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Diss Factsheets

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:
13 December 2004 to 20 January 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 406 with deviations: age at study initiation, housing and feeding conditions not reported. These deviations do not affect the quality of the study and are not considered to be relevant.The substance is considered to be adequately characterised.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
17 July 1992.
Deviations:
yes
Remarks:
age at study initiation, housing and feeding conditions not reported
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Directive 96/54 E.E.C.
Deviations:
yes
Remarks:
age at study initiation, housing and feeding conditions not reported.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
13 september 2004
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
According to REACH regulation, in vivo skin sensitisation studies that were carried out or initiated before 10 May 2017 shall be considered appropriate to address this standard information requirement.

Test material

Constituent 1
Chemical structure
Reference substance name:
(3R)-3-benzyloxane
Molecular formula:
C12 H16 O
IUPAC Name:
(3R)-3-benzyloxane
Constituent 2
Chemical structure
Reference substance name:
(3S)-3-benzyloxane
Molecular formula:
C12 H16 O
IUPAC Name:
(3S)-3-benzyloxane
Test material form:
liquid
Remarks:
clear
Details on test material:
- Physical state: Colourless translucent liquid, characteristic odour
- Storage conditions : room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre de production Animale (45160 Olivet - FRANCE)
- Weight at study initiation: 270-377 g
- Housing: No data
- Diet: No data
- Water: No data
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-23 °C
- Humidity: 28-56 %

IN-LIFE DATES: 16 December 2004 to 20 January 2005

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
olive oil
Concentration / amount:
intradermic injection at 25%
Day(s)/duration:
8 days
Adequacy of induction:
other: No necrosis has been observed since the concentration of 25%, the first induction has been carried out by intradermal injection at the same concentration.
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
topical application at 100%
Day(s)/duration:
3 days
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
topical application at 100 and 50%
Day(s)/duration:
3 days
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
5 males and 5 females for treated group
Details on study design:
PRELIMINARY TESTS:
Maximum Non Necrotizing Concentration (M.N.N.C.) determination: 2 male guinea pigs were used. The test item was injected by intradermal route at the following concentrations: 100%, diluted at 50%, 25%, 12.5%, 6.25% and 3.125% in olive oil. No necrosis has been observed, at the concentration of 25%, the first induction has been carried out by intradermal injection at the same concentration.
Pre-Maximum Non Irritant Concentration (Pre -M.N.I.C.) determination: 2 male guinea pigs were used. The test item was applied under an occlusive dressing during 24 hours, at the following concentrations 100%, diluted at 50%, 25% and 12.5% in paraffin oil. 24 hours after the removal of the occlusive dressings, no cutaneous reaction was recorded. In view of these results, the concentration selected was 100% for the 2nd induction of the main study and the MNIC determination began at this concentration of 100%.
Maximum Non Irritant Concentration (M.N.I.C.) determination: 3 male guinea pigs were used. After induction by intradermal injection with olive oil and by topical application with paraffin oil and a 18-day rest phase, the challenge phase under occlusive dressing for 24 hours consists in a single topical application of the test item at the following concentrations: 100%, diluted at 50%, 25% and 12.5% in paraffin oil. 24 hours after removal of the occlusive dressings, no cutaneous reaction was recorded. In view of this result, the concentrations selected were 100% (MNIC) and 50% (1/2 MNIC) for the challenge phase.



MAIN STUDY
A. INDUCTION EXPOSURE (INTRADERMAL - 1st induction: Day 0)
- No. of exposures: One
- 2 intradermal injections of the test item at diluted at 25% in olive oil; 2 intradermal injections of Freund’s Complete Adjuvant diluted at 50% in a physiological saline solution; 2 intradermal injections of a mixture with equal volumes - Freund’s Complete Adjuvant at 50% and the test item at 50% in olive oil.
- Exposure period: Day 0-6
- Duration: 7 days
- Concentrations: 25% in olive oil

B. INDUCTION EXPOSURE (TOPICAL - 2nd induction: Day 7)
- No. of exposures: One
- Topical application, on the same zone, with the test item at 100%, 24 hours after brushing with 0.5 mL of a solution of Sodium lauryl sulfate.
- Duration: 3 days
- Concentrations: 100%

C. REST PHASE: 18 days

D. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Day 27
- Exposure period: 24 h
- Challenge phase (Groups 1 & 2): topical application under occlusive dressing at the following concentrations: 100% & 50%.
- Evaluation: 24 and 48 h after challenge
Challenge controls:
No. of animals: 3 males and 2 females
Challenge: 100% and 50%
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole [49-30-4]; Neomycin sulfate [1405-10-3]

Results and discussion

Positive control results:
The results of the 3 latest positive group (Reference substance: 2-Mercaptobenzothiazole [49-30-4] Test 8; Neomycin sulfate [1405-10-3] Tests 6 & 7) carried out as method sensibility indicated the validity of the study.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 and 50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 and 50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 and 50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 and 50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
NEOMYCIN SULFATE at 75%
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
historical data - 6th test
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
NEOMYCIN SULFATE at 75%
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
historical data - 6th test
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
NEOMYCIN SULFATE at 75%
No. with + reactions:
4
Total no. in group:
8
Remarks on result:
positive indication of skin sensitisation
Remarks:
historical data - 7th test
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
NEOMYCIN SULFATE at 75%
No. with + reactions:
3
Total no. in group:
8
Remarks on result:
positive indication of skin sensitisation
Remarks:
historical data - 7th test
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
2-Mercaptobenzothiazole at 50%
No. with + reactions:
4
Total no. in group:
9
Remarks on result:
positive indication of skin sensitisation
Remarks:
historical data - 8th test
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
2-Mercaptobenzothiazole at 50%
No. with + reactions:
4
Total no. in group:
9
Remarks on result:
positive indication of skin sensitisation
Remarks:
historical data - 8th test

Any other information on results incl. tables

Sensitising potential assessment: No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test item. No cutaneous intolerance reaction was recorded in animals from the negative control group.

Weight evolution: No abnormality was recorded in the weight growth of both groups.

Mortality: No mortality occurred during this study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, test substance is not classified as sensitiser according to the criteria of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In a Magnusson & Kligman maximisation study (GPMT) performed according to OECD Guideline 406 and in compliance with GLP, Guinea pigs were treated as follows:

After induction (intradermic injection at 25% and topical application at 100%) of 10 Guinea Pigs of treated group with the test substance and a 18-day rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test item at 100% and diluted at 50% in paraffin oil. The test concentrations for the main study were determined from a preliminary study.

 

No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test item. No cutaneous intolerance reaction was recorded in animals from the negative control group.

 

The sensitivity of the guinea-pig was checked with the results of the 3 latest positive group (Reference substance: 2-Mercaptobenzothiazole [49-30-4] Test 8; Neomycin sulfate [1405-10-3] Tests 6 & 7) indicating the validity of the study. 

Under the test conditions, test substance is not classified as sensitiser according to the criteria of the Regulation EC No. 1272 /2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for skin sensitisation endpoint.