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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
Study period:
17 NOV 1988 to 16 DEC 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: An OECD TG 406 study performed following GLP standards. This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
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
- Source: D. Hall, Darley Oaks, Burton-om-Trent, Staffordshire, UK.
- Age at study initiation: -
- Weight at study initiation: control mean 434g S.D. 27.7, test 432g S.D. 37.5
- Housing: groups of ten, stainless steel cages (85x57x25cm) with mesh floors
- Diet (e.g. ad libitum): FDI, SQC Guinea Pig Diet, (Special diets Services, Witham, Essex, UK) with additional C-vitamin.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 45-68
- Air changes (per hr):-
- Photoperiod (hrs dark / hrs light): 12
IN-LIFE DATES:
From: - To: 16 DEC 1988
Route:
intradermal
Vehicle:
other: Freund's complete adjuvant
Concentration / amount:
50% betaine solution for induction and for challenge test 50% and 20% v/v of betaine and 40% mixture of 20/20 of betaine and Freund's adjuvant.
Range test: 1. 5. 10. 20 and 50% from which 20% was chosen as the minimum as it was the lowest dose to cause minimum localised response.
Route:
epicutaneous, occlusive
Vehicle:
other: Freund's complete adjuvant
Concentration / amount:
50% betaine solution for induction and for challenge test 50% and 20% v/v of betaine and 40% mixture of 20/20 of betaine and Freund's adjuvant.
Range test: 1. 5. 10. 20 and 50% from which 20% was chosen as the minimum as it was the lowest dose to cause minimum localised response.
No. of animals per dose:
10 female Dunkin-Hartley albino guinea pigs.
Details on study design:
RANGE FINDING TESTS:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: Seven days, observation 24 / 48 hours
- Test groups: 2 animals
- Control group: 2 animals
- Site: shoulder region
- Frequency of applications: 7 days
- Duration: two weeks
- Concentrations: 50, 20, 10, 5 and 1% (w/v) aqueous concentrations.
B. CHALLENGE EXPOSURE
- No. of exposures: three pairs, 0.1ml
- Day(s) of challenge: 7, 14
- Exposure period:
- Test groups: 20
- Control group: 20
- Site: shoulder region and back (left / right flank)
- Concentrations: betaine 50%, 20% and 40% (20% betaine, 20% freund's adjuvant)
- Evaluation (hr after challenge): 24 and 48
Challenge controls:
1) 50% Freund's Complete Adjuvant emulsified in distilled water
2) distilled water
3)50% Freund's Complete Adjuvant emulsified in distilled water
Positive control substance(s):
not required
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Interpretation of results:
not sensitising
Remarks:
Migrated information Expert Judgement - Magnusson and Kligman scale
Conclusions:
Based on this OECD TG 406 study betaine is classified as a non sensitising substance (grade 1 sensitiser on the Magnusson and Kligman scale, having sensitisation rate of 0%). Range finding tests indicated that the lowest dose causing any reaction is 20% (v/v) so for the actual challenge test 50% (v/v) was chosen for induction. Neither of these caused any kind of sensitisation.

This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

Based on this OECD TG 406 study betaine is classified as a non sensitising substance (grade 1 sensitiser on the Magnusson and Kligman scale, having sensitisation rate of 0%). Range finding tests indicated that the lowest dose causing any reaction is 20% (v/v) so for the actual challenge test 50% (v/v) was chosen for induction. Neither of these caused any kind of sensitisation.

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

Betaine was tested on various settings for skin sensitisation, including in an OECD TG406 study. All results indicate that betaine does not cause sensitisation. Betaine is being used by the cosmetic industry as an anti-irritant and studies involving humans have been designed to study the anti-irritant properties of betaine.


Migrated from Short description of key information:
Betaine has been found not to have skin sensitative properties. It has been tested with guinea pigs for skin sensitisation in an OECD TG406 following study in accordance with GLP. Supporting studies have been performed on humans investigating the anti-irritating properties of betaine in various vehicles on skin and mucous membrane.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Migrated from Short description of key information:
Not relevant for betaine due to the physico-chemical properties of betaine (particle size, hygroscopic nature and vapour pressure) as well as metabolism and low toxic properties found in oral studies.

Justification for classification or non-classification

Skin sensitisation: Not-classified according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, based on key study (OECD 406, following GLP) and supporting studies on humans, which all indicate that betaine is not sensitizing.

Respiratory sensitisation: Not classified according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, based on the physico-chemical properties of betaine, this route is not relevant.