Regular articleBioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure
Introduction
Methylcyclopentadienyl manganese tricarbonyl (MMT) is one of the main sources of inorganic manganese (Mn) contamination in urban air, mainly in areas with high traffic density (Joselow et al., 1978). The main combustion products of MMT are essentially Mn-phosphate, Mn-sulfate, and a Mn-phosphate/sulfate mixture (Zayed et al., 1999). Exposure to high concentrations of atmospheric Mn can lead to adverse health outcomes, notably respiratory and neurological effects. Exposure to concentrations of >1 mg of Mn/m3 among miners and other industrial workers has been shown to persuade adverse respiratory, neurological, and reproductive effects (Iregren, 1999). The clinical syndrome of manganese neurotoxicity (manganism) can be divided into an early phase characterized by obvious mood and behavior changes, and a later stage somewhat similar to Parkinson's disease that is characterized by dystonia and severe gait disorder (Pal et al., 1999). However, little is known about the potential health effects that may result from long-term low-level exposure of populations through ambient air. Certain subpopulations such as children and patients with chronic liver disease could be more susceptible to different levels of Mn contamination.
It is clear that the route of exposure can influence the distribution, metabolism, and potential for neurotoxicity of Mn-containing compounds (Roels et al., 1997). Inhalation exposure is more efficient than ingestion at transporting Mn to the brain. Pharmacokinetic factors that may contribute to the increased efficiency of brain Mn delivery following inhalation include greater Mn absorption from the lungs and slower clearance of absorbed Mn from the circulation (Andersen et al., 1999). Moreover, inhalation exposure to soluble forms of Mn results in higher brain Mn concentration compared with insoluble form of Mn (Dorman et al., 2001). One study has shown that after intratracheal instillation, a surrogate for inhalation exposure, Mn concentrations were higher in brain following the administration of the soluble salt MnCl2, than following the administration of the insoluble oxide MnO2. Striatal Mn concentrations increased by 205% and 48% following MnCl2 and MnO2 administration, respectively (Roels et al., 1997).
The main brain target for Mn toxicity is the basal ganglia (caudate nucleus, globus pallidus, and putamen), which is involved in motricity. Disturbances of the basal ganglia can lead to unintentional contraction of the skeletal muscles, such as tremor and muscular rigidity, as in Parkinson's disease. Few studies have been conducted to describe the distribution of brain Mn following inhalation of different Mn species, the main route by which Mn intoxication occurs in workers. It seems likely that the neurotoxicity of inhaled Mn may be related to an uptake of this metal into the brain via olfactory neurons. The olfactory bulb in rats plays a significant role in the uptake of inhaled Mn and subsequent delivery to the brain (Tjälve and Henriksson, 1999). However, the route of delivery of Mn to the brain is not clear in human. The primary objective of this study is to determine the effects of subchronic exposure to an Mn phosphate/sulfate mixture on Mn tissue concentrations and locomotor activity.
Section snippets
Chemicals
Manganese phosphate/sulfate mixture, a fine crystalline powder, which includes Mn5(PO4)2(PO3(OH))24H2Ohureaulite mineral form, and manganese (II) sulfate monohydrate (MnSO4 · H2O), were obtained from Alfa Aesar (Johnson Matthey Company) and combined 50/50 (wt/wt). The chemistry of the mixture was confirmed by scanning electron microscopy (SEM) and energy dispersive x-ray spectrometry (EDS). Mn in both compounds has the same oxidation state (II). Whereas manganese sulfate is relatively water
Mn in the inhalation chamber
The average Mn concentrations obtained in this study were 34.8 ± 9.2, 290.8 ± 76.8, and 2841 ± 529 μg/m3 for target concentrations of 30, 300, and 3000 μg/m3 of Mn phosphate/sulfate mixture, respectively. Based on the cascade impactor, 80% of the Mn phosphate/sulfate mixture particles in the inhalation chamber were smaller than 1.55 μm in aerodynamic diameter (Table 1). Overall mean daily chamber temperatures ranged at 22–25°C, and relative humidity ranged at 25–40%. The results indicated that
Discussion
Different MMT combustion products are produced depending on fuel combustion and engine and catalytic converter thermodynamics. It is now well accepted that Mn is emitted from the tailpipe primarily as a mixture of Mn phosphate and Mn sulfate particles, with size ranging between 0.2 and 10 μm in aerodynamic diameters (Zayed et al., 1999). In the present study, 100% of the particles were <10 μm, while 87% were <3.5 μm.
In this study, equal weights of Mn phosphate and Mn sulfate were introduced
Acknowledgements
This research was supported by the Toxic Substances Research Initiative (TSRI), a research program managed jointly by Health Canada and Environment Canada. Additional support was provided by Dr. D. Krewski, who is the NSERC/SSHRC/McLaughlin Chair in Population Health Risk Assessment at the University of Ottawa, and G. Carrier, Chair of Risk Assessment Toxicology at the University of Montreal.
References (35)
Chronic manganese intake induces changes in the motor activity of rats
Exp. Neurol.
(1984)- et al.
Direct olfactory transport of inhaled manganese (MnCl2) to the rat braintoxicokinetic investigations in a unilateral nasal occlusion modle
Toxicol. Appl. Pharmacol.
(2000) - et al.
A synaptic mechanism underlying the behavioral abnormalities induced by manganese intoxication
Neurobiol. Dis.
(2001) - et al.
Influence of particle solubility on the delivery of inhaled manganese to the rat brainmanganese sulfate and manganese tetroxide pharmacokinetics following repeated (14 days) exposure
Toxicol. Appl. Pharmacol.
(2001) - et al.
Brain manganese concentrations in rats following tetroxide inhalation are unaffected by dietary manganese intake
Neurotoxicology
(2002) - et al.
The regional distribution and cellular localization of iron in the rat brain
Neuroscience
(1984) - et al.
Histochemical alteration in rabbit testis produced by manganese chloride
Toxicol. Appl. Pharmacol.
(1975) - et al.
Manganese induced testicular changes in monkeys
Exp. Pathol.
(1980) - et al.
Assessment of bioaccumulation, neurohistopathology and neurobehavioral following subchronic (90 days) inhalation in rats exposed to manganese phosphate
Toxicol. Appl. Pharmacol.
(2002) - et al.
Lung clearance, translocation and acute toxicity of arsenic, beryllium, cadmium, cobalt, lead, selenium, vanadium and ytterbium oxides following deposition in rat lung
Environ. Res.
(1985)
Pharmacokinetics of inhaled manganese phosphate in male Sprague-Dawley rats following subacute (14-days) exposure
Toxicol. Appl. Pharmacol.
Pharmacokinetic data needs to support risk assessments for inhales and ingested manganese
Neurotoxicology
Manganese uptake and distribution in the central nervous system
Neurotoxicology
Role of manganese in dystonia
Adv. Neurol.
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