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

Endpoint summary

Description of key information

Acute oral (OECDTG423): LD50 >2000 mg/kg bw

Acute dermal (OECDTG402)): LD50 >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:

02 September, 2003 - 18 September, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(1996)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(1996)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley Rj: SD (lOPS Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: males: 274 ± 3 g; females: 214 ± 4 g
- Fasting period before study: overnight of approximately 18 hours before dosing
- Housing: Group housing of 3 animals of the same sex per cage in polycarbonate cages with stainless steel lid
- Diet: Free access to A04 C 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): 22 ± 2
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 12
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 0.5% aqueous suspension of methylcellulose in purified water

Details on oral exposure:

GAVAGE METHOD: metal gavage tube fitted to a 5 mL glass syringe.

Frequency: single dosage, on Day 1.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight.

DOSAGE PREPARATION: On the day of treatment, the test item was ground to a fine powder using a mortar and pestle, and was prepared at the chosen concentration in the vehicle. The test item preparation was made freshly on the morning of administration and any unused material was discarded that same day.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
Body weights: The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15. The body weight gain of the treated animals was compared to that of CIT control animals with the same initial body weight.
- Necropsy of survivors performed: All study animals were subjected to a macroscopic examination as soon as possible after death. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.

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: No clinical signs were observed.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Interpretation of results:

other: Not classified

Remarks:

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

Conclusions:

In an acute oral toxicity study with KY-UN with male and female rats, performed according to OECD 423 test guideline and GLP principles, an LD50 >2000 mg/kg bw was determined.

Executive summary:

KY-UN was tested in an acute oral toxicity study with male and female rats, performed according to OECD 423 test guideline and GLP principles. No deaths occurred and no clinical signs were observed. Macroscopic examination of the main organs of the animals revealed no apparent abnormalities. The overall body weight gain of the other animals was not affected by treatment with the test item. Based on the results an LD50 >2000 mg/kg bw was determined and KY-UN 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 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:

17 September, 2003 - 01 October, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

other: Sprague-Dawley Rj: SD (lOPS Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: males: 310 ± 8 g; females: 228 ± 6 g
- Housing: Individually housed in polycarbonate cages with stainless steel lid
- Diet: Free access to A04 C 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): 22 ± 2
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 12
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

other: moisted with purified water

Details on dermal exposure:

On the day before treatment, the dorsal area of each animal was clipped (i.e. approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females) using an electric clipper.

The test item in its original form was placed on a hydrophilic gauze pad (pre-moistened with 2 mL of purified water) and then applied to an area of the skin representing approximately 10% of the total body surface of the animals. The test item and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

Frequency: Single dosage, on Day 1.

Washing: On removal of the dressing, any residual test item was removed using a moistened cotton pad.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

DOSAGE PREPARATION: The test item preparation was made freshly on the morning of administration and any unused material was discarded that same day.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15.
Type, time of onset and duration of clinical signs were recorded for each animal individually. Time of death was recorded individually, in terms of the number of hours or days after dosing. From day 2, any local cutaneous reaction was recorded.
Body weights: The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15. Individual weights of animals found dead during the study were measured at necropsy when survival exceeded 24 hours. The body weight gain of the treated animals was compared to that of CIT control animals with a similar initial body weight.
- Necropsy of survivors performed: All study animals were subjected to a macroscopic examination as soon as possible after death. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.

Statistics:

None.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female was found dead on day 2.

Clinical signs:

other: No clinical signs were observed prior to death of the female. No clinical signs were recorded in the other animals. No cutaneous reactions were observed.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Interpretation of results:

other: Not classified.

Remarks:

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

Conclusions:

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

Executive summary:

KY-UN was tested in an acute dermal toxicity study with male and female rats, performed according to OECD 402 test guideline and GLP principles. One female was found dead on day 2. No clinical signs were observed prior to death of the female. No clinical signs were recorded in the other animals. No cutaneous reactions were observed. A reduced body weight gain was seen in 2 females between day 1 and day 8, without any relevant consequence at the end of the observation period. The overall body weight gain of the other animals was similar to that of CIT historical control animals. Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Based on the results, an LD50 >2000 mg/kg bw was determined and KY-UN 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 klimisch code 1.

Additional information

Acute oral:

KY-UN was tested in an acute oral toxicity study with male and female rats, performed according to OECD 423 test guideline and GLP principles. No deaths occurred and no clinical signs were observed. Macroscopic examination of the main organs of the animals revealed no apparent abnormalities. The overall body weight gain of the other animals was not affected by treatment with the test item. Based on the results an LD50 >2000 mg/kg bw was determined and KY-UN does not have to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008.

Acute dermal:

KY-UN was tested in an acute dermal toxicity study with male and female rats, performed according to OECD 402 test guideline and GLP principles. One female was found dead on day 2. No clinical signs were observed prior to death of the female. No clinical signs were recorded in the other animals. No cutaneous reactions were observed. A reduced body weight gain was seen in 2 females between day 1 and day 8, without any relevant consequence at the end of the observation period. The overall body weight gain of the other animals was similar to that of CIT historical control animals. Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

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