Fatty acids, C16-18 (even numbered) saturated and C16-20 (even numbered) unsaturated, lithium salts

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

26 March 2012 to 30 April 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant, guideline study, available as an unpublished report.

Justification for type of information:

See IUCLID section 13 for read across justification

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2102

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Lithium myristate

EC Number:

243-743-8

EC Name:

Lithium myristate

Cas Number:

20336-96-3

Molecular formula:

C14H28O2.Li

IUPAC Name:

lithium myristate

Test material form:

solid

Details on test material:

- Physical state: White solid
- Purity: >99%
- Substance identity: 10634 Lithium myristate, synthetic sample
- Batch number: 10074
- Analysis code: A194/99
- Expiration date: 2012-12-31
- 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:

- Test animals: Two New Zealand White (Hsdlf:NWZ) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At test initiation, rabbits were twelve to twenty weeks old and weighed 2.25 to 3.13 kg. After at least five days acclimatisation, a number unique within the study was written in black, indelible marker-pen on the inner surface of the ear and on the cage label. Immediately prior to test initiation, both eyes of the provisionally selected rabbit were examined for evidence of occular irritation or defect with a standard opthalmoscope and only animals free of ocular damage were used.
- Housing: Animals were housed individually in suspended cages 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.
- Feeding: Throughout the study, animals were allowed free access to mains drinking water and food (2930 Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK). The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose of the study.
- Environmental conditions: The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose of the study. The rate of air exchange was at least fifteen changes per hour. The lighting was controlled by a time switch to give twelve hours continuous light (06:00-18:00) and twelve hours darkness.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

- Volume of application: 0.1 mL lithium myristate (found to weigh approximately 68 mg after gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye.

Duration of treatment / exposure:

- Duration of treatment: Single administration, no irrigation used
- Duration of observation: 14 days

Observation period (in vivo):

- Observation period: 14 days. After approximately 1, 24, 48 and 72 hours after application, the ocular damage/irritation was assessed according to Draize JH (1977) "Dermal and eye toxicity tests" in Principles and procedures for evaluating the toxicity of household substances, National Academy of Sciences, Washington DC, pp. 48-49 and any other ocular effects or clinical signs of toxicity were also noted. The reversibility of ocular effects was assessed by observations on days 7 and 14. Individual bodyweights were recorded on days 0 and at test termination.

Number of animals or in vitro replicates:

- Number of animals: 2

Details on study design:

- Irrigation of eyes: No evidence of residual test item in the treated eyes; no rinsing required.
- Interpretation methods: The numerical values corresponding to each animal, tissue and observation time were recorded using the Draize evaluation scale (Draize J H, 1977, "Dermal and eye toxicity tests" in: Principles and procedures for evaluating the toxicity of household substances, National Academy of Sciences, Washington DC). Using the numerical data obtained for cornea, iris and conjunctivae scores, the irritation potential was determined according to Regulation (EC) No 1272/2008, Relating to Classification, Labelling and Packaging of Dangerous Substances.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 7

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

- Conjunctivae: Moderate conjunctival irritation was noted in the treated eyes of both rabbits one hour after treatment and at the 24, 48 and 72 hour observations with minimal conjunctival irritation noted at the 7 day observation.
- Iris: Iridial inflammation was noted in the treated eyes of both rabbits one hour after treatment and at the 24 and 48 hour observations and persisted in one treated eye at the 72 hour observation.
- Cornea: Scattered or difuse corneal opacity was noted in the treated eyes of both animals one hour after treatment and at the 24, 48 and 72 hour observations and persisted in one treated eye at the 7 day observation.
- Reversibility: Treated eyes of both rabbits appeared normal at the 14 day observation.
- Result: Irritating to eyes (category 2) according to Regulation (EC) No. 1272/2008

Other effects:

- Bodyweight: Both animals showed expected bodyweight gain during the study.

Any other information on results incl. tables

Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit number and sex	71855 Male						71855 Male
	IPR = 2						IPR = 2
Time after treatment	1 hour	24 hour	48 hour	72 hour	7 day	14 day	1 hour	24 hour	48 hour	72 hour	7 day	14 day
CORNEA
E = Degree of Opacity	1	1	1	1	1	0	1	1	1	1	0	0
F = Area of Cornea Involved	1	2	2	2	1	0	1	1	1	1	0	0
Score (E x F) x 5	5	10	10	10	5	0	5	5	5	5	0	0
IRIS
D	1	1	1	1	0	0	1	1	1	0	0	0
Score (D x 5)	5	5	5	5	0	0	5	5	5	0	0	0
CONJUNCTIVAE
A = Redness	2	2	2	2	1	0	2	2	2	2	1	0
B = Chemosis	2	2	2	2	1	0	2	2	2	2	1	0
C = Discharge	2	2	2	1	0	0	2	2	2	1	0	0
Score (A + B + C) x 2	12	12	12	10	4	0	12	12	12	10	4	0
Total score	22	27	27	25	9	0	22	22	22	15	4	0

Individual Total Scores and Group Mean Scores for Ocular Irritation

Time after treatment	1 hour	24 hour	48 hour	72 hour	7 day	14 day
71855 Male	22	27	27	25	9	0
17923 Male	22	22	22	15	4	0
Group Total	44	49	49	40	13	0
Group Mean Score	22.0	24.5	24.5	20.0	6.5	0.0

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Lithium myristate is classified as irritating to eye (category 2) according to Regulation (EC) No. 1272/2008.

Executive summary:

Lithium myristate is classified as irritating to eye (category 2) according to Regulation (EC) No. 1272/2008. The potential irritiancy of lithium myristate to the eye of the New Zealand white rabbit was assessed following OECD guideline 405 (adopted 2002) in a proprietary, experimental study (Harlan 2012). A single application of 0.1 mL lithium myristate to the non-irrigated eye of two rabbits produced scattered or diffuse corneal opacity, iridial inflamation and moderate conjunctival irritation. Both treated eyes appeared normal at the 14 day observation.