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Description of key information

Skin irritation (in vivo): not irritating (OECD 404)

In the skin irritation /corrosion key study the Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, was applied to the shorn skin of 3 (female) New Zealand White albino rabbits at a dose of 0.5 mL under semi-occlusive dressing during 4 hours. No cutaneous reactions (erythema or oedema) were observed up to 72 hours after the exposure. Based on these results, the test substance was considered to be not irritating, under the conditions of this study, in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

Eye irritation (in vivo): not irritating (OECD 405)

In the eye irritation key study three male albino New Zealand White rabbits were administered a single ocular dose of 0.1 ml of the test substance and observed up to eight days after instillation. Moderate conjunctiva reactions (redness and chemosis) were observed, which were totally reversible within 8 days. Based on these results, the test item was considered not to be irritating to the eyes, under the conditions of this study, in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

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:
18-28 September 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed in compliance with GLP and according to OECD guideline 404.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
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: Elevage de Gérome, Linxe.
- Age at study initiation: 12 weeks
- Weight at study initiation:2.42-2.68 kg
- Housing: Individual box
- Diet (e.g. ad libitum): ad libitium
- Water (e.g. ad libitum): ad libitium
- Acclimation period: 5 days
- Other: Albino rabbits, female

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 31-55 %
- Photoperiod (hrs dark / hrs light): (12/12)
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after removal of the patches
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2 on an undamaged skin area of one flank of each animal.
- Type of wrap if used: patch with strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: treated area was rinsed with distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: scored in accordance with OECD404
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, and 72h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No cutaneous reactions (erythema and oedema) were observed (1, 24, 48 and 72 hours).
Other effects:
No other effects were observed
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The skin irritating potential of the substance was investigated in a dermal skin irritating study which was performed in accordance with OECD404 and under GLP conditions. Based on the result the test item does not need to be classified in accordance with the criteria outlined in Annex I of 67/548/EEC and Annex VI of 1272/2008?EC, under the conditions of this study.
Executive summary:

The skin irritating potential of sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate was investigated in a dermal skin irritating study which was performed in accordance with OECD404 and under GLP conditions. The test material was applied to the shorn skin of 3 (female) New Zealand White albino rabbits at a dose of 0.5 mL under semi-occlusive dressing during 4 hours. No cutaneous reactions (erythema and oedema) were observed. Based on these results, the test substance does not need to be classified in accordance with the criteria outlined in Annex I of 67/548/EEC and Annex VI of 1272/2008?EC, under the conditions of this study.

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:
24 September -02 Oktober 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed in compliance with GLP and according to OECD guideline 405.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome, Linxe
- Age at study initiation: 18 weeks
- Weight at study initiation: 3.20-3.84 kg
- Housing: Individual box
- Diet (e.g. ad libitum): ad libitium
- Water (e.g. ad libitum): ad libitium
- Acclimation period: 5 days
- Other: Albino rabbits (male)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25 °C
- Humidity (%): 36-70 %
- Photoperiod (hrs dark / hrs light): (12/12)
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0,1 mL of test item was instilled into conjunctival sac of one eye, the other eye remained untreated as control.
Duration of treatment / exposure:
Single dose.
Observation period (in vivo):
1, 24, 48, and 72 hours following treatment and daily thereafter up to 8 days after treatment
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: In accordance with OECD 405
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
ca. 1.8
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
ca. 0.8
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
ca. 0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
The conjunctiva reactions observed during the study have been moderate, and totally reversible in the three animals: a moderate redness, noted 24 hours after the test item instillation and totally reversible between day 6 and day 8, associated with a moderate chemosis, noted 1 hour after the test item instillation and totally reversible between day 3 and day 6.
Other effects:
No other effects were observed
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The eye irritating potential of Amphotensid EH was investigated in an acute eye irritation study, which was performed according to OECD 405 and under GLP conditions. Based on the results, the test item does not need to be classified according to the criteria outlined in Annex I of 67/548/EEC and Annex VI of 1272/2008, under the conditions of this study.
Executive summary:

The eye irritating potential of Amphotensid EH was investigated in an acute eye irritation study, which was performed according to OECD 405 and under GLP conditions. Three male albino New Zealand White rabbits were administered a single ocular dose of 0.1 ml of the test substance and observed up to eight days after instillation. Moderate conjunctiva reactions (redness and chemosis) were observed, which were totally reversible within 8 days. Based on these results, the test item does not need to be classified according to the criteria outlined in Annex I of 67/548/EEC and Annex VI of 1272/2008, under the conditions of this study.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin
Three in vivo skin irritation studies are available
on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, which were all performed according to OECD 404 and under GLP conditions. In the key study the test material was applied to the shorn skin of 3 (female) New Zealand White albino rabbits at a dose of 0.5 mL under semi-occlusive dressing during 4 hours. No cutaneous reactions (erythema or oedema) were observed up to 72 hours after the exposure. Based on these results, the test substance was considered to be not irritating, under the conditions of this study, in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC. The results of the key study were in agreement with the results of the two supporting studies.


Eye 

Two in vivo eye irritation studies are available onSodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6. Both were both performed according to OECD 405 and under GLP conditions. In the key study three male albino New Zealand White rabbits were administered a single ocular dose of 0.1 ml of the test substance and observed up to eight days after instillation. Moderate conjunctiva reactions (redness and chemosis) were observed, which were totally reversible within 8 days. Based on these results, the test item was considered not to be irritating to the eyes, under the conditions of this study. The results of the key study were in agreement with the results of the supporting study. In the third study an alternative method the hen's egg chorioallantoic membrane test (CAM test) was used. There are some experimental difficulties with this test, the method is not validated, the test was not performed under GLP, the study is only limited reported and there is no information on batch and only limited information on composition of the substance. The reliability rating of this report is 4, not assignable and the study is therefore disregarded. Based on these results the test substance was not considered to be irritating to the eyes, under the conditions of this test.


Inhalation 

Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate) CAS 94441-92-6was not found to be irritating to neither skin or eye. This indicates that the substance is unlikely to cause any respiratory irritation.Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6, is a paste with a low vapour pressure of 1.5 mPa at 20°C and therefore inhalation exposure is unlikely. Data on acute inhalation is lacking, but taking the result from the skin and eye irritation / corrosion studies and the low potential for inhalation exposure into consideration, the substance is not to be classified as a respiratory irritating substance in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

Justification for selection of skin irritation / corrosion endpoint:

There are three skin irritation / corrosion studies available for Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6. Both the key and the two supporting studies were performed according to OECD 404 and under GLP conditions. The oldest supporting study is lacking information on batch number and composition, and is therefore considered to have reliability rating 2. The two newer studies have been given the reliability rating 1, and the most recent study was chosen as the key study. The results from the three studies coincide, and the substance is not classified as irritating to skin in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

Justification for selection of eye irritation endpoint:

There are three eye irritation studies available for Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, two which are performed according to OECD 405 and under GLP conditions. These two studies are therefore given reliability 1, and the most recent study was chosen to be the key study, as in this study some (reversible) effects were observed. In the third study an alternative method, the hen's egg chorioallantoic membrane test (CAM test), was used. There are some experimental difficulties with this test, the method is not validated, the test was not performed under GLP, the study is only limited reported and there is no information on batch and only limited information on composition of the substance. The reliability rating of this report is 4, not assignable, and the study is therefore disregarded. The results from the two reliable studies coincide, and the substance is not classified as irritating to eye in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

Justification for classification or non-classification

Skin

The conclusion from the three available studies is that the substanceSodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6, is not to be classified according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 and is considered “not irritating” to skin.

 

Eye

The conclusion from the two available relevant studies is that the substanceSodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate) CAS 94441-92-6 is not classified according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 and is considered “not irritating” to eye.

 

Inhalation

Data on acute inhalation is lacking, but taken the result from the skin and eye irritation / corrosion studies and the low potential for inhalation exposure into consideration, the substance is not classified as a respiratory irritating substance in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.