Natural mineral fibers: conducting inhalation toxicology studies—part B: development of a nose-only exposure system for repeat-exposure in vivo study of Libby amphibole aerosol

Abstract

Background

Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber.

Results

The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m³. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material.

Conclusion

The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.

Keywords:

• Asbestos
• Libby amphibole
• fiber
• aerosol generation
• inhalation toxicology

Author contributions

AW and AG designed and supervised the experimental work and MG and DP executed the experiments. BE and RR conducted the TEM with SAED and EDS analysis. JR and JS coordinated the TEM samples collection and interpreted the data. AW drafted the manuscript and PLY wrote the ‘Background’ section. BS, KE, GR, PLY, and MS supervised the work and critically reviewed and revised the manuscript. The manuscript was written through contributions of all authors. All authors read and approved the final manuscript.

Ethical approval

Not applicable.

Consent form

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The dataset supporting the conclusions of this article is included within the article.

Additional information

Funding

This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS), Intramural Research projects ES103316- 05 and ES103374, and NIEHS Contract HHSN273201400015C (Battelle Memorial Research Institute, Columbus, OH).]