Registration Dossier

Administrative data

Description of key information

Skin irritation

Key, rabbit, semiocclusive, OECD 404, GLP: negative

Eye irritation

Key, rabbit, OECD 405, GLP: negative

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:
09 MAR 2000 - 19 JUN 2000
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:
July 1992
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL(NZW)BR
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 25 weeks
- Weight at study initiation: mean 4.14 kg (range from 3.32 to 4.86 kg)
- Housing: All rabbits were housed in an air-conditioned room of about 28 m² in the Institute of Toxicology. They were kept separately in special rabbit cages (manufacturer: Becker; type K99/30 KU, floor area about 5400 cm², a shelter with an integrated sitting board of about 1820 cm²; overall height: 60 cm) with plastic grids placed on mobile racks. The collection pans underneath the cages were cleaned at least three times a week. The cages were cleaned before the start of the study.
- Diet (e.g. ad libitum): ad libitum, the diet is checked periodically according to the specifications of the manufacturer by an independent laboratory, approved by the German government. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.
- Water (e.g. ad libitum): ad libitum, the drinking water is periodically analyzed according to the German regulations for human drinking water.
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22
- Humidity (%): 46 - 65
- Photoperiod (hrs dark / hrs light): 12/12
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): 500 mg
- Concentration (if solution): in some drops of Aqua pro injectione

VEHICLE
- Amount(s) applied (volume or weight with unit): some drops of Aqua pro injectione
- Lot/batch no. (if required): 0189
Duration of treatment / exposure:
4 h
Observation period:
The rabbits were examined for skin alterations, behavior, and general condition 1 hour after removal of the patches, after 24, 48, 72 hours, and then daily up to day 8 of the study.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: patch, the patches were fastened to the left side of the animals backs and kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any test material residues were wiped off
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1 hour after removal of the patches, after 24, 48, 72 hours, and then daily up to day 8 of the study

SCORING SYSTEM:
- Method of calculation: Skin changes at the application sites were evaluated according to the DRAIZE-, OECD- and EEC recommendations.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
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
Reversibility:
other: not applicable
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
Reversibility:
other: not applicable
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
Reversibility:
other: not applicable
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
Reversibility:
other: not applicable
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
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation were observed in the treated areas.
Other effects:
Symptoms
No signs of clinical toxicity were detected.

Mortality
All animals survived the observation period.

Body weight
Body weight development of the treated rabbits was inconspicuous.
Interpretation of results:
other: EU GHS criteria not met
Conclusions:
The test substance was shown to cause no skin irritation when applied under semiocclusive conditions.
Executive summary:

The skin irritation potential of the registered substance was tested in rabbits according to OECD Guideline 404 and GLP. The test item was mixed with some drops of Aqua pro injectione to ensure good contact to the skin. Afterwards the test material was spread onto patches and applied to the intact skin of three previously shaven rabbits for a 4 hours period under semiocclusive conditions. 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. The test substance was shown to cause no skin irritation.

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:
15 MAR 2000 - 19 JUN 2000
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:
24 February 1987
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL(NZW)BR
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 25 weeks
- Weight at study initiation: 4.25 kg (range 3.98 - 4.73 kg)
- Housing: All rabbits were housed in an air-conditioned room of about 28 m² in the Institute of Toxicology. They were kept separately in special rabbit cages (manufacturer: Becker; type K99/30 KU, floor area about 5400 cm², a shelter with an integrated sitting board of about 1820 cm²; overall height: 60 cm) with plastic grids placed on mobile racks. The collection pans underneath the cages were cleaned at least three times a week. The cages were cleaned before the start of the experimental part.
- Diet (e.g. ad libitum): ad libitum, the diet is checked periodically according to the specifications of the manufacturer by an independent laboratory, approved by the German government. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.
- Water (e.g. ad libitum): ad libitum, the drinking water is periodically analyzed according to the German regulations for human drinking water.
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22
- Humidity (%): 46 - 65
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
After instillation, the eyelids were closed for about 30 seconds. The test item was not removed.
Observation period (in vivo):
1 hour after treatment, after 24, 48, and 72 hours, then daily up to day 8 of the experimental part
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
no

SCORING SYSTEM: Eye changes were evaluated according to the DRAIZE- , OECD- and EEC- recommendations.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 5 d
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 4 d
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 3 d
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
Reversibility:
other: not applicable
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: not applicable
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: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
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: not applicable
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: not applicable
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: not applicable
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: not applicable
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: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation were observed at the cornea and iris. The conjunctivae showed redness (score 1), Chemosis (score 1), and discharge (score 2) from day 1 up to day 5 of the study. Redness of conjunctivae on days 4 and 5 of the study concerned the nictating membrane. Later on no signs of irritation were observed. The untreated eyes were unchanged.
Other effects:
- Other observations: Body weight development of the treated rabbits was inconspicuous. All animals survived the observation period. No signs of clinical toxicity were detected.

for details on results, please refer to tables under 'Attached background material'

Interpretation of results:
other: EU GHS criteria not met
Conclusions:
No signs of irritation were observed at the cornea and iris. The conjunctivae showed redness (score 1), chemosis (score 1), and discharge (score 2) from day 1 up to day 5 of the study. Later on no signs of irritation were observed. The untreated eyes were unchanged.
Executive summary:

The test item was tested for eye irritation according to OECD Guideline 405 and GLP. 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 examinations were performed daily for further 7 days. No signs of irritation were observed at the cornea and iris. The conjunctivae showed redness (score 1), chemosis (score 1), and discharge (score 2) from day 1 up to day 5 of the study. Later on no signs of irritation were observed. The untreated eyes were unchanged.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The skin irritation potential of the registered substance was tested in rabbits according to OECD Guideline 404 and GLP. The test item was mixed with some drops of Aqua pro injectione to ensure good contact to the skin. Afterwards the test material was spread onto patches and applied to the intact skin of three previously shaven rabbits for a 4 hours period under semiocclusive conditions. 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. The test substance was shown to cause no skin irritation.

Eye irritation

The registered substance was tested for eye irritation according to OECD Guideline 405 and GLP. 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 examinations were performed daily for further 7 days. No signs of irritation were observed at the cornea and iris. The conjunctivae showed redness (score 1), chemosis (score 1), and discharge (score 2) from day 1 up to day 5 of the study. Later on no signs of irritation were observed. The untreated eyes were unchanged.

Justification for classification or non-classification

Based on the available results no classification for irritation is triggered in accordance with Regulation (EC) No 1272/2008.