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]

Endpoint summary

Description of key information

An acute oral study was performed according to OECD Guideline 401 and GLP principles and an acute dermal study was performed according to OECD Guideline 402 and GLP principles. The oral and dermal LD50 were determined to be >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 October, 1994 - 02 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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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. 8 weeks
- Weight at study initiation: males: 177 - 208 g; females: 152 - 162 g
- Fasting period before study: overnight prior to dosing until approx. 3-4 hours after administration of the test substance
- Housing: Group housed of 5 animals per sex 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

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 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.

Frequency: single dosage, on Day 1.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded.
- Necropsy of survivors performed: All animals assigned to the study were subjected to necropsy and descriptions of all macroscopic abnormalities recorded.

Statistics:

No statistical analysis was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: Lethargy and uncoordinated movements were observed in all animals on days 1 and/or 2.

Gross pathology:

Macroscopic post mortem examination of the animals at termination did not reveal any abnormalities.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute oral toxicity study with KY-RB with male and female rats, performed according to OECD 401 test guideline and GLP principles, an LD50 >2000 mg/kg bw was determined.

Executive summary:

KY-RB was tested in an acute oral toxicity study with male and female rats, performed according to OECD 401 test guideline and GLP principles. No deaths occurred. Lethargy and uncoordinated movements were observed in all animals on days 1 and/or 2. Macroscopic post mortem examination of the 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 oral toxicity according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study has a klimisch code 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

no

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study has a klimisch code 1.

Additional information

Acute oral:

KY-RB was tested in an acute oral toxicity study with male and female rats, performed according to OECD 401 test guideline and GLP principles. No deaths occurred. Lethargy and uncoordinated movements were observed in all animals on days 1 and/or 2. Macroscopic post mortem examination of the animals at termination did not reveal any abnormalities. Based on the results an LD50 >2000 mg/kg bw was determined.

Acute dermal:

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.

Justification for selection of acute toxicity – oral endpoint
One study available.

Justification for selection of acute toxicity – dermal endpoint
One study available.

Justification for classification or non-classification

Based on results from acute oral and dermal toxicity studies, KY-RB does not have to be classified and has no obligatory labelling requirement for acute oral toxicity and acute dermal toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.