Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers.
BACKGROUND
Aluminum oxide-based nanowhiskers (AO nanowhiskers) have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols.


METHODS
Primary dimensions of AO nanowhiskers specified by manufacturer were 2-4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH)3 and AlOOH]. Male mice (C57Bl/6 J) were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure) were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL) fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines), blood (total and differential cell counts), lung histopathology and pulmonary mechanics.


RESULTS
Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt) respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p < 0.01, p < 0.001, respectively). However no neutrophilic inflammation in BAL fluid was found and neutrophils were below 1% in all groups. No significant differences were found in total protein, activity of LDH, or cytokines levels (IL-6, IFN-γ, MIP-1α, TNF-α, and MIP-2) between shams and exposed mice.


CONCLUSIONS
Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.
Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA.
Andrea
A
Adamcakova-Dodd
Larissa V
LV
Stebounova
Patrick T
PT
O'Shaughnessy
Jong Sung
JS
Kim
Vicki H
VH
Grassian
Peter S
PS
Thorne
D000280:Administration, Inhalation; D000336:Aerosols; D000537:Aluminum Oxide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D019570:Inhalation Exposure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D014018:Tissue Distribution; D018675:Toxicity Tests
D000336:Aerosols; D016207:Cytokines; D007770:L-Lactate Dehydrogenase; D000537:Aluminum Oxide