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Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July-September 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No info on batch no. and composition. Well reported and conducted study according to guideline/standards.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
An alternative adequate study was already available. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 671548/EEC).
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd., Burton-on-Trent, UK
- Age at study initiation: ca. 8-12 weeks
- Weight at study initiation: 300-392 g
- Housing: singly or in pairs in polypropylene cages with woodflakes
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 54-78
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From:30 July To: 3 September 1997
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 100% (undiluted)
Challenge: 100% and 75% (v/v) in distilled water
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 100% (undiluted)
Challenge: 100% and 75% (v/v) in distilled water
No. of animals per dose:
20 test and 10 control animals
Details on study design:
RANGE FINDING TESTS:
Induction (2 guinea pigs): 25, 50, 75 (v/v) and 100&% (undiluted); 100% was selected
Challenge: not done due to a lack of test material; 100% and 75% (v/v) were selected.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: days 0, 2, 4, 7, 9, 11, 14, 16 and 18
- Test groups: yes
- Control group: no (blank patch)
- Site: left flank
- Frequency of applications: 9 times
- Duration: 6 h each time
- Concentrations: 100% (undiluted)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28
- Exposure period: 6 h
- Test groups: yes
- Control group: yes
- Site: right flank
- Concentrations: 100% (undiluted) and 75% (v/v)
- Evaluation (hr after challenge): 24 and 48 h after patch removal

Challenge controls:
Yes, silimar to test group
Positive control substance(s):
no
Positive control results:
Not used.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75 and 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75 and 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75 and 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75 and 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of this test, Ampholak YJH-40 is not a sensitiser to guinea pig skin.
Executive summary:

A study was performed to assess the contact sensitisation potential of the test material in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 671548/EEC). Twenty test and ten control animals were used for the main study.

Based on the results of a sighting test, the concentration of test material for the induction phase was selected as follows:

Topical Induction: undiluted as supplied;

Based on the results of the induction phases of the study the concentrations of test material for the challenge phase were as follows:

Topical Challenge : undiluted as supplied and 75% v/v in distilled water.

The test material produced a 0% (0/20) sensitisation rate and was classified as a non-sensitiser to guinea pig skin. The test material did not meet the criteria for classification as a sensitiser according to OECD/GHS.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The potential of the test itemSodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6to induce delayed contact hypersensitivity have been evaluated in two skin sensitisation studies.

The guinea pig maximization test following the method of Magnusson and Kligman was performed in 1993 and since then the production process has changed and the residue levels of potential corrosive/irritating components have been reduced. This study shows some deficiencies which makes the result ambiguous. In the report the positive findings in the controls and the responses to the substance already in the induction phase are not commented upon. Furthermore the big difference in response between the neat product and the 30% dilution indicates more probably an enhanced irritant effect rather than true skin sensitisation. In 1997, after the modification of the production process, the substance was evaluated in guinea pigs according to the Bühler skin sensitsation method. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. It may have been preferable to perform yet another Magnusson and Kligman study, but since there is no indication on sensitising potential at all in the Bühler test, it is seen to be a true evaluation of the endpoint.

Based on preliminary testing in the Bühler test, the induction by topical application was performed with the substance as supplied, i.e. 40% in water. The induction of the test animals were performed on days 0, 2, 4, 7, 9, 11, 14, 16 and 18. The hair was removed from an area on the left flank of each animal and the substance was applied to the clipped area under occlusive dressing for 6 hours during each occasion. The animals of the control group received an application of the distilled water under the same experimental conditions.

 

On day 28 the hair on the right flank was removed and both the undiluted test substance and a concentration of 75% v/v in distilled water were applied for 6 hours under occlusive dressing. The treatment sites were decontaminated using distilled water and the skin reactions were evaluated approximately 24 and 48 hours after dressing removal.

 

No systemic clinical signs, no changes in body weight gains compared to control animals and no deaths were noted during the study. An isolated incident of desquamation was noted during the induction phase on day 7. No other signs of skin irritation were noted following topical induction. No skin reactions were observed at 24 and 48 hours after the challenge application.

 

Under the experimental conditions and according to the Bühler delayed contact hypersensitivity method, the test substance Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6 does not induce delayed contact hypersensitivity in guinea pigs.

Migrated from Short description of key information:

The potential of the test item AMPHOLAK YJH-40 (Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate) CAS 94441-92-6 to induce delayed contact hypersensitivity was evaluated in guinea pigs according to the Bühler delayed contact hypersensitivity method and to OECD (No. 406, 17th July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 671548/EEC) and in compliance with Good Laboratory Principles. In this study with reliability rating 2, AMPHOLAK YJH-40 (Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate) CAS 94441-92-6, did not induce delayed contact hypersensitivity in guinea pigs.

Justification for selection of skin sensitisation endpoint:

There are two skin sensitisation studies available for Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6. Only a draft report is available on the study from 1993, which has reliability rating 3 due to this and also for the unexplained response seen after the topical induction. The reaction to the topical induction and then the complete lack of effects with the 30% dilution suggests more of an enhanced irritant effect rather than true skin sensitisation. This result together with the available negative result in the Bühler test from 1997 supports the classification as not sensitising to skin. The production process has changed during the time for the two tests and the residue levels of potential corrosive/irritating components have been reduced. As this newer Bühler study is available, it is not scientifically justified on animal welfare grounds to perform yet another study on this test substance.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no guidelines for an animal test for respiratory sensitisation, however in general respiratory sensitisers are also skin sensitisers. Sodium N-(2-carboxyethyl)-N-(2 -ethylhexyl)-β-alaninate), CAS 94441-92 -6 was not found to be a skin sensitiser in the OECD 406 GLP study performed in 1997. This indicates that the substance is unlikely to posses any significant potential for respiratory sensitisation. 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.

Justification for selection of respiratory sensitisation endpoint:

Data on respiratory sensitisation of Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6 is lacking, but it is a paste with a low vapour pressure of 1.5 mPa at 20°C and therefore inhalation exposure is unlikely.

Justification for classification or non-classification

Skin

Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6 was not found to be a skin sensitiser when tested in the OECD 406 GLP study.

Inhalation
Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6 was not found to be a skin sensitiser in the OECD 406 GLP study. This indicates that the substance is unlikely to possess any significant potential for respiratory sensitisation
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 taken the result from the skin sensitisation study and the low potential for inhalation exposure into consideration, the substance is not classified as a respiratory sensitiser.