N,N''-(methylenedi-4,1-phenylene)bis[N'-cyclohexylurea];N-(4-[[4-[[(phenylamino)carbonyl]amino]phenylmethyl]phenyl]-N'-cyclohexylurea;reaction mass of: N,N''-(methylenedi-4,1-phenylene)bis[N'-phenylurea]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 November, 1994 - 10 November, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

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:

423-070-8

EC Name:

-

Cas Number:

58890-25-8

Molecular formula:

not applicable (reaction mass)

IUPAC Name:

3-cyclohexyl-1-[4-({4-[(cyclohexylcarbamoyl)amino]phenyl}methyl)phenyl]urea; 3-cyclohexyl-1-[4-({4-[(phenylcarbamoyl)amino]phenyl}methyl)phenyl]urea; 3-phenyl-1-[4-({4-[(phenylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): KY-RB
- Description: White powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: Approx. 9 weeks
- Weight at study initiation: 1589 - 2106 g
- Housing: Individually housed in labelled cages with perforated floors.
- Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day
- Water: Free access to tap-water diluted with decalcified water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approx. 15
- 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: 26 ± 2 mg (a volume of approximately 0.1 mL)

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 after instillation of the test substance.

Number of animals or in vitro replicates:

3 males

Details on study design:

TREATMENT
On test day 1, the test substance was instilled in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance.

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation).
- Necropsy: not performed.
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours 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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: 24, 48 and 72 hrs.

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: 24, 48 and 72 hrs.

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

animal #1 and #2

Time point:

other: 24, 48 and 72 hrs.

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean)

Time point:

other: 24, 48 and 72 hrs.

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: 24, 48 and 72 hrs.

Score:

0

Max. score:

4

Irritant / corrosive response data:

Slight redness of the conjuctival tissues was observed in all animals. The irritation had resolved within 48 hours in two animals and within 72 hours after instillation in the third animal. There was no evidence of ocular corrosion.
Treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.

Other effects:

Remnants of the test substance were noted on the outside of the eyelids in one animal during the observation period.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an eye irritation study with KY-RB with male rabbits, performed according to OECD 405 test guideline and GLP principles, limited irritation was observed.

Executive summary:

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

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Slight redness of the conjuctival tissues was observed in all animals. The irritation had resolved within 48 hours in two animals and within 72 hours after instillation in the third animal. There was no evidence of ocular corrosion.

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