[No public or meaningful name is available]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between the 19th June 2017 and 30th June 2017.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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:

bis(cyclohexylmethyl) ether

Cas Number:

14315-63-0

Molecular formula:

C14H26O

IUPAC Name:

bis(cyclohexylmethyl) ether

Test material form:

liquid

Remarks:

Clear, colorless

Specific details on test material used for the study:

Identification: FRET 13-0460
Physical state/Appearance: clear colorless liquid
Storage Conditions: approximately 4 °C in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Envigo RMS (UK) Limited, Leicestershire, UK
- Age at study initiation: 12 to 52 weeks old
- Weight at study initiation: Body weights were 3.81 or 3.94 kg
- Housing: Individually
- Diet:Food was allowed throughout the entire study (2930C Teklad Global Rabbit diet supplied by Envigo RMS (UK) Limited, Oxon, UK)
- Water: Free access to mains drinking water.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS:
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 12 hours continuous light and 12 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: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

Amount applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single instillation on Day 0

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

2 females

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 anesthesia of ocular anesthetic (two drops of 0.5% proxymetacaine 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, a second animal was 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.
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

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

75799 Female

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Remarks:

75799 Female

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Remarks:

75799 Female

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible

Results 4

Irritation parameter:

conjunctivae score

Remarks:

75714 Female

Basis:

mean

Time point:

24/48/72 h

Score:

2.7

Max. score:

6

Reversibility:

fully reversible

Results 5

Irritation parameter:

cornea opacity score

Remarks:

75714 Female

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 6

Irritation parameter:

iris score

Remarks:

75714 Female

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 7

Irritation parameter:

chemosis score

Remarks:

75799 Female

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible

Results 8

Irritation parameter:

chemosis score

Remarks:

75714 Female

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in the other treated eye 1 hour after treatment with minimal conjunctival irritation noted in both treated eyes at the 24 and 48 Hour observations.
Both treated eyes appeared normal at the 72-Hour observation.

Other effects:

Both animals showed body weight loss during the study.

Any other information on results incl. tables

Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	75799Female				75714Female
	IPR= 1				IPR = 1
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E = Degree of Opacity	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	1	1	1	0	1	1	1	0
B = Chemosis	1	1	0	0	1	1	0	0
C = Discharge	1	0	0	0	2	1	0	0
Score (A + B + C) x 2	6	4	2	0	8	6	2	0
Total Score	6	4	2	0	8	6	2	0

IPR=Initial pain reaction

Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
75799Female	6	4	2	0
75714Female	8	6	2	0
Group Total	14	10	4	0
Group Mean Score	7.0	5.0	2.0	0.0

Individual Body Weights and Body Weight Change

Rabbit Number and Sex	Individual Body Weight (kg)		Body Weight Change (kg)
	Day 0	Day 3
75799Female	3.81	3.75	-0.06
75714Female	3.94	3.88	-0.06

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an eye irritation study with rabbits, performed according to OECD 405 (1981), limited irritation was observed. Based on the results of this study, the substance is not considered an eye irritant.

Executive summary:

In an eye irritation study with rabbits, performed according to OECD 405 (1981), the test item produced corneal opacity scores and iritis scores of 0 in both animals at all timepoints. Limited irritation was observed in the conjunctivae assessment, which was reversible within 72 hrs. The results showed that the subsance is not an ocular irritant.