Biological effects of inhaled hydraulic fracturing sand dust. V. Pulmonary inflammatory, cytotoxic and oxidant effects

Abstract

The pulmonary inflammatory response to inhalation exposure to a fracking sand dust (FSD 8) was investigated in a rat model. Adult male Sprague-Dawley rats were exposed by whole-body inhalation to air or an aerosol of a FSD, i.e., FSD 8, at concentrations of 10 or 30 mg/m³, 6 h/d for 4 d. The control and FSD 8-exposed rats were euthanized at post-exposure time intervals of 1, 7 or 27 d and pulmonary inflammatory, cytotoxic and oxidant responses were determined. Deposition of FSD 8 particles was detected in the lungs of all the FSD 8-exposed rats. Analysis of bronchoalveolar lavage parameters of toxicity, oxidant generation, and inflammation did not reveal any significant persistent pulmonary toxicity in the FSD 8-exposed rats. Similarly, the lung histology of the FSD 8-exposed rats showed only minimal changes in influx of macrophages following the exposure. Determination of global gene expression profiles detected statistically significant differential expressions of only six and five genes in the 10 mg/m³, 1-d post-exposure, and the 30 mg/m³, 7-d post-exposure FSD 8 groups, respectively. Taken together, data obtained from the present study demonstrated that FSD 8 inhalation exposure resulted in no statistically significant toxicity or gene expression changes in the lungs of the rats. In the absence of any information about its potential toxicity, a comprehensive rat animal model study (see Fedan, J.S., Toxicol Appl Pharmacol. 000, 000-000, 2020) has been designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems.

Keywords: Fracking sand dust; Gene expression; Inflammation; Lung; Pulmonary toxicity; Rats.

Fig. 1.

FSD 8 particles in alveolar macrophages following inhalation of 10 or 30 mg/m³. (FSD 8 is abbreviated as FSD in the figures.) AMs obtained from rats at 1, 7 and 27 d post-exposure were observed under a light microscope to detect FSD 8 particles. The cells were stained with H&E.

Fig. 2.

BALF LDH activity in rat lung. Rats were exposed to FSD 8 at 10 or 30 mg/m³. BALF LDH was determined as described in the text at post exposure intervals as indicated in the figures following the exposure.

Fig. 3.

BAL cells in rat lungs. Rats were exposed to FSD 8 at 10 or 30 mg/m³. The number of total cells in the BAL was determined at the post-exposure time intervals indicated in the figures as described in the text. The data represents the total number of cells obtained from rats at the indicated post-exposure time intervals following the exposure. AMs accounted for >97% of all cells in all groups.

Fig. 4.

BAL PMNS in rat lungs. Rats were exposed to FSD 8 at 10 or 30 mg/m³. The number of PMNs in the BAL was determined as described in the text. The data represents the total number of cells PMNs obtained from rats at the post-exposure time intervals as indicated in the figure following the exposure.

Fig. 5.

Reactive oxidant generation in the BAL cells of rats. Rats were exposed to FSD 8 at 10 or 30 mg/m³. The chemiluminisence activity was determined as described in the text at post-exposure intervals as indicated in the figure following the exposure.