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Toxicological information

Eye irritation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): tetraamminepalladous chloride
- Substance type: yellow powder
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Purity test date: no data
- Lot/batch No.: 041232
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data


Test animals / tissue source

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


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


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

Results and discussion

Results of in vivo studyopen allclose all
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.

Applicant's summary and conclusion

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 dihydroxide 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 hydroxide 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 hydroxide 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 dihydroxide is scientifically justified and suitably reliable.