Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 September 2003 to 2 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Butanoic acid, 4-[[4-[7-chloro-6-(1,1-dimethylethyl)-1H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]phenyl]amino]-4-oxo-, tetradecyl ester
- HAEL Number: 2003-0090
- KAN: 632021-1
- CIN: 10084241
- SRID or Lot No.: DEV84241
- Physical state and appearance: brown powder
- Storage conditions of test material: at room temperature
- Purity determination: 96.5 weight percent
- Stability: stable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: The male rats were 8 to 9 weeks of age and the female rats were 10 to 11 weeks of age.
- Weight at study initiation: The male rats weighed 250.90 to 278.64 grams and the female rats weighed 215.20 to 252.91 grams.
- Fasting period before study: Not reported
- Housing: Animals were housed in an Association for Assessment and Accreditation of Laboratory Animal Care International-accredited vivarium in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, 1996). The rats were singly housed in suspended, stainless-steel, wire mesh cages. Cages and racks were washed once a week. Absorbent paper, used to collect excreta, was changed at least three times a week.
- Diet: Certified Rodent Diet (pelleted) was available ad libitum.
- Water: Water was available ad libitum through an automatic watering system. The source of the water was the local public water system.
- Acclimation period: The animals were isolated upon arrival and allowed to acclimate for a period of 5 days. Animals were judged to be healthy prior to testing.

ENVIRONMENTAL CONDITIONS
- Temperature: 21.4 - 23.8 °C
- Humidity: 41.3 - 60.7 %
- Photoperiod: A photoperiod of 12 hours of light was maintained.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Not reported
- % coverage: Not reported
- Type of wrap if used: A fiber pad and an occlusive wrap to hold the test substance in place

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, any residual test substance was removed with running water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test substance, a solid, was administered at 2000 mg/kg moistened with water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five male and five female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were measured on Days 0 (prior to treatment), 7, and 14. Animals were observed at least once during the exposure period, and once each day thereafter for the duration of the experiment. Observations included, but were not limited to, examination of the hair, skin, eyes, mucous membranes, motor activity, feces, urine, respiratory system, circulatory system, autonomic nervous system, central nervous system, and behavior patterns.
- Necropsy of survivors performed: yes
Statistics:
No statistical procedures were required during the study. No dose/mortality curve was constructed since graphs become statistically useful only with the use of large numbers of animals and dose groups.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the 14-day observation period for rats administered a dose of 2000 mg/kg of the test substance.
Clinical signs:
No abnormal clinical signs were observed.
Body weight:
All animals gained weight during both weeks of the study.
Gross pathology:
No treatment-related changes were observed at necropsy, and no tissue was collected for microscopic examination.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of the test, the acute dermal LD50 for the test substance was determined to be greater than 2000 mg/kg for male and female rats.
Executive summary:

In a GLP compliant study conducted in line with OECD Guideline 402 and EU Method B.3, the acute toxicity of butanoic acid, 4-[[4-[7-chloro-6-(1,1-dimethylethyl)-3H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]phenyl]amino]-4-oxo, tetradecyl ester to rats was investigated.

Male and female rats were administered a single limit dose of 2000 mg/kg of the test substance topically. The test substance was administered moistened with water. No abnormal clinical signs were noted at any time during the 14-day observation period. No mortality was observed, and all animals gained weight. No treatment-related changes were observed at necropsy, and no tissues were collected for histological examination.

The acute dermal LD50 for this test substance was greater than 2000 mg/kg for male and female rats and requires no toxicity classification in line with current EU requirements.