Raymond Vincent

Occupational exposure to carcinogens in the European Union

OBJECTIVES To construct a computer assisted information system for the estimation of the numbers of workers exposed to established and suspected human carcinogens in the member states of the European Union (EU). METHODS A database called CAREX (carcinogen exposure) was designed to provide selected exposure data and documented estimates of the number of workers exposed to carcinogens by country, carcinogen, and industry. CAREX includes data on agents evaluated by the International Agency for Research on Cancer (IARC) (all agents in groups 1 and 2A as of February 1995, and selected agents in group 2B) and on ionising radiation, displayed across the 55 industrial classes. The 1990–3 occupational exposure was estimated in two phases. Firstly, estimates were generated by the CAREX system on the basis of national labour force data and exposure prevalence estimates from two reference countries (Finland and the United States) which had the most comprehensive data available on exposures to these agents. For selected countries, these estimates were then refined by national experts in view of the perceived exposure patterns in their own countries compared with those of the reference countries. RESULTS About 32 million workers (23% of those employed) in the EU were exposed to agents covered by CAREX. At least 22 million workers were exposed to IARC group 1 carcinogens. The exposed workers had altogether 42 million exposures (1.3 mean exposures for each exposed worker). The most common exposures were solar radiation (9.1 million workers exposed at least 75% of working time), environmental tobacco smoke (7.5 million workers exposed at least 75% of working time), crystalline silica (3.2 million exposed), diesel exhaust (3.0 million), radon (2.7 million), and wood dust (2.6 million). CONCLUSION These preliminary estimates indicate that in the early 1990s, a substantial proportion of workers in the EU were exposed to carcinogens.

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.

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.

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.

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.

CONFIDENCE INTERVALS FOR PROBABILITIES OF EXCEEDING THRESHOLD LIMITS WITH CENSORED LOG-NORMAL DATA

In enforcing safety regulations in the context of occupational health, the question of the probability of exceeding the so-called threshold limit value (TLV) in homogeneous exposure groups (HEG) arises. Because data are usually few, a simple non-parametric approach based on numbers of exceedances over the TLV cannot be usefully adopted. However, the distribution of airborne concentrations in the exposures within HEGs is often compatible with a log-normal distribution. Therefore inference based on this distribution may be adopted. There remain two problems for which there has been no satisfactory solution: the treatment of left censoring due to the detection limits of the exposure determinations, and the absence of a confidence interval (CI) for the probability of exceedance. In the non-censored case we present an exact confidence interval based on the non-central T-distribution and two Monte Carlo solutions based on the bootstrap and on the Gibbs sampler. The Monte Carlo methods are extended in various ways to treat the censored case. A large scale simulation study shows that the Gibbs Sampling CIs has coverage close to nominal in nearly all situations. The parametric bootstrap, after bias correction, performs nearly as well. We also present some extensions of the Gibbs sampling method to the analysis of fibre exposure data, and to the analysis of the effect of finite precision and measurement error. A worked example is presented.

Comparison of Formaldehyde Exposure Levels in Two Multi-Industry Occupational Exposure Databanks Using Multimodel Inference

The recent increase in international multicenter epidemiologic studies of occupational hazards and the current development of risk analysis tools based on multinational exposure data provide an incentive to evaluate the extrapolation of exposure data across countries. We compared formaldehyde measurements in the French (COLCHIC) and U.S. (IMIS) occupational exposure databases for 1986–2001 using multimodel inference. In this approach, conclusions are based on a set of plausible models rather than on a single model. Modeled variables included data source, industry, year, and sample type (short-term or long-term). The model set included 72 models corresponding to testing all variables and 5 interactions and estimation of 93 coefficients. As it is impossible to classify non-detects (ND) as short-term or long-term samples, they were removed from IMIS prior to analysis. Respectively, 3143 and 2646 IMIS and COLCHIC data, spread across 28 common industries, were analyzed. The full model explained 21% of the total variability. All fixed effects and the source-industry interaction were shown as strong predictors of exposure. The temporal trend (5% yearly decrease) and difference between short-term and long-term data (short-term greater than long-term by two-fold) were similar across the two databanks. Industry-specific differences between IMIS and COLCHIC were detected only for health-related activities for which COLCHIC levels were higher (∼ four-fold). Sensitivity analyses were conducted to assess the impact of excluding NDs from IMIS. They showed initial predicted industry-specific geometric means for IMIS data potentially multiplied by factors from 0.42 to 0.98 (long-term data) and from 0.11 to 1.4 (short-term data) when NDs were included with various distributions across the short-term and long-term categories. The most realistic scenario yielded 0.82 for long-term (18% overestimation) data and 1.05 (5% underestimation) for short-term data. Although tempered by a probable non-detect bias, our analysis showed that both databanks provide a similar multi-industry portrait of formaldehyde exposure despite a potential for very different occupational settings. Our results offer encouraging insight about extrapolation of exposure data across countries.

Occupational Exposure to Beryllium in French Enterprises: A Survey of Airborne Exposure and Surface Levels

An assessment survey of occupational exposure to beryllium (Be) was conducted in France between late 2004 and the end of 2006. Exposure estimates were based on the analytical results of samples collected from workplace air and from work surfaces in 95 facilities belonging to 37 sectors of activity. The results of this study indicated airborne Be concentrations in excess of the occupational exposure limit value of 2 microg m(-3) recommended in France. Metallurgy and electronic component manufacturing represented the activities and occupations where workers had the highest arithmetic mean exposures to Be. Surface contamination levels were also high and frequently exceeded thresholds recommended by different bodies. These results should prompt the development of prevention programmes that include Be substitution, process control and surface decontamination, in conjunction with suitable medical surveillance.

Sensitivity Analyses of Exposure Estimates from a Quantitative Job-exposure Matrix (SYN-JEM) for Use in Community-based Studies

OBJECTIVES We describe the elaboration and sensitivity analyses of a quantitative job-exposure matrix (SYN-JEM) for respirable crystalline silica (RCS). The aim was to gain insight into the robustness of the SYN-JEM RCS estimates based on critical decisions taken in the elaboration process. METHODS SYN-JEM for RCS exposure consists of three axes (job, region, and year) based on estimates derived from a previously developed statistical model. To elaborate SYN-JEM, several decisions were taken: i.e. the application of (i) a single time trend; (ii) region-specific adjustments in RCS exposure; and (iii) a prior job-specific exposure level (by the semi-quantitative DOM-JEM), with an override of 0 mg/m(3) for jobs a priori defined as non-exposed. Furthermore, we assumed that exposure levels reached a ceiling in 1960 and remained constant prior to this date. We applied SYN-JEM to the occupational histories of subjects from a large international pooled community-based case-control study. Cumulative exposure levels derived with SYN-JEM were compared with those from alternative models, described by Pearson correlation ((Rp)) and differences in unit of exposure (mg/m(3)-year). Alternative models concerned changes in application of job- and region-specific estimates and exposure ceiling, and omitting the a priori exposure ranking. RESULTS Cumulative exposure levels for the study subjects ranged from 0.01 to 60 mg/m(3)-years, with a median of 1.76 mg/m(3)-years. Exposure levels derived from SYN-JEM and alternative models were overall highly correlated (R(p) > 0.90), although somewhat lower when omitting the region estimate ((Rp) = 0.80) or not taking into account the assigned semi-quantitative exposure level (R(p) = 0.65). Modification of the time trend (i.e. exposure ceiling at 1950 or 1970, or assuming a decline before 1960) caused the largest changes in absolute exposure levels (26-33% difference), but without changing the relative ranking ((Rp) = 0.99). CONCLUSIONS Exposure estimates derived from SYN-JEM appeared to be plausible compared with (historical) levels described in the literature. Decisions taken in the development of SYN-JEM did not critically change the cumulative exposure levels. The influence of region-specific estimates needs to be explored in future risk analyses.

Occupational exposure to chrome VI compounds in French companies: results of a national campaign to measure exposure (2010-2013).

A campaign to measure exposure to hexavalent chromium compounds was carried out in France by the seven CARSAT chemistry laboratories, CRAMIF laboratory, and INRS over the 2010-2013 period. The survey included 99 companies involved in various activity sectors. The inhalable fraction of airborne particles was sampled, and exposure levels were determined using ion chromatography analysis combined with post-column derivatization and UV detection. The quality of the measurement results was guaranteed by an inter-laboratory comparison system involving all the laboratories participating in this study. Exposure levels frequently exceeded the French occupational exposure limit value (OELV) of 1 µg m(-3), in activities such as thermal metallization and manufacturing and application of paint in the aeronautics sector. The results also reveal a general trend for a greater proportion of soluble Chromium VI (Cr VI) compounds compared with insoluble compounds. Qualitative and quantitative information relating to the presence of other metallic compounds in the air of workplaces is also provided, for example for Cr III, Ni, Fe, etc. The sampling strategy used and the measurement method are easy to implement, making it possible to check occupational exposure with a view to comparing it to an 8 h-OELV of 1 µg m(-3).