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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to guideline; under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(allyloxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]benzoate
EC Number:
603-837-5
Cas Number:
134605-64-4
Molecular formula:
C20H18ClF3N2O6
IUPAC Name:
1-(allyloxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]benzoate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: Solid (tan powder)
- Storage condition of test material: The test and control materials were stored at room temperature.

Test animals

Species:
rat
Strain:
other: Crl :CO®(SD)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: not reported.
- Weight at study initiation: 214 - 247 g
- Fasting period before study: not applicable
- Housing: Test animals were individually housed in screen-bottom stainless steel cages.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: At least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 50 +/- 20
- Air changes (per hr): not reported.
- Photoperiod: 12 h light / 12 hour dark

IN-LIFE DATES: From: To: 1995-06-07 to 1995-20-07

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: distilled water, to moisten only
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area
- % coverage: Approximately 20% of total body surface
- Type of wrap if used: The area of application was covered with a 2-in. x 4-in. gauze patch secured with paper tape and overwrapped with Saran Wrap® and Elastoplast® tape to provide an occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test sites were washed using tap water and disposable paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): the solid test material was moistened with distilled water.
- Constant volume or concentration used: not applicable
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): distilled water, for moistening test material only.
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable
Duration of exposure:
24 hours
Doses:
0 and 2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted at approximately 1, 2.5, and 4 hours after test or control material administration. Additional clinical observations (including dermal effects) and twice a day mortality checks (morning and afternoon) were conducted daily thereafter for 14 days. Body weights were determined before test or control material application (Day 0), at Day 7, and at termination of the in-life phase (Day 14).
- Necropsy of survivors performed: yes
Statistics:
No statistical analyses were 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 was observed.
Clinical signs:
All animals treated at 0 mg/kg appeared normal throughout the study with the exception of two male and two female animals. Clinical signs observed in these animals included red-stained face, wet and/or yellow-stained urogenital area, and soft stool. These four animals returned to a normal appearance by Day 3 after treatment. All animals treated at 2,000 mg/kg appeared normal throughout the study with the exception of two female animals. Clinical signs observed in these two animals included red-stained face and/or yellow-stained urogenital area. Both animals returned to a normal appearance by Day 3 after treatment. No dermal irritation was observed in either group of animals.
Body weight:
All animals exhibited normal body weight gain throughout the study.
Gross pathology:
No test material-related lesions were observed at necropsy.
Other findings:
At necropsy, the mandibular lymph node in one male given 2,000 mg/kg had multiple pinpoint red foci. This was considered an incidental finding and
unrelated to the test material.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: US EPA pesticides
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in male and female Crl :CO®(SD)BR rats was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Crl :CO®(SD)BR strain rat. The study was performed to GLP and the method was designed to meet the requirements of the EPA Guideline 81 -2.10 test animals (5 males and 5 females) were given a single, 24 -hour, semi-occluded dermal application of the test material (slightly moistened using distilled water) to intact skin at a dose of 2000 mg/kg body weight. Bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No signs of dermal irritation were noted. Animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. Clinical signs were observed in 2 control males, 2 control females and 2 test females; these included: red-stained face, wet and/or yellow-stained urogenital area, and soft stool. These four animals returned to a normal appearance by Day 3 after treatment. The acute dermal median lethal dose (LD50) of the test material in male and female Crl :CO®(SD)BR rats was found to be greater than 2000 mg/kg bodyweight.

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