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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
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:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
The study report claims that the method was conducted according to the OECD guidelines of May 1981.
The following deviations from OECD Test Guideline 405 (adopted 24 April 2002) were noted:
• The report does not provide a rational for in vivo testing,
• The following information on test animals were not provided: sex, age of animals at the start of the study, individual animal weights at the start and conclusion of test (however weight range reported) and source,
• In this test six rather than the guideline recommended three animals were used.
• Reversibility of ocular changes has not been fully evaluated in this study,
According to OECD Test Guideline 405 the test material should be applied undiluted. For this reasons the results from the three animals receiving
undiluted test material will not be considered for classification purposes.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Lot/batch number: Not provided.
Description: Orange crystalline powder (inscription on pot: 84.5 p.c Cu.).
Purity: From information provided, assumed to be 84.5 %.
Stability: Not available.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Source: Not provided.
Sex: Female.
Weight at study initiation: 3.0 to 3.5 kg.
Age at study initiation: Age not provided.

Test system

Vehicle:
other: The test substance was applied undiluted or diluted (10% cuprous oxide diluted in water).
Controls:
no
Amount / concentration applied:
Amount of active substance instilled: 0.1 ml or 1g.
Duration of treatment / exposure:
The test material was placed into the conjunctival pouch of the left eye of each animal. Apparently eyes were not rinsed.
Observation period (in vivo):
10 days (animals that were administered undiluted test substance).
7 days (animals that were administered diluted test substance).
Number of animals or in vitro replicates:
3 (test material applied undiluted).
3 (test material applied as a 10% dilution).
Details on study design:
Opthalmoscopic examination: Yes.
Scoring system: Lesions of the cornea (degree and area of opacity), iris and conjunctiva (redness, chemosis and lacrimation) were scored according
to the Draize code. The scoring system is presented in detail on pages 4 and 5 of the study report.
Examination time points: Readings for eye alterations were made after 1, 2, 4, 12 and 24 hrs, and every day until day 7 (animals that were
administered diluted test substance) or day 10 (animals that were administered undiluted test substance).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(mean - degree of opacity)
Basis:
animal #1
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
(mean - degree of opacity)
Basis:
animal #2
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not fully reversible within: 10 days
Remarks on result:
other: Irritation (1) appeared on day 5
Irritation parameter:
cornea opacity score
Remarks:
(mean - degree of opacity)
Basis:
animal #3
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
(mean - area of opacity)
Basis:
animal #1
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
(mean - area of opacity)
Basis:
animal #2
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not fully reversible within: 10 days
Remarks on result:
other: Irritation (1) appeared on day 5
Irritation parameter:
cornea opacity score
Remarks:
(mean - area of opacity)
Basis:
animal #3
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Remarks:
(mean)
Basis:
animal #1
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Remarks:
(mean)
Basis:
animal #2
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Remarks:
(mean)
Basis:
animal #3
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Remarks:
(mean)
Basis:
animal #1
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Remarks:
(mean)
Basis:
animal #2
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Remarks:
(mean)
Basis:
animal #3
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
(mean - redness)
Basis:
animal #1
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Remarks:
(mean - redness)
Basis:
animal #2
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Remarks:
(mean - redness)
Basis:
animal #3
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Remarks:
(mean - discharge)
Basis:
animal #1
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
(mean - discharge)
Basis:
animal #2
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Remarks:
(mean - discharge)
Basis:
animal #3
Remarks:
(undiluted)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 8 days
Other effects:
Clinical signs: Not reported.
Reversibility:
Undiluted test material application - Observations were not made beyond day 10. As ocular changes were still evident in all three animals at this time point, reversibility was not fully assessed in this study.
Diluted test material application - All three animals were free of ocular signs by day 4.

Any other information on results incl. tables

Overall result: See Figure 1 (attached) for ocular scores obtained using both diluted and undiluted test material.

Table 1. Average scores after 24, 48 and 72 hours for each animal that received undiluted test material.

Mean scores

(24, 48, 72 h)

Cornea

opacity

Iris

lesion

Conjunctivae

redness

chemosis

Animal No. 1

0

0

2

1.7

Animal No. 2

0

0

2

2

Animal No. 3

0

0

2

1

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this study cuprous oxide showed a slight potential to induce eye irritation. According to Annex VI of Commission Directive 2001/59/EC cuprous
oxide, applied undiluted, does not meet the criteria for classification as irritant in this study (mean scores for each finding did not reach the
trigger values indicated). However, reversibility has not been fully evaluated in this study.
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). Some deviations from test guidelines occurred.

 

Eye irritation potential of cuprous oxide was investigated in 6 New Zealand rabbits. Three rabbits received undiluted test material and 3 rabbits received the 10% test material diluted in water.

 

Before and after the test the eyes of all animals were examined with fluorescin 0.15% Thilo®. After weighing (16 hours starved) 0.1 ml or 0.1g of the test substance was administered into the conjuctival pouch of the left eye. The right eye stayed untreated and served as control.

 

Readings for eye alterations were made after 1, 2, 4, 12 and 24 h, and every day until day 7 (animals that were administered diluted test substance) or day 10 (animals that were administered undiluted test substance).

 

At the start of the study the animals weighed between 3.0 and 3.5 kg.

 

 

Results and Discussion

 

Refer to the attached Figure 1 for ocular scores.

 

Average scores after 24, 48 and 72 hours are presented for each animal that received undiluted test material (see Table 1 - 'Other information on results').

According to OECD Test Guideline 405 the test material should be applied undiluted. For this reasons the results from the three animals receiving diluted test material shall not be considered for classification purposes.

 

According to Annex VI of Commission Directive 2001/59/EC cuprous oxide, applied undiluted, does not meet the criteria for classification as irritant in this study as mean scores (24, 48 and 72 h) for corneal opacity, iris lesion, redness of the conjunctivae, and oedema of the conjunctivae did not reach the trigger values indicated. However the above mentioned directive also indicates that ocular lesions are considered to be severe when they are still present at the end of the observations. In this study observations were made up to day 10 only whereas OECD guideline 405 recommends that animals should be observed for reversibility for up to 21 days. As reversibility was not fully examined a clear conclusion on the potential of cuprous oxide to induce eye irritation cannot be reached on the basis of this study alone. Nevertheless, this study provides relevant information which can be used to support the conclusions of other available studies.