Analysis of particles from hamster lungs following pulmonary talc exposures: implications for pathogenicity

Our plain-English summary of Analysis of particles from hamster lungs following pulmonary talc exposures: implications for pathogenicity, by E. Sato, S.A. McDonald, Y. Fan, et al (Particle and Fibre Toxicology, 2020).

The study

• Authors: E. Sato, S.A. McDonald, Y. Fan, S. Peterson, J.D. Brain, J.J. Godleski
• Journal: Particle and Fibre Toxicology
• Published: 2020;17(1):20
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials. A previous study by (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) used a hamster model to study talc and granite dust exposure effects on various biochemical and cellular inflammatory markers. Our current study accessed key materials used in that 1987 study; we re-analyzed the original talc dust with contemporary scanning electron microscopy and energy dispersive x-ray analysis (SEM/EDX) for contaminants. We also examined the original bronchoalveolar lavage (BAL) cells with polarized light microscopy to quantify cell-associated birefringent particles to gain insight into the talc used.

Results: SEM/EDX analyses showed that asbestos fibers, quartz, and toxic metal particulates were below the limits of detection in the original talc powder. However, fibers with aspect ratios ≥3:1 accounted for 22% of instilled material, mostly as fibrous talc. Talc (based on Mg/Si atomic weight % ratio) was the most abundant chemical signature, and magnesium silicates with various other elements made up the remainder. BAL cell counts confirmed the presence of acute inflammation, which followed intratracheal instillation. Measurements of cell associated birefringent particles phagocytosis revealed significant differences among talc, granite, and control exposures with high initial uptake of talc compared to granite, but over the 14-day experiment, talc phagocytosis by lavaged cells was significantly less than that of granite. Phagocytosis of talc fibers by macrophages was observed, and birefringent particles were found in macrophages, neutrophils, and multinucleate giant cells in lavaged cells from talc-exposed animals.

Conclusion: Our data support the contention that talc, even without asbestos and other known toxic contaminants, may elicit inflammation and contribute to lung disease. Our findings support the conclusions of (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) study. By analyzing particulate exposures with polarized light microscopy and SEM/EDX, fibrous talc was identified and a distinctive pattern of impaired particulate ingestion was demonstrated.

In plain English

This study re-examined materials saved from a 1987 hamster experiment. In it, talc, granite, or a control solution was instilled into the windpipes of male hamsters. The authors analyzed the original talc powder by electron microscopy and re-read the lung-wash slides under polarized light. Of 200 particles and fibers examined from the talc powder, 78% were non-fibrous and 22% were fibers. No fiber had the composition of any asbestos type, and 68% of the fibers were fibrous talc. No quartz was found, and potentially toxic elements appeared only as traces, except one particle with over 5% chromium. One day after instillation, nearly 25% of lung-wash cells in the talc group carried particles, versus very few with granite or control. By day 7 the granite value was more than twice the talc value. Giant cells reached 3% in the talc group, against 0% in controls. The authors concluded that talc, even without contaminating asbestos, is a cause of lung inflammation and impaired cell function. The original granite dust was no longer available, so it could not be analyzed by electron microscopy.

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: Re-analysis of archived dust samples and lung-wash slides from a 1987 hamster intratracheal instillation experiment (Beck et al.); no live animals were used in the current study
• Who was studied: Archived bronchoalveolar lavage slides from male Syrian Golden Hamsters given talc, granite, or control instillation at the 3.75 mg/100 g body weight dose, examined at days 1, 4, 7 and 14. The original study used four animals per exposure group and three controls per experiment.
• Exposure: Talc dust from the original batch of the 1987 study, with granite dust as a comparison, given as a single suspension instilled into the hamster lungs
• Main results:
  • Talc powder sample (200 particles and fibers analyzed, all magnesium silicates): 78% non-fibrous particles and 22% fibers (aspect ratio 3:1 or greater)
  • Talc powder sample: of the 200 particles and fibers, 107 (53.5%) met the authors' compositional criteria for talc
  • Talc powder sample: 68% of the fibers were fibrous talc, and no fiber had the elemental composition of any asbestos type
  • Talc powder sample: no particles with the composition of quartz were found
  • Talc powder sample: potentially toxic elements, including nickel and vanadium, appeared only at trace levels and never above 1%. The exception was one magnesium silicate particle with more than 5% chromium.
  • Lung-wash cells, day 1: nearly 25% of cells in the talc group had associated particles, against very few in the control and granite groups
  • Lung-wash cells, day 7: the percentage of cells with particles in the granite group was more than twice that in the talc group, a significant difference
  • Talc group: no more than 2% of cells contained fibers at any time point. This was still statistically significantly higher than in the granite and control groups.
  • Giant cells, control group: 0% across the 14 days
  • Giant cells, talc group: less than 1% on day 1, rising to 3% by day 4
  • Macrophages with more than 3 particles: on day 1, almost 10% in the talc group versus 0% in the granite group. On days 4, 7 and 14, the granite group had more such macrophages than the talc group.
• The authors' conclusion: The authors concluded that their results add to understanding of talc, even without contaminating asbestos, as a cause of inflammation and impaired cell function in the lung. They also concluded that their findings support the 1987 Beck et al. study.
• Limitations the authors state:
  • The original granite dust was no longer available and could not be analyzed by electron microscopy; only the slides from granite-exposed animals were examined
  • It is unknown whether the granite dust contained fibrous particles
  • The counting method could not tell particles inside cells from particles attached to them
  • Hamsters given dust by intratracheal instillation may not represent humans or inhalation exposure
  • Only male hamsters were used
  • The relevance of the single chromium-containing particle is uncertain

Topics

The National Library of Medicine indexes this study under subjects our site covers: Talc and vermiculite.

Medical terms in this study, explained in our Lexicon: Talc, Silicate, Carcinoma, Inflammation, Scanning Electron Microscopy (SEM), Bronchoalveolar Lavage (BAL), Polarized Light Microscopy (PLM), Aspect Ratio (Length-to-diameter ratio).

Related studies

• The pulmonary toxicity of talc and granite dust as estimated from an in vivo hamster bioassay — B.D. Beck, H.A. Feldman, et al. (1987)
• Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure — D.M. Bernstein, R.A. Rogers, et al. (2011)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)
• Mineralogical features associated with cytotoxic and proliferative effects of fibrous talc and asbestos on rodent tracheal epithelial and pleural mesothelial cells — A.G. Wylie, H.C. Skinner, et al. (1997)
• Gender differences in murine pulmonary responses elicited by cellulose nanocrystals — A.A. Shvedova, E.R. Kisin, et al. (2016)
• Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure — E.E. McConnell, C. Axten, et al. (1999)

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