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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:
key study
Study period:
May 29, 2001 - June 11, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(1992)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): CITRATHAL R
- Description: Colourless to pale yellow liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): CITRATHAL R
- Description: Colourless to pale yellow liquid
- Analytical purity: not applicable (as it is an UVCB substance)
- Composition of test material, percentage of components: as defined in section 1.2
- Lot/batch No.: 9000416199
- Expiration date of the lot/batch: August 27, 2001
- Storage condition of test material: In the original container, at room temperature (range of 17-23 'C), away from direct sunlight

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne, France
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 2.1-2.4 kg
- Housing: Animals were housed individually in stainless steel cages
- Diet: Free access to pelleted diet for rabbits (Provimi Kliba 3418). Haysticks were available during the study period.
- Water: Free access to tap water (ad libitum)
- Acclimation period: 6 days (1 female) and 7 days (other 2 animals)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 23
- Humidity (%): 30 - 70
- Air changes (per hr): approx 10-15
- Photoperiod (hrs dark / hrs light): 12/12

TREATMENT DATES: June 5, 2001 (1 female) and June 6, 2001 (other 2 animals)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
Not applicable (as the eyes were not rinsed)
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
1 female and subsequently 1 male and 1 female
Details on study design:
STUDY DESIGN
As it was suspected that the test substance might produce irritancy (based on the earlier performed skin irritation study in rabbits), one female was treated first. As neither a corrosive effect nor a severe irritant effect was observed, the test was completed using 2 additional animals the following day.

TREATMENT
On the day of treatment, the test substance was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance.

REMOVAL OF TEST SUBSTANCE
The treated eyes were not rinsed.

OBSERVATIONS (beschrijf beperkt)
- Mortality/Viability: Daily
- Clinical signs: Daily
- Body Weight: At start of acclimatization, on the day of application and at termination
- Necropsy: not performed
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
The irritation was assessed according to OECD 405.
Also staining of sclera and cornea by the test substance was examined. Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel, Switzerland).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Mean score following grading at 24, 48 and 72 hours after installation
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other:
Remarks:
Mean score following grading at 24, 48 and 72 hours after installation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #1 and #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Remarks:
Mean score following grading at 24, 48 and 72 hours after installation
Irritation parameter:
chemosis score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Mean score following grading at 24, 48 and 72 hours after installation
Irritant / corrosive response data:
- Slight reddening of the conjunctivae was noted in all animals from 1 to 24 hours and was still evident in one female at the 48-hour reading
Other effects:
- A slight watery discharge was observed in 2 animals at the 1-hour reading and a slight mucus discharge was evident in the other animal at this reading
- Moderate reddening of the sclera was observed in all animals 1 hour after treatment and slight reddening persisted in 2 animals up to and including the 48-hour reading
- At the 72 hour reading nothing was observed anymore

Any other information on results incl. tables

- No clinical signs of systemic toxicity were observed and no mortality occurred

- Body weights were within the normal range of variability

- No staining of the treated eyes by the test substance was observed

- No corrosion of the cornea was observed at any of the reading times

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an eye irritation study with rabbits, performed in accordance with OECD 405 (1987) and according to GLP principles, limited irritation was observed.
Executive summary:

In an eye irritation study in rabbits, conducted in accordance with OECD 405 (1987), EU Method B.5 (1992) and according to GLP principles, 0.1 mL of the substance was placed in the conjunctival sac of the left eye of 1 female rabbit and subsequently of 1 male and 1 female rabbit the following day. The eyes were not rinsed and were examined approximately 1, 24, 48 and 72 hours after instillation. Slight reddening of the conjunctivae was noted in all animals from 1 to 24 hours and was still evident in one female at the 48-hour reading. No abnormal findings were observed in the cornea or iris of any animal at any reading. A slight watery discharge was observed in 2 animals at the 1-hour reading and a slight mucus discharge was evident in the other animal at this reading. Moderate reddening of the sclera was observed in all animals 1 hour after treatment and slight reddening persisted in 2 animals up to the 48-hour reading. No clinical signs of systemic toxicity nor mortalities were observed. Based on the results of this study, the substance does not need to be classified for eye irritation/corrosion in accordance with the CLP Regulation.