Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation, other
Remarks:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo study are already available
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
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:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Lot/batch number: 02-0084
Description: Brown/black powder
Purity: 97.7% cupric oxide
Stability: Stable at room temperature
Molecular formula: CuO
Molecular weight: 79.55
Smiles notation: O=[Cu]
InCHI: 1s/Cu.O

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
Sex: Male.
Age/weight at study initiation: At the start of the study the mean bodyweights ranged from 2.0 to 3.5 kg and test animals were 12-16 weeks old.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: No - the test material was instilled into one eye, the untreated eye acted as a control.
Amount / concentration applied:
Amount of active substance instilled: 0.1 ml of test material (approximately 38 mg).
Duration of treatment / exposure:
Exposure period: 72 hours.
Observation period (in vivo):
Postexposure period: 7 days.
Number of animals or in vitro replicates:
Number of animals per group: 3
Details on study design:
Preparation of test substance: Test substance was used as supplied with no additional preparation.
Removal of test substance: The test substance was not removed from the eye. Irritancy was determined on the unrinsed eye.
Scoring system: Draize scoring system and modified Kay and Calandra classification system.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(Degree of opacity)
Basis:
mean
Remarks:
for 3 animals
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Remarks:
(Area of opacity)
Basis:
mean
Remarks:
for 3 animals
Time point:
other: 24, 48 and 72 hours
Score:
0.44
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Remarks:
for 3 animals
Time point:
other: 24, 48 and 72 hours
Score:
0.22
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
(Redness)
Basis:
mean
Remarks:
for 3 animals
Time point:
other: 24, 48 and 72 hours
Score:
0.77
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
for 3 animals
Time point:
other: 24, 48 and 72 hours
Score:
0.55
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
(Discharge)
Basis:
mean
Remarks:
for 3 animals
Time point:
other: 24, 48 and 72 hours
Score:
0.66
Max. score:
3
Reversibility:
fully reversible
Other effects:
According to the 6 point scale used by the investigators, copper oxide caused slight initial pain (class 2), whereby the rabbit blinked and tried to open the eye, but reflex closed it. Black residual material was noted in all treated eyes during the study.

In one animal, scattered or diffuse corneal opacity was noted in the treated eye at the 24, 48 and 72-hour observation time points. In the same animal, iridial inflammation was noted in the treated eye one hour after treatment and at the 24 and 48-hour observation time points.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in one treated eye
with minimal conjunctival irritation in the remaining treated eyes at the 24-hour observation. Moderate conjunctival irritation persisted in one treated eye at the 48-hour observation with minimal conjunctival irritation at the 72-hour observation.

Two treated eyes appeared normal at the 48-hour observation and the remaining treated eye appeared normal at the 7-day observation.

For further details see Table 1 ('Any other information on results').

Any other information on results incl. tables

Clinical signs: Not reported.

Further remarks: The pH of a 10 % w/v aqueous preparation of the test material was approximately 9.2.

Overall result: A single application of the test material to the non-irrigated eye of three rabbits resulted in scattered or diffuse corneal opacity in one treated eye up to the 72-hour observation time point, as well as iridial inflammation up to the 48-hour observation time point. Moderate conjunctival irritation was noted in all treated eyes 1-hour after treatment.

 

Two treated eyes appeared normal at the 48-hour observation and the remaining treated eye appeared normal at the 7-day observation time point.

 

The test material produced a maximum group mean score of 13.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

 

The test material did not meet the criteria for classification as an eye irritant according to EU labelling regulations Commission Directive 93/21/EEC.

Table 1. Acute Eye Irritation - Summary of Results

 

 

CORNEA

IRIS

(Congestion)

CONJUNCTIVA

(Degree of opacity)

(Area of Opacity)

Redness

Chemosis

Discharge

Score (average of animals investigated)

0-4

0-4

0-2

0-3

0-4

0-3

1 hour

0

0

0.33

2

1.33

2.33

24 hour

0.33

0.66

0.33

1.33

1

1.33

48 hour

0.33

0.33

0.33

0.66

0.33

0.33

72 hour

0.33

0.33

0

0.33

0.33

0.33

Average 24h, 48h and 72h

0.33

0.44

0.22

0.77

0.55

0.66

Area effected

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Maximum average score

(including area affected, max 110)

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Reversibility

Completely reversible

Completely reversible

Completely reversible

Completely reversible

Completely reversible

Completely reversible

Maximum time for reversion

7 days

7 days

72 hours

7 days

7 days

7 days

Justification of the read-across from copper (II) oxide to copper sulphide:

In order to minimise animal testing, available data on copper(II) oxide have been read-across to copper sulphide (copper (II) oxide is unclassified on the basis of acute toxicity, irritation and sensitisation potential). These are both simple inorganic copper(II) compounds with very low water solubility and an anion of no toxicological concern. In fact, theoretical estimates for the solubility of copper sulphide are orders of magnitude lower than those of the oxide, ranging from 3.31E-11 µg/L to 2.4E-10 µg/L (see the attached document "The Solubility Products of Copper Sulphide" for further information). It is generally accepted that lower water solubility can be equated to lower bioavailability and hence acute toxicity; an effect clearly seen by a comparison of copper(II) oxide toxicity with that of the more soluble copper(I) oxide. On this basis, it is considered that a read-across of the acute toxicological, irritation and sensitisation properties from copper(II) oxide to copper sulphide represents a reasonable worst-case approach, and leads to that conclusion that copper sulphide is similarly unclassified. This conclusion is supported by the fact that acute oral and irritation testing carried out with dicopper sulphide confirms that this marginally more soluble compound is also unclassified.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Classification according to Directive 67/548/EEC: Not classified.
Classification according to CLP/GHS: Not classified.
Executive summary:

Materials and Methods:

This study was conducted to assess the irritancy potential of copper oxide to the eye of the New Zealand White rabbit.

Three New Zealand White rabbits (male) were given a single dose of 0.1 ml copper oxide (38 mg) applied directly into the conjunctival sac of the right eye. The left eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made 1, 24, 48 and 72 hours following treatment, according to the Draize scoring system and a modified version of the Kay and Calandra classification system. Any other ocular effects were also noted.

An additional observation was made in one treated eye on day 7 to assess the reversibility of the ocular effects.

The study was conducted according to OECD Guidelines for the Testing of Chemicals No. 405 'Acute Eye Irritation/Corrosion' (adopted 24 February 1987) and Commission Directive 92/69/EEC Method B5 Acute Toxicity (Eye Irritation). The study was also conducted according to GLP.

No deviations from the test guidelines, or deficiencies in the method were reported.

Results and Discussion:

A single application of the test material to the non-irrigated eye of three rabbits resulted in scattered or diffuse corneal opacity in one treated eye up to the 72-hour observation time point, as well as iridial inflammation up to the 48-hour observation time point. Moderate conjunctival irritation was noted in all treated eyes 1-hour after treatment. Two treated eyes appeared normal at the 48-hour observation and the remaining treated eye appeared normal at the 7-day observation time point.

The test material did not meet the criteria for classification as an eye irritant.