Registration Dossier

Administrative data

Description of key information

Skin irritation / corrosion: not irritating
Eye irritation: not irritating
Respiratory irritation: not formally assessed but not expected to be a respiratory irritant as the test item is not classified as irritating to skin or eyes and there is no indication of irritant potential in acute oral/dermal studies performed in rats with the substance

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:
07-DEC-1999 to 18-JAN-2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This GLP-compliant study was conducted in accordance with OECD guideline 404 and EU method B.4.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (as cited in study report): Perfluorosulfonyl vinyl-ether
- Purity: 100%
- Impurities, purity test date: no data available
- Physical state: colourless liquid
- Lot/batch No.: 6-99
- Manufacturing date: 24 May 1999
- Expiration date of the lot/batch: May 2001
- Storage condition of test material: at room temperature, away from humidity
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Conelli S.n.c. / Via Milano, 61 - 28041 ARONA (Novara) / ITALY
- Age at study initiation: 2-3 months old when received
- Weight at study initiation: 2.5-2.8 kg when received; on arrival at RBM, all animals were clinically observed and 20% of them were weighed: their weight conformed to that required.
- Housing: in the same room in which the treatment was performed; in metal cages with stainless steel feeders
- Diet: ad libitum with a diet coded "2 RB 15 GLP Certificate" (Charles River Italia's feed licensee Mucedola S.r.l., Settimo Milanese) supplemented by the producer with vitamins and trace elements
- Water: ad libitum, filtered water from municipal water main system
- Acclimation period: from 14-JUL-1999 to 07-DEC-1999

ENVIRONMENTAL CONDITIONS
- Temperature: 19 ± 2°C
- Humidity: 55 ± 10%
- Air changes: about 15-20 per hour filtered on HEPA 99.97%
- Photoperiod: 12 hrs dark / 12 hrs light (7 a.m. - 7 p.m.)

IN-LIFE DATES: From 14-JUL-1999 to 10-DEC-1999
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL/site

VEHICLE
Not applicable
Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours
Observation period:
Immediately and 72 hrs after the 3-min and the 1-hr exposure period in the first rabbit and at 1, 24, 48 and 72 hrs after the 4-hr exposure period (all rabbits)
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: approximately 24 hours before the test, fur was clipped from the trunk of the animals. Care was taken not to abrade the skin. Only animals with intact skin were 0.5 mL of the test article were applied to a small area (approximately 6 cm²) of skin.
- % coverage: no data available
- Type of wrap if used: gauze patch

Firstly one rabbit was used and three treatment sites of the skin were prepared. On the first site the test article was applied for an exposure period of 3 minutes. Since no gross skin reactions were noted, the test article was applied for an exposure period of 1 hour on the second site. The application area was covered with a gauze patch loosely held in contact with the skin by an impermeable, non-irritant, hypoallergenic tape (occlusive patch). Since no gross reactions were observed after the one-hour exposure periods the test article was applied for an exposure period of 4 hours on the third skin site. This area was covered with a gauze patch as above. The test was completed using two additional animals with a 4-hour exposure period.
Adjacent areas of untreated skin of each animal served as control for the test.

REMOVAL OF TEST SUBSTANCE
- Washing: residual substance was wiped off.
- Time after start of exposure: at the end of each exposure period

SCORING SYSTEM:
The skin reaction was scored according to the scale presented in Table 1 below in "any other information on materials and methods incl. tables".
The dermal irritation was evaluated in conjunction with the nature and reversibility or otherwise of the responses observed.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 3 min and 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: exposure period: 3 min
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 hr and 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: exposure period: 1 hr
Irritation parameter:
erythema score
Basis:
animal: #1, #2 and #3
Time point:
other: 60 min, 24, 48 and 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: exposure period: 4 hrs
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 3 min and 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: exposure period: 3 min
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 hr and 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: exposure period: 1 hr
Irritation parameter:
edema score
Basis:
animal: #1, #2 and #3
Time point:
other: 60 min, 24, 48 and 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: exposure period: 4 hrs
Irritant / corrosive response data:
No changes were seen at any test article application site.
Other effects:
Neither mortality nor adverse general clinical modifications were seen during the study.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to this study, the test article was not classified as a dermal irritant.
Executive summary:

In a dermal irritation study performed according to OECD guideline 404 and in compliance with good laboratory practices (GLP), New-Zealand rabbits (3 males) were dermally exposed to 0.5 mL of test article (purity: 100 %) applied as such on 6 cm2 body surface area, on the skin of the trunk. Test sites were covered with an occlusive dressing for up to 4 hours. Irritation was scored based on erythema and oedema observed 3 min, 1, 24, 48 and 72 hrs after the end of application.

 

No general clinical signs were noted in any rabbit. No skin reactions were observed during the study. The mean score for the reading times 24, 48 and 72 hours of the 3 rabbits for both erythema and oedema was equal to 0. Therefore, in this study, the test article was not a dermal irritant.

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:
14-DEC-1999 to 22-MAR-2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This GLP-compliant study was conducted in accordance with OECD guideline 405 and EU method B.5.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (as cited in study report): Perfluorosulfonyl vinyl-ether
- Purity: 100%
- Impurities, purity test date: no data available
- Physical state: colourless liquid
- Lot/batch No.: 6-99
- Manufacturing date: 24 May 1999
- Expiration date of the lot/batch: May 2001
- Storage condition of test material: at room temperature, away from humidity
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Conelli S.n.c. / Via Milano, 61 - 28041 ARONA (Novara) / ITALY
- Age at study initiation: 2-3 months old when received
- Weight at study initiation: 2.5-2.8 kg when received; on arrival at RBM, all animals were clinically observed and 20% of them were weighed: their weight conformed to that required.
- Housing: in the same room in which the treatment was performed; in metal cages with stainless steel feeders
- Diet: ad libitum with a diet coded "2 RB 15 GLP Certificate" (Charles River Italia's feed licensee Mucedola S.r.l., Settimo Milanese) supplemented by the producer with vitamins and trace elements
- Water: ad libitum, filtered water from municipal water main system
- Acclimation period: from 14-JUL-1999 to 14-DEC-1999

ENVIRONMENTAL CONDITIONS
- Temperature: 19 ± 2°C
- Humidity: 55 ± 10%
- Air changes: about 15-20 per hour filtered on HEPA 99.97%
- Photoperiod: 12 hrs dark / 12 hrs light (7 a.m. - 7 p.m.)

IN-LIFE DATES: From 14-JUL-1999 to 17-DEC-1999
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL

VEHICLE
Not applicable
Duration of treatment / exposure:
Single administration
Observation period (in vivo):
1, 24, 48 and 72 hrs after the test article application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing and time after start of exposure: at 24 hours post-instillation a washout was performed.
Both eyes of each experimental animal selected for the study were examined within 24 hours of testing. Only animals without eye irritation, ocular defects or pre-existing corneal injury were used. The test article (0. 1 mL) was placed in the conjunctival sac of the right eye of each animal, after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about 3-4 seconds in order to prevent loss of the material. The other eye (the left eye), remaining untreated, served as control.
After the 24-hour reading, the cornea was examined after instillation of one drop of 1% sodium fluorescein and successive washing out with sterile saline solution.

SCORING SYSTEM:
The ocular reactions were scored according to the scale presented in Table 1 below in "any other information on materials and methods incl. tables".
The illustrated guide issued by the U.S. Consumer Product Safety Commission (CPSC) was used as a reference source for evaluating and scoring the reactions. The ocular irritation scores were evaluated in conjunction with the nature and reversibility or otherwise of the responses observed.

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2 and #3
Time point:
other: 1 hr
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2 and #3
Time point:
other: 24, 48 and 72 hrs
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal: #1, #2 and #3
Time point:
other: 1, 24, 48 and 72 hrs
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 and #3
Time point:
other: 1, 24, 48 and 72 hrs
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3
Time point:
other: 1, 24, 48 and 72 hrs
Score:
0
Max. score:
0
Irritant / corrosive response data:
Slight (grade 1) conjunctival redness was noted in all rabbits at the reading carried out 1 hour after treatment. No eye changes were subsequently observed.
Negative results were obtained at the fluorescein staining performed 24 hours after the test article application.
Other effects:
Neither mortality nor adverse general clinical modifications were seen during the study.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to this study, the test article was not classified as an ocular irritant.
Executive summary:

The ocular irritancy potential of the test substance was assessed in vivo in accordance with the standardised guidelines OECD 405 and EU Method B.5 and in compliance with good laboratory practices (GLP).

 

A single ocular application of 0.1 mL of the test substance (purity: 100 %) was instilled into the conjunctival sac of New-Zealand rabbits (3 males). The other eye remained untreated and served as the control. The animals were observed for ocular effects 1, 24, 48 and 72 h after administration of the test material.

 

No general clinical signs were noted in any rabbit. Locally, at the application site, slight conjunctival redness (grade 1) was transiently observed at 1 hr post-instillation in all 3 rabbits (fully reversible within 24 hrs).The mean scores at 24, 48 and 72 hrs of the 3 rabbits were 0 for corneal opacity, 0.66 for iritis, 0 for redness and 0 for chemosis of the conjunctivae.

 

Therefore, in this study, the test article was not an ocular irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

 

In a dermal irritation study performed according to OECD guideline 404 and EU method B.4, and in compliance with GLP (Renoldi A., 2000), New-Zealand rabbits (3 males) were dermally exposed to 0.5 mL of test article (purity: 100 %) applied as such on 6 cm2  body surface area, on the skin of the trunk. Test sites were covered with an occlusive dressing for up to 4 hours. Irritation was scored based on erythema and oedema observed 3 min, 1, 24, 48 and 72 hrs after the end of application.

No general clinical signs were noted in any rabbit. No skin reactions were observed during the study. The mean score for the reading times 24, 48 and 72 hours of the 3 rabbits for both erythema and oedema was equal to 0. In conclusion, in this study, the test article was not a dermal irritant in vivo.

 

This result was further corroborated by the acute dermal toxicity study available in the test substance (Yu P., 2000): no skin irritation was described in rats at the limit dose level of 2000 mg/kg bw.

 

Therefore, no classification for skin irritation / corrosion was warranted according to the criteria of Regulation (EC) No. 1272/2008.

 

Eye irritation

 

The ocular irritancy potential of the test substance was assessed in vivo in accordance with the standardised guidelines OECD 405 and EU Method B.5 and in compliance with GLP (Renoldi A., 2000).

A single ocular application of 0.1 mL of the test substance (purity: 100 %) was instilled into the conjunctival sac of New-Zealand rabbits (3 males). The other eye remained untreated and served as the control. The animals were observed for ocular effects 1, 24, 48 and 72 h after administration of the test material.

No general clinical signs were noted in any rabbit. Locally, at the application site, slight conjunctival redness (grade 1) was transiently observed at 1 hr post-instillation in all 3 rabbits (fully reversible within 24 hrs).The mean scores at 24, 48 and 72 hrs of the 3 rabbits were 0 for corneal opacity, 0.66 for iritis, 0 for redness and 0 for chemosis of the conjunctivae.

In conclusion, in this study, the test article was not an ocular irritant in vivo, therefore warranting no classification for eye irritation according to the criteria of Regulation (EC) No. 1272/2008.

 

Respiratory irritation

 

There was no respiratory irritation study available on the test substance. However, such effect was not expected as the substance showed no skin/eye irritation potential and, furthermore, no irritation-like injury were observed in the acute oral/dermal studies performed on the test substance.

Justification for selection of skin irritation / corrosion endpoint:
The key study was conducted on the test item in compliance with GLP and according to OECD guideline 404 and EU method B.4. Well described and meeting the generally acceptable scientific principles, this study was awarded a reliability score of 1 in accordance with the Klimisch cotation criteria (1997).

Justification for selection of eye irritation endpoint:
The key study was conducted on the test item in compliance with GLP and according to OECD guideline 405 and EU method B.5. Well described and meeting the generally acceptable scientific principles, this study was awarded a reliability score of 1 in accordance with the Klimisch cotation criteria (1997).

Justification for classification or non-classification

The available in vivo data on the test substance showed that irritation / corrosion to either skin or eyes did not occur after exposure to the test item. Thus, the test substance is not classified as skin, eye, or respiratory irritant according to the criteria of Regulation (EC) No. 1272/2008.