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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:
27 November 27, 2001 to 25 December, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted in 2001 according to OECD Method # 405 and in accordance with GLP. The study material is well characterized.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2002

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Substance is an off- white powder. Stored at room temperature in the dark; received at testing laboratory on 2001-24-10.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
At the start of the study the males rabbits weighed 2.0 to 3.5 kg and were twelve to sixteen weeks old. Free access to mains drinking water and food was allowed throughout the study. The temperature and relative humidity were set to achieve limits of 17 to 23 C and 30 to 70% respectively. The rate of air exchange was at least 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours of darkness.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: left eye of each animal was untreated
Amount / concentration applied:
0.1 ml - equivalent to 36 mg test material
Duration of treatment / exposure:
Initially a single animal was treated. A single application of 0.1 ml of test material to the non-irrigated eye of one rabbit was performed by placing test material in the conjunctival sac of the right eye and gently pulling the lower eye lid away from the eyeball. The upper and lower eyelid were held closed for about one second after treatment to prevent loose of material and then released. The left eye was left untreated to serve as the control.
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were perfomed on day 7 and 14 to assess the reversibilityof the ocular effects.
Number of animals or in vitro replicates:
3 males rabbits
Details on study design:
Before treatment both eyes were checked for sign of ocular irritation or defect with the aid of a direct light source. Only animals free of ocular damage were used in the study. Initially a single rabbit was treated with 0.1 ml of test material by placing the test material in the conjunctival sac of the right eye and gently pulling the lower eye lid away from the eyeball. The upper and lower eyelid were held closed for about one second after treatment to prevent loose of material and then released. The left eye of each test animal remained untreated and used as a control. An initial assessment of pain was completed immediately after treatment. After evaluating the first animal's ocular response, 2 additional animals were treated. To minimize pain on application of the test material, one drop of a local anesthetic was added to both eyes 1 to 2 minutes before treatment.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 7 dy
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 7 dy
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 7 dy
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
animal #1
Time point:
other: overall at 24,48 and 72 hr
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
animal #2
Time point:
other: overall at 24,48 and 72 hr
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: max duration 7 dy
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
animal #3
Time point:
other: overall at 24,48 and 72 hr
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: max duration 7 dy
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 7 dy
Irritation parameter:
cornea opacity score
Remarks:
degree of opacity
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
cornea opacity score
Remarks:
degree of opacity
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
cornea opacity score
Remarks:
degree of opacity
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: overall at 24, 48 and 72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Max. duration: 72 hr
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hr
Score:
19
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hr
Score:
32.3
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hr
Score:
30.7
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hr
Score:
25.3
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 7 day
Score:
4
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 14 days.The maximum duration for both conjunctival redness achemosis is 7 days.The test material produced an overall maximum group score of 32.3 and was classified as a moderate irritant (class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system
Other effects:
Dulling of the normal lustre of the cornea was noted in all treated eyes one hour after treatment. Scattered or diffuse corneal opacity was noted in one treated eye and scattered or diffuse corneal opacity was noted in two treated eyes at the 48 and 72-hour observations. No other corneal effects were noted during the study. Duration for both conjunctival redness achemosis is 7 days.
Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24,48 and 72-hour observations. No other iridial effects were
noted.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation at the 7-day observation.

Discharge with moistening of the lids and hairs in a considerable area around the eye was noted in all animals at the one, 24 and 48 hour observationtimes. It was reduced in all at 72 hours and slight discharge was noted in two animals at 7 days.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was classified as an irritant according to EU labeling regulations assigned the symbol "Xi", the indication of danger " Irritant" and the risk phrase R36 "Irritating to the eyes."
Executive summary:

Studies were assigned reliability of 2 and followed acceptable OECD, EU or recognised standards and were in accordance with GLP.

The maximum duration for both conjunctival redness and chemosis is 7 days and all treated eyes aooeared irnak at the 14-day observation. The test material produced an overall maximum group score of 32.3 and was classified as a moderate irritant (class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Based on the results of the eye irritation study and according to EU labeling regulations the test material is classified as follows:

According to Annex 1 to the CLP Regulation (GHS):

classification: eye irritation - category 2,

symbol: exclamation mark

signal word: Warning

hazard statement: "causes serious eye irritation"