Registration Dossier

Administrative data

Description of key information

One modified Bühler test on Sodium cocoamphopolycarboxyglycinate (Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts with CAS no 2060541-51-5) and one Guinnea pig maximization test on Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopro yl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9) are available within the amphoteric, glycinate substance group. The results indicate lack of sensitisation, although the testing had not been performed with pure compounds, but the technical 40% aqueous solutions. However, if the pure freeze-dried substances were to be tested, testing of solids in LLNA generally results to about 50% concentrations, which is not far from the available data using 40%. Based on animal welfare grounds further testing at higher concentrations was therefore not proposed.

 

Profiling the amphoteric, glycinate substances for skin sensitizing properties using Derek Nexus, TOPKAT as well as the QSAR Toolbox indicates that no alerts are found for protein binding or structural alerts. The query structure does not contain any unclassified or misclassified features and is consequently predicted to be a non-sensitiser. There are no reports on incidences of sensitisation from industrial production and use of the substances. Taken all the available information together, read across using the available data is considered applicable within the substance group.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
9 July 1985 - 2 August 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed similar to OECD guidelines and under GLP.
Justification for type of information:
One modified Bühler test on Sodium cocoamphopolycarboxyglycinate (Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts with CAS no 2060541-51-5) and one Guinnea pig maximization test on Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopro yl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9) are available within the amphoteric, glycinate substance group. The results indicate lack of sensitisation, although the testing had not been performed with pure compounds, but the technical 40% aqueous solutions. However, if the pure freeze-dried substances were to be tested, testing of solids in LLNA generally results to about 50% concentrations, which is not far from the available data using 40%. Based on animal welfare grounds further testing at higher concentrations was therefore not proposed.
 
Profiling the amphoteric, glycinate substances for skin sensitizing properties using Derek Nexus, TOPKAT as well as the QSAR Toolbox indicates that no alerts are found for protein binding or structural alerts. The query structure does not contain any unclassified or misclassified features and is consequently predicted to be a non-sensitiser. There are no reports on incidences of sensitisation from industrial production and use of the substances. Taken all the available information together, read across using the available data is considered applicable within the substance group.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Specific details on test material used for the study:
Appearance: clear amber liquid
Container: a screw capped plastic bottle
Identification: Ampholak 7TX
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Darley Oaks, Burton-on-Trent , Staffordshire.
- Age at study initiation: young, not specified
- Weight at study initiation: 300-500g
- Housing: groups of five in grid bottomed polypropylene cages
- Diet (e.g. ad libitum): A commercially available pelleted diet with additional vitamin C (type TR2 supplied by Pilsbury's Limited of Birmingham) ad libitum.
- Water (e.g. ad libitum): Tap water containing 0.01% vitamin C were provided ad libitum
- Acclimation period: at least 3 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 50-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 9 July 1985 - 2 August 1985
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Prior to each stage of the study the supplied test material was treated with a 50% aqueous solution of citric acid in order to adjust its pH to 6.6.

Induction:
Intradermal: 0.1ml
Epicutaneous: undiluted

Challenge:
Epicutaneous: undiluted and 50%
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Prior to each stage of the study the supplied test material was treated with a 50% aqueous solution of citric acid in order to adjust its pH to 6.6.

Induction:
Intradermal: 0.1ml
Epicutaneous: undiluted

Challenge:
Epicutaneous: undiluted and 50%
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: The procedures followed require that both the maximum non-irritating concentration of the test material be found and a concentration of the material that, although irritating , did not cause severe irritation to the skin (minimum irritant concentration). A dose-ranging study was carried out on four animals, weighing less than 650g, and previously treated with Freund's Complete Adjuvant by injection. This was necessary as the Adjuvant can also enhance irritation as well as sensitisation response in the animal, serial dilutions of the test material were made in distilled water to give concentrations of, 100%, 50%, 25% and 12.5%. An area 8cm x 5cm was clipped free of fur over the back and flanks of the four animals and four patches of Whatman No. 3 filter paper, 2mx2cm, each saturated with a different concentration of the test material placed onto the skin, two patches on each flank, Strips of 5m wide Blenderm surgical tape were placed over the patches - to act as occlusive barriers and the patches held i n place for twenty four hours by encircling the trunk of the animal with lengths of 5cm wide "Elastoplast" elastic adhesive bandage.' Twenty four and, forty eight hours a f t e r removing the patches and.dressings the animals were examined and skin reaction at the treated sites assessed under the same conditions and skin reaction at the treated sites assessed under the same conditions and using the Draize numerical scoring system. No skin reaction was seen in one of the four treated animals after 24 hours. Therefore 100% was chosen as the concetration for topical induction.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Intradermal exposure: the test animals were treated with two injections each of 0.1ml Freund's Complete Adjuvant, two injections each of 0.1ml test material and two injections each of 0.1ml Freund's Complete Adjuvant mixed with an equal volume of the test material.The control animals were treated similarly by these animals were exposed to distilled water in stead of the test substance.
Epicutaneous exposure:
- Exposure period: on day 0 the animals were exposed intradermally and 7 days later the animals were exposed epicutaneously.
- Test groups: 10 animals
- Control group: 10 animals
- Site: Intradermal and epicutaneous exposure: the dorsal area between the shoulders.
- Frequency of applications: single applications
- Duration: the epicutaneous patches were kept in place for 48 hours.
- Concentrations:
Intradermal exposure: 0.1 ml testsubstance
Epicutaneous exposure: 100% concentration (shown to cause some irritancy in range finding study)

B. CHALLENGE EXPOSURE
- No. of exposures: single epicutaneous exposure
- Day(s) of challenge: 21 days after the start of the stuyd, 14 days after induction
- Exposure period: 24 hours
- Test groups: 10 animals
- Control group: 10 animals
- Site: flanks
- Concentrations: 50% and 100%
- Evaluation (hr after challenge): 24 and 48 hours after patch removal


OTHER:
Challenge controls:
The controls were treated similar to the test group but the test substance was replaced by water
Positive control substance(s):
not required
Key result
Reading:
other: Challenge phase
Hours after challenge:
24
Group:
test group
Dose level:
100% test material (corresponds to 40% a.i)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
48
Group:
test group
Dose level:
100% test material (corresponds to 40% a.i.)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
24
Group:
test group
Dose level:
50% test material (corresponds to 20% a.i.)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
48
Group:
test group
Dose level:
50% test material (corresponds to 20% a.i.)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Not described
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Challenge phase
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

No reaction was observed in any of the animals exposed to the test substance or in the control group.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
On challenge with the test material, consisting of 40% active ingredient and 60% water, no visible response was exhibited by any animal in the test or control group when challenged with the undiluted test material and 50% aqueous concentration of the test material. From the results of this study there was no evidence to suggest that the active ingredient Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopro yl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9) acts as a sensitiser in the guinea pig.
Executive summary:

Accoring to methods similar to OECD 406 and under GLP ten guinea pigs were treated by intradermal injection in the shoulder region with the test material, Freund's Complete Adjuvant and a mixture of the test material and Freund's Complete Adjuvant. Seven days later this induction procedure was boosted by the topical application of the test material over the injection site. A second group of ten animals were similarly treated but distilled water was substituted for the test material. Two weeks after the induction phase all animals of both test and control groups were challenged with two concentrations of the test material applied topically to the flanks. On challenge with the test material no visible response was exhibited by any animal in the test or control group when challenged with the undiluted test material and 50% aqueous concentration of the test material. From the results of this study there was no evidence to suggest that the active ingredient of the test material, Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopro yl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9) acts as a sensitiser in the guinea pig.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed similar to OECD guidelines and under GLP. No data on substance identity (SURFACTANT HDC 94-05-20-03). Concentrations did not elicit required irritation levels
Justification for type of information:
One modified Bühler test on Sodium cocoamphopolycarboxyglycinate (Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts with CAS no 2060541-51-5) and one Guinnea pig maximization test on Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3-aminopro yl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9) are available within the amphoteric, glycinate substance group. The results indicate lack of sensitisation, although the testing had not been performed with pure compounds, but the technical 40% aqueous solutions. However, if the pure freeze-dried substances were to be tested, testing of solids in LLNA generally results to about 50% concentrations, which is not far from the available data using 40%. Based on animal welfare grounds further testing at higher concentrations was therefore not proposed.
 
Profiling the amphoteric, glycinate substances for skin sensitizing properties using Derek Nexus, TOPKAT as well as the QSAR Toolbox indicates that no alerts are found for protein binding or structural alerts. The query structure does not contain any unclassified or misclassified features and is consequently predicted to be a non-sensitiser. There are no reports on incidences of sensitisation from industrial production and use of the substances. Taken all the available information together, read across using the available data is considered applicable within the substance group.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Principles of method if other than guideline:
The induction procedure was repeated for three weeks to give a total of nine 6-hour exposure instead of three 6 hour induction exposures.
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Reading:
other: all readings
Group:
other: all test groups
Dose level:
25% or undiluted as supplied
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: other: all readings. Group: other: all test groups. Dose level: 25% or undiluted as supplied. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Skin Reactions Observed After Topical lnduction

One animal was killed for humane reasons on day 13 due to respiratory problems, and one animal was found dead on day 16 (the cause of death was not investigated). The absence of these animals did not affect the purpose or integrity of the study.

Group 1 (Undiluted as Supplied)

Very slight to well defined erythema and very slight to slight oedema were elicited by the test material. Other skin reactions noted were desquamation, hardened light brown-coloured scab, hardened dark browdblack-coloured scab and small superficial scattered scabs. On occasions the skin reactions prevented the accurate evaluation of oedema and/or erythema. On occasions the test sites were changed due to severe reactions.

Group 2 (25% v/v in Distilled Water)

One test group animal was killed for humane reasons on day 13. One test group animal was found dead on day 16. The cause of death was not determined. The absence of these animals was considered not to affect the purpose or integrity of the study. Very slight erythema and very slight oedema were elicited by the test material. Other skin reactions noted were desquamation, hardened light brown-coloured scab and small superficial scattered scabs. On one occasion desquarnation prevented accurate evaluation of erythema in one test group animal. On occasions the test sites were changed due to severe reactions.

Vehicle Control

No skin reactions were noted at the vehicle control sites of control group animals following topical induction.

Skin Reactions Observed After Topical Challenge

No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-hour observations.

Bodyweight Individual

Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 30, were comparable to those observed in the control group animals over the same - period.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The test material, consisting of 40% active ingredient and 60% water, produced a 0% (0/20) sensitisation rate and was classified as a non-sensitiser to guinea pig skin under the conditions of the study. Therefore the active ingredient Sodium cocoamphopolycarboxyglycinate (Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts with CAS no 2060541-51-5) is considered to be non sensitising.
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" B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). Two groups of twenty test animals and ten control animals were used for the main study. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows: Topical Induction Group 1 : undiluted as supplied Group 2 : 25% v/v in distilled water Topical Challenge : undiluted as supplied and 25% v/v in distilled water. No effects were observed. The test material, consisting of 40% active ingredient and 60% water, produced a 0% (0/20) sensitisation rate and was classified as a non-sensitiser to guinea pig skin under the conditions of the study. Therefore the active ingredient Sodium cocoamphopolycarboxyglycinate (Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts with CAS no 2060541-51-5) is considered to be non sensitising.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There are no guidelines for an animal test for respiratory sensitization, however in general respiratory sensitizers are also skin sensitizers. Based on read across within the group of amphoteric, glycinate substances Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) was not found to be a skin sensitizer based on two GLP studies performed similar to OECD guidelines. This indicates that the substance is unlikely to possess any significant potential for respiratory sensitization.  Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) is anaqueous solution with a low vapour, therefore inhalation exposure is unlikely.

Justification for classification or non-classification

Skin

Based on read across within the group of amphoteric, glycinate substances Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) and the other three substances within the amphoteric, glycinate substane group, are not found to be skin sensitizers. This is based on the two available in-vivo studies, one performed on Sodium cocoamphopolycarboxyglycinate (Amines, N-(3-aminopropyl)-N’-C12-18 -alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts with CAS no 2060541-51-5) and the other on Sodium tallowamphopolycarboxyglycinate (Amines, N-[3-[(3 -aminopro yl)amino]propyl]-N’-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(carboxymethyl) derivs., sodium salts with CAS no 2060541-47-9). Together with the available QSAR data, the overall conclusion is that the four amphoteric glycinate substances have low potential for skin sensitising properties.

Inhalation 

Coco iminodiglycinate, (Amines, N-C12-18-alkyltrimethylenedi-, reaction products with chloroacetic acid, sodium salts with CAS no 2098351-38-1) has no skin sensitising properties, based on the read across within the group of four amphoteic substances. All of the amphoteric glycinate substances are produced and handled as aqueous solutions with low vapour pressures, therefore inhalation exposure is unlikely. Data on acute inhalation is lacking, but taken the result from the skin sensitization study and the low potential for inhalation exposure into consideration, the substance it is not classified as a respiratory sensitizer.