Uptake, distribution and behavioral effects of inhalation exposure to manganese (MnO2) in the adult mouse.

Adult male mice were exposed either to sublethal levels of MnO2 dust or filtered air (control group) 7 hours/day, 5 days/week for 16 to 32 weeks. Following a 16 week initial exposure period, randomly selected samples (8 animals) from both the control and Mn-exposed groups were observed for behavioral performance (ambulations and rearings in the open-field, "hole-in-board" explorations, rotarod) and learning (passive avoidance) and tissue Mn levels were determined via atomic absorption spectrometry. Exposure continued for the remaining animals and the sampling procedure was repeated biweekly for an additional 8 time points. At week 32, Mn exposure was terminated. However, biweekly testing of the remaining animals continued for an additional 3 time points. Mn-exposed animals had significantly higher blood, liver, kidney, lung, cerebrum, cerebellum plus brainstem, and testis Mn levels than control animals. With the exception of the liver, these levels declined with increasing exposure time. No histopathologic effects attributable to Mn-exposure were observed. However, significant overall effects on growth and behavior were obtained. Specifically, Mn-exposed subjects weighed more, executed more rearings in the open-field, and tended to exhibit longer latencies to enter the open-field. When the post-exposure data were analyzed separately, no significant effects were obtained. While no general relationship was obtained between tissue Mn levels and behavior, selected behavioral measures did correlate with tissue Mn levels. Animals exposed via feeding to comparable Mn levels across the same length of exposure employed in the inhalation study did not demonstrate any significant behavioral alterations.