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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:
13-14 May 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD); to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
Reference substance 002
Cas Number:
10102-05-3
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Palladium dinitrate hydrate - solid
- Physical state: yellow-brown solid
- Analytical purity: Not specified.
- Impurities (identity (concentration in ppm)): Pt (8), Ru (<2), Rh (<5), Ir (<10), Au (<3), Ag (<3), Al (<2), Ca (<1), Co (<2), Cr (<1), Cu (<2), Fe (5), Mg (<2), Mn (<5), Ni (1), Pb (<2), Sb (<10), Si (<10), Sn (<5), Zn (<2)
- Composition of test material, percentage of components: palladium content w/w 40.10%
- Isomers composition: Not specified.
- Purity test date: Not specified.
- Lot/batch No.: 10212
- Expiration date of the lot/batch: 31 December 2015
- Stability under test conditions: Not specified.
- Storage condition of test material: Room temperature.

Test animals

Species:
other: Not applicable.
Strain:
other: Not applicable.
Details on test animals or test system and environmental conditions:
The CORROSITEX™ Assay is a standardized, quantitative in vitro test for skin corrosivity and has been validated by the ECVAM for testing acids, bases and their derivatives.

The test was performed on a synthetic macromolecular bio-barrier membrane resting on top of a chemical detection system (CDS). The BIOBARRIER was prepared at least 2 hours prior to tests. BIOBARRIER diluent and matrix powder were combined and heated to 68 deg C under smooth agitation. After complete dissolution, the solution was allowed to sit for 5 minutes. 200 µl of the BIOBARRIER were pipetted into each membrane disc, set on the tray and kept in the cold (2-8 deg C) for at least 2 hours.

Test system

Type of coverage:
other: Not applicable.
Preparation of test site:
other: Not applicable.
Vehicle:
unchanged (no vehicle)
Controls:
other: Negative control: citric acid (10% aq.); positive controls: nitric acid (69%), phosphoric acid (85%)
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
Up to 4 hours.
Observation period:
The test system was observed until a reaction was detected (or for a total of 4 hours).
Number of animals:
Not applicable.

The test was performed on a total of eight BIOBARRIERS (four BIOBARRIERS for the test item).
Details on study design:
Test system:
The CORROSITEX™ test system was purchased from Invitro International, Irvine, CA 92614.

Qualification test:
This stage was carried out to ensure the sample is compatible with the CORROSITEX™ test system. 100 mg of the test substance was added to the Qualify test tube, shaken and left to stand for one minute. A colour change or change in consistency of the CDS indicates that the test material is qualified for the assay.

Categorisation test:
To establish the category cut-off times for the sample, 100 mg of the test substance was added to tubes labelled A and B. After shaking, a colour change observed in either tube was matched to the corresponding CORROSITEX™ colour charts. Test materials with high acid/alkaline reserves are defined as category 1, and those with low acid/alkaline reserves as category 2. If no colour is observed or if the test item is strongly coloured, a CONFIRM reagent is used followed by pH testing.

Classification test:
The test was performed in vials that came pre-filled with the CDS. Four replicate vials were used for the test substance. The CDS vials were warmed to room temperature (17-25 deg C) before use. A BIOBARRIER membrane disc was placed on top of a vial filled with CDS. 500 mg of the test item was placed on top of the BIOBARRIER membrane disc and starting time recorded. This was repeated with the remaining test vials, staggering each start time. The vials were observed for a colour-change reaction. The exact time to react was recorded for each vial.

Testing of positive and negative control substances:
Positive (nitric acid and phosphoric acid) and negative (citric acid) control substances were tested following the same procedure as the test substance assay. The expected reaction time ranges of the positive and negative control substances are within 3 minutes, 3 - 60 minutes and >60 minutes, respectively.

Data compilation:
The CORROSITEX™ time was calculated for each replicate by subtracting the start time from the detection time. The mean CORROSITEX™ time was calculated for the four test vials. Using the corrosivity assignment time table the appropriate Packing Group Classification was assigned.

Results and discussion

In vitro

Results
Irritation / corrosion parameter:
other: CORROSITEX time (minutes)
Run / experiment:
mean of 4 replicates
Value:
13.96
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation

In vivo

Irritant / corrosive response data:
The mean time of the test substance to activate the CDS was 13.96 minutes.

Any other information on results incl. tables

Qualification/categorisation test:

The test substance was compatible with the CORROSITEX™ test system. As the sample was intensely coloured, any colour-change reaction in the categorisation tubes was indistinct. Based on pH measurement the test substance was assigned to Category 1.

 

Positive and negative control test substances:

The reaction time of positive controls nitric acid and phosphoric acid were 1.40 and 16 minutes, respectively. The reaction time of the negative control was 83 minutes. The acceptance criteria for the control substances were therefore fulfilled.

 

CORROSITEX™ Assay:

The mean time of the test substance to activate the CDS was 13.96 minutes.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an in vitro membrane barrier test (CORROSITEX™ Assay) conducted according to OECD Test Guideline 435 and GLP, palladium dinitrate hydrate (solid) displayed a mean breakthrough time of about 14 minutes and was considered corrosive to the skin.
Executive summary:

In a good quality GLP study, conducted according to OECD Test Guideline 435, the potential of palladium dinitrate hydrate (solid) to induce skin corrosion was assessed in the "in vitro membrane barrier test (CORROSITEX™ Assay)".

The test item was placed on top of a synthetic macromolecular bio-barrier membrane which was sat on a chemical detection system (CDS) in a vial. Corrosivity is determined on the ability (measured by the time taken) of a chemical to break through the barrier and subsequently activate the underlying CDS (as seen by a colour or consistency change).

The mean time required for palladium dinitrate hydrate (solid) to activate the CDS was 13.96 minutes (mean of 4 replicates). The test substance is therefore classified as "corrosive" sub category 1B, according to EU CLP criteria (EC 1272/2008), as the mean time to activate the CDS was between >3-60 minutes.