Registration Dossier

Administrative data

Description of key information

No skin and eye irritating potential of the test item could be detected in an in vivo skin irritation study according to OECD guideline 404 and in an vivo eye irritation study according to OECD guideline 405 (reference 7.3.1-1 and 7.3.2-1).

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:
April 23, 2003 - July 23, 2003
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:
April 24, 2002
Deviations:
no
Qualifier:
according to guideline
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. QA statement)
Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: About 31 weeks
- Weight at study initiation: 4.23 - 4.50 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): 21 - 23°C
- Humidity (%): 19 - 59%
- 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:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g per animal

VEHICLE
Name: Aqua pro injectione
Manufacturer: Merck KGaA, Darmstadt
Batch: 0189
Released until: June 08, 2009
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 6 cm^2, left side of the animal back,
- Type of wrap: 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 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.
Other effects:
- Clinical signs: No signs of clinical toxicity were detected.
- Mortality: All animals survived the observation period.
- Body weights: Body weight development of the treated rabbits was inconspicious.
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 guideline 404.To test the primary skin irritation, 0.5 g of the test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto 6 cm^2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with one animal and followed by the confirmatory test with 2 further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 7 days. 24/48/72 hour irritation scores for both erythema and edema were 0 for all animals. Body weight development of the treated rabbits was inconspicuous. Thus, under the conditions of the present study, no signs of irritation were seen.

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:
April 17, 2003 - August 05, 2003
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:
April 24, 2002
Deviations:
no
Qualifier:
according to guideline
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. QA statement)
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 35 weeks
- Weight at study initiation: 4.04 - 4.26 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): 22 - 24°C
- Humidity (%): 37 - 66%
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12hrs light

IN-LIFE DATES: From day 1 to day 8
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g per animal
Duration of treatment / exposure:
8 days
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 females
Details on study design:
REMOVAL OF TEST SUBSTANCE

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
Reversibility:
other: no indication of irritation
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
Reversibility:
other: no indication of irritation
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
Reversibility:
other: no indication of irritation
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
Reversibility:
other: no indication of irritation
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
Reversibility:
other: no indication of irritation
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
Reversibility:
other: no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.333
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no indication of irritation
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
Reversibility:
other: no indication of irritation
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
Reversibility:
other: no indication of irritation
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation were observed at the cornea or iris.The conjunctivae showed redness (score 1) at the first reading (1 hour) in all animals and in one animal at the second reading (24 hours). Thereafter no signs of irritation were observed. No abnormalities were detected in the untreated eyes.
Other effects:
- Clinical signs: No signs of clinical toxicity were detected.
- Mortality: All animals survived the observation period.
- Body weights: Body weight development of the treated rabbits was inconspicious.
Interpretation of results:
GHS criteria not met
Conclusions:
In this in vivo eye irritation study according to OECD guideline 405, the test item showed no relevant eye irritating potential.
Executive summary:

The study was performed according to OECD guideline 405 under GLP conditions. The test item 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. No signs of irritation were observed at the cornea or iris. The conjunctivae showed redness (score 1) at the first reading (1 hour) in all animals and in one animal at the second reading (24 hours). Thereafter no signs of irritation were observed. No abnormalities were detected in the untreated eyes. No relevant eye irritating potential could be detected. The test item 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

In vivo skin irritation, key study


This study was performed according to GLP and methods applied are fully compliant with OECD guideline 404.To test the primary skin irritation, 0.5 g of the test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto 6 cm^2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with one animal and followed by the confirmatory test with 2 further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 7 days. 24/48/72 hour irritation scores for both erythema and edema were 0 for all animals. Body weight development of the treated rabbits was inconspicuous. Thus, under the conditions of the present study, no signs of irritation were seen.


 


In vivo eye irritation, key study


The study was performed according to OECD guideline 405 under GLP conditions. The test item 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. No signs of irritation were observed at the cornea or iris. The conjunctivae showed redness (score 1) at the first reading (1 hour) in all animals and in one animal at the second reading (24 hours). Thereafter no signs of irritation were observed. No abnormalities were detected in the untreated eyes. No relevant eye irritating potential could be detected. The test item should not be classified as an eye irritant.

Justification for classification or non-classification

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


The available data for skin and eye irritation are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The test item is not considered to be classified for skin and eye irritation/corrosion according to EU Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217.