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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Allergenicity of epoxy-reactive diluents in the guinea pig.
Author:
Thorgeirsson A., Fregert S., Magnusson B.
Year:
1975
Bibliographic source:
Berufsdermatosen. 1975 Oct;23(5):178-83. cited in US Environmental Protection Agency TSCATS: OTS0523514 Doc. I.D.: 40-7840108

Materials and methods

Principles of method if other than guideline:
The skin sensitising potential of the test substance was evaluated in the guinea pig maximisation test.
GLP compliance:
no
Remarks:
Study pre-dates GLP regulation
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
When this study was performed, the LLNA method was not yet well known or validated for skins sensitisation testing.

Test material

Constituent 1
Chemical structure
Reference substance name:
Butyl 2,3-epoxypropyl ether
EC Number:
219-376-4
EC Name:
Butyl 2,3-epoxypropyl ether
Cas Number:
2426-08-6
Molecular formula:
C7H14O2
IUPAC Name:
2-(butoxymethyl)oxirane
Test material form:
liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Albino, not further specified.
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 300 - 400 gram
- Housing: caged in pairs
- Diet: a pellet diet.
- Water: tap, ad libitum.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
Three injections in a row: 0.1 mL Freund's complete adjuvant, 0.1 mL of 10% of Epoxide No. 8 or 0.1 mL of 10% of the test substance and 0.1 mL of a mixture of 10% of Epoxide No. 8 or 10% test substance and equal amount of Freund's adjuvant.
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
A 2 X 4 cm patch saturated with Epoxide No. 8 or the test substance (10 % in vehicle)
Day(s)/duration:
48 hours
Adequacy of induction:
not specified
Challenge
No.:
#1
Route:
epicutaneous, open
Vehicle:
propylene glycol
Concentration / amount:
1 drop of 0.1% of Epoxide No. 8, the test substance, cresylglycidyl ether and epoxy resin (Ferroclere 900)
Day(s)/duration:
24 hours
Adequacy of challenge:
other: non-irritant concentration
No. of animals per dose:
12
Details on study design:
Twelve animals were exposed to Epoxide No. 8 and 12 to the test substance. Another twelve served as controls. They were injected with Freund`s complete adjuvant as were the animals in the experimental group. The intradermal and topical irritancy of Epoxide No. 8 and the test substance was investigated in a preliminary study. A 10 % concentration in propylene glycol was found to be a suitable concentration for induction. A 0.1 % concentration in propylene glycol owas found to be non-irritant in a 24 hour occluded patch test.

Intradermal injections:
The animals in the experimental groups were exposed to the reactive diluents in a two stage procedure. The first stage of induction was performed by intradermal injections in the shoulder region. The hair in a 4 by 6 cm area in the scapular region was clipped with an electric clipper. Three injections of the following mixtures were made on each side in a row.
- 0.1 mL Freund`s complete adjuvant blended with an equal amount of water.
- 0.1 mL 10% Epoxide No. 8 or 0.1 mL 10% test substance.
- 0.1 mL of a mixture containing 10% Epoxide No. 8 or 10% test substance in propylene glycol and an equal amount of Freund`s adjuvant.

Topical application:
One week after the injections the same 4 by 6 cm area was clipped and shaved, after which the 2nd phase of induction was performed by closed patch exposure to Epoxide No. 8 or the test substance over the shoulder region. A 2 by 2cm patch of Whatmann No.3 MM paper was saturated with the reactive diluent 10% in propylene glycol. The patch was placed on the shaved skin and covered by an overlapping, impermeable plastic adhesive tape. This in turn was firmly secured by an elastic adhesive bandage wound around the torso of the animal. The dressing was left in place for 48 hours.

Challenge:
Challenge, also of the control animals was performed 2 weeks after the topical exposure. All the animals were patch tested with a 0.1% concentration of Epoxide No. 8, the test substance, cresylglycidyl ether and epoxy resin (Ferroclere 900) in propylene glycol. Hair was removed from a 5 by 5 cm area of the flank by clipping and shaving. The test substance (one drop) was applied to cellulose test patches, 80 mm of Whatmann No.3 MM, which were sealed to the flank for 24 hours under overlapping, impermeable plastic adhesive tape secured by Elastoplast wound around the trunk. The challenge sites were evaluated 24 hours after removal of the patches. Evaluation was facilitated by shaving the hair with an electric razor 3 hours before hand. The examiner was unware of the reactive diluent with which a given animal had been treated. Only diffuse or intense redness and/or swelling was regarded as a positive reaction.
Challenge controls:
yes, 12 animals tested simultaneously.
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
other: animals treated and challenged with the test substance
Dose level:
0.1 %
No. with + reactions:
6
Total no. in group:
12
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Animals treated with the test substance and challenged with Epoxide No.8
Dose level:
0.1 %
No. with + reactions:
12
Total no. in group:
12
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Animals exposed to the test substance and challenged with Cresylglycidyl ether.
Dose level:
0.1 %
No. with + reactions:
8
Total no. in group:
12
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Animals exposed to the test substance and challenged with Epoxy resin
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
12
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
12
Reading:
1st reading
Hours after challenge:
24
Group:
other: Animals exposed to Epoxide No.8 and challenged with Epoxide No.8
Dose level:
0.1 %
No. with + reactions:
12
Total no. in group:
12
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Animals exposed to Epoxide No.8 and challenged with the test substance
Dose level:
0.1 %
No. with + reactions:
4
Total no. in group:
12
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Animals exposed to Epoxide No.8 and challenged with Cresylglycidyl ether
Dose level:
0.1%
No. with + reactions:
4
Total no. in group:
12
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: Animals exposed to Epoxide No.8 and challenged with Epoxide resin
Dose level:
0.1 %
No. with + reactions:
9
Total no. in group:
12
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

All of the 12 animals exposed to Epoxide NO.8 became sensitised. Cross reactions to the test substance and cresylglycidyl ether occurred in 4 of the animals, and to the epoxy resin in 9.

Of the 12 animals exposed to the test substance 6 became positive. Cross-sensitivity to Epoxide No.8 was found in all of them and to cresylglycidyl ether in 8. None of the animals in this group reacted to the epoxy resin. Of the 12 control animals, none reacted to any of the 4 compounds.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Remarks:
Based on ≥ 30% responding at > 1% intradermal induction dose