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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation, other
Remarks:
in vivo study performed prior to change in information requirements
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
of 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
of 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
of 1998
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Number and Sex: 3 males
- Animal supplier: S&K-LAP Kft., 2173 Kartal, Császár út 135, Hungary
- Age on day of dosing (Day 0): Ca. 11 weeks old (young adult)
- Weight prior to dosing (Day 0): Minimum 2744 g, maximum 2931 g
- Housing: Individual housing in AAALAC approved metal wire rabbit cages allowing for some
social interaction with rabbit(s) in adjacent cages
- Diet (ad libitum): Commercially available rabbit diet, AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Hungary
- Water (ad libitum): Tap water from municipal supply
- Acclimation period: 7 days prior to study start under laboratory conditions.

Water was regularly analysed for contaminants, detailed information on the diet was provided by the supplier. Water and diet used in the present study were not considered to adversely affect the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS

Controlled environment, environmental conditions were:
- Ventilation, air changes per hour: 15-20
- Temperature (°C): 19.7 to 27.1°C
- Relative Humidity (%): 32 to 83%
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night
Relative humidity and temperature at times slightly exceeding the upper target limits of 70% and 23°C, respectively, were not considered to have compromised the integrity or validity of the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL of the undiluted wax-like test material was administered into the conjunctival sac of one eye per rabbit (left eye). The contralateral eye (right eye) remained untreated to serve as a control.
Duration of treatment / exposure:
Residual test material was seen in the treated eyes. Therefore, the eyes were rinsed with physiological saline at 1 hour after test material instillation.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 adult male rabbits
Details on study design:
EYE EVALUATION:

Within 2.5 hours before treatment start both eyes of each animal were investigated to ensure that there were no pre-existing corneal damage, eye irritation or ocular defects.

One animal was initially treated and, in the absence of a severe effect at 1 hour post instillation, the remaining two animals were committed to the study.

Eyes were evaluated in all animals at approximately 1, 24, 48 & 72 hours and 7, 14 & 21 days after test material instillation adopting the numerical scoring system listed in Table 1 in the field below. Grades attained at 24, 48 and 72 hours after instillation were included in the mean gradings of ocular lesions and used for evaluation of the necessity of eye irritation/corrosion classification.

????Equipment used for eye evaluation: Ophthalmoscope or pencil beam torch

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Corneal findings were confined to 1 animal
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: This was the only animal with corneal opacity findings
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: Corneal ulceration or opacity were not evident
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: Corneal ulceration or opacity were not evident
Irritation parameter:
other: corneal area affected
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: This was the only animal with corneal opacity findings
Irritation parameter:
iris score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: Iridic changes were not evident
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.8
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
other: Discharge
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: Discharge
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: Discharge
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
other: Discharge
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
Iridic lesions were not evident throughout the study, and corneal lesions (opacity grade 1) were confined to one animal (#1) from 1 to 72 hours after test material instillation entirely disappearing thereafter. The area of cornea involved was scored grade 4 to 0. Conjunctival redness grade 2, chemosis grade 2 or 3 and discharge, grade 2 or 3, were seen in all animals at 1 h after instillation, therafter gradually decreasing in severity and incidence and having fully disappeared in all animals by three weeks after instillation. Control eyes were without ocular findings throughout the 21 day observation period.
Other effects:
Observation of the animals for defined behavioural criteria led to the conclusion that instillation of the test material induced slight initial pain (grade 2). Any other signs of systemic toxicity or ill health were not evident and bodyweight was unaffected by treatment with the test material.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The outcome of the present in vivo study does not necessitate any labelling regarding eye irritation according to EU classification rules [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008]. The findings noted were fully reversible and their incidence is within the category “not irritating to eyes”.