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Description of key information

Key value for chemical safety assessment

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study. GLP.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
July 17th, 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 360.2 ± 20.5 g (test group) and 340.3 ± 18.6 g (control group)
- Housing: 2 or 3 animals in Makrolon-cages No. IV
- Diet (e.g. ad libitum): type "3023" from Altromin International, Lage, Germany as pelleted diet, ad libitum
- Water (e.g. ad libitum): tap water from municipal source, ad libitum
- Acclimation period: 13 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
other: tap water, filter sterilized
Concentration / amount:
Intradermal induction: 0.5 % (w/w) in vehicle
Dermal induction: 35 % (w/w) in vehicle
Challenge: 5 % (w/w) in vehicle
Route:
epicutaneous, occlusive
Vehicle:
other: tap water, filter sterilized
Concentration / amount:
Intradermal induction: 0.5 % (w/w) in vehicle
Dermal induction: 35 % (w/w) in vehicle
Challenge: 5 % (w/w) in vehicle
No. of animals per dose:
Number of animals in the test group: 10
Number of animals in the negative control group: 5
Number of animals in the dose range finding study: 3
Details on study design:
RANGE FINDING TESTS:
Intradermal: 0.1 mL of 5 %, 3.5 %, 2 % and 0.5 % (w/w) solution in vehicle.
Dermal: soaked patch with 50 %, 35 %, 20 % and 5 % (w/w) solution in vehicle.
Challenge: soaked patch with Duhring chamber with 20 % and 5 % (w/w) solution in vehicle.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal application (day 0)
- No. of exposures: 1
- Test groups:
(1) 0.1 mL FCA (1 + 1).
(2) 0.1 mL per side of the solution 0.5% test substance
(3) 0.1 mL per side of the solution 0.5% test substance experiment in FCA (1 + 1).
- Control group:
(1) 0.1 mL FCA (1 + 1).
(2) 0.1 mL per side of the solution of the vehicle
(3) 0.1 mL per side of the solution of the vehicle in FCA (1 + 1)
- Site: Ieft and right shoulder

Topical application (day 7)
- No. of exposures: 1
- Exposure period: 48 h
- Test groups: 35 % (w/w) in vehicle
- Control group: vehicle
- Site: same as for intradermal induction

As the applied test substance concentration was slightly irritating, no pretreatment to generate local irritation was required.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24 h
- Test groups: left flank: 5 % (w/w) in vehicle in Duhring chamber; right flank: vehicle in Duhring chamber
- Control group: left flank: 5 % (w/w) in vehicle in Duhring chamber; right flank: vehicle in Duhring chamber
- Evaluation (hr after challenge): 24 + 48 h
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole
Positive control results:
Sensitisation rate of 90 % (9 of 10 animals positive) (experiment: 2008-02-25 to 2008-03-28)
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Skin reactions after induction

 

 

Intradermal Induction

Epicutanous Induction

Group

Animal

Erythema

Edema

Erythema

Edema

Test group

1

0

0

0

0

2

0

0

0

0

3

1

0

0

0

4

0

0

0

0

5

1

0

1

0

6

1

1

1

0

7

0

0

0

0

8

0

0

0

0

9

1

0

0

0

10

1

0

1

0

Control group

1

0

0

0

0

2

0

0

0

0

3

0

0

0

0

4

0

0

0

0

5

0

0

0

0

 

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this study, Undecylenamidopropyl Betaine is not a dermal sensitiser.
Executive summary:

In a dermal sensitisation study according to OECD TG 406, 1992 with Undecylenamidopropyl Betaine (84% a.i.) in filter-sterilised tap water, female Dunkin-Hartley guinea pigs were tested using the Maximization test method. Positive control substance was 2-Mercaptobenzothiazole with a sensitisation rate of 90%.

In the main experiment ten animals were treated intradermally with a 0.5% (w/w) solution of the test substance in vehicle; for the dermal induction a 35% (w/w) concentration of the test substance in vehicle was used (= test group). Further five female animals were treated similarly - with the exception that they received only the vehicle instead of the test substance (= control group).

On day 21 of the application period the challenge application was performed on all control and test group animals. Duhring chambers with a 5% (w/w) solution of the test substance in vehicle were used. 

Besides slight crust formation at the injection sides after intradermal application with FCA no symptoms of systemic toxicity or other toxic reactions were observed at any time during the study. Body weight development of the animals was positive and within normal ranges.

In the challenge no visible changes (no erythema and no edema) were observed at any time point; i.e, there was no positive challenge result in the test and the control group animals. Thus, the sensitisation rate was 0%.

In this study, Undecylenamidopropyl Betaine is not a dermal sensitiser.

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

In a dermal sensitisation study according to OECD Guideline 406 (1992) with Undecylenamidopropyl Betaine (84% a.i.) in filter-sterilised tap water, female Dunkin-Hartley guinea pigs were tested using the Maximization test method. The positive control substance was 2-Mercaptobenzothiazole with a sensitisation rate of 90%.

In the main experiment ten animals were treated intradermally with a 0.5% (w/w) solution of the test substance in vehicle; for the dermal induction a 35% (w/w) concentration of the test substance in vehicle was used (= test group). Further five female animals were treated similarly - with the exception that they received only the vehicle instead of the test substance (= control group).

On day 21 of the application period the challenge application was performed on all control and test group animals. Duhring chambers with a 5% (w/w) solution of the test substance in vehicle were used. 

Besides slight crust formation at the injection sites after intradermal application with FCA no symptoms of systemic toxicity or other toxic reactions were observed at any time during the study. Body weight development of the animals was positive and within normal ranges.

At challenge, no visible changes (no erythema and no edema) were observed at any time point; i.e, there was no positive challenge result in the test and the control group animals. Thus, the sensitisation rate was 0%.

In this study, Undecylenamidopropyl Betaine is not a dermal sensitiser.

 

Similarly negative results were also obtained with the closely related source substances Formamidopropylbetaine and C8-18 and C18 unsatd. AAPB (Coco AAPB). These results are included into the dossier to justify the read-across approach for other endpoints.

 

In a dermal sensitisation study according to OECD Guideline 406 (1992) with Formamidopropylbetaine female young adult Pirbright White guinea pigs were tested using the Maximization test method.

The maximum compatible doses for the intradermal and dermal application as well as the subirritative dose for the challenge were determined in a pilot experiment. In the main experiment the animals were treated intradermally with 0.1 mL of a 3.5 % (w/w) dilution of the test substance in saline. For the dermal induction the undiluted test substance was used. Intradermal application of the 3.5 % (w/w) dilution of the test substance in saline caused slight to moderate erythema and edema formation and the topical application of the undiluted test substance caused slight erythema and edema formation. In the challenge application Duhring chambers with a 30 % (w/w) dilution of the test substance in saline were used, a test concentration which was definitely non-irritating.

Besides crust formation at the injection sides after intradermal application with FCA no other systemic toxic symptoms or toxic reactions were observed at any time during the study. Body weight development of the animals was positive and within normal ranges. In the challenge no visible changes on the skin (no erythema and no edema) were observed at any time point; i.e. there was no positive challenge result in the test and the control group animals. Thus, the sensitisation rate was 0 %. Therefore, Formamidopropylbetaine has to be regarded as non-sensitising under the applied test conditions when exposed to the skin of experimental animals.

 

In a dermal sensitisation study with Coco AAPB (30 % a.i.) Pirbright white guinea pig (10 male, 10 female) were tested using the Maximisation Test method according to OECD Guideline 406, May 12, 1981.

The analytical purity of the test item is not stated in study report, according to producer information test material is Coco AAPB and has 30 % a.i. , impurities relevant to sensitisation and referred to a.i. are max 1.7% Alkylamidopropylamine and 33 ppm DMAPA (3-dimethylaminopropylamine).

Responses to the challenge procedure were evaluated 24 and 48 h after the end of the exposure period.

There were no skin reactions at the first reading. At the second reading 4/20 test animals and 5/20 control animals showed skin reactions score 1 (scattered mild redness). As incidence and severity of reactions seen in the test group were not higher than responses seen in the negative control group, the calculated sensitisation rate was 0.

In this study, Coco AAPB is not a dermal sensitiser.

 

In a dermal sensitisation study with Coco AAPB (commercial product) 20 male Pirbright white guinea pig were tested using the MAXIMIZATION TEST described by b. Magnusson and A.M. Kligman (1970). The test method is similar to OECD Guideline 406 (Skin Sensitisation).

The analytical purity of the test item is not stated in study report, according to producer information test material has 30 % a.i., impurities relevant to sensitisation and referred to a.i. are 8.3 % Alkylamidopropylamine and 33 -50 ppm DMAPA (3-dimethylaminopropylamine).

At the first scoring, 24 h after challenge, 2/15 showed a skin reaction score 1 (slight erythema (barely perceptible)). The animals were free of erythema and edema at the second (48 h) and the third (72 h) scoring. None of the five negative animals showed up to and including the third scoring a positive skin reaction to challenge treatment.

In this study, Coco AAPB (30 % a.i.) is not a dermal sensitiser.

 

There is no information available for respiratory sensitisation. Therefore, there is a data gap in this respect. However, the data gap cannot be fulfilled with experimental data, since there is no internationally accepted animal model for respiratory sensitisation. In case human data for respiratory sensitisation emerges, this will be taken into account.


Migrated from Short description of key information:
not sensitising; OECD TG 406, in vivo, Guinea pig maximisation test, guinea pig (GLP, RL1)
intradermal induction: 0.5% (w/w) solution of the test substance in vehicle
dermal induction: 35% (w/w) concentration of the test substance in vehicle
challenge: 5% (w/w) solution of the test substance in vehicle, Duhring chambers
sensitisation rate 0%

Justification for selection of skin sensitisation endpoint:
Guideline study without deviations, GLP

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on reliable, adequate and relevant data, Undecylenamidopropyl Betaine does not need to be classified for skin sensitisation according to regulation (EC) 1272/2008.