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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a contract research organization. The study is scientifically valid and the report is fully adequate for assessment, despite some minor restrictions (e.g. due to limited reporting).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
of 1981
Deviations:
no
Qualifier:
according to
Guideline:
other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA
Deviations:
not specified
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
other: Tattooed New Zealands (albino rabbit)
Details on test animals or tissues and environmental conditions:
- Number: 6 animals,
- Bodyweight: 2.5 to 3.0 kg
- Housing: Individual housing in cages.
- Diet: Commercially available standard laboratory diet for rabbits ( Altromin, Lage, Germany).
Prior to dosing the animals were starved for 16 hours.
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS

Room temperature kept constant at 18±2°C, the relative humidity at 50-60%. 12 hours illumination per day.

Test system

Vehicle:
other: CMC (carboxymethyl cellulose "Tylose") containing 40% test substance
Controls:
not required
Amount / concentration applied:
Undiluted test substance could not be administered. Therefore, a dose formulation was prepared containing 40.5% WS400130.
After warming this test substance dilution to 40°C, 0.1 ml of it was administered into the conjunctival sac of one eye per rabbit. The contralateral eye remained untreated to serve as a control.
Duration of treatment / exposure:
There was no mentioning in the report that eyes were rinsed after treatment. Consequently the treatment/exposure period was equivalent to the entire observation period following administration, which was 7 days, or lasted until removal of the test material by physiological mechanisms, whichever happened sooner.
Observation period (in vivo):
7 days (i.e. the final observation time point was 7 days post instillation)
Number of animals or in vitro replicates:
6 adult rabbits
Details on study design:
Eyes were evaluated for occular lesions using ultraviolet light. Before and after the test the eyes of all animals were examained after staining with 2% fluorescein thus supporting the recognition of corneal lesions.

The numerical scoring system listed in Table 1 in the field below was adopted. Time points of evaluation were: Pretest (prior to treatment), 1, 2, 4, 8, 24, 48, 72 and 96 hours after administration and daily thereafter until 7 days after administration. Grades attained at 24, 48 and 72 hours after administration were included in the mean gradings of ocular lesions used for eye irritation/corrosion classification.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over 6 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: Corneal irritation or opacity was not evident during the study
Remarks on result:
other: Treated with a dose formulation containing 40.5% WS400130
Irritation parameter:
iris score
Basis:
mean
Remarks:
over 6 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: Iridal changes were not evident during the study
Remarks on result:
other: Treated with a dose formulation containing 40.5% WS400130
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
over 6 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 4 hours
Remarks on result:
other: Treated with a dose formulation containing 40.5% WS400130
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over 6 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: Chemosis was not evident during the study
Remarks on result:
other: Treated with a dose formulation containing 40.5% WS400130
Irritation parameter:
other: lacrimation score
Basis:
mean
Remarks:
over 6 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 4 hours
Remarks on result:
other: Treated with a dose formulation containing 40.5% WS400130
Irritant / corrosive response data:
Corneal and iridic lesions and chemosis were not evident throughout the study. Conjunctival redness and lacrimation, both findings grade 1, were seen in all treated eyes at 1 and 2 hours post instillation having completely disappeared in all animals by 4 hours post instillation. Examination of the eyes at 4 and 8 hours post instillation and daily afterwards until 7 days post instillation did not reveal any findings.
Other effects:
There was no mentioning of any other effects in the report.

Applicant's summary and conclusion

Interpretation of results:
other: not irritating according to EU regulation
Conclusions:
WS400130 could not be administered undiluted. Therefore, a dilution in CMC (Tylose) containing 40.5% WS400130 was tested. The outcome of the present study does not necessitate any labelling regarding eye irritation according to EU classification rules [REGULATION (EC) 1272/2008]. The findings noted were very minor in degree, restricted to the 1 and 2 hour post instillation time points and fully reversible within 4 hours. Therefore, they fell within the category “not irritating to eyes”.