Registration Dossier

Administrative data

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

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 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

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 throughout the test period “according to the sponsor”
- Storage condition of test material: no data
- Other:

Test animals / tissue source

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:

Test system

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

Results and discussion

Results of in vivo studyopen allclose all
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.