Orthoperiodic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

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

Adequacy of study:

supporting study

Justification for type of information:

Read-across to structurally similar substance sodium periodate (CAS 7790-28-5). Sodium periodate is the sodium salt of periodic acid.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

3 July 2012 to 24 August 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

A GLP study conducted to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data. Some of the analytical techniques employed were not conclusive.

Objective of study:

other: Gastric hydrolysis

Qualifier:

equivalent or similar to guideline

Guideline:

other: Guideline 111 (Hydrolysis as a Function of pH)

Qualifier:

equivalent or similar to guideline

Guideline:

other: EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Principles of method if other than guideline:

Gastric hydrolysis of the test material was investigated using a procedure based on EU Method C.7 and OECD 111. During the study, the test material was dissolved in either Fasted State Simulated Gastric Fluid (FaSSGF), or Fed State Simulated Gastric Fluid (FeSSGF), in the dark at body temperature. The concentration of the test material was determined as a function of time. Furthermore, the quantities, and nature of the decomposition products, was investigated.

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Details on exposure:

PREPARATION OF SOLUTIONS
Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 5.0 g/L in the two test media (pre-warmed to 38 °C). The test solutions were split into individual vessels for each data point. The solutions were shielded from light whilst maintained at the test temperature. The sample solutions were maintained at 38.0 ± 0.5 °C for a period of at least 0.75 hours.

Dose / conc.:

5 other: g/L (nominal conc.)

Type:

other: Gastric hydrolysis

Results:

the test material quickly degraded in both the fasted and fed state simulated gastric simulations solutions. The half-life of the test material in fasted and fed state simulated gastric fluids was significantly less than 1 hour 38.0 ± 0.5 °C

Key result

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: < 1 hour at 28 ± 0.5 °C

Metabolites identified:

no

- Definitive Test

The test material concentrations at the given time points are given in the following table:

Fasted state
Time (hours)	conc (g/L) NaIO4		% NaIO4 of "weighed-out" conc.
	A	B	A	B
0	0.075	0.153	1.5	3.1
0.75	<0.005	0.014	<0.1	0.3
Fed state
Time (hours)	conc (g/L) NaIO4		% NaIO4 of "weighed-out" conc.
	A	B	A	B
0	<0.005	<0.005	<0.1	<0.1
0.75	<0.005	<0.005	<0.1	<0.1

The above results indicate that the test material was quickly degraded in both the fasted and fed state simulated gastric fluids.

Furthermore, a scientific review of the titration method used indicated that it measures the potential of the (remaining) oxidising species in the solution to convert potassium iodide into iodine, which is then titrated to the end point with the arsenate titrant. The problem with this is that the oxidising potential includes periodate (oxidation state: +7) and its degradation (reduction) product iodate (oxidation state: +5), as both species will oxidise iodide to iodine. Thus, all of the periodate will have been reduced to iodate when the oxidation potential had diminished by (7 - 5) / 7, i.e. 29 %. Consequently, as the initial and 0.75 to 1.5 hours time point samples indicated essentially no oxidising potential remaining, it is clear that all of the periodate had been reduced to (at least) iodate almost instantaneously on contact with the two test media.

Consequently, it was concluded that the half-life of the test material in both fasted and fed state simulated gastric fluids was significantly less than 1 hour at 38 °C.

- Additional Tests

Part A): On addition of the hydrochloric acid, the solution became yellow in colour. After addition of at least 15 mL of 0.05M potassium iodate titrant, the solution was still yellow in color. More importantly, the chloroform layer remained colourless throughout. An aliquot of each gastric fluid treated as the samples gave similar results, i.e. the chloroform layer remained colourless throughout the titrations. However, on adding the hydrochloric acid, the solutions did not become yellow in colour. This test was undertaken to assess whether iodine or an iodide salt had formed in the test solutions. The observations indicated a negative result.

Part B): On addition of the potassium iodide, the fasted state sample became brown in colour, whereas, the fed state supernatant turned yellow/brown in colour. This test was undertaken to assess whether there was an oxidising component in the test solutions to oxidise iodide to iodine, e.g. iodate or periodate. The result indicated there may be such a component although further test work would be required.

Part C): After addition of the silver nitrate solution, the fasted state sample became white in colour; however, after a few minutes, a precipitate formed at the bottom of the beaker and the sample had turned grey in colour with a few grey specks present. A 5 g/L potassium iodide solution treated similarly turned from a clear solution to a milky white/yellow solution. Furthermore, after approximately 30 minutes standing, the fasted state sample had become a purple coloured solution with a precipitate at the bottom of the beaker; the fed state sample had become a brown solution with large amounts of a silver coloured precipitate present; and the potassium iodide control sample had become a lime green coloured, milky opaque solution. This test was undertaken to assess whether iodide could be identified in the solutions by the presence of a yellow silver iodide precipitate, with silver (grey deposits) also being a common component. It was clear the test results were ambiguous and no clear conclusion could be drawn.

Validation

Definitive Test: The linearity of the detector response with respect to concentration was assessed over the concentration range of 1.01 x 10³ to 7.58 x 10³ mg/L. This was satisfactory with a correlation coefficient (r) of 1.000 being obtained.

Conclusions:

Interpretation of results: Periodate rapidly transforms to iodate in the stomach
Under the conditions of the study, the test material quickly degraded in both the fasted and fed state simulated gastric simulations solutions. The half-life of the test material in fasted and fed state simulated gastric fluids was determined to be significantly less than 1 hour at 38.0 ± 0.5 °C.
The definitive analytical technique used to determine the test material concentration of the initial and final reaction solutions was satisfactory in confirming the reduction of the periodate ion in both solutions.
Additional analytical techniques employed were not conclusive in proving the presence of iodate, iodide or iodine in the reacted test solutions. However, as there was essentially zero oxidising potential remaining in the degraded solutions, as well as no visible evidence of purple coloured elemental iodine in these solutions, it was considered that the periodate had been reduced all of the way down to iodide. This, however, could not be proved by the analytical techniques on hand.

Executive summary:

Gastric hydrolysis of the test material was investigated using a procedure based on EU Method C.7 and OECD 111. During the study, the test material was dissolved in either Fasted State Simulated Gastric Fluid (FaSSGF), or Fed State Simulated Gastric Fluid (FeSSGF), in the dark at body temperature. The concentration of the test material was determined as a function of time. Furthermore, the quantities, and nature of the decomposition products, was investigated.

Under the conditions of the study, the test material quickly degraded in both the fasted and fed state simulated gastric simulations solutions. The half-life of the test material in fasted and fed state simulated gastric fluids was determined to be significantly less than 1 hour at 38.0 ± 0.5 °C.

The definitive analytical technique used to determine the test material concentration of the initial and final reaction solutions was satisfactory in confirming the reduction of the periodate ion in both solutions.

Additional analytical techniques employed were not conclusive in proving the presence of iodate, iodide or iodine in the reacted test solutions. However, as there was essentially zero oxidising potential remaining in the degraded solutions, as well as no visible evidence of purple coloured elemental iodine in these solutions, it was considered that the periodate had been reduced all of the way down to iodide. This, however, could not be proved by the analytical techniques on hand.

Alternative analytical techniques would therefore be required to analyse the nature of the complex solutions. However, this was outside of the scope of the current study.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Orthoperiodic acid

EC Number:

233-937-0

EC Name:

Orthoperiodic acid

Cas Number:

10450-60-9

Molecular formula:

H5IO6

IUPAC Name:

tetrahydroxyiodous acid

Results and discussion

Any other information on results incl. tables

Interpretation of results: Periodate rapidly transforms to iodate in the stomach