Registration Dossier

Administrative data

Description of key information

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
no
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Animals of weight range 340-458 g (males) and 312-439 g(females)
Route:
intradermal and epicutaneous
Vehicle:
other: Saline (0.9%) or ethanol (70%)
Concentration / amount:
the test substance was used undiluted
Route:
epicutaneous, occlusive
Vehicle:
other: Saline (0.9%) or ethanol (70%)
Concentration / amount:
the test substance was used undiluted
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
Range findings study was conducted to select appropriate concentrations for the intradermal and epicutaneous procedures. At 24 and 48 f after dosing, the intradermal sites were evaluated for severity of tissue damage, and the epicutaneous sites were graded for irritation. The concentration which produced only local tissue damage (i.e. no extensive ulceration) was used for the intradermal induction. The highest concentration that produced only mild irritation was considered appropriate for the epicutaneous induction, and the highest concentration which did not produce irritation was used for the epicutaneous challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (1 intradermal and 1 epicutaneous)
- Exposure period: 48 hours in case of epicutaneous induction
- Test groups: 0.1 mL intradermal injections:
1. 50% (v/v) Freund's Complete Adjuvant (FCA) wate emulsion
2. The test material in propylene glycol
3. The test material in FCA/water.
- Duration: epicutaneous induction was performed 7 days after the intradermal induction: The test material (undiluted, or diluted with 0.9% saline or 70% ethanol) was applied to saturation (0.2 mL) to a 2x4 cm filter paper, which was then placed on thetest side and secured with tape.

- Site: 2 sites each of clipped shoulder skin:

- Concentrations: 5% in propylene glycol for the intradermal induction and 25% for the epicutaneous induction

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after epicutaneous induction (21 day from initiation of the study).
- Exposure period: 24 hours
- Test groups: 10 males and 10 females
- Control group:5 males and 5 females received the same challenge proceduresas in the definitive sensitization study, but were treated with only the vehicle and/or FCA/water emulsion during the intradermal and/or epicutaneous induction proc edures. This allows differentiation between primary skin irritation due to the test material and that produced by a hypersensitivity reaction.
- Site: previously untreated site (right flank) by applying 2x2 cm filter paper squares soaked in the appropriate concentration of the test material
- Concentrations: 5% in propylene glycol
- Evaluation (hr after challenge): 24 and 48

OTHER:
Challenge controls:
5 males and 5 females received the same challenge procedures as in the definitive sensitization study, but were treated with only the vehicle and/or FCA/water emulsion during the intradermal and/or epicutaneous induction procedures. This allows differentiation between primary skin irritation due to the test material and that produced by a hypersensitivity reaction.
Positive control substance(s):
not required
Positive control results:
No skin response
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5% in propylene glycol
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
slight, well-defined erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% in propylene glycol. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: slight, well-defined erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5% in propylene glycol
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% in propylene glycol. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.
Interpretation of results:
sensitising
Remarks:
Migrated information according to the authors
Conclusions:
As postulated by the authors, N-methylethanolamine showed potential to induce allergic contact dermatitis.
Executive summary:

The skin sensitization potential of N-methyethanolamine was evaluated in a guinea pig maximation procedure by the method of Magnusson and Kligman. Eighteen of the 20 animals challenged with a 5% concentration of MMEA were free of skin response, and the 2 remaining animals had clear skin response (scores of 1) at 24 h but not at 48 h following dosing. No skin response occured in the irritation control animals treated at the same concentration.

MMEA is considered to have sensitization potential.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitization potential of N-methyethanolamine was evaluated in a guinea pig maximization procedure by the method of Magnusson and Kligman (Leung and BlaszcaK, 1998). Pretest screening allowed the selection of test concentrations for induction and challenge phases. Intradermal injection of 5 % MMEA in propylene glycol produced only minor local reaction, 25 % MMEA was the highest concentration that produced only mild irritation and was used for the epicutaneous induction. 5 % of MMEA was the highest concentration which did not produce irritation and was used for the epicutaneous challenge. Eighteen of the 20 animals challenged with a 5 % concentration of MMEA were free of skin response, and the 2 remaining animals had clear skin response (scores of 1) at 24 h but not at 48 h following dosing. No skin response occurred in the irritation control animals treated at the same concentration. MMEA is considered to have a mild potential to produce skin sensitization in guinea pigs.


Migrated from Short description of key information:
Leung and Blaszcak, 1998. The Skin Sensitization Potential of Four Alkylalkanolamines. Publication. Comparable to the OECD guideline 406.

Justification for selection of skin sensitisation endpoint:
Only one study is available

Respiratory sensitisation

Endpoint conclusion
Additional information:
Migrated from Short description of key information:
no data

Justification for classification or non-classification

The classification is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulations No 1272/2008. According to the table 3.4.2.3.4. in the Guidance on the Application of Regulation (EC) No. 1272/2008, MMEA does not possess a significant skin sensitizing effect, since the positive response was seen only in two out of twenty animals (10%) instead of 30 % and more. Moreover, the concentration for intradermal induction used (properly chosen, according to the OECD guideline 406) was 5 %, while specific concentration limit is fixed up to 1 % (Table 3.4.2.3.4.2.).