Registration Dossier

Administrative data

Description of key information

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 (Lehmeier, 2013a).


In another in vitro membrane barrier test (CORROSITEX™ Assay), conducted according to OECD Test Guideline 435 and to GLP, palladium dinitrate solution type H displayed mean breakthrough times of 3.24 and 5.98 minutes in experiment 1 and 2, respectively (Lehmeier, 2013b).


In a third in vitro membrane barrier test (CORROSITEX™ Assay), conducted according to OECD Test Guideline 435 and to GLP, palladium(II) nitrate solution displayed a mean breakthrough times of 4.09 minutes (Lehmeier, 2014).


No relevant eye or respiratory tract irritation data were identified. However, such testing is not considered appropriate as palladium dinitrate is classified as corrosive to the skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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

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.

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.

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 May - 27 August 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD), to GLP
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)
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.
Type of coverage:
other: Not applicable.
Preparation of test site:
other: Not applicable.
Vehicle:
unchanged (no vehicle)
Controls:
other: Negative control: citric acid (10%); positive controls: nitric acid (69%), phosphoric acid (85%)
Amount / concentration applied:
500 µL
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.

Each test (experiment 1 and 2) 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. 150 µl 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, 150 µl 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 material 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, a CONFIRM reagent is used followed by pH testing.

Classification test:
Two identical classification experiments were performed using different batches of palladium(II) nitrate solution type H.

Each test was performed in vials that came pre-filled with the CDS. Four replicate vials were performed on 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 µl 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 reaction. The exact time of reactions were recorded.

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.
Irritation / corrosion parameter:
other: CORROSITEX time (minutes)
Run / experiment:
mean of 4 replicates
Value:
3.24
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritation / corrosion parameter:
other: CORROSITEX time (minutes)
Run / experiment:
mean of 4 replicates
Value:
5.98
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
The mean time of the test substance to activate the CDS was 3.24 minutes (in Experiment 1) and 5.98 minutes (in Experiment 2).

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.

Experiment 1

 Positive and negative control test substances:

The reaction times of positive controls nitric acid and phosphoric acid were 1.67 and 17.25 minutes, respectively. The reaction time of the negative control was 97.50 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 3.24 minutes.

Experiment 2

 Positive and negative control test substances:

The reaction times of positive controls nitric acid and phosphoric acid were 2.0 and 26.67 minutes, respectively. The reaction time of the negative control was >60 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 5.98 minutes.

Interpretation of results:
Category 1B (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In two in vitro membrane barrier tests (CORROSITEX™ Assays), conducted according to OECD Test Guideline 435 and to GLP, palladium dinitrate solution type H displayed mean breakthrough times of 3.24 and 5.98 minutes in experiment 1 and 2, respectively
Executive summary:

In a good quality GLP study, conducted according to OECD Test Guideline 435, the potential of palladium dinitrate solution type H to induce skin corrosion was assessed in two independent "in vitro membrane barrier tests (CORROSITEX™ Assays)", using two different batches of test material.

The test item was placed on top of asynthetic macromolecular bio-barrier membrane which was sat on a chemical detection system (CDS) in a vialfilled with a chemical detection system (CDS). 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 times required for palladium dinitrate solution type H to activate the CDS were 3.24 and 5.98 minutes (mean of 4 replicates) for experiment 1 and 2, respectively.

The test substance is therefore classified as "corrosive" sub category 1B, according to EU CLP criteria (EC 1272/2008), as the mean times to activate the CDS were between 3-60 minutes for both batches (category 1B).

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13-14 August 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD); to GLP
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)
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.
Type of coverage:
other: Not applicable.
Preparation of test site:
other: Not applicable.
Vehicle:
unchanged (no vehicle)
Controls:
other: control: citric acid (10%); positive controls: nitric acid (69%), phosphoric acid (85%)
Amount / concentration applied:
500 µL
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. 150 µl 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, 150 µl 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 material 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, a CONFIRM reagent is used followed by pH testing.

Classification test:
Each test was performed in vials that came pre-filled with the CDS. Four replicate vials were performed on 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 µl 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 reaction. The exact time of reactions were recorded.

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.
Irritation / corrosion parameter:
other: CORROSITEX time (minutes, seconds)
Run / experiment:
mean of 4 replicates
Value:
4.09
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation

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 times of positive controls nitric acid and phosphoric acid were 1:55 and 19:30 minutes, respectively. The reaction time of the negative control was 120 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 4:09 minutes.

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
In an vitro membrane barrier test (CORROSITEX™ Assay), conducted according to OECD guidelines and to GLP, palladium(II) nitrate solution displayed a mean breakthrough times of 4:09 minutes. The test substance is therefore classified as "corrosive" sub category 1B, according to UN GHS, as the mean time to activate the CDS was between 3-60 minutes (category 1).
Executive summary:

In a good quality GLP study, conducted according to OECD test guideline 435, the potential of palladium(II) nitrate solution to induce skin corrosion was assessed in the "in vitro membrane barrier test (CORROSITEX™ Assay)".

The test item was placed on top of a BIOBARRIER membrane which was on top of a vial filled with a chemical detection system (CDS). 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(II) nitrate solution to activate the CDS was 4:09 minutes (mean of 4 replicates).

The test substance is therefore classified as "corrosive" sub category 1B, according to UN GHS, as the mean times to activate the CDS were between 3-60 minutes (category 1).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No relevant human irritation/corrosion data were identified.

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 by 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(Lehmeier, 2013a).

 

In a good quality GLP study, conducted according to OECD Test Guideline 435, the potential of palladium dinitrate solution type H to induce skin corrosion was assessed in two independent "in vitro membrane barrier tests (CORROSITEX™ Assays)", using two different batches of test material. The mean times required for palladium dinitrate solution type H to activate the CDS were 3.24 and 5.98 minutes (mean of 4 replicates) for experiment 1 and 2, respectively. The test substance is therefore classified as "corrosive" sub category 1B,according to EU CLP criteria (EC 1272/2008),as the mean times to activate the CDS were between 3-60 minutes for both batches (category 1B) (Lehmeier, 2013b).

 

In a further good quality GLP study, conducted according to OECD test guideline 435, the potential of palladium(II) nitrate solution to induce skin corrosion was assessed in the "in vitro membrane barrier test (CORROSITEX™ Assay)". The mean time required for palladium(II) nitrate solution to activate the CDS was 4:09 minutes (mean of 4 replicates). The test substance is therefore classified as "corrosive" sub category 1B, according to EU CLP, as the mean times to activate the CDS were between 3-60 minutes (category 1) (Lehmeier, 2014).

 

No eye or respiratory tract data were identified. However, eye irritation testing is not considered appropriate as palladium dinitrate is classified as corrosive to the skin.


Justification for selection of skin irritation / corrosion endpoint:
OECD guideline study, to GLP. All these in vitro assays indicate corrosive response and an identical classification (category 1B).

Justification for classification or non-classification

Based on the results of the available reliable in vitro skin corrosion studies, palladium dinitrate should be classified as corrosive to the skin (category 1B) according to EU CLP criteria (EC 1272/2008). Substances that are corrosive to the skin are considered as leading to serious damage to the eyes. Consequently, palladium dinitrate should be classified for eye effects in Category 1 according to EU CLP criteria (EC 1272/2008).