Mecrilate

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: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1983

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Various methods tested

GLP compliance:

not specified

Type of study:

other: Polak method / Split adjuvant method / Maximization method / Epicutaneous methods

Justification for non-LLNA method:

Historical data before LLNA method was implemented

Test material

Test material information

Constituent 1

Reference substance name:

Mecrilate

EC Number:

205-275-2

EC Name:

Mecrilate

Cas Number:

137-05-3

Molecular formula:

C5H5NO2

IUPAC Name:

methyl 2-cyanoprop-2-enoate

Test material form:

other: emulsion or solution

Details on test material:

Different acrylic compounds have been tested in this study:

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

ANIMALS:

Outbred Hartley strain guinea-pigs of either sex weighing 400-500 g were used. The animals were from stocks bred either at the Royal College of Surgeons or from David Hall, Newchurch, Staffordshire, England. The animals were fed a Labsure RGP diet (F. Dixon & Son, Ware, Hertfordshire) liberally supplemented with cabbage and hay.

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: ethanol/saline

Concentration / amount:

See "Any other information on materials and methods"

Day(s)/duration:

See "Any other information on materials and methods"

Challenge

No.:

#1

Route:

intradermal and epicutaneous

Vehicle:

other: ethanol/saline

Concentration / amount:

See "Any other information on materials and methods"

Day(s)/duration:

See "Any other information on materials and methods"

Details on study design:

See "Any other information on materials and methods"

Results and discussion

Positive control results:

no data

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

other: Depending on test method

Hours after challenge:

48

Group:

test chemical

Dose level:

Depending on test method

No. with + reactions:

0

Remarks on result:

no indication of skin sensitisation

Results 2

Reading:

other: Not reported

Group:

negative control

Remarks on result:

not measured/tested

Results 3

Reading:

other: Not reported

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

RESULTS

Previous work has shown that, in our hands, the Polak method of sensitization was better than the maximization or split adjuvant methods in

inducing sensitivity to the metals nickel and zirconium. Consequently, attempts were made, using the Polak method, to sensitize guinea pigs to 21 different acrylic compounds.

Table 1 Iists the chemicals that induced contact sensitivity to a non-irritant skin test dose. As can be seen, from the time of the first positive skin test, acrylic acid, tripropylene glycol diacrylate and pentaerythritol triacrylate (PETA) appeared to be not as strong sensitizers as the other 5 compounds. This difference could, however, be the result of using different molar concentrations.

TABLE 1: Contact skin reactions in guinea pigs immunized by the Polak method:

Compound	No. of animals	Time of first positive skin test
Acrylic acid	6	28 days
Methyl acrylate	15	7 days
Butyl acrylate	11	7 days
2 -ethyl hexyl acrylate	6	7 days
1 -6 -hexanediol diacrylate	6	7 days
Tripropylene glycol diacrylate	6	28 days
Trimethylol propane triacrylate	11	7 days
Pentaerythritol triacrylate	6	14 days

Below listed are the chemicals that, during the 3 months of the experiment. never induced a contact sensitivity skin reaction to the immunizing chemical:

Methacrylic acid

Trichloracrylic acid

Methyl methacrylate

Butyl methacrylate

2-hydroxyethyl methacrylate

Tetrahydrofurfuryl methacrylate

Ethoxy ethyl methacrylate

Allyl methacrylate

Triethylene glycol dimethacrylate

Ethylene glycol dimethacrylate

Trimethyl propane trimethacrylate

Methyl cyanoacrylate

Butyl cyanoacrylate

Attempts were made to sensitize guinea pigs to methyl and butyl acrylate and methyl methacrylate using the split adjuvant and maximization

techniques. Although the contact skin reactions were not as strong as when the animals were immunized using the Polak method, all the guinea pigs immunized by the split adjuvant method, showed positive reactions to butyl acrylate and 4 out of 6 to methyl acrylate on the first skin test.

Using the maximization method, 30% of the animals developed contact reactions to methyl acrylate on day 21. This did not increase with subsequent skin testing. Again, it was not possible to induce contact sensitivity skin reactions to methyl methacrylate using either immunization

protocol. Because of reports that the methacrylates are volatile, closed patch tests were performed on occasions, but this still did not induce positive skin reactions.

Contact reactions develop in humans due to continuous and repeated exposure to the acrylic compound through the skin. In consequence, 2

methods of epicutaneous sensitization were developed which involved repeated exposure to the chemical. The epicutaneous method A, which involved a total of 6 exposures, was not able to induce contact skin reactions even to methyl acrylate. However. epicutaneous method B induced good contact sensitivity to both trimethylol propane triacrylate and pentaerythritol triacrylate. 4 out of 6 guinea pigs were also sensitized to methyl acrylate and 3 out of 6 to butyl acrylate using this method. Again, it was not possible, in this laboratory, to induce contact reactions to methyl methacrylate even when in one experiment the animals were exposed to methyl methacrylate for 3 weeks (15 exposures) instead of 2 weeks.

ADDENDUM

A recent paper by Van der Walle el aI. (Contact Dermatitis 8, 223 -235, 1982) reports the successful induction of contact sensitivity skin reactions to methyl methacrylate in guinea pigs. Using the guinea pig maximization test and a Freund's complete adjuvant test, they induced contact reactions in 2 out of 10 and 2 out of 8 guinea pigs respectively. The reason for this difference could be that Van der Walle and his colleagues immunized each guinea pig with either 25 or 20 mg of methyl methacrylate, whereas in this study between 250 µg and 4 mg of the chemical per animal were used in the intradermal immunization procedures.

Evidently, if sufficient chemical is used for immunization, a % of guinea pigs will give contact sensitivity reactions to methyl methacrylate.

However, it does not sensitize guinea pigs as easily as do the comparable acrylate compounds.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Methyl cyanoacrylate did not induce contact sensitivity in the respective tests.

Executive summary:

SUMMARY

Beside butyl cyanoacrylate, many different acrylic compounds have been tested using various methods:

- Polak method

- Split adjuvant method

- Maximization method (modified)

- Epicutaneous methods (Levene and Draize (modified))

Methyl cyanoacrylate did not induce contact sensitivity in these tests.