Occupational exposure to respirable crystalline silica and acute myocardial infarction among men and women in Sweden.

OBJECTIVES: Occupational exposure to respirable crystalline silica (RCS) is common. The study aimed to assess the risk for acute myocardial infarction (AMI) after long-term exposure to RCS and to explore differences in risk between men and women. METHODS: The cohort included all manual workers identified from the Swedish National Census in 1980 using data on job titles and demography altogether from five censuses from 1960 to 1990, in total 605 246 men and 480 607 women. Information on AMI was obtained from nationwide registers from 1992 to 2006. Exposure to RCS was assessed with a job-exposure matrix. HRs and 95% CIs were estimated by Cox regression, adjusted for age, socioeconomic status and urbanisation index. RESULTS: Among manual workers ever exposed to RCS, the adjusted risk of AMI was HR 1.29 (95% CI 1.15 to 1.46) in women, and HR 1.02 (95% CI 1.00 to 1.04) in men. In the highest quartile of cumulative exposure, the risk of AMI was HR 1.66 (95% CI 1.27 to 2.18) for women, and HR 1.06 (95% CI 1.03 to 1.10) for men, respectively. The risk of AMI increased with cumulative exposure to RCS both in women (p=0.001) and in men (p=0.016). An interaction analysis showed that the relative risk from exposure to RCS was statistically significantly lower in men than in women at similar exposure levels. CONCLUSIONS: Occupational exposure to RCS was related to the risk of AMI. Women were more sensitive to exposure to RCS than men.

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.

Down-regulation of the inflammatory response after short-term exposure to low levels of chemical vapours.

OBJECTIVE: To investigate the relation between signs and symptoms of irritation and biomarkers of inflammatory markers in blood in healthy volunteers exposed to different chemical vapours for 2 or 4 hours in an exposure chamber. METHODS: The investigated chemicals were: acetic acid (5 and 10 ppm), acrolein (0.05 and 0.1 ppm), 1,4-dioxane (20 ppm), n-hexanal (2 and 10 ppm), hydrogen peroxide (0.5 and 2.2 ppm), 2-propanol (150 ppm), m-xylene (50 ppm), standard and dearomatised white spirit (100 and 300 mg/m3). C reactive protein (CRP), serum amyloid A protein and interleukin 6 were measured in plasma immediately before and 2 or 4 hours after the exposures. Symptoms were rated from 0 to 100 mm in Visual Analogue Scales and covered 10 questions whereof four related to irritation: discomfort in the eyes, nose and throat and dyspnoea. The effect measurements included blink frequency by electromyography, nasal swelling by acoustic rhinometry and lung function by spirometry. RESULTS: Logistic quantile regression analyses revealed no significant associations except a negative relation between ratings of irritation and CRP. CONCLUSION: The results suggest a down-regulation of CRP after short-term exposure to low levels of vapours of irritating chemicals. This response might be mediated by the cholinergic anti-inflammatory pathway and further studies are recommended in order to refute or confirm this hypothesis.

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.

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.

Acute effects of acrolein in human volunteers during controlled exposure.

CONTEXT: Acrolein is a reactive aldehyde mainly formed by combustion. The critical effect is considered to be irritation of the eyes and airways; however, the scarce data available make it difficult to assess effect levels. OBJECTIVE: The aim of the study was to determine thresholds for acute irritation for acrolein. METHODS: Nine healthy volunteers of each sex were exposed at six occasions for 2 h at rest to: clean air, 15 ppm ethyl acetate (EA), and 0.05 ppm and 0.1 ppm acrolein with and without EA (15 ppm) to mask the potential influence of odor. Symptoms related to irritation and central nervous system effects were rated on 100-mm Visual Analogue Scales. RESULTS: The ratings of eye irritation were slightly but significantly increased during exposure to acrolein in a dose-dependent manner (p < 0.001, Friedman test) with a median rating of 8 mm (corresponding to "hardly at all") at the 0.1 ppm condition and with no influence from EA. No significant exposure-related effects were found for pulmonary function, or nasal swelling, nor for markers of inflammation and coagulation in blood (IL-6, C-reactive protein, serum amyloid A, fibrinogen, factor VIII, von Willebrand factor, and Clara cell protein) or induced sputum (cell count, differential cell count, IL-6 and IL-8). Blink frequency recorded by electromyography was increased during exposure to 0.1 ppm acrolein alone but not during any of the other five exposure conditions. CONCLUSION: Based on subjective ratings, the present study showed minor eye irritation by exposure to 0.1 ppm acrolein.

Fatal carbon monoxide intoxication after acetylene gas welding of pipes.

Acetylene gas welding of district heating pipes can result in exposure to high concentrations of carbon monoxide. A fatal case due to intoxication is described. Measurements of carbon monoxide revealed high levels when gas welding a pipe with closed ends. This fatality and these measurements highlight a new hazard, which must be promptly prevented.

Occupational exposure to particles and incidence of acute myocardial infarction and other ischaemic heart disease.

BACKGROUND: Ambient particulate air pollution has been linked to cardiovascular disease. Occupational particle exposure levels may be several times higher than ambient levels but has been less studied. OBJECTIVES: The authors investigated the association between occupational exposure to particles and the incidence of ischaemic heart disease (IHD). METHODS: The cohort included all manual workers in the Swedish national census of 1980 with information on demographic data and occupation. Information on hospital admissions for acute myocardial infarction or other IHDs and cause of death were obtained from nation-wide registers. A job-exposure matrix for exposure to small (<1 µm) and large (>1 µm) particles was developed. HRs were calculated with Cox regression with adjustment for sex, age, socioeconomic group and urban/rural residential area. RESULTS: Exposure to small particles was associated with an increased HR for acute myocardial infarction of 1.12 (95% CI 1.09 to 1.15), and HR for exposure to large particles was 1.14 (95% CI 1.10 to 1.18). The association was somewhat stronger for workers exposed to small particles for more than 5 years, 1.21 (95% CI 1.11 to 1.31), but no trend with exposure intensity was found. The risk associated with exposure to small particles was higher among women than among men, 1.30 (95% CI 1.12 to 1.51) and 1.10 (95% CI 1.07 to 1.14), respectively. Findings were essentially similar for other IHDs. CONCLUSIONS: This explorative study gives some support to the hypothesis that occupational exposure to particles increases the risk of acute myocardial infarction and other IHD. The findings must be interpreted cautiously due to lack of smoking data.

Inflammatory markers and exposure to occupational air pollutants.

OBJECTIVES: To study the possible relationship between inhalation of airborne particles in the work environment and inflammatory markers in blood. METHODS: Total dust was sampled in the breathing zone of 73 subjects working with welding, cutting, grinding and in foundries such as iron, aluminium, and concrete. Stationary measurements were used to study different size fractions of particles including respirable dust, particulate matter (PM)(10) and PM(2.5), the particle number concentration, the number of particles deposited in the alveoli, and total particle surface area concentration. Inflammatory markers such as interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, d-dimer, and urate were measured in plasma or serum before the first shift after the summer vacation and after the first, second, and fourth shift. RESULTS: The mean level of total dust in the breathing zone was 0.93 mg/m(3). The proxies for mean respirable dust fraction was 0.27 mg/m(3), PM(10) 0.60 mg/m(3), and PM(2.5) was 0.31 mg/m(3). The IL-6 values increased by 50% after the first day, but decreased after shift on the second and fourth day. CRP did not increase after the first shift but increased by 17% after the second shift. Other biomarkers were unaffected. A multiple linear regression analysis of a subgroup of 47 subjects showed a statistically significant positive relationship between particle exposure and post-shift IL-6. CONCLUSION: This study supports previous investigations observing increases of IL-6 at air concentrations of PM(10) or PM(2.5) between 0.13 and 0.3 mg/m(3) among healthy subjects. This increase of IL-6 may indicate an increased risk of coronary heart disease.

Respiratory Health and Inflammatory Markers-Exposure to Cobalt in the Swedish Hard Metal Industry.

OBJECTIVE: To study the relationship between inhalable dust and cobalt, and respiratory symptoms, lung function, exhaled nitric oxide in expired air, and CC16 in the Swedish hard metal industry. METHODS: Personal sampling of inhalable dust and cobalt, and medical examination including blood sampling was performed for 72 workers. Exposure-response relationships were determined using logistic, linear, and mixed-model analysis. RESULTS: The average inhalable dust and cobalt concentrations were 0.079 and 0.0017 mg/m, respectively. Statistically significant increased serum levels of CC16 were determined when the high and low cumulative exposures for cobalt were compared. Nonsignificant exposure-response relationships were observed between cross-shift inhalable dust or cobalt exposures and asthma, nose dripping, and bronchitis. CONCLUSIONS: Our findings suggest an exposure-response relationship between inhalable cumulative cobalt exposure and CC16 levels in blood, which may reflect an injury or a reparation process in the lungs.

Acute effects of exposure to vapours of standard and dearomatized white spirits in humans. 2. Irritation and inflammation.

Low aromatic and dearomatized white spirits (deWS) are often considered less hazardous to health than 'standard' or aromatic white sprit (stdWS, 15-20% aromatics). However, data on health effects of deWS in humans are sparse and controlled exposure studies are lacking. The aim of this study was to compare deWS and stdWS with respect to irritation and inflammation. Six female and six male healthy volunteers were exposed on five occasions in balanced order to 100 or 300 mg m(-3) deWS (0.002% aromatics) or stdWS (19% aromatics), or to clean air, for 4 h at rest. Discomfort in the eyes, nose and throat and breathing difficulty were assessed by ratings on visual analogue scales. The only significant increases in ratings (compared to clean air) were seen for eye irritation at the high stdWS exposure and for solvent smell at all but the low deWS exposure. Excluding smell, all average ratings were at the lower end of the 0-100 mm scale, and did not exceed the verbal expression 'somewhat'. Ratings during stdWS exposure tended to be higher than during deWS exposure. No exposure-related effects on pulmonary function, nasal swelling, nasal airway resistance, breathing frequency, blinking frequency, plasma inflammatory markers (C-reactive protein, interleukin-6) or biochemical variables (sodium, potassium, amylase, creatine kinase, urate) were seen. In conclusion, stdWS appears to be slightly more irritating than deWS. This could, however, not be confirmed by objective measurements.

Rapid effects of air pollution on ventricular arrhythmias.

AIMS: Air pollution has been associated with ventricular arrhythmias in patients with implantable cardioverter defibrillators (ICDs) for exposure periods of 24-48 h. Only two studies have investigated exposure periods <24 h. We aimed to explore such effects during the 2 and 24 preceding hours as well as in relation to distance from the place of the event to the air pollution monitor. METHODS AND RESULTS: We used a case-crossover design to investigate the effects of particulate matter <10 microm in diameter (PM10) and nitrogen dioxide (NO2) in 211 patients with ICD devices in Gothenburg and Stockholm, Sweden. Events interpreted as ventricular arrhythmias were downloaded from the ICDs, and air pollution data were collected from urban background monitors. We found an association between 2 h moving averages of PM10 and ventricular arrhythmia [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.00-1.72], whereas the OR for 24 h moving averages was 1.24 (95% CI 0.87-1.76). Corresponding ORs for events occurring closest to the air pollution monitor were 1.76 (95% CI 1.18-2.61) and 1.74 (95% CI 1.07-2.84), respectively. Events occurring in Gothenburg showed stronger associations than in Stockholm. CONCLUSION: Moderate increases in air pollution appear to be associated with ventricular arrhythmias in ICD patients already after 2 h, although future studies including larger numbers of events are required to confirm these findings. Representative geographical exposure classification seems important in studies of these effects.

Experimental exposure to 1,1,1-trifluoroethane (HFC-143a): uptake, disposition and acute effects in male volunteers.

The aim of this study was to determine the toxicokinetics and some effects of 1,1,1-trifluoroethane (HFC-143a) in humans. Nine male volunteers were experimentally exposed to 500ppm HFC-143a for 2h during light physical exercise (50W) in an exposure chamber. Blood, urine and exhaled air were sampled before, during and up to 19h after exposure and analysed for HFC-143a by gas chromatography. These data were described by a physiologically based toxicokinetic (PBTK) model. The electrocardiograms of the volunteers were monitored during exposure. Before, during and after exposure the volunteers rated symptoms related to irritation and CNS-symptoms on a visual analogue scale. Inflammatory markers (C-reactive protein, serum amyloid A protein, D-dimer, fibrinogen) and uric acid were analysed in plasma collected before and 21h after exposure. The exposures were performed after informed consent and ethical approval. The plasma concentration of HFC-143a increased promptly at start of exposure, and decreased in the same manner post-exposure. A stable level of 4.8+/-2.0 microM (mean+/-S.D.) was reached within 30min of exposure. The HFC-143a concentration in plasma and exhaled air decreased fast and in parallel when exposure was stopped. The urinary excretion of HFC-143a after exposure was 0.0007% of the inhaled amount. The half-time in urine, calculated from pooled data, was 53min. The experimental and simulated time courses in blood and exhaled air were in agreement. The simulated relative uptake during the exposure was 1.6+/-0.3%. The fibrinogen level in plasma had increased by 11% 1 day post-exposure. No statistically significant increase was seen for the other inflammatory markers or for uric acid. No effects of exposure were seen either in the electrocardiographic monitorings or as symptom ratings on the visual analogue scale.

Non-positive autoimmune responses against CYP2E1 in refrigeration mechanics exposed to halogenated hydrocarbons.

The aim of the study was to determine if occupational exposure to hydrofluorocarbons (HFC) and hydrochlorofluorocarbons (HCFC) generates autoimmune responses against CYP2E1. HFCs and HCFCs have replaced the chlorofluorocarbons (CFC) in e.g. refrigeration installations and air-conditioning systems. During the substitution period, refrigeration mechanics reported symptoms like asthma, influenza-like reactions, and joint troubles. These symptoms resemble those of chronic inflammatory diseases with an autoimmune component. Since exposure to structurally similar chemicals, e.g. halothane, has previously been associated with autoimmune responses and diseases, autoimmunity among the refrigeration mechanics might hypothetically explain the reported inflammatory symptoms. Serum from 44 Swedish men, occupationally exposed to halogenated hydrocarbons, was screened for antibodies against CYP2E1 with enzyme-linked immunosorbent assay. Thirty of the workers had asthma, joint problems or influenza-like symptoms whereas 14 of them had no such symptoms. They were all selected from a cohort of 280 refrigeration mechanics. Unexposed, healthy, Swedish men (n=35) constituted control group. The study was approved by the Ethics Committee at Karolinska Institutet. No increase in autoantibodies against CYP2E1 was detected among the occupationally exposed workers as compared to the unexposed controls. Further, there was no difference in antibody titer between the exposed workers with symptoms and the exposed, asymtomatic workers or the unexposed controls. The present study does not completely exclude a connection between exposure and effect but makes the relation less likely at these exposure levels.

Toxicokinetics of 1,1,1,2-tetrafluoroethane (HFC-134a) in male volunteers after experimental exposure.

The aim of this study was to determine the uptake and disposition of inhaled 1,1,1,2-tetrafluoroethane (HFC-134a) in humans. Ten male volunteers were exposed to 500 ppm HFC-134a (2 h, 50 W exercise). The HFC-134a levels were monitored in blood, exhaled air and urine up to 19 h post-exposure. The concentration in blood increased rapidly, reaching a plateau of 9.4+/-1.9 microM (mean+/-S.D.) within 30 min, followed by a fast post-exposure decrease. HFC-134a in expired air decreased rapidly as well and in parallel with that in blood. The post-exposure urinary excretion was 0.002% of the inhaled amount, and the half-time was 58 min (pooled data). A physiologically based toxicokinetic (PBTK) model was developed for further analysis. Experimental and simulated time courses in blood and exhaled air agreed well in all 10 subjects. Further, the late decay in blood was consistent with a wash-out of HFC-134a from fat tissues, with a half-time of 114+/-21 min. The simulated relative uptake during exposure was 3.7+/-0.5%. No remarkable findings were observed in the electrocardiographic recordings. Fibrinogen in plasma increased 1 day after exposure, whereas no effects on C-reactive protein, serum amyloid A protein, D-dimer or uric acid were seen. Further studies are needed to investigate the possible inflammatory response.

Acute effects of exposure to vapours of acetic acid in humans.

Acetic acid is used in plastics, chemical and pharmaceutical industries. Despite a widespread use, information of possible health effects is sparse. The aim of this study was to evaluate acute irritation during controlled exposure to vapours of acetic acid. Six female and six male healthy volunteers were exposed to 0 ppm (control exposure), 5 and 10 ppm acetic acid vapour for 2 h at rest in a balanced order. Subjective ratings of nasal irritation and smell increased significantly with exposure level. Except for smell, all average ratings at 10 ppm were at the lower end of the 0-100mm visual analogue scale, and did not exceed the verbal expression "somewhat" (26 mm). No effects on pulmonary function, nasal swelling, nasal airway resistance or plasma inflammatory markers (C-reactive protein, and interleukin-6), measured before and after exposure, were seen. There was a non-significant tendency to increased blinking frequency, as measured continuously during exposure, after exposure to 10 ppm acetic acid. In conclusion, our study suggests a mild irritative effect at 10 ppm acetic acid.