Occupations with mineral oil exposure have been associated with bladder cancer in population-base... more Occupations with mineral oil exposure have been associated with bladder cancer in population-based case-control studies. The authors report results from the first cohort study to examine bladder cancer incidence in relation to quantitative exposures to metalworking fluids (MWFs), based on 21,999 male Michigan automotive workers, followed from 1985 through 2004. Cox regression was used to estimate hazard ratios based on categorical exposure variables for straight, soluble, and synthetic MWFs, as well as duration of exposure to ethanolamines and nitrosamines. Penalized splines were also fit to estimate the functional form of the exposure-response relation. Increased bladder cancer risk was associated with straight MWFs but not with any other exposure. The hazard ratio increased with cumulative exposure to a maximum of 2-fold observed at 75 mg/m(3)-year straight MWF exposure (lagged 20 years). Calendar time windows relevant to polycyclic aromatic hydrocarbon exposure were examined but ...
We examined how state characteristics in early life are associated with individual chronic diseas... more We examined how state characteristics in early life are associated with individual chronic disease later in life. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Characteristics of the state in which an indiv...
To examine gender and racial disparities in ischaemic heart disease (IHD) mortality related to me... more To examine gender and racial disparities in ischaemic heart disease (IHD) mortality related to metalworking fluid exposures and in the healthy worker survivor effect. A cohort of white and black men and women autoworkers in the USA was followed from 1941 to 1995 with quantitative exposure to respirable particulate matter from water-based metalworking fluids. Separate analyses used proportional hazards models and g-estimation. The HR for IHD among black men was 3.29 (95% CI 1.49 to 7.31) in the highest category of cumulative synthetic fluid exposure. The HR for IHD among white women exposed to soluble fluid reached 2.44 (95% CI 0.96 to 6.22). However, no increased risk was observed among white men until we corrected for the healthy worker survivor effect. Results from g-estimation indicate that if white male cases exposed to soluble or synthetic fluid had been unexposed to that fluid type, then 1.59 and 1.20 years of life would have been saved on average, respectively. We leveraged t...
To examine gender and racial disparities in heart disease mortality related to metalworking fluid... more To examine gender and racial disparities in heart disease mortality related to metalworking fluid exposures and in the healthy worker survivor effect. We examined ischaemic heart disease (IHD) mortality from 1941 to 1995 in a cohort of autoworkers with quantitative exposure to cumulative respirable particulate matter from water-based metalworking fluids. Cox models were used to estimate the exposure-response to soluble and synthetic fluids separately in white men, black men, and white women. In separate analyses, we used g-estimation to adjust for the healthy worker survivor effect. The risk of IHD was increased among black men (295 deaths) exposed to synthetic fluid with a hazard ratio (HR) of 3.47 (95% CI: 1.52, 7.92) in the highest cumulative exposure category. White women (119 deaths) had increased risk of IHD with increased soluble fluid (HR: 2.44 (0.93, 6.38)) in the second to highest category. However, Cox models show no increased risk in white men (2246 deaths). In contrast,...
To apply Marginal Structural Models (MSM) to address healthy workers survivor effect in a cohort ... more To apply Marginal Structural Models (MSM) to address healthy workers survivor effect in a cohort study of active workers when time varying variables on health status and exposure are measured. We used Cox MSMs and inverse probability weighting to assess the effect of PM-2.5 exposure on incident ischaemic heart disease (IHD) in an active cohort of 11 966 US aluminium workers. The outcome was assessed using medical claims data from 1998 to 2012. Quantitative exposure metrics of current exposure to PM2.5 were dichotomized using different cutoffs and effects were assessed separately for smelters and fabrication. Risk score based on insurance claims was available as a time varying health status variable. Defining binary PM2.5 exposure by the 10th percentile cut-off, health status was affected by past exposure and predicted subsequent exposure in smelters, but not in fabrication. A Traditional cox model was appropriate for fabricators; the hazard ratio was 1.51(95% CI: 1.12 - 2.06) and wa...
Marginal structural models (MSMs) and inverse probability weighting can be used to estimate risk ... more Marginal structural models (MSMs) and inverse probability weighting can be used to estimate risk in a cohort of active workers if there is a time-varying confounder (e.g., health status) affected by prior exposure-a feature of the healthy worker survivor effect. We applied Cox MSMs in a study of incident ischemic heart disease and exposure to particulate matter with aerodynamic diameter of 2.5 μm or less (PM2.5) in a cohort of 12,949 actively employed aluminum workers in the United States. The cohort was stratified by work process into workers in smelting facilities, herein referred to as "smelters" and workers in fabrication facilities, herein referred to as "fabricators." The outcome was assessed by using medical claims data from 1998 to 2012. A composite risk score based on insurance claims was treated as a time-varying measure of health status. Binary PM2.5 exposure was defined by the 10th-percentile cutoff for each work process. Health status was associated ...
The healthy worker survivor effect (HWSE) is a well-recognised bias usually described as a form o... more The healthy worker survivor effect (HWSE) is a well-recognised bias usually described as a form of selection bias or confounding. A more precise epidemiologic explanation, however, has been elusive. We distinguish several components of the HWSE and suggest methods for bias correction in occupational cohort studies. Although generally referred to a single effect, we demonstrate using simulation studies that there are in fact four distinct aspects of the HWSE. Two aspects, (1) time-varying confounding by variables on the causal pathway and (2) heterogeneity in susceptibility, are functions of the underlying process of the exposure and disease under study. The other two, (3) left truncation and (4) right truncation, are functions of how the data are collected, ie the study design. We quantify the bias induced by each aspect of HWSE on dose-response parameter estimates and apply methods designed to reduce the bias. We find that causal techniques, eg, g-estimation and IPTW, can correct f...
To examine further the association between endotoxin and risk of lung cancer among Shanghai women... more To examine further the association between endotoxin and risk of lung cancer among Shanghai women textile workers in an extended follow-up of the cohort. The initial follow-up indicated an inverse exposure-response relation. We updated a case-cohort study nested within a cohort of 267 400 women. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. Endotoxin exposures were based on a quantitative job/exposure matrix. Relative risks (hazard ratios [HR]) associated with cumulative exposure, adjusted for age and smoking history, were estimated by Cox proportional hazards modelling adapted for the case-cohort design. We conducted exposure-response trend analyses for cumulative exposures lagged by 0, 10, and 20 years, and separately for time windows of <15 and >15 years since first exposure. Overall, we observed no associations between cu...
We estimated the effect of cumulative exposure to PM2.5 on the incidence of ischaemic heart disea... more We estimated the effect of cumulative exposure to PM2.5 on the incidence of ischaemic heart disease (IHD) in aluminium workers followed for 15 years, adjusting for the healthy worker survivor effect. In previous analyses, higher cumulative exposure was found to be associated with lower mortality in this population. We used longitudinal TMLE to estimate the cumulative risk of ischaemic heart disease in the cohort if constantly exposed above an exposure cut-off and compared it to the risk if constantly exposed below. We stratified all analyses by work process because exposures were an order of magnitude higher in smelters than fabrication facilities. We selected cut-offs a priori at the median and 10th percentile exposure within each sub-cohort. Among the smelter workers, we estimated an increase in IHD risk of 2.1% (p = 0.22) after 15 years, comparing the always exposed to never exposed cohort using the median cut-off of 1.77 mg/m(3). The difference was 2.9% (p = 0.01) using the 10th...
Journal of Exposure Science and Environmental Epidemiology, 2014
Fine particulate matter (PM 2.5 ) in air pollution, primarily from combustion sources, is recogni... more Fine particulate matter (PM 2.5 ) in air pollution, primarily from combustion sources, is recognized as an important risk factor for cardiovascular events but studies of workplace PM 2.5 exposure are rare. We conducted a prospective study of exposure to PM 2.5 and incidence of ischemic heart disease (IHD) in a cohort of 11,966 US aluminum workers. Incident IHD was identified from medical claims data from 1998 to 2008. Quantitative metrics were developed for recent exposure (within the last year) and cumulative exposure; however, we emphasize recent exposure in the absence of interpretable work histories before follow-up. IHD was modestly associated with recent PM 2.5 overall. In analysis restricted to recent exposures estimated with the highest confidence, the hazard ratio (HR) increased to 1.78 (95% CI: 1.02, 3.11) in the second quartile and remained elevated. When the analysis was stratified by work process, the HR rose monotonically to 1.5 in both smelter and fabrication facilities, though exposure was almost an order of magnitude higher in smelters. The differential exposure-response may be due to differences in exposure composition or healthy worker survivor effect. These results are consistent with the air pollution and cigarette smoke literature; recent exposure to PM 2.5 in the workplace appears to increase the risk of IHD incidence.
Due to the heavy and expanding agricultural use of neurotoxic pesticides suspected to affect dopa... more Due to the heavy and expanding agricultural use of neurotoxic pesticides suspected to affect dopaminergic neurons, it is imperative to closely examine the role of pesticides in the development of Parkinson's disease (PD). We focus our investigation on pesticide use in California's heavily agricultural central valley by utilizing a unique pesticide use reporting system. From 2001 to 2007, we enrolled 362 incident PD cases and 341 controls living in the Central Valley of California. Employing our geographic information system model, we estimated ambient exposures to the pesticides ziram, maneb, and paraquat at work places and residences from 1974 to 1999. At workplaces, combined exposure to ziram, maneb, and paraquat increased risk of PD three-fold (OR: 3.09; 95% CI: 1.69, 5.64) and combined exposure to ziram and paraquat, excluding maneb exposure, was associated with a 80% increase in risk (OR:1.82; 95% CI: 1.03, 3.21). Risk estimates for ambient workplace exposure were greater than for exposures at residences and were especially high for younger onset PD patients and when exposed in both locations. Our study is the first to implicate ziram in PD etiology. Combined ambient exposure to ziram and paraquat as well as combined ambient exposure to maneb and paraquat at both workplaces and residences increased PD risk substantially. Those exposed to ziram, maneb, and paraquat together experienced the greatest increase in PD risk. Our results suggest that pesticides affecting different mechanisms that contribute to dopaminergic neuron death may act together to increase the risk of PD considerably.
Background: Occupational exposure to mineral oil-based metalworking fluids has been consistently ... more Background: Occupational exposure to mineral oil-based metalworking fluids has been consistently linked with skin conditions such as contact dermatitis and squamous cell skin cancer, especially of the scrotum. We examined the incidence of malignant melanoma in a study of autoworkers. Methods: We followed a cohort of autoworkers from 1985 through 2004 for cancer incidence. Hazard ratios (HRs) were estimated in Cox models for cumulative exposure to total particulate of straight fluid (neat oil), soluble fluid (oil emulsified in water), and synthetic fluid (no oil). Exposure was partitioned into time windows by latency and by calendar periods defined by changes in the content of polycyclic aromatic hydrocarbon in the refined oils. The population was restricted to workers born after 1935. We examined the dateof-birth restriction in a sensitivity analysis. Results: On the basis of 76 incident cases of malignant melanoma in the cohort of 14,139 white males, the HR was 1.99 (95% confidence interval ϭ 1.00 -3.96) for the highest category of straight fluid. Risk was greatest in the most recent time window. Penalized splines suggested a linear exposure-response over the full range of exposure. The change in HR for malignant melanoma per mg/m 3year of straight fluid increased monotonically from 1.01 to 1.04, when the date-of-birth restriction increased from 1925 to 1945 in 5-year intervals. Results for soluble fluid were more modest. There was no association with synthetic fluid. Conclusions: Results provide evidence, based on quantitative measures of metalworking fluid, that oil-based fluid, particularly straight mineral oils, are associated with the incidence of malignant melanoma.
Objective-Exposure to endotoxin has been consistently associated with a reduced risk of lung canc... more Objective-Exposure to endotoxin has been consistently associated with a reduced risk of lung cancer. However, there is a paucity of information regarding temporal aspects of this relationship. The objective of this study was to investigate the associations between contiguous windows of endotoxin exposure and risk of lung cancer.
Background-Metalworking fluids (MWF) -straight, soluble, and synthetic -have overlapping componen... more Background-Metalworking fluids (MWF) -straight, soluble, and synthetic -have overlapping components. We derived constituent-based metrics of polycyclic aromatic hydrocarbons (PAHs), water-based MWF, biocides, and nitrosamines to account for this overlap and examined their relations with cancer incidence.
Exposure to metalworking fluid (MWF) causes respiratory outcomes such as asthma and chronic bronc... more Exposure to metalworking fluid (MWF) causes respiratory outcomes such as asthma and chronic bronchitis, as well as symptoms including phlegm and wheezing. Chronic obstructive pulmonary disease (COPD) encompasses these outcomes, and so is a potential result of MWF exposure. Recent evidence based on g-estimation suggests that reducing exposure to MWF would substantially decrease years of life lost due to COPD. The objective of this analysis is to examine the exposure-response relationship between direct exposure to MWF and COPD mortality in a large occupational cohort. Hazard ratios were estimated using Cox proportional hazards models for the association between cumulative exposure to the thoracic fraction (PM9.8) of straight, synthetic, or soluble MWF and COPD mortality. Subjects directly exposed to each fluid type were compared to those who were never directly exposed (assembly workers). Hazard ratios for exposure quartiles increased in a non-monotonic fashion, with a maximum of 1.6...
Occupations with mineral oil exposure have been associated with bladder cancer in population-base... more Occupations with mineral oil exposure have been associated with bladder cancer in population-based case-control studies. The authors report results from the first cohort study to examine bladder cancer incidence in relation to quantitative exposures to metalworking fluids (MWFs), based on 21,999 male Michigan automotive workers, followed from 1985 through 2004. Cox regression was used to estimate hazard ratios based on categorical exposure variables for straight, soluble, and synthetic MWFs, as well as duration of exposure to ethanolamines and nitrosamines. Penalized splines were also fit to estimate the functional form of the exposure-response relation. Increased bladder cancer risk was associated with straight MWFs but not with any other exposure. The hazard ratio increased with cumulative exposure to a maximum of 2-fold observed at 75 mg/m(3)-year straight MWF exposure (lagged 20 years). Calendar time windows relevant to polycyclic aromatic hydrocarbon exposure were examined but ...
We examined how state characteristics in early life are associated with individual chronic diseas... more We examined how state characteristics in early life are associated with individual chronic disease later in life. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Characteristics of the state in which an indiv...
To examine gender and racial disparities in ischaemic heart disease (IHD) mortality related to me... more To examine gender and racial disparities in ischaemic heart disease (IHD) mortality related to metalworking fluid exposures and in the healthy worker survivor effect. A cohort of white and black men and women autoworkers in the USA was followed from 1941 to 1995 with quantitative exposure to respirable particulate matter from water-based metalworking fluids. Separate analyses used proportional hazards models and g-estimation. The HR for IHD among black men was 3.29 (95% CI 1.49 to 7.31) in the highest category of cumulative synthetic fluid exposure. The HR for IHD among white women exposed to soluble fluid reached 2.44 (95% CI 0.96 to 6.22). However, no increased risk was observed among white men until we corrected for the healthy worker survivor effect. Results from g-estimation indicate that if white male cases exposed to soluble or synthetic fluid had been unexposed to that fluid type, then 1.59 and 1.20 years of life would have been saved on average, respectively. We leveraged t...
To examine gender and racial disparities in heart disease mortality related to metalworking fluid... more To examine gender and racial disparities in heart disease mortality related to metalworking fluid exposures and in the healthy worker survivor effect. We examined ischaemic heart disease (IHD) mortality from 1941 to 1995 in a cohort of autoworkers with quantitative exposure to cumulative respirable particulate matter from water-based metalworking fluids. Cox models were used to estimate the exposure-response to soluble and synthetic fluids separately in white men, black men, and white women. In separate analyses, we used g-estimation to adjust for the healthy worker survivor effect. The risk of IHD was increased among black men (295 deaths) exposed to synthetic fluid with a hazard ratio (HR) of 3.47 (95% CI: 1.52, 7.92) in the highest cumulative exposure category. White women (119 deaths) had increased risk of IHD with increased soluble fluid (HR: 2.44 (0.93, 6.38)) in the second to highest category. However, Cox models show no increased risk in white men (2246 deaths). In contrast,...
To apply Marginal Structural Models (MSM) to address healthy workers survivor effect in a cohort ... more To apply Marginal Structural Models (MSM) to address healthy workers survivor effect in a cohort study of active workers when time varying variables on health status and exposure are measured. We used Cox MSMs and inverse probability weighting to assess the effect of PM-2.5 exposure on incident ischaemic heart disease (IHD) in an active cohort of 11 966 US aluminium workers. The outcome was assessed using medical claims data from 1998 to 2012. Quantitative exposure metrics of current exposure to PM2.5 were dichotomized using different cutoffs and effects were assessed separately for smelters and fabrication. Risk score based on insurance claims was available as a time varying health status variable. Defining binary PM2.5 exposure by the 10th percentile cut-off, health status was affected by past exposure and predicted subsequent exposure in smelters, but not in fabrication. A Traditional cox model was appropriate for fabricators; the hazard ratio was 1.51(95% CI: 1.12 - 2.06) and wa...
Marginal structural models (MSMs) and inverse probability weighting can be used to estimate risk ... more Marginal structural models (MSMs) and inverse probability weighting can be used to estimate risk in a cohort of active workers if there is a time-varying confounder (e.g., health status) affected by prior exposure-a feature of the healthy worker survivor effect. We applied Cox MSMs in a study of incident ischemic heart disease and exposure to particulate matter with aerodynamic diameter of 2.5 μm or less (PM2.5) in a cohort of 12,949 actively employed aluminum workers in the United States. The cohort was stratified by work process into workers in smelting facilities, herein referred to as "smelters" and workers in fabrication facilities, herein referred to as "fabricators." The outcome was assessed by using medical claims data from 1998 to 2012. A composite risk score based on insurance claims was treated as a time-varying measure of health status. Binary PM2.5 exposure was defined by the 10th-percentile cutoff for each work process. Health status was associated ...
The healthy worker survivor effect (HWSE) is a well-recognised bias usually described as a form o... more The healthy worker survivor effect (HWSE) is a well-recognised bias usually described as a form of selection bias or confounding. A more precise epidemiologic explanation, however, has been elusive. We distinguish several components of the HWSE and suggest methods for bias correction in occupational cohort studies. Although generally referred to a single effect, we demonstrate using simulation studies that there are in fact four distinct aspects of the HWSE. Two aspects, (1) time-varying confounding by variables on the causal pathway and (2) heterogeneity in susceptibility, are functions of the underlying process of the exposure and disease under study. The other two, (3) left truncation and (4) right truncation, are functions of how the data are collected, ie the study design. We quantify the bias induced by each aspect of HWSE on dose-response parameter estimates and apply methods designed to reduce the bias. We find that causal techniques, eg, g-estimation and IPTW, can correct f...
To examine further the association between endotoxin and risk of lung cancer among Shanghai women... more To examine further the association between endotoxin and risk of lung cancer among Shanghai women textile workers in an extended follow-up of the cohort. The initial follow-up indicated an inverse exposure-response relation. We updated a case-cohort study nested within a cohort of 267 400 women. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. Endotoxin exposures were based on a quantitative job/exposure matrix. Relative risks (hazard ratios [HR]) associated with cumulative exposure, adjusted for age and smoking history, were estimated by Cox proportional hazards modelling adapted for the case-cohort design. We conducted exposure-response trend analyses for cumulative exposures lagged by 0, 10, and 20 years, and separately for time windows of <15 and >15 years since first exposure. Overall, we observed no associations between cu...
We estimated the effect of cumulative exposure to PM2.5 on the incidence of ischaemic heart disea... more We estimated the effect of cumulative exposure to PM2.5 on the incidence of ischaemic heart disease (IHD) in aluminium workers followed for 15 years, adjusting for the healthy worker survivor effect. In previous analyses, higher cumulative exposure was found to be associated with lower mortality in this population. We used longitudinal TMLE to estimate the cumulative risk of ischaemic heart disease in the cohort if constantly exposed above an exposure cut-off and compared it to the risk if constantly exposed below. We stratified all analyses by work process because exposures were an order of magnitude higher in smelters than fabrication facilities. We selected cut-offs a priori at the median and 10th percentile exposure within each sub-cohort. Among the smelter workers, we estimated an increase in IHD risk of 2.1% (p = 0.22) after 15 years, comparing the always exposed to never exposed cohort using the median cut-off of 1.77 mg/m(3). The difference was 2.9% (p = 0.01) using the 10th...
Journal of Exposure Science and Environmental Epidemiology, 2014
Fine particulate matter (PM 2.5 ) in air pollution, primarily from combustion sources, is recogni... more Fine particulate matter (PM 2.5 ) in air pollution, primarily from combustion sources, is recognized as an important risk factor for cardiovascular events but studies of workplace PM 2.5 exposure are rare. We conducted a prospective study of exposure to PM 2.5 and incidence of ischemic heart disease (IHD) in a cohort of 11,966 US aluminum workers. Incident IHD was identified from medical claims data from 1998 to 2008. Quantitative metrics were developed for recent exposure (within the last year) and cumulative exposure; however, we emphasize recent exposure in the absence of interpretable work histories before follow-up. IHD was modestly associated with recent PM 2.5 overall. In analysis restricted to recent exposures estimated with the highest confidence, the hazard ratio (HR) increased to 1.78 (95% CI: 1.02, 3.11) in the second quartile and remained elevated. When the analysis was stratified by work process, the HR rose monotonically to 1.5 in both smelter and fabrication facilities, though exposure was almost an order of magnitude higher in smelters. The differential exposure-response may be due to differences in exposure composition or healthy worker survivor effect. These results are consistent with the air pollution and cigarette smoke literature; recent exposure to PM 2.5 in the workplace appears to increase the risk of IHD incidence.
Due to the heavy and expanding agricultural use of neurotoxic pesticides suspected to affect dopa... more Due to the heavy and expanding agricultural use of neurotoxic pesticides suspected to affect dopaminergic neurons, it is imperative to closely examine the role of pesticides in the development of Parkinson's disease (PD). We focus our investigation on pesticide use in California's heavily agricultural central valley by utilizing a unique pesticide use reporting system. From 2001 to 2007, we enrolled 362 incident PD cases and 341 controls living in the Central Valley of California. Employing our geographic information system model, we estimated ambient exposures to the pesticides ziram, maneb, and paraquat at work places and residences from 1974 to 1999. At workplaces, combined exposure to ziram, maneb, and paraquat increased risk of PD three-fold (OR: 3.09; 95% CI: 1.69, 5.64) and combined exposure to ziram and paraquat, excluding maneb exposure, was associated with a 80% increase in risk (OR:1.82; 95% CI: 1.03, 3.21). Risk estimates for ambient workplace exposure were greater than for exposures at residences and were especially high for younger onset PD patients and when exposed in both locations. Our study is the first to implicate ziram in PD etiology. Combined ambient exposure to ziram and paraquat as well as combined ambient exposure to maneb and paraquat at both workplaces and residences increased PD risk substantially. Those exposed to ziram, maneb, and paraquat together experienced the greatest increase in PD risk. Our results suggest that pesticides affecting different mechanisms that contribute to dopaminergic neuron death may act together to increase the risk of PD considerably.
Background: Occupational exposure to mineral oil-based metalworking fluids has been consistently ... more Background: Occupational exposure to mineral oil-based metalworking fluids has been consistently linked with skin conditions such as contact dermatitis and squamous cell skin cancer, especially of the scrotum. We examined the incidence of malignant melanoma in a study of autoworkers. Methods: We followed a cohort of autoworkers from 1985 through 2004 for cancer incidence. Hazard ratios (HRs) were estimated in Cox models for cumulative exposure to total particulate of straight fluid (neat oil), soluble fluid (oil emulsified in water), and synthetic fluid (no oil). Exposure was partitioned into time windows by latency and by calendar periods defined by changes in the content of polycyclic aromatic hydrocarbon in the refined oils. The population was restricted to workers born after 1935. We examined the dateof-birth restriction in a sensitivity analysis. Results: On the basis of 76 incident cases of malignant melanoma in the cohort of 14,139 white males, the HR was 1.99 (95% confidence interval ϭ 1.00 -3.96) for the highest category of straight fluid. Risk was greatest in the most recent time window. Penalized splines suggested a linear exposure-response over the full range of exposure. The change in HR for malignant melanoma per mg/m 3year of straight fluid increased monotonically from 1.01 to 1.04, when the date-of-birth restriction increased from 1925 to 1945 in 5-year intervals. Results for soluble fluid were more modest. There was no association with synthetic fluid. Conclusions: Results provide evidence, based on quantitative measures of metalworking fluid, that oil-based fluid, particularly straight mineral oils, are associated with the incidence of malignant melanoma.
Objective-Exposure to endotoxin has been consistently associated with a reduced risk of lung canc... more Objective-Exposure to endotoxin has been consistently associated with a reduced risk of lung cancer. However, there is a paucity of information regarding temporal aspects of this relationship. The objective of this study was to investigate the associations between contiguous windows of endotoxin exposure and risk of lung cancer.
Background-Metalworking fluids (MWF) -straight, soluble, and synthetic -have overlapping componen... more Background-Metalworking fluids (MWF) -straight, soluble, and synthetic -have overlapping components. We derived constituent-based metrics of polycyclic aromatic hydrocarbons (PAHs), water-based MWF, biocides, and nitrosamines to account for this overlap and examined their relations with cancer incidence.
Exposure to metalworking fluid (MWF) causes respiratory outcomes such as asthma and chronic bronc... more Exposure to metalworking fluid (MWF) causes respiratory outcomes such as asthma and chronic bronchitis, as well as symptoms including phlegm and wheezing. Chronic obstructive pulmonary disease (COPD) encompasses these outcomes, and so is a potential result of MWF exposure. Recent evidence based on g-estimation suggests that reducing exposure to MWF would substantially decrease years of life lost due to COPD. The objective of this analysis is to examine the exposure-response relationship between direct exposure to MWF and COPD mortality in a large occupational cohort. Hazard ratios were estimated using Cox proportional hazards models for the association between cumulative exposure to the thoracic fraction (PM9.8) of straight, synthetic, or soluble MWF and COPD mortality. Subjects directly exposed to each fluid type were compared to those who were never directly exposed (assembly workers). Hazard ratios for exposure quartiles increased in a non-monotonic fashion, with a maximum of 1.6...
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Papers by Sadie Costello