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

Our plain-English summary of Mesothelioma in rats following intrapleural injection of chrysotile and phosphorylated chrysotile (chrysophosphate), by A. Van der Meeren, J. Fleury, M. Nebut, et al (International Journal of Cancer, 1992).

The study

• Authors: A. Van der Meeren, J. Fleury, M. Nebut, G. Monchaux, X. Janson, M.C. Jaurand
• Journal: International Journal of Cancer
• Published: 1992;50(6):937-42
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This was an animal experiment from France. The authors injected 20 mg of fibers in saline into the chest (pleural) cavity of 2-month-old male Sprague-Dawley rats and followed them for life. They compared one untreated chrysotile sample with four chrysotile samples whose fiber surface had been chemically modified by phosphorylation, called chrysophosphate. Two control groups received either saline or no treatment. In all, 278 rats were used, counting both control groups; 273 had usable tissue and were examined under the microscope. No mesothelioma was found in either control group. In the fiber groups, 28% to 41% of rats developed mesothelioma. Untreated chrysotile produced 11 cases among 38 rats (29%). The difference between phosphorylated and untreated chrysotile was not statistically significant. Within this experiment, links between mesothelioma rates and fiber numbers were not statistically significant. The authors then combined these five samples with four chrysotile samples from two earlier studies. In that combined data, mesothelioma rates correlated with the number of fibers longer than 8 micrometres and thinner than 0.25 micrometres (r = 0.740, p less than 0.05). The authors concluded that phosphorylation did not reduce the fibers' cancer-causing potency.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: lifetime study of rats given a single intrapleural injection of fibers, with untreated and saline (sham) control groups
• Who was studied: 2-month-old male SPF outbred Sprague-Dawley rats. There were 278 rats in total, including both control groups: groups of 40, except the unmanipulated control group, which had 38. Of these, 273 rats (controls included) were used for histological analysis. They were housed for their lifespan and killed only when moribund.
• Exposure: 20 mg of one of five chrysotile samples: unmodified chrysotile; ChrP1, ChrP2 and ChrP3 (phosphorylated chrysotile from the first, second and third passages through an Alpine classifier); and P milled (a phosphorylated fraction defibrillated in a Pallman apparatus). The samples were provided by the Société Nationale de l'Amiante, Sherbrooke, Canada. Phosphorylated samples contained 0.15 to 0.57 million fibers per microgram longer than 8 micrometres and thinner than 0.25 micrometres, compared with 0.06 million per microgram for unmodified chrysotile.
• Main results:
  • No mesothelioma was found in the untreated control rats or in the saline-injected (sham) rats.
  • Mesothelioma developed in every fiber-treated group. The percentage ranged from 28% to 41% across groups. Untreated chrysotile produced mesothelioma at a rate of 29% (11 of 38 rats studied).
  • Mesothelioma counts in the other groups whose labels survived in the table: ChrP3, 13 of 40 rats studied (32.5%); P milled, 12 of 40 rats studied (30%). The authors stated that the highest percentages were with the phosphorylated samples P2 and P3.
  • Mesothelioma incidence was significantly higher in all fiber-treated groups than in controls (n = 273, chi-square greater than 32, p less than 0.001). This also held for chrysophosphate-treated rats alone (n = 235).
  • No statistically significant difference in mesothelioma incidence was found between chrysophosphate-treated and unmodified-chrysotile-treated rats (n = 196, chi-square = 0.2), or among the different chrysophosphates (n = 158, chi-square = 1.7).
  • Survival time was not significantly different between treated and untreated groups.
  • Within this study's five samples, the correlation between mesothelioma percentage and total number of fibers injected was r = 0.675. This was not statistically significant. For fibers meeting the length criteria, r was 0.506 (longer than 8 micrometres) and 0.573 (longer than 4 micrometres).
  • The authors combined these samples with chrysotile samples from earlier studies (Monchaux et al., 1981; Jaurand et al., 1987), giving 9 samples. Mesothelioma percentage then correlated with the number of fibers longer than 8 micrometres and thinner than 0.25 micrometres (r = 0.740, p less than 0.05). No correlation was found with the total number of fibers.
  • Most tumors were mixed-type mesotheliomas (52%), followed by spindle-cell (33%) and epithelial-cell (4%). No histological difference was seen between untreated chrysotile and chrysophosphate.
  • Some pleural plaques and mesothelial hyperplasia were seen in all asbestos-treated groups but not in the control groups.
• The authors' conclusion: The authors concluded that phosphorylation did not reduce the carcinogenic potency of chrysotile, because unmodified and phosphorylated chrysotile did not differ significantly in inducing mesothelioma. They also concluded that, across chrysotile samples, mesothelioma percentage correlated with the number of fibers meeting Stanton's criteria (longer than 8 micrometres, thinner than 0.25 micrometres), whatever the surface treatment.
• Limitations the authors state:
  • Only a small number of fiber groups was tested, which made it harder to detect a statistically significant trend between fiber numbers and mesothelioma.
  • Short-term measurement of chemical stability may not reflect long-term durability, and intrapleural injection may not allow durability to be assessed.
  • In the combined analysis, one earlier sample (SCF) may have been altered by its preparation method, which affected the correlation with total fiber number.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Chrysotile, Pleural Cavity, Transmission Electron Microscopy (TEM).

Related studies

• Evaluation of the tumorigenic potential of vermiculite by intrapleural injection in rats — B. Hunter, C. Thomson (1973)
• Incidence of various types of thoracic malignancy induced in rats by intrapleural injection of 2 mg of various mineral dusts after inhalation of 222Ra — J. Bignon, G. Monchaux, et al. (1983)
• Inhalation and injection studies in rats using dust samples from chrysotile asbestos prepared by a wet dispersion process — J.M. Davis, J. Addison, et al. (1986)
• Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres — G. Monchaux, J. Bignon, et al. (1981)
• Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers — D.B. Warheit, S.I. Snajdr, et al. (1997)
• Effects of chrysotile asbestos on lung and pleural carcinogenesis of N-bis(2-hydroxypropyl)nitrosamine in rats — H. Katada, R. Higashiguchi, et al. (1983)

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