2-dimethylaminoethyl methacrylate

Endpoint summary

Description of key information

In a reliable study, the substance was found to be weak skin sensitizer.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Test was performed before non-animal testing became current priority.

Specific details on test material used for the study:

TEST MATERIAL:
- Name of test material (as cited in study report): Dimethylaminoethyl methacrylate (MADAME)

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Shamrock Bio Service breeding centre (78950 Gambais, France)
- Weight at study initiation: mean males 361±13, mean females 344±19
- Housing: individually in sterilizable polycarbonate cages (48 x 27 x 20 cm)
- Diet: certified pellet diet "Guinea-pigs sustenance ref. 106" (U.A.R. 91360 Villemoisson-sur-Orge, France) ad libitum
- Water: filtered water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light): 12 / 12

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Concentration / amount:

Intradermal induction: 0.1 mL with a concentration of 1%
Epicutaneous induction: 0.5 mL with a concentration of 25%
Challenge: 0.5 mL with a concentration of 5%

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

Intradermal induction: 0.1 mL with a concentration of 1%
Epicutaneous induction: 0.5 mL with a concentration of 25%
Challenge: 0.5 mL with a concentration of 5%

No. of animals per dose:

Vehicle control group: 5 males and 5 females
Treated group: 10 males and 10 females

Details on study design:

- INDUCTION EXPOSURE (10 days)
Induction by intradermal route: On day 1, three doses of 0.1 ml were injected into each side of the spine on 4 x 2 cm of the scapular area. In the first set of injections, the animals of both groups received Freund's complete adjuvant at 50% in an isotonic injectable solution of 0.9% NaCl. In the second set of injections, the animals of the control group received the vehicle only while the animals of the treated group received the TS at 1% suspended in the vehicle. The third set of injections was a mixed solution 50/50 (v/v) of Freund's complete adjuvant at 50% in an isotonic injectable solution of 0.9% NaCl and the vehicle given to the control animals, or the TS at 1% in its vehicle to the treated animals.

Induction by cutaneous route: As the TS showed irritant characteristics at the concentration of 25% in the vehicle by cutaneous application under an occlusive dressing during the preliminary test, a local irritation was not necessary on day 7. On day 8, 0.5 ml of the vehicle in the control group or 0.5 ml of the TS at 25% in the treated group were applied to the scapular region of the animals and were held in contact with the skin for 48 hours by means of an occlusive dressing. One hour after removal of the occlusive dressing, the cutaneous reactions were recorded.

- REST PERIOD (12 days)

- CHALLENGE EXPOSURE
On day 22, the animals from both groups received an application of 0.5 ml of the TS at the concentration of 5% in vehicle on an area of 4 cm² on the posterior right flank and 0.5 ml of the vehicle on the posterior left flank. This application was prepared using a sterile 1 ml glass syringe on a 4 cm²sterile patch. An adhesive hypoallergic dressing and an adhesive anallergic plastic waterproof plaster were then placed around the animals' trunk in order to cover the TS for 24 hours. Twenty-four and 48 hours after removal of the occlusive dressing, the flanks of the animals were observed in order to evaluate any cutaneous reactions. After the final scoring period, the animals were sacrificed and cutaneous samples were taken from the challenge application sites in all surviving animals. Due to the absence of "doubtful" macroscopic cutaneous reactions, no histological examination was performed.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

16

Total no. in group:

20

Clinical observations:

Very slight edema (score 1).

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 16.0. Total no. in groups: 20.0. Clinical observations: Very slight edema (score 1)..

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Reactions observed at the 24 hrs reading were reversible at the 48 hrs scoring period.

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Reactions observed at the 24 hrs reading were reversible at the 48 hrs scoring period..

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Group:

positive control

Remarks on result:

not measured/tested

The general behaviour and the body weight gain of the animals were not influenced by the treatment. After the challenge cutaneous application of the test substance, a very slight erythema (score 1) was observed on the right flank of 16 out of 20 treated animals. As the cutaneous reactions were very slight and the reactions observed at the 24 hrs scoring period were reversible at the 48 hrs scoring period, the cutaneous reactions were attributed to autoreactive effects. In both readings, no oedema were observed. No cutaneous reactions likely to be caused by the sensitization potential of this test substance were observed.

Macroscopic examinations of the cutaneous reactions:

 

Group	Sex	Erythema score	Scoring of the cutaneous parameters
			24 hours		48 hours
			LF	RF	LF	RF
Control	male	0	5/5	5/5	5/5	5/5
Treated	male	0	10/10	2/10	10/10	10/10
		1		8/10
Control	female	0	5/5	5/5	5/5	5/5
Treated	female	0	10/10	2/10	10/10	10/10
		1		8/10

LF = left flank (untreated); RF = right flank (treated); erythema score: 0 = no erythema, 1 = very slight erythema, 2 = well-defined erythema, 3 = moderate to severe erythema, 4 = severe erythema to slight eschar formation

Interpretation of results:

other:

Remarks:

RECENT RE-EVALUATION OF THE STUDY INDICATED A SENSITISING POTENTIAL.

Conclusions:

No cutaneous reactions likely to have been caused by the sensitization potential of the test substance were observed in guinea-pigs.
RECENT RE-EVALUATION OF THE STUDY INDICATED A SENSITISING POTENTIAL.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

There was only one study available for assessment. The sensitising potential of the test substance was evaluated by a Guinea Pig Maximazation Test (modified Magnusson and Kligman method) according to OECD guideline No. 406 in compliance with GLP and was identified as the key study (Atochem, 1991). The general behaviour and the body weight gain of the animals were not influenced by the treatment. After the challenge test, a very slight erythema (score 1) was observed on the right flank of 16 out of 20 treated guinea pigs. As the cutaneous reactions were very slight and the reactions observed at the 24 hours scoring timepoint were reversible at the 48 hours scoring timepoint, the cutaneous reactions were attributed to autoreactive effects. No cutaneous reactions likely to be caused by a sensitisation potential of the test substance were observed.

RECENT RE-EVALUATION OF THE STUDY INDICATED A SENSITISING POTENTIAL.

However, according to Annex I of the Directive 67/548/EEC and to Annex VI of EU GHS, the substance is classified as skin sensitiser (R43; Cat. 1).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

There are no data available concerning respiratory sensitisation.

Justification for classification or non-classification

According to the well-conducted GLP guideline key study (OECD TG 406) the test substance is not sensitising to the skin. Therefore, the following classification of the test substance concerning sensitisation is suggested:

GHS classification according to Annex I 1272/2008 CLP (EU GHS):

- Skin sensitisation: No classification.

However, the test substance is listed in Annex I of the Directive 67/548/EEC and in Annex VI 1272/2008 CLP (EU-GHS). Accordingly, in spite of the contradictory database, the test substance has to be classified as follows:

EU classification according to Annex I of the Directive 67/548/EEC:

- Skin sensitisation: May cause sensitisation by skin contact, R43

GHS classification according to Annex VI 1272/2008 CLP (UN GHS):

- Skin sensitisation: Skin sensitiser - Cat. 1