title: Pulmonary clearance of manganese phosphate, manganese sulfate, and manganese tetraoxide by CD rats following intratracheal instillation.
abstract: Manganese (Mn) is ubiquitous in ambient air due to both industrial and crustal sources. It is also a component of the octane-enhancing fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT). The combustion of MMT by the automobile engine results in the formation of Mn particulates including phosphate, sulfate, and oxide forms. The objectives of this study were to determine the contribution of particle dissolution on pulmonary clearance rates of Mn sulfate (MnSO(4)), Mn phosphate, and Mn tetraoxide (Mn(3)O(4)) in CD rats following an intratracheal instillation exposure. In addition, brain (striatal) Mn concentrations were evaluated following exposure. Adult CD rats were intratracheally instilled with 0, 0.04, 0.08, or 0.16 microg Mn/g of either MnSO(4), Mn phosphate, or Mn(3)O(4). Rats were euthanized at 0, 1, 3, or 14 days after instillation. Lung and striatal Mn concentrations were measured by neutron activation analysis. Pulmonary clearance following single intratracheal instillation of MnSO(4), Mn phosphate, or Mn(3)O(4) was similar for each of the three compounds at each of the three doses used. All pulmonary clearance half-times were less than 0.5 day. At the concentrations used, striatal Mn levels were unaffected, and lung pathology was unremarkable. The dissolution rate constant of the Mn particles was determined in vitro using lung simulant fluids. The solubility of the Mn compounds was in general 20 to 40 times greater in Hatch artificial lung lining fluid than in Gamble lung simulant fluid. The dissolution rate constant of the water-soluble MnSO(4) particles in Hatch artificial lung fluid containing protein was 7.5 x 10(-4) g (Mn)/cm(2)/day, which was 54 times that of relatively water-insoluble Mn phosphate and 3600 times that of Mn(3)O(4). The dissolution rate constants for these compounds were sevenfold slower in Gamble lung fluid simulant. For both solutions, the time for half the material to go into solution differed only by factors of 1/83 to 1/17 to 1 for MnSO(4), Mn phosphate, and Mn(3)O(4), respectively, consistent with measured differences in size distribution, specific surface, and dissolution rate constant. These data suggest that dissolution mechanisms only played a role in the pulmonary clearance of MnSO(4), while nonabsorptive (e.g., mechanical transport) mechanisms predominate for the less soluble phosphate and oxide forms of Mn.
authors.affiliation: Chemical Industry Institute of Toxicology, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA.
authors.forename: D
authors.initials: D
authors.lastname: Vitarella
authors.forename: O
authors.initials: O
authors.lastname: Moss
authors.forename: D C
authors.initials: DC
authors.lastname: Dorman
mesh_terms: D000393:Air Pollutants; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019570:Inhalation Exposure; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D010087:Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D012995:Solubility; D013431:Sulfates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D000393:Air Pollutants; D017895:Manganese Compounds; D009942:Organometallic Compounds; D010087:Oxides; D013431:Sulfates; C027424:manganese oxide; C406182:manganese phosphate; C039798:manganese sulfate