Historical occupational trichloroethylene air concentrations based on inspection measurements from Shanghai, China.

PURPOSE: Trichloroethylene (TCE) is a carcinogen that has been linked to kidney cancer and possibly other cancer sites including non-Hodgkin lymphoma. Its use in China has increased since the early 1990s with China's growing metal, electronic, and telecommunications industries. We examined historical occupational TCE air concentration patterns in a database of TCE inspection measurements collected in Shanghai, China to identify temporal trends and broad contrasts among occupations and industries. METHODS: Using a database of 932 short-term, area TCE air inspection measurements collected in Shanghai worksites from 1968 through 2000 (median year 1986), we developed mixed-effects models to evaluate job-, industry-, and time-specific TCE air concentrations. RESULTS: Models of TCE air concentrations from Shanghai work sites predicted that exposures decreased 5-10% per year between 1968 and 2000. Measurements collected near launderers and dry cleaners had the highest predicted geometric means (GM for 1986 = 150-190 mg m(-3)). The majority (53%) of the measurements were collected in metal treatment jobs. In a model restricted to measurements in metal treatment jobs, predicted GMs for 1986 varied 35-fold across industries, from 11 mg m(-3) in 'other metal products/repair' industries to 390 mg m(-3) in 'ships/aircrafts' industries. CONCLUSIONS: TCE workplace air concentrations appeared to have dropped over time in Shanghai, China between 1968 and 2000. Understanding differences in TCE concentrations across time, occupations, and industries may assist future epidemiologic studies in China.

Reliability and validity of expert assessment based on airborne and urinary measures of nickel and chromium exposure in the electroplating industry.

The reliability and validity of six experts' exposure ratings were evaluated for 64 nickel-exposed and 72 chromium-exposed workers from six Shanghai electroplating plants based on airborne and urinary nickel and chromium measurements. Three industrial hygienists and three occupational physicians independently ranked the exposure intensity of each metal on an ordinal scale (1-4) for each worker's job in two rounds: the first round was based on responses to an occupational history questionnaire and the second round also included responses to an electroplating industry-specific questionnaire. The Spearman correlation (r(s)) was used to compare each rating's validity to its corresponding subject-specific arithmetic mean of four airborne or four urinary measurements. Reliability was moderately high (weighted kappa range=0.60-0.64). Validity was poor to moderate (r(s)=-0.37-0.46) for both airborne and urinary concentrations of both metals. For airborne nickel concentrations, validity differed by plant. For dichotomized metrics, sensitivity and specificity were higher based on urinary measurements (47-78%) than airborne measurements (16-50%). Few patterns were observed by metal, assessment round, or expert type. These results suggest that, for electroplating exposures, experts can achieve moderately high agreement and (reasonably) distinguish between low and high exposures when reviewing responses to in-depth questionnaires used in population-based case-control studies.

Calibrating a population-based job-exposure matrix using inspection measurements to estimate historical occupational exposure to lead for a population-based cohort in Shanghai, China.

The epidemiologic evidence for the carcinogenicity of lead is inconsistent and requires improved exposure assessment to estimate risk. We evaluated historical occupational lead exposure for a population-based cohort of women (n=74,942) by calibrating a job-exposure matrix (JEM) with lead fume (n=20,084) and lead dust (n=5383) measurements collected over four decades in Shanghai, China. Using mixed-effect models, we calibrated intensity JEM ratings to the measurements using fixed-effects terms for year and JEM rating. We developed job/industry-specific estimates from the random-effects terms for job and industry. The model estimates were applied to subjects' jobs when the JEM probability rating was high for either job or industry; remaining jobs were considered unexposed. The models predicted that exposure increased monotonically with JEM intensity rating and decreased 20-50-fold over time. The cumulative calibrated JEM estimates and job/industry-specific estimates were highly correlated (Pearson correlation=0.79-0.84). Overall, 5% of the person-years and 8% of the women were exposed to lead fume; 2% of the person-years and 4% of the women were exposed to lead dust. The most common lead-exposed jobs were manufacturing electronic equipment. These historical lead estimates should enhance our ability to detect associations between lead exposure and cancer risk in the future epidemiologic analyses.

Occupational exposure to chlorinated solvents and risks of glioma and meningioma in adults.

OBJECTIVES: Chlorinated solvents are classified as probable or possible carcinogens. It is unknown whether exposure to these agents increases the risk of malignant or benign brain tumours. Our objective was to evaluate associations of brain tumour risk with occupational exposure to six chlorinated solvents (i.e., dichloromethane, chloroform, carbon tetrachloride, 1,1,1-trichloroethane, trichloroethylene and perchloroethylene). METHODS: 489 glioma cases, 197 meningioma cases and 799 controls were enrolled in a hospital-based case-control study conducted at three U.S.A. hospitals in Arizona, Massachusetts and Pennsylvania. Information about occupational history was obtained through a detailed inperson interview that included job-specific modules of questions such that the interview was tailored to each individual's particular work history. An industrial hygienist assessed potential solvent exposure based on this information and an exhaustive review of the relevant industrial hygiene literature. Unconditional logistic regression models were used to calculate OR and 95% CI for each solvent for ever/never, duration, cumulative, average weekly and highest exposure. RESULTS: Overall, we found no consistent evidence of an increased risk of glioma or meningioma related to occupational exposure to the six chlorinated solvents evaluated. There was some suggestion of an association between carbon tetrachloride and glioma in analyses restricted to exposed subjects, with average weekly exposure above the median associated with increased risk compared with below the median exposure (OR = 7.1, 95% CI 1.1 to 45.2). CONCLUSIONS: We found no consistent evidence for increased brain tumour risk related to chlorinated solvents.

Comparison of two expert-based assessments of diesel exhaust exposure in a case-control study: programmable decision rules versus expert review of individual jobs.

OBJECTIVES: 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 questionnaire responses to assess diesel exhaust exposure in the population-based case-control New England Bladder Cancer Study. METHODS: 2631 participants reported 14 983 jobs; 2749 jobs were administered questionnaires ('modules') with diesel-relevant questions. We applied decision rules to assign exposure metrics based either on the occupational history (OH) responses (OH estimates) or on the module responses (module estimates); we then combined the separate OH and module estimates (OH/module estimates). Each job was also reviewed individually to assign exposure (one-by-one review estimates). We evaluated the agreement between the OH, OH/module and one-by-one review estimates. RESULTS: 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 estimates had moderately high agreement for all jobs (κ(w)=0.68-0.81) and for jobs with diesel-relevant modules (κ(w)=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. CONCLUSIONS: 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.

Using multiple imputation to assign pesticide use for non-responders in the follow-up questionnaire in the Agricultural Health Study.

The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and North Carolina. A follow-up questionnaire administered 5 years later was completed by 36,342 (63%) of the original participants. Missing pesticide use information from participants who did not complete the second questionnaire impedes both long-term pesticide exposure estimation and statistical inference of risk for health outcomes. Logistic regression and stratified sampling were used to impute key variables related to the use of specific pesticides for 20,968 applicators who did not complete the second questionnaire. To assess the imputation procedure, a 20% random sample of participants was withheld for comparison. The observed and imputed prevalence of any pesticide use in the holdout dataset were 85.7% and 85.3%, respectively. The distribution of prevalence and days/year of use for specific pesticides were similar across observed and imputed in the holdout sample. When appropriately implemented, multiple imputation can reduce bias and increase precision and can be more valid than other missing data approaches.

Methyl bromide exposure and cancer risk in the Agricultural Health Study.

PURPOSE: Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects. METHODS: We used Poisson regression to calculate rate ratios (RR) and 95 % confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007. We also evaluated interactions with a family history for four common cancers (prostate, lung, colon, and lymphohematopoietic). We categorized methyl bromide exposure based on lifetime days applied weighted by an intensity score. RESULTS: A total of 7,814 applicators (14.6 %) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use (RR = 1.42; 95 % CI, 0.51-3.95 and RR = 3.13; 95 % CI, 1.25-7.80 for low and high use compared with no use; p (trend) = 0.02). No other sites displayed a significant monotonic pattern. Although we previously observed an association with prostate cancer (follow-up through 1999), the association did not persist with longer follow-up. We observed a nonsignificant elevated risk of prostate cancer with methyl bromide use among those with a family history of prostate cancer, but the interaction with a family history did not achieve statistical significance. CONCLUSIONS: Our results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, we observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.

The Diesel Exhaust in Miners Study: V. Evaluation of the Exposure Assessment Methods.

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.

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.

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/m(3)-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/m(3)-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.

Combining a job-exposure matrix with exposure measurements to assess occupational exposure to benzene in a population cohort in shanghai, china.

BACKGROUND: Generic job-exposure matrices (JEMs) are often used in population-based epidemiologic studies to assess occupational risk factors when only the job and industry information of each subject is available. JEM ratings are often based on professional judgment, are usually ordinal or semi-quantitative, and often do not account for changes in exposure over time. We present an empirical Bayesian framework that combines ordinal subjective JEM ratings with benzene measurements. Our aim was to better discriminate between job, industry, and time differences in exposure levels compared to using a JEM alone. METHODS: We combined 63 221 short-term area air measurements of benzene exposure (1954-2000) collected during routine health and safety inspections in Shanghai, China, with independently developed JEM intensity ratings for each job and industry using a mixed-effects model. The fixed-effects terms included the JEM intensity ratings for job and industry (both ordinal, 0-3) and a time trend that we incorporated as a b-spline. The random-effects terms included job (n = 33) and industry nested within job (n = 399). We predicted the benzene concentration in two ways: (i) a calibrated JEM estimate was calculated using the fixed-effects model parameters for calendar year and JEM intensity ratings; (ii) a job-/industry-specific estimate was calculated using the fixed-effects model parameters and the best linear unbiased predictors from the random effects for job and industry using an empirical Bayes estimation procedure. Finally, we applied the predicted benzene exposures to a prospective population-based cohort of women in Shanghai, China (n = 74 942). RESULTS: Exposure levels were 13 times higher in 1965 than in 2000 and declined at a rate that varied from 4 to 15% per year from 1965 to 1985, followed by a small peak in the mid-1990s. The job-/industry-specific estimates had greater differences between exposure levels than the calibrated JEM estimates (97.5th percentile/2.5th percentile exposure level, (B)(G)R(95)(B): 20.4 versus 3.0, respectively). The calibrated JEM and job-/industry-specific estimates were moderately correlated in any given year (Pearson correlation, r(p) = 0.58). We classified only those jobs and industries with a job or industry JEM exposure probability rating of 3 (>50% of workers exposed) as exposed. As a result, 14.8% of the subjects and 8.7% of the employed person-years in the study population were classified as benzene exposed. The cumulative exposure metrics based on the calibrated JEM and job-/industry-specific estimates were highly correlated (r(p) = 0.88). CONCLUSIONS: We provide a useful framework for combining quantitative exposure data with expert-based exposure ratings in population-based studies that maximized the information from both sources. Our framework calibrated the ratings to a concentration scale between ratings and across time and provided a mechanism to estimate exposure when a job/industry group reported by a subject was not represented in the exposure database. It also allowed the job/industry groups' exposure levels to deviate from the pooled average for their respective JEM intensity ratings.

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.

Validity and reliability of exposure assessors' ratings of exposure intensity by type of occupational questionnaire and type of rater.

BACKGROUND: In epidemiologic studies that rely on professional judgment to assess occupational exposures, the raters' accurate assessment is vital to detect associations. We examined the influence of the type of questionnaire, type of industry, and type of rater on the raters' ability to reliably and validly assess within-industry differences in exposure. Our aim was to identify areas where improvements in exposure assessment may be possible. METHODS: Subjects from three foundries (n = 72) and three textile plants (n = 74) in Shanghai, China, completed an occupational history (OH) and an industry-specific questionnaire (IQ). Six total dust measurements were collected per subject and were used to calculate a subject-specific measurement mean, which was used as the gold standard. Six raters independently ranked the intensity of each subject's current job on an ordinal scale (1-4) based on the OH alone and on the OH and IQ together. Aggregate ratings were calculated for the group, for industrial hygienists, and for occupational physicians. We calculated intra-class correlation coefficients (ICCs) to evaluate the reliability of the raters. We calculated the correlation between the subject-specific measurement means and the ratings to evaluate the raters' validity. Analyses were stratified by industry, type of questionnaire, and type of rater. We also examined the agreement between the ratings by exposure category, where the subject-specific measurement means were categorized into two and four categories. RESULTS: The reliability and validity measures were higher for the aggregate ratings than for the ratings from the individual raters. The group's performance was maximized with three raters. Both the reliability and validity measures were higher for the foundry industry than for the textile industry. The ICCs were consistently lower in the OH/IQ round than in the OH round in both industries. In contrast, the correlations with the measurement means were higher in the OH/IQ round than in the OH round for the foundry industry (group rating, OH/IQ: Spearman rho = 0.77; OH: rho = 0.64). No pattern by questionnaire type was observed for the textile industry (group rating, Spearman rho = 0.50, both assessment rounds). For both industries, the agreement by exposure category was higher when the task was reduced to discriminating between two versus four exposure categories. CONCLUSIONS: Assessments based on professional judgment may reduce misclassification by using two or three raters, by using questionnaires that systematically collect task information, and by defining intensity categories that are distinguishable by the raters. However, few studies have the resources to use multiple raters and these additional efforts may not be adequate for obtaining valid subjective ratings. Thus, improving exposure assessment approaches for studies that rely on professional judgment remain an important research need.

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: III. Interrelations between respirable elemental carbon and gaseous and particulate components of diesel exhaust derived from area sampling in underground non-metal mining facilities.

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 (NO(x)) and carbon oxides (CO(x)) 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.

The diesel exhaust in miners study: I. Overview of the exposure assessment process.

This report provides an overview of the exposure assessment process for an epidemiologic study that investigated mortality, with a special focus on lung cancer, associated with diesel exhaust (DE) exposure among miners. Details of several components are provided in four other reports. A major challenge for this study was the development of quantitative estimates of historical exposures to DE. There is no single standard method for assessing the totality of DE, so respirable elemental carbon (REC), a component of DE, was selected as the primary surrogate in this study. Air monitoring surveys at seven of the eight study mining facilities were conducted between 1998 and 2001 and provided reference personal REC exposure levels and measurements for other agents and DE components in the mining environment. (The eighth facility had closed permanently prior to the surveys.) Exposure estimates were developed for mining facility/department/job/year combinations. A hierarchical grouping strategy was developed for assigning exposure levels to underground jobs [based on job titles, on the amount of time spent in various areas of the underground mine, and on similar carbon monoxide (CO, another DE component) concentrations] and to surface jobs (based on the use of, or proximity to, diesel-powered equipment). Time trends in air concentrations for underground jobs were estimated from mining facility-specific prediction models using diesel equipment horsepower, total air flow rates exhausted from the underground mines, and, because there were no historical REC measurements, historical measurements of CO. Exposures to potentially confounding agents, i.e. respirable dust, silica, radon, asbestos, and non-diesel sources of polycyclic aromatic hydrocarbons, also were assessed. Accuracy and reliability of the estimated REC exposures levels were evaluated by comparison with several smaller datasets and by development of alternative time trend models. During 1998-2001, the average measured REC exposure level by facility ranged from 40 to 384 µg m⁻³ for the underground workers and from 2 to 6 µg m⁻³ for the surface workers. For one prevalent underground job, 'miner operator', the maximum annual REC exposure estimate by facility ranged up to 685% greater than the corresponding 1998-2001 value. A comparison of the historical CO estimates from the time trend models with 1976-1977 CO measurements not used in the modeling found an overall median relative difference of 29%. Other comparisons showed similar levels of agreement. The assessment process indicated large differences in REC exposure levels over time and across the underground operations. Method evaluations indicated that the final estimates were consistent with those from alternative time trend models and demonstrated moderate to high agreement with external data.

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.

Assessment of a pesticide exposure intensity algorithm in the agricultural health study.

The accuracy of the exposure assessment is a critical factor in epidemiological investigations of pesticide exposures and health in agricultural populations. However, few studies have been conducted to evaluate questionnaire-based exposure metrics. The Agricultural Health Study (AHS) is a prospective cohort study of pesticide applicators who provided detailed questionnaire information on their use of specific pesticides. A field study was conducted for a subset of the applicators enrolled in the AHS to assess a pesticide exposure algorithm through comparison of algorithm intensity scores with measured exposures. Pre- and post-application urinary biomarker measurements were made for 2,4-D (n=69) and chlorpyrifos (n=17) applicators. Dermal patch, hand wipe, and personal air samples were also collected. Intensity scores were calculated using information from technician observations and an interviewer-administered questionnaire. Correlations between observer and questionnaire intensity scores were high (Spearman's r=0.92 and 0.84 for 2,4-D and chlorpyrifos, respectively). Intensity scores from questionnaires for individual applications were significantly correlated with post-application urinary concentrations for both 2,4-D (r=0.42, P<0.001) and chlorpyrifos (r=0.53, P=0.035) applicators. Significant correlations were also found between intensity scores and estimated hand loading, estimated body loading, and air concentrations for 2,4-D applicators (r-values 0.28-0.50, P-values<0.025). Correlations between intensity scores and dermal and air measures were generally lower for chlorpyrifos applicators using granular products. A linear regression model indicated that the algorithm factors for individual applications explained 24% of the variability in post-application urinary 2,4-D concentration, which increased to 60% when the pre-application urine concentration was included. The results of the measurements support the use of the algorithm for estimating questionnaire-based exposure intensities in the AHS for liquid pesticide products. Refinement of the algorithm may be possible using the results from this and other measurement studies.

A comprehensive review of the literature on exposure to metalworking fluids.

An extensive literature review was conducted of studies with exposure measurements to metalworking fluids (MWFs). A database of 155 arithmetic means based on 9379 aerosol measurements from published studies was compiled. Weighted arithmetic means (WAMs) and their variance calculated across studies were summarized based on decade (prior to 1970s through 2000s), industry (auto, auto parts, small job shops, and others), operation (grinding and machining), and fluid type (straight, soluble, synthetic, and semisynthetic). Total mass and total extractable mass measurements that were simultaneously collected were compared. Average concentrations by size fractions and mass median aerodynamic diameters (MMADs) were also analyzed. Analysis of the WAMs indicated a reduction in exposure levels over time regardless of industry or type of operation or fluid, with mean levels prior to the 1970s of 5.4 mg/m(3), which dropped to 2.5 mg/m(3) in the 1970s, to 1.2 mg/m(3) in the 1980s, and to 0.5 mg/m(3) in the 1990s. No further reduction was seen in the 2000s. A comparison by industry, operation, and fluid type found no consistent patterns in the measurement results. The percent extractable mass in the total aerosol samples varied by fluid type, with an average 84% in straight fluids, 58% in synthetic fluids, 56% in soluble fluids, and 42% in the semisynthetic fluids. Exposure means from the thoracic fraction (0.3-0.5 mg/m(3)) were slightly less than those for total aerosol for both the 1990s and 2000s, the only decades for which thoracic data were available. Respirable means did not change from the 1980s to the 2000s (generally about 0.2-0.3 mg/m(3)). The MMADs of the MWF aerosols averaged 4-6 microm. These measurement data indicate a clear reduction of exposure levels over time. They will be used for the retrospective assessment of exposure levels to MWFs in a population-based, case-control study of bladder cancer.

Determinants of exposure to metalworking fluid aerosols: a literature review and analysis of reported measurements.

An extensive literature review of published metalworking fluid (MWF) aerosol measurement data was conducted to identify the major determinants that may affect exposure to aerosol fractions (total or inhalable, thoracic and respirable) and mass median diameters (MMDs). The identification of determinants was conducted through published studies and analysis of published measurement levels. For the latter, weighted arithmetic means (WAMs) by number of measurements were calculated and compared using analysis of variance and t-tests. The literature review found that the major factors affecting aerosol exposure levels were, primarily, decade, type of industry, operation and fluid and engineering control measures. Our analysis of total aerosol levels found a significant decline in measured levels from an average of 5.36 mg m(-3) prior to the 1970s and 2.52 mg m(-3) in the 1970s to 1.21 mg m(-3) in the 1980s, 0.50 mg m(-3) in the 1990s and 0.55 mg m(-3) in the 2000s. Significant declines from the 1990s to the 2000s also were found in thoracic fraction levels (0.48 versus 0.40 mg m(-3)), but not for the respirable fraction. The WAMs for the auto (1.47 mg m(-3)) and auto parts manufacturing industry (1.83 mg m(-3)) were significantly higher than that for small-job machine shops (0.68 mg m(-3)). In addition, a significant difference in the thoracic WAM was found between the automotive industry (0.46 mg m(-3)) and small-job machine shops (0.32 mg m(-3)). Operation type, in particular, grinding, was a significant factor affecting the total aerosol fraction [grinding operations (1.75 mg m(-3)) versus other machining (0.95 mg m(-3))], but the levels associated with these operations were not statistically different for either the thoracic or the respirable fractions. Across all decades, the total aerosol fraction for straight oils (1.49 mg m(-3)) was higher than for other fluid types (soluble = 1.08 mg m(-3), synthetic = 0.52 mg m(-3) and semisynthetic = 0.50 mg m(-3)). Fluid type was also found to be partly associated with differences in the respirable fraction level. We found that the total aerosols were measured by a variety of sampling media, devices and analytical methods. This diversity of approaches makes interpretation of the study results difficult. In conclusion, both the literature review and the measurement data analyzed found that decade and type of industry, operation and fluid were important determinants of total aerosol exposure. Industry type and fluid type were associated with differences in exposure to the thoracic and respirable fraction levels, respectively.