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Toxicological information

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991
Reference Type:
publication
Title:
Atochem (1991), Skin Sensitization Test, CIT 7305 TSG
Author:
Atochem
Year:
2003
Bibliographic source:
cited in: OECD SIDS, 2-Dimethylaminoethylmethacrylate, CAS No: 2867-47-2, 07/2003

Materials and methods

Test guideline
Qualifier:
according to
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.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
TEST MATERIAL:
- Name of test material (as cited in study report): Dimethylaminoethyl methacrylate (MADAME)

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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%
Challengeopen allclose all
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.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
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 group
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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.