A Comparison of Methods of Determining and Predicting the Pathogenicity of Mineral Fibers

Abstract

Most authors consider that long-term inhalation studies represent the most reliable method of obtaining data on the pathogenicity of mineral fibers. However, because of the length of time required and the great cost of inhalation work, other methods of examining the biological effects of mineral fibers have been used. The program of work described here was designed to compare a wide range of techniques, including inhalation, for determining the biological effects of a selection of man-made mineral fibers. Silicon carbide whiskers were examined as a very durable material and also a less durable glass microfiber (code 100/475/ as a relatively soluble man-made vitreous fiber. Amosite asbestos was used as a positive control. long-term inhalation studies with full-life-span follow-up demonstrated that amosite and silicon carbide were both fibrogenic and carcinogenic in rats, while glass microfiber produced very little fibrosis and a few benign pulmonary tumors in numbers similar to those found in controls. Silicon carbide was unusual in that most of the tumors produced were pleural mesotheliomas. Early effects of the fibers were examined after a short period of inhalation, and the pathogenic dusts amosite and silicon carbide were found to produce rapid pulmonary inflammation as determined by the presence of significant numbers of neutrophils in pulmonary lavage fluid. Less pulmonary inflammation followed the inhalation of glass microfiber. Similarly, amosite and silicon carbide inhalation was found to cause a rapid increase in the rate of proliferation of bronchoalveolar lining cells, while the rate of cell division in animals treated with microfiber remained normal. When injected into the peritoneal cavities of rats, all three fiber types produced mesothe liomas, although the glass microfiber produced many fewer and these took much longer to develop. An examination of early inflammation in the peritoneal cavity of mice following injection showed little difference between the fiber types, all of which caused raised numbers of neutrophils in peritoneal fluid. fiber durability was examined both in vivo and in vitro. Following inhalation it was found that fewer very long glass microfibers (>20 pm in length) remained in rats lungs after 12 mo of inhalation than amosite or silicon carbide.Subsequently, however, amosite and microfiber were removed from the lung at similar rates for most fiber dimensions, in contrast to silicon carbide fibers, where clearance was much less. When dust was administered by intratracheal injection, these differences in fiber removal from lung tissue were much less marked. An examination of the in vitro solubility of fibers and their chemical composition after extraction from lung tissue demonstrated that glass microfiber showed significant leaching while amosite showed much less and silicon carbide showed almost no change in chemical composition. The possibility of using short-term in vivo and in vitro tests to provide a screening system to eliminate the need for some of the longer and more expe...

Short-term inhalation and in vitro tests as predictors of fiber pathogenicity.

“…In our study the proliferative response to code 100/475 was no greater than that in unexposed control animals, whereas amosite and SiC both produced significant increases in proliferation. In a concurrent study (14), we showed that deposition, in terms of the numbers of fibers greater than 10 pm recovered from lungs at the end of a 12-month inhalation at 1000 fibers/ml, was roughly equivalent for the three fiber types. However, the code 100/475 microfiber differed from long amosite and SiC in the very high numbers of fibers that were less than 5 pm in length.…”

“…Evidence is emerging from both in vitro (21,22) and in vivo (14,23) studies that SiC whiskers can be as toxic as asbestos fibers. In this study we examined a number (20).…”

“…The processes of inflammation and epithelial cell injury with consequential cell proliferation may be important in the development of disease associated with the inhalation of fibers (1,2,6,9,14,20). Evidence is emerging from both in vitro (21,22) and in vivo (14,23) studies that SiC whiskers can be as toxic as asbestos fibers.…”

“…The results of this study are discussed in terms of the pathogenicities of the fibers, known from published long-term animal studies (3,(11)(12)(13)(14).…”

Magnetometric Evaluation of the Effects of Man-Made Mineral Fibers on the Function of Macrophages Using the Macrophage Cell Line RAW 264.7

“…Increases in LDH in the supernatants of RAW 264.7 cells exposed to high concentrations of PT or SiC were confirmed in this study at relatively lower levels. In inhalation studies of PT and SiC in rats, pulmonary fibrosis 26) , and mesotheliomas and pulmonary fibrosis 27) were observed, respectively. This suggested the possible injurious nature of PT and SiC to the lungs.…”