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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:
The study was conducted between 11 November 2013 and 16 December 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is considered to be reliability 1 as it has been conducted according to OECD Test Guideline 405 using an in vivo method and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
Identification: IFF TM 10-202
Storage Conditions: Room temperature in the dark under nitrogen

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.44 to 2.83 kg and were twelve to twenty weeks old. After an acclimatization period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of 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 fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated for control purposes
Amount / concentration applied:
0.1 mL of the test item

Test Item Formulation and Experimental Preparation
For the purpose of the study the test item was used as supplied. The absorption of the test item was not determined.


Duration of treatment / exposure:
The test material was not removed.
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
Three
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre-dose anaesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.
A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale.
Eight hours after test item application, a subcutaneous injection of post-dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 hours later. No further analgesia was required.
After consideration of the ocular responses produced in the first treated animal, two additional animals were similarly treated.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977).
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Any clinical signs of toxicity, if present, were also recorded.
Additional observations were made on Days 7 and 14 to assess the reversibility of the ocular effects.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
73723 Male
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
73798 Male
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
73799 Male
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
73723 Male
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
73798 Male
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
73799 Male
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Remarks:
73723 Male
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Remarks:
73798 Male
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Remarks:
73799 Male
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
Chemosis
Basis:
animal #1
Remarks:
73723 Male
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
Chemosis
Basis:
animal #2
Remarks:
73798 Male
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
Chemosis
Basis:
animal #3
Remarks:
73799 Male
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
No corneal effects were noted during the study.
Iridial inflammation was noted in one treated eye one hour after treatment.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in two treated eyes with minimal conjunctival irritation noted in one treated eye at the 24 and 48-Hour observations. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in one other treated eye at the 72-Hour observation. Minimal conjunctival irritation was noted in one treated eye at the 7-Day observation.
One treated eye appeared normal at the 72-Hour observation, one other treated eye appeared normal at the 7-Day observation and the remaining treated eye appeared normal at the 14-Day observation.
Other effects:
Body weight
All animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit No. & Sex

73723 Male

73798 Male

73799 Male

IPR = 0

IPR = 0

IPR = 0

Time after Treatment

1 h

24 h

48 h

72 h

7 days

14 days

1 h

24 h

48 h

72 h

7 days

1 h

24 h

48 h

72 h

Cornea

E = degree of opacity

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

F = Area of cornea involved

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Score = (E x F) x 5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Iris

D

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Score (D x 5)

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctivae

A = redness

2

2

2

2

1

0

2

2

2

1

0

2

1

1

0

B = Chemosis

2

1

1

1

1

0

2

2

2

1

0

2

1

0

0

C = discharge

2

1

1

1

1

0

1

1

1

0

0

2

1

0

0

Score (A + B + C) x 2

12

8

8

8

6

0

10

10

10

4

0

12

6

2

0

Total Score

17

8

8

8

6

0

10

10

10

4

0

12

6

2

0

IPR = Initial pain reaction

Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit No. & Sex

Individual total scores at:

1 h

24 h

48 h

72 h

7 days

14 days

73723 Male

17

8

8

8

6

0

73798 Male

10

10

10

4

0

-

73799 Male

12

6

2

0

-

-

Group Total

39

24

20

12

6

0

Group Mean Score

13.0

8.0

6.7

4.0

3.0

0.0

- Observation not required - considered to be zero for calculation of Group Mean Score

Individual body weights and body weight changes

Rabbit No. & Sex

Individual Body Weight (kg)

Body Weight Change (kg)

73723 Male

Day 0

Day 14

0.31

2.83

3.14

73798 Male

Day 0

Day 7

0.08

2.59

2.67

73799 Male

Day 0

Day 3

0.07

2.44

2.51

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a maximum group mean score of 13.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test item, TM 10-202, does not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals.

The test item, TM 10-202, does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.
Executive summary:

The eye irritation potential of the test substance, TM 10-202, was assesed as not an eye irritant according to OECD Test Guideline 405 using an in vivo method.