Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): palladium(II)-acetate trimer
- Substance type: brown powder
- Physical state: solid
- Analytical purity: 47.15% palladium
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Purity test date: no data
- Lot/batch No.: 6597
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable “according to information from the sponsor”
- Storage condition of test material: room temperature
- Other:

Test animals

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:

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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).