N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 October, 2003 - 15 October, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

451-060-3

EC Name:

-

Cas Number:

122886-55-9

Molecular formula:

C31H48N4O2

IUPAC Name:

3-octyl-1-[4-({4-[(octylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): KY-UN
- Stability under test conditions: not stated
- Storage condition of test material: at room temperature and protected from light

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: 2 to 4 months
- Weight at study initiation: 3.4 ± 0.2 kg
- Housing: Individually housed in polystyrene cages.
- Diet: Free access to 110 pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France).
- Water: Free access to drinking water filtered by a FG Millipore membrane (0.22 micron).
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 12
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL- Amount applied: 100 mg

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance.

Number of animals or in vitro replicates:

3 males

Details on study design:

STUDY DESIGN
As possible irritant effects were anticipated, the test substance was administered to a single animal in the first instance. Since the test item was not severely irritant on this first animal, it was then evaluated on two other animals.

TREATMENT
A single dose of the test substance was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of the test substance.

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to OECD 405.

For the evaluation of corneal opacification (presence or absence, affected area), the eyes were examined under a UV lamp after instillation of one or two drops of 0.5% sodium fluorescein solution (a clear fluorescence is visible in the areas of opacification). This evaluation was performed on day 2 and repeated thereafter whenever necessary.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 8

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 5 days

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Very slight to moderate conjunctival reactions were observed in all animals from day 1: a very slight to moderate chemosis (grades 1 to 3), a very slight to moderate redness of the conjunctiva (grades 1 to 3) and a clear discharge were noted. Some of these reactions persisted up to day 3 (one animal), 4 (one animal) or 6 (one animal). A slight iritis (grade 1) was noted in one animal, on days 1 and 2. A very slight corneal opacity (grade 1) was recorded in the same animal, on day 2 only.

Applicant's summary and conclusion

Interpretation of results:

other: Not eye irritating

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

In an eye irritation study with rabbits, performed according to OECD 405 test guideline and GLP principles, limited irritation was observed, which was fully reversible within 7 days.

Executive summary:

KY-UN was tested in an eye irritation study with rabbits, performed according to OECD 405 test guideline and GLP principles.

Very slight to moderate conjunctival reactions and chemosis were observed in all animals from day 1. A slight iritis was noted in one animal, on days 1 and 2. All of the effects were fully reversible within 7 days.

Based on the results KY-UN does not have to be classified for eye irritation according to Regulation (EC) No 1272/2008.