Sodium permanganate

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please see the read across justification.

Reason / purpose for cross-reference:

read-across source

Toxicokinetic parameters:

other: Not specified

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: review

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Review of literature data

Objective of study:

toxicokinetics

Qualifier:

no guideline available

Principles of method if other than guideline:

Literature review

GLP compliance:

no

Remarks:

Literature review

Radiolabelling:

no

Species:

other: various

Strain:

other: Various

Details on test animals or test system and environmental conditions:

Not provided

Route of administration:

other: various

Details on absorption:

Manganese is required by the body and is found in virtually all diets. Adults consume between 0.7 and 10.9 mg of manganese per day in the diet, with higher intakes for vegetarians who may consume a larger proportion of manganese-rich nuts, grains, and legumes than non-vegetarians. Manganese intake from drinking water is substantially lower than intake from food. Exposure to manganese from air is considered negligible as compared to intake from diet, although persons in certain occupations may be exposed to much higher levels than the general public. Even though daily dietary intake of manganese can vary substantially, adult humans generally maintain stable tissue levels of manganese through the regulation of gastrointestinal absorption and hepatobiliary excretion. Following inhalation exposure, manganese can be transported into olfactory or trigeminal presynaptic nerve endings in the nasal mucosa with subsequent delivery to the brain, across pulmonary epithelial linings into blood or lymph fluids, or across gastrointestinal epithelial linings into blood after mucociliary elevator clearance from the respiratory tract

Details on distribution in tissues:

Manganese is found in the brain and all other mammalian tissues, with some tissues showing higher accumulations of manganese than others. For example, liver, pancreas, and kidney usually have higher manganese concentrations than other tissues.

Details on excretion:

The principal route of elimination of manganese from the body is fecal elimination via hepatobiliary excretion; contributions from pancreatic, urinary, and lactational elimination are expected to be small. Excess manganese is expected to be eliminated from the body rapidly. For example, following the intravenous bolus injection of manganese chloride in rats, manganese concentrations in plasma return to normal levels within 12 hours

Toxicokinetic parameters:

other: Not specified

Metabolites identified:

yes

Details on metabolites:

Follwoing oral exposure, it is likely that permanganate is converted to Mn (II) in the acidic conditions of the stomach.

Absorption

Following inhalation exposure, absorption from the lung is predicted as sodium permanganate is soluble. Studies with manganese salts have shown that absorption can occur via the trigeminal and olfactory nerves. Absorption from the gastrointestinal tract is variable but low (3 -5%) and is influenced by iron status and age. One of the key determinants of absorption appears to be dietary iron intake, with low iron levels leading to increased manganese absorption. Studies of oral absorption of manganese in animals have yielded results that are generally similar to those in humans. Dermal absorption is likely to be extremely limited, excpet in cases where exposure to corrosive forms such as permanganate disrupts the integrity of the skin barrier. Therefore in accidental exposure involving skin burns, dermal absorption may be significanlt greater.

Distribution

Manganese is a normal component of human and animal tissues and fluids. In humans, most tissue concentrations range between 0.1 and 1 μg manganese/g wet weight with the highest levels in the liver, pancreas, and kidney and the lowest levels in bone and fat. Inhaled manganese may be transported directly to the brain via the trigeminal and olfactory nerves.

Metabolism

Sodium permanganate is not metabolised per se, however it is predicted that it will react to form manganese salts in a physiological environment.

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. Small amounts of manganese can also be found in urine, sweat, and milk.

Conclusions:

Interpretation of results: No bioaccumulation potential based on study results
The toxicokinetic properties of various forms of manganese are well characterised and are relevant to sodium permanganate.

Executive summary:

The ATSDR document reviews and summarises the available data on the toxicokinetics of manganese compounds, including permanganate. Absorption is likely to be significant from the respiratory tract, low from the gastrointestinal tract and negligible through the skin. Manganese is an essential element and is well distributed in the body, however there is evidence that inhaled forms may distribute directly to the brain via the olfactory and trigeminal nerves. Excretion is primarily in the bile.

Description of key information

Absorption is likley to be significant from the respiratory tract, low from the gastrointestinal tract and neglibible through the skin.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

5

Absorption rate - dermal (%):

1

Absorption rate - inhalation (%):

100

Additional information

No experimental studies of the absorption, distribution, metabolism or elimination of the registered substance, sodium permanganate (CAS Number 10101-50-5, EC Number 233-251-1) in mammals are available. However, the physical chemical properties of the substance as well as the existing data on following inorganic manganese (Mn) compounds, have been used to infer as far as possible, its potential toxicokinetic behaviour. In addition to the registered substance, relevant information available for the following three source substances were used to supplement the toxicokinetic assessment for sodium permanganate.

•       Manganese (II) sulfate monohydrate (CAS Number 10034-96-5)

•       Manganese dichloride (CAS Number 7773-01-5, EC Number 231-869-6)

The toxicokinetic properties of manganese compounds, including permanganase (ATSDR, 2008), are well-characterised and are relevant to sodium permanganate.

Sodium permanganate is a mono-constituent inorganic dark violet odorless ionic salt. It is an inorganic manganese compound. It has molecular weight of 159 g/mol and water solubility of 1440 g/L at 20˚C. Sodium permanganate decomposes at a relatively low temperature and it can therefore be concluded that the vapor pressure of the solid is not measurable without decomposing the substance.

 

Absorption

Oral

The molecular weight of sodium permanganate is in the favorable range for oral absorption. Despite its high water solubility (1440 g/L at 20˚C), its low molecular weight (< 200 g/mol) may allow the molecule to pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water.

Data for manganese (ATSDR, 2008) indicate that absorption across the gastrointestinal tract is variable, but typically averages 3-5%. Oral absorption is influenced by iron status and age of the human subject. One of the key determinants of absorption appears to be dietary iron intake, with low iron levels leading to increased manganese absorption. Studies of oral absorption of manganese in animals have yielded results that are generally similar to those in humans.

Therefore, absorption rate of 3-5% is assumed for sodium permanganate following oral exposure.

There are no oral data for sodium permanganate. Effects, indicative of systemic toxicity, were demonstrated by the oral data (carcinogenicity, repeated dose toxicity) for the source substance, manganese (II) sulfate monohydrate. Therefore, indicating that some absorption takes place following administration of inorganic Mn compounds.

Inhalation

Following inhalation exposure, absorption is expected as sodium permanganate is water soluble (1440 g/L at 20˚C).

Data with manganese salts (ATSDR, 2008) have shown that absorption can occur via the trigeminal and olfactory nerves.

Therefore, as a worst-case scenario, inhalation absorption of 100% is assumed for sodium permanganate.

There are no inhalation data for the substance sodium permanganate. However, there are two-generation reproductive toxicity and prenatal developmental toxicity studies in rats for the source substance, manganese dichloride, which is also water soluble (799 g/L at 20˚C). Bioanalysis incorporated in the two-generation study shows the absorption of manganese content in the blood in the rat. Signs of absorption following exposure to aerosol of manganese dichloride are also seen as systemic effects, although they may be considered to be associated with local reaction in the respiratory tract.  

Dermal

Since sodium permanganate is solid, in order for dermal absorption to occur, it will have to be dissolved into the surface moisture of the skin before skin uptake can begin. Furthermore, due to its high water solubility (< 10000 mg/L), sodium permanganate may be too hydrophilic to cross the lipid rich stratum corneum of the skin. Therefore, dermal uptake through intact skin is expected to be low. This is also supported by the conclusion that manganese uptake across intact skin would be expected to be extremely limited (ATSDR, 2008). It should be noted, however, that sodium permanganate is corrosive to skin which can disrupt the integrity of the skin barrier.

There are no dermal data for the target substance sodium permanganate.

Distribution

Once absorbed, sodium permanganate is expected to behave similarly to manganese (Mn).

Manganese is a normal component of human and animal tissues and fluids. In humans, most tissue concentrations range between 0.1 and 1 μg manganese/g wet weight with the highest levels in the liver, pancreas, and kidney and the lowest levels in bone and fat. Inhaled manganese may be transported directly to the brain via the trigeminal and olfactory nerves (ATSDR, 2008).

 

Metabolism

Sodium permanganate is not metabolised. However, following absorption, its behavior is determined by the local physiological conditions, triggering multiple reactions resulting into manganese salts.

Excretion

Since sodium permanganate is converted to manganese salts under physiological conditions, the excretion pathway for manganese is relevant to sodium permanganate. 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 feces. However, some of the manganese in the intestine is reabsorbed through enterohepatic circulation. Small amounts of manganese can also be found in urine, sweat, and milk (ATSDR, 2008).