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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards.

Data source

Reference
Reference Type:
publication
Title:
The sensitizing capacity of multifunctional acrylates in the guinea pig.
Author:
Bjoerkner B
Year:
1984
Bibliographic source:
Contact Dermatitis 11: 236-246

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
additional intradermal challenge to boost reactions, simultaneous challenge with several acrylates and methacrylates, potential repetition of induction procedure - deviations likely increased the number of positive reactions
Principles of method if other than guideline:
The guinea pig maximization (GPM)-test was performed in accordance with the original description by Magnusson and Kligman (J Invest Dermatol 1969: 52: 268-276 and Magnusson B, Kligman AM. Allergic contact dermatitis in the guinea pig. Identification of contact allergens. Springfield III: CC Thomas Publisher, 1970).

GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Older study available

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in publication): 1,6-Hexanedioldiacrylate (HDDA)
- Analytical purity: 85 %. The purity was analyzed by means of HPLC
- Impurities: Identity and concentrations of impurities were not specified

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 300-400 g

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Induction: Mixture of olive oil and acetone (9:1); Challenge: Petrolatum
Concentration / amount:
Pretest:
The concentrations used for the pretest are not reported.

Main Test:
Intradermal induction: 1 % (w/w) test substance in olive oil/acetone (9:1)
Epicutaneous induction: 25 % in petrolatum
Intradermal Challenge: 1 % (w/w) in petrolatum
Epicutaneous Challenge: 0.2 % (w/w) in petrolatum

Challengeopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Induction: Mixture of olive oil and acetone (9:1); Challenge: Petrolatum
Concentration / amount:
Pretest:
The concentrations used for the pretest are not reported.

Main Test:
Intradermal induction: 1 % (w/w) test substance in olive oil/acetone (9:1)
Epicutaneous induction: 25 % in petrolatum
Intradermal Challenge: 1 % (w/w) in petrolatum
Epicutaneous Challenge: 0.2 % (w/w) in petrolatum

No. of animals per dose:
30 animals: 15 animals in the test group and 15 animals in the control group
Details on study design:
PRETEST:
3 animals were used to evaluate the optimal concentration for intradermal and topical induction. The animals were not subsequently used in the sensitization experiments. No further data were given.

MAIN STUDY:
The details of the test design were as described in Björkner et al. 1984 (Contact Dermatitis, Vol 10: 286-304) and can be summarized as follows:
INDUCTION EXPOSURE
Intradermal application:
- No. of exposures: 3 pairs of injections are made simultaneously (2x 50 µl of Freund´s Complete Adjuvant (FCA) alone, 2x 50 µl of test substance alone and 2x 50 µl of the test agent emulsified in the adjuvant).
- Test groups: 15 animals
- Control group: 15 animals. The control animals were sensitized in the same way as the experimental group but without the test material.
- Site: Shoulder region
- Frequency of applications: One time

Epicutaneous application:
- Time of application: 1 week after the injections
- Exposure period: 48 hours
- Test groups: 15 animals
- Control group: 15 animals
- Site: Shoulder region; the same area which was used for injections
- Frequency of applications: One time

CHALLENGE EXPOSURE
- Two challenges were conducted.
- The amount of test material was approximately 0.015 g.
- The first challenge using 6 different (meth) acrylates including HDDA was 2 weeks after the epicutaneous induction.
- 48 h later, the animals additionally received a booster dose of HDDA intradermally in the same concentration and vehicle as used for the intradermal induction, but without FCA.
- The second challenge was one week after the first challenge and also consisted of 6 different (meth)acrylates: HDDA and 5 new substances (different from challenge 1)
- Control group: 15 animals. When the sensitized animals were challenged, the control animals were also patch-tested with the same chemicals and the same concentrations. As a booster dose, the control animals received olive oil intradermally.
- Site: clipped, shaved flank of the animal.
- Evaluation (hr after challenge): 24 hours after removal of the patch.

REMARK:
- If no animals or just a few showed positive reactions, the GPM test procedure was repeated once more.
- In all animals, challenge with hydroquinone (0.1 % w/w in alcohol), which is a possible additive in acrylate products, was performed. The authors reported that challenge with hydroquinone gave no response in any tested animal.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
0.2 % (w/w) in petrolatum
No. with + reactions:
9
Total no. in group:
15
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 0.2 % (w/w) in petrolatum. No with. + reactions: 9.0. Total no. in groups: 15.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.2 % (w/w) in petrolatum
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.2 % (w/w) in petrolatum. No with. + reactions: 0.0. Total no. in groups: 15.0.

Any other information on results incl. tables

Cross reactivity for 1,6 -Hexandioldiacrylate was checked by challenge reactions with 1,4 -butandioldiacrylate (BUDA), diethyleneglycoldiacrylate (DEGDA), tetraethyleneglycoldiacrylate (TEGDA), tripropyleneglycoldiacrylate (TPGDA), neopentylglycoldiacrylate (NPGDA).

Positive reaction was seen with BUDA (1/15), DEGDA (4/15) and TEGDA (4/15).

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information