An adenomatous polyp case-control study to assess occupational risk factors following a workplace colorectal cancer cluster

To assess potential etiologic factors among a population of Texas polypropylene workers previously found to have an excess of colorectal cancer (concentrated among mechanical and process workers), the authors conducted an adenomatous polyp case-control study. Cases (n = 24) were workers found to have adenomatous polyps during a company-sponsored colorectal cancer screening program, while controls (n = 72) were workers found to be free of polyps. Exposure assessment utilized a thorough industrial hygiene and toxicologic review of operations in conjunction with work activity interviews of cases and controls to develop chemical-specific exposure scores weighted by time, exposure level, and frequency of exposure. Stratified analyses and logistic regression found that cases tended to have higher exposure to pre-extrusion polymer plus additives (odds ratio (OR) = 2.6, 90% confidence interval (CI) 1.1-6.3) and higher exposure to certain finishing additives (OR = 4.8, 90% CI 1.5-15.3). Analyses by job category or area of the plant did not indicate additional risk factors. The exposures identified in this study are discussed in light of the available toxicologic data on these and related compounds. The need for confirmatory experimental and epidemiologic studies is noted.     

Occupational case-control studies: II. Recommendations for exposure assessment

Obtaining valid and reliable quantitative exposure estimates is a significant challenge in community-based case-control studies in part, because industrial hygiene monitoring data are usually not available and detailed information on the job and work environment is usually not systematically obtained or assessed. To improve the quality and credibility of disease risk information obtained from occupational case-control studies, we recommend that standardized exposure assessment methods be used to derive quantitative exposure estimates. We identify sources of variation inherent to the assessment process, including: the quality of the information reported on the job, industry, activities, and materials; the industrial hygienist's familiarity with the reported job/industry; the probability that the job/industry was exposed, which depends on plant preferences for particular substances, on process technology, and on customer specifications; and variability in workplace characteristics. To improve the reliability of estimating job-related exposures both within and between studies, we recommend that the epidemiologic analyses be conducted with and without data rated to be of poor quality; that contact be made with experts when the study industrial hygienist is unfamiliar with the manufacturing process in question; that existing data bases be used to estimate the probability of exposure; that a data base be developed that describes manufacturing processes; and that explicit criteria based on industrial hygiene principles be used to evaluate workplace characteristics. In addition, a procedure is described for deriving quantitative exposure estimates by using a reference scale of frequently monitored jobs with their associated mean exposure levels. Areas of research are identified to improve exposure assessment in community-based case-control studies.     

An investigation of secondary exposure misclassification effects of lifelong occupational history in exposure estimation

The effects of exposure misclassification on the interpretation of results of occupational epidemiological studies has been widely investigated and reported. Usually, only the direct effects of misclassification have been considered or simple estimates of misclassification rates have been assigned to various types of exposure estimation processes. Lifelong job profile data obtained from a previously published case-control study provided complete or nearly complete job histories of 511 decedents. An analysis of these work histories and the comparison of exposures related to longest-held job to estimated total lifetime exposures suggest that single job-based exposure estimates may lead to significant exposure misclassification rates. In addition, the appearance of shorter duration jobs in a study population occurring predominantly early in the work history may exacerbate problems associated with exposure misclassification. While few specific suggestions emerge from this analysis, the inclusion of extensive recording of the work history of study subjects emerges as a reasonable basis for the investigation and potential reduction of secondary misclassification of exposures in occupational epidemiological studies.     

Comparability of different methods of retrospective exposure assessment of metals in manufacturing industries

Many occupational case-control studies have relied on either self-report or exposure assessment based on job titles linked to a job exposure matrix (JEM) as opposed to the generally considered more accurate, but labor intensive, method of expert review of job histories. Our study examined the comparability of these different methods in assessing occupational exposure to the metals copper (Cu), lead (Pb), and iron (Fe) in manufacturing industries. Subjects were older people from a case-control study of a neurologic disease, and consisted of 188 individuals (72% male, 85% white) who had worked an average of 22.4 years in the manufacturing industry. An industrial hygienist review (IHR) of occupational history data from a comprehensive questionnaire was used as the reference method. The percent agreement (%A), sensitivity (SE), and specificity (SP) for direct self-report of metal exposures were: Cu, %A = 94.6, SE = 83.6, SP = 96.1; Pb, %A = 91.9, SE = 72.5, SP = 93.5; and Fe, %A = 82.7, SE = 64.5, SP = 88.1. Using the National Institute for Occupational Safety and Health (NIOSH) JEM, we analyzed the jobs of 115 of the 188 study subjects who had all their jobs listed in the JEM. Exposure assessment based on the NIOSH JEM compared with the IHR resulted in greater misclassification relative to direct self-report: Cu, %A = 81.5, SE = 21.2, SP = 89.2; Pb, %A = 86.0, SE = 0.0, SP = 92.6; and Fe, %A = 69.2, SE = 15.5, SP = 86.4. For all three study metals, combining the information from both direct self-report and the JEM did not improve upon the results compared with direct self-report alone. Due to the complex nature of metal exposure assessment, we suggest using an expert review of job histories whenever possible to minimize potential misclassification. Am. J. Ind. Med. 31:36–43 © 1997 Wiley-Liss, Inc.     

Comparison of occupational exposure using three different methods: hygiene panel, job exposure matrix (JEM), and self reports

This study was undertaken to compare the agreement of occupational exposure assessment by a panel of occupational hygienists with a job exposure matrix and self-reported exposures in a community-based case-control study. We also investigated the intra-rater reliability and degree of attenuation of the hypothetical odds ratio of the panel in retrospective chemical exposure assessment. A panel of three occupational hygienists was recruited to assess exposure to chemicals for 5,620 jobs. The agreement between the panel, a job exposure matrix (FINJEM), and the self-reported exposures was then assessed. A further 172 jobs were resubmitted to the panel to assess intra-rater reliability. The kappa for intra-rater reliability ranged from 0.60-0.71. The agreement between the panel and FINJEM ranged from 0.07 to 0.46 (for similar exposures), and agreement between the panel and among the self-reports ranged from 0.00 to 0.48. Agreement between hygienists when rating exposure to the same chemical ranged from 0.48 to 0.57. Based on these findings, the degree of exposure misclassification by the panel where the true odds ratio was 2 would result in the observed odds ratio ranging between 1.70 and 1.88. The results indicated good intra-rater reliability for the hygiene panel. However, the agreement among the panel, FINJEM, and self-reported exposures was found to be only poor to fair. The attenuation of the odds ratios due to exposure misclassification by the panel was variable and dependent upon the exposure.     

Challenges to retrospective exposure assessment

Retrospective exposure assessment has become a crucial component in the interpretation of occupational epidemiologic results. Many advances have been made over the last 2 decades, but substantial progress is still necessary to reduce the misclassification of exposure. The efforts needed include evaluating the validity and reliability of assessment methods, better documentation of the methods, use of exposure determinants to estimate exposure levels more accurately and reliably, and an increase in the understanding of industrial hygiene and biological measurement data and questionnaires, their limitations, and how to use them best. In addition, better characterization of exposures is necessary. This need includes evaluating dermal and ingestion hazards, incorporating nonoccupational sources of exposures, particularly hobbies, evaluating the effect of multiple chemicals, and exploring different exposure metrics.     

Integrating workplace exposure databases for occupational medicine services and epidemiologic studies at a former nuclear weapons facility

We outline methods for integrating epidemiologic and industrial hygiene data systems for the purpose of exposure estimation, exposure surveillance, worker notification, and occupational medicine practice. We present examples of these methods from our work at the Rocky Flats Plant--a former nuclear weapons facility that fabricated plutonium triggers for nuclear weapons and is now being decontaminated and decommissioned. The weapons production processes exposed workers to plutonium, gamma photons, neutrons, beryllium, asbestos, and several hazardous chemical agents, including chlorinated hydrocarbons and heavy metals. We developed a job exposure matrix (JEM) for estimating exposures to 10 chemical agents in 20 buildings for 120 different job categories over a production history spanning 34 years. With the JEM, we estimated lifetime chemical exposures for about 12,000 of the 16,000 former production workers. We show how the JEM database is used to estimate cumulative exposures over different time periods for epidemiological studies and to provide notification and determine eligibility for a medical screening program developed for former workers. We designed an industrial hygiene data system for maintaining exposure data for current cleanup workers. We describe how this system can be used for exposure surveillance and linked with the JEM and databases on radiation doses to develop lifetime exposure histories and to determine appropriate medical monitoring tests for current cleanup workers. We also present time-line-based graphical methods for reviewing and correcting exposure estimates and reporting them to individual workers.     

Accounting for error due to misclassification of exposures in case-control studies of gene-environment interaction

We consider analysis of data from an unmatched case-control study design with a binary genetic factor and a binary environmental exposure when both genetic and environmental exposures could be potentially misclassified. We devise an estimation strategy that corrects for misclassification errors and also exploits the gene-environment independence assumption. The proposed corrected point estimates and confidence intervals for misclassified data reduce back to standard analytical forms as the misclassification error rates go to zero. We illustrate the methods by simulating unmatched case-control data sets under varying levels of disease-exposure association and with different degrees of misclassification. A real data set on a case-control study of colorectal cancer where a validation subsample is available for assessing genotyping error is used to illustrate our methods.     

Comparison of industrial hygienists' exposure evaluations for an epidemiologic study

OBJECTIVES: A study was conducted to determine what level of information is required by industrial hygienists before they can develop exposure estimates comparable with those developed from a more in-depth evaluation. METHODS: Three industrial hygienists evaluated formaldehyde exposures of 300 jobs selected from an earlier epidemiologic study. The jobs were evaluated over the following 6 cycles: (i) job title and industry; (ii) job title, industry, dates; (iii) job and department title and industry; (iv) cycle 3 information with dates; (v) cycle 3 information with a plant report; and (vi) job and department title, industry, dates, and the report. Each hygienist assigned jobs to 1 of 4 exposure categories, which were compared with the categories in the original epidemiologic study. RESULTS: Overall, the mean differences between the hygienists' evaluations and the standard, although small, changed little over the cycles. The kappa statistic was poor to moderate for all the cycles, but the agreement was greater than expected due to chance. There was moderate improvement in overall agreement over the cycles using the weighted kappa statistic, but little improvement in the intraclass correlation coefficients of the hygienists' evaluations, which ranged from 0.4 to 0.5. Department information improved the agreement with the standard by 5--10%, but dates did not the improve agreement. There were some differences by type of plant, job function, exposure level, and date of the estimate. Using a hypothetical exposure-response scenario, this level of misclassification would have resulted in missing an association. CONCLUSIONS: Although there was slight improvement with increasing levels of information, these findings suggest that the subjective categorical assessment of exposures by industrial hygienists will not produce exposure estimates comparable to more in-depth evaluations of exposure.     

Estimating historical exposures of workers in a beryllium manufacturing plant

BACKGROUND: Beryllium is known to be toxic to the lungs, causing beryllium lung disease and associated with increased lung cancer risk. Airborne beryllium exposures have been monitored since the 1940s. This study describes methods used to measure airborne beryllium concentrations and how historical measurements from a beryllium manufacturing plant were used to estimate workers' exposures in a lung cancer case-control study. METHODS: Airborne beryllium concentrations had been measured using all-glass impingers, high-volume air filters, and personal respirable and total dust samplers. To provide consistency in exposure estimates over time, measurements collected by the other monitoring methods were converted to approximate the most frequently used high-volume, time-weighted average measurements. Because industrial hygiene measurements were not collected in every year for all jobs throughout the duration of the case-control study, exposure estimates had to be extrapolated from the existing measurements over time and across jobs. RESULTS: Over 7,000 historical measurements were available to estimate beryllium exposures of workers over time. Average exposures between jobs varied considerably and exposures for all jobs decreased dramatically between the 1940s and 1970s due to major plant production changes. CONCLUSIONS: Although error in the exposure metrics for the cases and controls likely occurred due to limitations of the exposure assessment data, the exposure estimates for each job over time provided a reasonable, objective mechanism for categorizing workers by the relative exposures they were likely to have encountered during their tenure. Published 2001 Wiley-Liss, Inc.     

Validation of exposure estimation for benzene in the Australian petroleum industry

A nested case-control study was undertaken to investigate whether an excess of lympho-haematopoietic cancers in the Australian petroleum industry was associated with benzene exposure. The benzene exposures of the cases and controls were estimated using a quantitative algorithm based largely on exposures measured in the Australian petroleum industry. The algorithm was used to estimate, for each subject, the benzene exposure in parts per million (ppm) for each job held in the industry, and the cumulative exposure in ppm years. Because of the critical importance of the exposure assessment in this design of epidemiological study, particular attention was paid to the reliability of the inputs to the algorithm. The inputs [base estimates (BEs) of exposure and technology-specific exposure modifiers (EMs)] were compared to data from other sources including the occupational hygiene literature. Where such comparison data were available, they were generally found to confirm the values used in the algorithm, although four input values were changed as a result of the validation exercise. The integrity of the task-based algorithm was validated by employing it to calculate the exposures of the tanker drivers in the study and comparing these with measured daily exposure for tanker drivers in the Australian petroleum industry and exposure values found in the occupational hygiene literature. After adjustment for the mix of products carried by the Australian tanker drivers, the estimates from the algorithm were found to be comparable to the measured and literature values. This exercise provided evidence that the exposure assessment for the epidemiological study was reliable and that the results of the study can be used as the basis for evaluating the relationship between exposure to benzene and the risk of lympho-haematopoietic cancer.     

Occupational exposure assessment in case-control studies: opportunities for improvement

Community based case-control studies are an efficient means to study disease aetiologies, and may be the only practical means to investigate rare diseases. However, exposure assessment remains problematic. We review the literature on the validity and reliability of common case-control exposure assessment methods: occupational histories, job-exposure matrices (JEMs), self reported exposures, and expert assessments. Given the variable quality of current exposure assessment techniques, we suggest methods to improve assessments, including the incorporation of hygiene measurements: using data from administrative exposure databases; using results of studies identifying determinants of exposure to develop questionnaires; and where reasonable given latency and biological half life considerations, directly measuring exposures of study subjects.     

Bias in studies of parental self-reported occupational exposure and childhood cancer

Several case-control studies have demonstrated positive associations between parental occupational exposures and childhood cancer. However, an overestimation of risk estimates due to recall bias is of concern. The magnitude and nature of this bias were explored using data from a German case-control study on childhood leukemia conducted between 1992 and 1997. A moderate overreporting of occupational exposures by fathers was observed, particularly for the prenatal period. Overreporting was most apparent when the time between exposure and interview was short. It was also found that job titles were no satisfactory substitute for information on specific occupational exposures. The results of this analysis emphasize the need for more sophisticated exposure assessment methods in epidemiologic studies of childhood cancer. However, because future case-control studies will at least partially rely on questionnaire data, improvements including probing questions, better interview techniques, and validation studies are indicated.     

Tiered exposure-assessment strategy in the semiconductor health study

The Semiconductor Health Study included 14 U.S. companies with 82 silicon-based wafer-fabrication rooms and a complex array of processes and chemicals. Its epidemiologic components were a historical examination of spontaneous abortion rates among 902 women, a prospective evaluation of reproductive outcomes in 483 women, and a cross-sectional review of MAle fertility and of respiratory, ergonomic, neurologic, or gastrointestinal problems among 3,175 men and women. Designing an exposure assessment strategy presented unique problems, and multiple agents had to be evaluated. A three-tiered approach to exposure assessment was developed to reflect increasing specificity of exposures. At the first tier, employees were divided into fabrication and nonfabrication groups. At the second tier, work groups with qualitatively different exposures were determined. At the third tier, intensity of exposures to specific chemical, physical, and ergonomic agents was evaluated. Evaluations were based on worker reports of tasks performed, moderated by fabrication-specific factors observed by study industrial hygienists during site visits.     

Historical estimation of exposure to 1,3-butadiene, styrene, and dimethyldithiocarbamate among synthetic rubber workers

Quantitative estimates of exposure to 1,3-butadiene (BD), styrene (STY), and dimethyldithiocarbamate (DMDTC) were developed for a follow-up study of workers at six North American synthetic rubber plants. Procedures entailed identifying tasks and jobs involving exposure, identifying factors influencing historical changes in exposure potential, and using mathematical models to calculate job- and time-period-specific exposures. Exposure metrics included 8-hour time-weighted average (TWA) intensity, the annual number of peak exposures (BD: >100 ppm, STY: >50 ppm) and TWA intensity below and above the peak threshold. The 5th and 95th percentiles of the approximate probability distribution of each exposure estimate served as its 90% uncertainty interval. Job- and year-specific estimates were linked with subjects' work histories to obtain cumulative exposure indices. Exposure estimates varied among tasks, jobs, plants, and time periods. BD TWAs were approximately 10 ppm during the 1940s-1960s and declined during the 1970s and 1980s. STY TWAs were always <2 ppm. DMDTC exposure began in the 1950s, was high through the 1960s, and later declined. BD peak exposure accounted for a large proportion of cumulative BD exposure, whereas almost none of the STY exposure was experienced at levels >50 ppm. Exposure indices were correlated. Exposures were higher than previously estimated. Multiple correlations among DMDTC, BD, and STY exposure estimates make it difficult to estimate agent-specific effects. Limitations of the methodology include the potential inaccuracy of the estimates, the lack of adequate industrial hygiene data to validate the estimates, the additional inaccuracy of linkage with poorly specified job groups, and the potential for differential exposure misclassification because the jobs and work areas where excess leukemia mortality occurred were well-known at the time of this study. Nevertheless, the new exposure estimates were highly correlated with the old, yielding equivalent exposure ranking of workers and were comparable to limited industrial hygiene data published by NIOSH.     

Characterization of dust exposure for the study of chronic occupational lung disease: a comparison of different exposure assessment strategies

Various exposure assessment strategies were compared in the study of the relation between dust exposure and 11-year lung function change in 1,172 miners with 36,824 concurrently measured personal dust samples available from the 1969-1981 US National Study of Coal Workers' Pneumoconiosis. A miner's average exposure was assessed by calculating average exposures based on dust samples taken from each individual and by using different job exposure matrices (JEMs) with different underlying exposure categorizations, based on occupational categories, job title, mine, and time, to obtain average exposure estimates. For each grouping procedure, intragroup and intergroup variances and the pooled standard error of the mean were calculated to assess relative efficiency. The results show that considerable variation in slopes of exposure-response relations was found using different exposure assessment strategies. Standard errors of the slopes of the exposure-response relations with exposure on an individual basis compared with JEMs. Exposure assessment on an individual basis was extremely sensitive to the number of exposure measurements per individual. The study demonstrates the advantages and disadvantages of different exposure assessment strategies and shows the need for explicit publication of exposure assessment strategies for epidemiologic studies. Careful assessment of the influence of misclassification error in the exposure assessment on exposure-response modeling is warranted.     

A retrospective assessment of occupational exposure to elemental carbon in the U.S. trucking industry

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.     

Comparison of task-based exposure metrics for an epidemiologic study of isocyanate inhalation exposures among autobody shop workers

Because many occupational epidemiologic studies use exposure surrogates rather than quantitative exposure metrics, the UMass Lowell and Yale study of autobody shop workers provided an opportunity to evaluate the relative utility of surrogates and quantitative exposure metrics in an exposure response analysis of cross-week change in respiratory function. A task-based exposure assessment was used to develop several metrics of inhalation exposure to isocyanates. The metrics included the surrogates, job title, counts of spray painting events during the day, counts of spray and bystander exposure events, and a quantitative exposure metric that incorporated exposure determinant models based on task sampling and a personal workplace protection factor for respirator use, combined with a daily task checklist. The result of the quantitative exposure algorithm was an estimate of the daily time-weighted average respirator-corrected total NCO exposure (microg/m(3)). In general, these four metrics were found to be variable in agreement using measures such as weighted kappa and Spearman correlation. A logistic model for 10% drop in FEV(1) from Monday morning to Thursday morning was used to evaluate the utility of each exposure metric. The quantitative exposure metric was the most favorable, producing the best model fit, as well as the greatest strength and magnitude of association. This finding supports the reports of others that reducing exposure misclassification can improve risk estimates that otherwise would be biased toward the null. Although detailed and quantitative exposure assessment can be more time consuming and costly, it can improve exposure-disease evaluations and is more useful for risk assessment purposes. The task-based exposure modeling method successfully produced estimates of daily time-weighted average exposures in the complex and changing autobody shop work environment. The ambient TWA exposures of all of the office workers and technicians and 57% of the painters were found to be below the current U.K. Health and Safety Executive occupational exposure limit (OEL) for total NCO of 20 microg/m(3). When respirator use was incorporated, all personal daily exposures were below the U.K. OEL.     

Environmental determinants of Parkinson's disease

Increasing toxicologic and epidemiologic evidence suggests that pesticides and other environmental exposures are associated with idiopathic Parkinson's disease. Using a case-control study, the authors examined the impact of farming, pesticide use, rural residence, and well water use (including critical periods of childhood exposure) on the risk of Parkinson's disease. After adjustment for confounding, > or = 40 years of well-water exposure (compared to no well water use) was associated with an increased risk of Parkinson's disease (OR = 7.1; 95% CI: 2.3-22.1). The authors found an increased risk of Parkinson's disease (OR = 2.1; 95% Cl: 0.7-6.4) for well water use during the first 20 years of life (compared with <20 years of exposure) and saw some suggestion of an exposure-response relationship with increasing childhood exposure. Farming and pesticide use (occupational or residential) was not associated with Parkinson's disease but exposure assessment limitations warrant further investigation.