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1.  The Diesel Exhaust in Miners Study: V. Evaluation of the Exposure Assessment Methods 
Annals of Occupational Hygiene  2012;56(4):389-400.
Exposure to respirable elemental carbon (REC), a component of diesel exhaust (DE), was assessed for an epidemiologic study investigating the association between DE and mortality, particularly from lung cancer, among miners at eight mining facilities from the date of dieselization (1947–1967) through 1997. To provide insight into the quality of the estimates for use in the epidemiologic analyses, several approaches were taken to evaluate the exposure assessment process and the quality of the estimates. An analysis of variance was conducted to evaluate the variability of 1998–2001 REC measurements within and between exposure groups of underground jobs. Estimates for the surface exposure groups were evaluated to determine if the arithmetic means (AMs) of the REC measurements increased with increased proximity to, or use of, diesel-powered equipment, which was the basis on which the surface groups were formed. Estimates of carbon monoxide (CO) (another component of DE) air concentrations in 1976–1977, derived from models developed to predict estimated historical exposures, were compared to 1976–1977 CO measurement data that had not been used in the model development. Alternative sets of estimates were developed to investigate the robustness of various model assumptions. These estimates were based on prediction models using: (i) REC medians rather AMs, (ii) a different CO:REC proportionality than a 1:1 relation, and (iii) 5-year averages of historical CO measurements rather than modeled historical CO measurements and DE-related determinants. The analysis of variance found that in three of the facilities, most of the between-group variability in the underground measurements was explained by the use of job titles. There was relatively little between-group variability in the other facilities. The estimated REC AMs for the surface exposure groups rose overall from 1 to 5 μg m−3 as proximity to, and use of, diesel equipment increased. The alternative estimates overall were highly correlated (∼0.9) with the primary set of estimates. The median of the relative differences between the 1976–1977 CO measurement means and the 1976–1977 estimates for six facilities was 29%. Comparison of estimated CO air concentrations from the facility-specific prediction models with historical CO measurement data found an overall agreement similar to that observed in other epidemiologic studies. Other evaluations of components of the exposure assessment process found moderate to excellent agreement. Thus, the overall evidence suggests that the estimates were likely accurate representations of historical personal exposure levels to DE and are useful for epidemiologic analyses.
PMCID: PMC3324483
diesel exhaust; elemental carbon; exposure assessment; mining
2.  The Diesel Exhaust in Miners Study: IV. Estimating Historical Exposures to Diesel Exhaust in Underground Non-metal Mining Facilities 
Annals of Occupational Hygiene  2010;54(7):774-788.
We developed quantitative estimates of historical exposures to respirable elemental carbon (REC) for an epidemiologic study of mortality, including lung cancer, among diesel-exposed miners at eight non-metal mining facilities [the Diesel Exhaust in Miners Study (DEMS)]. Because there were no historical measurements of diesel exhaust (DE), historical REC (a component of DE) levels were estimated based on REC data from monitoring surveys conducted in 1998–2001 as part of the DEMS investigation. These values were adjusted for underground workers by carbon monoxide (CO) concentration trends in the mines derived from models of historical CO (another DE component) measurements and DE determinants such as engine horsepower (HP; 1 HP = 0.746 kW) and mine ventilation. CO was chosen to estimate historical changes because it was the most frequently measured DE component in our study facilities and it was found to correlate with REC exposure. Databases were constructed by facility and year with air sampling data and with information on the total rate of airflow exhausted from the underground operations in cubic feet per minute (CFM) (1 CFM = 0.0283 m3 min−1), HP of the diesel equipment in use (ADJ HP), and other possible determinants. The ADJ HP purchased after 1990 (ADJ HP1990+) was also included to account for lower emissions from newer, cleaner engines. Facility-specific CO levels, relative to those in the DEMS survey year for each year back to the start of dieselization (1947–1967 depending on facility), were predicted based on models of observed CO concentrations and log-transformed (Ln) ADJ HP/CFM and Ln(ADJ HP1990+). The resulting temporal trends in relative CO levels were then multiplied by facility/department/job-specific REC estimates derived from the DEMS surveys personal measurements to obtain historical facility/department/job/year-specific REC exposure estimates. The facility-specific temporal trends of CO levels (and thus the REC estimates) generated from these models indicated that CO concentrations had been generally greater in the past than during the 1998–2001 DEMS surveys, with the highest levels ranging from 100 to 685% greater (median: 300%). These levels generally occurred between 1970 and the early 1980s. A comparison of the CO facility-specific model predictions with CO air concentration measurements from a 1976–1977 survey external to the modeling showed that our model predictions were slightly lower than those observed (median relative difference of 29%; range across facilities: 49 to –25%). In summary, we successfully modeled past CO concentration levels using selected determinants of DE exposure to derive retrospective estimates of REC exposure. The results suggested large variations in REC exposure levels both between and within the underground operations of the facilities and over time. These REC exposure estimates were in a plausible range and were used in the investigation of exposure–response relationships in epidemiologic analyses.
PMCID: PMC2953557  PMID: 20876235
elemental carbon; miners; exposure assessment; carbon monoxide; diesel exhaust
3.  The Diesel Exhaust in Miners Study: II. Exposure Monitoring Surveys and Development of Exposure Groups 
Annals of Occupational Hygiene  2010;54(7):747-761.
Air monitoring surveys were conducted between 1998 and 2001 at seven non-metal mining facilities to assess exposure to respirable elemental carbon (REC), a component of diesel exhaust (DE), for an epidemiologic study of miners exposed to DE. Personal exposure measurements were taken on workers in a cross-section of jobs located underground and on the surface. Air samples taken to measure REC were also analyzed for respirable organic carbon (ROC). Concurrent measurements to assess exposure to nitric oxide (NO) and nitrogen dioxide (NO2), two gaseous components of DE, were also taken. The REC measurements were used to develop quantitative estimates of average exposure levels by facility, department, and job title for the epidemiologic analysis. Each underground job was assigned to one of three sets of exposure groups from specific to general: (i) standardized job titles, (ii) groups of standardized job titles combined based on the percentage of time in the major underground areas, and (iii) larger groups based on similar area carbon monoxide (CO) air concentrations. Surface jobs were categorized based on their use of diesel equipment and proximity to DE. A total of 779 full-shift personal measurements were taken underground. The average REC exposure levels for underground jobs with five or more measurements ranged from 31 to 58 μg m−3 at the facility with the lowest average exposure levels and from 313 to 488 μg m−3 at the facility with the highest average exposure levels. The average REC exposure levels for surface workers ranged from 2 to 6 μg m−3 across the seven facilities. There was much less contrast in the ROC compared with REC exposure levels measured between surface and underground workers within each facility, as well as across the facilities. The average ROC levels underground ranged from 64 to 195 μg m−3, while on the surface, the average ROC levels ranged from 38 to 71 μg m−3 by facility, an ∼2- to 3-fold difference. The average NO and NO2 levels underground ranged from 0.20 to 1.49 parts per million (ppm) and from 0.10 to 0.60 ppm, respectively, and were ∼10 times higher than levels on the surface, which ranged from 0.02 to 0.11 ppm and from 0.01 to 0.06 ppm, respectively. The ROC, NO, and NO2 concentrations underground were correlated with the REC levels (r = 0.62, 0.71, and 0.62, respectively). A total of 80% of the underground jobs were assigned an exposure estimate based on measurements taken for the specific job title or for other jobs with a similar percentage of time spent in the major underground work areas. The average REC exposure levels by facility were from 15 to 64 times higher underground than on the surface. The large contrast in exposure levels measured underground versus on the surface, along with the differences between the mining facilities and between underground jobs within the facilities resulted in a wide distribution in the exposure estimates for evaluation of exposure–response relationships in the epidemiologic analyses.
PMCID: PMC2953556  PMID: 20876232
diesel exhaust; miners; elemental carbon; exposure assessment; job groups
4.  Evaluation of an exposure assessment used in epidemiological studies of diesel exhaust and lung cancer in underground mines 
Critical Reviews in Toxicology  2012;42(7):599-612.
NIOSH/NCI (National Institute of Occupational Safety and Health and National Cancer Institute) developed exposure estimates for respirable elemental carbon (REC) as a surrogate for exposure to diesel exhaust (DE) for different jobs in eight underground mines by year beginning in the 1940s—1960s when diesel equipment was first introduced into these mines. These estimates played a key role in subsequent epidemiological analyses of the potential relationship between exposure to DE and lung cancer conducted in these mines. We report here on a reanalysis of some of the data from this exposure assessment. Because samples of REC were limited primarily to 1998–2001, NIOSH/NCI used carbon monoxide (CO) as a surrogate for REC. In addition, because CO samples were limited, particularly in the earlier years, they used the ratio of diesel horsepower (HP) to the mine air exhaust rate as a surrogate for CO. There are considerable uncertainties connected with each of these surrogate-based steps. The estimates of HP appear to involve considerable uncertainty, although we had no data upon which to evaluate the magnitude of this uncertainty. A sizable percentage (45%) of the CO samples used in the HP to CO model was below the detection limit which required NIOSH/NCI to assign CO values to these samples. In their preferred REC estimates, NIOSH/NCI assumed a linear relation between C0 and REC, although they provided no credible support for that assumption. Their assumption of a stable relationship between HP and CO also is questionable, and our reanalysis found a statistically significant relationship in only one-half of the mines. We re-estimated yearly REC exposures mainly using NIOSH/NCI methods but with some important differences: (i) rather than simply assuming a linear relationship, we used data from the mines to estimate the CO—REC relationship; (ii) we used a different method for assigning values to nondetect CO measurements; and (iii) we took account of statistical uncertainty to estimate bounds for REC exposures. This exercise yielded significantly different exposure estimates than estimated by NIOSH/NCI. However, this analysis did not incorporate the full range of uncertainty in REC exposures because of additional uncertainties in the assumptions underlying the modeling and in the underlying data (e.g. HP and mine exhaust rates). Estimating historical exposures in a cohort is generally a very difficult undertaking. However, this should not prevent one from recognizing the uncertainty in the resulting estimates in any use made of them.
PMCID: PMC3423303  PMID: 22594934
Exposure assessment; underground mines; diesel exhaust; carbon monoxide; respirable elemental carbon
5.  The Diesel Exhaust in Miners Study: III. Interrelations between Respirable Elemental Carbon and Gaseous and Particulate Components of Diesel Exhaust derived from Area Sampling in Underground Non-metal Mining Facilities 
Annals of Occupational Hygiene  2010;54(7):762-773.
Diesel exhaust (DE) has been implicated as a potential lung carcinogen. However, the exact components of DE that might be involved have not been clearly identified. In the past, nitrogen oxides (NOx) and carbon oxides (COx) were measured most frequently to estimate DE, but since the 1990s, the most commonly accepted surrogate for DE has been elemental carbon (EC). We developed quantitative estimates of historical exposure levels of respirable elemental carbon (REC) for an epidemiologic study of mortality, particularly lung cancer, among diesel-exposed miners by back-extrapolating 1998–2001 REC exposure levels using historical measurements of carbon monoxide (CO). The choice of CO was based on the availability of historical measurement data. Here, we evaluated the relationship of REC with CO and other current and historical components of DE from side-by-side area measurements taken in underground operations of seven non-metal mining facilities. The Pearson correlation coefficient of the natural log-transformed (Ln)REC measurements with the Ln(CO) measurements was 0.4. The correlation of REC with the other gaseous, organic carbon (OC), and particulate measurements ranged from 0.3 to 0.8. Factor analyses indicated that the gaseous components, including CO, together with REC, loaded most strongly on a presumed ‘Diesel exhaust’ factor, while the OC and particulate agents loaded predominantly on other factors. In addition, the relationship between Ln(REC) and Ln(CO) was approximately linear over a wide range of REC concentrations. The fact that CO correlated with REC, loaded on the same factor, and increased linearly in log–log space supported the use of CO in estimating historical exposure levels to DE.
PMCID: PMC2953555  PMID: 20876234
carbon dioxide; carbon monoxide; diesel exhaust; elemental carbon; miners; nitric oxide; nitrogen dioxide; particulates
6.  The Diesel Exhaust in Miners Study: A Cohort Mortality Study With Emphasis on Lung Cancer 
Current information points to an association between diesel exhaust exposure and lung cancer and other mortality outcomes, but uncertainties remain.
We undertook a cohort mortality study of 12 315 workers exposed to diesel exhaust at eight US non-metal mining facilities. Historical measurements and surrogate exposure data, along with study industrial hygiene measurements, were used to derive retrospective quantitative estimates of respirable elemental carbon (REC) exposure for each worker. Standardized mortality ratios and internally adjusted Cox proportional hazard models were used to evaluate REC exposure–associated risk. Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death.
Standardized mortality ratios for lung cancer (1.26, 95% confidence interval [CI] = 1.09 to 1.44), esophageal cancer (1.83, 95% CI = 1.16 to 2.75), and pneumoconiosis (12.20, 95% CI = 6.82 to 20.12) were elevated in the complete cohort compared with state-based mortality rates, but all-cause, bladder cancer, heart disease, and chronic obstructive pulmonary disease mortality were not. Differences in risk by worker location (ever-underground vs surface only) initially obscured a positive diesel exhaust exposure–response relationship with lung cancer in the complete cohort, although it became apparent after adjustment for worker location. The hazard ratios (HRs) for lung cancer mortality increased with increasing 15-year lagged cumulative REC exposure for ever-underground workers with 5 or more years of tenure to a maximum in the 640 to less than 1280 μg/m3-y category compared with the reference category (0 to <20 μg/m3-y; 30 deaths compared with eight deaths of the total of 93; HR = 5.01, 95% CI = 1.97 to 12.76) but declined at higher exposures. Average REC intensity hazard ratios rose to a plateau around 32 μg/m3. Elevated hazard ratios and evidence of exposure–response were also seen for surface workers. The association between diesel exhaust exposure and lung cancer risk remained after inclusion of other work-related potentially confounding exposures in the models and were robust to alternative approaches to exposure derivation.
The study findings provide further evidence that exposure to diesel exhaust increases risk of mortality from lung cancer and have important public health implications.
PMCID: PMC3373218  PMID: 22393207
7.  The Diesel Exhaust in Miners Study: A Nested Case–Control Study of Lung Cancer and Diesel Exhaust 
Most studies of the association between diesel exhaust exposure and lung cancer suggest a modest, but consistent, increased risk. However, to our knowledge, no study to date has had quantitative data on historical diesel exposure coupled with adequate sample size to evaluate the exposure–response relationship between diesel exhaust and lung cancer. Our purpose was to evaluate the relationship between quantitative estimates of exposure to diesel exhaust and lung cancer mortality after adjustment for smoking and other potential confounders.
We conducted a nested case–control study in a cohort of 12 315 workers in eight non-metal mining facilities, which included 198 lung cancer deaths and 562 incidence density–sampled control subjects. For each case subject, we selected up to four control subjects, individually matched on mining facility, sex, race/ethnicity, and birth year (within 5 years), from all workers who were alive before the day the case subject died. We estimated diesel exhaust exposure, represented by respirable elemental carbon (REC), by job and year, for each subject, based on an extensive retrospective exposure assessment at each mining facility. We conducted both categorical and continuous regression analyses adjusted for cigarette smoking and other potential confounding variables (eg, history of employment in high-risk occupations for lung cancer and a history of respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death (case subjects)/reference date (control subjects). All statistical tests were two-sided.
We observed statistically significant increasing trends in lung cancer risk with increasing cumulative REC and average REC intensity. Cumulative REC, lagged 15 years, yielded a statistically significant positive gradient in lung cancer risk overall (P trend = .001); among heavily exposed workers (ie, above the median of the top quartile [REC ≥ 1005 μg/m3-y]), risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure. Among never smokers, odd ratios were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less than 304, and 304 μg/m3-y or more, respectively. We also observed an interaction between smoking and 15-year lagged cumulative REC (P interaction = .086) such that the effect of each of these exposures was attenuated in the presence of high levels of the other.
Our findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.
PMCID: PMC3369553  PMID: 22393209
8.  Diesel exhaust in miners study: how to understand the findings? 
The Diesel Exhaust in Miners Study (DEMS) is an outstanding epidemiological project on the association between occupational diesel exhaust exposures, measured as long-term respirable elemental carbon (REC) estimates, and lung cancer mortality in a large cohort of US miners. Two articles published recently (Attfield et al. (J Natl Cancer Inst Epub, [2012]), Silverman et al. (J Natl Cancer Inst Epub, [2012])) dsescribed the epidemiological findings. These papers are expected to have considerable impact on the evaluation of the carcinogenic potential of diesel exhaust and, furthermore, on occupational and environmental limit value discussions related to diesel motor emissions and particle exposures. DEMS found remarkable exposure-response relationships between REC exposure estimates and lung cancer mortality - conditional on a pronounced effect of surface vs. underground work on lung cancer risk. If this risk factor is ignored the estimated REC-lung cancer association is attenuated substantially. The authors relied on this risk factor in their main analyses. However, this factor “surface/underground work” remained unexplained. The factor lead the authors to introduce unusual cross-product terms of location and smoking in adjustment procedures and even caused the authors to hypothesize that high REC exposures are protective against lung cancer excess risks due to smoking. To understand the reliability of these conclusions, we should ask basic questions about the data collection process in DEMS: Did the mortality follow-up procedures suffer from errors like those that affected the NCI formaldehyde cohort study? Are the REC and/or smoking data reliable, and are these data collected/constructed in such a way that the procedures allow valid comparisons between surface and underground workers? Without clarifying the issues raised in this Commentary the Diesel Exhaust in Miners Study remains to be difficult to interpret.
PMCID: PMC3403854  PMID: 22676299
Diesel exhaust in miners study; Epidemiology; Lung cancer; Respirable elemental carbon
9.  Exposure to silica and silicosis among tin miners in China: exposure-response analyses and risk assessment 
OBJECTIVES—To investigate the risk of silicosis among tin miners and to investigate the relation between silicosis and cumulative exposure to dust (Chinese total dust and respirable crystalline silica dust).
METHODS—A cohort study of 3010 miners exposed to silica dust and employed for at least 1 year during 1960-5 in any of four Chinese tin mines was conducted. Historical total dust data from China were used to create a job exposure matrix for facility, job title, and calendar year. The total dust exposure data from China were converted to estimates of exposure to respirable crystalline silica for comparison with findings from other epidemiological studies of silicosis. Each worker's work history was abstracted from the complete employment records in mine files. Diagnoses of silicosis were based on 1986 Chinese pneumoconiosis Roentgen diagnostic criteria, which classified silicosis as stages I-III—similar to an International Labour Organisation (ILO) classification of 1/1 or greater.
RESULTS—There were 1015 (33.7%) miners identified with silicosis, who had a mean age of 48.3 years, with a mean of 21.3 years after first exposure (equivalent to 11.0 net years in a dusty job). Among those who had silicosis, 684 miners (67.4%) developed silicosis after exposure ended (a mean of 3.7 years after). The risk of silicosis was strongly related to cumulative exposure to silica dust and was well fitted by the Weibull distribution, with the risk of silicosis less than 0.1% when the Chinese measure of cumulative exposure to total dust (CTD) was under 10 mg/m3-years (or 0.36 mg/m3-years of respirable crystalline silica), increasing to 68.7% when CTD exposure was 150 mg/m3-years (or 5.4 mg/m3-years of respirable crystalline silica). Latency period was not correlated to the risk of silicosis or cumulative dose of exposure. This study predicts about a 36% cumulative risk of silicosis for a 45 year lifetime exposure to these tin mine dusts at the CTD exposure standard of 2 mg/m3, and a 55% risk at 45 years exposure to the current United States Occupational Safety and Health Administration and Mine Safety and Health Administration standards of 0.1 mg/m3 100% respirable crystalline silica dust.
CONCLUSIONS—A clear exposure-response relation was detected for silicosis in Chinese tin miners. The study results were similar to most, but not all, findings from other large scale exposure-response studies.

Keywords: silicosis; exposure to silica; dose-response relation
PMCID: PMC1740032  PMID: 11119632
10.  A Retrospective Assessment of Occupational Exposure to Elemental Carbon in the U.S. Trucking Industry 
Environmental Health Perspectives  2011;119(7):997-1002.
Background: Despite considerable epidemiologic evidence about the health effects of chronic exposure to vehicle exhaust, efforts at defining the extent of risk have been limited by the lack of historical exposure measurements suitable for use in epidemiologic studies and for risk assessment.
Objectives: We sought to reconstruct exposure to elemental carbon (EC), a marker of diesel and other vehicle exhaust exposure, in a large national cohort of U.S. trucking industry workers.
Methods: We identified the predictors of measured exposures based on a statistical model and used this information to extrapolate exposures across the cohort nationally. These estimates were adjusted for changes in work-related conditions over time based on a previous exposure assessment of this industry, and for changes in background levels based on a trend analysis of historical air pollution data, to derive monthly estimates of EC exposure for each job and trucking terminal combination between 1971 and 2000.
Results: Occupational exposure to EC declined substantially over time, and we found significant variability in estimated exposures both within and across job groups, trucking terminals, and regions of the United States. Average estimated EC exposures during a typical work shift ranged from < 1 μg/m3 in the lowest exposed category in the 1990s to > 40 μg/m3 for workers in the highest exposed jobs in the 1970s.
Conclusions: Our results provide a framework for understanding changes over time in exposure to EC in the U.S. trucking industry. Our assessment should minimize exposure misclassification by capturing variation among terminals and across U.S. regions, and changes over time.
PMCID: PMC3222985  PMID: 21447452
air pollution; diesel; lung cancer; occupational health; traffic exposure; trucking industry
11.  Mobility of diesel versus non-diesel coal miners: some evidence on the healthy worker effect. 
Workers who are particularly susceptible to the effects of their occupational exposure, from the perspective of the healthy worker effect, soon leave the workplace. The result of this mobility, called survival bias, is that cross sectional studies based on the survivors underestimate the true risk of occupational exposures. Two questions are addressed in this empirical study of the "survival bias" component of the "healthy worker" effect. Do miners with respiratory impairment or symptoms disproportionately leave jobs that have a potentially harmful respiratory exposure? And does the presence of an additional potentially harmful respiratory exposure, in this case diesel emissions, accelerate the rate of mobility for miners with respiratory impairment or symptoms? No confirmation was found for the survival effect in a study of 738 diesel and 420 non-diesel US underground coal miners. No additional increment in mobility was associated with exposure to both coal mine dust and diesel emissions.
PMCID: PMC1009283  PMID: 6722047
12.  Comparison of Algorithm-based Estimates of Occupational Diesel Exhaust Exposure to Those of Multiple Independent Raters in a Population-based Case–Control Study 
Annals of Occupational Hygiene  2012;57(4):470-481.
Algorithm-based exposure assessments based on patterns in questionnaire responses and professional judgment can readily apply transparent exposure decision rules to thousands of jobs quickly. However, we need to better understand how algorithms compare to a one-by-one job review by an exposure assessor. We compared algorithm-based estimates of diesel exhaust exposure to those of three independent raters within the New England Bladder Cancer Study, a population-based case–control study, and identified conditions under which disparities occurred in the assessments of the algorithm and the raters.
Occupational diesel exhaust exposure was assessed previously using an algorithm and a single rater for all 14 983 jobs reported by 2631 study participants during personal interviews conducted from 2001 to 2004. Two additional raters independently assessed a random subset of 324 jobs that were selected based on strata defined by the cross-tabulations of the algorithm and the first rater’s probability assessments for each job, oversampling their disagreements. The algorithm and each rater assessed the probability, intensity and frequency of occupational diesel exhaust exposure, as well as a confidence rating for each metric. Agreement among the raters, their aggregate rating (average of the three raters’ ratings) and the algorithm were evaluated using proportion of agreement, kappa and weighted kappa (κw). Agreement analyses on the subset used inverse probability weighting to extrapolate the subset to estimate agreement for all jobs. Classification and Regression Tree (CART) models were used to identify patterns in questionnaire responses that predicted disparities in exposure status (i.e., unexposed versus exposed) between the first rater and the algorithm-based estimates.
For the probability, intensity and frequency exposure metrics, moderate to moderately high agreement was observed among raters (κw = 0.50–0.76) and between the algorithm and the individual raters (κw = 0.58–0.81). For these metrics, the algorithm estimates had consistently higher agreement with the aggregate rating (κw = 0.82) than with the individual raters. For all metrics, the agreement between the algorithm and the aggregate ratings was highest for the unexposed category (90–93%) and was poor to moderate for the exposed categories (9–64%). Lower agreement was observed for jobs with a start year <1965 versus ≥1965. For the confidence metrics, the agreement was poor to moderate among raters (κw = 0.17–0.45) and between the algorithm and the individual raters (κw = 0.24–0.61). CART models identified patterns in the questionnaire responses that predicted a fair-to-moderate (33–89%) proportion of the disagreements between the raters’ and the algorithm estimates.
The agreement between any two raters was similar to the agreement between an algorithm-based approach and individual raters, providing additional support for using the more efficient and transparent algorithm-based approach. CART models identified some patterns in disagreements between the first rater and the algorithm. Given the absence of a gold standard for estimating exposure, these patterns can be reviewed by a team of exposure assessors to determine whether the algorithm should be revised for future studies.
PMCID: PMC3629988  PMID: 23184256
case–control; diesel exhaust; expert judgement; exposure assessment
13.  Lung Cancer and Vehicle Exhaust in Trucking Industry Workers 
Environmental Health Perspectives  2008;116(10):1327-1332.
An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties.
We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure.
Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey.
Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk.
Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.
PMCID: PMC2569090  PMID: 18941573
diesel exhaust; lung cancer; occupational exposure; particulate matter; traffic
14.  A case–control study relating railroad worker mortality to diesel exhaust exposure using a threshold regression model 
A case–control study of lung cancer mortality in U.S. railroad workers in jobs with and without diesel exhaust exposure is reanalyzed using a new threshold regression methodology. The study included 1256 workers who died of lung cancer and 2385 controls who died primarily of circulatory system diseases. Diesel exhaust exposure was assessed using railroad job history from the US Railroad Retirement Board and an industrial hygiene survey. Smoking habits were available from next-of-kin and potential asbestos exposure was assessed by job history review. The new analysis reassesses lung cancer mortality and examines circulatory system disease mortality. Jobs with regular exposure to diesel exhaust had a survival pattern characterized by an initial delay in mortality, followed by a rapid deterioration of health prior to death. The pattern is seen in subjects dying of lung cancer, circulatory system diseases, and other causes. The unique pattern is illustrated using a new type of Kaplan–Meier survival plot in which the time scale represents a measure of disease progression rather than calendar time. The disease progression scale accounts for a healthy-worker effect when describing the effects of cumulative exposures on mortality.
PMCID: PMC2642623  PMID: 19221608
Biostatistics; Cardiovascular disease; Death; Disease progression; Environmetrics; Epidemiology; Exposure risk; First hitting time; Health status; Healthy worker effect; Kaplan–Meier plot; Latent process; Lung cancer; Occupational health; Stochastic process; Survival analysis; Wiener process; Work environment
15.  Lung Cancer and Elemental Carbon Exposure in Trucking Industry Workers 
Environmental Health Perspectives  2012;120(9):1301-1306.
Background: Diesel exhaust has been considered to be a probable lung carcinogen based on studies of occupationally exposed workers. Efforts to define lung cancer risk in these studies have been limited in part by lack of quantitative exposure estimates.
Objective: We conducted a retrospective cohort study to assess lung cancer mortality risk among U.S. trucking industry workers. Elemental carbon (EC) was used as a surrogate of exposure to engine exhaust from diesel vehicles, traffic, and loading dock operations.
Methods: Work records were available for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. A statistical model based on a national exposure assessment was used to estimate historical work-related exposures to EC. Lung cancer mortality was ascertained through the year 2000, and associations with cumulative and average EC were estimated using proportional hazards models.
Results: Duration of employment was inversely associated with lung cancer risk consistent with a healthy worker survivor effect and a cohort composed of prevalent hires. After adjusting for employment duration, we noted a suggestion of a linear exposure–response relationship. For each 1,000-µg/m3 months of cumulative EC, based on a 5-year exposure lag, the hazard ratio (HR) was 1.07 [95% confidence interval (CI): 0.99, 1.15] with a similar association for a 10-year exposure lag [HR = 1.09 (95% CI: 0.99, 1.20)]. Average exposure was not associated with relative risk.
Conclusions: Lung cancer mortality in trucking industry workers increased in association with cumulative exposure to EC after adjusting for negative confounding by employment duration.
PMCID: PMC3440130  PMID: 22739103
diesel exhaust; elemental carbon; lung cancer; occupational exposure; particulate matter; traffic
16.  Occupational Exposure to Volatile Organic Compounds and Aldehydes in the U.S. Trucking Industry 
Environmental science & technology  2007;41(20):7152-7158.
Diesel exhaust is a complex chemical mixture that has been linked to lung cancer mortality in a number of epidemiologic studies. However, the dose–response relationship remains largely undefined, and the specific components responsible for carcinogenicity have not been identified. Although previous focus has been on the particulate phase, diesel exhaust includes a vapor phase of numerous volatile organic compounds (VOCs) and aldehydes that are either known or suspected carcinogens, such as 1,3-butadiene, benzene, and formaldehyde. However, there are relatively few studies that quantify exposure to VOCs and aldehydes in diesel-heavy and other exhaust-related microenvironments. As part of a nationwide assessment of exposure to diesel exhaust in the trucking industry, we collected measurements of VOCs and aldehydes at 15 different U.S. trucking terminals and in city truck drivers (with 6 repeat site visits), observing average shift concentrations in truck cabs and at multiple background and work area locations within each terminal. In this paper, we characterize occupational exposure to 18 different VOCs and aldehydes, as well as relationships with particulate mass (elemental carbon in PM < 1 μ m and PM2.5) across locations to determine source characteristics. Our results show that occupational exposure to VOCs and aldehydes varies significantly across the different sampling locations within each terminal, with significantly higher exposures noted in the work environments over background levels (p < 0.01). A structural equation model performed well in predicting terminal exposures to VOCs and aldehydes as a function of job, background levels, weather conditions, proximity to a major road, and geographic location (R2 = 0.2–0.4 work area; R2 = 0.5–0.9 background).
PMCID: PMC2386139  PMID: 17993162
17.  Economic Activity and Trends in Ambient Air Pollution 
Environmental Health Perspectives  2010;118(5):614-619.
One challenge in assessing the health effects of human exposure to air pollution in epidemiologic studies is the lack of widespread historical air pollutant monitoring data with which to characterize past exposure levels.
Given the availability of long-term economic data, we relate economic activity levels to patterns in vehicle-related particulate matter (PM) over a 30-year period in New Jersey, USA, to provide insight into potential historical surrogate markers of air pollution.
We used statewide unemployment and county-level trucking industry characteristics to estimate historical coefficient of haze (COH), a marker of vehicle-related PM predominantly from diesel exhaust. A total of 5,920 observations were included across 25 different locations in New Jersey between 1971 and 2003.
A mixed-modeling approach was employed to estimate the impact of economic indicators on measured COH. The model explained approximately 50% of the variability in COH as estimated by the overall R2 value. Peaks and lows in unemployment tracked negatively with similar extremes in COH, whereas employment in the trucking industry was positively associated with COH. Federal air quality regulations also played a large and significant role in reducing COH levels over the study period.
This new approach outlines an alternative method to reconstruct historical exposures that may greatly aid epidemiologic research on specific causes of health effects from urban air pollution. Economic activity data provide a potential surrogate marker of changes in exposure levels over time in the absence of direct monitoring data for chronic disease studies, but more research in this area is needed.
PMCID: PMC2866675  PMID: 20056563
air pollution; business cycle; chronic disease; diesel; economy; epidemiology; traffic exposure; trucking industry
18.  Chronic obstructive pulmonary disease mortality in railroad workers 
There is little information describing the risk of non-malignant respiratory disease and occupational exposure to diesel exhaust.
US railroad workers have been exposed to diesel exhaust since diesel locomotives were introduced after World War II. In a retrospective cohort study we examined the association of chronic obstructive pulmonary disease (COPD) mortality with years of work in diesel-exposed jobs. To examine the possible confounding effects of smoking, multiple imputation was used to model smoking history. A Cox proportional hazards model was used to estimate an incidence rate ratio, adjusted for age, calendar year, and length of follow-up after leaving work (to reduce bias due to a healthy worker survivor effect).
Workers in jobs with diesel exhaust exposure had an increased risk of COPD mortality relative to those in unexposed jobs. Workers hired after the introduction of diesel locomotives had a 2.5% increase in COPD mortality risk for each additional year of work in a diesel-exposed job. This risk was only slightly attenuated after adjustment for imputed smoking history.
These results support an association between occupational exposure to diesel exhaust and COPD mortality.
PMCID: PMC2658724  PMID: 19039098
19.  Lung cancer and diesel exhaust: an updated critical review of the occupational epidemiology literature 
Critical Reviews in Toxicology  2012;42(7):549-598.
A recent review concluded that the evidence from epidemiology studies was indeterminate and that additional studies were required to support the diesel exhaust-lung cancer hypothesis. This updated review includes seven recent studies. Two population-based studies concluded that significant exposure-response (E-R) trends between cumulative diesel exhaust and lung cancer were unlikely to be entirely explained by bias or confounding. Those studies have quality data on life-style risk factors, but do not allow definitive conclusions because of inconsistent E-R trends, qualitative exposure estimates and exposure misclassification (insufficient latency based on job title), and selection bias from low participation rates. Non-definitive results are consistent with the larger body of population studies. An NCI/NIOSH cohort mortality and nested case-control study of non-metal miners have some surrogate-based quantitative diesel exposure estimates (including highest exposure measured as respirable elemental carbon (REC) in the workplace) and smoking histories. The authors concluded that diesel exhaust may cause lung cancer. Nonetheless, the results are non-definitive because the conclusions are based on E-R patterns where high exposures were deleted to achieve significant results, where a posteriori adjustments were made to augment results, and where inappropriate adjustments were made for the “negative confounding” effects of smoking even though current smoking was not associated with diesel exposure and therefore could not be a confounder. Three cohort studies of bus drivers and truck drivers are in effect air pollution studies without estimates of diesel exhaust exposure and so are not sufficient for assessing the lung cancer-diesel exhaust hypothesis. Results from all occupational cohort studies with quantitative estimates of exposure have limitations, including weak and inconsistent E-R associations that could be explained by bias, confounding or chance, exposure misclassification, and often inadequate latency. In sum, the weight of evidence is considered inadequate to confirm the diesel-lung cancer hypothesis.
PMCID: PMC3441149  PMID: 22656672
Cumulative exposure; diesel exhaust; elemental carbon; epidemiology; exposure-response; latency; lung cancer; odds ratio
20.  Comparison of two expert-based assessments of diesel exhaust exposure in a case-control study: Programmable decision rules versus expert review of individual jobs 
Professional judgment is necessary to assess occupational exposure in population-based case-control studies; however, the assessments lack transparency and are time-consuming to perform. To improve transparency and efficiency, we systematically applied decision rules to the questionnaire responses to assess diesel exhaust exposure in the New England Bladder Cancer Study, a population-based case-control study.
2,631 participants reported 14,983 jobs; 2,749 jobs were administered questionnaires (‘modules’) with diesel-relevant questions. We applied decision rules to assign exposure metrics based solely on the occupational history responses (OH estimates) and based on the module responses (module estimates); we combined the separate OH and module estimates (OH/module estimates). Each job was also reviewed one at a time to assign exposure (one-by-one review estimates). We evaluated the agreement between the OH, OH/module, and one-by-one review estimates.
The proportion of exposed jobs was 20–25% for all jobs, depending on approach, and 54–60% for jobs with diesel-relevant modules. The OH/module and one-by-one review had moderately high agreement for all jobs (κw=0.68–0.81) and for jobs with diesel-relevant modules (κw=0.62–0.78) for the probability, intensity, and frequency metrics. For exposed subjects, the Spearman correlation statistic was 0.72 between the cumulative OH/module and one-by-one review estimates.
The agreement seen here may represent an upper level of agreement because the algorithm and one-by-one review estimates were not fully independent. This study shows that applying decision-based rules can reproduce a one-by-one review, increase transparency and efficiency, and provide a mechanism to replicate exposure decisions in other studies.
PMCID: PMC3439531  PMID: 22843440
21.  Chronic Obstructive Pulmonary Disease Mortality in Diesel-Exposed Railroad Workers 
Environmental Health Perspectives  2006;114(7):1013-1017.
Diesel exhaust is a mixture of combustion gases and ultrafine particles coated with organic compounds. There is concern whether exposure can result in or worsen obstructive airway diseases, but there is only limited information to assess this risk. U.S. railroad workers have been exposed to diesel exhaust since diesel locomotives were introduced after World War II, and by 1959, 95% of the locomotives were diesel. We conducted a case–control study of railroad worker deaths between 1981 and 1982 using U.S. Railroad Retirement Board job records and next-of-kin smoking, residential, and vitamin use histories. There were 536 cases with chronic obstructive pulmonary disease (COPD) and 1,525 controls with causes of death not related to diesel exhaust or fine particle exposure. After adjustment for age, race, smoking, U.S. Census region of death, vitamin use, and total years off work, engineers and conductors with diesel-exhaust exposure from operating trains had an increased risk of COPD mortality. The odds of COPD mortality increased with years of work in these jobs, and those who had worked ≥ 16 years as an engineer or conductor after 1959 had an odds ratio of 1.61 (95% confidence interval, 1.12–2.30). These results suggest that diesel-exhaust exposure contributed to COPD mortality in these workers. Further study is needed to assess whether this risk is observed after exposure to exhaust from later-generation diesel engines with modern emission controls.
PMCID: PMC1513327  PMID: 16835052
chronic obstructive pulmonary disease; COPD; nonmalignant respiratory disease; occupational exposure; vehicle emissions
22.  Carcinogenic and Cocarcinogenic Effects of Radon and Radon Daughters in Rats. 
It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of lung cancers was higher by a factor of 2-4 according to the cumulative radon exposure and the duration of tobacco smoke exposure. When mineral fibers were injected intrapleurally, an increased incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures.
PMCID: PMC1567245  PMID: 9719670
23.  Occupational risk factors for male bladder cancer: results from a population based case cohort study in the Netherlands 
OBJECTIVES—This study was conducted to estimate risk of bladder cancer associated with occupational exposures to paint components, polycyclic aromatic hydrocarbons (PAHs), diesel exhausts, and aromatic amines among the general population in The Netherlands.
METHODS—A prospective cohort study was conducted among 58 279 men. In September 1986, the cohort members (55-69 years) completed a self administered questionnaire on risk factors for cancer including job history. Follow up for incident bladder cancer was established by linkage to cancer registries until December 1992. A case-cohort approach was used based on 532 cases and 1630 subcohort members. A case by case expert assessment was carried out to assign to the cases and subcohort members a cumulative probability of occupational exposure for each carcinogenic exposure.
RESULTS—Men in the highest tertiles of occupational exposure to paint components, PAHs, aromatic amines, and diesel exhaust had non-significantly higher age and smoking adjusted incident rate ratios (RRs) of bladder cancer than men with no exposure: 1.29 (95% confidence interval (95% CI) 0.71 to 2.33), 1.24 (95% CI 0.68 to 2.27), 1.32 (95% CI 0.41 to 4.23) and 1.21 (95% CI 0.78 to 1.88), respectively. The associations between paint components and PAHs and risk of bladder cancer were most pronounced for current smokers. Among former smokers it seemed that for cumulative probability of exposure to paint components and PAHs, men who had smoked more than 15 cigarettes a day had RRs below unity compared with men who had smoked less than 15 cigarettes a day, whereas among current smokers the opposite was found. Exposure to diesel exhaust was positively associated with risk of bladder cancer among current and former smokers who had smoked more than 15 cigarettes a day.
CONCLUSIONS—This study provided only marginal evidence for an association between occupational exposure to paint components, PAHs, aromatic amines, and bladder cancer. Despite the small proportion of exposed subjects, an interaction with cigarette smoking was found, specifically for paint components, suggesting that the carcinogenic effect on the bladder might decrease after stopping smoking.

Keywords: bladder cancer; occupation; epidemiology
PMCID: PMC1740187  PMID: 11511746
24.  A cross-sectional survey on knowledge and perceptions of health risks associated with arsenic and mercury contamination from artisanal gold mining in Tanzania 
BMC Public Health  2013;13:74.
An estimated 0.5 to 1.5 million informal miners, of whom 30-50% are women, rely on artisanal mining for their livelihood in Tanzania. Mercury, used in the processing gold ore, and arsenic, which is a constituent of some ores, are common occupational exposures that frequently result in widespread environmental contamination. Frequently, the mining activities are conducted haphazardly without regard for environmental, occupational, or community exposure. The primary objective of this study was to assess community risk knowledge and perception of potential mercury and arsenic toxicity and/or exposure from artisanal gold mining in Rwamagasa in northwestern Tanzania.
A cross-sectional survey of respondents in five sub-villages in the Rwamagasa Village located in Geita District in northwestern Tanzania near Lake Victoria was conducted. This area has a history of artisanal gold mining and many of the population continue to work as miners. Using a clustered random selection approach for recruitment, a total of 160 individuals over 18 years of age completed a structured interview.
The interviews revealed wide variations in knowledge and risk perceptions concerning mercury and arsenic exposure, with 40.6% (n=65) and 89.4% (n=143) not aware of the health effects of mercury and arsenic exposure respectively. Males were significantly more knowledgeable (n=59, 36.9%) than females (n=36, 22.5%) with regard to mercury (x2=3.99, p<0.05). An individual’s occupation category was associated with level of knowledge (x2=22.82, p=<0.001). Individuals involved in mining (n=63, 73.2%) were more knowledgeable about the negative health effects of mercury than individuals in other occupations. Of the few individuals (n=17, 10.6%) who knew about arsenic toxicity, the majority (n=10, 58.8%) were miners.
The knowledge of individuals living in Rwamagasa, Tanzania, an area with a history of artisanal gold mining, varied widely with regard to the health hazards of mercury and arsenic. In these communities there was limited awareness of the threats to health associated with exposure to mercury and arsenic. This lack of knowledge, combined with minimal environmental monitoring and controlled waste management practices, highlights the need for health education, surveillance, and policy changes.
PMCID: PMC3585699  PMID: 23351708
Hazard risk knowledge; Perception; Artisanal mining; Arsenic and mercury; Tanzania
25.  Occupational exposure to diesel engine exhaust: A literature review 
Diesel exhaust (DE) is classified as a probable human carcinogen. Aims were to describe the major occupational uses of diesel engines and give an overview of personal DE exposure levels and determinants of exposure as reported in the published literature.
Measurements representative of personal DE exposure were abstracted from the literature for the following agents: elemental carbon (EC), particulate matter (PM), carbon monoxide (CO), nitrogen oxide (NO), and nitrogen dioxide (NO2). Information on determinants of exposure was abstracted.
In total, 3528 EC, 4166 PM, 581 CO, 322 NO, and 1404 NO2 measurements were abstracted. From the 10,001 measurements, 32% represented exposure from on-road vehicles, and 68% from off-road vehicles (30% mining, 15% railroad, and 22% other). Highest levels were reported for enclosed underground work sites where heavy equipment is used: mining, mine maintenance, and construction, (EC: 27-658 μg/m3). Intermediate exposure levels were generally reported for above ground (semi-)enclosed areas where smaller equipment was run: mechanics in a shop, emergency workers in fire stations, distribution workers at a dock, and workers loading/unloading inside a ferry (generally: EC< 50 μg/m3). Lowest levels were reported for enclosed areas separated from the source such as drivers and train crew, or outside such as surface mining, parking attendants, vehicle testers, utility service workers, surface construction and airline ground personnel (EC<25 μg/m3). The other agents showed a similar pattern. Determinants of exposure reported for enclosed situations were ventilation and exhaust after treatment devices.
Reported DE exposure levels were highest for underground mining and construction, intermediate for working in above ground (semi-)enclosed areas and lowest for working outside or separated from the source. The presented data can be used as a basis for assessing occupational exposure in population-based epidemiological studies and guide future exposure assessment efforts for industrial hygiene and epidemiological studies.
PMCID: PMC3073453  PMID: 19277070
diesel exhaust; occupational; review; exposure; determinant

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