2(3H)-Furanone, dihydro-3-hydroxy-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acute oral toxicity was determined according to OECD Guideline 402 (Acute Dermal toxicity)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-hydroxyoxolan-2-one

EC Number:

692-561-9

Cas Number:

19444-84-9

Molecular formula:

C4H6O3

IUPAC Name:

3-hydroxyoxolan-2-one

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMALS :
-Number: ten rats (five males and five nulliparous and non pregnant females).
-Strain and Sanitary status: Sprague-Dawley rat, Rj Han: SD, Indemn of Organism Pathogen Specific Han (IOPS Han).
-Breeder: Janvier, Le Genest-Saint-Isle, France.
-Age/Weight: on the day of treatment, the animals were approximately 8 weeks old. The males had a mean body weight of 347 g (range: 333 g to 357 g) and the females had a mean body weight of 237 g (range: 228 g to 246 g).
-Receipt: on arrival, the animals were given a clinical examination to ensure that they were in good condition.
-Acclimation: the animals were acclimated to the study conditions for a period of 5 (females) or 8 (males) days before treatment.
-Allocation to study: the day before treatment, the required number of animals (five males and five females) was allocated by sex to the group according to a computerized random procedure. The skin of each animal (previously clipped) was examined in order to use only animals with healthy intact skin.
-Identification: the day before treatment, the animals were individually identified by ear notches.

The animal room conditions were set as follows:
-temperature : 22 ± 2°C,
-relative humidity : 50 ± 20%,
-light/dark cycle : 12h/12h (7:00 - 19:00),
-ventilation : approximately 12 cycles/hour of filtered, non-recycled air.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment, an area representing approximately 10% of the total body surface [i.e. approximately 7 cm x 5 cm for males and 6 cm x 5 cm for females ] was clipped on the back of each animal, using electric clippers. Care was taken to avoid abrading the skin. Only animals with healthy intact skin were used in the study.

The test item was applied as a film (as thin and uniform as possible) to the clipped area of skin. The application site was covered with a hydrophilic gauze pad.

Duration of exposure:

The application site was covered by a semi-occlusive dressing for 24 hours.

No. of animals per sex per dose:

5 females 2000mg/kg
5 males 2000mg/kg

Control animals:

no

Details on study design:

Each animal was checked for mortality and morbidity, frequently during the hours following treatment, then once a day until the end of the observation period, including weekends and public holidays.
Each animal was observed after treatment as follows:
. at least once during the first 30 minutes,
. periodically during the first 4 hours,
. then once a day, at approximately same time, for the recording of clinical signs.
Any clinical signs observed were recorded individually for each animal, along with times of onset and
recovery. From day 2, any local reactions at the treatment site were also noted.
The body weight of each animal was recorded the day of allocation of the animals into groups then on the day of treatment and on days 8 and 15.

Results and discussion

Preliminary study:

The limit test was carried out by administering 2000 mg/kg to five females in the first instance.
As no mortalities occurred, the limit test was completed using five males. As no mortalities also occurred in males, the study was considered as complete.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: No clinical signs indicative of systemic toxicity were observed in any animals. A very slight erythema was noted on the interscapular region of two females, before dosing on day 1 and lasted until day 3. This clinical sign was considered to be consecutive

Gross pathology:

There was an enlargement of spleen in four out of five treated males. Although this finding was not recorded in treated females, this was considered to be related to the test item treatment.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this study, the dermal LD50 of the test item, 2-Hydroxy Gamma ButyroLactone, was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as toxic by dermal route according to the criteria of CLP Regulation.