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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Non-GLP, guideline study, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time of testing (1985), the LLNA method was not yet adopted as OECD Guideline and not yet identified as the standard information requirement.
For this reason the use of the guinea pig maximisation test (GPMT) was considered te be acceptable.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-Butyne-1,4-diol, polymer with 2-(chloromethyl)oxirane, brominated, dehydrochlorinated, methoxylated
EC Number:
614-503-3
Cas Number:
68441-62-3
Molecular formula:
(C3H7O2)xC4H4O2Br2(C4H9O2)y with x + y = 2.5
IUPAC Name:
2-Butyne-1,4-diol, polymer with 2-(chloromethyl)oxirane, brominated, dehydrochlorinated, methoxylated
Constituent 2
Chemical structure
Reference substance name:
Triethyl phosphate
EC Number:
201-114-5
EC Name:
Triethyl phosphate
Cas Number:
78-40-0
Molecular formula:
C6H15O4P
IUPAC Name:
triethyl phosphate
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): B 251
- Lot/batch No.: not specified
- Physical state: liquid

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, Newchurch, Staffordshire, England
- Age at study initiation: not specified
- Weight at study initiation: 412 g (mean)
- Housing: individually
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
unchanged (no vehicle)
Concentration / amount:
The intradermal irritancy of a range of dilutions of B251 in acetone, 5% v/v in Alembicol D and the topical irritancy of B251 in acetone were investigated to identify (a) irritant test substance concentrations suitable for the induction phase of the main study and (b) non-irritant concentrations by the topical route of administration for the challenge phase.

The following concentrations of B251 were selected:
Induction
Intradermal injection: 0.25% v/v in 5% v/v acetone in Alembicol D.
Topical application: B251, as supplied.

Challenge
10% and 5% v/v in acetone.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
The intradermal irritancy of a range of dilutions of B251 in acetone, 5% v/v in Alembicol D and the topical irritancy of B251 in acetone were investigated to identify (a) irritant test substance concentrations suitable for the induction phase of the main study and (b) non-irritant concentrations by the topical route of administration for the challenge phase.

The following concentrations of B251 were selected:
Induction
Intradermal injection: 0.25% v/v in 5% v/v acetone in Alembicol D.
Topical application: B251, as supplied.

Challenge
10% and 5% v/v in acetone.
No. of animals per dose:
20
Details on study design:
Treatment procedure
The method employed in this study for the detection of delayed contact hypersensitivity was the guinea-pig maximisation test described by B. Magnusson and A.M. Kligman (1970) in "Allergic Contact Dermatitis in the Guinea-Pig : Identification of contact allergens H , published by C.C. Thomas, Springfield, Illinois, U.S.A.

The procedure may be considered in two parts, (1) induction, (2) challenge.

Induction
Test animals
Intradermal injections
A 4 x 6 cm area of dorsal skin on the scapular region of the guinea-pig was clipped free of hair with electric clippers. Three pairs of intradermal injections were made simultaneously into this area.

Injectables were prepared as follows:
1. Freund's complete adjuvant* was diluted with an equal volume of water for irrigation.
2. B251, 0.25% v/v in acetone, 5% v/v in Alembicol D.
3. B251, 0.25% v/v in a 50:50 mixture of Freund's complete adjuvant and acetone, 5% v/v in Alembicol D.
* Difco Laboratories, Detroit 1, Michigan, U.S.A.

Topical application
One week after the injections, the same 4 x 6 cm interscapular area was clipped and shaved free of hair. A 2 x 4 cm patch of Whatman No. 3 paper was saturated with B251, as supplied. The patch was placed on the skin and covered by a length of impermeable plastic adhesive tape (5 cm width "Blenderm"). This in turn was firmly secured by elastic adhesive bandage ("Elastoplast" 5 cm width) wound round the torso of the animal and fixed with "Sleek" impervious plastic adhesive tape. The dressing was left in place for 48 hours.

Control animals
During the induction period the control animals were treated similarly to the test animals with the exception that the test compound was omitted from the intradermal injections and topical application.

Challenge
The test and control animals were challenged topically two weeks after the induction period using B251, 10% and 5% v/v in acetone. Hair was removed by clipping and then shaving from an area on the left flank of each guinea-pig. A 2 x 2 cm patch of Whatman No. 3 paper was saturated with approximately 0.2 ml of B251, 10% v/v in acetone and applied to an anterior site on the flank. B251, 5% v/v in acetone was applied in a similar manner to a posterior site. The patches were sealed to the flank for 24 hours under strips of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek".

Reading challenge reactions
The challenge sites were evaluated 24, 48 and 72 hours after removal of the patches.
Challenge controls:
None
Positive control substance(s):
no

Results and discussion

Positive control results:
not tested

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5 and 10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5 and 10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
5 and 10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

The substance was not a skin sensitiser in guinea pigs.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, no evidence was obtained that Polyol IXOL B251 has a skin sensitising potential.
Executive summary:

The skin sensitisation potential of Polyol IXOL B251 was investigated in a guinea pig maximisation test according to OECD guideline 406 (Huntingdon, 1985). 20 test and 20 control guinea pigs (Dunkin-Hartley) were induced by 3 pairs of injections (0.1 ml) into the scapular region:

- Freund’s Complete Adjuvant (FCA) 1:1 with water;

- 0.25% test substance in 5% (v/v) acetone in Alembicol D;

- 0.25% test substance in a 1:1 mixture of 5% (v/v) acetone in Alembicol D and FCA.

After one week, the test substance (as supplied, undiluted) was placed on the same area of skin for 48 hours under occlusive dressing.

Two weeks following topical induction, challenge was performed with 5% (v/v) and 10% (v/v) of the test substance in acetone under occlusive dressing for 24 hours. No evidence of delayed contact hypersensitivity was seen in any of the twenty test animals.