Copper iodide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Remarks:

This study was conducted in light of a negative result in an Enucleated Rabbit Eye Test.

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 iodide

EC Number:

231-674-6

EC Name:

Copper iodide

Cas Number:

7681-65-4

Molecular formula:

CuI

IUPAC Name:

λ¹-copper(1+) iodide

Details on test material:

- Name of test material (as cited in study report): Copper iodide
- Analytical purity: 99.7%
- Lot/batch No.: 108701/2 REACH STANDARD 290911
- 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: 2.24 or 2.48 kg
- Housing: The animals were individually housed in suspended cages.
- 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 96 mg.

Observation period (in vivo):

Up to 21 days.

Number of animals or in vitro replicates:

Two.

Details on study design:

Initially, a single animal was treated. A volume of 0.1 ml of the test item 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. After consideration of the ocular responses produced in the first treated animal, a second animal was treated.

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 eyes 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

Remarks:

degree of opacity

Basis:

mean

Remarks:

(two animals)

Time point:

24/48/72 h

Score:

1.5

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Results 2

Irritation parameter:

cornea opacity score

Remarks:

area of cornea involved

Basis:

mean

Remarks:

(two animals)

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

(2 animals)

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 21 days

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

(2 animals)

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 21 days

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(2 animals)

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Results 6

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

mean

Remarks:

(two animals)

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritant / corrosive response data:

Scattered or diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation were noted in one treated eye one hour after treatment and at the 24, 48 and 72-Hour observations. Moderate conjunctival irritation was noted in this treated eye at the 7-Day observation with minimal conjunctival irritation noted at the 14-Day observation. This treated eye appeared normal at the 21-Day observation. Scattered or diffuse corneal opacity was noted in the other treated eye one hour after treatment with translucent corneal opacity noted at the 24-Hour observation and all subsequent observations. Iridial inflammation was noted in this treated eye one hour after treatment and at the 24, 48, 72-Hour, 7 and 14-Day observations. Moderate conjunctival irritation was noted in this treated eye one hour after treatment with severe conjunctival irritation noted at the 24 and 48-Hour observations, moderate conjunctival irritation noted at the 72-Hour, 7 and 14-Day observations and minimal conjunctival irritation noted at the 21-Day observation. Areas of haemorrhage on the nictitating and upper conjunctival membranes were also noted in this treated eye at the 72-Hour and
7-Day observations. Vascularisation, approximately2 mm to 3 mm in size around approximately half of the outer edge of the cornea,was noted in this treated eye at the 7, 14 and 21-Day observations. The persistence of reactions in this treated eye at the 21-Day observation was considered to be indicative of irreversible ocular damage.

Other effects:

Staining of the fur was noted around one treated eye at the 24-Hour observation.
Both animals 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.

See Table 4 (attached) for the results of the initial Rabbit Enucleated Eye Test. These and indicated that the test item was unlikely to cause severe ocular irritancy.

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 iodide produced irreversible ocular damage and was considered to be corrosive to the rabbit eye (based on one rabbit only). The test item was classified as Irreversible effects on the eye (Category 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 two rabbits produced scattered or diffuse to translucent corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. Other ocular effects noted in one treated eye were areas of haemorrhage on the nictitating and conjunctival membranes and vascularisation of the cornea. One treated eye appeared normal at the 21 -Day observation. The persistence of reactions in one 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. The test item 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.