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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 July- 1 August 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
An upper temperature range of 28 oC occurred for a brief period (approximatelv 24 hours) during the study. This deviation was not considered to have affected the integrity or validity of the study.
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

1
Chemical structure
Reference substance name:
4-[2-Ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzamido]-1-3-propyl-1H-pyrazole-5-carboxamide
EC Number:
639-263-7
Cas Number:
200575-15-1
Molecular formula:
C22H32N6O5S
IUPAC Name:
4-[2-Ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzamido]-1-3-propyl-1H-pyrazole-5-carboxamide
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: 92,480/N/9/1
- Expiration date of the batch: Not supplied
- Purity test date: 95 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room Temperature


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- UK-220.955 was formulated at a maximum practical concentration of 62.5% w/v in 1% aqueous methylcellulose and administered at a volume of 3.2 ml/kg body-weight.
-The test substance was prepared on the day of dosing.
-The absorption of the test substance was not determined.
-The concentration, homogeneity and stability of the test substance in the vehicle was not evaluated.

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan O.K.. Ltd.. Bicester, Oxon. England.
- Male/Female
- Age at study initiation: seven to ten weeks of age prior to dosing
- Weight at study initiation: 215 to 242g

- Housing: Housed individually in metal cages with wire mesh floors
- Diet: Special Diet Services RMI (13) SQC expanded pellet) ad libitum
- Water: ad libitum
- Acclimation period: minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-28 (°C)
- Humidity (%): 45-62%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): I 2 hours of artificial light (0700 - 1900 hours) in each 24-hour period

IN-LIFE DATES: Day 0 to Day 15

Administration / exposure

Type of coverage:
occlusive
Vehicle:
methylcellulose
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lumbar region, approximately 50 mm x 50 mm
- Type of wrap if used: porous gauze held in place with a non irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 24 hours exposure period the dressings was carefully removed and the treated area of the skin was washed with warm water (30o to 40oC) and the treated area was blotted dry with absorbent paper.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3.2 ml/kg
- Concentration (if solution): 62.5 % w/v in 1 % aqueous methylcellulose
- Constant volume or concentration used: yes

VEHICLE
- Concentration (if solution): 1 % aqueous methylcellulose
Duration of exposure:
24 hrs
Doses:
2000 mg/kg
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed soon after dosing and at frequent intervals on Day 1. Subsequently, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15- morning only). Bodyweights were recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: All animals were killed on day 15 and all were subjected to a macroscopic examination
- Other examinations performed: mortality, clinical signs, dermal responses, body weight,macroscopic examination

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single dermal application of 2000 mg/kg UK-220.955 to a group of ten rats (5/sex/dose)
Clinical signs:
No systemic response was observed in any animal throughout the study.
Body weight:
All rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination of animals killed on Day 15 revealed no abnormalities.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
The acute lethal dermal dose to rats of UK-220, 955 was demonstrated to be greater than 2000 mg/kg bodyweight.
Executive summary:

A study was preformed to assess the acute dermal toxicity of UK-220 955 to the rat. The method followed was that described in EEC Methods for the determination of toxicity. Annex to Directive 92/69/EEC (OJ No. L383A. 29.12.92), Part B, Method B.3. Acute toxicity (dermal).

A group of ten rats (five males and five females) received a single dose by topical application of the test substance, formulated at a maximum practical concentration of 62.5 % w/v in 1 % aqueous methylcellulose and administered at a dose level of 2000 mg/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no signs of systemic reaction to treatment observed throughout the study.

Transient well-defined dermal irritation (Grade 1 or 2 erythema with up to Grade 3 oedema) was evident in four females following removal of the dressings (Day 2) and resolving in all instances by Day 4. No dermal response to treatment was observed in the remaining six animals throughout the study.

All rats were considered to have achieved satifactory bodyweight gains throughout the study.

Macroscopic examination of animals killed on Day 15 revealed no abnormalities.

The acute lethal dermal dose to rats of UK-220,955 was demonstrated to be greater than 2000 mg/kg bodyweight.

UK-220, 955 will not require labelling in accordance with GHS

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