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Diss Factsheets

Administrative data

Description of key information

The test substance tested positive for skin sensitization in both the GPMT and LLNA test.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
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.
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.
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
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
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

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.

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

Skin sensitisation:
The skin sensitizing potential of the test substance was evaluated in the guinea pig maximisation test (US EPA, 1973). Twelve animals were exposed to the test substance and 12 to Epoxide No.8 Another 12 served as controls. They were injected with Freund`s complete adjuvant as were the animals in the experimental group. 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. 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 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. One week after the injections the 2nd phase of induction was performed by closed patch exposure to Epoxide No.8 or the test substance over the shoulder region. The dressing was left in place for 48 hours. 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 in propylene glycol. The test substance (one drop) was applied to cellulose test patches, which were sealed to the flank for 24 hours under occlusieve conditions. The challenge sites were evaluated 24 hours after removal of the patches. All of the 12 animals exposed to Epoxide NO.8 became sensitized. 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 positve. Of the 12 control animals, none reacted to any of the 4 compounds. Based on these results, the test substance was determined to be sensitising to the skin.

In another GPMT (based on the methods of Buehler) on 20 test animals and 10 control animals induction was only performed percutaneous (US EPA, 1975). For the induction phase of the study the upper left quadrant of the backs of the test guinea pigs was clipped. Each sample was applied to the appropriate test animal using the appropriate concentrations (0.5 mL of 25 % solution in 80% ethanol). The patches were re-applied to the same site once each week for a total of 3 applications. After a 2-week rest period a fresh application site for primary challenge was prepared at the backs of the test and control guinea pigs of each group. On the following day a challenge patch was applied to the site using the appropriate concentration (0.5 mL of 1% solution in acetone). On the next day the sites were depilated and scored within three to five hours (24-hour reading). The sites were scored again for a 48-hour reading without additional depilation. Both in the 1st as in the 2nd reading 9 out of 20 animals showed positive reactions to the test substance whereas the treated control animals showed no clear positive reactions. Therefore the test substance was considered to be a skin sensitizer.

Hanneke et al (2001), describes the evaluation of the LLNA assay. LLNA results were compared with results obtained for the Guinea Pig Maximization test for 209 substances including the test substance. The LLNA results in this article were obtained by multiple labs under GLP. Reported stimulation index (SI) for the test substance was greater than 3. Therefore the test substance is considered to be sensitizing to the skin. The reported GPMT results were also positive regarding skin sensitization.

Similarly, Basketter et al (1999) investigated data from 134 chemicals (including the test substance) tested in the LLNA and in the guinea pig maximization test obtained from various sources. The data were subjected to a rigorous statistical evaluation. Only a tabulated overview of the results was presented. The test substance was found to be positive in both the LLNA and the GPMT.

Finally, in a published range finding study (Weil, 1963), the sensitisation of guinea pigs was determined by a technique consisting of 8 intra-cutaneous injections (three per week on alternate days) of 0.1 mL of the diluted test material. A three-week incubation period was followed by a challenge dose, and examinations for possible sensitization reactions were made 24 and 48 hours thereafter. The challenge resulted in 16/17 sensitized animals.

A maximisation test on humans (Kligman, 1966) was done on 24 volunteers (inmates of a prison). 19 of the 24 volunteers were sensitised to the test substance.

In several surveys on humans with dermatological problems, e.g. patients in a dermatological clinic (Kanerva et al, 1997 and 1999, Tarvainen, 1995. Fregert and Rorsman, 1964) or workers with symptoms in a plant manufacturing epoxy resins (Prens, 1986) a few cases of allergic reactions to the test substance were found in patch testing.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results obtained from the animal as well as human data, the test substance is considered to be sentizing to the skin. A distinction between category 1A and 1B cannot be made, the substance should therefore be classified as Skin Sens. 1, H317: May cause an allergic skin reaction in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.