Palladium (II) di(4-oxopent-2-en-2-oate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 March-17 April 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, to GLP, with minor humidity deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Remarks:

Minor humidity deviations were expected to have no impact on the study outcome

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Remarks:

Minor humidity deviations were expected to have no impact on the study outcom

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Remarks:

Minor humidity deviations were expected to have no impact on the study outcom

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Palladium di(4-oxopent-2-en-2-oate)

IUPAC Name:

Palladium di(4-oxopent-2-en-2-oate)

Constituent 2

Reference substance name:

Palladium (II) di(4-oxopent-2-en-2-oate)

EC Number:

237-859-8

EC Name:

Palladium (II) di(4-oxopent-2-en-2-oate)

Cas Number:

14024-61-4

Molecular formula:

C10H14O4Pd

IUPAC Name:

Palladium (II) di(4-oxopent-2-en-2-oate)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Palladium(II)di(4-oxopent-2-en-2-oate)
- Substance type: Technical product
- Physical state: Solid (yellow powder)
- Analytical purity:>99.5% (palladium content 34.96%)
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components (in ppm): Pt (30); Ru (<2); Rh (<5); Ir (<2); Au (<2); Ag (<2); Al (<2); Ca (32); Co (<2); Cr (<1); Cu (<2); Fe (2); Mg (5); Mn (<1); Ni (<1); Pb (<3); Sb (<5); Si (<10); Sn (<5); Zn (<1)
- Purity test date: 14 December 2011
- Lot/batch No.:11011
- Expiration date of the lot/batch: 13 December 2012
- Stability under test conditions: no data
- Storage condition of test material: Controlled Room Temperature (15-25°C, below 70 RH%)
- pH of test material: 6.01

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft., 2173 Kartal, Császár road 135, Hungary
- Age at study initiation: ~12 weeks
- Body weight range at the beginning of the in-life phase: 3119 – 3200 g
- Body weight range at the end of the in-life phase: 3658 – 3752 g
- Housing: individually in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages
- Diet (e.g. ad libitum): Purina and UNI diet (Lot number: 00701211, 0030 03 12 and 0060 04 12) for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum.
- Water (e.g. ad libitum): municipal tap water, as for human consumption, ad libitum
- Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 24 – 61 %
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

Following instillation into the conjunctival sac of one eye, the eyelids were held closed for several seconds. Washing with physiological saline was performed at 24, 48 and 72 hours.

Observation period (in vivo):

3 weeks (The eyes were examined at 1, 24, 48, 72 hours, 1, 2 and 3 weeks after treatment).

Number of animals or in vitro replicates:

3 (males)

Details on study design:

Washing with physiological saline was performed at 24, 48 and 72 hours.

The eyes were examined at 1, 24, 48, 72 hours, 1, 2 and 3 weeks after treatment. The nature, severity and duration of all lesions observed were described.

SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002).

TOOL USED TO ASSESS SCORE: none reported; presumably subjective observation by an experienced evaluator

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Remarks:

Conjunctival chemosis

Basis:

mean

Remarks:

of all 3 animals

Time point:

other: Mean of 24, 48 and 72-hour timepoints

Score:

3.78

Max. score:

4

Reversibility:

not fully reversible within: 3 weeks

Remarks on result:

other: In one animal, chemosis persisted until study termination at 3 weeks

Results 2

Irritation parameter:

other: Conjunctival discharge

Basis:

mean

Time point:

other: Mean of 24, 48 and 72-hour timepoints

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 3 weeks

Remarks on result:

other: Discharge persisted in one animal until study termination at 3 weeks

Results 3

Irritation parameter:

other: Conjunctival redness

Basis:

mean

Time point:

other: Mean of 24, 48 and 72-hour timepoints

Score:

2.56

Max. score:

3

Reversibility:

not fully reversible within: 3 weeks

Remarks on result:

other: Redness persisted in two animals until study termination at 3 weeks

Results 4

Irritation parameter:

cornea opacity score

Remarks:

opacity, degree of density

Basis:

mean

Time point:

other: Mean of 24, 48 and 72-hour timepoints

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 3 weeks

Remarks on result:

other: Corneal opacity persisted in one animal until study termination at 3 weeks

Results 5

Irritation parameter:

iris score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72-hour timepoints

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

other: The iris was not affected in any animal at any time point

Irritant / corrosive response data:

Initial Pain Reaction (IPR) (score 2) was observed in all animals.

One hour after the application: Conjunctival redness (score 2), discharge (score 3) and chemosis (score 2) were found in all animals. Two rabbits showed corneal opacity (score 1, area 4). The initial test in one rabbit showed no corneal effect at 1 hour.

At 24 hours after treatment: Conjunctival redness (score 2 or 3), discharge (score 3) and chemosis (score 3 or 4) were found in all animals. Additionally, corneal opacity (score 1 or 2, area 4) was seen in all animals.

At 48 hours after treatment: Conjunctival redness (score 2 or 3), discharge (score 3) and chemosis (score 4) were found in all animals. Additionally, corneal opacity (score 1 or 2, area 4) was seen in all animals. Surface damage on the conjunctivae and on the nictitating membrane was noted in all animals.

At 72 hours after treatment: Conjunctival redness (score 2 or 3), discharge (score 3) and chemosis (score 4) were found in all animals. Additionally, corneal opacity (score 1 or 2, area 4) was seen in all animals. Surface damage on the conjunctivae and on the nictitating membrane was noted in all animals.

At 1 week after treatment: Conjunctival redness (score 2 or 3), discharge (score 1, 2 or 3) and chemosis (score 1 or 2) were found in all animals. Additionally, corneal opacity (score 1 or 2, area 4) was seen in all animals. Surface damage on the conjunctivae and on the nictitating membrane was noted in one animal.

At 2 weeks after treatment: Conjunctival redness (score 1) and/or discharge (score 1) was found in two animals. Conjunctival chemosis (score 1) was observed in all animals. Corneal opacity (score 2, area 4) and surface damage on the conjunctivae and on the nictitating membrane was noted in one animal.

At 3 weeks after treatment: Conjunctival redness (score 1) was found in two animals. Conjunctival chemosis (score 1) and discharge (score 2) was observed in one animal. One rabbit showed corneal opacity (score 2, area 2).

During the study, the control eye of each animal was symptom-free.

The individual mean scores for each animal (considering readings at 24, 48 and 72 hours after the treatment) were as follows:
chemosis : 3.67, 3.67, 4.00
discharge : 3.00, 3.00, 3.00
redness : 2.67, 2.00, 3.00
cornea opacity : 1.00, 1.00, 2.00
iris : 0.00, 0.00, 0.00

Surface damage on the conjunctivae and on the nictitating membrane was seen in all animals at 48 and 72 hours, and in one animal at 1 and 2 weeks.

Other effects:

There were no clinical signs observed that could be related to treatment.

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 an OECD Test Guideline 405 study, to GLP, palladium di(4-oxopent-2-en-2-oate) was shown to cause significant conjunctival and corneal irritant effects in the eyes of New Zealand white rabbits within 1 hr of instillation, which were not fully reversible within the 3-week observation period.

Executive summary:

In an in vivo eye irritation study carried out in accordance with OECD Test Guideline 405, and to GLP, 0.1 g of powdered palladium di(4-oxopent-2-en-2-oate) was instilled into the conjunctival sac of one eye of 3 male New Zealand White rabbits. Following instillation the eyelids were held closed for several seconds. Washing with physiological saline was performed at 24, 48 and 72 hr. The eyes were examined at 1, 24, 48, 72 hr, 1, 2 and 3 weeks after treatment, and scored according to the Draize system.

Significant conjunctival redness, discharge, and chemosis were seen in all animals, and corneal opacity in 2 rabbits, within 1 hr of instillation. These were not fully reversible within the 3-week observation period. According to EU CLP criteria (EC 1272/2008), palladium di(4 -oxopent-2 -en-2 -oate) should be classified as Category 1 (irreversible effects on the eye).