Chronic inhalation and biopersistence of refractory ceramic fiber in rats and hamsters

Our plain-English summary of Chronic inhalation and biopersistence of refractory ceramic fiber in rats and hamsters, by R.W. Mast, T.W. Hesterberg, L.R. Glass, et al (Environmental Health Perspectives, 1994).

The study

• Authors: R.W. Mast, T.W. Hesterberg, L.R. Glass, E.E. McConnell, R. Anderson, D.M. Bernstein
• Journal: Environmental Health Perspectives
• Published: 1994;102 Suppl 5(Suppl 5):207-9
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Lifetime "nose-only" inhalation studies were conducted in rats using four types of refractory ceramic fibers (FCF), 1 micron in diameter x 22 to 26 microns length: High Purity, Kaolin, Zirconia, and After-Service; and on hamsters using Kaolin RCF. For comparison, animals also were exposed to chrysotile fibers. Rats were exposed 6 hr/day, 5 days/week for 24 months to concentrations ranging between 3 and 30 mg/m3. Time- and dose-dependent lesions in the rat included the development of interstitial fibrosis, pleural fibrosis, pulmonary tumors, and mesothelioma. Exposure to 3, 9 or 16 mg/m3 produced no excess lung tumors; no fibrosis was seen at 3 mg/m3. A significant increase in lung tumors and interstitial fibrosis was observed at 30 mg/m3. A single mesothelioma was observed in rats exposed to 9 mg/m3, while two occurred at 30 mg/m3. Hamsters were similarly exposed to 30 mg/m3 Kaolin RCF for 18 months; no lung tumors were induced, but pulmonary and pleural fibrosis were observed and there was a 42% incidence of mesothelioma. Multiple interim sacrifices together with recovery animals allowed detailed assessment of the lung burden of RCF, which was found to be dose related and, at the high doses, exceeded 10(5) fibers/mg of dry lung. During the various recovery periods there was a clear reduction in fiber burden. Mathematical modeling of these data for deposition, clearance, and retention and for species is currently underway.

In plain English

In this laboratory study, Fischer 344 rats and Syrian golden hamsters breathed refractory ceramic fiber (RCF), a man-made fiber, through nose-only exposure 6 hours a day, 5 days a week. Rats were exposed for 24 months to four RCF types (Kaolin, Zirconia, High-Purity and heat-treated "After-Service") at about 30 mg/m3. Kaolin RCF was also given to rats at 3, 9 and 16 mg/m3. Hamsters received Kaolin RCF at 30 mg/m3 for 18 months. Chrysotile asbestos served for comparison. At 30 mg/m3, rats had statistically significant lung tumor incidences: 15% (Kaolin), 9% (Zirconia) and 15% (High-Purity). Rats also developed mesotheliomas, but the incidence was not statistically significant. At the lower doses, Kaolin RCF produced no excess lung tumors, and no fibrosis was seen at 3 mg/m3. Hamsters given Kaolin RCF had a 42% incidence of pleural mesothelioma but no lung tumors. Of rats exposed to chrysotile, 21% developed lung tumors. Lung fiber levels rose with dose and fell after exposure stopped. The authors concluded that repeated exposure to extremely high RCF concentrations can produce progressive fibrosis, lung tumors and mesothelioma.

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: Lifetime nose-only inhalation experiment in animals (rats and hamsters), with interim sacrifices and recovery groups
• Who was studied: Weanling Syrian golden hamsters and Fischer 344 rats. Terminal sacrifice was at 29 months for rats and 20 months for hamsters. Group sizes are not stated in the text. The work was performed at the Research and Consulting Co., Geneva, Switzerland, and the Mountain Technical Center, Littleton CO.
• Exposure: Refractory ceramic fibers about 1 micrometre in diameter and 22 to 26 micrometres long. Rats received four types (Kaolin, Zirconia, High-Purity and After-Service) at about 30 mg/m3. Kaolin RCF alone was also given at 16, 9 and 3 mg/m3. Hamsters received Kaolin RCF at 30 mg/m3 for 18 months. Chrysotile (11 mg/m3) was used for comparison. Exposure ran 6 hr/day, 5 days/week, and rats were exposed for 24 months.
• Main results:
  • Rats exposed to 30 mg/m3 RCF had a statistically significant incidence of lung tumors: 15% with Kaolin RCF, 9% with Zirconia RCF and 15% with High-Purity RCF.
  • Mesotheliomas were seen in rats exposed to RCF. The authors described them as appearing biologically significant, but the incidence was not statistically significant.
  • Rats given lower doses of Kaolin RCF had no excess of lung tumors at 3, 9 or 16 mg/m3. A single mesothelioma occurred at 9 mg/m3.
  • No fibrosis was observed in rats exposed to 3 mg/m3 Kaolin RCF.
  • Rats exposed to After-Service fiber had fibrosis and "silicosis". Their tumor incidence (3.2% in the text) was comparable to the 1.6% seen in the control group.
  • Hamsters exposed to Kaolin RCF had a 42% incidence of pleural mesotheliomas (43 animals, 42%, in Table 2) and no lung tumors.
  • Hamsters exposed to chrysotile developed neither lung nor pleural tumors.
  • Among rats exposed to chrysotile, 21% developed lung tumors.
  • In hamsters, chrysotile caused more extensive fibrosis (grade 5) than RCF (grade 4).
  • RCF lung burdens were dose related. At the high doses they exceeded 10 to the 5th power (100,000) fibers per milligram of dry lung.
  • Fiber burden in the lungs fell substantially in animals removed from exposure (recovery animals).
  • Preliminary modeling suggested impaired clearance in rats at 30 mg/m3, with a half-life of about 200 days, compared with about 140 days at lower doses.
• The authors' conclusion: The authors concluded that repeated exposure to extremely high concentrations (about 200 fibers per cubic centimeter) of specially processed rodent-respirable RCF can produce progressive lung damage (fibrosis), lung tumors, and pleural tumors (mesothelioma). They also suggested that a no-effect level was observed for both fibrosis and tumor production, and they raised doubts about the hamster as a stand-in for humans.
• Limitations the authors state:
  • Mathematical modeling of fiber deposition, clearance and retention was still underway, so the clearance findings were preliminary.

Topics

Medical terms in this study, explained in our Lexicon: biopersistence, Chrysotile, Interstitial Fibrosis, Fibrosis, Mesothelioma, Fiber Burden, Deposition.

Related studies

• Pulmonary and pleural leukocytes from F344 rats produce elevated levels of fibronectin following inhalation of refractory ceramic fibers — T.R. Gelzleichter, J.B. Mangum, et al. (1996)
• The importance of fiber biopersistence and lung dose in determining the chronic inhalation effects of X607, RCF1, and chrysotile asbestos in rats — T.W. Hesterberg, G.A. Hart, et al. (1998)
• Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats — T.W. Hesterberg, W.C. Miiller, et al. (1994)
• Studies on the chronic toxicity (inhalation) of four types of refractory ceramic fiber in male Fischer 344 rats — R.W. Mast, E.E. McConnell, et al. (1995)
• Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers — H. Greim, M.J. Utell, et al. (2014)
• Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results — T.W. Hesterberg, C. Axten, et al. (1997)

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