Fibrogenic potentials of coal slags used as abrasive blasting substitutes.

This study was designed to examine the fibrogenic potentials of four coal slags that are being used as substitutes for silica sand in abrasive blasting. Six groups of 100 male Sprague-Dawley rats, including four coal slag groups, a vehicle control, and a positive control for fibrosis (Minusil quartz), were used. Each dust treatment group was given a single 40-mg dose of test agent via intratracheal instillation. Interim sacrifices of 15 animals per group were performed at 2 d, 3 mo, and 6 mo posttreatment, with the terminal sacrifice conducted at 12 mo. Hematoxylin and eosin stained histologic sections were prepared from designated formalin-fixed tissues collected at each necropsy and examined microscopically. Pulmonary silicon analyses were performed for each group at the 2-d and 12-mo sacrifices. Pulmonary function analyses were conducted for each group at the 3-, 6-, and 12-mo sacrifices. Lung hydroxyproline analyses were conducted for 15 animals in each group at the terminal sacrifice. The pulmonary fibrogenic potentials of the four coal slag groups were compared histologically with the Minusil and vehicle controls. A mild to moderate interstitial fibrosis, which was progressive with time, was noted in each of the coal slag groups. However, the coal slag-induced lung fibrosis was much less than that produced by Minusil. Differences in fibrosis among the individual coal slags were relatively minor and certainly not as striking as those between the slags and Minusil. Other data derived from this study, such as lung hydroxyproline content, pulmonary particulate burdens, pulmonary function, and animal body weights, provided further evidence of a reduced toxicity for the coal slags compared to Minusil.

Biological monitoring for occupational exposures to o-toluidine and aniline.

Epidemiological evidence that occupational exposure to o-toluidine and aniline is associated with an increased risk of bladder cancer led to efforts to identify biomarkers of workplace exposures to these aromatic amines. For the determination of o-toluidine and aniline in worker urine specimens, a method using high performance liquid chromatography (HPLC) followed by electrochemical detection was developed. The limits of detection were 0.6 microgram/l and 1.4 micrograms/l for o-toluidine and aniline, respectively. Recovery of o-toluidine and aniline from spiked urine averaged 86% and 93%, respectively, over a range of 4-100 micrograms/l. Reproducibility in the range 2-100 micrograms/l for analyses of split field samples was 13% (average RSD) for o-toluidine and 16% (average RSD) for aniline. Application of this method to pre- and post-shift samples collected from potentially exposed and unexposed workers indicated elevated concentrations of o-toluidine and aniline in urine from exposed workers. To develop methods for biomarkers of internal dose, o-toluidine binding to the blood proteins hemoglobin and albumin was investigated utilizing in-vivo (rodent) and in-vitro (hemoglobin and albumin) studies. Base-hydrolyzable protein adducts were analyzed by HPLC (fluorescence) and/or GC/electron capture (EC). The methods were compared for sample preparation requirements, selectivity and sensitivity. While the GC/EC method was more sensitive than HPLC, the presence of interfering peaks limited the utility of this approach. Results from these studies suggested that the HPLC method could be useful for determination of o-toluidine exposures in individuals acutely or chronically exposed to high levels.

Lung particulate burdens of subjects from the Cincinnati, Ohio urban area.

Because of the relatively small data base existing for lung particulate burdens of subjects with no overt pneumoconioses, the total exogenous lung particulate concentrations of 91 subjects from the Cincinnati, Ohio urban area were determined using an automated scanning electron microscope-energy dispersive x-ray analysis-image analysis system. Four of these subjects were foundry workers and had the highest exogenous particle concentrations seen in the 91 lungs, ranging from 1860 to 2990 x 10(6) particles per gram of dry lung (ppg). The average exogenous particle concentration for the remaining 87 subjects was 476 +/- 380 x 10(6) ppg with a range of 71 to 1860 x 10(6) ppg. The median size of the exogenous particles in the 87 lungs was narrow, ranging from 0.37 to 1.02 microns. The geometric mean particle size over all 87 lungs was 0.60 microns with a geometric standard deviation (sigma g) of 2.35. The total exogenous particle levels were elevated for the male subjects compared to females (p=0.015), and were positively associated with age (p=0.021). However, no correlation was seen between total particle concentration and race or smoking history.

Quantitative analysis of particulate burden in lung tissue.

Numerous methods have been used in the preparation and analysis of the particulate matter deposited in human lungs. Preparation techniques include those for particle isolation and for in situ analysis. Analytical techniques include bulk and particle-by-particle analysis. In this paper, a general discussion of many of these methods is presented along with examples of how two specific techniques have been used. In one study, individual particles from the lungs of 75 randomly selected autopsy cases were analyzed using an automated scanning electron microscopy (SEM)/energy dispersive X-ray microanalysis (EDX) system. An average of 613 million particles, of exogenous origin, per gram of dry lung tissue were found, the major classes of particles being silica, talc, aluminum silicates, and rutile. In the second study, lungs from 50 randomly selected autopsy cases were analyzed using gravimetric and X-ray diffraction (XRD) analysis. The median total particulate material was 0.33 grams, for cases in which samples were prepared by high temperature ashing, and 0.41 grams, for those in which nitric acid digestion was used. The median amount of quartz for all cases, was 0.044 grams. Samples of eighteen of the 75 lungs previously analyzed by automated SEM/EDX were also analyzed using gravimetric and XRD analysis. A good correlation was seen between the results of the two procedures (r = 0.91 for number of exogenous particles versus grams of particulate matter and r = 0.97 for number of silica particles versus amount of quartz).

Fibrogenicity and carcinogenic potential of smelter slags used as abrasive blasting substitutes.

This study was designed to examine the fibrogenic and carcinogenic potentials of three smelter slags (primary copper slag, secondary copper slag, and nickel slag) that have been used for a number of years as substitutes for sand in abrasive blasting operations. Seven groups of 85 male Fischer 344 rats (approximately 180 g) were used. Each group was given a single 20-mg dose of one of the following test materials via intratracheal instillation: primary copper slag, secondary copper slag, nickel slag, feldspar, Min-U-Sil, novaculite, or vehicle control. Chemical, particle size, and surface area analyses were performed for each test dust. Animals were weighed monthly, and ten animals per group were necropsied at the 6-, 12-, and 18-mo interim sacrifices. The terminal sacrifice was conducted at 22 mo. Hematoxylin and eosin stained histologic sections were prepared from designated formalin-fixed tissues collected at necropsy and examined microscopically. The pulmonary fibrogenic and carcinogenic potentials of the three smelter slags were compared histopathologically with feldspar, novaculite, Min-U-Sil, and vehicle controls. Only minimal to slight alveolar wall fibrosis was seen in the two copper slag groups, while the response seen with nickel slag was consistent with a foreign body reaction with minimal fibrosis seen in only an occasional animal. The major reaction seen in both the feldspar- and the novaculite-treated rats was a granulomatous inflammation with varying degrees of fibrosis associated with the granulomas. Significant numbers of primary lung tumors, principally adenocarcinomas and adenomas, were seen in the copper slag (p = 0.005 and p = 0.022 for the primary and secondary slags, respectively), in the feldspar (p = 0.007), in the novaculite (p less than 0.001), and in the Min-U-Sil (p less than 0.001) groups when compared to the vehicle control group. In addition, the Min-U-Sil and novaculite groups had significantly elevated pulmonary tumor proportions relative to the other treatments (p less than or equal to 0.002), with the Min-U-Sil being higher than the novaculite (p = 0.012). On the basis of the tumor incidence data, one must conclude that both copper slags tested in this study are carcinogenic to rats.

Carcinogenic effects of antimony trioxide and antimony ore concentrate in rats.

This study was initiated because of a suspected increase in incidence of lung cancer in antimony smelter workers in England. Three groups of 8-mo-old Wistar-derived rats (90 males and 90 females per group) were exposed by inhalation to either Sb2O3 [time-weighted average (TWA) 45 mg/m3], Sb ore concentrate (TWA 36 + 40 mg/m3), or filtered air (controls) for 7 h/d, 5 d/wk, for up to 52 wk and sacrificed 20 wk after terminating exposures. Serial sacrifices (5 rats/sex/group) were performed at 6, 9, and 12 mo. Autopsies and histopathological examinations were performed on all animals. The dusts and animal tissues were analyzed for Sb, arsenic, and other inorganic elements by atomic absorption and proton-induced X-ray emission methods. The most significant findings were the presence of lung neoplasms in 27% of females exposed to Sb2O3 and 25% of females exposed to Sb ore concentrate (p less than 0.01). None of the male rats in any group or the female controls developed lung neoplasms. There were no significant differences in incidences of cancer of other organs between exposed and control rats. These results were compared with other published results, including an animal inhalation study with Sb2O3 in which lung tumors were also induced. Higher concentrations of arsenic were found in tissues from female rats than from male rats. For example, arsenic levels in blood of control males, control females, Sb2O3 males, Sb2O3 females, Sb ore males, and Sb ore females were 60, 123, 115, 230, 71, and 165 micrograms arsenic/g dry blood, respectively, 9 mo after initiating exposures.

Chronic inhalation of short asbestos fibers.

An animal inhalation study was initiated to study the chronic biological effects of inhalation of short chrysotile asbestos fibers. Rats and monkeys were exposed for 18 months, 7 hr/day, 5 days/week to a specially prepared, chrysotile asbestos aerosol. Based upon daily chamber measurements, the mean concentration of fibers in the chamber air was 1.0 mg/m3. By phase contrast microscopy, the number of fibers greater than 5 micron in length was determined to be 0.79 fiber per cubic centimeter. Rats were autopsied for pathological and histochemical examination at 1, 3, 6, 12, 18, and 24 months after initiating exposures. No significant differences in the histochemical data were seen between the exposed and control groups. Gross and histopathologic examination of exposed and control groups of rats indicated no compound-related lesions, including fibrosis. Open lung biopsies were performed on the chrysotile-exposed and the control monkeys 28 months after initiating exposures. Histopathologic evaluation of the lung biopsy tissue showed the presence of asbestos bodies adjacent to the terminal bronchioles of the asbestos-exposed monkeys. There was no observed fibrosis in pulmonary tissue. All monkeys are being maintained for an indefinite period and observed for signs of latent pulmonary disease.

Mount St. Helens' volcanic ash: hemolytic activity.

Volcanic ash samples from four Mount St. Helens' volcanic eruptions were subjected to mineralogical, analytical, and hemolytic studies in order to evaluate their potential for cytotoxicity and fibrogenicity. Plagioclase minerals constituted the major component of the ash with free crystalline silica concentrations ranging from 1.5 to 7.2%. The in vitro hemolytic activity of the volcanic ash was compared to similar concentrations of cytotoxic and inert minerals. The ash was markedly hemolytic, exhibiting an activity similar to chrysotile asbestos, a known fibrogenic agent. The hemolysis of the different ash samples varied with particle size but not with crystalline silica concentration. The results of these studies taken in conjunction with the results of our animal studies indicate a fibrogenic potential of volcanic ash in heavily exposed humans.

Automated characterization of particles extracted from human lungs: three cases of tungsten carbide exposure.

An automated scanning electron microscope-energy dispersive x-ray analysis-image analysis system was used to characterize particles extracted from three human lung samples which had suspected occupationally-induced lung disease. The particles were isolated from the lung tissues by low temperature ashing and deposited on Nuclepore filters. Particles in randomly selected fields of view for each filter were automatically sized, analyzed for 32 elements, and classified according to their chemistry by the system. For each of the three lung specimens, large numbers of particles were found which indicated exposure to cemented tungsten carbide products. The particle analysis data was collected at a rate of 200 particles per hour which is considerably faster than the rate at which manual, in situ analyses can be performed.

Pneumoconiosis in animals exposed to poly(vinyl chloride) dust.

Rats, guinea pigs and monkeys were exposed by inhalation (6 hr/day, 5 days/week) for up to 22 months to a 13 mg/m3 concentration of PVC dust. Autopsies on rats and guinea pigs were performed after 12 months of exposure and on monkeys after 22 months after 22 months of exposure. Lung function tests were performed on monkeys after 9, 14 and 22 months of exposure. Aggregates of alveolar macrophages containing PVC particles were found in the lungs of all animals. These aggregates were more numerous in the monkey lungs. No fibrosis or significant cellular infiltrates were present in or near these cellular aggregates. No significant effects on pulmonary function could be demonstrated in the monkeys exposed to PVC. Under the conditions of this experiment, inhaled PVC produced a benign pneumoconiosis.

Fibrogenic potential of slags used as substitutes for sand in abrasive blasting operations.

The fibrogenic potentials of coal and copper slags used as substitutes for silica sand in abrasive blasting operations were assessed in rats. The test animals were given a single pulmonary intralobar instillation of 20 mg of test material and were sacrificed 10 months after dosing. Pulmonary fibrosis was seen in the coal slag-treated rats while no fibrosis was seen in the copper slag-treated animals. Granulomas were seen in the lungs from all treatment groups. The results of the study emphasize the need for bioassay of silica sand replacements for fibrogenic potential in spite of the low free silica contents of these materials.

Identification of stainless steel welding fume particulates in human lung and environmental samples using electron probe microanalysis.

Open lung biopsy specimens from two welders and air samples from their workplace environments were examined with the electron probe microanalyzer. X-ray analysis showed that the majority of particles found in the lung tissue from both workers and in the air samples to be composed of varying amounts of iron, chromium, manganese and nickel, the major components of some types of stainless steel. Based upon these analyses, it was concluded that the majority of the particles in both biopsy specimens were a result of the workplace environment.

The porosity of amosite and chrysotile asbestos.

A computer program has been set up in Fortran language to calculate pore size distribution using the Cranston-Inkley method of calculation. Nitrogen adsorption isotherms were determined on amosite and chrysotile asbestos at - 195 degrees C. Size reduction had a major effect on increasing pore volumes of both asbestos materials.

The adsorption of water and benzene on amosite and chrysotile asbestos.

In previous work the authors showed that chrysoltile is more porous than amostie and consequentd benzene with a high molecular cross-section are used as adsorbates. Benzene adsorption is extremely slow on both adsorbents with each point taking from 4 to 24 hours for equilibration. Evidently, the larger benzene molecule has a more difficult ime working its way thrugh the small pores. The water adsorption is predominait. In both cases hysteresis was found. Benzene adsorption on amosite resembled Type IV which relfects capillary condensation phenomena. With chrysotile some chemisorption may have occurred. BET surface areas and heats of adsorption are calculated.