The carcinogenicity of WHO fibers of silicon carbide: SiC whiskers compared to cleavage fragments of granular SiC

Our plain-English summary of The carcinogenicity of WHO fibers of silicon carbide: SiC whiskers compared to cleavage fragments of granular SiC, by K. Rödelsperger, B. Brückel (Inhalation Toxicology, 2006).

The study

• Authors: K. Rödelsperger, B. Brückel
• Journal: Inhalation Toxicology
• Published: 2006;18(9):623-31
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A steep dose-response relationship for tumors was reported after application of 0.05 to 25 mg of whiskers of SiC in 1991 in a chronic intraperitoneal injection study in rats. In contrast, doses of 250 and 1000 mg of granular SiC did not cause tumors. The whiskers contained 107,000,000 fibers longer than 5 mum, per milligram while the granular sample was assumed to be free of such fibers. However, it has since been realized that even granular SiC may contain fibrous fragments that fulfill the definition of WHO fibers. It was the objective of our study to reanalyze the quantity of WHO fibers that were administered with the granular SiC. In addition, we examined whether the potency per WHO fiber was different for the SiC fragments and the SiC whiskers. Samples of the original granular and fibrous SiC were suspended in water and filtered. One half of each filter was analyzed by scanning electron microscopy (SEM, magnification x 2500), and transmission electron microscopy (TEM, x 10,000) was also performed for the SiC whiskers. The concentration of WHO fibers was 58,000 fibers/mg for the granular sample compared to 48,000,000 (SEM) and 42,000,000 (TEM) fibers/mg for the whiskers. The aspect ratio of the WHO fibers exceeded 10/1 for only 3.3% of the fragments but in each analysis for 96% of the whiskers. In addition, 0% of the fragments compared to 44% and 30% of the whiskers were more than 10 mum long. In total, 15 and 58 x 106 WHO fibers were injected with the granular SiC even though only 0.8% and 0% tumors were recorded. However, 20.1% and 43.3% tumors would have been expected if the carcinogenic potency were the same for the fragments and for the whiskers. We therefore conclude that carcinogenic potency is a function of the shapes of the WHO fibers and is much lower for SiC fragments than for whiskers. Hence carcinogenicity mainly is restricted to a subgroup of WHO fibers longer than about 10 and thinner than about 1 mum. This conclusion is in line with the optimal exposure index, which recently has been proposed by the U.S. Environmental Protection Agency (EPA) for asbestos.

In plain English

This laboratory study re-examined original silicon carbide (SiC) samples from earlier rat experiments in which SiC was injected into the abdominal cavity. In those experiments, SiC whiskers caused tumors at doses of 0.05 to 25 mg, while 250 and 1000 mg of granular SiC gave tumor rates of 0.8% (1/118) and 0% (0/115). Using electron microscopy, the authors found 58,000 particles per mg (95% confidence interval 43,000 to 76,000) meeting the WHO fiber definition in the granular SiC. These were elongated cleavage fragments. The whiskers had 48,000,000 (SEM) and 42,000,000 (TEM) per mg. None of the fragments were longer than 10 µm, compared with 44% and 30% of the whiskers. The authors calculated that tumor rates of 20.1% and 43.3% would have been expected if fragments were as potent as whiskers. They estimated the whiskers were at least about 15 times more potent per WHO fiber. The authors concluded that SiC fragments have much lower carcinogenic potency than whiskers, if any. They noted that an infection killed about 34% of rats in the whisker experiment, which could have overestimated tumor rates.

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: Laboratory reanalysis by electron microscopy of archived samples from earlier rat intraperitoneal injection experiments, combined with recalculation of those experiments' published tumor data
• Who was studied: No new animals were used. Two samples (2.57 mg and 8.41 mg) of the original granular SiC and one sample (2.82 mg) of the original fibrous SiC (whiskers) were analyzed. Tumor data came from earlier rat studies (Pott et al., 1991; Roller et al., 1996).
• Exposure: Silicon carbide (SiC) whiskers (0.05 to 25 mg) and granular SiC containing cleavage fragments (250 and 1000 mg), injected intraperitoneally in rats in the earlier studies
• Main results:
  • Granular SiC contained a mean of 58,000 WHO fibers per mg (95% CI: 43,000 to 76,000). The mean was calculated as a function of the masses suspended.
  • SiC whiskers contained 48,000,000 (SEM) and 42,000,000 (TEM) WHO fibers per mg. This is lower than the 107,000,000 per mg reported in 1991.
  • Aspect ratio exceeded 10 to 1 for 3.3% of the fragments (1 in 30; median 3.6 to 1), compared with 96% of the whiskers in each analysis
  • Width less than 1 µm: 10% of fragments versus 96% and 92% of whiskers
  • Fibers longer than 10 µm: 0% of fragments versus 44% and 30% of whiskers
  • In the earlier experiments, 250 and 1000 mg of granular SiC gave tumor rates of 0.8% (1/118) and 0% (0/115). The upper 95% confidence limits were 4.29% and 2.84%.
  • From the whisker dose-response line, the numbers of WHO fibers injected with granular SiC (about 0.015 and 0.058 billion) would be expected to give tumor rates of 20.1% and 43.3%
  • The ratio of expected (whiskers) to observed (fragments) tumor rate per WHO fiber exceeded 15 to 1, based on the upper confidence limit for the 1000 mg granular dose
• The authors' conclusion: The authors concluded that WHO fibers from SiC cleavage fragments have much lower carcinogenic potency than SiC whiskers, if any. They also concluded that this supports the view that the WHO fiber definition is too encompassing.
• Limitations the authors state:
  • An infection in months 12 and 13 killed about 34% of rats in the whisker experiment. Tumor rates were calculated only among survivors or tumor-bearing animals, so they could have been overestimated. If dead animals were counted as at risk, expected rates would have been 11% and 24%.
  • Intraperitoneal injection bypasses the natural route of exposure, so the lung's mechanisms for eliminating fibers are not in effect
  • The whisker fiber counts in this reanalysis were lower than those reported in 1991. The authors suggest the sample analyzed earlier may have been more representative of the exposure.

Topics

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

Medical terms in this study, explained in our Lexicon: Cleavage Fragment, Dose-response relationship, intraperitoneal injection study, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Aspect Ratio (Length-to-diameter ratio), Carcinogenic.

Related studies

• In vitro activity of silicon carbide whiskers in comparison to other industrial fibers using four cell culture systems — N.F. Johnson, M.D. Hoover, et al. (1992)
• Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes — Y. Grosse, D. Loomis, et al. (2014)
• Pulmonary effects and biopersistence of deposited silicon carbide whisker after 1-year inhalation in rats — I. Akiyama, A. Ogami, et al. (2007)
• The immediate effects of silicon carbide whiskers upon ciliated tracheal epithelium — G.L. Vaughan, J.R. Kennedy, et al. (1991)
• Histopathological changes in rat lung following intratracheal instillation of silicon carbide whiskers and potassium octatitanate whiskers — A. Ogami, Y. Morimoto, et al. (2007)
• The toxicity, in vitro, of silicon carbide whiskers — G.L. Vaughan, J. Jordan, et al. (1991)

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