Reaction mass of (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene and (2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene and (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene

Eye irritation

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:

guideline study

Justification for type of information:

An existing in vivo test from 2009 was used to replace the required in vitro test.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Remarks:

The study was conducted according to guideline in effect at time of study conduct.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Remarks:

The study was conducted according to guideline in effect at time of study conduct.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene; (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene; (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene

EC Number:

700-755-2

Molecular formula:

C8H3F13O

IUPAC Name:

(2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene; (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene; (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene

Details on test material:

-Purity: >99% (wt.%)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 2534, 2710, 2530 g
- Housing: Singly in suspended stainless steel caging with mesh floors. Enrichment (e.g., toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least 3 times per week
- Diet: amount not reported
- Water: ad libitum
- Acclimation period: 12 or 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 30-59%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: other eye of each rabbit remained untreated and served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

After treatment, the upper and lower lids were gently held together for about one second before releasing to minimize loss of the test substance.

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: unwashed

SCORING SYSTEM: Draize Scale

TOOL USED TO ASSESS SCORE: High-intensity white lite in accordance with Draize, et al. Fluorescein dye evaluation was used in the treated eyes at 24 hours to verify the absence of corneal damage.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal:

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal:

Time point:

24/48/72 h

Score:

> 0 - < 1

Max. score:

2

Reversibility:

fully reversible within: 24 hours

Remarks on result:

probability of weak irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal:

Time point:

24/48/72 h

Score:

> 0 - < 1

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal:

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

other: Discharge

Basis:

other: range

Time point:

other: 1 to 72 hours

Score:

> 0 - < 1

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

There was no corneal opacity noted in any treated eye during the study. One hour after test substance instillation, all three treated eyes exhibited iritis and conjunctivitis. The overall incidence of irritation decreased with time. All animals were free of ocular irritation by 48 hours. The ocular scores from the animal with respect to observation time are presented in Table 1.

Other effects:

All animals appeared active and healthy and gained body weight during the study. Apart from the eye irritation noted, there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour.

Any other information on results incl. tables

Table 1: Individual Scores for Ocular Irritation
	Rabbit No.: 3401 (Female)				Rabbit No.: 3402 (Female)				Rabbit No.: 3403 (Female)
	Hours				Hours				Hours
	1	24	48	72	1	24	48	72	1	24	48	72
I. Cornea
A. Opacity	0	0^1	0	0	0	0^1	0	0	0	0^1	0	0
B. Area	4	4	4	4	4	4	4	4	4	4	4	4
II. Iris
A. Values	1	0	0	0	1	0	0	0	1	0	0	0
III. Conjunctivae
A. Redness	1	0	0	0	1	1	0	0	1	0	0	0
B. Chemosis	0	0	0	0	0	0	0	0	0	0	0	0
C. Discharge	1	0	0	0	1	1	0	0	1	0	0	0
^12% ophthalmic fluorescein sodium used to verify the absence of corneal opacity.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Iritis and conjunctivitis (score of 1) were observed. All animals were free of ocular irritation by 48 hours.

This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).

Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for the test substance to produce irritation from a single instillation via the ocular route. A skin irritation study was previously conducted. The test substance was not a severe skin irritant or corrosive to the skin. At the request of the Sponsor, the study was conducted in a stepwise fashion. Initially, one-tenth of a milliliter of the test substance was instilled into the conjunctival sac of the right eye of one healthy rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize et al. Since there was no significant irritation observed in this animal, the test was completed on two additional animals, as described above.

There was no corneal opacity noted in any treated eye during the study. One hour after test substance instillation, all three treated eyes exhibited iritis and conjunctivitis. The overall incidence of irritation decreased with time. All animals were free of ocular irritation by 48 hours.