Development of and Selected Performance Characteristics of CANJEM, a General Population Job-Exposure Matrix Based on Past Expert Assessments of Exposure.

Objectives: We developed a job-exposure matrix called CANJEM using data generated in population-based case-control studies of cancer. This article describes some of the decisions in developing CANJEM, and some of its performance characteristics. Methods: CANJEM is built from exposure information from 31673 jobs held by study subjects included in our past case-control studies. For each job, experts had evaluated the intensity, frequency, and likelihood of exposure to a predefined list of agents based on jobs histories and descriptions of tasks and workplaces. The creation of CANJEM involved a host of decisions regarding the structure of CANJEM, and operational decisions regarding which parameters to present. The goal was to produce an instrument that would provide great flexibility to the user. In addition to describing these decisions, we conducted analyses to assess how well CANJEM covered the range of occupations found in Canada. Results: Even at quite a high level of resolution of the occupation classifications and time periods, over 90% of the recent Canadian working population would be covered by CANJEM. Prevalence of exposure of specific agents in specific occupations ranges from 0% to nearly 100%, thereby providing the user with basic information to discriminate exposed from unexposed workers. Furthermore, among exposed workers there is information that can be used to discriminate those with high exposure from those with low exposure. Conclusions: CANJEM provides good coverage of the Canadian working population and possibly that of several other countries. Available in several occupation classification systems and including 258 agents, CANJEM can be used to support exposure assessment efforts in epidemiology and prevention of occupational diseases.

Investigation of occupational asthma: Do clinicians fail to identify relevant occupational exposures?

BACKGROUND: Specific inhalation challenges (SIC) enable the identification of the agent responsible of occupational asthma (OA). A clinician may fail to identify a specific agent in the workplace, which may potentially lead to a misdiagnosis. The expert assessment method performed by an occupational hygienist has been used to evaluate occupational exposures in epidemiological studies. OBJECTIVE: The broad aim of the present study was to evaluate the contribution of an expert assessment performed by an occupational hygienist to the diagnosis of OA. The specific aim was to compare workplace exposures identified by an occupational hygienist and by chest physicians in subjects with positive SICs and subjects with asthma, but with a negative SIC. METHODS: SICs were performed in 120 cases: 67 were positive and 53 were negative. A clinician assessed occupational exposures to sensitizers during a routine clinical evaluation preceding the performance of the SIC. An expert assessment of occupational exposures was performed by an occupational hygienist blind to the result of the SIC. RESULTS: The occupational hygienist identified the causal agent in 96.7% of the 61 cases of positive SIC. In 33 (62.3%) cases of negative SICs, the occupational hygienist identified ≥1 sensitizing agent(s) that had not been identified by the clinician. CONCLUSION: The hygienist identified the causal agent in almost all subjects with OA. In contrast, the clinician failed to identify potential exposures to sensitizers in >60% of the negative SIC subjects, which may have resulted in some subjects being misdiagnosed as not having OA.

IARC monographs: 40 years of evaluating carcinogenic hazards to humans.

BACKGROUND: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. OBJECTIVES: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. DISCUSSION: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

Screening for occupational asthma by using a self-administered questionnaire in a clinical setting.

OBJECTIVE: Because of its high prevalence, early screening for occupational asthma (OA) is crucial. We aimed to evaluate the screening performance of the Occupational Asthma Screening Questionnaire-11 items (OASQ-11) in a clinical setting. METHODS: Between January 2009 and December 2011, 169 workers referred for potential OA to our hospital completed the OASQ-11 and underwent workups to determine the final diagnosis. The discriminative abilities of the OASQ-11 as a whole and in relation to demographic and exposure parameters were determined by the area under the receiving operator characteristic curve (AUC). RESULTS: Model 1, consisting of the OASQ's items, showed fair discrimination (AUC, 0.69; 95% confidence interval, 0.58 to 0.80). Addition of age and exposure duration to model 1 improved discrimination (AUC, 0.80; confidence interval, 0.72 to 0.88). CONCLUSION: A simple model consisting of the OASQ-11's items, age, and exposure duration could well discriminate subjects with OA in a clinical setting.

Silica exposure during construction activities: statistical modeling of task-based measurements from the literature.

Many construction activities can put workers at risk of breathing silica containing dusts, and there is an important body of literature documenting exposure levels using a task-based strategy. In this study, statistical modeling was used to analyze a data set containing 1466 task-based, personal respirable crystalline silica (RCS) measurements gathered from 46 sources to estimate exposure levels during construction tasks and the effects of determinants of exposure. Monte-Carlo simulation was used to recreate individual exposures from summary parameters, and the statistical modeling involved multimodel inference with Tobit models containing combinations of the following exposure variables: sampling year, sampling duration, construction sector, project type, workspace, ventilation, and controls. Exposure levels by task were predicted based on the median reported duration by activity, the year 1998, absence of source control methods, and an equal distribution of the other determinants of exposure. The model containing all the variables explained 60% of the variability and was identified as the best approximating model. Of the 27 tasks contained in the data set, abrasive blasting, masonry chipping, scabbling concrete, tuck pointing, and tunnel boring had estimated geometric means above 0.1mg m(-3) based on the exposure scenario developed. Water-fed tools and local exhaust ventilation were associated with a reduction of 71 and 69% in exposure levels compared with no controls, respectively. The predictive model developed can be used to estimate RCS concentrations for many construction activities in a wide range of circumstances.

Occupational exposure to silica in construction workers: a literature-based exposure database.

We created an exposure database of respirable crystalline silica levels in the construction industry from the literature. We extracted silica and dust exposure levels in publications reporting silica exposure levels or quantitative evaluations of control effectiveness published in or after 1990. The database contains 6118 records (2858 of respirable crystalline silica) extracted from 115 sources, summarizing 11,845 measurements. Four hundred and eighty-eight records represent summarized exposure levels instead of individual values. For these records, the reported summary parameters were standardized into a geometric mean and a geometric standard deviation. Each record is associated with 80 characteristics, including information on trade, task, materials, tools, sampling strategy, analytical methods, and control measures. Although the database was constructed in French, 38 essential variables were standardized and translated into English. The data span the period 1974-2009, with 92% of the records corresponding to personal measurements. Thirteen standardized trades and 25 different standardized tasks are associated with at least five individual silica measurements. Trade-specific respirable crystalline silica geometric means vary from 0.01 (plumber) to 0.30 mg/m³ (tunnel construction skilled labor), while tasks vary from 0.01 (six categories, including sanding and electrical maintenance) to 1.59 mg/m³ (abrasive blasting). Despite limitations associated with the use of literature data, this database can be analyzed using meta-analytical and multivariate techniques and currently represents the most important source of exposure information about silica exposure in the construction industry. It is available on request to the research community.

Occupational risk factors associated with work-exacerbated asthma in Quebec.

BACKGROUND: There is limited information regarding the occupational exposures of subjects with a diagnosis of work-exacerbated asthma (WEA). OBJECTIVES: To: (1) identify potential specific occupational, chemical, biological and physical agents associated with incident cases of WEA and (2) compare these agents with occupational exposures of occupational asthma (OA) and non-work-related asthma (NWRA) cases. METHODS: Subjects were workers with work-related asthma (WRA) or NWRA referred between 2005 and 2008 to two Quebec clinics specialised in the field of WRA. Specific inhalation challenges were performed to differentiate OA from WEA. Work exposures were assessed using a detailed occupational questionnaire. Exposures to 41 chemical and biological agents were coded in a semiquantitative way according to a combination of indices for concentration in workplace air, frequency and confidence of exposure by an occupational hygienist expert in occupational exposure coding. This expert was blind to the medical status of WEA, OA or NWRA. Five physical agents were coded on a yes/no scale. RESULTS: 153 subjects were enrolled (53 WEA, 67 OA and 33 NWRA). WEA cases were significantly more exposed to ammonia, engine exhaust fumes, silica, mineral fibres, aerosol propellants and solvents, and significantly less exposed to animal derived dust and enzymes than were OA cases. Exposure to physical conditions did not differ between WEA and OA. CONCLUSIONS: Exposures associated with WEA differ from those associated with OA in this study. A proportion of subjects with WEA may suffer from low-dose irritant asthma, which remains a hypothesis to be tested.

Statistical modeling of crystalline silica exposure by trade in the construction industry using a database compiled from the literature.

A quantitative determinants-of-exposure analysis of respirable crystalline silica (RCS) levels in the construction industry was performed using a database compiled from an extensive literature review. Statistical models were developed to predict work-shift exposure levels by trade. Monte Carlo simulation was used to recreate exposures derived from summarized measurements which were combined with single measurements for analysis. Modeling was performed using Tobit models within a multimodel inference framework, with year, sampling duration, type of environment, project purpose, project type, sampling strategy and use of exposure controls as potential predictors. 1346 RCS measurements were included in the analysis, of which 318 were non-detects and 228 were simulated from summary statistics. The model containing all the variables explained 22% of total variability. Apart from trade, sampling duration, year and strategy were the most influential predictors of RCS levels. The use of exposure controls was associated with an average decrease of 19% in exposure levels compared to none, and increased concentrations were found for industrial, demolition and renovation projects. Predicted geometric means for year 1999 were the highest for drilling rig operators (0.238 mg m(-3)) and tunnel construction workers (0.224 mg m(-3)), while the estimated exceedance fraction of the ACGIH TLV by trade ranged from 47% to 91%. The predicted geometric means in this study indicated important overexposure compared to the TLV. However, the low proportion of variability explained by the models suggests that the construction trade is only a moderate predictor of work-shift exposure levels. The impact of the different tasks performed during a work shift should also be assessed to provide better management and control of RCS exposure levels on construction sites.

A population-based case-control study of occupational exposure to acids and the risk of lung cancer: evidence for specificity of association.

Occupational exposure to strong inorganic acid mists containing sulfuric acid has been recognized as a carcinogen (Group 1) since 1992. An augmented, secondary data analysis of a population-based case-control study of lung cancer was conducted to assess lung cancer-specific risks using 772 lung cancer cases diagnosed between 1981 and 1985. Individually matched controls--on age, gender, and borough of residence--were identified. Lifetime exposure to 10 acidic agents, including strong inorganic acids and some gases, was assessed from complete lifetime occupational histories in terms of concentration, frequency, and reliability of the various exposure assessments. Smoking-adjusted odds ratios and 95% confidence intervals were determined for overall and histology-categorized lung cancers using conditional logistic regression. No excess risk for overall lung cancer was associated with any of the acids, and effect modification by gender could not be identified. The absence of an acid lung cancer effect reinforces more recent toxicological data that suggest specificity to the larynx.

Frequency of work-related respiratory symptoms in workers without asthma.

BACKGROUND: Clinicians are faced with subjects complaining of work-related respiratory symptoms (WRS) without any evidence of asthma. We sought to assess the prevalence of subjects with WRS without asthma in a cohort of workers referred for possible work-related asthma (WRA) as well as compare the characteristics and the work environment of subjects with WRS to subjects with WRA. METHODS: A prospective observational study of workers referred for possible WRA over a 1-year period. Detailed medical and occupational questionnaires were administered. Pulmonary function tests as well as specific-inhalation challenges were performed. RESULTS: One hundred twenty workers were investigated. Fifty-one had WRA while 69 had WRS. The type and the severity of the respiratory symptoms were similar in both groups, except for wheezing which was more frequently reported in subjects with WRA (32 (62.7%)) than in subjects with WRS (16 (23.2%)) (P < 0.01). Both the workers with WRS and WRA were mainly employed in the manufacturing sector (64.7% (WRA) and 71% (WRS)). At the time of the first assessment 64.7% of subjects with WRA and 56.5% with WRS had left their workplace because of their bothersome respiratory symptoms. CONCLUSIONS: Subjects with WRS without asthma represent a large proportion of the subjects assessed in clinics specialized in the field of WRA. Like subjects with WRA, the population with WRS is likely to represent a significant medical burden. The similarity of the symptoms between the WRA and the WRS groups emphasizes the need to perform a thorough and objective investigation to diagnose WRA.

Formaldehyde exposure in U.S. industries from OSHA air sampling data.

National occupational exposure databanks have been cited as sources of exposure data for exposure surveillance and exposure assessment for occupational epidemiology. Formaldehyde exposure data recorded in the U.S Integrated Management Information System (IMIS) between 1979 and 2001 were collected to elaborate a multi-industry retrospective picture of formaldehyde exposures and to identify exposure determinants. Due to the database design, only detected personal measurement results (n = 5228) were analyzed with linear mixed-effect models, which explained 29% of the total variance. Short-term measurement results were higher than time-weighted average (TWA) data and decreased 18% per year until 1987 (TWA data 5% per year) and 5% per year (TWA data 4% per year) after that. Exposure varied across industries with maximal estimated TWA geometric means (GM) for 2001 in the reconstituted wood products, structural wood members, and wood dimension and flooring industries (GM = 0.20 mg/m(3). Highest short-term GMs estimated for 2001 were in the funeral service and crematory and reconstituted wood products industries (GM = 0.35 mg/m(3). Exposure levels in IMIS were marginally higher during nonprogrammed inspections compared with programmed inspections. An increasing exterior temperature tended to cause a decrease in exposure levels for cold temperatures (-5% per 5 degrees C for T < 15 degrees C) but caused an increase in exposure levels for warm temperatures (+15% per 5 degrees C for T >15 degrees C). Concentrations measured during the same inspection were correlated and varied differently across industries and sample type (TWA, short term). Sensitivity analyses using TOBIT regression suggested that the average bias caused by excluding non-detects is approximately 30%, being potentially higher for short-term data if many non-detects were actually short-term measurements. Although limited by availability of relevant exposure determinants and potential selection biases in IMIS, these results provide useful insight on formaldehyde occupational exposure in the United States in the last two decades. The authors recommend that more information on exposure determinants be recorded in IMIS.

Mortality and cancer experience of Quebec aluminum reduction plant workers. Part I: The reduction plants and coal tar pitch volatile (CTPV) exposure assessment.

OBJECTIVES: This paper presents the exposure assessment and job-exposure matrix (JEM) used to estimate coal tar pitch volatile (CTPV) exposure for a study of mortality and cancer incidence in aluminum smelter workers in Quebec, Canada. METHODS: Historical CTPV exposure was assessed by estimating benzene-soluble material (BSM) and benzo[a]pyrene (B[a]P) levels for combinations of job and time period. Estimates were derived by using several procedures including averaging measurement data, a deterministic mathematical model using process-related correction factors, and expert-based extrapolation. RESULTS: The JEM comprised 28,910 jobs, covering 7 facilities from 1916 to 1999. Estimated exposures ranged from 0.01 microg/m(3) to 68.08 microg/m(3) (B[a]P) and 0.01 mg/m(3) to 3.64 mg/m(3) (BSM) and were lowest before 1940 and after 1980. CONCLUSION: This methodology constitutes an improvement compared with methods used for previous studies of the Quebec cohort.

A web tool for the identification of potential interactive effects of chemical mixtures.

This project was undertaken to develop a toxicological database allowing the identification of possible additive or other interactive effects of mixtures present in the work environment. In the first phase of the project, whose findings have already been published, critical toxicological data were compiled for each of the 695 chemical substances in the Quebec Occupational Health Regulation, allowing the prediction of potential additivity among components of a mixture. In the second phase of this project, the types of interactions for mixtures most likely to be found in workplaces and for which primary literature data are available were specified. The toxicological data were evaluated only for realistic exposure concentrations up to the short-term exposure limit or ceiling value or five times the 8-hr time-weighted average (TWA) permissible exposure limit (PEL) for human data and up to 100 times the 8-hr TWA PEL or ceiling value for animal studies. In total, 675 studies were evaluated covering 209 binary mixtures of substances. For the majority of cases where potential additivity was identified in Phase 1, there is a lack of toxicological data in the primary literature. In these cases, the results of the first phase will be useful as the default hypothesis. The resulting database integrates the results from both phases of the project. A web-based computer tool allows the user to determine whether there is potential additivity or interaction among components of a mixture.

Statistical modelling of formaldehyde occupational exposure levels in French industries, 1986-2003.

Occupational exposure databanks (OEDBs) have been cited as sources of exposure data for exposure surveillance and exposure assessment in epidemiology. In 2003, an extract was made from COLCHIC, the French national OEDB, of all concentrations of formaldehyde. The data were analysed with extended linear mixed-effects models in order to identify influent variables and elaborate a multi-sector picture of formaldehyde exposures. Respectively, 1401 and 1448 personal and area concentrations were available for the analysis. The fixed effects of the personal and area models explained, respectively, 57 and 53% of the total variance. Personal concentrations were related to the sampling duration (short-term higher than TWA levels), decreased with the year of sampling (-9% per year) and were higher when local exhaust ventilation was present. Personal levels taken during planned visits and for occupational illness notification purpose were consistently lower than those taken during ventilation modification programmes or because the hygienist suspected the presence of significant risk or exposure. Area concentrations were related to the sampling duration (short-term higher than TWA levels), and decreased with the year of sampling (-7% per year) and when the measurement sampling flow increased. Significant within-facility (correlation coefficient 0.4-0.5) and within-sampling campaign correlation (correlation coefficient 0.8) was found for both area and personal data. The industry/task classification appeared to have the greatest influence on exposure variability while the sample duration and the sampling flow were significant in some cases. Estimates made from the models for year 2002 showed elevated formaldehyde exposure in the fields of anatomopathological and biological analyses, operation of gluing machinery in the wood industry, operation and monitoring of mixers in the pharmaceutical industry, and garages and warehouses in urban transit authorities.

Investigation of determinants of past and current exposures to formaldehyde in the reconstituted wood panel industry in Quebec.

OBJECTIVES: Past and present formaldehyde measurements made in facilities manufacturing reconstituted wood panels in Quebec have been collected in order to assess formaldehyde exposure and its determinants in this industry. METHODS: All 12 plants manufacturing Oriented-strand board (OSB), Medium density fibreboard (MDF) and Particle board (PB) in Quebec were visited by a research team which took area and personal measurements. Past measurements taken by governmental occupational health teams in these plants were also collected. Log-transformed formaldehyde concentrations were analysed with extended linear mixed-effects models. RESULTS: During 2001-2002, 275 measurements were taken by the research team, while 590 measurements dating back to 1984 were collected from governmental files. The area measurements had a global geometric mean (GM) of 0.28 p.p.m. [geometric standard deviation (GSD): 3.1]. The GM of the personal measurements was 0.17 p.p.m. (GSD: 2.3). The fixed-effects of the models for personal and area measurements explained 61 and 57% of the variance, respectively. Job (working area for area concentrations), process (PB, MDF, OSB), season of sampling, origin of the data (research, governmental) and year of sampling were significant determinants of exposure. Proximity to the press, winter conditions, PB and MDF processes and governmental data resulted in the highest exposures. Significant within-sampling campaign correlation was found for both personal and area models. The final models include different residual variances by process for personal measurements and by working area for area measurements. CONCLUSIONS: Several determinants of exposure to formaldehyde in the reconstituted wood panel industry were successfully identified. Higher levels found in governmental data as compared to research data may be explained by a 'worst-case' strategy bias. The observed intra-sampling campaign correlation supports existing results suggesting that measurements taken in a small time frame tend to be correlated. Exposures in this sector are low compared to most 8 h-TWA occupational exposure limits (e.g. 1 p.p.m.) but close to the most demanding ones (e.g. 0.3 p.p.m.).

Database for the toxicological evaluation of mixtures in occupational atmospheres.

Workers are regularly simultaneously exposed to multiple chemical substances. As in the ACGIH (American Conference of Governmental Industrial Hygienists) approach, the Québec Regulation prescribes that when two or more hazardous substances are present in workplaces and have similar effects on the same organs of the human body, their effects should be considered additive, unless established otherwise. This project was undertaken to develop a user-friendly toxicological database aid in identification of possible interactive effects of mixtures present in the work environment. In the first phase of the project, standard general literature references were used to compile critical data, such as target organs, effects on the target organs, mechanisms of action, and toxicokinetic characteristics of each of the 668 chemical substances appearing in the regulation. Each substance was assigned to one or more of 32 classes of biological effects retained by a group of toxicologists. The resulting database allows the user to find if there is potential additivity among components of a mixture.

Sinonasal cancer and occupational exposures: a pooled analysis of 12 case-control studies.

OBJECTIVE: In order to examine the associations between sinonasal cancer and occupational exposures other than wood dust and leather dust, the data from 12 case-control studies conducted in seven countries were pooled and reanalyzed. METHODS: The pooled data set included 195 adenocarcinoma cases (169 men and 26 women), 432 squamous cell carcinomas (330 men and 102 women), and 3136 controls (2349 men and 787 women). Occupational exposures to formaldehyde, silica dust, textile dust, coal dust, flour dust, asbestos, and man-made vitreous fibers were assessed with a job-exposure matrix. Odds ratios (ORs) were adjusted for age, study, wood dust, and leather dust, or other occupational exposures when relevant. 95% confidence intervals (CIs) were estimated by unconditional logistic regression. RESULTS: A significantly increased risk of adenocarcinoma was associated with exposure to formaldehyde. The ORs for the highest level of exposure were 3.0 (Cl = 1.5-5.7) among men and 6.2 (CI=2.0-19.7) among women. An elevated risk of squamous cell carcinoma was observed among men (OR=2.5, CI=0.6-10.1) and women (OR = 3.5, CI = 1.2-10.5) with a high probability of exposure to formaldehyde. Exposure to textile dust was associated with non-significantly elevated risk of adenocarcinoma, among women only: the OR for the high level of cumulative exposure was 2.5 (CI = 0.7-9.0). High level of asbestos exposure was associated with a significantly increased risk of squamous cell carcinoma among men (OR = 1.6, CI = 1.1-2.3). CONCLUSIONS: The results of this pooled analysis support the hypothesis that occupational exposure to formaldehyde increases the risk of sinonasal cancer, particularly of adenocarcinoma. They also indicate an elevated risk of adenocarcinoma among women exposed to textile dust, and suggest that exposure to asbestos may increase the risk of squamous cell carcinoma.