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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
Study period:
1991-10-28 to 1994-11-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
31 July 1992
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 17 July 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid GPMT conducted according to guideline is available, which is reliable without restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): 2-ethoxyethyl methacrylate, MAEE

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 353±23 g
- Housing: individually in polycarbonate cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 30-70
- Air changes (per hr): app. 12
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
intadermal induction: 10% in paraffin oil
epicutaneous induction: 100%
challenge: 100%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
intadermal induction: 10% in paraffin oil
epicutaneous induction: 100%
challenge: 100%
No. of animals per dose:
10 (test group), 5 (control group)
Details on study design:
RANGE FINDING TESTS:
determination of the minimal irritant concentration which did not provoke necrosis or ulceration by intradermal route: 10%
application by cutaneous route: 100% did not induce local irritation

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal induction
- No. of exposures: 1
- Test groups: test substance, 10% in paraffin oil
- Control group: vehicle
- Site: shoulder region
- Frequency of applications: 1x
- Concentrations:
0.1 mL Freund’s complete adjuvant (FCA)
0.1 mL 10% test substance (or vehicle only in control)
0.1 mL 50:50 mixture of 10% test substance (or vehicle only in control) and FCA

Epicutaneous induction on day 8
- No. of exposures: 1
- Exposure period: 48 h
- Test groups: 100% test substance
- Control group: vehicle
- Site: shoulder region, same as for intradermal injections
- Concentrations: 100% test substance (or vehicle in control)
- pretreatment with 10% sodium laurylsulphate in Vaseline to provoke local skin irritation one day before epicutaneous induction

B. CHALLENGE EXPOSURE on day 22
- No. of exposures: 1
- Day(s) of challenge: day 22
- Exposure period: 24 h
- Test groups: 100% test substance (right), vehicle (left)
- Control group: 100% test substance (right), vehicle (left)
- Site: posterior flanks
- Concentrations: 100%
- Evaluation (hr after challenge): 24 h, 48 h
Challenge controls:
yes, vehicle
Positive control substance(s):
yes
Remarks:
DINITRO 2,4 CHLOROBENZENE

Results and discussion

Positive control results:
The positive control substance Dinitro-2,4-chlorobenzene (performed January 1994) induced positive skin sensitisation reactions in 100% of the guinea-pigs at a concentration of 0.5%.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
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:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5% left flank, 0.1% right flank
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5% left flank, 0.1% right flank
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

No clinical signs or mortalities were observed during the study. The body weight gain of the treated animals was normal when compared to that of the control animals.

At the end of the induction period, on day 10, after removal of the dressing, signs of irritation were observed at the intradermal injection sites in control and treated groups.

No cutaneous reactions were observed 24 and 48 hours after removal of the dressing of the challenge cutaneous application of the test substance.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
ETMA is not a dermal sensitiser in this study.
Executive summary:

In a dermal sensitisation study according to OECD guideline 406, adopted 17 July 1992, and EU method B.6, 31 July 1992, with ETMA (99.94% a.i.), 10 young adult female Dunkin-Hartley guinea pigs were tested using the method of Magnusson & Kligman (Guinea Pig Maximisation Test).

Test concentrations were selected based on pretest results: 10% in paraffin oil was the minimal irritant concentration which did not provoke necrosis or ulceration by intradermal route. 100% was used for topical induction as well as for challenge. As the test substance was not irritating, the skin was preteated with 10% sodium laurylsulphate in Vaseline to provoke local skin irritation prior to epicutaneous induction.

At the end of the induction period, on day 10, after removal of the dressing, signs of irritation were observed at the intradermal injection sites in control and treated groups.

No cutaneous reactions were observed 24 and 48 hours after removal of the dressing of the challenge cutaneous application of the test substance.

The positive control substance Dinitro-2,4-chlorobenzene induced positive skin sensitisation reactions in 100% of the guinea-pigs at a concentration of 0.5%.

ETMA is not a dermal sensitiser in this study.