Registration Dossier

Administrative data

Description of key information

No relevant irritation data were identified for tetraamminepalladium (II) nitrate and none is required to be generated as an Annex III registration. As a health precautionary approach, read-across from the structurally-related compound tetraamminepalladium dichloride was considered appropriate in order to inform the potential toxicity and classification for tetraamminepalladium (II) nitrate.
In a guideline in vivo skin irritation study, no irritant or corrosive reactions were observed following 4-hr application of tetraamminepalladium dichloride (under occlusion) to the intact shaved skin of three rabbits (Driscoll, 1981).
In a guideline eye irritation study with rabbits, moderate to severe irritation was seen following instillation of undiluted tetraamminepalladium dichloride (Driscoll and Collier, 1981).
Tetraamminepalladium dichloride is closely related to tetraamminepalladium (II) nitrate and is considered a suitable surrogate for read-across for these endpoints.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
18 to 21 November 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, on closely-related surrogate.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
individual experimental studies were not inspected for GLP compliance. Inspections of skin irritation studies were reported to be carried out 19-20 February 1981
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Nottingham University
School of Agriculture
Sutton Bonington
Leicestershire
UK
- Age at study initiation: no data
- Weight at study initiation: 2.34-3.19 kg
- Housing: Individually in suspended metal cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): no data
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: no concurrent control site
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg moistened with water to make a paste


VEHICLE
no data

Duration of treatment / exposure:
4 hr
Observation period:
72 hr with an additional 7 day observation period if irritation was still apparent at 72 hr
Number of animals:
Three
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: no data
- Type of wrap if used: absorbent lint covered with polythene, secured by adhesive tape. The trunk of each rabbit was wrapped in an elasticated bandage (Tubigrip)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool soaked in warm water
- Time after start of exposure: 4 hr

SCORING SYSTEM: assessed at 1, 24, 48 and 72 hr. Scored using the method of Draize (1959) for erythema/eschar formation and edema at all time points and the total scores were divided by 12 to hive the primary irritation index.
Primary irritation index Classification
0 non-irritant
> 0-2 mild irritant
> 2-5 moderate irritant
> 5-8 severe irritant

Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: Mean of 1, 24, 48 and 72 hr time points
Score:
0
Max. score:
8
Reversibility:
other: no irritation observed
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Mean of 1, 24, 48 and 72 hr time points
Score:
0
Max. score:
8
Reversibility:
other: no irritation observed
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Mean of 1, 24, 48 and 72 hr time points
Score:
0
Max. score:
8
Reversibility:
other: no irritation observed
Irritant / corrosive response data:
None seen at any time point
Other effects:
No indication of whether systemic effects were assessed

Very slight yellowing staining of the test site which did not interfere with the assessment of irritation

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guideline study, no irritation potential was observed when tetraammine palladous chloride was applied (under occlusion for 4 hr) to the intact shaved skin of three rabbits.
Executive summary:

In an OECD Test Guideline 404 study, tetraammine palladous chloride (0.5 g, moistened) was applied (occluded) to the clipped but intact skin of three New Zealand white rabbits. After 4 hours, the dressings were removed and the skin sites assessed for signs of irritation (oedema and erythema/eschar) and corrosion at 1, 24, 48 and 72 hours.

 

No irritation (erythema/eschar formation or erythema) or corrosion of the skin was seen at any time point during the 72 hr study period. The primary irrational index was therefore 0, and tetraammine palladous chloride is classified as non-irritating.

 

No skin classification, according to EU CLP criteria (EC 1272/2008), is required on the basis of this study.

Tetraamminepalladium dichloride is closely related to tetraamminepalladium (II) nitrate and is considered a suitable surrogate for read-across for this endpoint. The proposed read-across is appropriate because it is expected that the target and source substances undergo biotransformation to a common product. In solution, the chloride and nitrate anions are expected to dissociate from the tetraamminepalladium cation; thus, this can be regarded as the common product and toxicologically-active species of both salts. The nitrate and chloride counterions would not have an impact on the overall skin irritation potential of the target or source substance, respectively. Therefore, it is considered that use of in vivo skin irritation data obtained in a test on tetraamminepalladium dichloride to fill a gap in the standard information requirements for tetraamminepalladium dinitrate is scientifically justified and suitably reliable.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
21 to 28 December 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study, to GLP, on closely-related surrogate
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.36-3.16 kg
- Housing: metal cages
- Diet (e.g. ad libitum): conventional; ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): no data
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12


Vehicle:
unchanged (no vehicle)
Controls:
other: yes, concurrent no treatment; other eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg


Duration of treatment / exposure:
After 30 seconds (“with rinsing” group) or throughout observation period ("without rinsing” group)
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 in the “without rinsing” group; 3 in the “with rinsing” group
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes in one group
- Time after start of exposure: 30 seconds with 100 ml sterile distilled water at 37oC (one group)

SCORING SYSTEM: According to the numerical evaluation of Draize. For each tissue the total score was calculated as follows:
Total score for conjunctivae = (redness + chemosis + discharge) x 2
Total score for iris = any changes x 5
Total score for cornea = (degree of opacity x area of opacity) x 5

TOOL USED TO ASSESS SCORE: no data

Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hr, and 7 days
Score:
27
Reversibility:
not fully reversible within: 7 days in two of the three animals
Irritation parameter:
maximum mean total score (MMTS)
Remarks:
with rinsing
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hr, and 7 days
Score:
31
Reversibility:
not fully reversible within: 7 days in two of the rabbits
Irritant / corrosive response data:
Without washing: One hour after treatment irritation showed as iridial congestion, conjunctival reness and severe chemosis. By seven days post treatment minimal chemosis was present in one animal and minimal chemosis and redness in another.

With washing: One hour following treatment irritation was exhibited as slight corneal opacity and iridial congestion in two rabbits, and slight to moderate conjunctival redness and moderate to severe chemosis in all three animals, which had not improved by 72 hours. By day 7 significant irritation was still persistent in the cornea and conjunctivae of two rabbits.
Other effects:
There is no indication that clinical signs of systemic toxic effects were evident.
Interpretation of results:
Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an OECD Guideline study, to GLP, instillation of undiluted tetraamminepalladium dichloride to one eye of each of three rabbits without washing caused moderate to severe irritation and severe irritation in three rabbits when the eye was rinsed after 30 seconds.
Executive summary:

In an OECD Test Guideline 405 study, to GLP, undiluted tetraamminepalladium dichloride (100 mg, powdered) was instilled into the right eye of each of six New Zealand white rabbits. The contralateral eye remained untreated and was used for control purposes. In half of the animals, the eyes were rinsed after 30 seconds with 100 ml of sterile distilled water.

 

Moderate to severe irritation was observed in the ‘non-rinsed group’, which (although had reduced in severity) was not fully reversible in two of the 3 rabbits within seven days after treatment. When the eyes were rinsed after a 30-second exposure, the test substance caused severe eye irritation in all three rabbits which (although reduced in severity) still persisted at day 7 in two of the animals. No clinical signs of systemic toxic effects were reported. Tetraamminepalladium dichloride caused severe irritation to the eye of rabbits observed for a 7-day period.

 

Overall, tetraamminepalladium dichloride caused severe irritation to the eye of rabbits observed for a seven day period. Classification as an eye irritant (category 2), is required on the basis of the findings of this study and according to EU CLP criteria (EC 1272/2008).

 

Tetraamminepalladium dichloride is closely related to tetraamminepalladium (II) nitrate and is considered a suitable surrogate for read-across for this endpoint. The proposed read-across is appropriate because it is expected that the target and source substances undergo biotransformation to a common product. In solution, the chloride and nitrate anions are expected to dissociate from the tetraamminepalladium cation; thus, this can be regarded as the common product and toxicologically-active species of both salts. The nitrate and chloride counterions would not have an impact on the overall eye irritation potential of the target or source substance, respectively. Therefore, it is considered that use of in vivo eye irritation data obtained in a test on tetraamminepalladium dichloride to fill a gap in the standard information requirements for tetraamminepalladium dinitrate is scientifically justified and suitably reliable

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an OECD Test Guideline 404 study, neat tetraamminepalladium dichloride (0.5 g, moistened) was applied (occluded) to the clipped but intact skin of three New Zealand white rabbits. After 4 hours, the dressings were removed and the skin sites assessed for signs of irritation (oedema and erythema/eschar) and corrosion at 1, 24, 48 and 72 hours. No irritation (erythema/eschar formation or erythema) or corrosion of the skin was seen at any time point during the 72-hr study period. The primary irrational index was therefore 0, and tetraamminepalladium dichloride was classified as non-irritating (Driscoll, 1981).

 

In an OECD Test Guideline 405 study, to GLP, undiluted tetraamminepalladium dichloride (100 mg, powdered) was instilled into the right eye of each of six New Zealand white rabbits. The contralateral eye remained untreated and was used for control purposes. In half of the animals, the eyes were rinsed after 30 seconds with 100 ml of sterile distilled water. Moderate to severe irritation was observed in the ‘non-rinsed group’, which (although reduced in severity) was not fully reversible in two of the three rabbits within 7 days after treatment. When the eyes were rinsed after a 30-second exposure, the test substance caused severe eye irritation in all three rabbits which (although reduced in severity) still persisted at day 7 in two of the animals. No clinical signs of systemic toxicity were reported. Tetraamminepalladium dichloride caused severe irritation to the eye of rabbits observed for a 7-day period (Driscoll and Collier, 1981).

 

Tetraamminepalladium dichloride is closely related to tetraamminepalladium (II) nitrate and is considered a suitable surrogate for read-across for these endpoints. The proposed read-across is appropriate because it is hypothesised that the target and source substances undergo biotransformation to a common product. In solution, the chloride and nitrate anions are expected to dissociate from the tetraamminepalladium cation; thus, this can be regarded as the common product and toxicologically-active species of both salts. The nitrate and chloride counterions would not have an impact on the overall irritation potential of the target or source substance, respectively. Therefore, it is considered that use of in vivo irritation data obtained in tests on tetraamminepalladium dichloride to fill gaps in the standard information requirements for tetraamminepalladium dinitrate is scientifically justified and suitably reliable.


Justification for selection of skin irritation / corrosion endpoint:
OECD guideline study on a read-across compound. No skin irritation was seen, supporting a lack of classification for this compound.

Justification for selection of eye irritation endpoint:
OECD guideline study on a read-across compound. This study informs the health precautionary classification of this compound as an eye irritant.

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the results of the available in vivo skin irritation study on tetraamminepalladium dichloride, tetraamminepalladium (II) nitrate does not require classification for skin irritation according to EU CLP criteria (EC 1272/2008).

 

Based on the results of the available in vivo eye irritation study with tetraamminepalladium dichloride, tetraamminepalladium (II) nitrate should also be classified as an eye irritant (category 2), according to EU CLP criteria (EC 1272/2008).