Effects of phosphorylation of chrysotile on pleuropulmonary fibrogenicity and carcinogenicity

Our plain-English summary of Effects of phosphorylation of chrysotile on pleuropulmonary fibrogenicity and carcinogenicity, by H. Daniel, A. Wastiaux, P. Sébastien, et al (British Journal of Industrial Medicine, 1993).

The study

• Authors: H. Daniel, A. Wastiaux, P. Sébastien, R. Bégin
• Journal: British Journal of Industrial Medicine
• Published: 1993;50(2):167-71
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

As well as fibre size, fibre chemistry is a determinant of toxicity of mineral fibres. On these grounds, a few years ago, the asbestos industry in Québec developed a process to modify the surface chemistry of chrysotile asbestos by fixing phosphorous atoms. The pleuropulmonary fibrogenicity and carcinogenicity of the native and surface treated chrysotile, called chrysophosphate, were tested. Both products initiated similar pulmonary fibrogenicity in rats exposed by inhalation and sheep exposed by injection in the tracheal lobe. Tumour production in rats after long term inhalation or intrapleural injection was not different between chrysotile and chrysophosphate. These findings clearly show that modification of the phosphate surface of chrysotile fibres does not appear to alter the pleuropulmonary activities of the mineral, thus arguing against the earlier contention of less biological activity for chrysophosphate, a contention essentially based upon results of in vitro tests. This study strongly argues for in vivo testing of new fibrous materials before making definite conclusions about their biological activities.

In plain English

This animal study tested whether chrysotile asbestos treated to fix phosphorus onto its fiber surface (called chrysophosphate) caused less lung inflammation, scarring (fibrosis) and tumours than untreated chrysotile. The authors ran three experiments. In one, 24 sheep received saline, chrysotile or chrysophosphate into one lung lobe. In another, rats received a single injection into the chest cavity. In the third, rats breathed the dusts for 24 months. Titanium dioxide served as a comparison dust in the rat experiments. Both fibers caused similar lung inflammation and fibrosis in sheep and rats. After chest-cavity injection, mesothelioma developed in 16 chrysotile rats and 11 chrysophosphate rats (40 rats per group); the authors reported the difference was not significant. In the inhalation experiment, lung tumours occurred in 1 of 39 control rats, 5 of 43 chrysotile rats and 9 of 42 chrysophosphate rats counted. Only the chrysophosphate group differed significantly from controls, and the two fibers did not differ significantly. No mesothelioma was found. The authors concluded that the phosphate treatment did not reduce the fibers' effects in these animals. They noted that the treatment may not have reached every fibril.

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 experiments: three sets of experiments comparing untreated chrysotile with phosphorus-treated chrysotile (chrysophosphate). These were injection into the tracheal lobe of sheep, a single intrapleural (chest cavity) injection in rats, and long-term inhalation in rats.
• Who was studied: 24 sheep, in three groups of eight. Four groups of 40 Wistar rats (20 male, 20 female) for intrapleural injection. Three groups of 48 Wistar rats (24 female, 24 male) for inhalation, plus a control group kept in a similar chamber. The authors were based in France (Cerchar) and Quebec, Canada (CHU Sherbrooke). The article does not state where or when the experiments were carried out.
• Exposure: The fiber was Canadian chrysotile, either untreated or treated with POCl3 vapours and heat to fix phosphorus atoms on its surface (chrysophosphate). Titanium dioxide was used as an inert dust. Doses: sheep received 100 mg of fibres in 100 ml saline infused into the tracheal lobe. Intrapleural rats received 20 mg in 2 ml isotonic glucose. Inhalation rats were exposed 5 hours a day, 5 days a week for 24 months. Mean respirable dust concentrations were 5.8 (SEM 1.5) mg/m3 for chrysotile, 5.8 (1.4) for chrysophosphate and 6.2 (3.2) for titanium dioxide.
• Main results:
  • In sheep, lung lavage measurements increased in the chrysophosphate group. The levels did not differ significantly from those in the chrysotile group.
  • In sheep lung tissue, the mean pathological score was 2.86 (SEM 0.14) in the chrysotile group and 2.2 (0.5) in the chrysophosphate group. The chrysophosphate score was lower but not significantly different. Control sheep lungs were normal.
  • In intrapleural rats, there were 16 mesotheliomas in the chrysotile group and 11 in the chrysophosphate group (40 rats each). There was 1 in the titanium dioxide group and none in controls. The authors stated that the lower incidence with chrysophosphate was not significant.
  • In intrapleural rats, an invasive thoracic tumour was present in 56.5% of the chrysotile group, 24.4% of the chrysophosphate group and 2.8% of the titanium dioxide group.
  • In inhalation rats, fibre-exposed rats developed more lung tumours than controls, and the difference was significant only for the chrysophosphate group. Tumour occurrence did not differ statistically between chrysotile and chrysophosphate. Table 4 lists rats with lung tumours as follows: controls 1 (of 39 dead or killed), titanium dioxide 1 (of 44), chrysotile 5 (of 43) and chrysophosphate 9 (of 42).
  • In inhalation rats, pulmonary carcinomas, especially squamous carcinomas, were more frequent with chrysophosphate than with chrysotile, but the difference was not statistically significant. Table 4 shows 3 squamous carcinomas and 2 adenocarcinomas in the chrysophosphate group, compared with 0 and 1 in the chrysotile group.
  • In inhalation rats, no mesothelioma was detected.
  • In inhalation rats, mean lung pathological scores were 2.08 (1.0) for chrysotile, 1.96 (1.0) for chrysophosphate and 0.34 (0.2) for titanium dioxide.
  • In inhalation rats, the chrysophosphate group had the highest reported rate of premature death, 40%. The authors attributed this excess to interstitial nephritis, a kidney disease.
• The authors' conclusion: The authors concluded that the phosphate surface modification did not appear to alter chrysotile's effects on the lung and pleura. They wrote that the POCl3 treatment was ineffective in reducing chrysotile's long-term fibrogenicity and carcinogenicity in experimental animals. They argued that new fibrous materials should be tested in live animals before conclusions are drawn about their biological activity.
• Limitations the authors state:
  • The authors suggested that in their materials the POCl3 treatment may not have reached all of the chrysotile fibrils within the fibre bundles. They noted it could have been more effective in the materials used in earlier studies.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile.

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