Registration Dossier

Administrative data

Description of key information

No respiratory irritation was observed in rats exposed to 2000 ppm (20123 mg/m3) PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) in a 28-day repeated exposure inhalation toxicity study.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline equivalent study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hrs
Observation period:
48 hrs
Number of animals:
6
Details on study design:
Six male albino rabbits were clipped free of hair on the trunk and lateral area and placed in FDA-type stocks. Doses of 0.5 ml of undiluted test material were applied to intact skin under 1 ½ inch x 1 ½ inch 12-ply gauze squares. Rubber sheeting was then loosely wrapped around the trunk and secured with adhesive tape. After 24 hours, the rabbits were removed from the stocks, the patches taken off and the reactions observed. Observations were also made at 48 hours.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0

Table 1: Results of PFBE Skin Irritation Test in Rabbits.

24-Hour Observation

48-Hour Observation

Erythema

Oedema

Erythema

Oedema

None 6/6

None 6/6

None 6/6

None 6/6

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) caused no skin irritation in 24 or 48 hrs when tested on the shaved intact skin of 6 male rabbits.
Executive summary:

PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) caused no skin irritation in 24 or 48 hrs when tested on the shaved intact skin of 6 male rabbits.

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
Reliability:
2 (reliable with restrictions)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.1 ml
Observation period (in vivo):
3-days
Number of animals or in vitro replicates:
2
Details on study design:
0.1 ml of undiluted test material was placed into the right conjunctival sac of each of 2 male New Zealand White Rabbits. After 20 seconds, 1 treated eye was washed with tap water for 1 minute. The treated eye of the other rabbit was not washed. Observations of the cornea, iris and conjunctiva were made with an ophthalmoscope at 1 and 4 hours, and at 1, 2 and 3-days. Fluor-I-strip® and a slit lamp biomicroscope were used at examinations after the day of treatment.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
1
Irritation parameter:
iris score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
1

Table 1: Results of PFBE Eye Irritation Test in the Rabbit

Dose

Treatment

Ocular Effects

Cornea

Iris

Conjunctiva

0.1 ml

Not washed

General area of slight clouding at 1 hr; decreasing to a small area at 4 hr

No involvement

Redness:None

Swelling:Slight 1 – 4 hr

Discharge:Mild at 4 hr

0.1 ml

Washed

Small area of slight clouding at 1 hr decreasing to a local area 4 hr – 1 day

No involvement

Redness:None

Swelling:Slight 1 – 4 hr

Discharge:None

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) may produce slight to mild eye irritation.
Executive summary:

PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) caused slight corneal clouding and mild conjunctivitis in a treated rabbit eye. It caused slight corneal clouding and slight conjunctivitis in an eye, when treated and promptly washed. Both washed and unwashed eyes were normal 2 days after treatment.

PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) may produce slight to mild eye irritation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

1) In a dermal irritation/corrosion study to a protocol equivalent/similar to OECD Test Guideline 404, PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) caused no irritation to the shaved intact skin of six male rabbits.

2) In an acute eye irritation/corrosion study to a protocol equivalent or similar to OECD Test Guideline 405, PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) caused slight corneal clouding and mild conjunctivitis in a treated rabbit eye. It caused slight corneal clouding and slight conjuctivitis in an eye when treated and promptly washed, . Both washed and unwashed eyes were normal 2 days (48 hr) after treatment. As a result, PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) was judged to be a slight/mild irritant to the eye.


Justification for selection of skin irritation / corrosion endpoint:
Study conducted to a protocol equivalent/similar to OECD Guideline 404

Justification for selection of eye irritation endpoint:
Study conducted to a protocol equivalent/similar to OECD Guildline 4

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

In a dermal irritation/corrosion study to a protocol equivalent/similar to OECD Test Guideline 404, PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) caused no irritation to the shaved intact skin of six male rabbits. Therefore classification for skin irritation/corrosion is not warranted according to EU Directive 67/548/EEC or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

In an acute eye irritation/corrosion study to a protocol equivalent or similar to OECD Test Guideline 405, PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) caused slight corneal clouding and mild conjunctivitis in a treated rabbit eye. It caused slight corneal clouding and slight conjuctivitis in an eye when treated and promptly washed. Both washed and unwashed eyes were normal 2 days (48 hr) after treatment. As a result, PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) was judged to be a slight/mild irritant to the eye. Since the effects had totally disappeared after 48 hrs, the mean scores for corneal opacity and conjuctivitis graded at the 24hr, 48hr and 72hrs after treatment were likely to be <1. Therefore the irritant effects observed were not sufficently severe for PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) to be classified as Irritating to Eyes (Category 2) according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Similarly, classification as Irritating to Eyes (R38) is not warranted according to EU Directive 67/548/EEC.

No respiratory irritation was observed in rats exposed to 2000 ppm (20123 mg/m3) PFBE (3,3,4,4,5,5,6,6,6-nonafluorohexene) in a 28-day repeated exposure inhalation toxicity study. Therefore, classification for respiratory irritation is not warranted according to EU Directive 67/548/EEC or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.