODS: Standardized mortality ratios (SMR) were computed for the most recent 10 years of follow-up, as well as for the entire study period. Adjusted relative risks (RR) were estimated in Poisson regression models with categorical variables for cumulative exposure to each type of MWF and in proportional hazards models with continuous exposure variables. RESULTS: Associations were found between straight MWF and esophageal, laryngeal and rectal cancer; soluble MWF and cancer of the esophagus, larynx, skin, and brain; synthetic MWF and cancer of the esophagus, liver, and prostate. The elevated RR values were modest in magnitude (1.5 to 2.0). SMR values were increased for stomach, liver, and pancreatic cancer and also for leukemia in the last 10 years of follow-up. The SMR values were also elevated for stomach and liver cancer among the persons recently hired. CONCLUSIONS: The results provide further evidence that exposure to metalworking fluids causes cancer among workers in automobile manufacturing. Although airborne exposures declined over the study period, this study suggests that modest risk of several digestive cancers, as well as prostatic cancer and leukemia, may persist at current levels of exposure to water-based metalworking fluids.     

Smoothing in survival models: an application to workers exposed to metalworking fluids

BACKGROUND In occupational epidemiology it is typically assumed that the relation between exposure, possibly transformed, and the risk of an adverse health outcome is linear in the parameters. Alternatively, exposure is transformed into a categorical variable.METHODS We used nonparametric regression to examine the linearity assumption for prostate and brain cancer mortality in a cohort of 46,400 autoworkers exposed to metalworking fluids. Using a nested case-control sample, we fit Cox proportional hazards models with penalized splines, in which we allowed the risk to be a smooth function of exposure to each of three types of metalworking fluids. Two dose metrics in addition to cumulative exposure were considered.RESULTS The shape of the dose-response curve for soluble metalworking fluids and each cancer was approximately piecewise linear, with a small increase in risk at lower exposures followed by a larger increase at exposures above a critical point.CONCLUSIONS This example illustrates that the penalized spline methodology can be easily applied to cohort studies to estimate smooth exposure-response curves.     

Occupational exposure to metalworking fluids and risk of breast cancer among female autoworkers

BACKGROUND: Metalworking fluids (MWF) are used for lubrication during metal manufacturing. Previous studies have observed increased risks of several cancers among MWF-exposed workers. We hypothesized that MWF may be associated with risk of breast cancer because they can contain carcinogenic or endocrine-disrupting chemicals. METHODS: We conducted a case-control study nested in a cohort of 4,680 female automobile workers employed for at least 3 years between 1/1/41 and 1/1/85, with follow-up through 1994. Cases were identified using the National Death Index (NDI), Michigan cancer registries, and company records. Detailed quantitative MWF exposure data were available for each subject, although data on known breast cancer risk factors were not. RESULTS: Ninety-nine cases of breast cancer and 626 matched controls were identified. There was a weak positive association between lifetime cumulative exposure to soluble MWF and breast cancer risk, but no evidence of association with either straight or synthetic fluids. When exposure was divided into time-windows, the association was strongest for soluble MWF in the decade preceding diagnosis. Controlling for earlier exposures, there was an odds ratio of 1.18 (95% CI=1.02-1.35) per mg/m3-year of cumulative exposure to soluble MWF in this 10-year period. CONCLUSION: This hypothesis-generating study provides some preliminary evidence for an association between exposure to soluble MWF and increased risk of breast cancer. Additional studies of MWF and breast cancer, with data on known breast cancer risk factors, are warranted.     

Causes of death among workers in a bearing manufacturing plant

Recent studies identify digestive cancer excesses among workers exposed to cutting fluids, abrasive dusts, and oil smoke. Standardized proportional mortality and mortality odds ratio studies were carried out for a ball bearing plant. Cause of death and work histories were obtained for 702 of 768 hourly employees with ten or more years' service who died between 1969 and 1982. Union and company records were used to define exposure measures. The major findings were significant excesses in proportional mortality ratios (PMR) from stomach cancer (PMR = 2.0) and rectal cancer (PMR = 3.1) among white men. After control for age at death, there was a significant association between stomach cancer and precision grinding exposures, consisting primarily of direct contact with water-based cutting fluids (usually emulsified oils) and their aerosols. Some straight oils and synthetic cutting fluids were used as well. The pattern of stomach cancer is consistent with previous findings and suggests an association with the soluble oil cutting fluids.     

Occupational exposure to machining fluids and laryngeal cancer risk: Contrasting results using two separate control groups

This death certificate-based case-control study linked Connecticut Tumor Registry and Connecticut Division of Vital Statistics death data to determine whether machining fluid exposure is associated with laryngeal cancer risk. Laryngeal cancer cases were compared with oral cancer controls and general population controls. Level of exposure to machining fluids was imputed from the usual occupation and industry on the death certificate. Because exposure was infrequent among females, analysis was limited to males. When cases were compared to oral cancer controls, high exposure to machining fluids was associated with laryngeal cancer (odds ratio = 1.48; 95% confidence interval = 1.01–2.16), with a p–value for trend of 0.08. When cases were compared to population controls, no association between machining fluid exposure and laryngeal cancer was observed. A possible reason for the contrasting results, other than chance, is that exposure data quality for the cases and oral cancer controls may have differed from that of the population controls. Am. J. Ind. Med. 31:166–171, 1997. © 1997 Wiley-Liss, Inc.     

Estimation of the Probability of Exposure to Machining Fluids in a Population-Based Case-Control Study

We describe an approach for estimating the probability that study subjects were exposed to metalworking fluids (MWFs) in a population-based case-control study of bladder cancer. Study subject reports on the frequency of machining and use of specific MWFs (straight, soluble, and synthetic/semi-synthetic) were used to estimate exposure probability when available. Those reports also were used to develop estimates for job groups, which were then applied to jobs without MWF reports. Estimates using both cases and controls and controls only were developed. The prevalence of machining varied substantially across job groups (0.1–>0.9%), with the greatest percentage of jobs that machined being reported by machinists and tool and die workers. Reports of straight and soluble MWF use were fairly consistent across job groups (generally 50–70%). Synthetic MWF use was lower (13–45%). There was little difference in reports by cases and controls vs. controls only. Approximately, 1% of the entire study population was assessed as definitely exposed to straight or soluble fluids in contrast to 0.2% definitely exposed to synthetic/semi-synthetics. A comparison between the reported use of the MWFs and U.S. production levels found high correlations (r generally >0.7). Overall, the method described here is likely to have provided a systematic and reliable ranking that better reflects the variability of exposure to three types of MWFs than approaches applied in the past.

[Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a list of keywords in the occupational histories that were used to link study subjects to the metalworking fluids (MWFs) modules; recommendations from the literature on selection of MWFs based on type of machining operation, the metal being machined and decade; popular additives to MWFs; the number and proportion of controls who reported various MWF responses by job group; the number and proportion of controls assigned to the MWF types by job group and exposure category; and the distribution of cases and controls assigned various levels of probability by MWF type.]     

Mortality and cancer morbidity in workers exposed to cutting fluids

This cohort study includes 792 men exposed to cutting fluids that contain mineral oils and additives in a machining industry. Their cancer mortality and morbidity was compared with that of the general population of the same city. The total mortality was not found to be increased, and there were no increased incidences of lung cancer or death resulting from nonmalignant respiratory diseases. Seven of the turners but none of the grinders had squamous cell carcinomas on the skin of the scrotum. There was no increased incidence of cancer of the urinary bladder.     

Respiratory health of automobile workers exposed to metal-working fluid aerosols: Respiratory symptoms

A total of 1,811 automobile workers at three General Motors facilities were evaluated by questionnaire for possible respiratory effects resulting from airborne exposures to metal-working fluids (MWF): 1,042 currently worked as machinists and were exposed to one of three types of MWF aerosols (straight mineral oils, soluble oil emulsions, or water-based synthetic fluids that contained no oils); 769 assembly workers, without direct exposure, served as an internal reference group (of these, 239 had never worked as machinists). Symptoms of usual cough, usual phlegm, wheezing, chest tightness, and breathlessness, as well as physician-diagnosed asthma, and chronic bronchitis were the primary outcomes examined. Machinists as a whole had higher prevalence of cough, phlegm, wheezing, and breathlessness than that of assembly workers. Adjusting for confounding, phlegm and wheeze were associated with increasing levels of current exposure to straight oils; cough, phlegm, wheeze, chest tightness, and chronic bronchitis were associated with increasing levels of current exposure to synthetics. In models that included both past and current exposure, only current exposures to straight and synthetic fluids were associated with current symptoms. Am. J. Ind. Med. 32:450–459, 1997. © 1997 Wiley-Liss, Inc.     

A case-control study of cancer mortality at a transformer-assembly facility

Summary To address earlier reports of excess cancer mortality associated with employment at a large transformer manufacturing plant, each plant operation was rated for seven exposures: Pyranol (a mixture of poly chlorinated biphenyls and trichlorobenzene), trichloroethylene, benzene, mixed solvents, asbestos, synthetic resins, and machining fluids. Site-specific cancer deaths among active or retired employees were cases; controls were selected from deaths (primarily cardiovascular deaths) presumed to be unassociated with any of the study exposures. Using job records, we then computed person-years of exposure for each subject. All subjects were white males. The only unequivocal association was that of resin systems with lung cancer (odds ratio = 2.2 at 16.6 years of exposure, P = 0.001, in a multiple logistic regression including asbestos, age, year of death, and year of hire). Certain other odds ratios appeared larger, but no other association was so robust and remained as distinct after considering the multiplicity of comparisons. Study power was very limited for most associations, and several biases may have affected our results. Nevertheless, further investigation of synthetic resin systems of the type used in the study plant appears warranted.This research was conducted under contracts with the University of Lowell Research Foundation and General Electric Corporation.     

Registry-based case-control studies of liver cancer and cancers of the biliary tract nested in a cohort of autoworkers exposed to metalworking fluids

OBJECTIVE: Results are presented for a registry-based study of hepatobiliary cancer (liver and biliary tract) nested in a cohort of workers from three automobile manufacturing plants with potential exposure to metalworking fluids. METHODS: Altogether 63 cases of hepatobiliary cancer were identified from the cohort by the Michigan cancer registries. Each case was matched to 10 controls. Odds ratios (OR) were estimated in conditional logistic regression models for lifetime exposure to straight, soluble, and synthetic metalworking fluid and fluid components. RESULTS: Overall, hepatobiliary cancer was not associated with exposure to metalworking fluids. However, when the cases were stratified into liver cancer (N = 39) and biliary tract cancer (N = 24) the risk was nonhomogeneous across the two categories. While liver cancer was not associated with exposure to metalworking fluids, the results suggested a possible excess risk of biliary tract cancer with more than 1.0 mg/m3-years of exposure to straight metalworking fluids [OR 2.7, 95% confidence interval (95% CI) 0.9-7.6], as well as any exposure to chlorinated paraffins (OR 3.9, 95% CI 0.9-17). When exposures to straight metalworking fluids were separated into 10-year exposure periods, the odds ratio increased to 6.24 (95% CI 1.62-24.16) for exposures occurring > 20 years prior to the risk date. CONCLUSIONS: There is limited evidence that exposure to straight metalworking fluids is associated with biliary tract cancer. The small numbers of cases of these rare cancers were reflected in the wide confidence intervals, and these findings need to be examined further in other exposed populations.     

Epidemiologic evidence on the carcinogenicity of metalworking fluids

The purpose of this review is to organize and evaluate the epidemiologic evidence regarding the potential carcinogenicity of metalworking fluids. Published literature was initially examined to identify the key contributions, with a strong emphasis on the series of studies by Eisen et al. A key challenge to addressing the issue is the diversity of metalworking fluids, additives, and by-products produced in use, along with the notable changes in the composition and use of such agents over time. Although several smaller cohort studies provided useful data on this issue through the 1980s, the Eisen et al. studies offer unique information given the size of the cohort, sophistication in exposure assessment, and detailed analysis of cancer mortality risks within the cohort as a function of estimated exposure. The most notable associations, based on precision, magnitude, and evidence for increasing risk with increasing exposure are those between straight metalworking fluids and both rectal and laryngeal cancer, as well as soluble metalworking fluids and laryngeal cancer. Further progress will require additional studies of the scale of Eisen et al.'s as well as a more systematic approach to integrating information from toxicology and industrial hygiene into the interpretation of the epidemiologic literature.