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.

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.

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.

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.

Short-term departures from an optimum ambient temperature are associated with increased risk of out-of-hospital cardiac arrest.

BACKGROUND: Associations have been reported between daily ambient temperature and all-cause and cardiovascular mortality. However, the potential harmful effect of temperature on out-of-hospital cardiac arrest (OHCA) is insufficiently studied. OBJECTIVES: The objective of this study was to investigate the short-term association between ambient temperature and the occurrence of OHCA. METHODS: In 5961 cases of OHCAs treated by Emergency Medical Service occurring in Stockholm County we investigated the association between the preceding 24-h and 1h mean ambient temperature, obtained from a fixed monitoring station, and OHCA using a time-stratified case-crossover design. RESULTS: We observed a V-shaped relationship between preceding mean 24-h and 1-h ambient temperature and the occurrence of OHCAs. For mean 24-h temperature we observed an odds ratio (OR) of 1.05 (1.00-1.11) for each 5°C below the optimum temperature and 1.05 (0.96-1.18) for each 5°C above the optimum. We observed similar results for 1-h mean temperature exposure. Results for temperatures above the optimum temperature showed evidence of confounding by ozone. CONCLUSION: Ambient temperature below an optimum temperature was associated with increased risk of OHCA in Stockholm. Temperature above an optimum temperature was not significantly associated with OHCA.

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.

Blood and exhaled air can be used for biomonitoring of hydrofluorocarbon exposure.

Various hydrofluorocarbons (HFCs) have replaced the ozone-depleting chlorofluorocarbons and hydrochlorofluorocarbons during the last decades. The objective of this study was to examine the usefulness of blood and breath for exposure biomonitoring of HFCs. We compared data on blood and exhaled air from a series of experiments where healthy volunteers were exposed to vapors of four commonly used HFCs; 1,1-difluoroethane, 1,1,1-trifluoroethane, 1,1,1,2-tetrafluoroethane, and 1,1,1,3,3-pentafluoropropane. All four HFCs had similar toxicokinetic profiles in blood with a rapid initial increase and an apparent steady-state reached within a few minutes. For all HFCs, the inhalation uptake during exposure was low (less than 6%), most of which was exhaled post-exposure. No metabolism could be detected and only minor amounts were excreted unchanged in urine. The observed time courses in blood and breath were well described by physiologically-based pharmacokinetic (PBPK) modeling. Simulations of 8-h exposures show that the HFC levels in both blood and breath drop rapidly during the first minutes post-exposure, whereafter the decline is considerably slower and mainly reflects washout from fat tissues. We conclude that blood and exhaled air can be used for biological exposure monitoring. Samples should not be taken immediately at the end of shift but rather 20-30 min later.

The neurobehavioral impact of manganese: results and challenges obtained by a meta-analysis of individual participant data.

Results from a meta-analysis of aggregated data provoked a new analysis using individual data on the neuropsychological performance of occupationally exposed workers. Data from eight studies examining 579 exposed and 433 reference participants were included, 28 performance variables analyzed. The performance scores were adjusted for well-known individual-level covariates; the influence of possible, but unknown study-level covariates was attenuated by means of a z-normalization. Associations between performance and exposure were estimated by ANOVAs and ANCOVAs, the latter representing multi-level models. Four cognitive and motor performance variables each indicated significantly lower performances of exposed individuals when confounding was considered; slowed motor performances and deficits in attention and short-term memory were found. Performance on a single test was significantly related to the biomarker manganese in blood. The outcomes on susceptibility were weak. The slowing of responses was the most distinct feature of performances of exposed workers. It remains unclear, whether this result is related to the employed tests or provides important information about early stages of the neurotoxic impairment. More specific cognitive tests need to be employed to answer this question. The lack of dose-response relationships was related to features of the biomarker: it does not reflect the Mn in brain responsible for changes in performances.

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.

Incidence of myocardial infarction among cooks and other restaurant workers in Sweden 1987-2005.

OBJECTIVES: The aim of this study was to investigate the incidence of myocardial infarction (MI) among cooks and other restaurant workers. METHODS: A prospective cohort study comprised manual workers in the service sector in the Swedish National Census of 1985, totaling 543 497 women and 233 999 men. Restaurant workers were identified by occupational codes. Information on first time MI during 1987-2005 was obtained from nation-wide registers. We used Cox proportional hazards modeling, with separate analyses for men and women, adjusting for age, hypertension, diabetes, and socioeconomic status. RESULTS: Female cooks, restaurant and kitchen assistants, and wait staff all showed a statistically significant increase in risk of MI [hazard ratio (HR) 1.34, 95% confidence interval (95% CI) 1.21-1.48; HR 1.12, 95% CI 1.03-1.21; and HR 1.25, 95% CI 1.06-1.47, respectively]. No increased risk was found among female cold-buffet managers. Among men, there was no statistically significant increase in risk for any of these occupations. The association was not stronger for subjects working ≥5 years. Group level information on smoking habits showed a similar percentage of daily smokers among female cooks compared to female manual workers in general. CONCLUSIONS: We found an increased risk of MI among female but not male cooks, restaurant and kitchen assistants, and wait staff. The excess risk may be related to occupational factors, but the results do not clearly support the hypothesis of cooking fumes as a risk factor for MI. Job strain could be a potential explanation for the findings.

Occupational exposure to particles and incidence of stroke.

OBJECTIVES: This paper aims to investigate the relation between occupational exposure to particles, particle size, and the incidence of ischemic and hemorrhagic stroke. METHODS: The cohort included all manual workers identified from the Swedish National Census in 1980, who were alive as of 1 January 1987. First time events of ischemic or hemorrhagic stroke during the period 1987-2005 were identified through linkage to the Hospital Discharge Register and the National Cause of Death Register. A job-exposure matrix for exposure to small (<1 µm) and large (>1 µm) particles was developed and applied. Hazard ratios (HR) were estimated by Cox regression with adjustment for age, socioeconomic group, and residential area. RESULTS: Increased HR of ischemic stroke were found among both women and men occupationally exposed to small as well as large particles for ≥5 years. The risks were higher for workers exposed for ≥5 years compared to "ever exposed" participants indicating a dose-response relationship, but no trend with exposure intensity was observed. A tentative association between particle exposure and hemorrhagic stroke was also found. CONCLUSIONS: Occupational exposure to small and large particles was associated with increased risks of ischemic stroke. Further studies are needed to explore the relationships between exposure to different types of particles and various doses and the occurrence of stroke among women as well as men.

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.

Acute effects of exposure to vapors of hydrogen peroxide in humans.

Hydrogen peroxide is a reactive chemical mainly used for bleaching, as a disinfectant, and as a general oxidizing agent. The aim of this study was to investigate subtle acute effects of inhaled hydrogen peroxide vapors. Eleven healthy volunteers were exposed to 0 (clean air), 0.5 and 2.2 ppm for 2h at rest. Symptoms related to irritation and central nervous system effects were rated with Visual Analog Scales. The ratings varied considerably but were generally low and with no significant differences between exposure conditions, although the ratings of smell (p=0.09, Friedman's test), nasal irritation (p=0.06) and throat irritation (p=0.06) showed borderline tendencies to increase at 2.2 but not at 0 and 0.5 ppm. Nasal airway resistance increased after exposure to 2.2 ppm hydrogen peroxide (p=0.04, paired t-test) but not after 0.5 ppm. No exposure-related effects on pulmonary function, nasal swelling, breathing frequency and blinking frequency were detected. Furthermore, no clear effects were seen on markers of inflammation and coagulation (interleukin-6, C-reactive protein, serum amyloid A, fibrinogen, factor VIII, von Willebrand factor and Clara cell protein in plasma). In conclusion, our study suggests that hydrogen peroxide is slightly irritating at 2.2 ppm, but not at 0.5 ppm.

Uptake and disposition of 1,1-difluoroethane (HFC-152a) in humans.

The aim of this study was to determine the toxicokinetics of inhaled 1,1-difluoroethane (HFC-152a) in humans. Healthy volunteers were exposed to 0, 200 or 1000 ppm 1,1-difluoroethane for 2h at light exercise in an exposure chamber. Capillary blood, urine and exhaled air were sampled up to 22 h post-exposure and analyzed for 1,1-difluoroethane. Fluoride and other potential metabolites were analyzed in urine. Symptoms of irritation and central nervous system effects were rated and inflammatory markers were analyzed in blood. Within a few minutes of exposure to 200 and 1000 ppm, 1,1-difluoroethane increased rapidly in blood and reached average levels of 7.4 and 34.3 µM, respectively. The post-exposure decreases in blood were fast and parallel to those in exhaled air. The observed time courses in blood and breath agreed well with those obtained with the PBPK model. The PBPK simulations indicate a net uptake during exposure to 1000 ppm of 6.6 mmol (6.7%) which corresponds to the amount exhaled post-exposure. About 20 µmol excess fluoride (0.013% of inhaled 1,1-difluoroethane on a molar basis) was excreted in urine after exposure to 1000 ppm, compared to control. No fluorine-containing metabolites were detected in urine. Symptom ratings and changes in inflammatory markers revealed no exposure-related effects.