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TEST MATERIAL: Trimanganese Tetraoxide (Mn3O4); (EC Number 215-266-5, CAS Number 1317-35-7)

The test material, trimanganese tetraoxide, occurs naturally as the mineral Hausmannite. It is a red/brown crystalline powder and particle size analysis has shown that over 10% of the particles were smaller than 100 µm diameter. In this test material, Mn exists in two oxidation states of +2 and +3 and as such the chemical formula is sometimes written as MnO.Mn2O3.

Absorption

The test material, trimanganese tetraoxide, has a low water solubility of 5.6 x 10-4g/L of manganese in solution at 20.0°C, which is equivalent to 7.9 x 10-4g/L of the test material in solution at 20.0oC based on the manganese content of the test material (Butler and White 2009). The test material also has an extremely low solubility (0.00005%) in artificial alveolar fluid based upon the extractable manganese (Anderson 2009). As the test material had greater than 81% of particles diameter 4 µm or less, it was subjected to an acute inhalation toxicity (nose only) study in the rat (Griffiths 2010). In order to facilitate aerosolisation and reduce particle size, the test material was ground using a centrifugal ball mill prior to use. A group of 10 rats were exposed to a mean atmosphere concentration of 5.17 mg/L test material with a mean mass median aerodynamic diameter of 2.69 µm. The results concluded that the acute inhalation median lethal concentration (4 hr LC50) of trimanganese tetraoxide was greater than 5.17 mg/L in the rat. As such, although trimanganese tetraoxide has the potential to be inhaled due to its particle size distribution, it doesn’t exhibit acute inhalation toxicity at a high dose in the rat. Since the test material has exceedingly low solubility (0.00005%) in artificial alveolar fluid it is likely that most of the inhaled test material was not absorbed but instead was cleared from the lungs by the mucocilliary elevator into the gastrointestinal (GI) tract.

Trimanganese tetraoxide has limited solubility (13±3.2%) in artificial gastric juice (Anderson 2009). As the oral absorption of even soluble manganese salts is still relatively low, typically less than 5%, this means that trimanganese tetraoxide has a relatively low potential for substantial oral absorption ( ≤ 5%). The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was demonstrated to be greater than 2000 mg/kg bodyweight (Pooles 2010). As such the test material has a very low potential for acute toxicity by oral absorption. As the test material has a low solubility in water coupled with its physical inorganic nature (crystalline powder) means that it is very unlikely to be absorbed through the skin.

In conclusion, the test material has a low potential for any absorption by oral ingestion, inhalation or dermal absorption.

Metabolism, Distribution and Excretion

Since the test material has a low potential for absorption by any route it means that the test material will not be readily bioavailable. The majority of excess test material that is ingested orally is likely to pass through the GI tract unchanged and be excreted in the faeces. Any small amount of manganese from the test material that is absorbed by the gut will enter the essential manganese pool along with that which is absorbed from the daily nutritional supply of manganese; manganese itself is an essential element, and the typical daily manganese intake from dietary sources is estimated to be in the range of 2-9 mg (Goyer & Clarkson, 2001). Manganese is transported in plasma bound to a β1-globulin thought to be transferrin. Manganese is an essential cofactor in certain enzymatic reactions, so concentrates in mitochondria (Goyer & Clarkson, 2001); hence must be assumed to be widely distributed. The circulating amount of manganese will be controlled by the normal homeostatic mechanism provided by the liver that controls the manganese balance; manganese is eliminated in bile with a half-life in the (human) body of 37 days. Any test material that is inhaled is likely to be primarily cleared from the lungs by the mucocilliary elevator into the GI tract and again excreted unchanged in the faeces.

Further information

A comprehensive toxicokinetic assessment has been made on manganese and its inorganic compounds, the full report is attached to this endpoint summary (Bounds 2009).

References

Anderson, K. A. (2009). Bioaccessibility of manganese from manganese Materials in Gastric and Lung (Alveolar) Biofluids, Oregon State University.

Bounds, S.V.J (2009). A toxicokinetic assessment for the Registration, Evaluation and Authorisation of Chemicals, Regulation (EC) No. 1907/2006 (REACH), Manganese and it inorganic compounds, Bounds Consulting Ltd.

Butler, R. E. and D. F. White (2009). Mn3O4(Erachem/Eramet): Determination of Water Solubility. Project Number 2702/0003, Harlan Laboratories Ltd.

Goyer, R.A. and Clarkson, T.W. (2001) Toxic Effects of Metals (in) Klaassen,CD (Ed) Cassarett and Doull’s Toxicology: The basic science of poisons. 6th Edn. McGraw Hill, New York.

Griffiths, D. R. (2010). Mn3O4: Acute inhalation Toxicity (Nose Only) Study in the Rat. Project Number 2702/0141, Harlan Laboratories Ltd.

Pooles, A. (2010). Mn3O4(Erachem): Acute Oral Toxicity in the rat - Fixed Dose Method. Project Number 2702/0091, Harlan Laboratories Ltd.

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