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Administrative data

Description of key information

In a guideline study, to GLP, slight irritation was observed following a single 4-hr occluded application of palladium (II)-acetate trimer to the intact skin of three rabbits. The test item would not be classified for skin irritation under EU CLP (Zechel, 1989).
In a guideline eye irritation study, to GLP, instillation of palladium (II)-acetate trimer (0.1 g, powdered) into one eye of a single rabbit caused severe corrosive effects which were evident within 24 hr of exposure (Jahn, 1989).
No relevant respiratory tract data were identified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 January 1989 to 24 January 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive patch rather than the semi-occlusive one recommended in the guidelines
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive patch rather than the semi-occlusive one recommended in the guidelines
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
other: White Russian (albino)
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ASTA Pharma AG
D-4800 Bielefeld 14
- Age at study initiation: 10 months
- Weight at study initiation: male 2.75 kg; females 2.37 and 2.70 kg
- Housing: stainless steel cages with grating floor
- Diet (e.g. ad libitum): conventional; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-22.5
- Humidity (%): 40-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g applied as a paste

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.25 ml to make a paste
- Purity: demineralized

Duration of treatment / exposure:
4 hr
Observation period:
1, 24, 48 and 72 hr, then once daily until day 14 post treatment
Number of animals:
3, (1 male, 2 females)
Details on study design:
TEST SITE
- Area of exposure: 6.25 cm2
- % coverage:
- Type of wrap if used: site covered with a linen patch, kept in place with a synthetic film glue and a bandage wrapped several times around the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test material gently washed off as far as possible
- Time after start of exposure: 4 hr

SCORING SYSTEM: Assessed for primary irritation at 1, 24, 48 and 72 hrs after removal of the patch using the Draize system of scoring. Scores for erythema/eshcar and oedema at these time points were totalled for all animals and divided by 12 to give the primary irritation index. The test material was classified as follows:
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:
1.3
Max. score:
8
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Mean of 1, 24, 48 and 72 hr time points
Score:
0.75
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Mean of 1, 24, 48 and 72 hr time points
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
A slight irritant effect (edema, erythema/eschar formation) was observed in the rabbits, 1 day after exposure, which was fully reversible within 7 days (edema) or 8 days (erythema/eschar). In two of the rabbits skin scales were formed but immediately peeled off. No signs of corrosion were observed.
Other effects:
No systemic effects were evident

Table 1: Individual irritation scores at each observation time

 Skin reaction     Time after termination of exposure     Draize score      
 1969  1994  2000
 Erythema/eschar formation                    1 hr  0  0  0
 24 hr  1  1  2
 48 hr  1  1  1
 72 hr  0  1  1
 4 d  0  1  1
 7 d  0  1  1
 14 d  0  0  0
 Edema                    1 hr  0  0  0
 24 hr  0  1  1
 48 hr  0  1  1
 72 hr  0  1  1
 4 d  0  1  1
 7 d  0  0  0
 14 d  0  0  0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guideline study, to GLP, slight irritation was observed following a single 4-hr occluded application of palladium(II)-acetate trimer to the intact skin of three rabbits. The test item would not be classified for skin irritation under EU CLP.
Executive summary:

The irritant potential of palladium(II)-acetate trimer was assessed in a guideline study, to GLP. The test item (0.5 g as a paste), applied to the intact skin of three White Russian albino rabbits (4-hr occluded), caused slight irritation within 24 hr of removal of the patch.

 

Edema was observed in two animals which was fully reversible within 7 days after exposure. Erythema/eschar formation which occurred in all three rabbits was fully reversible within 8 days after exposure. The primary irritation index was calculated to be 1.3. The test substance was not corrosive and no systemic effects were observed.

 

Mean erythema/eschar and edema scores were below 2.3 for all three animals. Accordingly, palladium(II)-acetate trimer does not require classification for skin irritation according to EU CLP criteria (EC 1272/2008).

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:
experimental study
Adequacy of study:
key study
Study period:
13 March 1989 to 14 March 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
other: White Russian albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ASTA Pharma AG
D-4800 Bielefeld 14
- Age at study initiation: 9 months
- Weight at study initiation: 2.62 kg
- Housing: Stainless steel cage with grating floor
- Diet (e.g. ad libitum): conventional; ad libitum
- Water (e.g. ad libitum): mains drinking water; ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5-22
- Humidity (%): 45-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

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

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:
24 hr (animal sacrificed at 24 hr)
Observation period (in vivo):
1 and 24 hr
Number of animals or in vitro replicates:
1 male
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure:

SCORING SYSTEM: SCORING SYSTEM: 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
The irritation index was calculated as the sum of these scores.

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
other: 24 hr
Score:
40
Reversibility:
other: not applicable due to severe corrosive effects
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 hr
Score:
20
Reversibility:
other: not applicable due to severe corrosive effects
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 hr
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 hr
Score:
20
Reversibility:
other: not applicable due to severe corrosive effects
Irritant / corrosive response data:
A yellowish viscous secretion was seen which moistened a considerable area around the eye. The test substance caused severe corrosive effects. Microscopic examination showed severe diffuse, subacute, deep ulcerations, severe inflammatory cell infiltration with mainly neutrophilic granulocytes and moderate edema in the conjunctiva including the nictitating membrane. Flattening of the corneal epithelium, focal mixed inflammatory cell infiltration of the stroma and the beginning of ingrowth of peripheral blood vessels were observed in the cornea. Marked mixed inflammatory cell infiltration was seen in the episclera. The rabbit was sacrificed at 24 hr for humane reasons.
Other effects:
No clinical signs of systemic toxic effects were evident.

An irritation index was not calculated in the study report because of the corrosive effects.

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guideline study, instillation of palladium (II)-acetate trimer (0.1 g, powdered) into one eye of a single rabbit caused severe corrosive effects which were evident within 24 hr of exposure.
Executive summary:

In an OECD Test Guideline 405 study, conducted to GLP, palladium (II)-acetate trimer, as a brown powder, was applied to one conjunctival sac of a single White Russian albino rabbit.

 

Instillation of the test material (0.1 g) caused diffuse corneal opacity extending over the whole area. White foci and a diffuse beefy redness were evident in the conjunctiva and swelling of the eyelids caused the eye to nearly completely close. A yellowish viscous secretion was observed that moistened a considerable area around the eye. Due to the severity of the effects, the animal was sacrificed 24 hr after treatment and no further animals were tested.

 

Microscopic examination of fixed and stained sections of the eye showed severe diffuse, subacute, deep ulcerations, severe inflammatory cell infiltration with mainly neutrophilic granulocytes and moderate edema in the conjunctiva including the nictitating membrane. Flattening of the corneal epithelium, focal mixed inflammatory cell infiltration of the stroma and the beginning of ingrowth of peripheral blood vessels were observed in the cornea. Marked mixed inflammatory cell infiltration was seen in the episclera.

 

As the results were based on only one rabbit, it is not possible to give a definitive interpretation according to EU CLP criteria (EC 1272/2008). However, it is considered appropriate to classify the test material for serious eye damage (Category 1), as the severe corrosive effects observed within 24 hr are not expected to be reversible.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No relevant human irritation/corrosion data were identified.

 

The irritant potential of palladium (II)-acetate trimer was assessed in a guideline study, to GLP. The test item (0.5 g as a paste), applied to the intact skin of three White Russian albino rabbits (4-hr occluded), caused slight irritation within 24 hr of removal of the patch. Edema was observed in two animals which was fully reversible within 7 days after exposure. Erythema/eschar formation which occurred in all three rabbits was fully reversible within 8 days after exposure. The primary irritation index was calculated to be 1.3. The test substance was not corrosive and no systemic effects were observed (Zechel, 1989). Mean erythema/eschar and edema scores were below 2.3 for all three animals. Accordingly, palladium (II)-acetate trimer does not require classification for skin irritation according to EU CLP criteria (EC 1272/2008).

 

In an OECD Test Guideline 405 study, conducted to GLP, palladium (II)-acetate trimer (0.1 g) was applied to one conjunctival sac of a single White Russian albino rabbit. The test material caused diffuse corneal opacity extending over the whole area. White foci and a diffuse beefy redness were evident in the conjunctiva and swelling of the eyelids caused the eye to nearly completely close. A yellowish viscous secretion was observed that moistened a considerable area around the eye. Due to the severity of the effects, the animal was sacrificed 24 hr after treatment and no further animals were tested (Jahn, 1989).

 

No respiratory tract data were identified. A new study was not conducted as it is not a REACH Standard Information Requirement.


Justification for selection of skin irritation / corrosion endpoint:
OECD guideline study, and the only skin irritation study available.

Justification for selection of eye irritation endpoint:
OECD guideline study, and the only eye irritation study available.

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the results of the available in vivo skin and eye irritation studies, palladium (II) acetate should not be classified for skin irritation, but should be classified for serious eye damage (Category 1), according to EU CLP criteria (EC 1272/2008).