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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-12-18
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 guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexanoic acid, molybdenum salt
EC Number:
251-807-1
EC Name:
2-ethylhexanoic acid, molybdenum salt
Cas Number:
34041-09-3
Molecular formula:
C8H16O2.xMo
IUPAC Name:
2-ethylhexanoic acid, molybdenum salt
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): 2-ethylhexanoic acid, molybdenum salt
- Chemical Name: molybdenum 2-ethylhexanoate
- Physical state: brown, liquid
- Storage condition of test material: at room temperature, under nitrogen (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): 500 μL of the test item were 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:
Name: Corrositex™
Supplier: Transia GmbH, 61239 Ober-Mörlen, Germany
Lot No.: CT052112)

- 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 turned-off 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
- Qualify Test: to test whether the test system is suitable for the test item, 150 μL of the test item were applied into the “Qualify Test Vial”. The vial was shaken until the solution appeared homogenous, and incubated for at least 1 minute. Afterwards, the colour change was noted. Since a change in colour was visible in the “Qualify Test Vial”, the test item was considered to be suitable for the next step.
- Categorisation Test: the test item was categorised according to the pH value method described in the manufacturer’s manual.
A 10% dilution (v/v) of the test item in deionised water was prepared. The pH value of the dilution was determined. Test items with a pH value of < 7 were added to the “Category A Vial” and test item with a pH value of > 7 were added to the “Category B Vial”. The vial was closed, shaken, and the pH value was determined. Test items showing a pH value ≤ 5 in the “Category A Vial” were assigned to category 1 and test items showing a pH value of ≥ 5
were assigned to category 2. Test items showing a pH value of ≥ 9 in “Category B Vial” were assigned to category 1 and test items showing a pH value of ≤ 9 were assigned to category 2. Since the pH value of the test item dilution in the category A vial was 7.5 the test item was assigned to category 2.
- Classification Test: 7 vials containing the CDS were pre-warmed to room temperature. 4 vials were used for quadruplicate measurement of the test item, one vial was used for the positive control (single measurement), and one vial was used for the negative control (single measurement). The one vial was used as colour reference for the CDS.
The prepared bio-barriers were placed atop the CDS vials (not longer than 2 min prior to application) and 500 μL of the test item or 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)), respectively, were applied per bio-barrier for 1 hour or 4 hours, depending on the results of the categorisation test. The time interval of the possible colour change or precipitation in the CDS solution was recorded.

INTERPRETATION OF THE RESULTS
For each vial the time until observable change in CDS solution was determined. The mean of the quadruplicate measurement the mean was calculated. The test item was categorised according to the following table as can be seen in the field "Any other information on materials and methods incl. tables" below (Table 1).

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 qualify 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. Remarks: A change of colour of CDS reagent after treatment of bio-barriers with test item was not observed during the test, i.e. for 60 minutes. . (migrated information)

In vivo

Irritant / corrosive response data:
A change of colour of the CDS reagent after treatment of the bio-barriers with the test item was not observed up to 60 minutes. According to the classification criteria the test item was classified as non corrosive.

Any other information on results incl. tables

HISTORICAL DATA:

Table: Historical data

Mean time till colour change of positive control [min]

1.313

Standard Deviation [min]

0.45

Data of 46 studies performed from 2006 till 2012.

QUALIFY TEST:

The test item induced a change in colour in the qualify test after 1 minute incubation. Since a change in colour was visible in the “Qualify Test Vial”, the test item was considered to be suitable for the next step.

CATEGORISATION TEST:

Since the pH value of the test item in the “Category A Vial” was 7.5 and therefore above 7 the test item was assigned to category 2.

CLASSIFICATION TEST:

 

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

 

 

 

The test item was classified as non corrosive.

- The negative control did not induce a change in the colour of the CDS reagent after 60 minutes. The positive control showed a distinct change in the colour of the CDS reagent in the time interval of 0 – 3 minutes (after 1 minute). These results ensured the validity of the test.

Applicant's summary and conclusion

Interpretation of results:
other: the test item is not corrosive.
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item 2-ethylhexanoic acid, molybdenum salt 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.