Divanadium tris(sulphate)

Endpoint summary

Description of key information

Divanadium tris(sulphate) tested corrosive to the skin. Further, the pH of a saturated solution is very acidic (pH < 0). Divanadium tris(sulphate) is only manufactured and marked as aqueous solution, and inhalation of divanadium tris(sulphate) solution can be considered negligible. Hence, divanadium tris(sulphate) solution cannot possess an irritation potential in the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-11-29 to 2012-11-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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.

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: qualified test substance is classified into categories (Category 1: strong acids or bases; Category 2: less strong acids and bases) by a screening test. The category, that a test substance is assigned to, will determine how the breakthrough time (if one occurs) will be interpreted. A test substance is assigned to a category based on its ability to induce a pH change in one of two defined buffers. One buffer is designed for detecting acids, the other for detecting bases.
The test item was categorised according to the pH value method to distinguish between weak and strong acids or bases as described in the Corrositex™ Instruction Manual (1995)*. The pH of the solution containing the test item in a “Category A Vial” and a “Category B Vial” was measured using pH sticks, where the Category A vial contained the acid buffer and Category B contained the base buffer. Test items with a solution pH that is ≤ 5 in the “Category A Vial” and ≥ 9 in the “Category B Vial”, i.e. strong acids or bases, were assigned to Category 1. Test items with a solution pH that is ≥ 5 in the “Category A Vial” and ≤ 9 in the “Category B Vial”, i.e. less strong acids and bases, were assigned to Category 2.
- 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.

* Reference
- Corrositex™ instruction manual (1995). In Vitro International, 16632 Millikan Avenue, Irvine, CA 92606, USA.

Irritation / corrosion parameter:

penetration time (in minutes)

Value:

51

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: positive indication of corrosion

Other effects / acceptance of results:

A change in the CDS was observed after 51.5 ± 3.8 minutes in all four replicates of the test item indicating that it penetrated the bio-barrier. The test item was classified as corrosive.

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:

Since the pH value of the test item was ≥ 5 in the “Category A Vial” and ≤ 9 in the “Category B Vial”, 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. Thepositive 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 observed after 51.5 ± 3.8 minutes in all four replicates of the test item indicating that it penetrated the bio-barrier.

Test Group	Time Interval of Colour Change	UN Packaging Group	R-Sentence	GHS and 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	Mean time: 51.5 ± 3.8 minutes (50, 49, 49, and 58 minutes)	III	R34	1C

No other effects were observed in any of the treatments.

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

Divanadium tris(sulphate) tested corrosive to skin in the In Vitro Membrane Barrier Test for Skin Corrosion (OECD Guideline 435).
According to the EC-Regulation 1272/2008 and subsequent adaptations, divanadium tris(sulphate) meets the classification criteria as corrosive to the skin (Category 1C).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation:

Divanadium tris(sulphate) possesses a corrosive potential and requires classification in Skin Corrosive subcategory 1C ( H314: Causes severe skin burns and eye damage) according to Regulation (EC) 1272/2008.

Eye irritation:

Divanadium tris(sulphate) possesses a corrosive potential and requires classification for irreversible effects on the eye (Category 1; H318: Causes serious eye damage) according to Regulation (EC) 1272/2008.

Respiratory irritation:

Divanadium tris(sulphate) is only manufactured and marked as aqueous solution, and inhalation of divanadium tris(sulphate) (solution) can be considered negligible. Hence, divanadium tris(sulphate) (solution) cannot possess an irritation potential in the respiratory tract and therefore does not require classification as respiratory irritant according to Regulation (EC) 1272/2008.