Registration Dossier

Administrative data

Description of key information

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, pre-GLP but in compliance with OECD GLP principles.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
GPMT
GLP compliance:
no
Remarks:
Pre-GLP, but in compliance with OECD GLP priciples.
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: AJ Tuck and Son Ltd, Battlesbridge, Essex, UK
- Age at study initiation: 5 - 8 weeks
- Weight at study initiation: 263 - 328 g
- Housing: in solid-floor polypropylene cages, groups of up to 4 animals
- Diet (e.g. ad libitum): ad libitum, Guinea pig FD1 diet, supplied by Special Diet Services Ltd., Witham, Essex, UK
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 ± 3.5 °C
- Humidity (%): 45 - 60 %
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
water
Remarks:
for intradermal induction only
Concentration / amount:
1st application: Induction 5 % aqueous solution: intradermal injection
2nd application: Induction undiluted occlusive epicutaneous
3rd application: Challenge undiluted occlusive epicutaneous
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
for intradermal induction only
Concentration / amount:
1st application: Induction 5 % aqueous solution: intradermal injection
2nd application: Induction undiluted occlusive epicutaneous
3rd application: Challenge undiluted occlusive epicutaneous
No. of animals per dose:
10 for control group and 10 for the test group
Details on study design:
The Intradermal Induction Phase consisted of intradermal injections of the test substance, the test substance in Freund’s adjuvant and Freund’s adjuvant alone. The test substance was dissolved at a concentration of 5.0% v/v in both the vehicle water and adjuvant.
The fur was removed from the shoulder region of each animal and a 0.1 ml injection of each preparation was made on each side of the animal (for a total of 6 injections).
The Topical Induction Phase consisted of occluded topical application of the test substance under conditions of mild to moderate irritation.
At day 7, the areas were again closely clipped free of hair. The test material at the (non-irritating) concentration of 100 % was applied to a 2 x 4 cm patch of Whatman filter paper, applied and held in position with two strips (cross-form). The patch was further secured by a 3.5 x 25 cm elastic adhesive bandage. The dressing and patches were removed after 48 hours.

Challenge Phase: two weeks after the topical induction phase, the fur was clipped from the flank of each animal and the test substance (100 %) was applied to this area.
An occlusive patch was used to hold the test substance in contact with the skin for 24 hours. Thereafter, 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.
Any reaction produced in response to the challenge phase was evaluated 24 and 48 hours after removal of the occluded patch.
Three hours prior to the first reading, the test sites were slightly clipped free of hair again.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
scattered mild redness (Score 1) or moderate and diffuse redness (Score 2)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: scattered mild redness (Score 1) or moderate and diffuse redness (Score 2).
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
scattered mild redness (Score 1)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: scattered mild redness (Score 1).
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0 % (Vehicle: water)
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: 0 % (Vehicle: water). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0 % (Vehicle: water)
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: 0 % (Vehicle: water). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
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: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
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: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Either mild or well-defined erythema was observed in 5 of 10 animals 24 and hours following challenge applications of the test substance. Slight edema persisted in all 5 animals at 72 hours. This represents a 50% sensitization rate; therefore, the product is considered to be a Grade III Moderate Contact Allergen according to the Maximization grading system.

Interpretation of results:
sensitising
Remarks:
Migrated information Category 1B Criteria used for interpretation of results: EU
Conclusions:
N-methylol methacrylamide (60 % aqueous solution) was found to be a moderate sensitizer in Guinea pigs when tested in tested in the GPMT according to Magnusson and Kligman (EU-GHS category 1B)
Executive summary:

Sensitizing potential of N-METHYLOL METHACRYLAMIDE (60 % aqueous solution, commercial product) was evaluated by intradermal injection and topical applications on Guinea Pigs according to a the Magnusson and Kligman method using Freuds complete adjuvant. The substance was used as 5 % aqueous solution for intradermal induction. Challenge was performed with the undiluted commercial product. The cutaneous reactions were scored 24 and 48 hours after the challenge phase. Mild or moderate erythema were observed in 5 of 10 animals after 24 hours. Slight edema remained in all 5 positive tested animals after 48 hours. This represents a 50% sensitization rate; therefore, the product is considered to be a Grade III Moderate Contact Allergen according to the Maximization grading system.

According to EU-GHS criteria, N-methylol methacrylamide is classified as sensitizing category 1B.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:
Migrated from Short description of key information:
In a valid Guinea Pig Maximisation Test according to Magnusson and Kligman, N-methylol methacrylamide (commercial product, 60 % aqueous solution) was demonstrated to be a moderate skin sensitizer (EU-GHS category 1B). For the 15 % aqueous solution, the absence of a sensitising potential was demonstrated in Guinea pigs. Taking into account the rules for mixtures and with respect to the specific concentration limit of formaldehyde (< 0.2%) both compositions (15 % and 60 % aqueous solution) have to be classified as sensitizing (EU-GHS category 1).

Justification for selection of skin sensitisation endpoint:
Valid GPMT with commercial product (60 % aqueous solution).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no evidence for any respiratory sensitisation potential of N-methylol methacrylamide itself or structurally related substances as methacrylamide or N-methylol acrylamide. The product has negligible vapour pressure and is handled as aqueous solution only.


Migrated from Short description of key information:
There is no evidence for any respiratory sensitisation potential of N-methylol methacrylamide itself or structurally related substances as methacrylamide or N-methylol acrylamide. The product has negligible vapour pressure and is handled as aqueous solution only.

Justification for classification or non-classification

In a valid GPMT on the 60 % aqueous solution of N-methylol methacrylamide, the intradermal induction was performed with a 5 % aqueous solution. The results showed a 50% sensitization rate. According to EU-GHS criteria, the substance is classified as sensitizing category 1B. For the 15 % aqueous solution, the absence of a sensitizing potential was demonstrated in Guinea pigs. Taking into account the rules for mixtures and with respect to the specific concentration limit of formaldehyde (< 0.2%) both compositions (15% and 60% aqueous solution) have to be classified as sensitizing (EU-GHS category 1).