Mesothelioma in rats following intrapleural injection of chrysotile and phosphorylated chrysotile (chrysophosphate)

Abstract

Pathological effects of asbestos are probably dependent on the size and surface properties of the fibers. Surface-modified chrysotile fibers were injected into the pleural cavity of rats to investigate the potency of the fiber to induce mesothelioma. Chrysotile fibers were modified by a phosphorylation process, resulting in the presence of phosphorus at the fiber surface. Phosphorylated samples were characterized by enhanced durability and reduced affinity for biological macromolecules. Five samples were tested: 1 untreated and 4 phosphorylated. ChrP1, ChrP2 and ChrP3 corresponded to phosphorylated samples obtained by first, second and third passages through an Alpine classifier; Pm was defibrillated ChrP1. The number of fibers per microgram and the size distribution were determined by transmission electron microscopy and classified in 4 size groups. Groups of 35 rats were inoculated with 20 mg of fibers suspended in 0.9% NaCl solution. No mesothelioma was found in the saline controls. All fiber samples were proficient in producing mesothelioma; the percentages were different between groups and untreated chrysotile but not significantly so. The differences may be explained on the basis of the number of fibers injected which were greater than 8 microns in length and less than 0.25 microns in diameter. The findings of a proficiency of long fibers to produce mesothelioma, previously reported by others for glass fibers, could be applied to chrysotile.

Quantification of short and long asbestos fibers to assess asbestos exposure: a review of fiber size toxicity

“…The important role of fibers corresponding to Stanton’s criteria (L > 8 μm; d ≤ 0.25 μm) has been evidenced in other reports where asbestos fibers were injected in the pleural cavity [74-76]. In these studies, other factors playing a role in the toxicity of fibers were identified and investigated.…”

Review of Animal/In Vitro Data on Biological Effects of Man-Made Fibers

“…By intrapleural inoculation, it has been concluded that the probability of tumor formation was dependent on fiber size, based on results obtained with MMF and asbestos (21); this assumption was confirmed recently (35,36,71). Asbestos used as positive control entailed a globally significant tumor enhancement, except in SW and RW studies (13).…”

Factors that Impact Susceptibility to Fiber-Induced Health Effects

“…Erionite was found to induce MM in rodents both by injection into the pleural or peritoneal cavities and by inhalation (Wagner et al, 1985; Johnson et al, 1984; Maltoni et al, 1982; Van der Meeren et al, 1992). Further investigations in rodents showed that erionite disrupts the balance between cell proliferation and apoptosis toward cell proliferation.…”