1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d] pyrimidin-5-yl)phenylsulphonyl]-4-methylpiperazine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 to 27 August 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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))

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-{2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-7-one

EC Number:

918-045-8

Cas Number:

139755-83-2

Molecular formula:

C22H30N6O4S

IUPAC Name:

5-{2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-7-one

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 92480/J/17/1
- Expiration date of the lot/batch: Not supplied

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


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: 50% w/v concentration (maximum practical)
- Final dilution of a dissolved solid: 1% w/v aqueous methylcellulose

FORM AS APPLIED IN THE TEST (if different from that of starting material)
UK-92,480 was formulated at a maximum practical concentration of 50% w/v in I% ww/v aqueous methylcellulose and administered at a volume of 4 ml/kg bodyweight

Test animals

Species:

rat

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U.K. Ltd
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 228-257 g
- Fasting period before study: 0 days
- Housing: Metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 day minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-27.5
- Humidity (%): 46-62
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

methylcellulose

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 mm x 50 mm
- % coverage: 10
- Type of wrap if used: porous gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Warm water (30-40 degrees centigrade)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodywight
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 ml/kg
- Concentration (if solution): 1% w/v
- Lot/batch no. (if required):
- Purity:

Duration of exposure:

24 hours

Doses:

1

No. of animals per sex per dose:

5 males/females each revieved a dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Animals were observed soon after dosing and at frequent intervals for the remainder of Day I. On
subsequent days animals were observed once in the morning and again at the end of the experimental
day (with the exception of Day 15 - morning only). The nature and severity of the clinical signs and
time were recorded at each observation.

All surviving animals were observed for 14 days after dosing.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

Cages of rats were checked at least twice daily for any mortalities.

Clinical signs:

other: No systemic response was observed in any animal during the study.

Gross pathology:

Macroscopic examination of the animal killed on humane grounds revealed muscularitive trauma to the
forelimbs only. No abnormalities were revealed for animals killed at study termination.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance LD 50 > 2000 mg/kg and is not classified per GHS criteria.