Cerium vanadium tetraoxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2012-11-29 to 2012-11-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)

Version / remarks:

adopted 2006-07-19

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: ICCVAM Minimum Performance Standards: In Vitro Membrane Barrier Test Systems for Skin Corrosion, June 23, 2003

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: ICCVAM Recommended Performance Standards for in vitro Test Methods for Skin Corrosion (May 2004)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2009-03-30

Test material

Test material information

Constituent 1

Reference substance name:

Vanadium dioxide

EC Number:

234-841-1

EC Name:

Vanadium dioxide

Cas Number:

12036-21-4

Molecular formula:

VO2

IUPAC Name:

vanadium dioxide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Vanadium dioxide
- Trivial name: vanadium tetraoxide
- Physical state: darkgreen-black powder, odourless
- Storage condition of test material: at room temperature in tightly closed container (further detailed: Harlan CCR SOP SUBST.doc)

Test animals

Details on test animals or test system and environmental conditions:

Not applicable - Since this is an in vitro study there is no information on test animals.

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 500 mg of the test item was dispensed directly atop the bio-barrier.

Duration of treatment / exposure:

60 minutes

Observation period:

not applicable

Number of animals:

not applicable

Details on study design:

TEST SYSTEM
- Test kit:
The test kit (Name: Corrositex™; Supplier: Transia GmbH, 61239 Ober-Mörlen, Germany; Lot No.: CT052112) consists of a bio-barrier (collagen gel) and a chemical detection system separated by a cellulose membrane.
- Preparation of the bio-barrier:
One day prior to testing the bio-barrier matrix was prepared. The bio-barrier powder was solved in the bio-barrier diluent and heated for 20 ± 2 minutes at 68 – 70 °C in a water bath under continuous stirring. The temperature did not exceed 70 °C. The mixture was allowed to cool in the non-heated water bath for another 10 minutes. The mixture was then filled into the membrane holders (200 µL per membrane holder). Air bubbles were avoided. The filled membrane holders were sealed with parafilm and were stored at 2 – 8 °C until further use.

EXPERIMENTAL PERFORMEANCE
- Qualification Test: to test whether the test system is suitable for the test item, i.e. the test substance is detectable by the CDS, approx. 100 mg of the test item were transferred into the “Qualification Test Vial”. The vial was shaken until the solution appeared homogenous, and incubated for at least 1 minute. Afterwards, the colour change was recorded. Since a change in colour was visible in the “Qualification Test Vial”, the test item was considered to be suitable for the next step.
- Categorisation Test: approx. 100 mg of the test item were applied into the “Category A Vial” as well as into the “Category B Vial”. The vials were shaken until the solution appeared homogenous. After at least 1 minute the colour change was recorded.
Based on the observed colour change, a test item is assigned to a category. If an intense colour change (similar to the category 1 colour chart) is observed in “Category A Vial” or in “Category B Vial” the test item is assigned to category 1. If a less intense colour change (similar to the category 2 colour chart) is observed in “Category A Vial” or in “Category B Vial” the test item will be assigned to category 2. If a colour change is not observed in either of the vials, a confirmation test is conducted. For the confirmation test two drops of the confirm reagent are added to the “Category B Vial”. The vial would be shaken for 5 seconds. The colour of the solution would match one of the colours shown in the accompanying colour chart, confirming that the test item is a category 2 substance.
- Classification Test: 7 vials containing the CDS were acclimated at room temperature. A total of 4 vials was used for quadruplicate measurements of the test item, one vial was used as positive control (single measurement), and one vial was used as negative control (single measurement). One vial was used as colour reference for the CDS.
The prepared bio-barriers were placed on top of the CDS vials (not longer than 2 minutes prior to an application) and approx. 500 mg of the test item or 500 µL of the respective controls (positive control: sulfuric acid 95-97% (lot no. K40281631 929, Merck, 64295 Darmstadt, Germany); negative control: citric acid (lot no. 140986235008107, Sigma, 89555 Steinheim, Germany, 10% (w/v) solution in deionised water)) were applied per bio-barrier for 1 hour or 4 hours, depending on the results of the categorisation test. The time of the first colour change or precipitation in the CDS solution, i.e. bio-barrier penetration, was recorded.

INTERPRETATION OF THE RESULTS
Each vial was monitored for 60 minutes or 240 minutes depending on the results of the classification test, and the time of the first observable change in the CDS solution was recorded. The elapsed time between application and penetration of the bio-barrier was determined, and the mean of the quadruplicate measurements was calculated. The test item was categorised according to the criteria in table 1, which can be seen in the field "Any other information on materials and methods incl. tables" below.

ACCEPTABILITY OF THE ASSAY
The results are considered as valid if the following acceptance criteria are met:
The test item induces a physical change (colour or precipitation) in the CDS solution in the qualification test.
The negative control does not induce a physical change (colour or precipitation) < 60 minutes in the CDS solution in the classification test.
The positive control induces a physical change (colour or precipitation) in the CDS solution in the classification test after 0 – 3 minutes.

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

other: other: time interval of colour change of CDS reagent after treatment of bio-barrier

Value:

0

Remarks on result:

other:

Remarks:

Basis: other: minutes (mean of 4 replicates). Time point: after 60 minutes of treatment. (migrated information)

Any other information on results incl. tables

HISTORICAL DATA:

Table: Historical range of breakthrough times for the positive control

Historical mean time of first colour change of positive control [minutes]	1.31
Standard deviation [minutes]	0.45

Data of 46 studies performed at Harlan CCR from 2006 until 2012.

QUALIFICATION TEST:

The test item induced a change in colour in the qualification test after 1 minute of incubation. Since a change in colour was visible in the “Qualification Test Vial”, the test item was thus detected by the CDS and considered suitable for the next step.

CATEGORISATION TEST:

The test item induced a colour change in the Category A vial and in the Category B vial after 1 minute of incubation. According to the colour scheme, the test item does not appear to be a strong acid or base and was assigned to category 2. It was concluded that the required duration of the classification test was 60 minutes.

CLASSIFICATION TEST:

The negative control did not induce a change in the colour of the CDS reagent over 60 minutes. The positive control showed a distinct change in the colour of the CDS reagent in the time interval of 0 – 3 minutes. The breakthrough time of the positive control fell within ± two standard deviations of the positive control historical mean breakthrough time. Thus, all validity criteria of the test were met.

A change in the CDS was not observed for 60 minutes in any of the four replicates of the test item indicating that it did not break through the bio-barrier.

Test Group	Time Interval of Colour Change	UN Packaging Group	R-Sentence	GHSand Regulation (EC) No 1272/2008 (CLP)
Negative Control	Colour change was not observed for 60 minutes	-	-	-
Positive Control	1 minute	I	R35	1A
Test Item	Colour change was not observed for 60 minutes	Non-corrosive	-	-

No other effects were observed in any of the treatments.

Applicant's summary and conclusion

Interpretation of results:

other: the test item is not corrosive.

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

According to the test, vanadium dioxide is not corrosive to skin.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not classified as corrosive to the skin.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as corrosive to the skin.