2-hydroxyethyl methacrylate

Skin sensitisation

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

Test material information

Constituent 1

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)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: soybean oil; soybean oil + 2-butanone; sterile water

Induction 2

Concentration / amount:

1% soybean oil, 25% soybean oil, 25% soybean oil+2-butanone, 1% aqueous, 10% aqueous, 25% aqueous

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: soybean oil; soybean oil + 2-butanone; sterile water

Challenge 2

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)

Results

Results 1

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

Results 2

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.