Manganese dichloride

Endpoint summary

Description of key information

Oral absorption is low at approximately 5% ranging from 3-13%

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

5

Absorption rate - dermal (%):

1

Absorption rate - inhalation (%):

100

Additional information

 TOXICOKINETIC ASSESSMENT

TEST MATERIAL: Manganese Dichloride (MnCl₂); (EC Number 231-869-6,
CAS Number 7773-01-5)

 

The test material, manganese dichloride, is a light pink solid and commercially significant manganese salt. It forms a variety of hydrates: anhydrous, monohydrate, dihydrate and tetrahydrate (most common). Commercial anhydrous manganese dichloride is supplied as either flakes or prills (aggregated material), both of which have a very large particle size.   

 

Absorption

 

The test material, manganese dichloride, is exceedingly soluble in water with a water solubility of 799 g/L of solution at 20.0°C (O'Connor and Butler 2009). As such, manganese dichloride would be expected to be readily bioavailable after oral administration, which for soluble manganese substances is around 5% (3-13%) in humans. Several factors influence the oral uptake of soluble manganese substances, primarily the body’s natural homeostatic regulation of manganese which includes iron status, dietary matrix, fasted status and existing body burden of manganese. After an oral dose of 50 mg of test material to humans increases in plasma manganese levels were measured, however at this dose level gastric discomfort was reported (Bales, Freeland-Graves et al. 1987). The acute oral toxic dose (LD₅₀) of the test material in the rat was estimated (95% confidence limits) to be 540 mg/kg bodyweight MnCl₂ (Vrcic and Kello 1988). As such, although the test material still has a potential for toxicity by oral absorption, a combination of good hygiene practice, its un-palatability, the body’s natural homeostatic regulation of manganese and its low orally bioavailable should limit exposure and hence toxicity in humans by this route. 

 

Particle size analysis of a sample of commercial manganese dichloride powder (prills) showed that 100% of the particles of manganese dichloride powder were > 1,410 µm diameter and approximately 70% greater than 2,000 µm diameter. As such, commercial manganese dichloride powder has a very low potential to be inhaled and respired due to its very large particle size. Commercial manganese dichloride is a very dense (2.54) solid with a high melting point (> 720 ± 0.5 K) with large particles and low dustiness and is not classified as a dermal irritant.

 

There has been a considerable interest in the toxicity and toxicokinetics of manganese dichloride aerosol by inhalation (Drown, Oberg et al. 1986; Tjalve, Henriksson et al. 1996; Henriksson, Tallkvist et al. 1999; Brenneman, Wong et al. 2000) primarily due to manganese being present as a combustion product from automobiles where methylcyclopentadienyl manganese tricarbonyl (MMT) is used as a fuel additive. The particle size of the manganese dichloride used in animal inhalation studies is typically around 2μm mass median aerodynamic diameters (MMAD) so as to optimise respiration of the particles and absorption by the lungs. This situation is presumably to reflect the small particle size of the manganese that is seen in automobile exhaust fumes as opposed to the commercial product of manganese dichloride where the particles are approximately 1000-fold greater. Using this small particle size for these studies means that the soluble test material is readily absorbed by the lungs and nasal mucosa and distributed around the body and is not representative of exposure to commercial manganese dichloride flakes or prills.

An in vitro OECD 428 dermal absorption study (Jaeger, 2010) estimated dermal absorption through human skin to be in the region of 1%.

With respect to absorption values to be used in risk and exposure assessments, 5% is adopted for oral absorption, 1% for dermal absorption and 100% for inhalation absoprtion.

 

Metabolism, Distribution and Excretion

 

The majority (~95%) of any test material that is ingested orally is likely to pass through the GI tract unchanged and be excreted in the faeces. 

 

When adult male rats were exposed to 0.5% manganese as MnCl₂ in their drinking water for 1, 4, or 6 weeks, the manganese concentrations in the blood, brain, liver and kidney, were highest after one week of exposure (Hietanen, Kilpio et al. 1981). The authors concluded that the results suggested an adaptation to manganese absorption during continuous exposure. The distribution of manganese in rats following repeated oral dosing of MnCl₂ (75 mg Mn/kg/day) showed the highest accumulation of manganese in the femur and the brain (Missy, Lanhers et al. 2000).

 

There has been a considerable volume of data published on the toxicokinetics of manganese dichloride, primarily due to manganese being present as a combustion product from automobiles where methylcyclopentadienyl manganese tricarbonyl (MMT) is used as a fuel additive. However, studies looking at the inhalation of an aerosol of manganese dichloride (small particle size) are not particularly relevant to the commercial manganese dichloride powder (large particle size). In a study comparing the toxicokinetics of manganese dichloride to MMT it was reported that the MMT-derived manganese displayed higher and more prolonged plasma concentration-time profiles than manganese dichloride-derived manganese following oral administration (Zheng, Kim et al. 2000).

 

In conclusion, the test material has a small potential for absorption by oral ingestion. Exposure by inhalation to the test material in as a fine particle aerosol (MMAD ~2μm) means that it is a hazard by the inhalation route in this form, whereupon it can be absorbed and widely distributed throughout the body, including the brain, where considerable scientific focus is investigating the potential of the neurotoxicity of manganese. However, the commercially available manganese dichloride has relatively large particles (70% >2,000 µm diameter) and as such is not considered to be such a potential hazard by inhalation in this form.

 

 

References

 

Bales, C. W., J. H. Freeland-Graves, et al. (1987).Plasma Uptake of Manganese - Influence of Dietary factors. Washington DC, American Chemical Society.

Brenneman, K. A., B. A. Wong, et al. (2000). "Direct olfactory transport of inhaled manganese ((54)MnCl(2)) to the rat brain: toxicokinetic investigations in a unilateral nasal occlusion model."Toxicol Appl Pharmacol169(3): 238-48.

Drown, D. B., S. G. Oberg, et al. (1986). "Pulmonary clearance of soluble and insoluble forms of manganese."J Toxicol Environ Health17(2-3): 201-12.

Henriksson, J., J. Tallkvist, et al. (1999). "Transport of manganese via the olfactory pathway in rats: dosage dependency of the uptake and subcellular distribution of the metal in the olfactory epithelium and the brain."Toxicol Appl Pharmacol156(2): 119-28.

Hietanen, E., J. Kilpio, et al. (1981). "Neurochemical and biotransformational enzyme responses to manganese exposure in rats."Arch Environ Contam Toxicol10(3): 339-45.

Missy, P., M. C. Lanhers, et al. (2000). "Effects of Subchronic Exposure to Manganese Chloride on Tissue Distribution of Three Essential Elements in Rats."International Journal of Toxicology19: 313-321.

O'Connor, B. and R. E. Butler (2009). MnCl2 (Eramet): Determination of Water Solubility, Harlan Laboratories Ltd.

Tjalve, H., J. Henriksson, et al. (1996). "Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats."Pharmacol Toxicol79(6): 347-56.

Vrcic, H. and D. Kello (1988). "Acute oral manganese toxicity in relation to the type of exposure."Rad Med Fak Zagrebu29(2-3): 145-148.

Zheng, W., H. Kim, et al. (2000). "Comparative toxicokinetics of manganese chloride and methylcyclopentadienyl manganese tricarbonyl (MMT) in Sprague-Dawley rats."Toxicol Sci54(2): 295-301.