Pathogenicity of a special-purpose glass microfiber (E glass) relative to another glass microfiber and amosite asbestos

Our plain-English summary of Pathogenicity of a special-purpose glass microfiber (E glass) relative to another glass microfiber and amosite asbestos, by R.T. Cullen, A. Searl, D. Buchanan, et al (Inhalation Toxicology, 2000).

The study

• Authors: R.T. Cullen, A. Searl, D. Buchanan, J.M. Davis, B.G. Miller, A.D. Jones
• Journal: Inhalation Toxicology
• Published: 2000;12(10):959-77
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This article describes the activity of an E-glass microfiber (104E) during chronic inhalation and intraperitoneal injection studies in rats. Results are compared with another microfiber of similar dissolution rate (k(dis)), code 100/475, and the more durable amosite asbestos, both of which we had previously used in similar experiments (Davis et al., 1996). Rats were exposed to aerosol concentrations of 1000 fibers (longer than 5 microm)/ml, as measured by optical microscopy, for 7 h/day, 5 days/wk. Subgroups of rats were followed for mean lung burden, early and late signs of fibrosis, and tumor incidence. At the end of 12 mo of exposure, the mean number of 104E fibers of all lengths in the lungs was approximately double that for amosite but two-thirds of that for 100/475. For fibers longer than 15 microm, the mean 104E burden was similar to that for the amosite and more than twice that of the 100/475. After a 12-mo recovery period, the retained lung burdens (of fibers of all lengths) were approximately 30% of those at 12 mo for both microfibers, and somewhat higher (approximately 44%) for amosite. Amosite and 100/475 fibers longer than 15 microm were more persistent in the lungs than 104E fibers. The chemical composition of 104E fibers did not appear to have been significantly altered by up to 24 mo of residence in lung tissue, whereas the composition of 100/475 was substantially altered over the same time period. From the inhalation study, out of the pathology subgroup of 43 animals exposed to 104E microfibers, 10 had lung tumors (7 carcinoma, 3 adenoma) and 2 had mesotheliomas, whereas in 42 rats exposed to amosite asbestos, there were 16 lung tumors (7 carcinoma, 9 adenoma) and 2 mesotheliomas. The 104E- and amosite-treated animals had similar levels of fibrosis. In contrast, 38 animals treated with 100/475 had little fibrosis, 4 lung tumors (adenomas), and no mesotheliomas. The greater pathogenicity of the 104E fibers, compared to 100/475 fibers, might be partly explained by the greater numbers of long fibers retained in the lung after 12 mo of inhalation. However, we speculate that modification of surface properties by extensive selective leaching of some glass components reduces the toxic potential of 100/475. In a parallel intraperitoneal injection study, 104E caused considerably more mesotheliomas (21 rats out of 24) than 100/475 (8 rats out of 24). In addition, 104E appeared to be more active than amosite asbestos, since mesotheliomas appeared much more quickly in the 104E-treated animals. In conclusion, we have shown that two microfiber types, 100/475 and 104E, of similar dissolution rates, had markedly different pathogenicity in rats. We believe that this contrast is only partly due to differences in numbers of long fibers and that differences in surface properties of the fibers, possibly due to proportionately greater leaching of 100/475 fibers, play an important role.

In plain English

The authors exposed rats to an E-glass microfiber, 104E, comparing results with their earlier tests of amosite asbestos and another glass microfiber, 100/475. Rats breathed about 1000 fibers longer than 5 µm per ml, 7 hours a day, 5 days a week, for 12 months. Lung carcinomas, adenomas and mesotheliomas numbered 7, 3 and 2 in 43 rats given 104E; 7, 9 and 2 in 42 amosite rats; 0, 4 and 0 in 38 rats given 100/475; and 1, 1 and 0 in 38 controls. Lung tumors overall significantly exceeded controls with 104E but did not differ significantly from either other fiber; carcinomas alone were significantly more frequent than with 100/475. In small groups examined late, advanced fibrosis averaged 8.0% of lung area with 104E, 7.6% with amosite and 0.2% with 100/475. After abdominal injection, 21 of 24 rats in the 104E and amosite groups had mesotheliomas, versus 8 of 24 with 100/475; mesothelioma deaths came soonest with 104E. The authors concluded the two microfibers differed markedly, noting that in humans amosite's greater persistence would imply greater cancer risk than 104E.

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: chronic inhalation study and intraperitoneal injection study in rats with an E-glass microfiber (104E). The results are compared with earlier experiments by the same group using amosite asbestos and glass microfiber 100/475 (Davis et al., 1996).
• Who was studied: Inhalation study: 83 male Wistar (AF/HAN) rats exposed to 104E. Of these, 47 were assigned to pathology: 4 were killed at 12 months and 43 were followed for life. There was also a control group of 38 rats. Injection study: 24 male SPF Wistar rats, about 12 weeks old. Institute of Occupational Medicine, Edinburgh, UK.
• Exposure: Inhalation: E-glass microfiber 104E (Johns Manville) for up to 12 months, 7 hours a day, 5 days a week. The target was 1000 fibers/ml counting fibers longer than 5 µm by phase contrast optical microscopy; the achieved average was 1022 such fibers/ml. This was followed by up to 12 months of recovery. Injection: a single intraperitoneal injection of a fixed number of fibers, which was 12.6 mg for 104E, 6.1 mg for amosite and 8.3 mg for 100/475.
• Main results:
  • Lung tumors in the 43 long-term 104E-exposed rats: 7 carcinomas and 3 benign adenomas (10 rats, 23.2%).
  • Comparison groups: among 42 amosite rats, 7 carcinomas and 9 adenomas (16, 38.1%) and 2 mesotheliomas. Among 38 rats given 100/475, 0 carcinomas, 4 adenomas and 0 mesotheliomas. Among 38 controls, 1 carcinoma and 1 adenoma.
  • Total lung tumors (adenoma plus carcinoma) were significantly higher in 104E rats than in controls (p = .026).
  • Total lung tumor incidence with 104E was higher than with 100/475 and lower than with amosite. Neither difference was statistically significant.
  • The carcinoma incidence in 104E rats was comparable with amosite and significantly higher than in 100/475 rats (p = .02).
  • In the inhalation study, mesotheliomas occurred only in 104E rats (2 of 43) and amosite rats (2 of 42), each about 5%.
  • Advanced fibrosis was measured in small groups of late-examined rats, not in all exposed rats. In the 9 104E rats that survived until within 2 months of the end of the study, it averaged 8.0% of lung parenchyma. This was similar to amosite (7.6%, 9 rats) and much higher than 100/475 (0.2%, 11 rats). The figure for 15 controls was 0.08%.
  • After 12 months of exposure, 104E rats' lungs held 2.4 times as many fibers longer than 15 µm, and 7.5 times as many longer than 20 µm, as 100/475 rats' lungs.
  • After 12 months of recovery, the share of fibers of all lengths still in the lung was similar across fiber types: 30% for 104E, 28% for 100/475 and 44% for amosite. For 104E, the share was lower for long fibers: 20% (15 to 20 µm) and 2% (longer than 20 µm).
  • The estimated clearance half-life of 104E fibers from the lung was 7.1 months (95% confidence interval 5.8 to 9.0 months).
  • The composition of 104E and amosite fibers did not change significantly in the lung. 100/475 fibers lost barium, calcium and potassium and gained iron.
  • Intraperitoneal injection: 21 of 24 rats in the 104E and amosite groups had mesotheliomas, compared with 8 of 24 in the 100/475 group.
  • Intraperitoneal injection: survival curves were for deaths from mesothelioma, adjusted for deaths from other causes. Median survival was 642 days for 100/475 and became progressively shorter for amosite and then for 104E.
• The authors' conclusion: The authors concluded that 104E and 100/475, despite similar dissolution rates, had markedly different effects in rats. In the inhalation study, 104E was as fibrotic and as tumorigenic as amosite. They believe the contrast between the two microfibers is only partly due to differences in numbers of long fibers, and that differences in fiber surface properties play an important role, possibly due to greater leaching of 100/475.
• Limitations the authors state:
  • In the injection study, the equal fiber-number doses meant different masses for each fiber type. The authors do not know whether these mass differences explain the differences in tumors or survival.
  • The intraperitoneal test has been criticized because large doses are put, unlike natural exposure, into an enclosed site with no clearance other than dissolution.
  • The long-fiber lung burden estimates were based on small numbers of fibers counted.
  • Overload of lung clearance was likely in the inhalation study, though the authors judged it not severe enough to seriously impair clearance.
  • The 104E-versus-amosite comparisons apply to the short-lived rat. In humans, amosite's greater biopersistence would imply a greater carcinogenic risk than 104E.

Topics

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

Medical terms in this study, explained in our Lexicon: Amosite, Fibrosis, Pathology, Carcinoma, Mesothelioma, intraperitoneal injection study.

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