Registration Dossier

Administrative data

Description of key information

- GPMT: negative (modified Magnusson-Kligman Test)
- GPMT: negative (according to OECD 406)
- Patch Test: negative

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:
key study
Study period:
1984-03-23 to 1984-04-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Equivalent or similar to OECD guideline, GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
Principles of method if other than guideline:
The test method is based on that originally described by Magnusson B. and Kligman A.M., J. Invest. Derm. 1969, 52, 268-276 with modifications as indicated in the U.K. Health and Safety Commission publication "Approved Code of Practice: Methods for determination of toxicity" to comply with the Notification of New Substances Regulations, 1982.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The non-LLNA study was performed in 1984 before LLNA test method was available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tuck & Sons Ltd., Battlesbridge, Essex
- Age at study initiation: approximately five to eight weeks of age
- Weight at study initiation: 288 - 338 g
- Housing: in groups of up to four
- Diet: standard laboratory guinea pig diet (Guinea Pig FD1 Diet supplied by Special Diet Services Limited, Witham, Essex), ad libitum;
- Water: tap water, ad libitum
- Acclimation period: for a minimum period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 25
- Humidity (%): Humidity was not controlled but remained within a range of 48-60 % RH recorded daily on a wet and dry bulb hygrometer.
- Air changes (per hr): approximately 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
intradermal and epicutaneous
Vehicle:
other: arachis oil BP and ethanol, respectively
Concentration / amount:
1st: Induction 5% (in arachis oil BP);
2nd: Induction undiluted;
3rd: Challenge 50% (in absolute ethanol);
Route:
epicutaneous, occlusive
Vehicle:
other: arachis oil BP and ethanol, respectively
Concentration / amount:
1st: Induction 5% (in arachis oil BP);
2nd: Induction undiluted;
3rd: Challenge 50% (in absolute ethanol);
No. of animals per dose:
Control: 10 female animals; treated: 10 female animals;
Details on study design:
RANGE FINDING TESTS:

Intradermal Injection: Into the clipped shoulder area of one animal four 0.1 mL intradermal injections of the test material at a concentration of 1% in a suitable vehicle were administered simultaneously; similarly four 0.1 mL aliquots of a 5% concentration of the test material were injected into a second guinea pig. Animals were observed 24, 48 and 72 hours and 7 days following treatment.
Topical Application: Both flanks of each of two guinea pigs were closely clipped free of hair. These animals had been intradermally injected with Freunds complete adjuvant between one and three weeks previously. The test material at a number of different concentrations in a suitable vehicle was applied to the clipped flanks under occlusive patches. The patches were left in position for 24 hours. Following the 24 hour exposure period the dressings
and patches were removed and any residual test material was washed from the application sites using cotton wool soaked in lukewarm water or ether. Approximately one hour following removal of the patches and 24 and 48 hours later, the reactions at the application sites were evaluated. The concentrations of the test material to be used on a further two guinea pigs were chosen, applied and then evaluated after similar time intervals.
On the basis of the results of this study the concentrations for the main study were identified.


MAIN STUDY
A. INDUCTION EXPOSURE

- Intradermal Induction:

Day 0: EXPERIMENTAL GROUP: three pairs of intradermal injections in the shoulder region were given simultaneously:
(1) 0.1 mL of Freunds complete adjuvant (Difco Laboratories, Detroit, Michigan USA)
(2) 0.1 mL of a 5 % concentration of the test material
(3) 0.1 mL of a 50 : 50 mixture of a 5 % concentration of the test material emulsified in the adjuvant

DAY 0: CONTROL GROUP: treated in a similar manner to the Experimental Group except that they were not exposed to the test material:
(1) 0.1 mL of Freunds complete adjuvant
(2) 0.1 mL of vehicle alone
(3) 0.1 mL of a 50 : 50 mixture of vehicle emulsified in Freunds complete adjuvant

- Epicutaneous Induction:

DAY 7: EXPERIMENTAL GROUP: The same area in the shoulder region of each guinea pig used for intradermal inductions was again closely clipped free of hair. The test material at a concentration of 100% was applied to a patch of Whatman No 4 filter paper. This patch was applied to the clipped shoulder region and held in position with two strips of Sleek waterproof adhesive strapping in the form of a cross. The patch was further secured by a 3.5 cm x 25 cm length of Elastoplast elastic adhesive bandage which was wound in a double layer around the torso of the animal. The dressing and patches were removed following a 48 hour exposure period.

DAY 7: CONTROL GROUP: The control group guinea pigs were treated in an identical manner to the Experimental Group animals except that the vehicle alone was applied to the induction site.

B. CHALLENGE EXPOSURE

DAY 21: EXPERIMENTAL AND CONTROL GROUPS: An area measuring 5 cm x 5 cm on both flanks of each Experimental and Control Group guinea pig was closely clipped free of hair. The test material, at the highest non-irritant concentration indicated by the topical siting test (50 %) was applied to the clipped right flank of each animal under an occlusive patch. The vehicle alone was similarly applied to the clipped left flank. Both patches were covered with an overlapping length of aluminium foil and then held firmly in position for 24 hours by means of a 7.5 cm x 25 cm length of Elastoplast elastic adhesive bandage wound in a double layer around the torso of the animal.

DAY 22: Following the 24 hour exposure period the dressings and patches were removed from all Experimental and Control Group guinea pigs and any residual test material or vehicle was washed from the challenge sites using cotton wool soaked in lukewarm water or ether. The sites were marked using an indelible pen.

DAY 23: Twenty-one hours following removal of the patches the challenge sites of all Experimental and Control Group guinea pigs were lightly clipped free of hair. Three hours later (ie 24 hours following removal of the patches) the reactions observed at the test material and vehicle control sites were evaluated.

DAY 24: The reactions observed at the challenge sites were again observed and scored i.e. 48 hours following removal of the patches.
Challenge controls:
The control group guinea pigs were treated in an identical manner to the Experimental Group animals except that the vehicle alone was applied to the induction site.
Positive control substance(s):
yes
Remarks:
The sensitivity of the guinea pigs is checked at regular intervals using known positive sensitizers.
Positive control results:
The sensitivity of the guinea pigs is checked at regular intervals using known positive sensitizers.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Group:
positive control
Remarks on result:
not measured/tested
Remarks:
The sensitivity of the guinea pigs is checked at regular intervals using known positive sensitizers.

Bodyweight gains of guinea pigs in the Experimantal Group between day 0 and day 24 were comparable to those observed in the Control Group animals over the same period.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material Allyl methacrylate [ Methacrylate D'Allyle (MALLY)] was found to be a non-sensitizer (0/10 animals were sensitised) in the guinea pig.
Executive summary:

The test material Methacrylate D'Allyle (MALLY) was found to be a non-sensitizer in the guinea pig.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are valid in vivo data available for the assessment of the skin sensitising potential of Allyl methacrylate.

 

In a guinea pig maximisation test (modified Magnusson-Kligman-Test; according to GLP) which was reliable with restrictions Allyl methacrylate was administered intradermal (as a 5% mixture with arachis oil BP) to each of the 10 female Dunkin-Hartley guinea pigs in the test group during the three-application induction phase of the study (Arkema, 1984). After 7 days the epicutaneous injection of the induction phase followed (with undiluted test substance, under occlusive conditions). The challenge period was carried out 2 weeks after the epidermal induction by a piece of filter paper saturated with the test material (10% in paraffin oil). 24 and 48 hours after the challenge period no effects were observed both in the test and in the control groups (Safepharm, 1984).

A second guinea pig maximisation test (according to OECD 406 and GLP) which was reliable with restrictions confirmed the negative result of the first assay (C.I.T., 1991). In the intradermal induction phase Allyl Methacrylate was administered to the 10 male and 10 female Dunkin-Hartley guinea pigs at a concentration of 10% (in paraffin oil). After 7 days the epicutaneous injection of the induction phase followed (with undiluted test substance, under occlusive conditions). The challenge period was carried out 2 weeks after the epidermal induction by a piece of filter paper saturated with the test material (10% in paraffin).

Additionally, a patch test was conducted in female Hartley albino guinea pigs (Siddiqui, 1982). Two groups of 10 guinea pigs were subjected to 4 insult patch tests in 10 days either with Allyl Methacrylate (undiluted) or with the positive control, dinitrochlorobenzene. No animal that received Allyl Methacrylate showed a positive result, whereas all animals of the positive control group showed a positive result.

In addition, allyl methacrylate did not induce contact sensitivity in guinea pigs using the Polak method (Parker, 1983).


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, there is no indication for a skin sensitising potential of the test substance. Thus, no classification is warranted according to 67/548/EEC and Regulation (EC) No 1272/2008 (GHS, CLP), respectively.