Registration Dossier

Administrative data

Description of key information

OECD 404: negative

OECD 405: 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:
August 19, 2004 - November 30, 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
April 24, 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)
Test material information:
Composition 1
Specific details on test material used for the study:

Purity : 99.9 %




TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Before application, the test material was mixed with some drops of Aqua pro injectione and ground 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 14 - 15 weeks
- Weight at study initiation: 3.20 - 3.42 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): 18 - 20°C
- Humidity (%): 46 - 71%
- 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(s) applied (volume or weight with unit): 0.5g per animal

VEHICLE
Name: Aqua pro injectione
Manufacturer: Merck KGaA, Darmstadt
Batch: 189
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: 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, 0.5 g of the test material, the test material, was mixed with some drops ofAqua pro injectioneto ensure good contact with the skin. Afterwards the test material was spread onto 6 cm2patches 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 two 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.

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
Reference
Endpoint:
eye irritation, other
Remarks:
in vivo Study
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 4, 2006 - November 15, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 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 L383 A, Vol. 15, 29. December 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Specific details on test material used for the study:

Purity : 99,9 %



TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test material was administered undiluted.
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: approx. 12 weeks
- Weight at study initiation: 2.56 - 2.86 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: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 20 °C
- Humidity (%): 48 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 females
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
Remarks:
redness
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
Remarks:
redness
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
other: discharge
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
other: discharge
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
other: discharge
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation were observed at the cornea or iris. One hour and 24 hours after treatment, the conjunctivae showed redness (score 1). Furthermore, discharge (score 1) was seen at the first reading. Thereafter no signs of irritation were observed. The untreated eyes were unchanged.
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 started as an initial test with one animal and followed by the confirmatory test with two further animals. For the test of primary eye irritation, 0.1 g of 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 further 7 days.


Results

No signs of irritation were observed at the cornea or iris. One hour and 24 hours after treatment, the conjunctivae showed redness (score 1). Furthermore, discharge (score 1) was seen at the first reading. Thereafter, no signs of irritation were observed. The untreated eyes were unchanged.


Conclusion

According to the EEC-Directive 2001/59 the test material should not be regarded as an irritant to the eyes.

Interpretation of results:
GHS criteria not met
Conclusions:
According to these results, for regulatory purposes the test material has to be classified as non-irritant for the eyes.
Executive summary:

The study was performed according to OECD 405 under GLP conditions. According to these results, for regulatory purposes the test material has to be classified as non-irritant for the eyes.


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

No adverse effects have been observed and thus no classification is needed.