Subacute intratracheal exposure of rats to manganese nanoparticles: behavioral, electrophysiological, and general toxicological effects.

The toxicity of manganese-containing airborne particles is an important occupational and environmental problem. In this work, adult male Wistar rats were treated with a nanosuspension of MnO(2) of approximately 23 nm nominal particle diameter, instilled into the trachea for 3, 6, and 9 wk in doses of 2.63 and 5.26 mg Mn/kg. The animals' body weight was checked weekly. At the end of treatment, the rats' spontaneous motility was tested in an open field box. Then, spontaneous and stimulus-evoked cortical activity and action potential of the tail nerve were recorded in urethane anesthesia. The rats were finally dissected, organs weights were measured, and the presence of excess Mn in lung and brain samples was determined using scanning electron microscopy with energy-dispersive x-ray spectroscopy. While control rats had normal weight gain, the body weights of the treated rats ceased to grow from wk 6 on. The relative weight of the lungs increased in the treated rats, and that of the liver decreased, in a dose- and time-dependent manner; Mn was detected in their lung and brain samples. In the open field activity, the percentage of ambulation and rearing decreased while local activity and immobility increased. The latency of the evoked potentials was lengthened, and the conduction velocity of the tail nerve decreased. These results indicate that the Mn content of instilled nanoparticles had access from the airways to the brain, and the resulting damage could be investigated in animals using neuro-functional and general toxicological endpoints.