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 (PM(2.5)) 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/m(3) (MMAD congruent with 1.5 micrometer). 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 (54)MnCl(2) 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 (54)MnCl(2) administration. Increased manganese concentrations were observed in olfactory bulb, lung, femur, and skeletal muscle following exposure to 3 mg Mn/m(3) (10 or 14 exposures). Increased manganese concentrations were also observed in olfactory bulb, striatum, 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) 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.

[1]  E. J. Massaro,et al.  Uptake, distribution and behavioral effects of inhalation exposure to manganese (MnO2) in the adult mouse. , 1985, Neurotoxicology.

[2]  N. Chu,et al.  Manganism and idiopathic parkinsonism , 1994, Neurology.

[3]  K. Arimura,et al.  Manganese intoxication during total parenteral nutrition: report of two cases and review of the literature , 1999, Journal of the Neurological Sciences.

[4]  L. L. Piper,et al.  Estimating distributions of long-term particulate matter and manganese exposures for residents of Toronto, Canada , 1999 .

[5]  A Mutti,et al.  Peripheral biomarkers and exposure to manganese. , 1999, Neurotoxicology.

[6]  I. H. Tipton,et al.  Essential trace metals in man: manganese. A study in homeostasis. , 1966, Journal of chronic diseases.

[7]  G. C. Cotzias,et al.  Dependence of manganese turnover on intake. , 1966, The American journal of physiology.

[8]  J. Wong,et al.  Manganese speciation in exhaust particulates of automobiles using MMT-containing gasoline. , 1999, Journal of synchrotron radiation.

[9]  G C Cotzias,et al.  Chronic manganese poisoning Clearance of tissue manganese concentrations with persistence of the neurological picture , 1968, Neurology.

[10]  G. Oberdörster,et al.  Kinetics of inhaled 54MnCl2 aerosols: influence of inhaled concentration. , 1989, Polish journal of occupational medicine.

[11]  M Aschner,et al.  Manganese uptake and distribution in the central nervous system (CNS). , 1999, Neurotoxicology.

[12]  R. Ingels,et al.  Origins of manganese in air particulates in California. , 1988, JAPCA.

[13]  J. Swenberg,et al.  Comparative morphometry of the nasal cavity in rats and mice. , 1982, Journal of anatomy.

[14]  J. Morris,et al.  Accumulation of manganese in rat brain following intranasal administration. , 1997, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[15]  G D Pfeifer,et al.  Environmental effects and exposures to manganese from use of methylcyclopentadienyl manganese tricarbonyl (MMT) in gasoline. , 1999, Neurotoxicology.

[16]  Division on Earth.  Guide for the Care and Use of Laboratory Animals , 1996 .

[17]  A. Iregren,et al.  Manganese neurotoxicity in industrial exposures: proof of effects, critical exposure level, and sensitive tests. , 1999, Neurotoxicology.

[18]  Furchner Je,et al.  Comparative metabolism of radionuclides in mammals. 3. retention of manganese-54 in the mouse, rat, monkey and dog. , 1966 .

[19]  J. Zayed,et al.  Airborne manganese particulates and methylcyclopentadienyl manganese tricarbonyl (MMT) at selected outdoor sites in Montreal. , 1999, Neurotoxicology.

[20]  G. D. Pfeifer,et al.  Particulate matter and manganese exposures in Toronto, Canada , 1999 .

[21]  M. Andersen,et al.  Pharmacokinetic data needs to support risk assessments for inhaled and ingested manganese. , 1999, Neurotoxicology.

[22]  S. Miller,et al.  Role of liver in regulating distribution and excretion of manganese. , 1966, The American journal of physiology.

[23]  J. Zayed,et al.  Environmental contamination and human exposure to airborne total and respirable manganese in Montreal. , 1997, Journal of the Air & Waste Management Association.

[24]  G. L’espérance,et al.  Characterization of Manganese-Containing Particles Collected from the Exhaust Emissions of Automobiles Running with MMT Additive , 1999 .

[25]  R. Cattley,et al.  Manganese-induced developmental neurotoxicity in the CD rat: is oxidative damage a mechanism of action? , 1999, Neurotoxicology.

[26]  Yung-sung Cheng,et al.  Inhalation Exposure Systems , 1995 .

[27]  C. E. Ulrich,et al.  Evaluation of the chronic inhalation toxicity of a manganese oxide aerosol. III. Pulmonary function, electromyograms, limb tremor, and tissue manganese data. , 1979, American Industrial Hygiene Association journal.

[28]  Leon Shargel,et al.  Applied biopharmaceutics and pharmacokinetics , 1980 .

[29]  D. Lison,et al.  Influence of the route of administration and the chemical form (MnCl2, MnO2) on the absorption and cerebral distribution of manganese in rats , 1997, Archives of Toxicology.

[30]  Air pollution emission profiles of toxic and trace elements from energy related sources: status and needs. , 1983 .

[31]  D B Calne,et al.  Manganese neurotoxicity: a review of clinical features, imaging and pathology. , 1999, Neurotoxicology.

[32]  D. Gardner,et al.  Acute exposure of laboratory mice to manganese oxide. , 1980, American Industrial Hygiene Association journal.

[33]  A. Scheuhammer,et al.  The influence of manganese on the distribution of essential trace elements. II. The tissue distribution of manganese, magnesium, zinc, iron, and copper in rats after chronic manganese exposure. , 1983, Journal of toxicology and environmental health.

[34]  J. Henriksson,et al.  Uptake of metals in the brain via olfactory pathways. , 1999, Neurotoxicology.

[35]  Rogene F. Henderson,et al.  Concepts In Inhalation Toxicology , 1995 .

[36]  J. Mahoney,et al.  Studies on manganese. 3. The biological half-life of radiomanganese in man and factors which affect this half-life. , 1968, The Journal of clinical investigation.

[37]  M C Newland,et al.  Animal models of manganese's neurotoxicity. , 1999, Neurotoxicology.

[38]  B S Larsson,et al.  Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. , 1996, Pharmacology & toxicology.