Occupational quartz and particle exposure affect systemic levels of inflammatory markers related to inflammasome activation and cardiovascular disease.

BACKGROUND: The inflammatory responses are central components of diseases associated with particulate matter (PM) exposure, including systemic diseases such as cardiovascular diseases (CVDs). The aim of this study was to determine if exposure to PM, including respirable dust or quartz in the iron foundry environment mediates systemic inflammatory responses, focusing on the NLRP3 inflammasome and novel or established inflammatory markers of CVDs. METHODS: The exposure to PM, including respirable dust, metals and quartz were determined in 40 foundry workers at two separate occasions per worker. In addition, blood samples were collected both pre-shift and post-shift and quantified for inflammatory markers. The respirable dust and quartz exposures were correlated to levels of inflammatory markers in blood using Pearson, Kendall τ and mixed model statistics. Analyzed inflammatory markers included: 1) general markers of inflammation, including interleukins, chemokines, acute phase proteins, and white blood cell counts, 2) novel or established inflammatory markers of CVD, such as growth/differentiation factor-15 (GDF-15), CD40 ligand, soluble suppressor of tumorigenesis 2 (sST2), intercellular/vascular adhesion molecule-1 (ICAM-1, VCAM-1), and myeloperoxidase (MPO), and 3) NLRP3 inflammasome-related markers, including interleukin (IL)-1ß, IL-18, IL-1 receptor antagonist (IL-1Ra), and caspase-1 activity. RESULTS: The average respirator adjusted exposure level to respirable dust and quartz for the 40 foundry workers included in the study was 0.65 and 0.020 mg/m3, respectively. Respirable quartz exposure correlated with several NLRP3 inflammasome-related markers, including plasma levels of IL-1ß and IL-18, and several caspase-1 activity measures in monocytes, demonstrating a reverse relationship. Respirable dust exposure mainly correlated with non-inflammasome related markers like CXCL8 and sST2. CONCLUSIONS: The finding that NLRP3 inflammasome-related markers correlated with PM and quartz exposure suggest that this potent inflammatory cellular mechanism indeed is affected even at current exposure levels in Swedish iron foundries. The results highlight concerns regarding the safety of current exposure limits to respirable dust and quartz, and encourage continuous efforts to reduce exposure in dust and quartz exposed industries.

Effects on white blood cell counts and the NLRP3 inflammasome due to dust and cobalt exposure in the hard metal industry.

INTRODUCTION: In light of potential negative health effects of cobalt exposure, a characterization of inflammatory mechanisms in exposed individuals is warranted. The current study investigated cobalt exposure in the Swedish hard metal industry and its relationship to inflammatory markers, including NLRP3 inflammasome activation and white blood cell (WBC) counts. MATERIALS AND METHODS: Inhalable cobalt and dust exposures, and systemic cobalt levels, were determined for 72 workers in the hard metal industry and linear regression models were applied to correlate exposure to markers of inflammasome activation and WBC counts. RESULTS: Mean exposures to inhalable dust (0.11 mg/m3) and cobalt (0.0034 mg/m3) were below the Swedish occupational exposure limits, and these low exposures did not correlate with any investigated outcomes. Instead, cobalt blood levels significantly correlated with a ca 10% decrease in IL-18 plasma levels per 10 nM cobalt increase. Furthermore, pre-shift cobalt blood and/or urine levels significantly correlated with some WBC measures, including decreased neutrophil-to-lymphocyte ratio, increased lymphocyte-to-monocyte ratio, and lymphocyte counts. CONCLUSION: The low inhalable particle exposures had no impact on WBC counts and inflammasome activation. Instead, systemic cobalt levels, which also include skin exposure, demonstrated possible suppressive effects on inflammatory responses in cobalt-exposed individuals in the hard metal industry.

Dermal exposure to cobalt studied in vitro in keratinocytes - effects of cobalt exposure on inflammasome activated cytokines, and mRNA response.

BACKGROUND: Cobalt is a dermal sensitizer, and keratinocytes respond to cobalt exposure by releasing proinflammatory mediators, regulating the immune response. OBJECTIVE: To determine the effect of cobalt on the inflammasome associated cytokine- and gene expression in cultured human keratinocytes (HaCaT). Cultivation in low- or high calcium conditions model separate differentiation states of keratinocytes in the skin. METHOD: HaCaT cells in two different states of differentiation were exposed to cobalt chloride and caspase-1 activity as well as the production of IL-1ß, IL-18 and gene expression of IL1B, IL18, NLRP3, CASP1, and PYCARD was quantified. RESULTS: High cobalt chloride exposure mediated significant increase in caspase-1 activity, cytokine levels, and IL1B and NLRP3 expression with a corresponding regulatory decrease for CASP1 and PYCARD expression. No difference between high- and low calcium culturing conditions modelling differentiation states was detected. CONCLUSIONS: Our data suggest that HaCaT cells respond with inflammmasome associated activity upon cobalt exposure in a concentration-dependent manner. These mechanisms could be of importance for the understanding of the pathophysiology behind allergic sensitization to dermal cobalt exposure.

Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in the Swedish hard metal industry, in particular to cobalt.

PURPOSE: To study the relationship between inhalation of airborne particles and cobalt in the Swedish hard metal industry and markers of inflammation and coagulation in blood. METHODS: Personal sampling of inhalable cobalt and dust were performed for subjects in two Swedish hard metal plants. Stationary measurements were used to study concentrations of inhalable, respirable, and total dust and cobalt, PM10 and PM2.5, the particle surface area and the particle number concentrations. The inflammatory markers CC16, TNF, IL-6, IL-8, IL-10, SAA and CRP, and the coagulatory markers FVIII, vWF, fibrinogen, PAI-1 and D-dimer were measured. A complete sampling was performed on the second or third day of a working week following a work-free weekend, and additional sampling was taken on the fourth or fifth day. The mixed model analysis was used, including covariates. RESULTS: The average air concentrations of inhalable dust and cobalt were 0.11 mg/m3 and 0.003 mg/m3, respectively. For some mass-based exposure measures of cobalt and total dust, statistically significant increased levels of FVIII, vWF and CC16 were found. CONCLUSIONS: The observed relationships between particle exposure and coagulatory biomarkers may indicate an increased risk of cardiovascular disease.

Quartz Dust Exposure Affects NLRP3 Inflammasome Activation and Plasma Levels of IL-18 and IL-1Ra in Iron Foundry Workers.

PURPOSE: To study the association between inhalation of particulate matter or quartz in Swedish iron foundries and the effects on NLRP3 inflammasome activation. METHODS: Particle exposure measurements were performed during an eight-hour work day for 85 foundry workers at three Swedish iron foundries. Personal sampling was used for measurement of respirable quartz and dust and stationary measurements to obtain exposure measurements for inhalable dust and PM10. The NLRP3 inflammasome markers, interleukin- (IL-) 1ß and IL-18, and inhibitors IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP) were measured in plasma. Inflammasome activation was measured by caspase-1 enzymatic activity in monocytes in whole blood by flow cytometry, and expression of inflammasome-related genes was quantified using real-time PCR. Multiple linear regression analysis was used to investigate associations between PM exposures and inflammatory markers. Sex, age, smoking, current infection, BMI, and single nucleotide polymorphism in the inflammasome regulating genes CARD8 (C10X) and NLRP3 (Q705K) were included as covariates. RESULTS: The average exposure levels of respirable dust and quartz were 0.85 and 0.052 mg/m3, respectively. A significant exposure-response was found for respirable dust and IL-18 and for inhalable dust and IL-1Ra. Whole blood, drawn from study participants, was stimulated ex vivo with inflammasome priming stimuli LPS or Pam3CSK4, resulting in a 47% and 49% increase in caspase-1 enzymatic activity in monocytes. This increase in caspase-1 activity was significantly attenuated in the higher exposure groups for most PM exposure measures. CONCLUSIONS: The results indicate that exposure levels of PM in the iron foundry environment can affect the NLRP3 inflammasome and systemic inflammation.

Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in Swedish iron foundries, in particular respirable quartz.

PURPOSE: To study the relationship between inhalation of airborne particles and quartz in Swedish iron foundries and markers of inflammation and coagulation in blood. METHODS: Personal sampling of respirable dust and quartz was performed for 85 subjects in three Swedish iron foundries. Stationary measurements were used to study the concentrations of respirable dust and quartz, inhalable and total dust, PM10 and PM2.5, as well as the particle surface area and the particle number concentrations. Markers of inflammation, namely interleukins (IL-1ß, IL-6, IL-8, IL-10 and IL-12), C-reactive protein, and serum amyloid A (SAA) were measured in plasma or serum, together with markers of coagulation including fibrinogen, factor VIII (FVIII), von Willebrand factor and D-dimer. Complete sampling was performed on the second or third day of a working week after a work-free weekend, and follow-up samples were collected 2 days later. A mixed model analysis was performed including sex, age, smoking, infections, blood group, sampling day and BMI as covariates. RESULTS: The average 8-h time-weighted average air concentrations of respirable dust and quartz were 0.85 mg/m3 and 0.052 mg/m3, respectively. Participants in high-exposure groups with respect to some of the measured particle types exhibited significantly elevated levels of SAA, fibrinogen and FVIII. CONCLUSIONS: These observed relationships between particle exposure and inflammatory markers may indicate an increased risk of cardiovascular disease among foundry workers with high particulate exposure.

Occupational exposure to trichloramine and trihalomethanes: adverse health effects among personnel in habilitation and rehabilitation swimming pools.

Personnel in swimming pool facilities typically experience ocular, nasal, and respiratory symptoms due to water chlorination and consequent exposure to disinfection by-products in the air. The aim of the study was to investigate exposure to trichloramine and trihalomethanes (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) from the perspective of adverse health effects on the personnel at Swedish habilitation and rehabilitation swimming pools. The study included 10 habilitation and rehabilitation swimming pool facilities in nine Swedish cities. The study population comprised 24 exposed swimming pool workers and 50 unexposed office workers. Personal and stationary measurements of trichloramine and trihalomethanes in air were performed at all the facilities. Questionnaires were distributed to exposed workers and referents. Spirometry, fraction of exhaled nitric oxide (FENO), and peak expiratory flow (PEF) were measured. Personal and stationary measurements yielded trichloramine levels of 1-76 µg/m3 (average: 19 µg/m3) and 1-140 µg/m3 (average: 23 µg/m3), respectively. A slightly higher, but not significant, prevalence of reported eye- and throat-related symptoms occurred among the exposed workers than among the referents. A significantly increased risk of at least one ocular symptom was attributed to trichloramine exposure above the median (20 µg/m3). Lung function (FVC and FEV1) was in the normal range according to the Swedish reference materials, and no significant change in lung function before and after shift could be established between the groups. Average FENO values were in the normal range in both groups, but the difference in the values between the exposed workers and referents showed a significant increase after shift. Hourly registered PEF values during the day of the investigation did not show any unusual individual variability. In conclusion, the increased risk of developing at least one ocular symptom at personal trichloramine concentrations over 20 µg/m3 combined with an increase in the difference in FENO during the work shift of the exposed workers should not be neglected as an increased risk of respiratory inflammation in the habilitation and rehabilitation swimming pool environment.

DNA methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons.

Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 µg/g creatinine) followed by chimney sweeps (0.34 µg/g creatinine) and controls (0.05 µg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1 and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B = -2.04; P < 0.057, adjusted for smoking and age) and lower average AHRR methylation (B = -2.05; P < 0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B = -0.81; P < 0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.

Biological monitoring of dermal and air exposure to cobalt at a Swedish hard metal production plant: does dermal exposure contribute to uptake?

BACKGROUND: Occupational exposure to cobalt is well established in hard metal manufacture. Cobalt is known to cause contact allergy, asthma, hard metal lung disease, and lung cancer. The relationship between skin exposure and uptake determined in blood has not been extensively investigated. OBJECTIVE: To examine whether skin and inhalable air exposure to cobalt contributes to uptake, determined as cobalt in blood, in a hard metal manufacturing factory. METHODS: The amount of cobalt on the skin found with an acid wash technique, the air concentrations of inhalable cobalt and cobalt blood concentrations were determined and correlated in exposed workers. RESULTS: We found a significant rank correlation for cobalt concentrations on the skin, in inhalable air, and in blood (0.376-0.498). Multiple linear regression showed significant regression coefficients for cobalt skin exposure and blood (B = 0.01, p < 0.05) and for inhalable cobalt in air and blood (B = 49.1, p < 0.001). According to our model based on data from the regression analyses, a twofold increase in skin exposure levels at different air concentrations caused a 3-14% increase in blood levels. CONCLUSIONS: Our data suggest that skin exposure to cobalt in the hard metal industry could affect the total uptake at the same order of magnitude as air exposure.

Occupational Exposure to Cobalt and Tungsten in the Swedish Hard Metal Industry: Air Concentrations of Particle Mass, Number, and Surface Area.

Exposure to cobalt in the hard metal industry entails severe adverse health effects, including lung cancer and hard metal fibrosis. The main aim of this study was to determine exposure air concentration levels of cobalt and tungsten for risk assessment and dose-response analysis in our medical investigations in a Swedish hard metal plant. We also present mass-based, particle surface area, and particle number air concentrations from stationary sampling and investigate the possibility of using these data as proxies for exposure measures in our study. Personal exposure full-shift measurements were performed for inhalable and total dust, cobalt, and tungsten, including personal real-time continuous monitoring of dust. Stationary measurements of inhalable and total dust, PM2.5, and PM10 was also performed and cobalt and tungsten levels were determined, as were air concentration of particle number and particle surface area of fine particles. The personal exposure levels of inhalable dust were consistently low (AM 0.15mg m(-3), range <0.023-3.0mg m(-3)) and below the present Swedish occupational exposure limit (OEL) of 10mg m(-3) The cobalt levels were low as well (AM 0.0030mg m(-3), range 0.000028-0.056mg m(-3)) and only 6% of the samples exceeded the Swedish OEL of 0.02mg m(-3) For continuous personal monitoring of dust exposure, the peaks ranged from 0.001 to 83mg m(-3) by work task. Stationary measurements showed lower average levels both for inhalable and total dust and cobalt. The particle number concentration of fine particles (AM 3000 p·cm(-3)) showed the highest levels at the departments of powder production, pressing and storage, and for the particle surface area concentrations (AM 7.6 µm(2)·cm(-3)) similar results were found. Correlating cobalt mass-based exposure measurements to cobalt stationary mass-based, particle area, and particle number concentrations by rank and department showed significant correlations for all measures except for particle number. Linear regression analysis of the same data showed statistically significant regression coefficients only for the mass-based aerosol measures. Similar results were seen for rank correlation in the stationary rig, and linear regression analysis implied significant correlation for mass-based and particle surface area measures. The mass-based air concentration levels of cobalt and tungsten in the hard metal plant in our study were low compared to Swedish OELs. Particle number and particle surface area concentrations were in the same order of magnitude as for other industrial settings. Regression analysis implied the use of stationary determined mass-based and particle surface area aerosol concentration as proxies for various exposure measures in our study.

Inflammatory markers and exposure to airborne particles among workers in a Swedish pulp and paper mill.

PURPOSE: To study the relationship between exposure to airborne particles in a pulp and paper mill and markers of inflammation and coagulation in blood. METHODS: Personal sampling of inhalable dust was performed for 72 subjects working in a Swedish pulp and paper mill. Stationary measurements were used to study concentrations of total dust, respirable dust, PM10 and PM2.5, the particle surface area and the particle number concentrations. Markers of inflammation, interleukins (IL-1b, IL-6, IL-8, and IL-10), C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen and markers of coagulation factor VIII, von Willebrand, plasminogen activator inhibitor, and D-dimer were measured in plasma or serum. Sampling was performed on the last day of the work free period of 5 days, before and after the shift the first day of work and after the shifts the second and third day. In a mixed model analysis, the relationship between particulate exposures and inflammatory markers was determined. Sex, age, smoking, and BMI were included as covariates. RESULTS: The average 8-h time-weighted average (TWA) air concentration levels of inhalable dust were 0.30 mg/m(3), range 0.005-3.3 mg/m(3). The proxies for average 8-h TWAs of respirable dust were 0.045 mg/m(3). Significant and consistent positive relations were found between several exposure metrics (PM 10, total and inhalable dust) and CRP, SAA and fibrinogen taken post-shift, suggesting a dose-effect relationship. CONCLUSION: This study supports a relationship between occupational particle exposure and established inflammatory markers, which may indicate an increased risk of cardiovascular disease.

Occupational Exposure to Trichloramine and Trihalomethanes in Swedish Indoor Swimming Pools: Evaluation of Personal and Stationary Monitoring.

INTRODUCTION: Chlorination is a method commonly used to keep indoor swimming pool water free from pathogens. However, chlorination of swimming pools produces several potentially hazardous by-products as the chlorine reacts with nitrogen containing organic matter. Up till now, exposure assessments in indoor swimming pools have relied on stationary measurements at the poolside, used as a proxy for personal exposure. However, measurements at fixed locations are known to differ from personal exposure. METHODS: Eight public swimming pool facilities in four Swedish cities were included in this survey. Personal and stationary sampling was performed during day or evening shift. Samplers were placed at different fixed positions around the pool facilities, at ~1.5 m above the floor level and 0-1 m from the poolside. In total, 52 personal and 110 stationary samples of trichloramine and 51 personal and 109 stationary samples of trihalomethanes, were collected. RESULTS: The average concentration of trichloramine for personal sampling was 71 µg m(-3), ranging from 1 to 240 µg m(-3) and for stationary samples 179 µg m(-3), ranging from 1 to 640 µg m(-3). The air concentrations of chloroform were well below the occupational exposure limit (OEL). For the linear regression analysis and prediction of personal exposure to trichloramine from stationary sampling, only data from personal that spent >50% of their workday in the pool area were included. The linear regression analysis showed a correlation coefficient (r2) of 0.693 and a significant regression coefficient ß of 0.621; (95% CI = 0.329-0.912, P = 0.001). CONCLUSION: The trichloramine exposure levels determined in this study were well below the recommended air concentration level of 500 µg m(-3); a WHO reference value based on stationary sampling. Our regression data suggest a relation between personal exposure and area sampling of 1:2, implying an OEL of 250 µg m(-3) based on personal sampling.

Comparison and Evaluation of Multiple Users' Usage of the Exposure and Risk Tool: Stoffenmanager 5.1.

Stoffenmanager is an exposure and risk assessment tool that has a control banding part, with risk bands as outcome and a quantitative exposure assessment part, with the 90th percentile of the predicted exposure as a default outcome. The main aim of the study was to investigate whether multiple users of Stoffenmanager came to the same result when modelling the same scenarios. Other aims were to investigate the differences between outcomes of the control banding part with the measured risk quota and to evaluate the conservatism of the tool by testing whether the 90th percentiles are above the measured median exposures. We investigated airborne exposures at companies in four different types of industry: wood, printing, metal foundry, and spray painting. Three scenarios were modelled and measured, when possible, at each company. When modelled, 13 users visited each company on the same occasion creating individual assessments. Consensus assessments were also modelled for each scenario by six occupational hygienists. The multiple users' outcomes were often spread over two risk bands in the control banding part, and the differences in the quantitative exposure outcomes for the highest and lowest assessments per scenario varied between a factor 2 and 100. Four parameters were difficult for the users to assess and had a large impact on the outcome: type of task, breathing zone, personal protection, and control measures. Only two scenarios had a higher measured risk quota than predicted by the control banding part, also two scenarios had slightly higher measured median exposure value than modelled consensus in the quantitative exposure assessment part. Hence, the variability between users was large but the model performed well.

COVID-19 Across Professions - Infection, Hospitalisation, and ICU Patterns in a Swedish County.

OBJECTIVE: To study infection, hospitalisation, and admission to ICU for COVID-19 in different occupations and pandemic waves in a Swedish county. METHODS: Individual registry data of infection and hospitalisation were merged with occupational data in, this cross-sectional study. Infected, hospital- and ICU-admission were analysed by occupational groups. RESULTS: 22,095 cases of COVID-19 from 21 February 2021 to 31 August 2022 were identified. Healthcare workers and others working in close physical proximity showed a higher rate of confirmed COVID-19 infections in all waves and higher risk for hospital admission early in the pandemic. Exposure to diseases and physical proximity played a decisive role. CONCLUSION: Workers in close-contact occupations experienced a higher rate of confirmed infections throughout the pandemic and higher hospitalisation rates in the first pandemic wave, suggesting a need for more effective initial safety measures in a future pandemic.

Cancer morbidity and quartz exposure in Swedish iron foundries.

PURPOSE: The aim of this study was to determine cancer morbidity amongst Swedish iron foundry workers with special reference to quartz exposure. In addition to respirable dust and quartz, phenol, formaldehyde, furfuryl alcohols, polycyclic aromatic hydrocarbons (PAHs), carbon black, isocyanates and asbestos are used or generated by foundry production techniques and exposure to any of these substances could have potentially carcinogenic effects. METHODS: Cancer morbidity between 1958 and 2004 was evaluated in a cohort of 3,045 male foundry workers employed for >1 year between 1913 and 2005. Standardised incidence ratios (SIRs) with 95 % confidence intervals (95 % CI) were determined by comparing observed numbers of incident cancers with frequencies in the Swedish cancer register. Exposure measures were assessed using information from the personal files of employees and modelling quartz measurement based on a database of 1,667 quartz measurements. Dose responses for lung cancer were determined for duration of employment and cumulative quartz exposure for latency periods >20 years. RESULTS: Overall cancer morbidity was not increased amongst the foundry workers (SIR 1.00; 95 % CI, 0.90-1.11), but the incidence of lung cancer was significantly elevated (SIR 1.61; 95 % CI, 1.20-2.12). A non-significant negative dose response was determined using external comparison with a latency period of >20 years (SIR 2.05, 1.72 1.26 for the low, medium and high exposure groups), supported by internal comparison data (hazard ratios 1, 1.01, 0.78) for the corresponding groups. For cancers at sites with at least five observed cases and a SIR > 1.25, non-significant risks with SIRs > 1.5 were determined for cancers of the liver, larynx, testis, connective muscle tissue, multiple myeloma plasmacytoma and lymphatic leukaemia. CONCLUSIONS: A significant overall risk of lung cancer was determined, but using external and internal comparison groups could not confirm any dose response at our cumulative quartz dose levels.

Cancer incidence among Swedish pulp and paper mill workers: a cohort study of sulphate and sulphite mills.

PURPOSE: Associations between various malignancies and work in the pulp and paper industry have been reported but mostly in analyses of mortality rather than incidence. We aimed to study cancer incidence by main mill pulping process, department and gender in a Swedish cohort of pulp and paper mill workers. METHODS: The cohort (18,113 males and 2,292 females, enrolled from 1939 to 1999 with >1 year of employment) was followed up for cancer incidence from 1958 to 2001. Information on the workers' department and employment was obtained from the mills' personnel files, and standardized incidence ratios (SIRs) were calculated using the Swedish population as reference. RESULTS: Overall cancer incidence, in total 2,488 cases, was not increased by work in any department. However, risks of pleural mesothelioma were increased among males employed in sulphate pulping (SIR, 8.38; 95 % CI, 3.37-17) and maintenance (SIR, 6.35; 95 % CI, 3.47-11), with no corresponding increase of lung cancer. Testicular cancer risks were increased among males employed in sulphate pulping (SIR, 4.14; 95 % CI, 1.99-7.61) and sulphite pulping (SIR, 2.59; 95 % CI, 0.95-5.64). Female paper production workers showed increased risk of skin tumours other than malignant melanoma (SIR, 2.92; 95 % CI, 1.18-6.02). CONCLUSIONS: Incidence of pleural mesothelioma was increased in the cohort, showing that asbestos exposure still has severe health consequences, and highlighting the exigency of strict asbestos regulations and elimination. Testicular cancer was increased among pulping department workers. Shift work and endocrine disruptors could be of interest in this context.

Silica Exposure and Cardiovascular, Cerebrovascular, and Respiratory Morbidity in a Cohort of Male Swedish Iron Foundry Workers.

OBJECTIVE: We present quantitative exposure-response data on silica exposure in male Swedish iron foundry workers for cardiovascular, cerebrovascular, and respiratory morbidity. METHODS: This research is a cohort study of 2063 male Swedish iron foundry workers. From the Swedish National Patient Registers, data on morbidity incidence were retrieved. A historical measurement database of 1667 respirable silica exposure measurements from 10 Swedish iron foundries was used to calculate the cumulative exposure dose for each worker. RESULTS: Increased morbidity risk for the whole group of foundry workers was determined for ischemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), bronchitis, and pneumonia. In addition, an increased risk for COPD at cumulative silica exposures ranging from 0.11 to 0.84 mg/m 3 year is presented. CONCLUSIONS: The study presents a significantly increased COPD risk at cumulative silica exposures below the Swedish occupational exposure limit.

Estimating trends in quartz exposure in Swedish iron foundries--predicting past and present exposures.

BACKGROUND: Swedish foundries have a long tradition of legally required surveys in the workplace that, from the late 1960s onwards, included measurements of quartz. The availability of exposure data spanning almost 40 years presents a unique opportunity to study trends over that time and to evaluate the validity of exposure models based on data from shorter time spans. The aims of this study were (i) to investigate long-term trends in quartz exposure over time, (ii) using routinely collected quartz exposure measurements to develop a mathematical model that could predict both historical and current exposure patterns, and (iii) to validate this exposure model with up-to-date measurements from a targeted survey of the industry. METHODS: Eleven foundries, representative of the Swedish iron foundry industry, were divided into three groups based on the size of the companies, i.e. the number of employees. A database containing 2333 quartz exposure measurements for 11 different job descriptions was used to create three models that covered time periods which reflected different work conditions and production processes: a historical model (1968-1989), a development model (1990-2004), and a validation model (2005-2006). A linear mixed model for repeated measurements was used to investigate trends over time. In all mixed models, time period, company size, and job title were included as fixed (categorical) determinants of exposure. The within- and between-worker variances were considered to be random effects. A linear regression analysis was performed to investigate agreement between the models. The average exposure was estimated for each combination of job title and company size. RESULTS: A large reduction in exposure (51%) was seen between 1968 and 1974 and between 1975 and 1979 (28%). In later periods, quartz exposure was reduced by 8% per 5 years at best. In the first period, employees at smaller companies experienced ~50% higher exposure levels than those at large companies, but these differences became much smaller in later years. The furnace and ladle repair job were associated with the highest exposure, with 3.9-8.0 times the average exposure compared to the lowest exposed group. Without adjusting for this autonomous trend over time, predicting early historical exposures using our development model resulted in a statistically significant regression coefficient of 2.42 (R(2) = 0.81), indicating an underestimation of historical exposure levels. Similar patterns were seen for other historical time periods. Comparing our development model with our validation model resulted in a statistically significant regression coefficient of 0.31, indicating an overestimation of current exposure levels. CONCLUSION: To investigate long-term trends in quartz exposure over time, overall linear trends can be determined by using mixed model analysis. To create individual exposure measures to predict historical exposures, it is necessary to consider factors such as the time period, type of job, type of company, and company size. The mixed model analysis showed systematic changes in concentration levels, implying that extrapolation of exposure estimates outside the range of years covered by measurements may result in underestimation or overestimation of exposure.

Exposure assessment and modeling of quartz in Swedish iron foundries for a nested case-control study on lung cancer.

Exposure assessment of quartz in Swedish iron foundries was performed based on historical and current measurement data. To evaluate the exposure-response relationship between quartz exposure and lung cancer, we modeled quartz exposure from our database of measurements using determinants job title, time period, and company. Based on these modeled exposure data, we conducted a nested case-control evaluation. In our database, the overall individual, daily time-weighted average (TWA) quartz concentrations of current and historical data varied between 0.0018 and 4.9 mg/m(3), averaging 0.083 mg/m(3). Job titles with mean TWAs for the whole study period exceeding the European Union recommended occupational exposure limit of 0.05 mg/m(3) were fettlers (0.087 mg/m(3)), furnace and ladle repair (0.42 mg/m(3)), and maintenance (0.054 mg/m(3)) workers. The mixed model analysis demonstrated significant determinants on the job level for furnace and ladle repair (ß = 4.06; 95% confidence interval [CI] 2.78-5.93). For all jobs, significantly higher exposure levels occurred only during the first time period, 1968-1979 (ß = 2.08; 95% CI 1.75-2.47), and a decreasing but not significant trend was noted for the three following 10-year time periods up to 2006 (ß = 1.0, 0.96 and 1, respectively). Two iron foundries had significantly higher quartz concentration levels than the others (ß = 1.31; 95% CI 1.00-1.71 and ß = 1.63; 95% CI 1.00-2.65, respectively). The individual cumulative quartz exposure measures were categorized in low, medium, and high exposure (0.5-<1, 1-1.9 and ≥ 2 mg/m(3)*years, respectively). In the nested case-control analysis, we found the highest odds ratios of lung cancer (OR 1.17; 95% CI 0.53-2.55) for the medium exposure group. No dose-response trend or significantly increased risk was determined for our high exposed group (≥2 mg/m(3)), representing 40 years of exposure at >0.05 mg/m(3) of quartz. To conclude, certain foundry workers are still exposed to high levels of quartz, but an increased risk of lung cancer caused by quartz exposure in these Swedish iron foundries could not be confirmed at our exposure levels.

Respirable Dust and Silica: Respiratory Diseases Among Swedish Iron Foundry Workers.

OBJECTIVE: The mortality and morbidity pattern for respiratory diseases was determined in a cohort of 1752 Swedish foundry workers, particularly for respirable silica dust exposure. METHODS: The morbidity follow-up in the Swedish National Non-primary Outpatient Register covered 2001 to 2017 (NPR; specialist not in care patients), the mortality from the National Causes of Death Register covered 2001 to 2017. Cumulative exposures to silica and dust were determined. RESULTS: The morbidity in COPD showed significantly increased risk for all exposure groups, as did silicosis in the high exposure group, these cases corresponded to silica exposure levels below 0.05 mg/m3. The mortality of all causes and respiratory diseases was significantly increased by cumulative silica exposure in the high exposure group. CONCLUSIONS: Significantly increased morbidity for respiratory diseases and COPD was determined at silica exposure levels below the current Swedish OEL.