Pharmacokinetics of Inhaled Manganese Phosphate in Male Sprague–Dawley Rats Following Subacute (14-Day) Exposure

Methylcyclopentadienyl manganese tricarbonyl (MMT) is used as a gasoline octane enhancer. Manganese phosphate is the primary respirable (PM2.5) MMT-combustion product emitted from the automobile tailpipe. The goal of this study was to determine the exposure–response relationship for inhaled manganese phosphate in adult male CD rats. Rats were exposed 6-h/day for either 5 days/week (10 exposures) or 7 days/week (14 exposures) to manganese phosphate at 0, 0.03, 0.3, or 3 mg Mn/m3 (MMAD ≅ 1.5 μm). The following tissues collected at the end of the 2-week exposure: plasma, erythrocytes, olfactory bulb, striatum, cerebellum, lung, liver, femur, and skeletal muscle (n = 6 rats/exposure group) were analyzed for manganese content by neutron activation analysis. Intravenous 54MnCl2 tracer studies were also conducted following the 14th exposure (n = 6 rats/concentration), and whole-body gamma spectrometry was performed immediately after injection and at 1, 2, 4, 8, 12, and 16 weeks after 54MnCl2 administration. Increased manganese concentrations were observed in olfactory bulb, lung, femur, and skeletal muscle following exposure to 3 mg Mn/m3 (10 or 14 exposures). Increased manganese concentrations were also observed in olfactory bulb, striatum, and lung following exposure to 0.3 mg Mn/m3 (14 exposures only). Red blood cell and plasma manganese concentrations were increased only in rats exposed to 3 mg Mn/m3 (10 exposures). Rats exposed to 3 mg Mn/m3 also had an increased whole-body manganese clearance rate when compared to air-exposed control animals. Our results suggest that the rat olfactory bulb may accumulate more manganese than other brain regions following inhalation exposure.