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other: Expert statement
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supporting study
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Reference
Reference Type:
other: statement report
Title:
The Bio-elution protocols cannot readily be applied to the investigation of potassium permanganate (KMnO4)
Author:
Brouwers Tony
Year:
2015
Report Date:
2015

Materials and methods

Principles of method if other than guideline:
This document describes some major difficulties that have to be faced when conducting bio-elution tests on KMnO4 according to the Standard Operating Procedures on Bio-elution that was validated during an inter-laboratory study on several metals and metal compounds.

Results and discussion

Any other information on results incl. tables

Potassium permanganate (KMnO4) is a strong oxidant (Mn+VII). It is not a common sparingly soluble metal or metal compound.

Depending on the test conditions (pH / temperature / composition of the test medium / presence of oxidizable components / redox potentials / ... ), multiple reactions with different oxidation stages and states of manganese will occur. However, the most likely and stable reaction products are, the ‘insoluble’ MnO2(Mn+IV) and the very soluble and stable Mn2+ion. Both states will fluctuate randomly together or separately one after another taking turns depending of the test conditions/study stage.

It is hard to obtain the test substance pure and completely free from manganese dioxide and or the Mn2+ion. Moreover, ordinary deionized water, used for preparing the test solutions, is likely to contain reducing substances (traces of organic matter, etc.) which will react with the potassium permanganate to form manganese dioxide. The presence of the latter is very objectionable because it catalyses the auto- decomposition of the permanganate solution on standing.

This makes the studies less accurate and not reproducible. The decomposition: 4MnO4-+ 2H2O => 4MnO2+ 3O2+ 4OH-

is catalysed by solid manganese dioxide. Permanganate is inherently unstable in the presence of manganese(II) ions:

2MnO4-+ 3Mn2++ 2H2O => 5MnO2+ 4H+;
this reaction is slow in acid solution but is very rapid in neutral solution.

Since the test item, KMnO4, is water-soluble up to 7.60g/100gH2O4, the prescribed test loadings will dissolve completely in the aqueous test media:

  • Loading for gastric studies: 0.2g test item per litre synthetic test fluid.

  • Loading for interstitial, Lysosomal, perspiration studies: 2g test item per litre synthetic test fluid.

The soluble reaction products (e.g. Mn2+) and the original test item (KMnO4) are both in solution and cannot be separated by filtration, centrifugation or any other readily applicable separation technique to allow the analysis of the ‘released’ Mn2+content. Usually, an ICP-MS/ ICP-OES or AAS apparatus is used to determine the dissolved metal fraction. However, these very accurate analytical techniques cannot distinguish different forms of a dissolved metal (MnO4-, Mn2+, ... in this case of manganese). To complicate matters, the possible reactions cannot be "halted" at the sampling point(s) (e.g. end of the test) because the reaction products cannot be quickly and quantitatively separated from the test item. The limitations of the usual analytical techniques mentioned above, will lead to the use of a “new” different, specific analytical method to measure the various components (KMnO4, Mn2+, MnO2, ...) by a set of analytical techniques. Even then, this would pose a significant challenge as the “new” different method will also determine specific requirements on sample volume, sample conservation, detection limits, measurement uncertainties, ... . Nevertheless, it is likely that the quantitative determination of a specific reaction product (like e.g. Mn2+) using this set of analytical techniques will be impossible. Due to the propagation of errors, each related to different measurement techniques for specific species or sum of species, the uncertainty of a specific reaction product as a result of the overall ‘new’ determination method will be larger than the quantity itself.

Applicant's summary and conclusion

Conclusions:
It is therefore, scientifically challenging and almost impossible to perform a reliable and reproducible bio-elution studies on potassium permanganate as described in the Standard Operating Procedure. A lot of changes to the original bio-elution protocol will be required – increasing room for error. A new investigation to set up an appropriate test- and analytical method would become very expensive especially due to the scientific challenges and will take months of research. Even then, success can still not be guaranteed.