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TOXICOKINETIC ASSESSMENT

 

TEST MATERIAL: Manganese Dinitrate (Mn(NO3)2); (EC Number 233-828-8,
CAS Number 10377-66-9)

 

The test material, manganese dinitrate, is a white crystalline solid with a melting point of 37 °C and can decompose at high temperatures (> 100 °C) to form manganese dioxide and nitrogen oxides. When present as the anhydrous salt it is very reactive and may explode when mixed with urea upon heating. It forms a variety of hydrates: monohydrate, trihydrate, tetrahydrate and hexahydrate, with the tetrahydrate being the most common commercial form. Commercially, it is commonly supplied as a ~50% aqueous solution and a ~50% aqueous solution with 5% nitric acid. 

 

Absorption

 

The test material, manganese dinitrate, is exceedingly soluble in water. As such, manganese dinitrate 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, including iron status, dietary matrix, fasted status and existing body burden of manganese. Once dissolved in water, the soluble Mn2+and NO3-ions are formed. After an oral dose of 50 mg of another soluble manganese substance to humans, increases in plasma manganese levels were measured, however at this dose level gastric discomfort was reported(Bales et al. 1987). The acute oral median lethal dose (LD50) of another Mn2+substance (MnSO4) in the mouse and rat was estimated to be greater than 2000 mg/kg bodyweight(Singh and Junnarkar 1991). However, the presence of the NO3-ions at high concentrations are likely to be a considerable irritant to the stomach lining, as large oral doses of nitrates are reported to cause dizziness, abdominal pain, vomiting, bloody diarrhoea, weakness, convulsions, and collapse in humans. As such, the determination of the acute oral toxicity of the test material is not likely to be possible due to the local irritancy effect of the test material on the stomach lining. Although the test material is orally bioavailable, it still has a low potential for systemic toxicity by oral absorption and good hygiene practice should limit exposure. The test material is reported as being a skin irritant and it may have some potential for skin absorption due to its deliquescent nature.

 

Since the test material is readily soluble in water, its uptake from the lungs would be expected to be similar to other soluble manganese substances.  

 

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. 

 

In conclusion, the test material has a small potential for absorption by oral ingestion, although it has a low potential for systemic toxicity by this route. It may have some potential for skin absorption due to its deliquescent nature. There is a lack of information on the inhalation of the test material.

 

 

 

 

References

 

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

Singh, P. P. and A. Y. Junnarkar (1991). "Behavioural and toxic profile of some essential trace metal salts in mice and rats."Indian Journal of Pharmacology23(3): 153-159.