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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Documentation sufficient for assessment.

Data source

Reference
Reference Type:
publication
Title:
Sensitizing potential of 2-hydroxyethyl-methacrylate
Author:
Clemmensen S.
Year:
1985
Bibliographic source:
Contact Dermatitis 12(4): 203-208

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Magnusson and Kligman (1970)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was performed in 1985 before LLNA-method has been developed.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-hydroxyethyl methacrylate
EC Number:
212-782-2
EC Name:
2-hydroxyethyl methacrylate
Cas Number:
868-77-9
Molecular formula:
C6H10O3
IUPAC Name:
2-hydroxyethyl methacrylate
Details on test material:
- Name of test material (as cited in study report): 2-Hydroxyethylmethacrylate

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Ssc:AL
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Statens Seruminstitut, Cpenhagen, Denmark
- Weight at study initiation: 300- 350 g
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22 deg C
- Humidity (%): 50-70%
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 21.00 to 09.00 hours

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: soybean oil; soybean oil + 2-butanone; sterile water
Concentration / amount:
1% soybean oil, 25% soybean oil, 25% soybean oil+2-butanone, 1% aqueous, 10% aqueous, 25% aqueous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: soybean oil; soybean oil + 2-butanone; sterile water
Concentration / amount:
1% soybean oil, 25% soybean oil, 25% soybean oil+2-butanone, 1% aqueous, 10% aqueous, 25% aqueous
No. of animals per dose:
1% soybean oil - 20
25% soybean oil - 12
25% soybean oil+2-butanone - 10
1% aqueous - 12
10% aqueous- 12
25% aqueous - 12
Details on study design:
Induction: 
Day 0:  3 pairs of injections; 1. 2 x 50 uL suspension of FCA in sterile water (1:1)
 2. 2 x 50 uL test substance 1-25 % in different vehicles
 3. 2 x 50 uL test substance in FCA (1:1)            
Day 7:  approx. 250 mg 10 % sodium dodecyl sulphate in petrolatum, 24 h, uncovered           
Day 8:  400 uL test substance undiluted, occlusive, 48 h
Challenge: Day 21: 25 uL test preparation, 25 - 100 % in different vehicles  24 h
Challenge controls:
Control and test animals received identical treatment.
Positive control substance(s):
yes
Remarks:
Cyclophosphamide

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Group:
other: test chemical (intradermal induction 1% soybean oil)
Dose level:
challenge 100%
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Group:
other: test chemical (intradermal induction 25% soybean oil)
Dose level:
challenge 25% pet.
No. with + reactions:
10
Total no. in group:
12

Any other information on results incl. tables

Guinea pigs exhibited none or slight responses to sensitization with low concentration of 2-Hydroxyethyl methacrylate in the guinea pig maximization test, while 60 -100 % reacted to high concentrations regardless of the vehicle used in induction. The major determinant of the frequency of response was the concentration used for intradermal induction. Positive responses ranged from 0/20 to 9/12 animals.


 


Influence of vehicle and concentration on sentization to 2-hydroxyethylmethacrylate in the guinea pig maximization test


 

































































Intradermal induction


% HEMA in



challenge



25% pet.



25% aq.



25% sbomek



25% sbo



100%



1% sbo



0/20



nt



nt



0/20



0/20



25% sbo



10/12



9/12



10/12



8/12



4/12



25% sbomek



9/10



10/10



9/10



9/10



5/10



1% aq.



4/12



0/12



0/12



0/12



0/12



10% aq.



6/12



4/12



6/12



5/12



4/12



25% aq.



9/12



7/12



7/12



9/12



2/12



sbo = soybean oil; sbomek = soybean oil + 2-butanone (1:2, v/v); aq. = sterile water; pet. = white petrolatum

Applicant's summary and conclusion

Interpretation of results:
sensitising
Conclusions:
The response of guinea pigs to HEMA in the Magnusson-Kligman protocol was highly dependent upon the concentration of HEMA in the vehicle used for intradermal injection. A low concentration of HEMA (1% in either aqueous or oil vehicle did not lead to a sensitization response while high concentrations (25%) in either vehicle did lead to a response in a large proportion of animals.
Executive summary:

Guinea pigs exhibited none or slight responses to sensitization with low concentrations or 2- hydroxyethylmethacrylate in the guinea pig maximization test, while 60-100% reacted to high concentrations regardless of the vehicle used for induction. Petrolatum, water, soybean oil and a mixture of oil and 2-butanone (sbomek) were used as vehicles for elicitation. The neat methacrylate was less effective than dilutions in any vehicle, petrolatum being the best. The major determinant of the frequency or response was the concentration used for intradermal induction. An increase in frequency and in duration of responsiveness after treatment with cyclophospliamide 2 days before challenge suggests that hydroxymethacrylate preferentially stimulates the suppressor cell function.