Joseph Coble

The Diesel Exhaust in Miners Study: A Nested Case–Control Study of Lung Cancer and Diesel Exhaust

Background 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. Methods 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. Results 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. Conclusion Our findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.

The Diesel Exhaust in Miners Study: A Cohort Mortality Study With Emphasis on Lung Cancer

BACKGROUND Current information points to an association between diesel exhaust exposure and lung cancer and other mortality outcomes, but uncertainties remain. METHODS 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. RESULTS 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/m(3)-y category compared with the reference category (0 to <20 μg/m(3)-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/m(3). 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. CONCLUSIONS The study findings provide further evidence that exposure to diesel exhaust increases risk of mortality from lung cancer and have important public health implications.

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% others). Highest levels were reported for enclosed underground work sites in which 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 in which 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.

Pesticide use and adult-onset asthma among male farmers in the Agricultural Health Study

Although specific pesticides have been associated with wheeze in farmers, little is known about pesticides and asthma. Data from 19,704 male farmers in the Agricultural Health Study were used to evaluate lifetime use of 48 pesticides and prevalent adult-onset asthma, defined as doctor-diagnosed asthma after the age of 20 yrs. Asthma cases were categorised as allergic (n = 127) and nonallergic (n = 314) based on their history of eczema or hay fever. Polytomous logistic regression, controlling for age, state, smoking and body mass, was used to assess pesticide associations. High pesticide exposure events were associated with a doubling of both allergic and nonallergic asthma. For ever-use, 12 individual pesticides were associated with allergic asthma and four with nonallergic asthma. For allergic asthma, coumaphos (OR 2.34; 95% CI 1.49–3.70), heptachlor (OR 2.01; 95% CI 1.30–3.11), parathion (OR 2.05; 95% CI 1.21–3.46), 80/20 mix (carbon tetrachloride/carbon disulfide) (OR 2.15; 95% CI 1.23–3.76) and ethylene dibromide (OR 2.07; 95% CI 1.02–4.20) all showed ORs of >2.0 and significant exposure–response trends. For nonallergic asthma, DDT (dichlorodiphenyltrichloroethane) showed the strongest association (OR 1.41; 95% CI 1.09–1.84), but with little evidence of increasing asthma with increasing use. Current animal handling and farm activities did not confound these results. There was little evidence that allergy alone was driving these associations. In conclusion, pesticides may be an overlooked contributor to asthma risk among farmers.

Cancer Incidence among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study

Background Permethrin is a synthetic pyrethroid insecticide widely used in agriculture, in public health, and in many U.S. homes and gardens. Objective In this study we evaluated the incidence of cancer among pesticide applicators exposed to permethrin in the Agricultural Health Study (AHS). Methods A total of 49,093 pesticide applicators were included in this analysis of the AHS, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed in 1993–1997. Average length of follow-up since applicator enrollment in the cohort was 9.14 years. We used two permethrin exposure metrics: a) lifetime days applicators personally mixed or applied permethrin and b) intensity-weighted lifetime days (lifetime days weighted by estimated intensity of exposure). We used Poisson regression analysis to estimate relative risks (RRs) and 95% confidence intervals (CIs) for malignancies by tertiles of exposure. Results We found no associations between permethrin and all malignant neoplasms combined, or between permethrin and melanoma, non-Hodgkin lymphoma, leukemia, or cancers of the colon, rectum, lung, or prostate. We found elevated and statistically significant risks for multiple myeloma in the highest tertiles of both lifetime exposure-days (RR = 5.72; 95% CI, 2.76–11.87) and intensity-weighted lifetime exposure-days (RR = 5.01; 95% CI, 2.41–10.42), compared with applicators reporting they never used permethrin; these results are based on only 15 exposed cases. These findings were similar across a variety of alternative exposure metrics, exposure categories, and reference groups. Conclusions This study found no association with most cancers analyzed. Although the suggested association with multiple myeloma was based on a small number of cases, it warrants further evaluation.

Atrazine and Cancer Incidence Among Pesticide Applicators in the Agricultural Health Study (1994–2007)

Background: Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association. Methods: The Agricultural Health Study (AHS) is a prospective cohort that includes 57,310 licensed pesticide applicators. In this report, we extend a previous AHS analysis of cancer risk associated with self-reported atrazine use with six additional years of follow-up and more than twice as many cancer cases. Using Poisson regression, we calculated relative risk estimates and 95% confidence intervals for lifetime use of atrazine and intensity-weighted lifetime days, which accounts for factors that impact exposure. Results: Overall, 36,357 (68%) of applicators reported using atrazine, among whom there were 3,146 cancer cases. There was no increase among atrazine users in overall cancer risk or at most cancer sites in the higher exposure categories compared with the lowest. Based on 29 exposed cases of thyroid cancer, there was a statistically significant risk in the second and fourth quartiles of intensity-weighted lifetime days. There was a similar pattern for lifetime days, but neither the risk estimates nor the trend were statistically significant and for neither metric was the trend monotonic. Conclusions: Overall, there was no consistent evidence of an association between atrazine use and any cancer site. There was a suggestion of increased risk of thyroid cancer, but these results are based on relatively small numbers and minimal supporting evidence.

Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study Cohort

Pancreatic cancer is a rapidly fatal disease that has been linked with pesticide use. Previous studies have reported excess risks of pancreatic cancer with organochlorines such as DDT, however, many other commonly used pesticides have not been examined. To further examine the potential associations between the use of a number of pesticides and pancreatic cancer, we conducted a case‐control analysis in the Agricultural Health Study, one of the largest prospective cohorts with over 89,000 participants including pesticide applicators and their spouses in Iowa and North Carolina. This analysis included 93 incident pancreatic cancer cases (64 applicators, 29 spouses) and 82,503 cancer‐free controls who completed an enrollment questionnaire providing detailed pesticide use, demographic and lifestyle information. Ever use of 24 pesticides and intensity‐weighted lifetime days [(lifetime exposure days) × (exposure intensity score)] of 13 pesticides was assessed. Risk estimates were calculated using unconditional logistic regression controlling for age, smoking, and diabetes. Among pesticide applicators, 2 herbicides (EPTC and pendimethalin) of the 13 pesticides examined for intensity‐weighted lifetime use showed a statistically significant exposure‐response association with pancreatic cancer. Applicators in the top half of lifetime pendimethalin use had a 3.0‐fold (95% CI 1.3–7.2, p‐trend = 0.01) risk compared with never users, and those in the top half of lifetime EPTC use had a 2.56‐fold (95% CI = 1.1–5.4, p‐trend = 0.01) risk compared with never users. Organochlorines were not associated with an excess risk of pancreatic cancer in this study. These findings suggest that herbicides, particularly pendimethalin and EPTC, may be associated with pancreatic cancer.

The diesel exhaust in miners study: II. Exposure monitoring surveys and development of exposure groups.

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.

The Diesel Exhaust in Miners Study: IV. Estimating Historical Exposures to Diesel Exhaust in Underground Non-metal Mining Facilities

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.

Prevalence of exposure to solvents, metals, grain dust, and other hazards among farmers in the Agricultural Health Study.

Exposures to multiple chemical, physical, and biological agents in agricultural work environments can result in confounding that may obscure or distort risks observed in epidemiologic studies. The Agricultural Health Study (AHS) is a large epidemiology study being conducted to investigate health risks among pesticide applicators and their families. During enrollment in the AHS, questionnaires were administered to over 52,000 licensed pesticide applicators from North Carolina and Iowa, who were mostly farmers. Questions about the frequency of various farming tasks were used to estimate the prevalence of exposure to solvents (25%), metals (68%), grain dusts (65%), diesel exhaust fumes (93%), and other hazards, including exposure to pesticides. Most of the farmers in the AHS reported performing routine maintenance tasks at least once a month, such as painting (63%), welding (64%), and repair of pesticide equipment (58%). The majority of farmers (74% in North Carolina; 59% in Iowa) reported holding nonfarm jobs, of which the most frequent were construction and transportation. The majority of the farmers enrolled in the AHS (55%) also reported that they mixed or applied pesticides on 10 or more days per year. The associations between the use of pesticides and the frequency with which the farmers in the AHS reported performing various types of specific farming activities were assessed to evaluate potential confounding. Confounding risk ratios calculated for these activities suggest that the magnitude of bias due to confounding is likely to be minimal.