Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies

Our plain-English summary of Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies, by F. Pott, M. Roller, K. Kamino, et al (Environmental Health Perspectives, 1994).

The study

• Authors: F. Pott, M. Roller, K. Kamino, B. Bellmann
• Journal: Environmental Health Perspectives
• Published: 1994;102 Suppl 5(Suppl 5):145-50
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This paper, presented at a 1992 workshop, reported two rat experiments by the authors and an argument based on published data. In a pilot study, 12 female Wistar rats were injected into the abdominal cavity with 50 mg of slag fibers and killed at intervals up to 673 days. The estimated half-time of slag fibers in the omentum (a fatty abdominal tissue) was 356 days, with a 95% confidence interval from 163 days with no upper limit. In a second experiment, still running when the paper was written, rats received very high doses of nonfibrous silicon carbide or of a glass fiber of low durability. No serosal tumors were found in 35 examined silicon carbide rats. Within 87 weeks, three rats in the 20 x 25 mg glass fiber group had serosal tumors, and 20 serosal tumors were found in the 40 x 25 mg group. The authors described the higher dose as associated with a tumor incidence of about 40%. Using other researchers' data, the authors estimated that the asbestos tumor risk per fiber is about 200 times higher in humans than in rats. They concluded that rat inhalation studies are too insensitive to identify the cancer-causing potential of mineral fibers.

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: Conference paper combining the authors' own animal experiments in rats with a comparison of published data. The experiments were a pilot study of how long fibers persist in the omentum after injection into the abdominal cavity, and an ongoing intraperitoneal carcinogenicity study. The comparison set published rat inhalation data against human asbestos data.
• Who was studied: Pilot study: 12 female Wistar rats aged 17 weeks; omenta from 5 rats of an earlier basalt wool study were measured for comparison. Carcinogenicity study: Wistar rats aged 8-10 weeks; 48 female and 72 male rats in the silicon carbide groups and 54 male rats per glass fiber group.
• Exposure: Pilot study: 50 mg of slag fibers from slagwool factory dust, injected into the abdominal cavity; basalt wool rats had received five weekly injections of 30 mg. Carcinogenicity study: nonfibrous silicon carbide given as 5 x 50 mg or 20 x 50 mg every two weeks. Low-durability glass fibers (Bayer ATF-3101) given as 20 x 25 mg every two weeks or 40 x 25 mg weekly.
• Main results:
  • The estimated half-time of slag fibers in the rat omentum was 356 days. The 95% confidence interval ran from 163 days to infinity, meaning it had no upper limit.
  • The authors stated that the pilot results do not support the earlier hypothesis that slag fibers are not durable enough to induce tumors.
  • The authors calculated that injecting 10 to the 9th power (one billion) fibers would give a fiber concentration in the omentum ash in the same range as that in rat lungs after 2 years of inhalation exposure.
  • Silicon carbide groups: mortality was less than 20% over 90 weeks in all groups.
  • Silicon carbide groups: no serosal tumors were found in the abdominal cavity of the 35 rats examined under the microscope.
  • Silicon carbide, 20 x 50 mg group: one year after the first injection, average body weight was about 5% lower than in saline-injected controls in both sexes. Six months later the difference was 7 to 8%.
  • Glass fiber groups, within 87 weeks: three rats had serosal tumors in the 20 x 25 mg group, and 20 serosal tumors were found in the 40 x 25 mg group.
  • The 1000 mg glass fiber dose (40 x 25 mg) was associated with a tumor incidence of about 40%.
  • Glass fiber groups: body weight was not lower than in the other groups.
  • Comparing published estimates for chrysotile textile workers with published rat inhalation studies, the authors estimated the difference between the human and rat dose-response relationships at 1 to 200.
  • From published data, the authors reported that the crocidolite fiber concentration in rat lungs in a negative inhalation study was more than 1000-fold higher than the median concentration of amphibole fibers in the lungs of asbestos workers with mesotheliomas.
• The authors' conclusion: The authors concluded that the rat inhalation model is too insensitive to identify the carcinogenic potential of mineral fibers. They considered the intraperitoneal model more reliable for identifying fiber cancer hazard. They proposed that preventive measures be based on risk estimates from epidemiological studies of asbestos workers, with correction factors for each fiber type.
• Limitations the authors state:
  • Fiber concentrations varied widely between omenta, possibly because the injected fibers were not evenly suspended.
  • There were too few data to estimate a half-time for basalt fibers.
  • Short fibers migrate substantially to the lymph nodes after intraperitoneal injection, which affects how fiber loss from the abdominal cavity can be interpreted.
  • The glass fiber experiment was still ongoing. The three mesotheliomas in the lower-dose group indicated a carcinogenicity that may become statistically significant, but was not stated to be so yet.
  • The authors' comparisons between ceramic, crocidolite and asbestos fibers in rat inhalation data could not be affirmed definitely because of substantial uncertainties in the experimental data.

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Carcinogenic, Chrysotile, Peritoneal Cavity, Carcinogenesis, Dose-response relationship, Omentum.

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• A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans — D.H. Garabrant, S.T. Pastula (2018)
• Contemporary issues in fiber toxicology — D.B. Warheit, K.E. Driscoll, et al. (1995)
• Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo[a]pyrene — J. Friemann, M. Varnai, et al. (1996)
• Carborundum pneumoconiosis. Fibers in the mineral activate macrophages to produce fibroblast growth factors and sustain the chronic inflammatory disease — R. Bégin, A. Dufresne, et al. (1989)

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