Propane, 1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 February 2005 to 22 March 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

(2004)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)propane

EC Number:

609-534-4

Cas Number:

382-26-3

Molecular formula:

C5H4F8O

IUPAC Name:

1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)propane

Details on test material:

- Name of test material (as cited in study report): Octafluoroisobutyl methyl ether
- Substance type: organic, mono-constituent substance
- Physical state: liquid
- Analytical purity: > 86%
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: not reported
- Isomers composition: n.a.
- Purity test date: not reported
- Lot/batch No.: 20/01/04 -161
- Expiration date of the lot/batch: 2006
- Storage condition of test material: in the refrigerator (range 5 +- 3°C), light protected.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories France
- Age at study initiation: 13 weeks (male); 12-13 weeks (females)
- Weight at study initiation: 2168 g (male); 1979 - 2115 g (females)
- Housing: individually housed stainless steel cages
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: 01-Feb-2005 To: 21-Feb-2005

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml, undiluted

VEHICLE : none

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 (1 male + 2 females)

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was flushed with lukewarm tap water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1, 24, 48, 72 hours, then 7, 10 and 14 days after removal of the dressing

SCORING SYSTEM:
- Method of calculation: mean scores across 24, 48, 72 hours scoring times for each animal, and for edema and erythema separately

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

mean score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 14 days

Results 2

Irritation parameter:

erythema score

Remarks:

mean score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 7 days

Results 3

Irritation parameter:

erythema score

Remarks:

mean score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 72 hours

Results 4

Irritation parameter:

edema score

Remarks:

mean score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 72 hours

Results 5

Irritation parameter:

edema score

Remarks:

mean score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 72 hrs

Results 6

Irritation parameter:

edema score

Remarks:

mean score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Other effects:

Scaling was observed at 72 hrs, days 7 and 10 in one animal

Any other information on results incl. tables

OTHER RESULTS

Viability/Mortality/Clinical signs

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Irritation

The mean score was calculated across 3 scoring times (24, 49 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

Well-defined erythema were observed in the male animal from the 1 -hour to 72 -hour reading and very slight erythema persisted up to the 10 -day reading. Very slight to well-defined erythema was also observed in one female from the 1 -hour reading to the 72 -hour reading, whereas in the other female only very slight erythema was noted from 1 -hour reading to the 48 -hour reading.

Very slight swelling was observed in two animals from the 24- to the 48 -hour reading. Scaling was present in the animal from the 72 -hour to the 10 -day reading.

No abnormal findings were observed on the treated skin of any animal 14 after treatment, the end on the observation time.

Coloration

No staining produced by the test item of the treated skin was observed.

Corrosion

Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Body weigh

The body weights of all rabbits were considered to be within the normal range of viability.

SKIN IRRITATION SCORE, individual results

ANIMAL NUMBER	Sex	Evaluation Interval *	Erythema	Oedema	Scaling
1 2 3	M F F	1 hour	2 1 1	0 0 0	0 0 0
1 2 3	M F F	24 hour	2 2 1	1 1 0	0 0 0
1 2 3	M F F	48 hours	2 2 1	1 1 0	0 0 0
1 2 3	M F F	72 hours	2 1 0	0 0 0	X 0 0
1 2 3	M F F	7 days	1 0 0	0 0 0	X 0 0
1 2 3	M F F	10 days	1 0 0	0 0 0	X 0 0
1 2 3	M F F	14 days	0 0 0	0 0 0	0 0 0

* Examination were performed at the specified times after the removal of the dressing.

X = Scaling present

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

According to Regulation EC No. 1272/2008, 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane does not meet the classification criteria for skin irritation.

Executive summary:

The primary skin irritation potential of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 mL to the intact lef flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7, 10 and 14 removal of the dressing.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

The mean erythema/eschar score of the three animals was 2.00, 1.67 and 0.67 respectively and the mean oedema score was 0.67, 0.67 and 0.00, respectively.

The application of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane to the skin resulted in mild to moderate signs of irritation. These included erythema, oedema and scaling. These effects were reversible and were no longer evident 14 days after treatment, the end of the observation period for all animals. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

Thus, the test item did not induce significant or irreversible damage to the skin.