1-[5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]ethanone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: MAFF Japan Agricultural Chemicals Regulation Laws Notification 12 Nousan 8147 (2000)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

solid

Details on test material:

- Purity: 99.9%

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: male average - 370.8 g; female average - 246.7 g
- Fasting period before study: no
- Housing: housed singly in polycarbonate pans
- Diet: PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum
- Water: ad libitum
- Acclimation period: 6-day quarantine period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26ºC
- Humidity (%): 30-70%
- Air changes (per hr): not reported
- Photoperiod: approximate 12-hour light/dark cycle

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: deionized water

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 5 cm x 7.4 cm
- % coverage: Thirty-seven square centimetres is equal to approximately 10 percent of the total body surface area of rats in the 200 - 300 g body weight range.
- Type of wrap if used: The test substance was covered with a 2-ply gauze patch. The rats were then wrapped with stretch gauze bandage and self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test substance was weighed for each animal on the day of treatment at a dose of 5000 mg/kg of body weight. The amount of test substance designated for each animal was calculated based on body weights collected prior to treatment.
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): The aliquot of test substance designated for an animal was moistened with 1.7 mL of deionized water to form a thick paste.

Duration of exposure:

24 hours

Doses:

1

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for mortality and signs of illness, injury, and abnormal behaviour were made daily throughout the study. Observations for clinical signs of toxicity and dermal irritation were made daily throughout the study (weekends excluded for dermal irritation).
- Frequency of weighing: The rats were weighed prior to treatment (test day 0) and on test days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One female rat was found dead the day after application of the test substance during the exposure period. The cause of death was not determined.

Clinical signs:

The rats exhibited no clinical signs of toxicity.

Body weight:

Two female rats exhibited body weight loss of 3 or 4% of the test day 0 weight on test day 7 but gained weight by test day 14. No other body weight losses were observed.

Gross pathology:

No test substance-related gross lesions were found in the study. Lung discoloration was nonspecific, occurred in a single incidence, and is a common finding in rats of this strain and age.

Other findings:

No dermal irritation was observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 5000 mg/kg

Executive summary:

A single dose of the test substance was applied to the shaved, intact skin of 5 male and 5 female rats at a dose of 5000 mg/kg of body weight. The application site was covered with a semi-occlusive dressing for 24 hours, after which the test substance was removed. The rats were observed for 14 days following application. The rats were necropsied to detect grossly observable evidence of organ or tissue damage at the end of the 15-day test period.

One female rat was found dead the day after application of the test substance during the exposure period. The cause of death was not determined. The rats exhibited no clinical signs of toxicity. Two female rats exhibited body weight loss of 3 or 4% of the test day 0 weight on test day 7 but gained weight by test day 14. No other body weight losses were observed. No dermal irritation was observed. No test substance-related gross lesions were found in the study. Lung discoloration was nonspecific, occurred in a single incidence, and is a common finding in rats of this strain and age. Under the conditions of this study, the dermal LD50 for the test substance was greater than 5000 mg/kg for male and female rats.