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Toxicological information

Skin sensitisation

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Administrative data

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not required as a 1989 guinea pig study with the test substance was availableto fill the requirement.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Betaine, >97% purity (product name Betafin AP)

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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.
Challengeopen allclose all
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

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
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
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
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
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
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
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
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
other: not required
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
other: not required

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
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.
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.