Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant, guideline study, available as an unpublished report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Physical state: White solid
- Purity: >98%
- Substance identity: 10649 Lithium palmitate synthetic sample
- Batch number: 10649
- Analysis code: A052/99
- Expiration date: 2014-08-24
- Storage of test material: Room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Selection of animals: Immediately prior to test initiation, both eyes of the provisionally selected test rabbits were examined and any animals showing evidence of ocular irritation or defect were rejected
- Age at test initiation: 12 to 20 weeks
- Acclimatisation period: At least 5 days
- Housing: Individually in suspended cages
- Feeding: Free access to mains drinking water and commercial food
- Temperature: 17 to 23°C
- Relative humidity: 30 to 70 %
- Air flow: At least fifteen changes per hour
- Photoperiod: Twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
- Volume: 0.1 mL of lithium palmitate, equivalent to approximately 66 mg, was applied to the conjunctival sac of the right eye and the upper and lower eyelids were held together for about one second immediately after treatment
Duration of treatment / exposure:
- Duration of exposure: The rabbits' eyes were not washed
Observation period (in vivo):
- Observations of eyes: Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment
- Observations of reversibility: An observation was made on Day 7 to assess the reversibility of the ocular effects
Number of animals or in vitro replicates:
- Number of animals: Initially, a single rabbit was treated and after consideration of the ocular response, a second animal was treated
Details on study design:
- Control: The left eye remained untreated and was used for control purposes
- Observations of rabbits: Any other ocular effects and any clinical signs of toxicity were also noted and individual bodyweights were recorded on the day of dosing and at the end of the observation period
- Assessment method: Occular irritation potential results were interpreted according to the Globally Harmonized System of Classification and Labelling of Chemicals

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Remarks:
mean
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible
Remarks:
within 48 h
Irritation parameter:
iris score
Remarks:
mean
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 7 days
Irritant / corrosive response data:
- Corneal effects: None were noted during the study
- Iridial effects: Inflammation was noted in both treated eyes one hour after treatment and in one treated eye at the 24 Hour observation
- Conjunctival effects: Moderate irritation in both treated eyes at 1 and 24 hours after treatment, with minimal irritation in both treated eyes at 48 hours and in 1 treated eye at 72 hours
- Reversibility: Both treated eyes appeared normal at 7 days
- Conclusion: Lithium palmitate produced a maximum group mean score of 17.0 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. Lithium palmitate does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.
Other effects:
- Body weight: Both animals showed expected gain in bodyweight during the study

Any other information on results incl. tables

Individual scores and individual total scores for occular irritation

Rabbit Number and Sex

72629Male

72644Male

IPR = 0

IPR = 0

Time After Treatment

1
Hour

24
Hours

48
Hours

72
Hours

7
Days

1
Hour

24
Hours

48
Hours

72
Hours

7
Days

CORNEA

 

 

 

 

 

 

 

 

 

 

E = Degree of Opacity

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

Score (E x F) x 5

0

0

0

0

0

0

0

0

0

0

IRIS

 

 

 

 

 

 

 

 

 

 

D

1

1

0

0

0

1

0

0

0

0

Score (D x 5)

5

5

0

0

0

5

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

 

 

A = Redness

2

2

2

1

0

2

2

1

1

0

B = Chemosis

2

2

1

1

0

2

2

1

1

0

C = Discharge

2

1

0

0

0

2

1

0

0

0

Score (A + B + C) x 2

12

10

6

4

0

12

10

4

4

0

Total Score

17

15

6

4

0

17

10

4

4

0

IPR = Initial pain reaction

Individual total scores and group mean scores for occular irritation

Rabbit Number

and Sex

Individual Total Scores At:

1 Hour

24 Hours

48 Hours

72 Hours

7 Days

72629Male

17

15

6

4

0

72644Male

17

10

4

4

0

Group Total

34

25

10

8

0

Group Mean Score

17.0

12.5

5.0

4.0

0.0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Lithium palmitate does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.
Executive summary:

The eye irritation of lithium palmitate was assessed in a GLP-compliant, in vivo eye irritation study following OECD guideline 405 (Harlan 2013). A single treatment of lithium palmitate was applied to the non-irrigated eye of two rabbits and observations made at 1, 24, 48 and 72 hours and 7 days for effects on conjunctivae, iris and cornea and for reversibility of effects. No irritation classifiable under CLP/GHS was observed. The study is considered relevant and reliable for use for this endpoint.