Jérôme Lavoué

Occupational Exposure to Silica and Lung Cancer: Pooled Analysis of Two Case-Control Studies in Montreal, Canada

Background: Respirable crystalline silica is a highly prevalent occupational exposure and a recognized lung carcinogen. Most previous studies have focused on selected high-exposure occupational groups. This study examines the relationship between occupational exposure to silica and lung cancer in an occupationally diverse male population. Methods: Two large population-based case-control studies of lung cancer were conducted in Montreal, one in 1979-1986 (857 cases, 533 population controls, 1,349 cancer controls) and the second in 1996-2001 (738 cases and 899 controls). Interviews provided descriptive lifetime job histories, smoking histories, and other information. Industrial hygienists translated job histories into histories of exposure to a host of occupational substances, including silica. Relative risk was estimated, adjusting for several potential confounders, including smoking. Results: The odds ratio for substantial exposure to silica was 1.67 (95% confidence interval, 1.21-2.31) and for any exposure was 1.31 (95% confidence interval, 1.08-1.59). Joint effects between silica and smoking were between additive and multiplicative, perhaps closer to the latter. In this population, it is estimated that approximately 3% of lung cancers were attributable to substantial silica exposure. Conclusions: The carcinogenicity of inhaled crystalline silica was observed in a population with a wide variety of exposure circumstances. Impact: The finding of carcinogenicity across a wide range of occupations complements prior studies of specific high-exposure occupations. This suggests that the burden of cancer induced by silica may be much greater than previously thought. Cancer Epidemiol Biomarkers Prev; 19(6); 1602–11. ©2010 AACR.

Development of an Exposure Measurement Database on Five Lung Carcinogens (ExpoSYN) for Quantitative Retrospective Occupational Exposure Assessment

BACKGROUND SYNERGY is a large pooled analysis of case-control studies on the joint effects of occupational carcinogens and smoking in the development of lung cancer. A quantitative job-exposure matrix (JEM) will be developed to assign exposures to five major lung carcinogens [asbestos, chromium, nickel, polycyclic aromatic hydrocarbons (PAH), and respirable crystalline silica (RCS)]. We assembled an exposure database, called ExpoSYN, to enable such a quantitative exposure assessment. METHODS Existing exposure databases were identified and European and Canadian research institutes were approached to identify pertinent exposure measurement data. Results of individual air measurements were entered anonymized according to a standardized protocol. RESULTS The ExpoSYN database currently includes 356 551 measurements from 19 countries. In total, 140 666 personal and 215 885 stationary data points were available. Measurements were distributed over the five agents as follows: RCS (42%), asbestos (20%), chromium (16%), nickel (15%), and PAH (7%). The measurement data cover the time period from 1951 to present. However, only a small portion of measurements (1.4%) were performed prior to 1975. The major contributing countries for personal measurements were Germany (32%), UK (22%), France (14%), and Norway and Canada (both 11%). CONCLUSIONS ExpoSYN is a unique occupational exposure database with measurements from 18 European countries and Canada covering a time period of >50 years. This database will be used to develop a country-, job-, and time period-specific quantitative JEM. This JEM will enable data-driven quantitative exposure assessment in a multinational pooled analysis of community-based lung cancer case-control studies.

Comparison of exposure estimates in the Finnish job-exposure matrix FINJEM with a JEM derived from expert assessments performed in Montreal

Context Retrospective exposure assessment in population-based case–control studies poses a major challenge due to the wide range of occupations and industries involved. The FINJEM is a generic job-exposure matrix (JEM) developed in Finland, which represents a potentially cost-effective exposure assessment tool. While FINJEM has been used in several studies outside Finland, little is known of its applicability in other countries. Methods We compared prevalence and intensity of exposure in FINJEM with a JEM developed from expert assessments of occupational histories obtained in a population-based case–control study in Montreal. Agreement for prevalence of exposure was measured by weighted κ coefficients between prevalence categories. Agreement for exposure intensity was measured by Spearman correlation coefficients between cells with non-null exposure. Results The comparison involved 27 chemicals, the time period 1945–1995 and included 4743 jobs initially assessed by the Montreal experts. 4293 combinations of agent, occupational title and period were available for comparison of prevalence. Agent-specific prevalence was consistently higher in the Montreal JEM (median difference 1.7%). Agent-specific κ values between prevalence categories varied from 0.89 (welding fumes) to 0.07 (flour dust). The comparison of exposure levels involved 14 agents and 198 cells with non-null exposure in both sources. Agent-specific Spearman correlation varied from 0.89 (flour dust) to −0.35 (benzo(a)pyrene). Conclusion Our observations suggest that information concerning several agents (eg, metals, welding fumes) can be successfully transported from Finland to Canada and probably other countries. However, for other agents, there was considerable disagreement, and hence, transportability of FINJEM cannot be assumed by default.

Modelling of occupational respirable crystalline silica exposure for quantitative exposure assessment in community-based case-control studies

We describe an empirical model for exposure to respirable crystalline silica (RCS) to create a quantitative job-exposure matrix (JEM) for community-based studies. Personal measurements of exposure to RCS from Europe and Canada were obtained for exposure modelling. A mixed-effects model was elaborated, with region/country and job titles as random effect terms. The fixed effect terms included year of measurement, measurement strategy (representative or worst-case), sampling duration (minutes) and a priori exposure intensity rating for each job from an independently developed JEM (none, low, high). 23,640 personal RCS exposure measurements, covering a time period from 1976 to 2009, were available for modelling. The model indicated an overall downward time trend in RCS exposure levels of -6% per year. Exposure levels were higher in the UK and Canada, and lower in Northern Europe and Germany. Worst-case sampling was associated with higher reported exposure levels and an increase in sampling duration was associated with lower reported exposure levels. Highest predicted RCS exposure levels in the reference year (1998) were for chimney bricklayers (geometric mean 0.11 mg m(-3)), monument carvers and other stone cutters and carvers (0.10 mg m(-3)). The resulting model enables us to predict time-, job-, and region/country-specific exposure levels of RCS. These predictions will be used in the SYNERGY study, an ongoing pooled multinational community-based case-control study on lung cancer.

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.

Creatinine and Specific Gravity Normalization in Biological Monitoring of Occupational Exposures

Reference values for the biological monitoring of occupational exposures are generally normalized on the basis of creatinine (CR) concentration or specific gravity (SG) to account for fluctuations in urine dilution. For instance, the American Conference of Governmental Industrial Hygienists (ACGIH®) uses a reference value of 1g/L for CR. The comparison of urinary concentrations of biomarkers between studies requires the adjustment of results based on a reference CR and/or SG value, although studies have suggested that age, sex, muscle mass, and time of the day can exert non-negligible influences on CR excretion, while SG appears to be less affected. The objective of this study was to propose reference values for urinary CR and SG based on the results of samples sent for analysis by occupational health practitioners to the laboratory of the Occupational Health and Safety Research Institute of Québec (IRSST). We analyzed a database containing 20,395 urinary sample results collected between 1985 and 2010. Linear mixed-effects models with worker as a random effect were used to estimate the influence of sex and collection period on urinary CR and SG. Median CR concentrations were 25–30% higher in men (1.6 g/L or 14.4 mmol/L) than in women (1.2 g/L or 10.2 mmol/L). Four percent of the samples for men and 12% for women were below the acceptable threshold for CR (4.4 mmol/L). For SG, 5% of samples for men and 12% for women were below the threshold of 1.010. The difference in SG levels between sexes was lower than for CR, with a median of 1.024 for men compared to 1.020 for women. Our results suggest that the normalization of reference values based on a standard CR value of 1 g/L as proposed by the ACGIH is a conservative approach. According to the literature, CR excretion is more influenced by physiological parameters than SG. We therefore suggest that correction based on SG should be favored in future studies involving the proposal of reference values for the biological monitoring of occupational exposures.

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/m3. Highest short-term GMs estimated for 2001 were in the funeral service and crematory and reconstituted wood products industries (GM = 0.35 mg/m3. 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°C for T < 15°C) but caused an increase in exposure levels for warm temperatures (+15% per 5°C for T >15°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.

Assessing Occupational Exposure to Chemicals in an International Epidemiological Study of Brain Tumours

The INTEROCC project is a multi-centre case-control study investigating the risk of developing brain cancer due to occupational chemical and electromagnetic field exposures. To estimate chemical exposures, the Finnish Job Exposure Matrix (FINJEM) was modified to improve its performance in the INTEROCC study and to address some of its limitations, resulting in the development of the INTEROCC JEM. An international team of occupational hygienists developed a crosswalk between the Finnish occupational codes used in FINJEM and the International Standard Classification of Occupations 1968 (ISCO68). For ISCO68 codes linked to multiple Finnish codes, weighted means of the exposure estimates were calculated. Similarly, multiple ISCO68 codes linked to a single Finnish code with evidence of heterogeneous exposure were refined. One of the key time periods in FINJEM (1960-1984) was split into two periods (1960-1974 and 1975-1984). Benzene exposure estimates in early periods were modified upwards. The internal consistency of hydrocarbon exposures and exposures to engine exhaust fumes was improved. Finally, exposure to polycyclic aromatic hydrocarbon and benzo(a)pyrene was modified to include the contribution from second-hand smoke. The crosswalk ensured that the FINJEM exposure estimates could be applied to the INTEROCC study subjects. The modifications generally resulted in an increased prevalence of exposure to chemical agents. This increased prevalence of exposure was not restricted to the lowest categories of cumulative exposure, but was seen across all levels for some agents. Although this work has produced a JEM with important improvements compared to FINJEM, further improvements are possible with the expansion of agents and additional external data.

SYN-JEM: A Quantitative Job-Exposure Matrix for Five Lung Carcinogens

OBJECTIVE The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons (by its proxy benzo(a)pyrene (BaP)) and respirable crystalline silica). A quantitative job-exposure matrix (JEM) was developed based on statistical modeling of large quantities of personal measurements. METHODS Empirical linear models were developed using personal occupational exposure measurements (n = 102306) from Europe and Canada, as well as auxiliary information like job (industry), year of sampling, region, an a priori exposure rating of each job (none, low, and high exposed), sampling and analytical methods, and sampling duration. The model outcomes were used to create a JEM with a quantitative estimate of the level of exposure by job, year, and region. RESULTS Decreasing time trends were observed for all agents between the 1970s and 2009, ranging from -1.2% per year for personal BaP and nickel exposures to -10.7% for asbestos (in the time period before an asbestos ban was implemented). Regional differences in exposure concentrations (adjusted for measured jobs, years of measurement, and sampling method and duration) varied by agent, ranging from a factor 3.3 for chromium-VI up to a factor 10.5 for asbestos. CONCLUSION We estimated time-, job-, and region-specific exposure levels for four (asbestos, chromium-VI, nickel, and RCS) out of five considered lung carcinogens. Through statistical modeling of large amounts of personal occupational exposure measurement data we were able to derive a quantitative JEM to be used in community-based studies.

An empirical hierarchical Bayesian unification of occupational exposure assessment methods

In occupational exposure assessment of airborne contaminants, exposure levels can either be estimated through repeated measurements of the pollutant concentration in air, expert judgment or through exposure models that use information on the conditions of exposure as input. In this report, we propose an empirical hierarchical Bayesian model to unify these approaches. Prior to any measurement, the hygienist conducts an assessment to generate prior distributions of exposure determinants. Monte-Carlo samples from these distributions feed two level-2 models: a physical, two-compartment model, and a non-parametric, neural network model trained with existing exposure data. The outputs of these two models are weighted according to the experts assessment of their relevance to yield predictive distributions of the long-term geometric mean and geometric standard deviation of the workers exposure profile (level-1 model). Bayesian inferences are then drawn iteratively from subsequent measurements of worker exposure. Any traditional decision strategy based on a comparison with occupational exposure limits (e.g. mean exposure, exceedance strategies) can then be applied. Data on 82 workers exposed to 18 contaminants in 14 companies were used to validate the model with cross-validation techniques. A user-friendly program running the model is available upon request.