Lloyd E. Stettler

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.

Enhanced Pulmonary Response to the Inhalation of Freshly Fractured Silica as Compared with Aged Dust Exposure

Abstract We have reported previously that grinding crystalline silica generates radicals on its cleavage planes and that this fresh dust is more cytotoxic in vitro than aged silica. The objective of the present study was to determine if freshly fractured silica was also more toxic and inflammatory in vivo than aged silica of the same composition and particle size. Fresh α-quartz was generated using a jet mill, while aged dust was milled and then stored for 2 months before use. Analysis of surface radicals by electron spin resonance spectroscopy verified the enhanced surface activity of this fresh silica compared with aged dust. Male Fischer 344 rats were exposed to fresh or aged α-quartz by inhalation (20 mg/m3, 5 hours per day, 5 days per week for 2 weeks) and pulmonary responses were determined 1 to 3 days after exposure. Exposure to aged silica resulted in an increase in total cells, red blood cells, lymphocytes, and granulocytes harvested by bronchoalveolar lavage, and in elevated acellular lavage pro...

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

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.

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.

Chronic Inhalation of Short Asbestos: Lung Fiber Burdens and Histopathology for Monkeys Maintained for 11.5 Years after Exposure

In an earlier report, presented the results of an 18-month inhalation exposure of rats and monkeys to short chrysotile asbestos. The mean chamber exposure level was 1.0 mg/m3with an average of 0.79 fibers/ml > 5 μ m in length. Gross and histopathological examination of exposed and control rats indicated no treatment-related lesions. Asbestos bodies adjacent to the terminal bronchioles, but no fibrosis, were found in lung biopsy tissue taken from the exposed monkeys at 10 months post-exposure. Fifteen monkeys (9 exposed and 6 controls) from this study were maintained for 11.5 years following exposure. Lung fiber burdens were determined by transmission electron microscopy. The mean lung burden (± standard deviation) for 59 samples from exposed monkeys was 63 ± 30× 106 fibers/g dry lung (range, 18–139 × 106). The geometric mean fiber length was 3.5 μ m with 35% of the fibers being > 5 μ m in length. These data indicate some chrysotile fibers are durable in vivo for a significant period of time. Lungs were examined grossly and microscopically. No lesions attributable to the inhalation exposure were noted. Asbestos bodies were seen in the lungs of treated monkeys, primarily in the interstitium near bronchioles or small pulmonary blood vessels (which also may have been near to bronchioles just out of the plane of section).

Chronic Effects of Inhaled Amorphous Silicas in Animals

Rats, guinea pigs, and monkeys were exposed by inhalation (5.5 to 6 h/day, 5 days/week) for up to 18 months at 15 mg/m 3 concentrations of three types of synthetic amorphous silicas: fume, gel, and precipitated. Autopsieson rats were performed after 3, 6, and 12 months of exposure, and on guinea pigs and monkeys after 10 to 18 months of exposure. The most significant finding was the deposition of large quantities of amorphous silica in macrophages in the lungs and tracheal lymph nodes of exposed monkeys. Relatively few or no macrophages containing particles of amorphous silica were found in the lungs and lymph nodes of the guinea pigs and rats. It is also significant that fume silica induced early nodular fibrosis in the lungs of the monkeys. Correlating these histological findings, lung-function studies indicated statistically significant differences in lung volume and ventilatory mechanics measurements between those monkeys exposed to fume silica and the control group. In addition, monkeys exposed to precipitated silica demonstrated significantly lower lung volumes compared with controls, while monkeys exposed to silica gel had significant changes in ventilatory performance and mechanical properties.

Chemical composition of coal and other mineral slags

The trace element contents of eighteen coal, copper, and nickel slags were determined by proton induced x-ray emission (PIXE) and atomic absorption spectrophotometry. Varying amounts of the suspect carcinogens, beryllium, chromium, nickel, and arsenic were found in the slags. As a class, the coal slags contain the lowest quantities of these elements while the slags from secondary copper smelters contain the greatest quantities.

The Surface Energetics of Asbestos Minerals

Nitrogen and argon isotherms were determined on amosite and on chrysotile asbestos at −183° and −195°C, and in three states of subdivision. BET surface area determinations showed that milling increased the amosite surface area from 1.3 to 11.0 m2/g, and the chrysotile from 15.3 to 48.4 m2/g. Changes in hysteresis of the adsorption isotherms indicated that the increased surface area after milling was mostly external for amosite and the increase for chrysotile was primarily caused by the greater availability of micropores. Measurements of pore size showed averages of 58.5 A for amosite and 80.5 A for chrysotile. Heat of adsorption determinations, calculated from the Clausius-Clapeyron equation, showed only minor differences between the two minerals.

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.

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.