Registration Dossier

Administrative data

Description of key information

No studies investigating the skin and eye irritating potential of the test item are available. However, suitable OECD Guideline studies (GLP conform) with a structural analogue substance exist which cover the endpoints adequately.

The structural analogue substance did not exert a skin irritating potential, however, showed an eye irritating potential.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-10-24 to 2006-11-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
04-2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Official Journal of the European Communities L383 A, Vol. 15, 29. December 1992.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 15 weeks
- Weight at study initiation: 3.22 kg mean
- Housing: separately in special rabbit cages (manufacturer: Becker, type K99/30 KU)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 20
- Humidity (%): 48 - 71
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Days 1 to 8
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
Aqua pro injectione
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 500 mg

VEHICLE
Name: Aqua pro injectione
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
3 f
Details on study design:
TEST SITE
- Area of exposure: left side of the animal back
- Type of wrap if used: self-adhesive fabric (Fixomull stretch, Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Method: wiped off dry
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1 hour after removal, after 24, 48, 72 hours, and then daily up to experimental day 8

SCORING SYSTEM:
- Method of calculation: according OECD GL 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritating potential could be detected.

Study design

The test item was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto patches and applied to the intact skin of previously shaven rabbits for 4 hours under semiocclusive conditions. The study was performed initially with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin was 1 hour after patch removal. Thereafter, examinations were performed daily for a further 7 days.

Results

Under the conditions of the present study, no signs of irritation were seen. Body weight development of the treated rabbits was inconspicuous.

Conclusions

No skin irritating potential could be detected.

Interpretation of results:
GHS criteria not met
Conclusions:
No skin irritating potential could be detected.
Executive summary:

This study was performed according to GLP and methods applied are fully compliant with OECD TG 404. For the test item no irritating potential could be detected.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For this endpoint information from structural similar compounds is available. The studies for these similar compounds were performed according to GLP and the methods applied are fully compliant with OECD TG 404. See chapter 13 report for a more detailed justification.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 404. The Read Across result is not irritating to skin. See chapter 13 report for a more detailed justification.
Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-11-15 to 2006-11-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
04-2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Official Journal of the European Communities L383 A, Vol. 15, 29. December 1992.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 18 weeks
- Weight at study initiation: 3.34 KG
- Housing: separately in special rabbit cages (manufacturer: Becker, type K99/30 KU)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 47 - 63
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Days 1 to 15
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
Single application into the conjunctival sac of the left eye, the right eye remained untreated and served as control. The eyelids were closed for 30 sec after installation.
Observation period (in vivo):
24, 48, and 72 hours, then daily up to day 15 of the experimental part
Number of animals or in vitro replicates:
1 f
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according OECD GL 405

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 9 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritant / corrosive response data:
The cornea developed diffuse areas of opacity from the first reading up to day 3 of the experimental part. At the iris signs of irritation were observed from the first reading up to day 4. The conjunctivae showed redness and chemosis from the first reading up to experimental day 8. Thereafter no signs of irritation were observed. The untreated eye was unchanged.
Other effects:
none

Study design

The test item was tested for its eye irritating potential with one rabbit in a GLP study according to OECD GL 405. Prior to testing, a hen's egg test on the chorioallantoic membrane was performed and no irritating potential could be detected. For the test of primary eye irritation, 100 mg of the test material was applied into the conjunctival sac. The first examination of the eyes followed 1 hour after instillation and the other examinations were performed daily for a further 14 days.

Results

There were no signs of pain immediately after instillation. The cornea developed diffuse areas of opacity (scores 1) from the first reading up to day 3 of the experimental part. At the iris signs of irritation were observed (score 1) from the first reading up to day 4. The conjunctivae showed redness (scores 1 and 2) and chemosis (score 1) from the first reading up to experimental day 8. Thereafter no signs of irritation were observed. The untreated eye was unchanged.

Conclusion

Based on the observed results the test item should be regarded as an irritant to the eyes.

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
The test item possess an irritating potential to eye.
Executive summary:

This GLP study was performed according to OECD GL 405. A eye irritating potential was noted and the test item should be regarded as an irritant to the eyes.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For this endpoint information from structural similar compounds is available. The studies for these similar compounds were performed according to GLP and the methods applied are fully compliant with OECD TG 405. See chapter 13 report for a more detailed justification.
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 9 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 3 days
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 405. The Read Across result is mildly irritating to eyes. See chapter 13 report for a more detailed justification.
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the results provided, the test item is not classified for skin irritation/corrosion, however, the test item is classified for eye irritation Cat. 2 and labelled with H319 according to Regulation (EC) No 1272/2008. According to UN GHS, 7th Rev., the test item is classified for eye irritation Cat. 2a and labelled with H319.