Worker exposure to high levels of respirable dust containing crystalline silica and diesel exhaust (DE) has become a concern during hydraulic fracturing operations. The goal of the current study was to investigate the effects of acute pulmonary co-exposures to silica and DE particulate (DEP) in vivo. Doses were derived from field measures using the high point values for respirable silica, applied to a human pulmonary deposition model, and normalized to the surface area of the rat lung. The silica dose of 230 ug/rat represents 2.5 mg/m3 for 12 hr/d for 14 d. The DEP dose of 7.9 ug represents 0.1 mg/m3 for the same duration in a deposition model for total carbon (TC). A 50 ug dose of DEP was also used to represent approximately 0.6 mg/ m3 TC for the same duration. Rats were exposed by a single intratracheal instillation of sterile PBS as vehicle or one of the following doses: 7.9 ug DEP, 50 ug DEP, 230 ug silica, or silica and DEP combined for each dose of DEP. At 1 d, 1 wk, and 1 mo post-exposure, bronchoalveolar lavage (BAL) was performed on the right lungs; cells and fluid were retained to assess pulmonary injury and inflammation. Lung-associated lymph nodes (LALN) were harvested to evaluate immune responses. Silica alone caused increased inflammation and lung injury at all times post-exposure, indicated by increased neutrophil influx, oxidant production, and lactate dehydrogenase (LDH) in BAL. DEP alone caused only slight inflammation 1 d post-exposure but no effects later. At 1 wk and 1 mo after exposure, 50 ug DEP significantly increased the inflammatory effects of silica. In addition, at 1 mo, both co-exposure doses significantly enhanced the phagocyte oxidant production over silica alone. Lymphocyte counts in LALN in the co-exposures were not elevated relative to silica exposure alone. In summary, DEP alone produced relatively no pulmonary toxicity; however, DEP in a co-exposure with silica has the capability to potentiate the adverse effects of silica in the lung.
Toxicology; Air-quality; Pollutants; Pollution; Environmental-pollution; Respiration; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-system; Pulmonary-system-disorders; Pulmonary-function; Exposure-levels; Lung; Fumes; Aerosols; Laboratory-animals; Animals; Particulates; Chemical-composition; Dust-particles; Dust-exposure; Dusts; Particulates; Silica-dusts; Silicates; Workers; Work-environment; Diesel-exhausts; Diesel-emissions; Hydraulic-equipment; In-vivo-study
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona