2,2-Difluoroethyl Acetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

FROM 31 AUGUST 2015 TO 21 NOVEMBER 2015.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2-difluoroethyl acetate

EC Number:

801-773-4

Cas Number:

1550-44-3

Molecular formula:

C4H6F2O2

IUPAC Name:

2,2-difluoroethyl acetate

Test material form:

liquid

Remarks:

Clear and colorless.

Test animals

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories International, Inc., Raleigh, North Carolina, U.S.A.
- Females nulliparous and non-pregnant: yes.
- Age at study initiation: the animals were approximately 9 weeks old on the day of dosing.
- Weight at study initiation: female weight was in the range 211.2 - 228.3 g and male weight was in the range 318.4 - 346.7 g.
- Fasting period before study: no.
- Housing: animals were housed individually in solid-bottom caging with bedding and appropriate species specific enrichment.
- Diet: the rats were fed PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002 ad libitum.
- Water: all rats were provided tap water ad libitum.
- Acclimation period: the rats were weighed and observed for general health during the 7-day quarantine period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26°C.
- Humidity (%): 30-70%.
- Photoperiod: animal rooms were artificially illuminated (fluorescent light) on an approximate12-hour light/dark cycle.

IN-LIFE DATES: From: 10 September 2015 To: 24 September 2015.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 5 cm x 7.4 cm.
- Preparation of animals for exposure and application conditions: approximately 24 hours before dosing, the fur of each rat was closely shaved to expose the back from the scapular to the lumbar region. The test substance was inverted to mix before the dosing procedure. An aliquot of test substance was spread evenly, directly on the skin, covering an area of approximately 37 square centimetres. The rats were reshaved as needed during the study.
- % coverage: approximately 10% of the total body surface.
- Type of wrap if used: the test material 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 and time after start of exposure: approximately 24 hours after treatment, the
wrappings were removed. Excess test material was washed from the dorsal skin of each rat with paper towels soaked in warm water, and the skin was dried.

TEST MATERIAL
- Amount(s) applied and concentration: the amount of neat test material designated for each animal was calculated based on body weights collected prior to treatment and the test material density of 1210 mg/mL, to obtain a dose level of 5000 mg/kg bw.

Duration of exposure:

24 hrs.

Doses:

5000 mg/kg bw (males and females).

No. of animals per sex per dose:

5 males and 5 females.

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: the rats were observed for clinical signs prior to and after dosing, immediately after wrapping removal/washing and then daily. Daily animal health observations were conducted throughout the study for mortality and signs of illness, injury, abnormal behavior. The rats were weighed on test days 1, 8, and 15.
- Necropsy of survivors performed: yes. All rats were euthanized at the end of the 15-day test period by exsanguination while under isoflurane anesthesia and examined to detect grossly observable evidence of organ or tissue damage.
- Other examinations performed: Dermal effects were scored according to the Draize Scale immediately after wrapping removal/washing. The rats were observed daily for dermal irritation (weekends and holidays excluded).

Statistics:

Not relevant for that study.

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:

There was no instances of mortality.

Clinical signs:

salivation

Body weight:

other body weight observations

Remarks:

There were no overall (test day 1-15) body weight losses among any animals.

Gross pathology:

No gross lesions were present in the rats at necropsy.

Other findings:

Skin responses:
At the beginning of the observation period (approximately 24 hours after exposure), on test day 2, erythema (with a score of 1) was observed in one male, which was resolved by test day 3. There were no instances of edema observed. A scab on the back was observed in one male between test days 4-6 and in one female between test days 4-5.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the dermal LD50 of 2,2-Difluoroethyl acetate was greater than 5000 mg/kg in male and female rats.

Executive summary:

The acute dermal toxicity of 2,2-Difluoroethyl acetate was investigated in a study performed according to OECD test guideline 402 under GLP compliance.

A single dose of 5000 mg/kg bwt was applied neat to the shaved, intact skin of five male and five female Crl:CD(SD) rats. The application site was covered with a semi-occlusive dressing for 24 h, after which the test substance was removed. The observation period lasted 14 days following application. All rats were observed for mortality, body weight effects, clinical signs and dermal response (according to the Draize scale, Draize et al. 1944). On day 15, the rats were necropsied to detect grossly observable evidence of organ or tissue damage.

There were no instances of mortality. A scab on the back was observed in one male, between days 4-6 and in one female, between days 4-5. Salivation was observed in one male on day 1 during the exposure period, which was likely a reaction to the wrapping procedure. No other clinical abnormalities were observed. At the beginning of the observation period (approximately 24 h after exposure), on day 2, erythema (with a score of 1) was observed in one male, which was resolved by day 3. There were no instances of edema observed. There were no overall (days 1-15) body weight losses among any animals. No gross lesions were present in the rats at necropsy.

Under the conditions of this study, the acute dermal LD₅₀ value of 2,2-Difluoroethyl acetate was determined to be greater than 5000 mg/kg bwt in male and female rats.