Meta-analysis of the quantitative effectiveness of risk management measures (RMM) in the workplace.

BACKGROUND AND OBJECTIVES: This paper describes an evaluation and analysis of an updated version of ECEL v3.0-an integrated risk management measure (RMM) library developed as part of a CEFIC LRI initiative. The occupational module contains extensive data on the quantitative effectiveness of RMMs to control inhalation and dermal exposure in the workplace. The objective was to investigate the effectiveness and variability in effectiveness of RMM and to explore the difference between optimal and non-optimal RMM applications in the workplace. METHODS: A new database structure and interface were developed and the content of the database was updated with a systematic literature review and integration with other databases (totalling 3373 records from 548 studies). To analyse the data, Bayesian linear mixed models were constructed with the study as a random effect and various study characteristics and RMM categories as fixed effects individually in separate models. A multivariate mixed model was used on a stratified dataset to test (amongst others) the conditions of RMM use. RESULTS: Analyses of the data indicated effectiveness values for each RMM category (for example ~87% for technical emission controls compared with ~60% for technical dispersion controls). Substantial variability in effectiveness was observed within and between different types of RMM. Seven study characteristics (covariables) were included in the analyses, which indicated a pronounced difference in as-built (optimal/experimental) and as-used (workplace) conditions of RMM use (93.3% and 74.6%, respectively). CONCLUSIONS: This library provides a reliable evidence base to derive base estimates of RMM effectiveness-beneficial for both registrant and downstream users. It stresses the importance of optimal use of RMMs in the workplace (technical design/functioning, use, and maintenance). Various challenges are foreseen to further update ECEL to improve guidance, for deriving improved estimates and ensure user-friendliness of the library.

Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY).

BACKGROUND: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents. OBJECTIVES: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking. METHODS: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI). RESULTS: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8). DISCUSSION: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.

Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Automated Coding of Job Descriptions From a General Population Study: Overview of Existing Tools, Their Application and Comparison.

OBJECTIVES: Automatic job coding tools were developed to reduce the laborious task of manually assigning job codes based on free-text job descriptions in census and survey data sources, including large occupational health studies. The objective of this study is to provide a case study of comparative performance of job coding and JEM (Job-Exposure Matrix)-assigned exposures agreement using existing coding tools. METHODS: We compared three automatic job coding tools [AUTONOC, CASCOT (Computer-Assisted Structured Coding Tool), and LabourR], which were selected based on availability, coding of English free-text into coding systems closely related to the 1988 version of the International Standard Classification of Occupations (ISCO-88), and capability to perform batch coding. We used manually coded job histories from the AsiaLymph case-control study that were translated into English prior to auto-coding to assess their performance. We applied two general population JEMs to assess agreement at exposure level. Percent agreement and PABAK (Prevalence-Adjusted Bias-Adjusted Kappa) were used to compare the agreement of results from manual coders and automatic coding tools. RESULTS: The coding per cent agreement among the three tools ranged from 17.7 to 26.0% for exact matches at the most detailed 4-digit ISCO-88 level. The agreement was better at a more general level of job coding (e.g. 43.8-58.1% in 1-digit ISCO-88), and in exposure assignments (median values of PABAK coefficient ranging 0.69-0.78 across 12 JEM-assigned exposures). Based on our testing data, CASCOT was found to outperform others in terms of better agreement in both job coding (26% 4-digit agreement) and exposure assignment (median kappa 0.61). CONCLUSIONS: In this study, we observed that agreement on job coding was generally low for the three tools but noted a higher degree of agreement in assigned exposures. The results indicate the need for study-specific evaluations prior to their automatic use in general population studies, as well as improvements in the evaluated automatic coding tools.

Occupational exposure to nickel and hexavalent chromium and the risk of lung cancer in a pooled analysis of case-control studies (SYNERGY).

There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.

Respirable Crystalline Silica Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Analysis of Case-Control Studies.

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

The current burden of cancer attributable to occupational exposures in Canada.

Exposure to occupational carcinogens is often overlooked as a contributor to the burden of cancer. To estimate the proportion of cancer cases attributable to occupational exposure in Canada in 2011, exposure prevalence and levels of 44 carcinogens were informed by data from the Canadian carcinogen exposure surveillance project (CAREX Canada). These were used with Canadian Census (between 1961 and 2011) and Labour Force Survey (annual surveys between 1976 and 2013) data to estimate the number of workers ever exposed to occupational carcinogens. Risk estimates of the association between each carcinogen and cancer site were selected mainly from published literature reviews. Population attributable risks were estimated using Levin's equation and applied to the 2011 cancer statistics from the Canadian Cancer Registry. It is estimated that 15.5 million Canadians alive in 2011 were exposed, during at least one year between 1961 and 2001, to at least one carcinogen in the workplace. Overall, we estimated that in 2011, between 3.9% (95% CI: 3.1%-8.1%) and 4.2% (95% CI: 3.3%-8.7%) of all incident cases of cancer were due to occupational exposure, corresponding to lower and upper numbers of 7700-21,800 cases. Five of the cancer sites - mesothelioma, non-melanoma skin cancer, lung, female breast, and urinary bladder - account for a total of 7600 to 21,200 cancers attributable to occupational exposures such as solar radiation, asbestos, diesel engine exhaust, crystalline silica, and night shift work. Our study highlights cancer sites and occupational exposures that need recognition and efforts by all stakeholders to avoid preventable cancers in the future.

Use and Reliability of Exposure Assessment Methods in Occupational Case-Control Studies in the General Population: Past, Present, and Future.

Introduction: Retrospective occupational exposure assessment has been challenging in case-control studies in the general population. We aimed to review (i) trends of different assessment methods used in the last 40 years and (ii) evidence of reliability for various assessment methods. Methods: Two separate literature reviews were conducted. We first reviewed all general population cancer case-control studies published from 1975 to 2016 to summarize the exposure assessment approach used. For the second review, we systematically reviewed evidence of reliability for all methods observed in the first review. Results: Among the 299 studies included in the first review, the most frequently used assessment methods were self-report/assessment (n = 143 studies), case-by-case expert assessment (n = 139), and job-exposure matrices (JEMs; n = 82). Usage trends for these methods remained relatively stable throughout the last four decades. Other approaches, such as the application of algorithms linking questionnaire responses to expert-assigned exposure estimates and modelling of exposure with historical measurement data, appeared in 21 studies that were published after 2000. The second review retrieved 34 comparison studies examining methodological reliability. Overall, we observed slightly higher median kappa agreement between exposure estimates from different expert assessors (~0.6) than between expert estimates and exposure estimates from self-reports (~0.5) or JEMs (~0.4). However, reported reliability measures were highly variable for different methods and agents. Limited evidence also indicates newer methods, such as assessment using algorithms and measurement-calibrated quantitative JEMs, may be as reliable as traditional methods. Conclusion: The majority of current research assesses exposures in the population with similar methods as studies did decades ago. Though there is evidence for the development of newer approaches, more concerted effort is needed to better adopt exposure assessment methods with more transparency, reliability, and efficiency.

Priority Setting for Occupational Cancer Prevention.

BACKGROUND: Selecting priority occupational carcinogens is important for cancer prevention efforts; however, standardized selection methods are not available. The objective of this paper was to describe the methods used by CAREX Canada in 2015 to establish priorities for preventing occupational cancer, with a focus on exposure estimation and descriptive profiles. METHODS: Four criteria were used in an expert assessment process to guide carcinogen prioritization: (1) the likelihood of presence and/or use in Canadian workplaces; (2) toxicity of the substance (strength of evidence for carcinogenicity and other health effects); (3) feasibility of producing a carcinogen profile and/or an occupational estimate; and (4) special interest from the public/scientific community. Carcinogens were ranked as high, medium or low priority based on specific conditions regarding these criteria, and stakeholder input was incorporated. Priorities were set separately for the creation of new carcinogen profiles and for new occupational exposure estimates. RESULTS: Overall, 246 agents were reviewed for inclusion in the occupational priorities list. For carcinogen profile generation, 103 were prioritized (11 high, 33 medium, and 59 low priority), and 36 carcinogens were deemed priorities for occupational exposure estimation (13 high, 17 medium, and 6 low priority). CONCLUSION: Prioritizing and ranking occupational carcinogens is required for a variety of purposes, including research, resource allocation at different jurisdictional levels, calculations of occupational cancer burden, and planning of CAREX-type projects in different countries. This paper outlines how this process was achieved in Canada; this may provide a model for other countries and jurisdictions as a part of occupational cancer prevention efforts.

Burden of lung cancer attributable to occupational diesel engine exhaust exposure in Canada.

OBJECTIVE: To estimate the population attributable fraction (PAF) and number of incident and fatal lung cancers in Canada from occupational exposure to diesel engine exhaust (DEE). METHODS: DEE exposure prevalence and level estimates were used with Canadian Census and Labour Force Survey data to model the exposed population across the risk exposure period (REP, 1961-2001). Relative risks of lung cancer were calculated based on a meta-regression selected from the literature. PAFs were calculated using Levin's equation and applied to the 2011 lung cancer statistics obtained from the Canadian Cancer Registry. RESULTS: We estimated that 2.4% (95% CI 1.6% to 6.6%) of lung cancers in Canada are attributable to occupational DEE exposure, corresponding to approximately 560 (95% CI 380 to 1570) incident and 460 (95% CI 310 to 1270) fatal lung cancers in 2011. Overall, 1.6 million individuals alive in 2011 were occupationally exposed to DEE during the REP, 97% of whom were male. Occupations with the highest burden were underground miners, truck drivers and mechanics. Half of the attributable lung cancers occurred among workers with low exposure. CONCLUSIONS: This is the first study to quantify the burden of lung cancer attributable to occupational DEE exposure in Canada. Our results underscore a large potential for prevention, and a large public health impact from occupational exposure to low levels of DEE.

Estimating National-Level Exposure to Antineoplastic Agents in the Workplace: CAREX Canada Findings and Future Research Needs.

OBJECTIVES: Occupational exposure to antineoplastic agents occurs in various environments and is associated with increased cancer risk and adverse reproductive outcomes. National-level information describing the location and extent of occupational exposure to antineoplastic agents is unavailable in Canada and most other countries. CAREX Canada aimed to estimate the prevalence and relative levels of occupational exposures to antineoplastic agents across work setting, occupation, and sex. METHODS: 'Exposure' was defined as any potential for worker contact with antineoplastic agents. Baseline numbers of licensed workers were obtained from their respective professional bodies. For unlicensed workers, Census data or data extrapolated from human resources reports (e.g., staffing ratios) were used. Prevalence was estimated by combining population estimates with exposure proportions from peer-reviewed and grey literature. Exposure levels (classified as low, moderate, and high) by occupation and work setting were estimated qualitatively by combining estimates of contact frequency and exposure control practices. RESULTS: Approximately 75000 Canadians (0.42% of the total workforce) are estimated as occupationally exposed to antineoplastic agents; over 75% are female. The largest occupational group exposed to antineoplastic agents is community pharmacy workers, with 30200 exposed. By work setting, 39000 workers (52% of all exposed) are located in non-hospital settings; the remaining 48% are exposed in hospitals. The majority (75%) of workers are in the moderate exposure category. CONCLUSIONS: These estimates of the prevalence and location of occupational exposures to antineoplastic agents could be used to identify high-risk groups, estimate disease burden, and target new research and prevention activities. The limited secondary data available for developing these estimates highlights the need for increased quantitative measurement and documentation of antineoplastic agent contamination and exposure, particularly in work environments where use is emerging.

Evaluation of Automatically Assigned Job-Specific Interview Modules.

OBJECTIVE: In community-based epidemiological studies, job- and industry-specific 'modules' are often used to systematically obtain details about the subject's work tasks. The module assignment is often made by the interviewer, who may have insufficient occupational hygiene knowledge to assign the correct module. We evaluated, in the context of a case-control study of lymphoid neoplasms in Asia ('AsiaLymph'), the performance of an algorithm that provided automatic, real-time module assignment during a computer-assisted personal interview. METHODS: AsiaLymph's occupational component began with a lifetime occupational history questionnaire with free-text responses and three solvent exposure screening questions. To assign each job to one of 23 study-specific modules, an algorithm automatically searched the free-text responses to the questions 'job title' and 'product made or services provided by employer' using a list of module-specific keywords, comprising over 5800 keywords in English, Traditional and Simplified Chinese. Hierarchical decision rules were used when the keyword match triggered multiple modules. If no keyword match was identified, a generic solvent module was assigned if the subject responded 'yes' to any of the three solvent screening questions. If these question responses were all 'no', a work location module was assigned, which redirected the subject to the farming, teaching, health professional, solvent, or industry solvent modules or ended the questions for that job, depending on the location response. We conducted a reliability assessment that compared the algorithm-assigned modules to consensus module assignments made by two industrial hygienists for a subset of 1251 (of 11409) jobs selected using a stratified random selection procedure using module-specific strata. Discordant assignments between the algorithm and consensus assignments (483 jobs) were qualitatively reviewed by the hygienists to evaluate the potential information lost from missed questions with using the algorithm-assigned module (none, low, medium, high). RESULTS: The most frequently assigned modules were the work location (33%), solvent (20%), farming and food industry (19%), and dry cleaning and textile industry (6.4%) modules. In the reliability subset, the algorithm assignment had an exact match to the expert consensus-assigned module for 722 (57.7%) of the 1251 jobs. Overall, adjusted for the proportion of jobs in each stratum, we estimated that 86% of the algorithm-assigned modules would result in no information loss, 2% would have low information loss, and 12% would have medium to high information loss. Medium to high information loss occurred for <10% of the jobs assigned the generic solvent module and for 21, 32, and 31% of the jobs assigned the work location module with location responses of 'someplace else', 'factory', and 'don't know', respectively. Other work location responses had ≤8% with medium to high information loss because of redirections to other modules. Medium to high information loss occurred more frequently when a job description matched with multiple keywords pointing to different modules (29-69%, depending on the triggered assignment rule). CONCLUSIONS: These evaluations demonstrated that automatically assigned modules can reliably reproduce an expert's module assignment without the direct involvement of an industrial hygienist or interviewer. The feasibility of adapting this framework to other studies will be language- and exposure-specific.

CAREX Canada: an enhanced model for assessing occupational carcinogen exposure.

OBJECTIVES: To estimate the numbers of workers exposed to known and suspected occupational carcinogens in Canada, building on the methods of CARcinogen EXposure (CAREX) projects in the European Union (EU). METHODS: CAREX Canada consists of estimates of the prevalence and level of exposure to occupational carcinogens. CAREX Canada includes occupational agents evaluated by the International Agency for Research on Cancer as known, probable or possible human carcinogens that were present and feasible to assess in Canadian workplaces. A Canadian Workplace Exposure Database was established to identify the potential for exposure in particular industries and occupations, and to create exposure level estimates among priority agents, where possible. CAREX EU data were reviewed for relevance to the Canadian context and the proportion of workers likely to be exposed by industry and occupation in Canada was assigned using expert assessment and agreement by a minimum of two occupational hygienists. These proportions were used to generate prevalence estimates by linkage with the Census of Population for 2006, and these estimates are available by industry, occupation, sex and province. RESULTS: CAREX Canada estimated the number of workers exposed to 44 known, probable and suspected carcinogens. Estimates of levels of exposure were further developed for 18 priority agents. Common exposures included night shift work (1.9 million exposed), solar ultraviolet radiation exposure (1.5 million exposed) and diesel engine exhaust (781 000 exposed). CONCLUSIONS: A substantial proportion of Canadian workers are exposed to known and suspected carcinogens at work.