While several recent reports have described the toxicity of water-soluble C60 fullerene nanoparticles, none have reported the toxicity resulting from the inhalation exposures to C60 fullerene nanoparticles or microparticles. To address this knowledge gap, we exposed male rats to C60 fullerene nanoparticles (2.22 mg/m3, 55 nm diameter) and microparticles (2.35 mg/m3, 0.93 microm diameter) for 3 h a day, for 10 consecutive days using a nose-only exposure system. Nanoparticles were created utilizing an aerosol vaporization and condensation process. Nanoparticles and microparticles were subjected to high-pressure liquid chromatography (HPLC), XRD, and scanning laser Raman spectroscopy, which cumulatively indicated no chemical modification of the C60 fullerenes occurred during the aerosol generation. At necropsy, no gross or microscopic lesions were observed in either group of C60 fullerene exposures rats. Hematology and serum chemistry results found statistically significant differences, although small in magnitude, in both exposure groups. Comparisons of bronchoalveolar (BAL) lavage fluid parameters identified a significant increase in protein concentration in rats exposed to C60 fullerene nanoparticles. BAL fluid macrophages from both exposure groups contained brown pigments, consistent with C60 fullerenes. C60 lung particle burdens were greater in nanoparticle-exposed rats than in microparticle-exposed rats. The calculated lung deposition rate and deposition fraction were 41 and 50% greater, respectively, in C60 fullerene nanoparticle-exposed group than the C60 fullerene microparticle-exposed group. Lung half-lives for C60 fullerene nanoparticles and microparticles were 26 and 29 days, respectively. In summary, this first in vivo assessment of the toxicity resulting from inhalation exposures to C60 fullerene nanoparticles and microparticles found minimal changes in the toxicological endpoints examined. Additional toxicological assessments involving longer duration inhalation exposures are needed to develop a better and more conclusive understanding of the potential toxicity of inhaled C60 fullerenes whether in nanoparticle or microparticle form.

AKR/J mice were exposed to cigarette smoke (CS) and/or lipopolysaccharide (LPS) via inhalation for 3 wk and pulmonary responses were evaluated. The objective was to explore the feasibility of coexposing LPS with cigarette smoke under a subacute exposure, as a surrogate for viral or bacterial insults, that would mimic the pathogenesis of infection-related chronic obstructive pulmonary disease (COPD) exacerbations. The study was the first step in an effort to develop a rodent COPD model in which morphologic lesions of COPD develop in a shorter period of exposure and more closely simulate human COPD. Mice were exposed 6 h/day, 5 days/wk for 3 wk to one of the following: (1) sham control: filtered air; (2) CS: 250 microg/L wet total particulate matter (WTPM) for 5 h/day followed by 1 h/day air; (3) LPS: 0.5 microg/L LPS (055:B5 Escherichia coli; 3,000,000 EU/mg) for the last 1 h/day 2 day/wk (following 5 h/day of filtered air); and (4) CS/LPS: CS 5 h/day followed by air or LPS (2 days/wk) for 1 h/day. After the last exposure, animals were necropsied and subjected to bronchoalveolar lavage (BAL) or histopathology. The BAL neutrophil counts were highest in the LPS group, while macrophage counts were higher in the CS/LPS group than other exposed groups. The LPS group displayed the greatest increases in BAL cytokines, while KC (keratinocyte-derived chemokine) and TARC (thymus and activation-regulated chemokine) were highest in the CS group. The CS/LPS group had generally lower cytokine levels relative to the LPS or CS groups, except for the levels of RANTES and G-CSF (granulocyte-colony stimulating factor) comparable to the LPS group. At microscopic examination of lung sections, cellular inflammatory infiltrates were most notable in the CS/LPS group, which had a diffuse, predominantly macrophage infiltrate with fewer neutrophils. The LPS group had predominantly neutrophils in the pulmonary infiltrate and the CS group had a predominantly macrophage infiltrate in alveolar ducts and adjacent alveoli. Apoptotic labeling of lung cells was highest with the CS/LPS group. In summary, the CS/LPS group displayed greater cellular infiltration and apoptotic responses in the lung with an indication of immunosuppressive effects (lower BAL cytokines) than the CS or LPS group, suggesting that the CS/LPS model shows promise to be further explored as an animal model for studying pathogenesis of COPD exacerbations. A longer term study with interim assessments is needed to confirm that the subacute responses observed in the CS/LPS group will result in greater severity of COPD-related pulmonary lesions following prolonged exposures.

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The acute toxicity of three obscurants was determined for nine freshwater organisms. The materials tested were white phosphorus-felt smoke, red phosphorus-butyl rubber (RP-BR) smoke, and smoke generator fue 1 (SGF) No. 2 fog oi 1 (bulk and vaporized). The chemistry of '1P-F and RP-BR smoke in water and the resulting effects on aquatic organisms are similar. Combustion of these two obscurants and their DO 1473 EDITION OF 1 NO\/

A chronic inhalation toxicity/carcinogenicity study of potassium octatitanate fibers (TISMO) was conducted in male Fischer 344 rats. Groups of 135 rats were exposed via whole-body inhalation to 0, 20, 60, or 200 WHO fibers/cc of TISMO, 6 h/day, 5 days/w for 24 mo. Six of 30 subgroup rats were killed after 3, 6, 12, 18, and 24 mo of exposure for lung burden evaluations. Another 30 subgroup rats were removed from the exposure chambers after 6 mo of exposure, placed in clean air, and from this group 6 rats were killed at 3, 6, 9, 12, and 18 mo later to study lung clearance. The remaining 75 rats in each group were subjected to 24 mo of exposure for chronic toxicity and carcinogenicity study. Rats exposed to HEPA-filtered air (chamber control) were used as a negative control in each study. The lung burden results indicated that a time point of equilibrium between lung burden and lung clearance at 20 WHO fibers/cc exposure was attained after approximately 18 mo of exposure. There was no difference in the number of WHO fiber from the lungs between 18 and 24 mo at 20 WHO fibers/cc exposure. But disproportional rapid increase in lung burden at 200 WHO fibers/cc exposure appeared to be saturation of lung clearance mechanism resulting from lung overloading. At 200 WHO fibers/cc exposure, approximately 22.9 and 70.5 million WHO fibers were retained in the lung after 3 and 6 mo of exposure, respectively, but lungs revealed normal in appearance. However, alveolar walls enclosing aggregated TISMO-laden alveolar macrophages (AMs) showed fibrotic thickening and approximately 197.3 million WHO fibers were retained in the lungs after 18 mo of exposure. Inhaled fibers were rapidly cleared during 3- and 6-mo recovery periods, and thereafter gradually progressive fiber reduction was observed throughout 18 mo of recovery. The number of WHO fibers decreased by approximately 72%, 74%, and 79% in the 200, 60, and 20 WHO fibers/cc groups, respectively, at the end of the 18-mo recovery period following 6 mo of exposure. Although inhaled TISMO fibers in the 20 WHO fibers/cc exposure group were phagocytized by alveolar macrophages (AMs) the lung morphology appeared normal throughout 24 mo of exposure. At 60 WHO fibers/cc exposure, a slight dose- and time-dependent increase in TISMO-laden AMs was observed throughout 3, 6, and 12 mo of exposure and some alveoli containing aggregated TISMO-laden AMs showed alveolar wall thickening at 18 mo of exposure and minimal alveolar fibrosis at 24 mo of exposure. The exposure concentration is interpreted as a borderline effect level. At 200 WHO fibers/cc exposure, lungs preserved normal architecture at 3 and 6 mo of exposure. Some alveolar walls enclosing aggregates of TISMO-laden AMs were slightly thickened after 12 mo of exposure and revealed slight alveolar fibrosis after 18 and 24 mo of exposure. Neither exposure related-pulmonary neoplasm nor mesothelioma was observed in 24 mo of exposure. The 20 WHO fibers/cc exposure concentration is considered to be a no-observable-adverse-effect level (NOAEL). TI...