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BASIC SUMMARY OF TOXICOKINETICS: MANGANESE BIS(DIHYDROGEN PHOSPHATE)

Absorption, metabolism and distribution

Manganese is an essential element that is found in most diets. In humans, manganese is homeostatically regulated to maintain stable tissue levels of manganese through the regulation of gastrointestinal absorption and hepatobiliary excretion. In addition, manganese is a normal component of human and animal tissues and fluids.

The solubility of manganese bis(dihydrogen phosphate) has been found to be 630 g/l of solution at 20.0 ± 0.5°C in un-buffered glass double-distilled water, resulting in sample solution pH’s of approximately 1.7 to 2.1 (Bulter R, 2010) and therefore the material is considered to be very soluble.  As such, the manganese is expected to be readily bioavailable after oral administration.

Several factors are known to influence the oral uptake of soluble manganese substances, including iron status, dietary matrix, fasting status and existing body burden of manganese. The LD50 of manganese bis(dihydrogen phosphate) has been determined to be >2,000 mg/kg bw (Bradshaw J, 2012) and therefore it can be considered that the material has a low potential for toxicity via the oral route. The majority of any test material that is ingested orally is likely to pass through the GI tract unchanged and be excreted in the faeces as absorption across the gastrointestinal tract in humans is considered to average between 3-5%,1 thus further supporting the conclusion that the test material has a small potential for absorption by oral ingestion.

The test material is not a considered to be a skin irritant (Warren N, 2013) and absorption via the dermal route is considered to be unfavourable as manganese is not considered to penetrate the skin readily.

 Particle size analysis of a sample manganese bis(dihydrogen phosphate) powder showed that less than 2% of the particles were greater than 100 µm diameter. As such manganese bis(dihydrogen phosphate) has a low potential to be inhaled and respired due to its particle size distribution, however in situations where the material may be ground or processed inhalation could occur. Tissue manganese concentrations following inhalation exposure of various inorganic forms of manganese have been extensively studied. It has been reported that inhalation exposure to soluble forms of manganese results in higher brain manganese concentrations than those achieved following exposure to an insoluble form of manganese.

Much research has been performed to investigate the effects of inhalation of manganese substances and it has been concluded that soluble inorganic Mn2+ containing substances are likely to result in neurotoxicity when inhaled. Fine powders (MMAD ca. 2μm), can be absorbed and widely distributed throughout the body, including the brain.

 

Excretion

In humans, absorbed manganese is removed from the blood by the liver where it conjugates with bile and is excreted into the intestine. Biliary secretion is the main pathway by which manganese reaches the intestines where most of the element is excreted in the faeces. However, some of the manganese in the intestine is reabsorbed through enterohepatic circulation.1

 

 

 

1.    TOXICOLOGICAL PROFILE FOR MANGANESE. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. Public Health Service Agency for Toxic Substances and Disease Registry. September 2012