Copper di(acetate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with Good laboratory Practice and internationally accepted guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Copper di(acetate)

EC Number:

205-553-3

EC Name:

Copper di(acetate)

Cas Number:

142-71-2

Molecular formula:

Cu(CO2CH3)2

IUPAC Name:

copper di(acetate)

Details on test material:

- Name of test material (as cited in study report): Copper acetate monohydrate
- Analytical purity: 99.9%
- Lot/batch No.: 11.6.1SD
- Storage condition of test material: room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.52 kg
- Housing: The animal was housed in a suspended cage.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C.
- Humidity (%): 30 to 70%.
- Air changes (per hr): At least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A volume of 0.1 ml of the test item, weighing approximately 94 mg.

Observation period (in vivo):

Up to 21 days.

Number of animals or in vitro replicates:

One.

Details on study design:

A volume of 0.1 ml of the test item, which was found to weigh approximately 94 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent lossof the test item, and then released. The left eye remained untreated and was used for control purposes.

Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Table 1 (attached). Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to Draize. Any other ocular effects were also noted. Additional observations were made on Days 7, 14 and 21 to assess the reversibility of the ocular effects. Any clinical signs of toxicity, if present, were also recorded. Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

1 animal

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

1 animal

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 21 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

1 animal

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

1 animal

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Irritant / corrosive response data:

Scattered or diffuse corneal opacity was noted in the treated eye one hour after treatment with translucent corneal opacity at the 24 and 48-Hour observations and scattered or diffuse corneal opacity at the 72-Hour, 7, 14 and 21-Day observations. A small area of translucent opacity, 3 mm x 3 mm in size on the lower half of the cornea, was also noted in the treated eye at the 7-Day and 14-Day observations. Vascularisation, with a generalised ingrowth of vessels for up to 2 mm in the centre of the cornea of the treated eye, was noted at the 7, 14 and 21-Day observations.
Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-Hour, 7 and 14-Day observations.
Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24, 48, 72-Hour, 7, 14 and 21-Day observations.

Other effects:

Staining of the fur was noted around the treated eye during the study.
The animal showed expected gain in bodyweight during the study.

Any other information on results incl. tables

The persistence of reactions in the treated eye at the 21-Day observation was considered to be indicative of irreversible ocular damage.

See Table 2 (attached) for detailed occular irritation scores.

See Table 3 (attached) for individual bodyweights and bodyweight change.

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:

Copper acetate monohydrate produced lesions that persisted until the end of the study.
Classification according to Directive 67/548/EEC: Irritant (Xi). R41, Risk of serious damage to eyes.
Classification according to CLP/GHS: Eye Damage 1, H318: Causes serious eye damage.

Executive summary:

A GLP-compliant study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with OECD Guideline 405 and EU Method B5. A single application of the test item to the non-irrigated eye of one rabbit produced translucent corneal opacity, iridial inflammation, moderate conjunctival irritation and vascularisation, with a generalised ingrowth of vessels for up to 2 mm. The persistence of reactions in the treated eye at the 21-Day observation was considered to be indicative of irreversible ocular damage.

The test item was considered to be corrosive to the rabbit eye and was classified as Irreversible effects on the eye (Category 1). The Signal Word “Danger” and the Hazard Statement “H318: Causes serious eye damage” are therefore required.