Registration Dossier

Administrative data

Description of key information

Skin irritation: OECD 404: negative

Eye irritation: Read Across from OECD 405 of structural analogues = negative

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo study
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 5, 2001 - December 12, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Before the application, the test material was mixed with some drops of liquid paraffin and grounded in a mortar using a pestle.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 22 weeks
- Weight at study initiation: 3.44 - 3.83 kg
- Housing: separately in special rabbit cages (manufacturer: Becker, type K99/30 KU)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20°C
- Humidity (%): 43 - 68%
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12hrs light

IN-LIFE DATES: From: day 1 To: day 8
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Liquid paraffin
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g per animal

VEHICLE
- Liquid paraffin
- Lot/batch no. (if required): K27510174016
- Released until: February 28, 2005
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
3
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
- 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 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritating potential could be detected.

Study design

To test for primary skin irritation, 0.5g of the test material was mixed with some drops of liquid paraffin to ensure good contact to the skin. Afterwards, the test material was spread onto 6 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions.

According to the result of a pre-test, the animal study was started with three animals.

The first examination of the treated skin sites followed 1 hour after removal of the patches. Then examinations were performed daily for 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 conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation, other
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
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
Reason / purpose:
read-across source
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Interpretation of results:
GHS criteria not met
Conclusions:
For this endpoint two one-to-one read across options were performed to chemical similar compounds of the same chemical class with a comparable phys. chem. profile and similar responses in biological assays. The relevant studies were performed according to GLP and the methods applied are fully compliant with OECD TG 405. The data demonstrate absence of eye irritation potential for this class of compounds.
Executive summary:

For this endpoint two one-to-one read across options were performed to chemical similar compounds of the same chemical class with a comparable phys. chem. profile and similar responses in biological assays. The relevant studies were performed according to GLP and the methods applied are fully compliant with OECD TG 405. The data demonstrate absence of eye irritation potential for this class of compounds.

Endpoint:
eye irritation, other
Remarks:
in vivo study
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 22 until April 29, 1996
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:
OECD 1981, updated Guideline adopted Februaty 24, 1987
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Name: ZLI-4603
Consistency: Crystals
Batch: E96635863
Released until: Feb 28, 1998


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test material was moistened with liquid paraffin.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: SAVO-Ivanovas, Kißlegg
- Age at study initiation: about 28-29 weeks
- Weight at study initiation:4.31 (3.94 - 5.00) kg
- Housing: separately in special rabbit cages (manufacturer: Hulskamp, type KK 017)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21°C
- Humidity (%): 41 - 53%


IN-LIFE DATES: From: day 1 To: day 8
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1g per animal
Observation period (in vivo):
24, 48, and 72 hours, then daily up to day 8 of the experimental part
Number of animals or in vitro replicates:
3 (1 male & 2 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according OECD-Guideline

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
In the primary eye irritation test, no abnormalities of the cornea and iris were observed. The conjunctivae showed redness (score 1) in all animals at 24h . Later on no abnormalities were seen.
Other effects:
none

Study design

To test for primary eye irritation, the test material was instilled into the conjunctival say of rabbits. The first examination of the treated eye followed 1 hour after instillation. The examinations were performed daily for further 7 days.

Results

In the primary eye irritation test, no abnormalities of the cornea and iris were observed. The conjunctivae showed redness (score 1) in all animals at 24h. Later on no abnormalities were seen.


Conclusion

According to these results, for regulatory purposes the test material has to be classified as non-irritant for the eyes.

Interpretation of results:
GHS criteria not met
Conclusions:
According to these results, for regulatory purposes there is no need for classification for eye irritation.
Executive summary:

The study was performed according to OECD 405 under GLP conditions. According to these results, for regulatory purposes there is no need for classification for eye irritation.


Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 5, 2007 - September 26, 2007
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:
April 24, 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Official Journal of the European Communities L152, 2004
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Batch No: E26001046
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:Charles River Wiga GmbH, Kisslegg
- Age at study initiation: appr. 26 weeks
- Weight at study initiation: 3.51 - 4.52 kg
- Housing: The animals were kept separately in special rabbit cages (manufacturer: Becker, type K99/30 KU) placed on mobile racks.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20 °C
- Humidity (%): 52 to 75 %.
- Air changes (per hr): --

IN-LIFE DATES: From: day 1 To: day 8
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1g per animal
Observation period (in vivo):
24, 48, and 72 hours, then daily up to day 8 of the experimental part
Number of animals or in vitro replicates:
3 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according OECD-Guideline

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
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No signs of irritation were observed at the cornea or iris. All animals showed discharge (score 1) one hour after instillation of the test material. In two animals redness (score 1) was observed one hour after treatment. No abnormalities were detected in the untreated eyes.
Other effects:
none

Study design

The test material was tested for its eye irritating properties. Prior to testing, the hen's egg test on the chorioallantoic membrane was performed and no irritating potential could be detected. The test for primary eye irritation was performed initially with one animal and followed by the confirmatory test with two further animals.For the test of primary eye irritation, the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations of the eyes were performed daily for a further 7 days.

Results

No signs of irritation were observed at the cornea or iris. All animals showed discharge (score 1) one hour after instillation of the test material. In two animals redness (score 1) was observed one hour after treatment. No abnormalities were detected in the untreated eyes.


Conclusion

No relevant eye irritating potential could be detected. The test material should not be classified as an eye irritant.

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

The study was performed according to OECD 405 under GLP conditions. No relevant eye irritating potential could be detected. The test material should not be classified as an eye irritant.




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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the provided information there is no need for classification according to the EU Regulation (EC) No 1272/2008 on Classification,Labelling and Packaging of Substances and Mixtures.