Melissa C. Friesen

OccIDEAS: Retrospective Occupational Exposure Assessment in Community-Based Studies Made Easier

Assessing occupational exposure in retrospective community-based case-control studies is difficult as measured exposure data are very seldom available. The expert assessment method is considered the most accurate way to attribute exposure but it is a time consuming and expensive process and may be seen as subjective, nonreproducible, and nontransparent. In this paper, we describe these problems and outline our solutions as operationalized in a web-based software application (OccIDEAS). The novel aspects of OccIDEAS are combining all steps in the assessment into one software package; enmeshing the process of assessment into the development of questionnaires; selecting the exposure(s) of interest; specifying rules for exposure assignment; allowing manual or automatic assessments; ensuring that circumstances in which exposure is possible for an individual are highlighted for review; providing reports to ensure consistency of assessment. Development of this application has the potential to make high-quality occupational assessment more efficient and accessible for epidemiological studies.

Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study

Objectives Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. Methods At enrolment (1993–1997), spouses provided information about ever use of specific pesticides, including 10 OPs, demographic information, reproductive health history and other potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% CIs for all cancers diagnosed through 2010 for North Carolina and through 2011 for Iowa. Results Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43). Conclusions We observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation.

Quantitative Exposure to Metalworking Fluids and Bladder Cancer Incidence in a Cohort of Autoworkers

Occupations with mineral oil exposure have been associated with bladder cancer in population-based case-control studies. The authors report results from the first cohort study to examine bladder cancer incidence in relation to quantitative exposures to metalworking fluids (MWFs), based on 21,999 male Michigan automotive workers, followed from 1985 through 2004. Cox regression was used to estimate hazard ratios based on categorical exposure variables for straight, soluble, and synthetic MWFs, as well as duration of exposure to ethanolamines and nitrosamines. Penalized splines were also fit to estimate the functional form of the exposure-response relation. Increased bladder cancer risk was associated with straight MWFs but not with any other exposure. The hazard ratio increased with cumulative exposure to a maximum of 2-fold observed at 75 mg/m(3)-year straight MWF exposure (lagged 20 years). Calendar time windows relevant to polycyclic aromatic hydrocarbon exposure were examined but could not be distinguished from the lagged (10-, 20-year) metrics. No association was observed between any exposure and incident lung cancer, suggesting that smoking is unlikely to confound the associations observed here. The quantitative relation with straight MWFs strengthens the evidence for mineral oils as a bladder carcinogen.

Predicting Historical Dust and Wood Dust Exposure in Sawmills: Model Development and Validation

Nonspecific dust measurements are used as a surrogate for wood dust exposure in sawmills. However, the wood dust component of dust has been found to vary by job and work area. Thus, the use of nonspecific dust exposure levels in epidemiologic studies may introduce exposure misclassification when assessing wood-related health effects. To improve exposure assessment in a retrospective cohort of 28,000 sawmill workers, we developed and evaluated the validity of two empirical models of exposure: one for nonspecific dust and one for wood dust. The dust model was constructed using 1395 dust measurements collected in 13 sawmills for research or regulatory purposes from 1981 to 1997. Inter-sampler conversion factors were used to obtain inhalable dust equivalents if necessary. The wood dust model was constructed after applying adjustment factors to subtract nonwood components of the dust from the original measurements. The validity of the two models was tested against measurements (n = 213) from a technologically similar mill that was not part of the cohort study. The proportions of variability explained by the dust and wood dust models were 35% and 54%, respectively. When tested against the validation mill, the biases in the dust model were − 33% for outdoor jobs and 2% for indoor jobs. The biases in the wood dust model were 2% for outdoor jobs and −3% for indoor jobs. Strong correlations were observed between the predicted and observed geometric means of jobs (0.79 and 0.70 for the dust model and wood dust model, respectively). Testing the validity of predictive models examines the generalizability of the models. The low overall bias, especially in the wood-specific model, increases our confidence in the use of these models for all sawmills to assess both nonspecific particulate and wood-related health effects in the historical cohort study.

Workplace Measurements by the US Occupational Safety and Health Administration since 1979: Descriptive Analysis and Potential Uses for Exposure Assessment

BACKGROUND Inspectors from the US Occupational Safety and Health Administration (OSHA) have been collecting industrial hygiene samples since 1972 to verify compliance with Permissible Exposure Limits. Starting in 1979, these measurements were computerized into the Integrated Management Information System (IMIS). In 2010, a dataset of over 1 million personal sample results analysed at OSHAs central laboratory in Salt Lake City [Chemical Exposure Health Data (CEHD)], only partially overlapping the IMIS database, was placed into public domain via the internet. We undertook this study to inform potential users about the relationship between this newly available OSHA data and IMIS and to offer insight about the opportunities and challenges associated with the use of OSHA measurement data for occupational exposure assessment. METHODS We conducted a literature review of previous uses of IMIS in occupational health research and performed a descriptive analysis of the data recently made available and compared them to the IMIS database for lead, the most frequently sampled agent. RESULTS The literature review yielded 29 studies reporting use of IMIS data, but none using the CEHD data. Most studies focused on a single contaminant, with silica and lead being most frequently analysed. Sixteen studies addressed potential bias in IMIS, mostly by examining the association between exposure levels and ancillary information. Although no biases of appreciable magnitude were consistently reported across studies and agents, these assessments may have been obscured by selective under-reporting of non-detectable measurements. The CEHD data comprised 1 450 836 records from 1984 to 2009, not counting analytical blanks and erroneous records. Seventy eight agents with >1000 personal samples yielded 1 037 367 records. Unlike IMIS, which contain administrative information (company size, job description), ancillary information in the CEHD data is mostly analytical. When the IMIS and CEHD measurements of lead were merged, 23 033 (39.2%) records were in common to both IMIS and CEHD datasets, 10 681 (18.2%) records were only in IMIS, and 25 012 (42.6%) records were only in the CEHD database. While IMIS-only records represent data analysed in other laboratories, CEHD-only records suggest partial reporting of sampling results by OSHA inspectors into IMIS. For lead, the percentage of non-detects in the CEHD-only data was 71% compared to 42% and 46% in the both-IMIS-CEHD and IMIS-only datasets, respectively, suggesting differential under-reporting of non-detects in IMIS. CONCLUSIONS IMIS and the CEHD datasets represent the biggest source of multi-industry exposure data in the USA and should be considered as a valuable source of information for occupational exposure assessment. The lack of empirical data on biases, adequate interpretation of non-detects in OSHA data, complicated by suspected differential under-reporting, remain the principal challenges to the valid estimation of average exposure conditions. We advocate additional comparisons between IMIS and CEHD data and discuss analytical strategies that may play a key role in meeting these challenges.

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 (κw=0.68–0.81) and for jobs with diesel-relevant modules (κw=0.62–0.78) for the probability, intensity and frequency metrics. For exposed subjects, the Spearman correlation statistic was 0.72 between the cumulative OH/module and one-by-one review estimates. 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.

Comparison of two indices of exposure to polycyclic aromatic hydrocarbons in a retrospective aluminium smelter cohort

Background: The association between coal tar-derived substances, a complex mixture of polycyclic aromatic hydrocarbons, and cancer is well established. However, the specific aetiological agents are unknown. Objective: To compare the dose–response relationships for two common measures of coal tar-derived substances, benzene-soluble material (BSM) and benzo(a)pyrene (BaP), and to evaluate which among these is more strongly related to the health outcomes. Methods: The study population consisted of 6423 men with ⩾3 years of work experience at an aluminium smelter (1954–97). Three health outcomes identified from national mortality and cancer databases were evaluated: incidence of bladder cancer (n = 90), incidence of lung cancer (n = 147) and mortality due to acute myocardial infarction (AMI, n = 184). The shape, magnitude and precision of the dose–response relationships and cumulative exposure levels for BSM and BaP were evaluated. Two model structures were assessed, where 1n(relative risk) increased with cumulative exposure (log-linear model) or with log-transformed cumulative exposure (log–log model). Results: The BaP and BSM cumulative exposure metrics were highly correlated (r = 0.94). The increase in model precision using BaP over BSM was 14% for bladder cancer and 5% for lung cancer; no difference was observed for AMI. The log-linear BaP model provided the best fit for bladder cancer. The log–log dose–response models, where risk of disease plateaus at high exposure levels, were the best-fitting models for lung cancer and AMI. Conclusion: BaP and BSM were both strongly associated with bladder and lung cancer and modestly associated with AMI. Similar conclusions regarding the associations could be made regardless of the exposure metric.

Inside the black box: starting to uncover the underlying decision rules used in a one-by-one expert assessment of occupational exposure in case-control studies.

Objectives Evaluating occupational exposures in population-based case-control studies often requires exposure assessors to review each study participants reported occupational information job-by-job to derive exposure estimates. Although such assessments likely have underlying decision rules, they usually lack transparency, are time consuming and have uncertain reliability and validity. We aimed to identify the underlying rules to enable documentation, review and future use of these expert-based exposure decisions. Methods Classification and regression trees (CART, predictions from a single tree) and random forests (predictions from many trees) were used to identify the underlying rules from the questionnaire responses, and an experts exposure assignments for occupational diesel exhaust exposure for several metrics: binary exposure probability and ordinal exposure probability, intensity and frequency. Data were split into training (n=10 488 jobs), testing (n=2247) and validation (n=2248) datasets. Results The CART and random forest models’ predictions agreed with 92–94% of the experts binary probability assignments. For ordinal probability, intensity and frequency metrics, the two models extracted decision rules more successfully for unexposed and highly exposed jobs (86–90% and 57–85%, respectively) than for low or medium exposed jobs (7–71%). Conclusions CART and random forest models extracted decision rules and accurately predicted an experts exposure decisions for the majority of jobs, and identified questionnaire response patterns that would require further expert review if the rules were applied to other jobs in the same or different study. This approach makes the exposure assessment process in case-control studies more transparent, and creates a mechanism to efficiently replicate exposure decisions in future studies.

Chronic and Acute Effects of Coal Tar Pitch Exposure and Cardiopulmonary Mortality Among Aluminum Smelter Workers

Air pollution causes several adverse cardiovascular and respiratory effects. In occupational studies, where levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) are higher, the evidence is inconsistent. The effects of acute and chronic PAH exposure on cardiopulmonary mortality were examined within a Kitimat, Canada, aluminum smelter cohort (n = 7,026) linked to a national mortality database (1957-1999). No standardized mortality ratio was significantly elevated compared with the provinces population. Smoking-adjusted internal comparisons were conducted using Cox regression for male subjects (n = 6,423). Ischemic heart disease (IHD) mortality (n = 281) was associated with cumulative benzo[a]pyrene (B(a)P) exposure (hazard ratio = 1.62, 95% confidence interval: 1.06, 2.46) in the highest category. A monotonic but nonsignificant trend was observed with chronic B(a)P exposure and acute myocardial infarction (n = 184). When follow-up was restricted to active employment, the hazard ratio for IHD was 2.39 (95% confidence interval: 0.95, 6.05) in the highest cumulative B(a)P category. The stronger associations observed during employment suggest that risk may not persist after exposure cessation. No associations with recent or current exposure were observed. IHD was associated with chronic (but not current) PAH exposure in a high-exposure occupational setting. Given the widespread workplace exposure to PAHs and heart diseases high prevalence, even modest associations produce a high burden.

A Review of Nonoccupational Pathways for Pesticide Exposure in Women Living in Agricultural Areas

Background Women living in agricultural areas may experience high pesticide exposures compared with women in urban or suburban areas because of their proximity to farm activities. Objective Our objective was to review the evidence in the published literature for the contribution of nonoccupational pathways of pesticide exposure in women living in North American agricultural areas. Methods We evaluated the following nonoccupational exposure pathways: paraoccupational (i.e., take-home or bystander exposure), agricultural drift, residential pesticide use, and dietary ingestion. We also evaluated the role of hygiene factors (e.g., house cleaning, shoe removal). Results Among 35 publications identified (published 1995–2013), several reported significant or suggestive (p < 0.1) associations between paraoccupational (n = 19) and agricultural drift (n = 10) pathways and pesticide dust or biomarker levels, and 3 observed that residential use was associated with pesticide concentrations in dust. The 4 studies related to ingestion reported low detection rates of most pesticides in water; additional studies are needed to draw conclusions about the importance of this pathway. Hygiene factors were not consistently linked to exposure among the 18 relevant publications identified. Conclusions Evidence supported the importance of paraoccupational, drift, and residential use pathways. Disentangling exposure pathways was difficult because agricultural populations are concurrently exposed to pesticides via multiple pathways. Most evidence was based on measurements of pesticides in residential dust, which are applicable to any household member and are not specific to women. An improved understanding of nonoccupational pesticide exposure pathways in women living in agricultural areas is critical for studying health effects in women and for designing effective exposure-reduction strategies. Citation Deziel NC, Friesen MC, Hoppin JA, Hines CJ, Thomas K, Beane Freeman LE. 2015. A review of nonoccupational pathways for pesticide exposure in women living in agricultural areas. Environ Health Perspect 123:515–524; http://dx.doi.org/10.1289/ehp.1408273