Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation in vivo (OECD TG 404): not irritating (reference 7.3.1 -1).

Eye irritation in vivo (OECD TG 405): not irritating (reference 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:
October 01, 2002 - May 19,2003
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:
yes
Remarks:
The body weight at the start of the study was outside the target range of 2.50-5.50 kg. This deviation did not influence the integrity of the study.
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: ~15 weeks
- Weight at study initiation: 2.05 kg (range from 2.00 to 2.13)
- Housing: separately in special rabbit cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 19
- Humidity (%): 45 to 72
- Photoperiod (hrs dark / hrs light): 12 / 12

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:
0.5 g of the test material mixed with some drops of Aqua pro injectione to ensure good contact
Duration of treatment / exposure:
4 hour period under semiocclusive conditions
Observation period:
1 hour after removal of the patches. Thereafter, examinations were performed daily for a further 7 days.
Number of animals:
3 female rabbits
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- % coverage: 100 %
- Type of wrap: Fixomull® stretch, Beiersdorf

REMOVAL OF TEST SUBSTANCE
- Washing: no
- Time after start of exposure: after 4 hours

SCORING SYSTEM: Draize (1959)
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 signs of irritation were observed at the treated areas.
Other effects:
- Other adverse systemic effects: No signs of clinical toxicity were detected.
Interpretation of results:
GHS criteria not met
Conclusions:
No skin irritating potential could be detected. The test material can be regarded as non irritant.
Executive summary:

The test performed in accordance with OECD TG 404. 0.5 g of the test material mixed with some drops aqua pro injectione were spread onto 6 cm² patches and applied to the intact skin of 3 previously shaven rabbits (females) for a 4 hours period under semiocclusive conditions. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for a further 7 days.

Under the conditions of the present study, no signs of toxicity were seen.

Evaluation of each animal:

 

Mean score (24h, 48h, 72h)

Maximum value (24h, 48h, or, 72h)

Animal No.

31

32

33

31

32

33

Erythema

0.0

0.0

0.0

0

0

0

Edema

0.0

0.0

0.0

0

0

0

No skin irritating potential could be detected. The test material should not be classified as a skin irritant.

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:
October 01, 2002 - May 19, 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 24th, 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
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: 17 weeks
- Weight at study initiation: 2.65 kg (range from 2.51 to 2.75)
- Housing: 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)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 20
- Humidity (%): 42 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: day 1 To: day 8
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
30 s
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
- Washing: no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: ophthalmoscope
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:
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
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Redness of the conjunctivae and discharge were regarded as slight transient signs of mechanical irritation. The test material should not be regarded as an irritant for the eyes.
Executive summary:
The primary eye irritation was assessed in accordance with OECD TG 405. For the test of primary eye irritation, 0.1 g of the test material was applied into the conjunctival sac of rabbits. The study was started as an initial test with 1 animal and followed by the confirmatory test with 2 further animals. 

No signs of irritation could be observed at the cornea or iris. The conjunctivae showed redness (score 1) at the first (1 hour) and second (24 hours) reading. Chemosis (score 1) was seen in the first reading. Furthermore discharge (score 1 and 2) at the first reading was observed. Thereafter no signs of irritation were observed. The untreated eyes were unchanged.

 

 

Mean score

(24h, 48h, 72h)

Maximum value

(24h, 48h or 72h)

Animal No.

34

32

39

34

32

39

Cornea

0.00

0.00

0.00

0

0

0

Iris

0.00

0.00

0.00

0

0

0

Conjunctivae (Redness)

0.33

0.33

0.00

1

1

0

Conjunctivae (Chemosis)

0.00

0.00

0.00

0

0

0

 

Redness of the conjunctivae and discharge were regarded as slight transient signs of mechanical irritation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

One GLP compliant study to assess skin irritation/corrosion potential and one GLP-compliant study to assess eye irritation potential of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid have been performed.

Skin irritation

The test was performed in accordance with OECD TG 404 (reference 7.3.1 -1). The test material was applied to the intact skin of 3 previously shaven rabbits (females) for a 4 hours period under semi-occlusive conditions. This study should provide a rational basis for risk assessment to the irritating potential of the test item in man. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for a further 7 days. Under the conditions of the present study, no signs of toxicity were seen (erythema score (24/48/72h):0; edema score (24/48/72h): 0). No skin irritating potential could be detected. The test material should not be classified as a skin irritant.

Eye irritation

The test was performed in accordance with OECD TG 405 (reference 7.3.2 -1). For the test of primary eye irritation, 0.1 g of the test material was applied into the conjunctival sac of rabbits. The study was started as an initial test with 1 animal and followed by the confirmatory test with 2 further animals. No signs of irritation could be observed at the cornea or iris. The conjunctivae showed redness (score 1) at the first (1 hour) and second (24 hours) reading. Chemosis (score 1) was seen in the first reading. Furthermore discharge (score 1 and 2) at the first reading was observed. Thereafter, no signs of irritation were observed. The untreated eyes were unchanged. Redness of the conjunctivae and discharge were regarded as slight transient signs of mechanical irritation. The test material should not be regarded as an irritant to the eyes.

Justification for classification or non-classification

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered not to be classified for eye and skin irritation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.