Inhalation toxicity of 316L stainless steel powder in relation to bioaccessibility.

The Globally Harmonized System for Classification and Labelling of Chemicals (GHS) considers metallic alloys, such as nickel (Ni)-containing stainless steel (SS), as mixtures of substances, without considering that alloys behave differently compared to their constituent metals. This study presents an approach using metal release, explained by surface compositional data, for the prediction of inhalation toxicity of SS AISI 316L. The release of Ni into synthetic biological fluids is >1000-fold lower from the SS powder than from Ni metal, due to the chromium(III)-rich surface oxide of SS. Thus, it was hypothesized that the inhalation toxicity of SS is significantly lower than what could be predicted based on Ni metal content. A 28-day inhalation study with rats exposed to SS 316L powder (<4 µm, mass median aerodynamic diameter 2.5-3.0 µm) at concentrations up to 1.0 mg/L showed accumulation of metal particles in the lung lobes, but no signs of inflammation, although Ni metal caused lung toxicity in a similar published study at significantly lower concentrations. It was concluded that the bioaccessible (released) fraction, rather than the elemental nominal composition, predicts the toxicity of SS powder. The study provides a basis for an approach for future validation, standardization and risk assessment of metal alloys.

Acute exposure to resveratrol inhibits AMPK activity in human skeletal muscle cells.

AIMS/HYPOTHESIS: Recent studies have suggested resveratrol (RSV) as a new natural therapeutic agent to treat type 2 diabetes and lipid-induced insulin resistance. Here, we investigated whether RSV could reverse palmitate-induced insulin resistance in human primary muscle cells. METHODS: Myotubes obtained from six healthy men (54 ± 3 years (mean ± SE), BMI 25.0 ± 1.7 kg/m(2), fasting plasma glucose concentration (fP-glucose) 5.47 ± 0.09 mmol/l) were treated for 4 h with 100 µmol/l RSV and/or 0.2 mmol/l palmitate, and stimulated with or without 100 nmol/l insulin. Assays of glucose uptake, glycogen synthesis, palmitate oxidation, intracellular signalling and AMP-activated protein kinase (AMPK) activity were performed. RESULTS: RSV did not reverse palmitate-induced impairment of glucose metabolism. Surprisingly, RSV decreased glucose uptake and glycogen synthesis in human skeletal muscle cells. Palmitate oxidation and phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase ß (ACCß) were inhibited by RSV, and RSV completely blocked the activity of AMPK isoform complexes α1/ß2/γ1 and α2/ß2/γ1 in in-vitro kinase activity assays. Endoplasmic reticulum (ER) stress was increased in response to RSV, as indicated by increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) and increased expression of CCAAT/enhancer binding protein homologous protein (CHOP). CONCLUSIONS/INTERPRETATION: Acute exposure to RSV inhibits AMPK activity, fatty-acid oxidation and glucose metabolism in human myotubes.

Computed tomography of asbestos-related pleural abnormalities.

OBJECTIVES: To study the observer agreement in several asbestos-related pleural abnormalities and to define criteria to discriminate between pleural changes in workers with occupational disease, and those in controls. METHODS: Pleural abnormalities in spiral computed tomography of 602 construction workers with asbestosis or bilateral pleural plaques and 49 controls were reviewed by three radiologists using structured forms. RESULTS: Intra- and inter-observer agreement (weighted kappa) was 0.4 or better with regard to the calcification, extent and thickness of pleural disease. These factors all correlated positively with the duration of asbestos exposure. There were significant differences in these pleural changes between the workers (mean extent per side 83 cm(2)) and controls (mean extent per side 40 cm(2)). Of the controls, 84% showed pleural lesions with an estimated extent of 10 cm(2) or more, bilateral in 64%. The extent of 45 cm(2) in pleural disease was the best value for discriminating between the controls and diseased workers, with a sensitivity of 82% and a specificity of 66%. The degree of pleural calcification, however, was the best discriminator between these groups, but quantitative methods are necessary for its use in the diagnostics of individuals. CONCLUSIONS: The extent, calcification and thickness were well-repeatable indicators of benign pleural pathology and thus their use in future classification systems in computed tomography is recommended. In our material, the extent of 45 cm(2) and the degree of calcification were helpful in discriminating between pleural changes in workers with occupational disease, and those in controls who also presented marked pleural pathology.

High-resolution computed tomography classification of lung fibrosis for patients with asbestos-related disease.

OBJECTIVES: This study tested a new high-resolution computed tomography (HRCT) scoring method for asbestos-induced parenchymal changes in the lung. METHODS: HRCT scans of 602 asbestos-exposed workers and 49 referents were reviewed by 3 radiologists. Structured forms were filled out for a semiquantitative HRCT fibrosis score based on several specified parenchymal abnormalities scored separately. Observer agreement was studied with the use of the quadratic-weighted kappa (kappaqw). The HRCT fibrosis score (from 0 to V with definitions and index images given retrospectively) was compared with the radiographic classification of the International Labour Office (ILO) for the same patients. Receiver-operating characteristic (ROC) curves were computed to compare the tests for diagnosing asbestosis. RESULTS: Good inter- and intraobserver agreements were achieved (kappaqw = 0.64 and 0.72, respectively) as regards the HRCT fibrosis score. All the specified computed tomography findings explained 86% of the variance in the HRCT fibrosis score. Age and occupational group were significant predictors of fibrosis. The area under the ROC curve was significantly greater for the HRCT fibrosis score (0.89) than for the ILO radiographic classification (0.76). The sensitivity (70%) and specificity (91%) of the HRCT fibrosis score (classes I/II-V representing asbestosis) were better than those of the classification published by the International Labour Office (51% and 89%, respectively, score > or = 1/0 representing asbestosis). CONCLUSIONS: The examined HRCT scoring method proved to be a simple, reliable, and reproducible method for classifying lung fibrosis and diagnosing asbestosis also in large populations with occupational disease, and it would be possible to use it as a part of an international classification.

Lung sounds in asbestos induced pulmonary disorders.

The aim of the study was to compare the lung sounds in patients with asbestos related pulmonary disorders with findings in high-resolution computed tomography (HRCT), and with lung function variables, in order to find out associations of acoustic changes with radiological fibrosis, emphysema or with pulmonary gas transfer functions. Sixty-four patients with asbestos-related pleural disease, with or without pulmonary disease, were studied. Lung sound recording and analysis was carried out with a computerized lung sound analyser, and HRCT of the chest, as well as forced spirometry and diffusing capacity measurement were performed. The fibrosis score correlated positively with the quartile frequencies of the power spectrum of lung sounds in inspiration (f50) and expiration (f50) and crackle count in inspiration, as well as negatively with diffusing capacity. When the patients with crackling sounds and significant fibrosis were excluded (n=18), emphysema correlated negatively with expiratory quartile frequencies of the power spectrum, with f25 and f50. Furthermore, diffusing capacity correlated with inspiratory f25 and forced expiratory volume in one second with inspiratory f50 when crackles and fibrosis were excluded. Changes in lung sounds were significantly associated with radiologically verified abnormalities and gas transfer of pulmonary tissue. High sound frequencies were associated with fibrotic changes of the lung while low sound frequencies with pulmonary emphysema. Acoustic analysis gives complementary clinical information for evaluation of asbestos-related pulmonary disorders.

Follow-up of asbestosis patients and predictors for radiographic progression.

OBJECTIVE: We followed a group of 85 Finnish asbestosis patients radiographically for an average of 6.5 (range 2-10) years to examine the progression of the disease and to assess possible explanations for the progression. METHODS: The examinations included full-size chest radiographs and a blood specimen analysis. The radiographs were classified according to the 1980 International Labor Office (ILO) classification. Progression was accepted if the second or third radiography was estimated (in a side-by-side comparison) to have more profusion of small opacities qualitatively than the first, even if the radiographs were classified into the same profusion category. RESULTS: In all, 38% of the patients showed progression during the follow-up period. The average progression of small opacities ranged from ILO 1/1 to ILO 2/2 (0.4 minor ILO categories/year). The asbestosis was progressive more often among the sprayers than among the insulators and asbestos factory workers [cross-tabulation, odds ratio (OR) 5.0, 95% confidence interval (95% CI) 1.2-20]. In the logistic regression model the ILO classification category at the beginning of the follow-up (OR 1.54; 95% CI 0.96-2.47), the fibronectin (OR 1.01; 95% CI 1.00-1.01) and angiotensin-converting enzyme (ACE; OR 1.10; 95% CI 1.00-1.20) levels, and the erythrocyte sedimentation rate (ESR; OR 1.05; 95% CI 1.00-1.10) were statistically associated with the radiographic progression of small opacities. Abnormalities of the pleura were found to progress more often among the patients with progressive parenchymal opacities. CONCLUSION: For the progression of small-opacity profusion the significant predictors in the logistic regression model were the ILO profusion category at the beginning of the follow-up period, the fibronectin level, the ACE value, and the ESR. The model correctly classified 94% of the patients with progression and 65% of those without progression. The differences in the mean values recorded for the biomarkers between the progressors and nonprogressors, however, were small and may therefore not be of any importance to the clinician.

Observer variation in classifying chest radiographs for small lung opacities and pleural abnormalities in a population sample.

BACKGROUND: The purpose of this study was to assess inter-and intraobserver variation in the radiographic categories of small lung opacities (profusion) and pleural abnormalities classified according to the ILO classification of pneumoconioses with some modifications. METHODS: Chest radiographs derived from a representative adult population sample (n = 7,095) were classified by two radiologists. Observer variation was assessed on the basis of kappa (kappa)-type statistics. RESULTS: The observers agreed on profusion categories in 69% of cases of the total material. Up to 98% of the classifications fell into the same category or deviated by no more than one category. The corresponding kappa (kappa) coefficient was 0.48 (95% CI = 0.46=0.49) and the weighted kappa 0.72. When a selected subsample was reclassified by the observers, the proportions of crude agreement on profusion of small opacities ranged from 42% to 47% (weighted kappa 0.52-0.55). The proportions of agreement on the main pleural abnormalities were 92% or over, and the corresponding kappa coefficients at least 0.73. CONCLUSION: The classification of lung opacities was subject to considerable observer variation, which calls for caution when results from different studies are compared. This variation, however, rarely exceeded one category, and thus appears to be small enough for meaningful comparisons between groups, at least within a single study.

Radiographic abnormalities among Finnish construction, shipyard and asbestos industry workers.

OBJECTIVES: The prevalence of asbestos-related radiographic abnormalities was surveyed among Finnish construction, shipyard, and asbestos industry workers. METHODS: The radiographic screening focused on active and retired workers who were under the age of 70 years and had been employed for at least 10 years in construction or for at least 1 year in shipyards or in the asbestos industry. In 1990-1992, 18,943 people participated in an X-ray examination of the lungs and an interview on work history and exposure. The criteria for a positive radiological finding were (i) small irregular lung opacities clearly consistent with interstitial pulmonary fibrosis (ILO 1/1 or higher), (ii) lung opacities indicating mild pulmonary fibrosis (ILO 1/0) with unilateral or bilateral pleural plaques, (iii) marked adhesions with or without thickening of the visceral pleura, or (iv) findings consistent with bilateral pleural plaques. RESULTS: Fulfilling the criteria were 4133 workers (22%) (22% from construction, 16% from shipyards, and 24% from the asbestos industry). The radiological findings included signs of pulmonary fibrosis (3%), changes in the visceral pleura (7%), bilateral plaques (17%), and unilateral plaques (10%). Occupational disease was diagnosed according to the Finnish insurance regulations for three-fourths of those referred for further examinations, 96% being abnormalities in the pleura and 4% being asbestosis. CONCLUSIONS: Exposure to asbestos dust has been common in ordinary construction work, and, consequently, radiographic abnormalities (mostly pleural) occur frequently among active and retired construction workers.

Fibrosis of the lung and pleura and long-term exposure to wollastonite.

OBJECTIVES: The purpose of this study was to determine whether long-term exposure to wollastonite causes fibrosis of the lung and pleura in humans. METHODS: Forty-nine workers (mean exposure 25 years) in a Finnish limestone-wollastonite mine and mill were examined. Their work histories and symptoms of chronic bronchitis were recorded. The chest radiographs were classified according to the classification of the International Labour Office (1980); a radiographic follow-up from 1981 to 1990 was included. Spirometry and diffusion capacity were measured. Four workers underwent high-resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL). Lung tissue specimens were available for 2 workers. Mineral fibers and asbestos bodies were analyzed from the BAL fluid and lung tissue specimens, which were also analyzed for lung fibrosis. RESULTS: Two workers (4%) had small irregular lung opacities (ILO 1/0), 1 worker (2%) ILO 0/1 of the s/t type. HRCT revealed no parenchymal fibrosis in the 2 workers with the ILO 1/0 classification. Of the 9 workers (18%) with pleural plaques, 5 had been exposed to asbestos. Multivariate logistic regression analyses revealed no association of plaques with the duration of wollastonite or asbestos exposure. Wollastonite fibers or bodies were not found in any of the 4 workers who underwent BAL, nor in either of the workers whose lung tissue specimens were available. CONCLUSIONS: No evidence was found that long-term exposure to wollastonite causes parenchymal fibrosis of the lung and pleura. Furthermore, the findings indicate that wollastonite fibers are poorly retained in human lungs.

Respiratory health of workers exposed to low levels of chromium in stainless steel production.

OBJECTIVES: To determine whether occupational exposure to chromite, trivalent chromium, or hexavalent chromium causes respiratory diseases, an excess of respiratory symptoms, a decrease in pulmonary function, or signs of pneumoconiosis among workers in an integrated chain of stainless steel production. METHODS: This cross sectional study was carried out in 1993 and the inclusion criterion was a minimum of eight years of employment in the same production department. A self administered questionnaire was collected, and spirometry, measurement of diffusing capacity, chest radiography, and laboratory tests were carried out by a mobile research unit. RESULTS: There were 221 workers in the exposure groups and 95 in the control group. The average duration of employment was 18 years. No significant differences in the odds ratios (ORs) of the symptoms were found between the exposure and the control groups. In a logistic regression analysis age and smoking significantly explained the occurrence of most of the respiratory symptoms. The smokers in the chromite group had significantly lower forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and diffusing capacity than the corresponding values of the control group. The analysis of variance between study groups, smoking, and exposure time, without modelling for interactions, showed that the chromite group had lower values for FVC, FEV1, and diffusing capacity than the other groups. The occurrence of small opacities was more frequent on the chest radiographs of the workers in the chromite group. CONCLUSIONS: An average exposure time of 18 years in ferrochromium and stainless steel production and exposure to dusts containing low concentrations of hexavalent or trivalent chromium do not lead to any respiratory changes detectable by lung function tests or radiography nor to any increase in symptoms of respiratory diseases. The lung function values were lower and the occurrence of radiological findings was more frequent among the workers from the chromite mine than among the controls. The difference was partly caused by differences in age and smoking habits, but evidently also partly by higher exposures more than two decades ago or by the fibrous components of the dust.

Screening for asbestos-induced diseases in Finland.

Screening for asbestos-induced diseases in Finland was carried out in 1990-1992 as a part of the Asbestos Program of the Finnish Institute of Occupational Health. The aim of the present study was to find the workers who had developed an asbestos-induced disease in certain occupations. Examination of active or retired workers included a personal interview on work history and asbestos exposure, and a chest X-ray. The target group for the screening comprised workers under 70 years of age who had worked at least for 10 years in construction, 1 year in a shipyard or in the manufacture of asbestos products. A preliminary questionnaire was sent to 54,409 workers, 18,943 of whom finally participated in the screening examination. The mean age of the workers was 53 years; 95% were employed in construction, 2% in shipyards, and 3% in the asbestos industry. The criteria for a positive screening result were (1) a radiographic finding clearly indicating lung fibrosis (at least ILO category 1/1), (2) a radiographic finding indicating mild lung fibrosis (ILO category 1/0) with unilateral or bilateral pleural plaques, (3) marked abnormalities of the visceral pleura (marked adhesions with or without pleural thickening), or (4) bilateral pleural plaques. The positive cases totalled 4,133 (22%) and were sent for further investigation. In addition to the screening, information on the presence of asbestos in the work environment, prevention of asbestos exposure, as well as on the health effects of asbestos exposure and smoking were given to the participating workers. The screening acted as a preliminary survey to prompt further national follow-up of asbestos-induced diseases among the workers who have been exposed to asbestos. This article presents the material, methods, and overall results of the screening.

Radiographic small lung opacities and pleural abnormalities in relation to smoking, urbanization status, and occupational asbestos exposure in Finland.

The role of smoking and an urban living environment in the etiology of radiographic pleural and pulmonary abnormalities was studied in a population sample that was representative of the Finnish adult population. A total of 7095 full-size chest radiographs were classified according to the International Labor Organization's 1980 classification of radiographs of pneumoconioses, with some modifications. The risk of bilateral pleural plaques was significantly higher among urban men (RR, 2.0) and women (RR, 3.8), even when adjusted for age and probability of occupational asbestos exposure and smoking. The risks of small lung opacities and abnormalities of the visceral pleura were not higher in urban areas. Risks of small lung opacities and thickening of the visceral pleura were positively associated with smoking, and the risk of small lung opacities was also higher among smokers than never-smokers in the population fraction with unlikely occupational asbestos exposure.

Radiographic small lung opacities and pleural abnormalities as a consequence of asbestos exposure in an adult population.

OBJECTIVES: The purpose of this study was to estimate the role of past asbestos exposure as a cause of radiographic small lung opacities and pleural abnormalities in the Finnish adult population. METHODS: The study was conducted in 1978-1981 and was based on a population sample (N = 8000) representative of the Finnish population aged 30 years or over. Full-size chest radiographs and a complete job title history were available for 3811 women and 3274 men. The radiographs were classified according to the 1980 classification of radiographs of pneumoconioses published by the International Labour Office and the work histories according to the probability of occupational asbestos exposure. Age- and smoking-adjusted relative risks of radiographic parenchymal and pleural abnormalities were calculated with the analysis of covariance according to the probability of asbestos exposure. RESULTS: About 13% of the men and 0.8% of the women were classified as probably exposed to asbestos. There was more than 90% agreement in the repeated work history evaluations. The risk of small lung opacities was significantly increased among the probably exposed men [risk ratio (RR) 1.7 for ILO profusion category 1/1 or more and RR 1.6 for profusion category 1/0]. The risk of pleural plaques was increased both among the men (RR 3.0) and the women (RR 4.8) with probable exposure. The risk of thickened horizontal interlobar fissure was also increased among the probably exposed men (RR 1.7). Among the men, the etiologic fraction attributable to occupational asbestos exposure was about 30% for small lung opacities, about 40% for pleural plaques, and about 20% for thickened horizontal fissure. Among the women the etiologic fractions for asbestos were similar for pleural abnormalities, but much lower for parenchymal ones. CONCLUSIONS: Occupational asbestos exposure has been common among Finnish men, and it plays a significant role in the etiology of both pleural and parenchymal abnormalities also at the level of the general population.

Prevalence of radiographic small lung opacities and pleural abnormalities in a representative adult population sample.

The prevalence of radiographic widespread small lung opacities and pleural abnormalities in the general population was assessed as part of the Mini-Finland Health Survey, which was based on a representative sample of people aged 30 years or over. Full-size chest radiographs of 7,095 persons (89% of the sample) were classified. Two radiologists classified all the radiographs according to the ILO 1980 Classification of Radiographs of Pneumoconioses. Small lung opacities and pleural abnormalities were considerably more prevalent in the older age groups and in men. Small lung opacities on the radiographs and pleural abnormalities were associated with work in industrial occupations, particularly in men. There was a clear association between small lung opacities and pleural abnormalities. The sex differences may be related to occupational factors, particularly dust exposure. The elevated risk of pleural plaques in persons with small lung opacities on the radiographs may indicate a fiber effect.

Nickel release from metals, and a case of allergic contact dermatitis from stainless steel.

The prevalence of allergic contact dermatitis (ACD) caused by nickel is increasing. The probable cause is the increased use of nickel-containing metals in intimate contact with the skin. The critical factor is the amount of nickel released from these metals (bioavailable nickel) onto the skin. In the present study, we determined, with flame atomic absorbtion spectrometry, the amount of nickel released into synthetic sweat from metal samples. The results of this method were compared with the results of the dimethylglyoxime (DMG) test, which is considered to be a reliable means of identifying whether nickel-containing metals may cause allergy symptoms in sensitive individuals. Out of 10 samples studied, only small amounts (< 0.5 microgram/cm2/week) were released from 2 samples, and the DMG test was negative. From 5 samples, more than 0.5 microgram/cm2/week was released, and the DMG test was positive. For 3 samples, however, the DMG test was negative, though the flame atomic absorption spectrometry test showed considerable release of nickel. Therefore, although the DMG test can be used as a first line test for determining nickel release, some DMG-negative metal materials probably induce nickel sensitization, and should by no means be advertised as safe in this respect. We also report a nickel-allergic patient who developed ACD from stainless steel, indicating that some types of stainless steel release enough nickel to elicit allergic symptoms.

Seven-year follow-up of white-finger symptoms and radiographic wrist findings in lumberjacks and referents.

OBJECTIVES: In 1978, a cross-sectional study of 279 lumberjacks exposed to hand-arm vibration and 178 unexposed referents was conducted. The aim of the present study was to provide a seven-year follow-up on (i) the changes in the white-finger symptoms among the lumberjacks and the referents, (ii) the effect of white-finger symptoms on the professional prognosis of the lumberjacks, and (iii) the relationship between hand-arm vibration and changes in wrist bones. METHODS: The methods consisted of a questionnaire, a routine clinical examination, and radiographs of the wrists and hands. The examinations were conducted as a field study using a mobile unit. RESULTS: The prevalence of white-finger symptoms was 18% among the lumberjacks and 3% among the referents in the original study. Seven years later 213 lumberjacks and 140 referents participated in the follow-up. The prevalence of white-finger symptoms was 24.9 among the lumberjacks and 5.7 among the referents, and the seven-year cumulative incidence was 14.7% among the lumberjacks and 2.3% among the referents. After allowance for age, there was no difference in the incidence of white-finger symptoms between the lumberjacks with fewer than 15 years of exposure and the referents, but the risk increased with increasing duration of exposure (risk ratio 8.9, 95% confidence interval 2.5-28.9 for those exposed at least 25 years). There was no difference between the two groups in the prevalence of radiographically detectable translucencies or osteoarthrotic changes in the wrists and hands. CONCLUSION: According to the results, white-finger symptoms are still a problem among lumberjacks who started chain-saw work before 1970.

Hyperostosis and osteoarthritis in patients surviving after tetanus.

Twenty patients (12 men and 8 women) who had survived tetanus were examined for bone and joint abnormalities, 1-9 years after the disease. The radiographic findings in the elbows were abnormal in 13 out of 20 patients, as were the shoulders of all 3 patients examined. Insertion hyperostoses were found at the elbow and/or in the shoulder region in 5 (25%) of the patients. The hyperostoses were bilateral in 3 patients. One of the patients with hyperostoses also had calcifications in the soft tissue of the elbow. The abnormalities were associated with mild clinical symptoms. Trauma to the periosteum caused by repeated traction of muscular contractions is possibly the causative mechanism. Twelve patients (60%) had osteoarthritis of the elbow joint presumably secondary to the violent stress to the joint.

High-resolution computed tomography in the early detection of asbestosis.

A group of 21 former asbestos sprayers was studied with high-resolution computed tomography (HRCT), and the findings were compared with radiographic, exposure and lung function variables. HRCT was superior to plain radiography in detecting parenchymal and pleural changes. It showed changes indicative of lung fibrosis, especially septal lines and parenchymal bands, in 9 of the 12 subjects (75%) with a plain radiographic category of 0/0 in the International Labour Office (ILO) 1980 classification of radiographs of pneumoconioses. The HRCT findings were classified according to a method developed by the authors, and an HRCT parenchymal score was calculated. The HRCT revealed pleural plaques in 19 of the 21 (90%) asbestos sprayers, whereas plain radiography detected pleural plaques in only 5 (24%) sprayers. Changes in the visceral pleura were detected twice as often with HRCT as with plain radiography. In the group without radiographic evidence of lung fibrosis (ILO < 1/0) and without evidence of emphysema in either the radiographs or the HRCT examination, there was a correlation between the HRCT parenchymal score and diffusion capacity (r = -0.64, P = 0.03) and total lung capacity (r = -0.61, P = 0.04). This finding indicates that parenchymal changes seen only with HRCT are of clinical importance. The study strongly suggests that for asbestos-exposed workers with an ILO classification of < 1/0 and functional impairment, an HRCT examination should always be considered.