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]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 October, 1994 - 03 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 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: Approx. 10 weeks
- Weight at study initiation: males: 253 - 323 g; females: 191 - 221 g
- Housing: Individually housed in labelled polycarbonate cages.
- Diet: Free access to standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle AG, Kaiseraugst, Switzerland)
- Water: Free access to tap-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

Administration / exposure

Type of coverage:

occlusive

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The formulation was applied to an area of approx. 25 cm² (5x5 cm) for males and 18 cm² (3.5x5 cm) for females by application on a gauze patch fixed successively to aluminium foil and flexible bandage, with drops of petrolatum.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using a tissue moistened with tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

Dose volume: 10 mL/kg body weight

DOSAGE PREPARATION: Formulation was prepared immediately prior to dosing. The test substance was prepared in propylene glycol and adjustment was made for the specific gravity of propylene glycol (1.036). Homogeneity was accomplished to a visually acceptable level.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily. The time of death was recorded as precisely as possible.
Body weights: Days 1 (pre-administration), 8 and 15 and at death
Clinical signs: At periodic intervals on the day of treatment (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: All animals assigned to the study were subjected to necropsy and descriptions of all macroscopic abnormalities recorded.
- Other examinations performed: none.

Statistics:

None.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One male was found dead early in the morning of day 2. No further mortality occurred during the observation period (15 days).

Clinical signs:

other: Lethargy was noted among the males and females on days 1 and/or 2.

Gross pathology:

Macroscopic post mortem examination of the animal that died during the study revealed fluid contents in the abdominal cavity.
Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

Other findings:

White staining of the treated skin, caused by the test substance, was noted in all animals after bandage removal on day 2 and had disappeared within the next 24 hours.
Erythema was seen in the treated skin-area in one female on day 4.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute dermal toxicity study with KY-RB with rats, performed according to OECD 402 test guideline and GLP principles, an LD50 >2000 mg/kg bw was determined.

Executive summary:

KY-RB was tested in an acute dermal toxicity study with male and female rats, performed according to OECD 402 test guideline and GLP principles. One male was found dead early in the morning of day 2. No further mortality occurred during the observation period (15 days). Lethargy was noted among the males and females on days 1 and/or 2. Erythema was seen in the treated skin-area in one female on day 4. Macroscopic post mortem examination of the animal that died during the study revealed fluid contents in the abdominal cavity. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

Based on the results an LD50 >2000 mg/kg bw was determined and KY-RB does not have to be classified for acute dermal toxicity according to Regulation (EC) No 1272/2008.