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

Endpoint summary

Description of key information

Skin irritation (OECDTG404): not skin irritating

Eye irritation (OECDTG405): not eye irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 September, 2003 - 28 September, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: 2 to 4 months
- Weight at study initiation: 3.1 ± 0.1 kg
- Housing: Animals were housed individually 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

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: The test substance was moistened with purified water

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 grams

VEHICLE
The test substance was moistened with purified water.

Duration of treatment / exposure:

Single application. 3 minutes; 4 hours

Observation period:

4 days.

Number of animals:

3 (male/female)

Details on study design:

STUDY DESIGN
The day before treatment, both flanks of each animal were clipped using electric clippers and the skin of each animal was examined in order to check the absence of any signs of skin irritation. Clipping was repeated thereafter on days 1 and 2 for 2 animals and on day 3 for 2 animals.
As possible irritant effects were anticipated, the test item was evaluated on a single animal in the first instance. The duration of exposure was 3 minutes on one flank and 4 hours on the other flank. Since the test item was not irritant on this first animal, it was then applied for 4 hours to two other animals.

TEST SUBSTANCE PREPARATION
The test substance was applied in its original form.

REMOVAL OF TEST SUBSTANCE
After removal of the dressing, any residual test item was wiped off by means of a moistened cotton pad.

OBSERVATIONS
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

In the first animal (3 minute exposure), no reactions were observed.
A very slight erythema (grade 1) was noted in 1 animal, at the 1-hour reading only. No other cutaneous reactions were noted during the study.

Interpretation of results:

other: Not skin irritating

Remarks:

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

Conclusions:

In a skin irritation study with rabbits, performed according to OECD 404 test guideline and GLP principles, no irritation was observed.

Executive summary:

KY-UN was tested in a skin irritation study with rabbits, performed according to OECD 404 test guideline and GLP principles.

In the first animal (3 minute exposure), no reactions were observed. Since the test item was not irritant on this first animal, the test substance was applied for 4 hours to two other animals.

A very slight erythema (grade 1) was noted in 1 animal, at the 1-hour reading only. No other cutaneous reactions were noted during the study. Based on the results KY-UN does not have to be classified for skin irritation according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes

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

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.

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

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

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

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

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

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

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

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

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

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.

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.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

KY-UN was tested in a skin irritation study with rabbits, performed according to OECD 404 test guideline and GLP principles.

In the first animal (3 minute exposure), no reactions were observed. Since the test item was not irritant on this first animal, the test substance was applied for 4 hours to two other animals.

A very slight erythema (grade 1) was noted in 1 animal, at the 1-hour reading only. No other cutaneous reactions were noted during the study. Based on the results KY-UN does not have to be classified for skin irritation according to Regulation (EC) No 1272/2008.

Eye irritation:

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.

Justification for classification or non-classification

Based on the available study results, KY-UN does not have to be classified and has no obligatory labelling requirement for skin and eye irritation/corrosion according to Regulation (EC) No 1272/2008 and its amendments.