Rabbit lung after inhalation of soluble nickel: I. Effects on alveolar macrophages

Alveolar macrophages from eight rabbits, exposed for about 1 month (5 days/week, 6 hr/day) to an aerosol of nickel chloride, 0.3 mg/m³ (as Ni), were studied. The number of macrophages in the lavage fluid and the variance of the cell diameter increased. The macrophages contained laminated structures and most cells had an active cell surface. A few macrophages had a large number of laminated structures and a smooth cell surface. The capacity of the macrophages to reduce nitroblue tetrazolium (NBT) tended to be increased at rest and was significantly increased after stimulation with Escherichia coli. The bactericidal capacity of the macrophages was decreased. The effects were similar to those earlier described after exposure of rabbits for 1 month to about 1 mg/m³ of metallic nickel dust. After exposure both to metallic and soluble nickel the effects are probably caused by an increased amount of surfactant produced by the type II cells in response to nickel ions.     

Morphology and function of alveolar macrophages after long-term nickel exposure

In a group of 24 rabbits, 12 were exposed to 1.0 mg/m³ (SD 0.7) of metallic nickel dust and 12 used as controls. Six rabbits were exposed for 3 months and six for 6 months (5 days/week, 6 hr/day). After exposure the lungs were extracted and lavaged. Macrophages were examined by light and electron microscopy and their oxidative metabolism studied by measuring the reduction of nitroblue tetrazolium. Most macrophages had a strikingly smooth surface and a cytoplasm containing closely packed, membrane-bound lamellar bodies. The proportion of this cell type was significantly larger after 6 months' than after 3 months' exposure. These macrophages differed not only from those of controls but also from macrophages in rabbits earlier exposed for 1 month to about the same concentration of metallic nickel dust. Macrophages from these rabbits had an active cell surface with numerous slender microvilli and long protrusions. The metabolism was significantly higher than in controls after both 3 and 6 months' exposure. In contrast to macrophages from the 1-month experiment and controls, these macrophages did not significantly increase their metabolism upon stimulation with bacteria.     

Rabbit lungs after long-term exposure to low nickel dust concentration: II. Effects on morphology and function

For 4 and 8 months (5 days/week, 6 hr/day) rabbits were exposed to 0.13 ± 0.05 (mean ± SD) mg/m³ of metallic nickel dust. Volume density of alveolar type II cells was estimated with electron microscopy. Lavaged alveolar macrophages were studied with light and electron microscopy and their abilities to reduce nitroblue tetrazolium (NBT) and to phagocytize particles were tested. The effects seemed to be similar after 4 and 8 months of exposure and when the exposed animals were combined, volume density of type II cells was increased and also significantly correlated with concentration of disaturated phosphatidylcholines in the lung. The macrophages had an active surface. Their NBT activity at rest was increased but a further increase during stimulation with E. coli was low, suggesting an impaired function. Phagocytic activity, however, was not significantly changed.     

Changes in pulmonary lipid composition of rabbits exposed to nickel dust

Eight male rabbits were exposed for 1 month (6 hr/day, 5 days/week) to metallic nickel dust at a concentration of 1.7 mg/m³, approximately 40% of which was respirable. Compared to eight control rabbits the nickel-exposed ones had increased lung weights and lung lipid concentrations as well as increased number, size, and size variation of lavaged macrophages. In the lungs of the nickel-exposed animals there was a twofold increase in the concentration of total phospholipids. The concentration of phosphatidylcholines was increased by a factor of 3 and that of phosphatidylinositols showed a small but significant increase. There was no change in the concentration of other phospholipid classes. Of the phosphatidylcholines the major increase was in the surface-active disaturated species. Changes were also seen in the molecular composition of the phosphatidylethanolamines. It seems likely that the highly complex changes in the phospholipids are caused by different mechanisms.     

Effects of nickel dust on rabbit alveolar epithelium

Eight male rabbits were exposed to metallic nickel dust, during 1 month (5 days/week, 6 hr/day) at a concentration of 1.7 mg/m³ (SD 0.5), about 40% of which was respirable. Morphometric measurements on the lungs of exposed rabbits showed about a twofold increase in volume density of type II alveolar epithelial cells compared to eight controls. This increment was about the same as the average increase in phospholipids in the lung parenchyma of the rabbits described elsewhere. The volume density of lamellar bodies within the cytoplasm of the type II cell was not significantly increased. Large amounts of laminated structures, resembling those in the alveolar type II cells, were also found free in the alveoli in the exposed rabbits.     

Effects of long-term nickel dust exposure on rabbit alveolar epithelium

Lungs from rabbits exposed to 1 mg/m³ metallic nickel dust for 3 and 6 months, 5 days/week, 6 hr/day, were examined by light and electron microscopy. Morphometric measurements showed threefold and twofold increases in volume density of alveolar type II cells after 3 and 6 months, respectively. The type II cells were extremely large, especially in the 3-month-exposed rabbits, and contained large amounts of lamellar bodies. Alveoli were rich in large, foamy macrophages and a granular material which previously has been found to consist mainly of phospholipid. This material probably represents an overproduction of surfactant by the type II cells. The 6-month-exposed rabbits had foci of pneumonia, suggesting a higher susceptibility to pulmonary infections, possibly due to a decreased function of alveolar macrophages.     

Rabbit alveolar macrophages after inhalation of soluble cadmium,cobalt, and copper: A comparison with the effects of soluble nickel

Rabbits were exposed to aerosols of chlorides of cadmium, copper, and cobalt (0.4–0.6 mg/m³ as metal) for 1 month (5 days/week and 6 hr/day). The effects on alveolar macrophages were compared with earlier reported effects of nickel chloride (0.3 mg/m³ as Ni). Effects of Cd²⁺ exposure resembled those of Ni²⁺ exposure. The number of macrophages in lavage fluid and the variance of cell diameters were thus increased and many cells contained lamellated inclusions. Contrary to macrophages from Ni²⁺-exposed rabbits, the surface of about 50% of the cells had cytoplasmic blebs. However, such cells were rarely seen by scanning electron microscopy. There were significantly more polymorphonucleated neutrophils and small lymphocytes, suggesting lung parenchymal damage. Cells from Cd²⁺-exposed animals, like cells from Ni²⁺-exposed ones, showed an increased oxidative metabolic activity after stimulation with Esherichia coli bacteria. Bactericidal capacity, on the other hand, tended to be enhanced rather than decreased, as in the nickel experiment. After Co²⁺ exposure, the number of macrophages was slightly increased in the lavage fluid and the cells showed an increased metabolic activity both at rest and upon stimulation with bacteria. Cu²⁺ exposure gave a slight increase in lamellated inclusions in the macrophages.     

Laboratory testing of biological activity of ore mine dust: fibrogenicity, cytotoxicity, and hemolytic activity

The biological activity of respirable dust (particle size below 5 μm) from three ore mines was compared with its quartz content (14 to 36%) and with the occurrence of lung silicosis in miners. Three months after intratracheal instillation of 50 mg of dust suspensions, silicotic changes of the first and second degree (King's classification) developed in the lungs of rats. The content of hydroxyproline in the lungs increased by 60 to 110% in comparison to control values. No correlation was found between the quartz content of the dust and the histological changes or hydroxyproline levels. Cytotoxicity of the dust for guinea pig peritoneal macrophages and hemolytic activity in vitro for human erythrocytes did not correlate with its fibrogenicity. No new cases of lung silicosis have developed in the last 20 years in miners exposed in these ore mines to total dust concentrations below 10 mg/m³, although the incidence of silicosis was frequent in the past, when the dust concentrations were much higher.     

The London Underground: dust and hazards to health

Aims: To assess hazards associated with exposure to dust in the London Underground railway and to provide an informed opinion on the risks to workers and the travelling public of exposure to tunnel dust.

Methods: Concentrations of dust, as mass (PM_2.5) and particle number, were measured at different underground stations and in train cabs; its size and composition were analysed; likely maximal exposures of staff and passengers were estimated; and in vitro toxicological testing of sample dusts in comparison with other dusts was performed.

Results: Concentrations on station platforms were 270–480 µg/m³ PM_2.5 and 14 000–29 000 particles/cm³. Cab concentrations over a shift averaged 130–200 µg/m³ and 17 000–23 000 particles/cm³. The dust comprised by mass approximately 67% iron oxide, 1–2% quartz, and traces of other metals, the residue being volatile matter. The finest particles are drawn underground from the surface while the coarser dust is generated by interaction of brakes, wheels, and rails. Taking account of durations of exposure, drivers and station staff would have maximum exposures of about 200 µg/m³ over eight hours; the occupational exposure standard for welding fume, as iron oxide, is 5 mg/m³ over an eight hour shift. Toxicology showed the dust to have cytotoxic and inflammatory potential at high doses, consistent with its composition largely of iron oxide.

Discussion: It is unjustifiable to compare PM_2.5 exposure underground with that on the surface, since the adverse effects of iron oxide and combustion generated particles differ. Concentrations of ultrafine particles are lower and of coarser (PM_2.5) particles higher underground than on the surface. The concentrations underground are well below allowable workplace concentrations for iron oxide and unlikely to represent a significant cumulative risk to the health of workers or commuters.

     

Comparative effects of inhaled silica or synthetic graphite dusts on rat alveolar cells

Alterations in population profiles, morphology, and phagocytic activity of lung cells followingin vivo exposure of Fischer 344 rats to a single dose of silica, were compared to similar changes following exposure to synthetic graphite. The effect of silica exposure on alveolar macro-phage mycocidal activity was also measured. Acute exposure by inhalation to 100 mg/m³ silica dust produced persistent pulmonary inflammation, as well as long-term changes in pulmonary alveolar macrophages (AM) typical of macrophage activation. Both particles were steadily cleared from the lungs; AM from the silica study, as well as from the 100 and 500 mg/m³ graphite studies, contained ingested particles throughout the entire 3 month experimental period. Lavaged pulmonary cells showed no reduction in viability as a result of exposure to either of the dusts. After silica inhalation, the following changes were observed constantly in bronchopulmonary lavage cell samples: increased numbers of polymorphonuclear leukocytes (PMN), hypersegmented PMN, binucleated AM, increased AM phagocytic indices and capacities, and increased mycocidal activity. Following inhalation of 1–100 mg/m³ synthetic graphite the above-mentioned effects were not seen. Exposure to 500 mg/m³ graphite produced transient inflammation and AM activation for about 24–48 hr.     

Nature, structure, and properties of asbestos cement dust

ABSTRACT Total dust samples produced by machining three commercial asbestos-cement products (autoclaved sheet, non-autoclaved sheet, pipe) were examined for their dimensional, surface, and physicochemical characteristics. Microscopic inspection of dust fractions with different settling characteristics in air allowed determination of the simple dimensional features that apply to respirable fibres—that is, the true diameter, length, and aspect ratio and the coil diameter, coil length, and coil aspect ratio. The respirable fraction as a percentage of the total dust varied with the type of machined product: 8·5% for non-autoclaved sheet, 10·5% for autoclaved sheet, and 35% for pipe.

Quantitative x-ray diffraction of different granulometric fractions showed that the asbestos content decreases with fraction size (thus the asbestos content will change with distance from the dust source). Electron microscopic examination of fine dust (aerodynamic diameter < 7 μm) showed that only about 10% of the inspected particles were optically virgin. From these observations it has been calculated that the threshold limit value of 2 fibres per cm³ of air corresponds to a total dust concentration of 1·2, 0·6, and 0·1 mg/m³ and to a maximum admissible respirable dust content of 0·1, 0·06, and 0·04 mg/m³ for non-autoclaved sheet, autoclaved sheet, and pipe respectively. The surface of optically virgin fibres may still be contaminated by calcium containing particles, as shown by analytical transmission and scanning electron microscope. Dust from the autoclaved product contains fewer calcium coated fibres. The physicochemical behaviour of dust, as shown by dissolution kinetics and absorption of carcinogens from tobacco smoke, is comparable to the behaviour of cement rather than of pure asbestos. In general, asbestos cement dust differs consistently from pure asbestos. Conclusions, drawn from studies on pure asbestos, cannot be applied as such to asbestos cement dust.

     

Lysozyme levels in rabbit lung after inhalation of nickel,cadmium, cobalt,and copper chlorides

Groups of rabbits were exposed to chlorides of nickel, cadmium, copper, and cobalt at concentrations ranging from 0.2 to 0.6 mg/m³ (as metal) for 4–6 weeks (5 days/week, 6 hr/day). Activity of lysozyme (muramidase) in lavage fluid, in alveolar macrophages, and in culture medium from macrophages incubated at 37°C for 1 and 20 hr was estimated using the lyso-plate technique, agar plates with heat-killed Micrococcus lysodeikticus. In the nickel-exposed rabbits lysozyme activity in the mucous membrane from the left main bronchus was also estimated. Following nickel exposure the lysozyme level was significantly decreased in lavage fluid, macrophages, and in culture medium from incubated macrophages but remained unchanged in the mucous membrane. After exposure to cadmium, copper, and cobalt, lysozyme levels increased or were unchanged.     

Rabbit alveolar macrophages after long-term inhalation of soluble cobalt

Rabbits were exposed to 2 or 0.4 mg/m3 of cobalt as CoCl2 for 14-16 weeks (5 days/week and 6 hr/day). More macrophages were lavaged from the lungs of rabbits exposed to the higher Co2+ concentration, and the diameter and variation of the diameter of the macrophages were significantly larger than in controls. The activity of lysozyme in the lavage fluid and in the macrophages was increased in the two exposed groups. Some macrophages in the exposed animals were large and engorged with intracellular lamellar inclusions and lipid droplets. Most of these cells had a smooth surface. The oxidative metabolic activity measured by reduction of nitroblue tetrazolium was increased in the exposed groups. The number of yeast cell particles attached to the surface of the macrophages was increased in the group exposed to the high concentration, but the number of ingested particles was not affected by cobalt exposure. Apart from the fact cobalt increased lysozyme activity whereas nickel decreased it, cobalt produced the same type of effects on macrophages as nickel did in earlier studies. Cobalt affected only a minor proportion whereas nickel affected most macrophages. This can be explained by the fact nickel produced a general increase in the volume density of the type II cells while cobalt affected the type II cells only in some areas of the lungs.     

Rabbit lung after inhalation of soluble nickel: II. Effects on lung tissue and phospholipids

Rabbits were exposed to soluble nickel chloride, about 0.3 mg/m³ as nickel, for about 1 month (5 days/week, 6 hr/day). The upper lobe in the left lung was examined with light microscopy and samples from the left lower lobe with electron microscopy. Nodular accumulation of macrophages and laminated structures occurred in alveoli of all exposed rabbits, but otherwise no inflammatory reactions. Volume density of the alveolar epithelial type II cells was doubled due to increased cell number as well as cell volume. The tissue content of phospholipids, determined in the lower lobe of the left lung, had increased by about 40%, mainly due to elevated disaturated phosphatidylcholines. The effect pattern was almost identical to that seen earlier in inhalation experiments with metallic nickel dust, strongly indicating that nickel ions are responsible also for the changes seen after exposure to metallic nickel. This suggests that all nickel compounds may produce the pathological condition, which is similar to that seen in the disease pulmonary alveolar proteinosis.     

A survey of respiratory disease in cotton operatives: Part II. Symptoms, dust estimations, and the effect of smoking habit

Fox, A. J., Tombleson, J. B. L., Watt, A., and Wilkie, A. G. (1973).Brit. J. industr. Med.,30, 48-53. A survey of respiratory disease in cotton operatives. Part II. Symptoms, dust estimations, and the effect of smoking habits. In association with a survey of cotton workers dust levels were measured in 11 of the mills. Levels varied from 1·15 mg/m³ to 4·8 mg/m³ excluding fly. Analysis of the survey of workers in relation to the dust levels showed an increase in abnormal symptoms and a greater reduction in ventilatory function in those exposed to the higher dust concentrations. No such relationship was found between dust concentration and prevalence of bronchitic symptoms. Smokers showed a higher frequency of byssinotic symptoms and a greater loss of ventilatory function than non-smokers at all levels of dust exposure. The correlation between dust levels and the frequency of byssinotic symptoms and the loss of ventilatory function was increased by including a time factor. By expressing the dust exposure as mg years/m³ it can be predicted that approximately 10% of subjects exposed to 0·5 mg/m³ of dust for 40 years will have the symptoms of byssinosis.     

Exposure assessment to dust and free silica for workers of Sangan iron ore mine in Khaf, Iran

We aimed to conduct an exposure assessment to dust and free silica for workers of Sangan iron ore mine in Khaf, Iran. The maximum concentrations of total dust and free silica were measured in crusher machine station at 801 ± 155 and 26 ± 7 mg/m³, respectively. Meanwhile, the minimum concentrations were measured in official and safeguarding station at 8.3 ± 2 and 0.012 ± 0.002 mg/m³, respectively. Also, the maximum concentrations of respirable dust and free silica were measured in Tappeh Ghermez drilling no. 1 at 66 ± 13 and 1.5 ± 0.4 mg/m³, respectively, while the minimum concentrations were measured in pneumatic hammer at 5.26 ± 3 and 0.01 ± 0.005 mg/m³, respectively. Considerate to Iranian standard for respirable dust concentrations (0.11 mg/m³) and international standards (ACGIH = 0.1 and NIOSH = 0.05 mg/m³), it was found that dust and free silica amounts were much higher than national and international standard levels in this mine.     

Bakers' exposure to flour dust

We aimed to characterize bakers' personal exposure to airborne flour dust with respect to the health-related aerosol fractions inhalable, extrathoracic, and thoracic dust, and to examine possible production-related determinants of dust exposure.

Sixty-eight bakers from 7 bakeries in Bergen, Norway (2009–2012) participated in the exposure assessment, comprising full-shift personal samples of inhalable dust (n = 107) and thoracic dust (n = 61). The relation between possible determinants and exposure was estimated using mixed effects models, while associations between the various aerosol fractions across task groups and type of bakeries were described by Pearson's correlation coefficients.

Bakers' overall geometric mean personal exposure to inhalable, extrathoracic, and thoracic dust were 2.6 mg/m³ (95% CI: 2.0, 3.2), 2.2 mg/m³ (95% CI: 1.9, 2.7), and 0.33 mg/m³ (95% CI 0.3, 0.4), respectively. A total of 29% of the measurements of inhalable dust were above the Norwegian Occupational Exposure Limit of 3 mg/m³. The exposure variability of inhalable dust could not be explained by any of the examined production-related determinants, while the daily production volume explained 18% of the variance in thoracic dust exposure. Overall, the thoracic dust represented 15% of the inhalable dust, being rather stable across the production-related determinants. The overall correlation between inhalable and thoracic dust was nevertheless moderate (r = 0.52, p < 0.001), with the highest correlation for craft bakers (r = 0.62) and no correlation during dough forming (r = 0.01).

Bakers are exposed to flour dust at a level that most likely represents an excess risk of developing chronic diseases of the respiratory system, and a decrease of present exposure level is imperative. Extrathoracic dust—likely the most relevant sub-fraction in respect to flour-induced sensitization and occupational rhinitis—represented the main proportion of the measured inhalable dust. The variation in correlation coefficients between the dust fractions across bakery types and task groups underlines the need of more knowledge about how these aerosol fractions are distributed across the production process and bakery types.     

Exposure to dust,endotoxin and micro-organisms in the potato processing industry

Exposure to organic dust components was studied in four potato processing plants because preliminary results showed high exposures accompanied by work-related health complaints. Ambient air concentrations of inhalable dust ranged from below 0.4 up to 44 mg m⁻³ [geometric mean (GM) 0.64 mg m⁻³]. Respirable dust concentrations were considerably lower. Personal concentrations of inhalable dust were somewhat higher, and strongly related to a few working tasks dealing with dried starch or protein. Ambient air concentrations of endotoxin ranged from 0.5 to more than 60 000 endotoxin units (EU) per m³ for the inhalable size fraction (GM = 280 EU m⁻³). For the respirable size fraction, endotoxin concentrations were lower (about the same factor as for dust). Personal endotoxin concentrations were lower than ambient air concentrations, probably because workers did not work the whole period of the shift near endotoxin sources. Endotoxin exposure was evaluated as very high; 23% of the workers had a mean exposure above 1000 EU m⁻³ (100 ng m⁻³). Differences between plants had a large influence on both dust and endotoxin exposure. A fairly good correlation was found between counts of airborne gram-negative bacteria and airborne endotoxin of the respirable size fraction. Ambient air levels of bacteria and endotoxin were strongly related to process water temperature, suggesting that exposure reduction can be achieved by lowering this temperature or by other measures that inhibit bacterial growth. We conclude that recycling of process water probably constitutes an exposure source of bacteria and endotoxin in many facilities.     

Effects of fly ash inhalation on murine immune function: Changes in macrophage-mediated activities

Mice were exposed to fly ash particles (<2.1 μm diameter) by inhalation for variable amounts of time at concentrations ranging from 535 to 2221 μg/m³. This fine fraction was approximately 32% by weight of the total dust generated. The effects of these exposures were assessed on macrophage-mediated functions. Phagocytosis of bacterial cells by the alveolar macrophages was depressed in the fly ash-exposed animals as was the ability to enhance T-cell mitogenesis. Fly ash exposure failed to produce a significant change in the cellular immune response (delayed-type hypersensitivity reaction) to antigenic challenge in the lungs of sensitized animals.     

Quantification of historical dust exposures in the diatomaceous earth industry

Quantitative estimates of dust exposure in a diatomaceous earth (DE) mining and milling operation have been derived based on air sampling records for the period 1948–1988. A total of 6395 records was included in the analysis. Conversion of results obtained by particle counting, expressed as millions of particles per cubic feet (mppcf) or gravimetrically from a filter cassette and expressed as mg m⁻³ total, were converted to mg m⁻³ respirable dust using a conversion factor derived from data obtained during the same periods at the plant. Conversion factors were calculated as the average difference of means on the log scale in order to provide stable and consistent conversions and as a ratio of arithmetic means so that the results could be compared with similar studies. After converting the available data to mg m⁻³ respirable dust, geometric mean (geometric standard deviation) concentrations were 0.37 (2.43) during the 1950s and 0.17 (2.35) during later periods. Exposures were estimated using two linear models, one estimating the changes in concentration over time, and the other providing job-specific mean exposures during the more recent period. Extrapolation of the estimates to periods prior to the availability of any data was done using a subjectively-determined scaling factor. The average estimated respirable dust concentrations for 135 jobs were 3.55 (±1.25), 1.37 (±0.48), 0.47 (±0.16) and 0.29 (±0.10) mg m⁻³ prior to 1949, 1949–1953, 1954–1973 and 1974–1988, respectively. Despite the limitations of the available data, the estimation procedures used are expected to provide reasonable quantitative estimates of silica-containing dust exposure for subsequent exposure-response analyses.