Occupational Dust Exposure as a Risk Factor for Developing Lung Function Impairment.

OBJECTIVE: Dust exposure is high in several industries. We investigated associations of exposure in paper mills, wood pellet plants, and iron foundries with lung function impairment. METHODS: Respirable silica, inhalable paper dust, or inhalable wood dust were collected as personal samples and spirometry was performed. Multiple linear regression analyzed associations with FEV 1 %pred and FVC%pred. RESULTS: Wood pellet workers with high exposure to inhalable dust had lower FEV 1 %pred (95% CI) (-9.4 [-16 to -2.6]) and FVC%pred (-9.8 [-15 to -4.0]) compared with lowest exposure level. Workers at paper mills and foundries had no dose-dependent association but lower FEV 1 %pred and FVC%pred than in workers at wood pellets plants. CONCLUSIONS: Increased exposure to inhalable wood dust is associated with decreased lung function. Foundry and paper mill workers have generally lower lung function than wood pellet workers. Spirometry should be considered in workers in industries with airborne particulate matter pollution.

The level of education and the risk for retinal detachments and breaks: A registry-based case-control study.

PURPOSE: Myopia is the most important risk factor for developing retinal tears and retinal detachment (RD). Due to altered lifestyle factors myopia is increasing in the world. In this study, the correlation between educational level and risk for retinal detachment were analysed. METHODS: A case-control registry study was conducted including a total of 10 268 individuals. Data were collected from registries of the Swedish National Board of Health and Welfare as well as the Swedish Central Bureau of Statistics. Cases were defined as ICD-10 H33 (retinal detachments and breaks). For each case, a matched control was selected with the same age and sex, living in the same county at the time of diagnosis. The study population was divided into seven groups with regard to educational level and compared using conditional logistic regression. RESULTS: In the total population, the odds ratio (OR) increased in a proportional fashion with a higher level of education. The odds ratio for the total population at the highest education level was 1.77 and increased to 2.00 when excluding individuals with diabetes. Out of the 5134 cases, 72% were men and 28% women. A statistically significant difference between sexes was only confirmed for the second highest education level. CONCLUSION: Individuals with a longer education have a significantly higher risk for retinal complications in the form of RD and breaks. Higher education is a risk factor for retinal complications in both sexes but seemingly more strongly in men.

Self-reported symptoms in Swedish hairdressers and association with exposure to volatile organic compounds (VOCs), including aldehydes.

BACKGROUND: Working as a hairdresser involves combined exposure to multiple chemicals in hair treatment products that may induce symptoms in airways and skin. METHODS: In this cross-sectional study, perceived symptoms among Swedish hairdressers at 10 hair salons were surveyed through a questionnaire. Associations with personal exposure to volatile organic compounds (VOCs), including aldehydes, and their corresponding hazard index (HI), based on the estimated risk for non-cancer health effects, were examined. The prevalence of four out of 11 symptoms was compared to available reference datasets from two other studies of office workers and school staff. RESULTS: All 11 surveyed symptoms were reported among the hairdressers (n = 38). For the whole study group, the most prevalent symptoms were dripping nose (n = 7) and headache (n = 7), followed by eczema (n = 6), stuffed nose (n = 5), cough (n = 5) and discomfort with strong odors (n = 5). Significant relationships between exposure and symptoms were scarce. The exception was total VOC (TVOC) exposure adjusted to worked years in the profession; a difference was observed for any symptom between hairdressers in the group with 20 + years compared to 0-5 years in the profession (logistic regression, OR 0.03, 95% CI 0.001-0.70). Out of the four symptoms available for comparison, the prevalence of headache and cough was significantly higher in hairdressers than in controls (OR 5.18, 95% CI 1.86-13.43 and OR 4.68, 95% CI 1.17-16.07, respectively). CONCLUSIONS: Adverse health effects related to occupation was common among the hairdressers, implying a need for exposure control measures in hair salons. Symptoms of headache and cough were more frequently reported by hairdressers than staff in offices and schools. A healthy worker effect among the hairdressers was indicated in the group with 20 + years compared to 0-5 years in the profession. Significant relationships between measured exposure and symptoms were scarce but gave information about advantages and disadvantages of the different exposure measures. The study design could be improved by increasing the size of the study population, using a better match of reference data and increasing the applicability and representability over time of the measured exposure.

Chloroform exposure in air and water in Swedish indoor swimming pools-urine as a biomarker of occupational exposure.

INTRODUCTION: Disinfection by-products are produced in water disinfected with chlorine-based products. One such group is trihalomethanes, and chloroform is the most abundant trihalomethane in swimming pool areas. Chloroform can be absorbed by inhalation, ingestion, and dermal absorption, and is classified as possibly carcinogenic. AIM: To investigate if chloroform concentrations in air and water affect the chloroform concentration in urine samples of exposed swimming pool workers. METHODS: Workers from 5 adventure indoor swimming pools carried personal chloroform air samplers and provided up to 4 urine samples during one workday. Chloroform concentrations were analyzed with a linear mixed model analysis to investigate a possible correlation between air and urine concentrations. RESULTS: The geometric mean chloroform concentration was 11 µg/m3 in air and 0.009 µg/g creatinine in urine among individuals with ≤2 h at work, 0.023 µg/g creatinine among those with >2-5 working hours, and 0.026 µg/g creatinine in the group with >5-10 working hours. A risk of higher levels of chloroform in urine was associated with longer hours at work (≤2 h versus >5-10 h, odds ratio [OR] 2.04, 95% confidence interval [CI] 1.25-3.34), personal chloroform concentrations in air (≤17.00 µg/m3 versus >28.00 µg/m3, OR 9.23, 95% CI 3.68-23.13) and working at least half the working day near the swimming pools (OR 3.16, 95% CI 1.33-7.55). Executing work tasks in the swimming pool water was not associated with higher chloroform concentrations in urine compared to only working on land (OR 0.82, 95% CI 0.27-2.45). CONCLUSION: There is an accumulation of chloroform concentrations in urine during a workday and a correlation between personal air and urine concentrations of chloroform among workers in Swedish indoor swimming pools.

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.

Effects on blood parameters from hand-arm vibrations exposure.

Vibration exposure from handheld tools can affect the hands with neurological symptoms and vibration-induced Raynaud's phenomenon (VRP). The underlying pathophysiological mechanisms are not fully known, however, changes in the composition of blood parameters may contribute to VRP with an increase in blood viscosity and inflammatory response. The aim of this study was to examine the effect on blood parameters in capillary blood from fingers that had been exposed to a vibrating hand-held tool. This study involved nine healthy participants who had been exposed to vibration and an unexposed control group of six participants. Capillary blood samples were collected before and after vibration exposure for the exposed group, and repeated samples also from the control group. The exposed groups were exposed to vibration for a 15-min period or until they reached a 5.0 m/s2 vibration dose. Analysis of blood status and differential counting of leucocytes was performed on the capillary blood samples. The results of the blood samples showed an increase in mean value for erythrocyte volume fraction (EVF), hemoglobin, red blood cell count, white blood cell count and neutrophils, as well as a decrease of mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration. The increase of EVF and neutrophils was statistically significant for samples taken from the index finger but not the little finger. Even though the study was small it showed that an acute vibration exposure to the hands might increase EVF and neutrophilic granulocytes levels in the capillary blood taken from index fingers.

Exposure to phthalates and DiNCH among preschool children in Sweden: Urinary metabolite concentrations and predictors of exposure.

Several plasticizing chemicals induce endocrine disrupting effects in humans, and the indoor environment is suggested to be a source of exposure. As children are particularly vulnerable to the effects from exposure to endocrine disrupting chemicals (EDCs), it is essential to monitor exposure to EDCs such as phthalates and non-phthalate plasticizers in indoor environments intended for use by children. The aim of this study was to assess everyday plasticizer exposure among preschool-aged children in Sweden by measuring urinary plasticizer metabolite concentrations. In addition, it was investigated whether the concentrations would be altered as a result of the children spending part of the day at preschool, in comparison with weekend exposure, when they may spend more time in home environments or engage in various weekend and leisure activities. For this purpose, fourteen metabolites from eight phthalates (di-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP; di-isobutyl phthalate, DiBP; butyl-benzyl phthalate, BBzP; di-iso-nonyl phthalate, DiNP; di-propylheptyl phthalate, DPHP; di-iso-decyl phthalate, DiDP; and di-ethyl phthalate, DEP) and one non-phthalate plasticizer (di-isononyl cyclohexane 1,2-dicarboxylate, DiNCH) were measured in 206 urine samples collected at four occasions, i.e. twice during the winter and twice during the spring from 54 children (mean 5.1 years, SD 0.94) enrolled at eight preschools in Sweden. A detection frequency (DF) of 99.9% for the 14 metabolites indicates a widespread exposure to plasticizers among children in Sweden. Compared to previous Swedish and international studies performed during approximately the same time period, high urinary concentrations of monobenzyl phthalate (MBzP), a metabolite from the strictly regulated BBzP, were measured in this study (median 17 ng/mL). Overall, high urinary phthalate metabolite concentrations were observed in this study compared to the US CDC-NHANES from the same time period and similar age-group. Compared to European studies, however, similar concentrations were observed for most metabolites and the urinary concentrations from few participating children exceeded the human biomonitoring guidance values (HBM-GV) for children. After days with preschool attendance, lower urinary concentrations of metabolites originating from DEP and phthalates that are strictly regulated within the EU REACH legislation (DEHP, DnBP, and DiBP) and higher concentrations of metabolites originating from DiNP, DPHP, and DiDP, i.e. less or non-regulated phthalates were found compared the urinary concentrations of these metabolites in weekends. This may indicate that factors in the indoor environment itself are important for the extent of the plasticizer exposure. All the analyzed metabolites were measured in lower concentrations in urine collected from children attending preschools built or renovated after the year 2000, while no seasonal differences were observed in this study.

Occupational Exposure to Volatile Organic Compounds (VOCs), Including Aldehydes for Swedish Hairdressers.

Working as a professional hairdresser involves the daily usage of many different hair treatment products containing chemicals in complex mixtures. Exposure may induce symptoms in the airways and on the skin. In this study, exposure of hairdressers to volatile organic compounds (VOCs), including aldehydes, was measured in the personal breathing zone in the spring of 2017. The study included 30 hairdressers evenly distributed over ten hair salons in the town of Örebro, Sweden. Work tasks and indoor climate were also surveilled. A hazard index (HI) based on chronic reference values for health was calculated to indicate combined exposure risk. In total, 90 VOCs, including nine aldehydes, were identified. Individual exposure expressed as a total concentration of VOCs (TVOCs) were in the range of 50-3600 µg/m3 toluene equivalent (median 460 µg/m3) and the HI was in the range 0.0046-13 (median 0.9). Exposure was more strongly influenced by variability among hairdressers than among salons. The HI indicated an increased risk of non-carcinogenic effects (HI ≥ 1) at four of the 10 hair salons. Individual working procedures, ventilation, volumetric usage of hair treatment products, certain chemicals in products (formaldehyde, isopropanol, and 2,4- and 2,6-toluene diisocyanate), and availability of reference values may have affected estimates of exposure risks. Nevertheless, the HI may be suitable as a screening tool to assess potential exposure risk posed to hairdressers since it considers the complexity of chemical mixtures and the chronic component of VOC exposure occurring in all indoor environments.

All-cause mortality trends in patients hospitalized for atrial fibrillation in Sweden: Role of age, stroke risk, and education.

Background: The incidence of atrial fibrillation (AF) has long been increasing, and AF is associated with increased mortality. Over time, mortality trends may differ between subgroups depending on their underlying risk patterns and treatments. Aim: To explore all-cause-mortality trends over time in patients hospitalized for incident AF, and the effects of age, stroke risk, and education level. Methods and results: Patients hospitalized for incident AF between January 1995 and December 2003 were selected from Swedish national registries. Based on date of index admission, patients were divided into four cohorts and followed for five years. Age- and sex-matched controls were selected. Kaplan-Meier estimates and Cox regressions with trend analysis were used for statistical evaluation. There were 64,489 patients (mean age 72 ± 10.1 years) and 116,893 controls. There was a significantly decreasing trend in the relative risk of all-cause mortality in AF patients over time, with a trend hazard ratio of 0.94 (95 % confidence interval [CI] 0.92-0.96, p < 0.001) in women and 0.91 (95 % CI 0.89-0.93, p < 0.001) in men. The mortality trends did not differ significantly between AF patients and controls. The mortality risk remained unchanged in women aged 18-64 years, in patients with low stroke risk, and in patients with post-secondary education. Conclusion: The all-cause mortality risk decreased over time in both patients and controls, but subgroup analysis revealed an unchanged mortality trend in women aged 18-64 years, in patients with low stroke risk, and in patients with post-secondary education.

Mortality Among Pediatric Patients With Acute Lymphoblastic Leukemia in Sweden From 1988 to 2017.

Importance: Acute lymphoblastic leukemia (ALL) constitutes 20% to 30% of all pediatric cancers. The 5-year overall survival among pediatric patients with ALL in high-income countries such as Sweden is currently more than 90%, but long-term unselected nationwide mortality data and mortality data in relation to the general population are lacking. Objective: To compare mortality between pediatric patients with ALL and the general population during a 30-year period in Sweden and to assess the incidence of ALL in Sweden. Design, Setting, and Participants: This cohort study included pediatric patients (aged <18 years) with a morphologically verified ALL diagnosis in the Swedish Cancer Register and/or at least 2 ALL diagnoses in the Swedish National Patient Register between January 1, 1988, and December 31, 2017. Data were cross-linked to the Swedish Cause of Death Register. Data were analyzed from May 2019 to January 2022. Main Outcomes and Measures: The main outcomes were mortality among patients with ALL compared with that in the general population and mortality in different subgroups within the cohort. Standardized mortality ratios (SMRs) were calculated using the general Swedish population as a reference. Within-cohort survival analyses were performed. Results: A total of 2397 patients (1354 [56%] male; mean [SD] age at diagnosis, 6.1 [4.7] years) were included in the study. The mean (SD) incidence of pediatric ALL during the study period was 4.11 (0.60) cases per 100 000 persons per year (females, 3.68 [0.65] cases per 100 000 persons per year; males, 4.52 [0.81] cases per 100 000 persons per year; P < .001). The observed number of deaths among pediatric patients with ALL was 409 vs the 9.5 deaths expected in the general population, resulting in an overall SMR of 43.1 (95% CI, 39.0-47.5); females had a higher SMR than males (57.8 [95% CI, 49.5-67.2] vs 34.5 [95% CI, 32.0-41.4]; P < .001). Analysis within the cohort showed a continued decrease in survival throughout the 30-year follow-up. The association between calendar year of ALL diagnosis, corresponding with different ALL treatment protocols, and mortality showed the lowest survival for the 1988-1991 group and the highest for the 2008-2017 group (χ2 = 20.3; P < .001). Conclusions and Relevance: In this cohort study, a consistently high SMR was seen among pediatric patients with ALL. Within the ALL cohort, survival evolved to a similar extent as in the young general population of Sweden. Furthermore, survival among patients with ALL decreased throughout the whole follow-up period without any trend difference after the 5-year follow-up time point. The changes in ALL treatment protocols were associated with overall improved absolute survival over time.

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.

Occupational Exposure to Trichloramine and Endotoxins: Adverse Health Effects Among Personnel in Adventure and Rehabilitation Swimming Pool Facilities.

OBJECTIVE: To study occupational exposure totrichloramine and endotoxins in air at adventure and rehabilitation swimming pool facilities from an adverse health effects perspective. METHODS: Air concentrations of trichloramine and endotoxins were measured in five adventure and 10 rehabilitation facilities. Respiratory and ocular symptoms were self-reported, and spirometry and fraction of exhaled nitric oxide (FEno) were measured. RESULTS: Compared to rehabilitation facilities, the mean trichloramine concentrations in the adventure facilities were higher, both personal (80 µg/m3 (n  = 41) vs 19 µg/m3 (n = 21)) and stationary (183 µg/m3 (n = 51) vs 23 µg/m3 (n = 32)), with higher frequency of ocular and respiratory symptoms. Low stationary endotoxin levels (<0.64 to 25 EU/m3) were found, compared to the reference value (90 EU/m3). CONCLUSIONS: Higher trichloramine concentrations in air and more ocular and respiratory symptoms in adventure facilities call for adequate occupational exposure limits.

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.

Contact allergy to haptens in the Swedish baseline series: Results from the Swedish Patch Test Register (2010 to 2017).

BACKGROUND: Allergic contact dermatitis has considerable public health impact and causative haptens vary over time. OBJECTIVES: To report the prevalence of contact allergy to allergens in the Swedish baseline series 2010 to 2017, as registered in the Swedish Patch Test Register. METHODS: Results and demographic information for patients tested with the Swedish baseline series in 2010 to 2017 were analysed. RESULTS: Data for 21 663 individuals (females 69%) were included. Females had significantly more positive patch tests (54% vs 40%). The reaction prevalence rates were highest for nickel sulfate (20.7%), fragrance mix I (7.1%), Myroxylon pereirae (6.9%), potassium dichromate (6.9%), cobalt chloride (6.8%), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; 6.4%), MI (3.7%), colophonium (3.5%), fragrance mix II (3.2%), and formaldehyde (3.2%). Myroxylon pereirae reaction prevalence increased from 5% in 2010 to 9% in 2017 and that for methyldibromo glutaronitrile from 3.1% to 4.6%. MCI/MI and MI reactions decreased in prevalence after 2014. Nickel reaction prevalence decreased among females aged 10 to 19 years. CONCLUSIONS: Nickel remains the most common sensitizing agent, with reaction prevalence decreasing among females younger than 20 years. The changes in MCI/MI and MI reaction prevalence mirrored those in Europe. The register can reveal changes in contact allergy prevalence over time among patients patch tested in Sweden.

Carpal Tunnel Syndrome and Hand-Arm Vibration: A Swedish National Registry Case-Control Study.

OBJECTIVE: To investigate the increased risk for carpal tunnel syndrome (CTS) in men and women with hand-arm vibration (HAV) exposure. DESIGN: Case-control study of CTS where 4396 cases was obtained from National Outpatient Register between 2005 through 2016. Cases were matched to controls and exposure was estimated using a job exposure matrix. RESULTS: Exposure to HAV increased the risk of CTS with an OR of 1.61 (95% CI 1.46-1.77). The risk was highest in men <30 years of age and among women <30 years no increased risk was observed. The risk increased with a mean year exposure above 2.5 m/s2 to OR 1.84 (95% CI 1.38-2.46). CONCLUSIONS: HAV exposure increase the risk of CTS in both genders, with highest risk increase in younger men. This emphasize identification of HAV exposure in patients with CTS.

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.

Occupational Exposure to Metalworking Fluid and the Effect on Health Symptoms-An Intervention Study.

Exposure to metalworking fluid has been shown to cause health problems among workers. The aim of this study was to compare health outcomes and levels of exposure among workers exposed to metalworking fluid before and after the implementation of preventive measures. The frequencies of self-reported symptoms, as well as the concentrations of measured substances were lower after the implementation of preventive measures. Logistic regression showed statistically significant differences in the report of irritations, a stuffy or runny nose, eye irritation, a hoarse or dry throat, and a cough with odds ratios of 0.31 (95% confidence interval [CI] 0.21 to 0.47), 0.12 (95% CI 0.05 to 0.29), 0.13 (95% CI 0.06 to 0.28), and 0.24 (95% CI 0.12 to 0.46), respectively. This confirms the efficiency of the performed intervention and highlights the importance of eliminating the recirculation of contaminated air.

Dose- and time-dependent changes in viability and IL-6, CXCL8 and CCL2 production by HaCaT-cells exposed to cobalt. Effects of high and low calcium growth conditions.

BACKGROUND: Sensitization requires exposure to an allergen with subsequent production of a "danger "signal. In the skin, keratinocytes are the main producers of these signals. OBJECTIVE: To compare dose- and time-effects of cobalt on the viability of and cytokine release from HaCaT cells cultured at low or high calcium. METHOD: To model two separate states of differentiation of keratinocytes, HaCaT cells were cultured under low or high calcium conditions. HaCaT were exposed to different concentrations of cobalt chloride (10 µm to 5 mM) over time (30 minutes- 48 hours). Cell viability was measured with the Cell-Titer Blue Viability assay. Cytokine production was measured using a bead-based immunoassay and flow cytometry. Gene expression was quantified using qPCR. Data was analyzed by ANOVA and linear mixed model. RESULTS: Viability of the cells was dose- and time-dependent. A linear mixed statistical model showed that cobalt exposure induces increase in IL-6, CXCL8 and CCL2 production over time and whereas increase of IL-6 and a decrease of CCL2 was associated with increasing cobalt chloride concentrations. When comparing the cells incubated under high and low calcium conditions, the more differentiated cells in the high concentration were found to exert a stronger response in terms of IL-6 release. CONCLUSIONS: Our data suggest that cobalt chloride triggered an alarm system in HaCaT cells, and proinflammatory cytokines/chemokines were secreted in a dose- and time-dependent manner. When high and low calcium incubations were compared, the difference was seen only for IL-6. These findings indicate that the effect of cobalt chloride on cell toxicity occurs throughout the living epidermis.

Silica Dust Exposure Increases Risk for Rheumatoid Arthritis: A Swedish National Registry Case-Control Study.

OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory disease with unknown etiology. This study examines if silica dust exposure increases the risk for seropositive and seronegative RA. METHODS: A nationwide registry case-control study was conducted that included all cases of RA in Sweden between 2005 and 2016. In total, 31,139 cases with two matched controls were included. A JEM was used to estimate exposure. RESULTS: Silica dust exposure was associated with a statistically significant increase in odds ratio (OR) for seropositive (OR 1.22, 95% CI 1.05 to 1.40) and seronegative (OR 1.23, 95% CI 1.04 to 1.46) RA among men. CONCLUSION: This study found an increased OR for RA in silica-exposed men. The OR was equal for seropositive and seronegative RA. These findings further support the hypothesis that silica dust may be a trigger for RA.

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.