4-(2-hydroxyethyl)piperazin-1-ylethanesulphonic acid

Endpoint summary

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.