Pharmacokinetics of inhaled manganese phosphate in male Sprague-Dawley rats following subacute (14-day) exposure

Methylcyclopentadienyl manganese tricarbonyl (MMT) is used as a gasoline oc tane enhancer. Manganese phosphate is the primary respirable (PM2.5) MMT-co mbustion product emitted from the automobile tailpipe. The goal of this stu dy was to determine the exposure-response relationship for inhaled manganes e phosphate in adult male CD rats. Rats were exposed 6-h/day for either 5 d ays/week (10 exposures) or 7 days/week (14 exposures) to manganese phosphat e at 0, 0.03, 0.3, or 3 mg Mn/m(3) (MMAD congruent to 1.5 mu m), The follow ing tissues collected at the end of the 2-week exposure: plasma, erythrocyt es, olfactory bulb, striatum, cerebellum, lung, liver, femur, and skeletal muscle (n = 6 rats/exposure group) were analyzed for manganese content by n eutron activation analysis. Intravenous (MnCl2)-Mn-54 tracer studies were a lso conducted following the 14th exposure (n = 6 rats/concentration), and w hole-body gamma spectrometry was performed immediately after injection and at 1, 2, 4, 8, 12, and 16 weeks after (MnCl2)-Mn-54 administration. Increas ed manganese concentrations were observed in olfactory bulb, lung, femur, a nd skeletal muscle following exposure to 3 mg Mn/m(3) (10 or 14 exposures). Increased manganese concentrations were also observed in olfactory bulb, s triatum, and lung following exposure to 0.3 mg Mn/m(3) (14 exposures only). Red blood cell and plasma manganese concentrations were increased only in rats exposed to 3 mg Mn/m(3) (10 exposures). Rats exposed to 3 mg Mn/m(3) a lso had an increased whole-body manganese clearance rate when compared to a ir-exposed control animals. Our results suggest that the rat olfactory bulb may accumulate more manganese than other brain regions following inhalatio n exposure. (C) 2000 Academic Press.