Registration Dossier

Administrative data

Description of key information

In reliable studies (RL 1, guideline studies) performed for submission substance no irritating potential on skin was found and only slight irritating effects on the eyes were observed. 

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:
1996-04-16 to 1996-04-19
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
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Chemical pharmaceutical factory Dr. K Thomae 88400 Biberach
- Weight at study initiation: 2.3 - 2.6 kg
- Housing: in fully air-conditioned rooms in separate cages arranged in a battery
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light):12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: polyethylene glycol 400
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.2 ml

Duration of treatment / exposure:
4 hours
Observation period:
30- 60 minutes as well as 24, 48 and 72 hours after removal of the patches
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 25 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm tap water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
30 - 60 minutes; 24, 48 and 72 hours

SCORING SYSTEM:
- Method of calculation: DRAIZE
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 30-60min
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 30-60min
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 30-60min
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 30-60min
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 30-60min
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 30-60min
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
no signs of irritation occurred during the whole ovservation period
Other effects:
no effect
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, the test itm is not irritating to skin.
Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no 404.The test item (0.5 g, pasted with 0.2 ml polyethylene glycol 400) was applied to the intact skin of three New Zealand White rabbits under semi-occlusive conditions for four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the test item. No erythema or edema were observed at any time point (score 0). Based on the results of this study, the test item is not 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:
1996-03-18 to 1996-03-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Chemical pharmaceutical factory Dr. K Thomae 88400 Biberach
- Weight at study initiation: 2.7 - 3.0 kg
- Housing: in fully air-conditioned rooms in separate cages arranged in a battery
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light):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:
24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with isotonic saline at 37°C
- Time after start of exposure: 24 hours

Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
One and 24 hours after application the conjuntivae of the animals showed a diffuse beefly red colour and obvious swellings up to swellings with lids about half closed. The iris was sporadically reddned. One hour after application clear, colourless eye discharge was noted. 24 hours after application the cornea showed diffuse opacity areas. 48 hours after application definitely injected blood vessels were observed in two animals. 72 hours after application all signs of irritation were reversible.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the testing for primary eye irritation in the rabbit, the substance is slightly irritating to eye. But the effect does not result in a classification of the test item.
Executive summary:

The test item was subject to an Acute Eye Irritation/Corrosion Test in the rabbit according to OECD TG 405. For this purpose 100 mg of test material were instilled in the left conjunctival sac of three New Zealand white rabbits. 24 hours after application the treated eyes were washed out thoroghtly with isotonic saline at 30°C. The eyes were examined 1, 24, 48, and 72 hours after application of the test item. One and 24 hours after application the conjuntivae of the animals showed a diffuse beefly red colour and obvious swellings up to swellings with lids about half closed. The iris was sporadically reddned. One hour after application clear, colourless eye discharge was noted. 24 hours after application the cornea showed diffuse opacity areas. 48 hours after application definitely injected blood vessels were observed in two animals. 72 hours after application all signs of irritation were reversible.

Based on the testing for primary eye irritation in the rabbit, the substance is slightly irritating to eye. But the effect does not result in a classification of the test item.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Both studies either on skin or eye irritation were performed with the submission substance and were rated as reliable without restriction (reliability category 1).

 

The primary skin irritation potential of the test item was investigated according to OECD test guideline no 404.The test item (0.5 g, pasted with 0.2 ml polyethylene glycol 400) was applied to the intact skin of three New Zealand White rabbits under semi-occlusive conditions for four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the test item. No erythema or edema were observed at any time point (score 0). Based on the results of this study, the test item is not irritating to skin.

 

The test item was subject to an Acute Eye Irritation/Corrosion Test in the rabbit according to OECD TG 405. For this purpose 100 mg of test material were instilled in the left conjunctival sac of three New Zealand white rabbits. 24 hours after application the treated eyes were washed out thoroghtly with isotonic saline at 30°C. The eyes were examined 1, 24, 48, and 72 hours after application of the test item. One and 24 hours after application the conjuntivae of the animals showed a diffuse beefly red colour and obvious swellings up to swellings with lids about half closed. The iris was sporadically reddned. One hour after application clear, colourless eye discharge was noted. 24 hours after application the cornea showed diffuse opacity areas. 48 hours after application definitely injected blood vessels were observed in two animals.72 hours after application all signs of irritation were reversible.

Based on the testing for primary eye irritation in the rabbit, the substance is slightly irritating to eye. But the effect does not result in a classification of the test item.


Justification for selection of skin irritation / corrosion endpoint:
Only reliable study performed with the submission substance

Justification for selection of eye irritation endpoint:
Only reliable study performed with the submission substance

Justification for classification or non-classification

Based on the results of available data the submission substance does not have to be classified for irritating effects on skin or eyes according to the criteria of Regulation (EC) No. 1272/2008 (CLP) as well as Council Directive 67/548/EEC.