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

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

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:

451-060-3

EC Name:

-

Cas Number:

122886-55-9

Molecular formula:

C31H48N4O2

IUPAC Name:

3-octyl-1-[4-({4-[(octylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): KY-UN
- Stability under test conditions: not stated
- Storage condition of test material: at room temperature and protected from light

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.