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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From August 23, 2011 - September 21, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD Guideline 402 and U. S. EPA OPPTS 870.1200, in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-phenyl-5-(2-thienyl)-1,2,4-oxadiazole
EC Number:
810-533-8
Cas Number:
330459-31-9
Molecular formula:
C12H8N2OS
IUPAC Name:
3-phenyl-5-(2-thienyl)-1,2,4-oxadiazole
Test material form:
other: Cream coloured solid
Details on test material:
- Name of test material (as cited in study report): MON 102100

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 295-318 grams (males) and 205-225 grams (females)
- Housing: Singly housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 21 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): 50-74%
- Air changes (per h): 12 and 14
- Photoperiod (h dark / h light): 12 h light/dark cycle

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- On the day prior to application of test substance, a group of animals was prepared by clipping the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial), and the skin checked for any abnormalities.
- Area of exposure: 2 inches x 3 inches.
- % coverage: Test substance was then applied evenly over a 2-inch x 3-inch, 4-ply gauze pad and placed on a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface). The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were gently cleansed with 3% soap solution and a water rinse.
- Time after start of exposure: 24 h.

TEST MATERIAL
- Ground test substance was moistened with distilled water to achieve a dry paste by preparing a 65% w/w mixture.
Duration of exposure:
24 h
Doses:
5,000 mg/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Body weights of the animals were recorded prior to test substance application (initial) and again on Day 7 and 14 (termination).
- Necropsy of survivors performed: Yes
- Other examinations performed: The animals were observed for mortality, signs of gross toxicity, and behavioural changes during the first several hours after application, and at least once daily thereafter for 14 d. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, and coma. All rats were euthanized via CO2 inhalation on Day 14. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed
Clinical signs:
All rats exhibited ocular and/or nasal discharge on Day 1 or 2, and three females showed signs of ano-genital staining from Days 1 through 13. Dermal irritation was noted at the dose site and/or mechanical damage due to unwrapping around the dose site for four of five males on Day 1.
Body weight:
Although three females lost body weight through Day 7, all animals gained weight over the entire observation period.
Gross pathology:
No gross abnormalities were noted for any of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the acute dermal LD50 of the test substance was >5,000 mg/kg bw in rats.
Executive summary:

A study was conducted to assess the acute dermal toxicity of the test substance to rats according to OECD Guideline 402 and OPPTS 870.1200. 5,000 mg/kg bw of the test substance were moistened with distilled water and then applied to the approximately 2 inches x 3 inches skin of ten healthy rats for 24 h (approximately 10% of the body surface). The animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 d. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed at terminal sacrifice. No mortality was observed. Following patch removal, all rats exhibited ocular and/or nasal discharge on Day 1 or 2, and three females showed signs of ano-genital staining from Day 1 through 13. Dermal irritation was noted at the dose site and/or mechanical damage due to unwrapping around the dose site for four of five males on Day 1. Although three females lost body weight through Day 7, all animals gained weight over the entire observation period. No gross abnormalities were noted when necropsied at the conclusion of the 14 d observations period. Based on the results, the acute dermal LD50of the test substance was >5,000 mg/kg bw in rats (Durando J, 2011b).