Ethylene dimethacrylate

Endpoint summary

Description of key information

Based on the available data showing various studies with EGDMA, EGDMA is likely to be a weak skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

now OECD 429 (LLNA local lymph node assay)

Principles of method if other than guideline:

Measurement of lymphocyte proliferative responses that are induced in draining lymph nodes following topical exposure of mice to test substance. An EC3 value is derived; this being the amount of a chemical sensitiser that is required to elicit a 3-fold increase in lymph node cell (LNC) 
proliferative activity.

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 6 to 16 wk-old
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Vehicle:

acetone/olive oil (4:1 v/v)

No. of animals per dose:

4 or 5

Details on study design:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: local lymph node assay (LLNA), standard protocol according to OECD 406
- Criteria used to consider a positive response:
A test material that, at one or more concentrations, causes an stimulation indices (SI) of 3 or greater is considered to have skin-sensitizing activity.

TREATMENT PREPARATION AND ADMINISTRATION:
Groups of mice (n = 4 or 5) are treated by topical a pplication, on the dorsum of both ears, with 25 µL of several concentrations of test material, or with an equal volume of the relevant vehicle alone. They are treated daily for 3 consecutive days, followed by a 2-day rest period before analysis. On the sixth day (5 days after initiation of treatment), the mice are injected intravenously, by the tail vein, with 250 µL of sterile phosphate-buffered saline (PBS) containing 20 µCi of [³H] methyl thymidine. Five hours later, the mice are killed.and the draining auricular lymph nodes are excised and pooled for each experimental group or for each individual animal. Single cell suspensions of lymph node cells are prepared. Lymph node cells are washed twice with an excess of PBS and precipitated with 5% trichloroacetic acid (TCA) at 4°C.The samples, pelleted by centrifugation, are resuspended 12 to 18 hours later in 1 mL of 5% TCA and transferred to 10 mL of scintillation cocktail. lncorporation of tritium­ labeled thymidine [³H-TdR] is measured by beta-scintillation counting and expressed as disintegrations per minute (dpm).

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

mercaptobenzothiazole (CAS No 149-30-4)

other: benzocaine

Key result

Parameter:

EC3

Value:

35

Test group / Remarks:

4 or 5 animals

Remarks on result:

other: extremely weak sensitiser

EC3: 35 % extremely weak sensitiser
EC3 value is the estimated concentration of a chemical necessary to give a 3-fold stimulation of proliferation in lymph nodes compared to concurrent 

vehicle-treated controls.

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Ethyleneglycol dimethacrylate was found to be a extremely weak sensitiser in the LLNA test according to OECD 406 now OECD 429 (EC3: 35 % ).

Executive summary:

In a dermal sensitization study (standard protocol) with Ethyleneglycol dimethacrylate (purity: no data) dissolved in acetone : olive oil (4 +1) as a vehicle, (4 or 5 animals per dose group) 6 to 16 weeks old female CBA/Ca mice were tested using the method of OECD 406 (now OECD 429 Local Lymph node Assay (LLNA)). 

Groups of mice are treated by topical application, on the dorsum of both ears, with 25 µL of several concentrations of test material, or with an equal volume of the relevant vehicle alone. They are treated daily for 3 consecutive days, followed by a 2-day rest period before analysis. On the sixth day (5 days after initiation of treatment), the mice are injected intravenously, by the tail vein, with 250 µL of sterile phosphate-buffered saline (PBS) containing 20 µCi of [³H] methyl thymidine. Five hours later, the mice are killed.and the draining auricular lymph nodes are excised and pooled for each experimental group or for each individual animal. Single cell suspensions of lymph node cells are prepared. Lymph node cells are washed twice with an excess of PBS and precipitated with 5% trichloroacetic acid (TCA) at 4°C. The samples, pelleted by centrifugation, are resuspended 12 to 18 hours later in 1 mL of 5% TCA and transferred to 10 mL of scintillation cocktail. lncorporation of tritium­ labeled thymidine [³H-TdR] is measured by beta-scintillation counting and expressed as disintegrations per minute (dpm).

The validation-/positive control experiment was performed with alpha-Hexyl cinnamic aldehyde, 2 -mercaptobenzothiazole, and benzocaine.

In this study a Stimulation Indice (S.I.) of EC3: 35% was determined with the test item in acetone : olive oil (4 +1), respectively.

Therefore Ethyleneglycol dimethacrylate was found to be a extremely weak sensitiser in the LLNA test according to OECD 406.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

All of the studies with EGDMA were obtained from the open literature and, therefore, have limited information for evaluation. Available studies include studies with (FCA, Polak, GPMT) as well as studies without adjuvant (LLNA, several solvents). The LLNA studies are considered to be the most predictive studies for the endpoint. Based on the weakly, but repeatedly positive findings, it is concluded that EGDMA is likely to be a skin sensitiser.

Justification for selection of skin sensitisation endpoint
Most relevant test system, acceptable reliability and documentation

Compliance to REACh requirements

The requirements are covered with reliable in vivo data, performed with the substance itself and before in vitro testing became current priority.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the positive outcomes of the LLNA assays with EGDMA, EGDMA is considered as weak skin sensitiser category 1B according to regulation (EC) 1272/2008.