Registration Dossier

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Administrative data

Description of key information

A Skin Irritation/Corrosion study performed according to OECD 404

guideline and an Eye Irritation study performed according to OECD 405 guideline are reported.
The substance does not meet the classification criteria of Regulation EC No. 1272/2008, both for Skin and Eye irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
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)
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
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
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
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
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
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
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
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

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 February 2005 to 18 August 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2004
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml, undiluted
Duration of treatment / exposure:
one single instillation (0.1 mL/animal)
Observation period (in vivo):
10 days
Number of animals or in vitro replicates:
3 (Animals of both sexes were used: 1 male + 2 females)
Irritation parameter:
cornea opacity score
Remarks:
mean
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
cornea opacity score
Remarks:
mean
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
cornea opacity score
Remarks:
mean
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Remarks:
mean
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Remarks:
mean
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Remarks:
mean
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours

Viability

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 mean (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately.

Very slight corneal opacity affecting the whole area was noted in all animals at the 24 -hour observation and persisted in one female animal up to the 72 -hour reading.

Moderate reddening of the conjunctivae was noted in all animals from the 1 -hour to the 24 -hour observation and persisted in one female animal up to the 72-hour reading . Slight reddening was noted in two animals at the 48 -hour reading and was still present at the 72 -hour observation in the male animal.

Slight swelling (chemosis) of the conjunctivae was observed in all animals at the 1 -hour reading. Slight swelling to obvious swelling with partial eversion of lids was noted in all animals at the 24 -hour reading and slight swelling persisted in one female up to the 72 -hour reading.

Moderate reddening of the sclerae was present in all animals at the 1 -hour reading. Slight to moderate reddening was noted in all animals at the 24 -hour reading and in two animals at the 48 -hour reading. Slight erddening was noted in all animals at the 72 -hour reading and persisted in one animal up to the 7 -day reading.

Slight ocular discharge was noted in all animals from the 1 -hour to the 24 -hour observation.

Coloration

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

Corrosion

No corrosion of the cornea was observed at any of the reading times.

Interpretation of results:
GHS criteria not met
Conclusions:
2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane is considered to be "not irritanting" to the rabbit eye.
Executive summary:

The primary eye irritation potential of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1ml into the left eye of three young adult New Zeland White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7 and 10 days after test item instillation.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean score were 0.33, 0.33 and 0.00 for corneal opacity and 0.00 for the iris for all three animals, respectively. The individual mean scores for the conjunctivae were 1.33, 2.00 and 1.00 for redness and 0.33, 1.33 and 0.33 for chemosis, respectively.

The instillation of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane into the eye resulted in moderate, early onset and transient ocular changes, such as corneal opacity, reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 10 days after treatment, the end of the observation period for all animals. No abnormal findings were observed in the iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed.

Thus the test item does not induce significant or irreversible damage to the rabbit eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

An in vivo study, performed in order to investigate the skin primary irritation potential of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane is reported. The study was performed according to OECD 404 guideline, based on a 4-hour semi-occlusive application. According to the conclusion of the study the substance is considered to be “not irritanting” to the rabbit skin. 

An in vivo study, performed in order to investigate the eye primary irritation potential of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane is reported. The study was performed according to OECD 405 guideline. According to the conclusion of the study the substance is considered to be “not irritanting” to the rabbit eye.


Justification for selection of skin irritation / corrosion endpoint:
Available study, conducted under GLP and according to recognized international standard guideline.

Justification for selection of eye irritation endpoint:
Available study, conducted under GLP and according to recognized international standard guideline.

Justification for classification or non-classification

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 and eye irritation

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