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Description of key information

Key value for chemical safety assessment

Skin sensitisation

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Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
other: T20-03: Magnusson-Kligman Maximization Test (Magnusson, B.,Kligman,A.M.,J.Invest.Dermat.,52,268-276,1969
Version / remarks:
1969
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Magnusson-Kligman Maximization Test (Magnusson, B.,Kligman,A.M.,J.Invest.Dermat.,52,268-276,1969) with guinea pics was carried out or initiated before 11 October 2016. The test meets the requirements set out in Article 13(3), first subparagraph, and Article 13(4) and shall, therefore, be considered appropriate to address this standard information requirement for the skin sensitization endpoint.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: supplied by David Hall Ltd., Darley Oaks, Newchurch, Burton-on-Trent, Staffordshire
- Age at study initiation: young adult (less than one year old)
- Weight at study initiation: 421 to 494 g
- Housing: 5 per cage in main test group and control group; 4 per cage in range finding test
- Diet (e.g. ad libitum): ad libitum (FD1 Guinea Pig Diet, supplied by Special Diets Services, 1 Stepfield, Witham, Essex, CM8 3AD)
- Water (e.g. ad libitum): ad libitum (tab water)
- Acclimation period: 7 days prior to test commencement

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 20 °C
- Humidity (%): 48 %
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark

IN-LIFE DATES: From: To:
Route:
intradermal and epicutaneous
Vehicle:
other: Distilled water
Concentration / amount:
INDUCTION
Intradermal: 10%
dermal: 100%
CHALLENGE
dermal: 100%
Route:
epicutaneous, occlusive
Vehicle:
other: Distilled water
Concentration / amount:
INDUCTION
Intradermal: 10%
dermal: 100%
CHALLENGE
dermal: 100%
No. of animals per dose:
Test group 10 guinea pigs
Control group 10 guinea pigs
Challenge dose ranging group 4 guinea pigs
Details on study design:
1st application: Induction 10 % intracutaneous
2nd application: Induction 100 % open epicutaneous
3rd application: Challenge 100 % open epicutaneous
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
slight reaction
Remarks on result:
other: challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no reaction
Remarks on result:
other: challenge
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
vehicle with 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no visible reaction
Remarks on result:
other: challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
vehicle with 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no visible reaction
Remarks on result:
other: challenge
Reading:
1st reading
Hours after challenge:
24
Group:
other: control with destilled water
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no visible reaction
Remarks on result:
other: challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control with destilled water
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no visible reaction
Remarks on result:
other: challenge

Induction: Slight irritation was noted in the test group.
Challenge: Following challenge with the test material at a concentration of 100%, none of the 10 test group showed positive reactions to this application.

Interpretation of results:
not sensitising
Conclusions:
A well conducted, well reported guinea-pig skin sensitization test (Magnusson-Kligman method) reported that a 10% concentration of the test material in water induced no sensitization response when challenged with 100% of the test substance. Appropriate concurrent negative compliance controls were included.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
06-02-1991 until 17-03-1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was conducted in compliance with GLP. The study was not conducted in accordance with an OECD guideline, however, the method used was based on that described in a published paper. The study was well performed and thoroughly described.
Qualifier:
equivalent or similar to
Guideline:
other: Harber, Armstrong, Ichikawa (JNCI, 1982, 69, 1).
Deviations:
not specified
GLP compliance:
yes
Type of study:
Freund's complete adjuvant test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall limited, Darley Oaks, Newchurch, Burton-on-Trent, Staffordshire, UK.
- Age at study initiation: less than 1 year
- Weight at study initiation: order weight 300-350 g
- Housing: Housed to 5 in a cage, aluminium cages had grid floors beneath which were peat moss filled trays.
- Diet (e.g. ad libitum): FD1 Guinea pig diet, supplied by Special Diets Service, Witham, Essex, UK, hay were given ad libitum.
- Water (e.g. ad libitum): tap water ad libitum.
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C - 21°C
- Humidity (%): mean rel. humidity 52%
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

Route:
epicutaneous, open
Vehicle:
water
Concentration / amount:
Solfit concentration was 100% both for the induction and challenge exposure.
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
Solfit concentration was 100% both for the induction and challenge exposure.
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
A preliminary test was performed with 5 previously untreated guinea pigs. They were exposed to 24h open epicutaneous topical applications of solfit at a concentration of 100%, 50%, 25% and 10% v/v in distilled water. The animals were exposed to 3 successive applications over 5 days. Test sites were assessed for irritation 24h after application of the test material using the scoring system described under the challenge procedure.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5
- Exposure period: 10 days
- Test groups: 1 test group
- Control group: 2 control groups
- Concentrations: 100% solfit

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Test groups: 1 test group
- Control group: 2 control groups
- Concentrations: 100% solfit
- Evaluation (hr after challenge): 24, 48, 72 hours

OTHER

Induction:
The test animals had hair removed from a 3 x 3cm area of the scapular region. 4 x 0.1 mL intradermal injections of Freund's Complete Adjuvant were administered at the corners of the shaved area.
Test animals: 0.1 mL of the test substance was applied open epicutaneously to the test site of each guinea pig. 30 minutes later, the test animals were exposed to UVA radiation through 3mm window glass (10.2 J * cm²).
The guinea pigs in control group 1 (see below for details) were similarly treated, but with distilled water instead of solfit.
The guinea pigs in control group 2 were treated with solfit but were not exposed to UVA radiation.
The procedure was repeated 4 further times.

Challenge:
20 days after the final induction exposure, the dorso lumbar area of the test animals was clipped and shaved. Four test sites were marked out on either side of the vertebral column of the test group and control group animals 1. 24h later 0.1 mL of solfit and the control material, distilled water, were applied to the prepared sites of the test and control group as described for the induction. The test sites on each animal were then covered with light proof tapel. For control group 2, the test material and the control material were applied, each to 2 prepared sites. The test group and control group 1 animals were exposed to UVA radiation after treatment. The test sites were assessed 24, 48 and 72hrs after irridation for evidence of erythmea and/or oedema using the following scoring system:

no reaction = 0
mild erythema without oedema = 1
moderate / strong erythema without oedema = 2
moderate/strong erythema with oedema = 3
Challenge controls:
see below
Positive control substance(s):
no

Induction:

No irritation was noted at any time in any of the test or control group animals. The injection sites showed normal erythemal responses.

Challenge:

None of the test group or control group animals showed any positive response.

Clinical signs:

No clinical signs, other than skin reactions induced by treament, were noted.

Interpretation of results:
not sensitising
Conclusions:
There is no evidence from the test results that Solfit is a photosensitiser in guinea pigs.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no reports of human skin or respiratory sensitisation associated with 3 -methoxy-3 -methyl-butan-1 -ol exposure.

A Magnusson-Kligman maximisation test ir reported. The animals showed no irritation after the challenge with the neat test article, except for transient slight to moderate irritation on the animals at the intradermal induction with 10% (v/v) test article in water. Based on these results, 3 -methoxy-3 -methylbutan-1 -ol is considered not to have skin sensitising potential.

The photoirritation potential of MMB was investigated in guinea pigs. The substance was applied dermally in various concentrations followed by exposure to UVA light. No photoirritant responses were noted in the test and control groups.


Migrated from Short description of key information:
Based on the result of the Magnusson-Kligman-Maximisation test with guinea pigs, 3-methoxy-3-methyl-butan-1-ol is not sensitising to skin. Following a photoirritation study with ghuinea pigs, MMB is not photosenitizing.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

 No data on respiratory sensitisation are available. However, in accordance with Section 1 of REACH Annex XI, the study is scientifically unjustified, as respiratory tract sensitisation is not expected based on the fact that 3 -methoxy-3 -methylbutan-1 -ol is not skin sensitizer and no human data are available indicating a concern for respiratory sensitisation.

Justification for classification or non-classification

Based on the absence of skin sensitising effect in a Kligman-Magnusson-Maximisation study with guinea pigs and the lack of data indicating the respiratory sensitisation of 3 -methoxy-3 -methylbutan-1 -ol, the substance is considered to be not sensitising according to Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.