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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
429-380-1
EC Name:
-
Cas Number:
133336-92-2
Molecular formula:
C29H28N4O2
IUPAC Name:
1-(4-methylphenyl)-3-{4-[(4-{[(4-methylphenyl)carbamoyl]amino}phenyl)methyl]phenyl}urea
Test material form:
solid: particulate/powder
Details on test material:
- Particle size distribution: 10%: < 23.94 µm
- Density: 1.32 g/cm3 (20°C)

Test animals

Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 9 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Individually in labeled polycarbonate cages containing purified sawdust as bedding material.
- Diet: Free access to pelleted rodent diet (from Carfil Quality BVBA, Oud-Turnhout, Belgium).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
set to maintain:
- Temperature (°C): 21
- Humidity (%): 30 -70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 08 December 1999 to 22 December 1999

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Remarks:
Adjusted for specific gravity 1.036
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 in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females . The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminium foil and Coban flexible bandage . A piece of Micropore tape was additionally used for fixation of the bandages in females only .

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
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:
VEHICLE \\weglaten indien onverdund gedoseerd.
- 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

DOSAGE PREPARATION:
The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level . Adjustment was made for specific gravity of vehicle.

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.
- Necropsy of survivors performed: Yes, all animals
- Other examinations performed: none.
Statistics:
No statistical analysis was performed .

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs of systemic toxicity were observed in any of the animals.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
Erythema was seen in the treated skin-area of one of the females on day 6 only .

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 rats, performed according to EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An assessment of acute dermal toxicity with KY-AF in the rat was performed according to EC test guideline and in accordance with GLP principles. KY-AF was administired by dermal application to 5 male and 5 female Wistar rats at 2000 mg/kg bw for 24 hours. No mortality occured and no clinical signs of systemic toxicity were observed in any of the animals. Erythema was seen in the treated skin-area of one of the females on day 6 only . The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of KY-AF in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, KY-AF does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

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