Registration Dossier

Administrative data

Description of key information

Skin irritation:
The test material was found to be non-irritating to rabbits' skin.
Eye irritation:
The test substance was found to be non-irritating to rabbits' eyes.

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:
2007-02-13 to 2007-02-14
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
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2-3.5 kg
- Housing: individually
- Diet: certified rabbit food, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
One animal was initially treated with three patches, one patch was removed at each of the three time points 3 min, 1 h and 4 h. Two additional animals were treated afterwards and the patches were removed after 4 hours.
Observation period:
Test sites were observed after 1, 24, 48 and 72 hours.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal/flank area
- Type of wrap if used: elasticated corset

REMOVAL OF TEST SUBSTANCE
- Washing: Any residual test material was removed by swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: directly after removal of the patch

SCORING SYSTEM:
Erythema and oedema formation were scored according to a 5 graded scale (0-4) each.
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:
The test material was not irritating to the rabbits' skin.
Executive summary:

A study according to OECD Guideline No. 404 was conducted to assess the irritating properties of the test substance when applied to rabbits’ skin. Three male New Zealand White rabbits were used. 0.5 mL of the undiluted test item were applied to clipped skin sites under semi-occlusive conditions. The first animal was exposed for 3 min, 1 hour and 4 hours and based on the skin findings the remaining two animals were exposed for 4 hours afterwards. After patch removal, the skin sites were examined after 1, 24, 48 and 72 hours. No signs of erythema/eschar or oedema formation was observed. Based on these results, the test material was considered to be non-irritating to 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:
2007-02-19 to 2007-03-01
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
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2-3.5 kg
- Housing: individually
- Diet: certified rabbit diet, ad libitum
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:
one application per animal
Observation period (in vivo):
Observations were made 1, 24, 48 and 72 hours after application.
Number of animals or in vitro replicates:
3 male animals
Details on study design:
SCORING SYSTEM: according to Draize scale

TOOL USED TO ASSESS SCORE: light source from a standard opthalmoscope
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis 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:
Conjunctivae redness was observed in all animals but was reversible within 48 h. Chemosis and discharge were only observed 1 hour after treatment (all animals).
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was not irritating at a concentration of 100 % in the rabbits' eyes.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The study was performed according to OECD Guideline 405 and according to GLP. Three rabbits were treated with a single application of 0.1 mL test substance. As a result, conjunctival irritation was observed in all animals, but all eyes appeared normal after 48 hours. Therefore, the substance was concluded to be not irritating to the eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Key study

A study according to OECD Guideline 404 was conducted to assess the irritating properties of the test substance when applied to rabbits’ skin. 0.5 mL of the undiluted test item was applied to clipped skin sites under semi-occlusive conditions on 3 animals. The first animal was exposed for 3 min, 1 hour and 4 hours and based on the skin findings the remaining two animals were exposed for 4 hours afterwards. After patch removal, the skin sites were examined after 1, 24, 48 and 72 hours. No signs of erythema/eschar or oedema formation were observed. Based on these results, the test material was considered to be non-irritating to skin.

Supporting study

The test material at a concentration of 10 % in olive oil was applied to skin sites on the backs and upper arms of 60 human volunteers under occlusion. The patches were removed after 24 hours and skin reactions were observed 24, 48 and 72 hours thereafter. As a result, no skin reactions were recorded and thus it was concluded that the test substance was not irritating at a concentration of 10 %. For details, please refer to IUCLID6, section 7.10.5.

Conclusion

The study conducted in rabbits according to OECD 404 was selected as key study as undiluted test substance was used in a standard animal test according to REACH requirements. The conclusion that the test substance is not irritating on skin was supported by the result of a study with 10 % test substance on human volunteers.

 

Eye irritation:

Key study

A study was performed to assess the irritancy potential of the test material to the eye of rabbits. The study was performed according to OECD Guideline 405 and according to GLP. Three rabbits were treated with a single application of 0.1 mL test substance. As a result, conjunctival irritation was observed in all animals, but all eyes appeared normal after 48 hours. Therefore, the substance was concluded to be not irritating to the eyes.

Supporting study

0.1 mL of the test substance was applied as a concentration of 10 % in olive oil in the eyes of 8 rabbits to assess its irritating property. The eyes of half of the animals were rinsed after application. As a result, no signs of irritation were observed. Therefore, the test substance at a concentration of 10 % was not irritating to the eyes.

Conclusion

The study conducted in rabbits according to OECD 405 was selected as key study as undiluted test substance was used in a standard animal test according to REACH requirements. The conclusion that the test substance is not irritating in eyes was supported by the result of a study with 10 % test substance in rabbits.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008.

Based on available data on skin and eye irritation/corrosion, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighth time in Regulation (EU) No 2016/918.