INFLUENCE OF PARTICLE SURFACE-AREA ON THE TOXICITY OF INSOLUBLE MANGANESE-DIOXIDE DUSTS

The objective of this study was to examine the influence of specific s urface area on the biological activity of insoluble manganese dioxide (MnO2) particles. The biological responses to various MnO2 dusts with different specific surface area (0.16, 0.5, 17 and 62 m(2)/g) were com pared in vitro and in vivo. A mouse peritoneal macrophage model was us ed to evaluate the in vitro cytotoxic potential of the particles via l actate dehydrogenase (LDH) release. In vivo, the lung inflammatory res ponse was assessed by analysis of bronchoalveolar lavage after intratr acheal instillation in mice (LDH activity, protein concentration and c ellular recruitment). In both systems, the results show that the ampli tude of the response is dependent on the total surface area which is i n contact with the biological system, indicating that surface chemistr y phenomena are involved in the biological reactivity. Freshly ground particles with a specific surface area of 5 m(2)/g were also examined in vitro. These particles exhibited an enhanced cytotoxic activity, wh ich was almost equivalent to that of 62 m(2)/g particles, indicating t hat undefined reactive sites produced at the particle surface by mecha nical cleavage may also con tribute to the toxicity of insoluble parti cles. We conclude that, when conducting studies to elucidate the effec t of particles on the lung, it is important for insoluble particles su ch as manganese dioxide to consider the administered dose in terms of surface area (e.g. m(2)/kg) rather than in gravimetric terms (e.g. mg/ kg).