Dicopper oxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Already evaluated by the Competent Authority for Biocides and Existing Substances Regulations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

The following minor deviations from OECD Test Guideline 405 (adopted 24 April 2002) were noted:
• The test report does not provide a rational for in vivo testing,
• Information on the test material including the batch no and the purity were not provided,
• The following information on test animals were not provided: sex and individual animal weights at the start and conclusion of the test (however the weight range was reported),
• Animal room temperature showed slightly lower limits than those recommended in the test guideline.
These minor deviations are not considered to have influenced the outcome or the integrity of the study.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dicopper oxide

EC Number:

215-270-7

EC Name:

Dicopper oxide

Cas Number:

1317-39-1

Molecular formula:

Cu2O

IUPAC Name:

copper (I) oxide

Details on test material:

Lot/batch number: Not provided.
Description: Red powder Cuprous Oxide Paint Grade.
Purity: Not provided.
Stability: Not provided.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Source: Nottingham University School of Agriculture, Sutton, Bonington, Leics, UK.
Sex: Not reported.
Age/weight at study initiation: At the start of the study, animals weighed 2.76 to 3.09 kg, and were approximately 12 to 16 weeks old.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Amount of active substance instilled: 100 mg.

Duration of treatment / exposure:

Exposure period: The test material was placed into the conjunctival pouch of the right eye of each animal. The upper and lower eyelids were held
together for about one second immediately after application to prevent loss of the test material from the eye. Eyes were apparently not washed.

Observation period (in vivo):

Postexposure period: 21 days.

Number of animals or in vitro replicates:

Number of animals per group: 3.

Details on study design:

Scoring system: Refer to the attached Figure 1.
Opthalmoscopic examination: Examination of the eye was facilitated by the use of a standard ophthalmoscope (Keeler). After scoring the degree of
irritation at 24 hours, corneal opacity was, where appropriate, further investigated under ultra violet illumination (Mineralight UVSL-58) preceded by
the instillation into the eye of 0.05 ml of fluorescein B.P.
Examination time points: Assessment of damage/irritation was made 1, 24, 48 and 72 hr, and 7, 14 and 21 days following treatment, according to
Draize, 1959 (see 'Other information on materials and methods.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

(mean)

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

cornea opacity score

Remarks:

(mean)

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

cornea opacity score

Remarks:

(mean)

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

other: Diffuse corneal opacity persisted in the remaining rabbit up to and including Day 21. However, as the severity of the corneal opacity had reduced over time this finding is not considered to be evidence of irreversible damage.

Results 4

Irritation parameter:

iris score

Remarks:

(mean)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

iris score

Remarks:

(mean)

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

iris score

Remarks:

(mean)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness - mean)

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

conjunctivae score

Remarks:

(redness - mean))

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness - mean)

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 10

Irritation parameter:

chemosis score

Remarks:

(mean)

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

chemosis score

Remarks:

(mean)

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 12

Irritation parameter:

chemosis score

Remarks:

(mean)

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Any other information on results incl. tables

Reversibility: 2/3 rabbits were free from ocular changes by Day 14.

Clinical signs: Not reported.

Overall result: Table 1 below shows the average scores after 24, 48 and 72 hours for each animal:

 

Table 1. Average ocular scores.

Mean scores (24, 48, 72 h)	Cornea opacity	Iris lesion	Conjunctivae
			redness	chemosis
Animal No. 1 (482)	2	1	2.7	2
Animal No. 2 (485)	2	1	2.7	3
Animal No. 3 (487)	2	1	2.7	2

 

Table 2. Ocular scores.

 

Animal No	1 (482)	2 (485)	3 (487)
Corneal opacity                       1h 24h 48h 72h 7d 14d 21d Mean (24, 48 & 72h)	1 2 2 2 1 0 0 2	1 2 2 2 D 0 0 2	1 2 2 2 2 1 1 2
Iris lesion                                1h 24h 48h 72h 7d 14d 21d Mean (24, 48 & 72h)	1 1 1 0 0 0 1 1	1 1 1 0 0 0 0 1	0 1 1 1 0 0 0 1
Conjuctival redness                1h 24h 48h 72h 7d 14d 21d Mean (24, 48 & 72h)	3 3 3 2 0 0 0 2.7	3 3 3 2 1 0 0 2.7	3 3 3 2 0 0 0 2.7
Conjunctival chemosis           1h 24h 48h 72h 7d 14d 21d Mean (24, 48 & 72h)	2 3 2 1 0 0 0 2	2 4 3 2 1 0 0 3	2 3 2 1 0 0 0 2

D = dulling of the cornea.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Ocular irritation was seen in all three test rabbits. According to Annex VI of Commission Directive 2001/59/EC cuprous oxide in this study meets the criteria for classification as an irritant. The test substance should be attributed the symbol Xi: Irritant and the Risk Phrase R:36 Irritating to eyes.

Executive summary:

Materials and Methods

This study was conducted according to GLP, and to OECD Test Guideline 405 'Acute Eye Irritation/Corrosion' (adopted 24 April 2002). Only minor deviations from test guideline occurred. These deviations are not considered to have influenced the outcome or the integrity of the study.

Eye irritation potential of cuprous oxide was investigated in 3 rabbits. Within 24 hours of commencement of the test both eyes of each test rabbit provisionally selected were examined for evidence of ocular irritation or defect. Animals showing evidence of ocular lesions were rejected and replaced.

On the day of the test each rabbit was held firmly but gently until quiet. A 100 mg aliquot of the test material was instilled into the right eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test material was dropped. The upper and lower eyelids were held together for about one second immediately after application to prevent loss of the test material from the eye. The contralateral eye remained untreated and was used for control purposes.

Assessment of damage/irritation was made 1, 24, 48 and 72 hrs, and 7, 14 and 21 days after treatment. The scoring system is given in the attached Figure 1.

At the start of the study animals weighed 2.76 to 3.09 kg, and were approximately 12 to 16 weeks old.

Results and Discussion

See Table 2 ('Other information on results') for ocular scores.

 

Table 1 (see 'Other information on results') shows the average scores after 24, 48 and 72 hours for each animal.

 

Diffuse corneal opacities were observed in all three rabbits at the one hour reading and by the 24 hours reading translucent opacities had developed in all three rabbits. The reactions had resolved in two rabbits by Day 14 but diffuse corneal opacity persisted in the remaining rabbit up to and including Day 21, accompanied by vascularisation. In addition, a small area of lenticular opacity was seen in one rabbit (1485) on Day 7. Iritis was observed in all three rabbits by the 24 hours reading. The reactions had ameliorated in all three rabbits by Day 7.

 

A diffuse, beefy red colouration of the conjunctivae, accompanied by considerable swelling with the eye about half or almost completely closed had developed in all three rabbits by the 24 hours reading. A reduction in severity of reaction was seen from this reading and the reactions had ameliorated in two rabbits by Day 7 and in the remaining rabbit by Day 14.