Comparative health effects in mice of Libby amphibole asbestos and a fibrous amphibole from Arizona

Our plain-English summary of Comparative health effects in mice of Libby amphibole asbestos and a fibrous amphibole from Arizona, by J.C. Pfau, B. Buck, R.V. Metcalf, et al (Toxicology and Applied Pharmacology, 2017).

The study

• Authors: J.C. Pfau, B. Buck, R.V. Metcalf, Z. Kaupish, C. Stair, M. Rodriguez, D.E. Keil
• Journal: Toxicology and Applied Pharmacology
• Published: 2017;334:24-34
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This project developed from studies demonstrating that Libby Amphibole Asbestos (LAA) causes a non-typical set of health outcomes not generally reported for asbestos, including systemic autoimmunity and an unusual and devastating lamellar pleural thickening that progresses to severe pulmonary dysfunction and death. Further, mineral fiber mixtures with some similarities to LAA have recently been discovered in southern Nevada and northwestern Arizona, where the material exists in extensive recreational areas and is present in yards, roads, parking lots and school yards. The objective was to compare the health outcomes in mice exposed to either LAA or the fibrous amphiboles collected in Arizona at the Lake Mead National Recreational Area at very low doses to represent environmental exposures. In this study, the fibrous amphibole asbestos sample from Arizona (AzA) is composed of winchite (69%), actinolite (22%), and non-amphibole minerals (9%) and has a mean aspect ratio of 16.7±0.9. Fibrous amphibole asbestos from Libby (LAA) is composed of winchite (70%), richterite (9%), tremolite (5%), and non-amphibole minerals (16%) with a mean aspect ratio of 8.4±0.7. C57BL/6 mice were exposed by oropharyngeal aspiration to fiber suspensions at a very low dose of 3μg/mouse. After seven months, both LAA- and AzA-exposed mice had indices of chronic immune dysfunction related to a TH17 cytokine profile, with B cell activation, autoantibody production and proteinuria, suggesting kidney involvement. In addition, both exposures led to significant lung and pleural fibrosis. These data suggest that there is risk of pulmonary disease and autoimmune outcomes with environmental exposure to amphibole asbestos, and that this is not limited to Libby, Montana.

Copyright © 2017 Elsevier Inc. All rights reserved.

In plain English

This was a laboratory experiment in mice. It compared Libby amphibole asbestos (LAA), from the W.R. Grace mine near Libby, Montana, with a fibrous amphibole collected in the Lake Mead Recreation Area of northwestern Arizona (AzA). The Arizona sample was mainly winchite (69%) and actinolite (22%). The Libby sample was mainly winchite (70%), with richterite and tremolite. Male and female mice had fiber suspensions placed in the throat twice, two weeks apart, for a total of 3 μg per mouse. The authors chose this dose to represent environmental rather than work exposure. Seven months later, 14 saline control, 9 LAA and 17 AzA mice remained. Both fibers raised blood immune signals of a type the authors call TH17 (TNF-alpha, IL-6, IL-17). Both were also followed by protein in the urine, which the authors said suggests kidney involvement. Autoantibodies rose mainly with AzA. Both fibers increased collagen in the diaphragm, used as a measure of pleural scarring. Lung collagen rose significantly in male mice. No tumors were found. The authors concluded that other environmental fibrous amphiboles can have effects very much like LAA at very low doses in mice.

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 comparing two amphibole fiber samples with a saline control in mice, with follow-up 7 months after the last exposure
• Who was studied: Wild-type C57BL/6 mice, both male and female, 6 to 8 weeks old at the start, housed at Montana State University. 20 mice per group were planned, but some died or were euthanized. The numbers at the end were 14 saline controls (9 male, 5 female), 9 LAA-exposed (4 male, 5 female) and 17 AzA-exposed (8 male, 9 female).
• Exposure: LAA was an EPA composite sample from the W.R. Grace mine outside Libby, Montana: winchite 70%, richterite 9%, tremolite 5%, non-amphibole minerals 16%. AzA was a single vein sample from the Wilson Ridge pluton in the Lake Mead Recreation Area, northwestern Arizona: winchite 69%, actinolite 22%, non-amphibole minerals 9%. Each mouse received 1.5 μg by oropharyngeal aspiration, repeated 2 weeks later, for a total of 3 μg per mouse. The authors chose this dose to represent environmental rather than occupational exposure.
• Main results:
  • Antinuclear autoantibodies (ANA): at 4 months, only AzA raised the percent positive above saline controls. At 7 months, both fibers had induced ANA, but the LAA increase was not statistically significant (p = 0.1). AzA was significant compared with saline (p less than 0.05). Most positive tests were in female mice.
  • Mesothelial cell autoantibodies (MCAA) were induced mainly by AzA. Positive counts were: males, 1 of 9 saline, 1 of 4 LAA, 4 of 8 AzA; females, 1 of 5 saline, 2 of 5 LAA, 6 of 9 AzA. Within each sex, the differences were not statistically significant.
  • Protein (albumin) in the urine, above 30 mg/dL, which the authors took as suggesting kidney involvement. Positive counts were: males, 2 of 9 saline, 4 of 4 LAA, 7 of 7 AzA; females, 0 of 5 saline, 3 of 4 LAA, 5 of 8 AzA.
  • Both fibers raised blood levels of all three cytokines the authors describe as a TH17 response: TNF-alpha, IL-6 and IL-17. Mean IL-17 was 1.4 pg/ml in saline mice, 12.6 in LAA mice and 9.7 in AzA mice. Neither fiber triggered IL-2 or IL-4.
  • In the spleen, both fibers increased B cells and the percentage of B1a B cells. The only significant change in T cell subsets was a reduction in the percentage of T regulatory cells with AzA.
  • Diaphragm collagen, used as a measure of pleural fibrosis, increased with both fibers in both sexes. In micrograms per milligram: males, 31.3 saline, 67.7 LAA, 98.5 AzA; females, 27.5 saline, 62.8 LAA, 65.6 AzA.
  • Lung collagen increased significantly with fiber treatment in male mice: 1.2 micrograms per milligram of lung in saline mice, 2.45 in LAA mice and 2.4 in AzA mice. Female control mice already had more lung collagen (2.1), and it did not increase significantly with treatment.
  • There were no significant differences between LAA and AzA in the amount of collagen in the lungs or diaphragms.
  • No tumors were found when tissues were collected.
• The authors' conclusion: The authors concluded that their data support the hypothesis that other environmental fibrous amphiboles can have effects very much like LAA, even at very low doses in mice. They said this should raise concern about exposures in southern Nevada, Arizona and other places where dust is generated.
• Limitations the authors state:
  • The fibers were not elutriated, meaning they were not sorted to keep only the respirable size range.
  • The two samples were measured with different microscopes: TEM for LAA and SEM for AzA. The SEM could not reliably measure the many tiny AzA fibers, so they were left out of the AzA measurements, which makes the fiber sizes hard to compare.

Topics

Medical terms in this study, explained in our Lexicon: Libby amphiboles, Amphibole Group, Pleural Thickening, Mineral Fiber, Environmental Exposure, Amphibole Asbestos, winchite, Actinolite.

Related studies

• Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice — M. Christofidou-Solomidou, R.A. Pietrofesa, et al. (2019)
• Libby amphibole-induced mesothelial cell autoantibodies promote collagen deposition in mice — J. Gilmer, K. Serve, et al. (2016)
• Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages — D.J. Blake, S.A. Wetzel, et al. (2008)
• Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice — A. Ferro, C.N. Zebedeo, et al. (2014)
• Evaluation of anti-nuclear antibodies and kidney pathology in Lewis rats following exposure to Libby amphibole asbestos — K.D. Salazar, C.B. Copeland, et al. (2013)
• Activation and trafficking of peritoneal B1a B-cells in response to amphibole asbestos — J.C. Pfau, K. Hurley, et al. (2014)

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