2-methylaminoethanol

Endpoint summary

Description of key information

Leung and Blaszcak, 1998. The Skin Sensitization Potential of Four Alkylalkanolamines. Publication. Comparable to the OECD guideline 406. 

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

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

not specified

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Intracutaneous in-vivo test with Guinea pigs was performed before the LLNA was set as preferred test method.

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 h 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 chemical

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 chemical

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.

Reading:

1st reading

Hours after challenge:

24

Group:

other: challenge control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: No skin response occured in the irritation control animals treated at the same concentration

Remarks:

.

Reading:

2nd reading

Hours after challenge:

48

Group:

other: challenge control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: No skin response occured in the irritation control animals treated at the same concentration

Remarks:

.

Group:

negative control

Remarks on result:

not measured/tested

Group:

positive control

Remarks on result:

not measured/tested

Interpretation of results:

sensitising

Remarks:

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-methylethanolamine (MMEA) 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-methylethanolamine 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. The failure to observe a response at 48 hours is suggestive of irritation and not sensitisation in these animals. Moreover, no skin response occurred in the irritation control animals treated at the same concentration.

In conclusion, MMEA is considered to have a mild potential to produce skin sensitization in guinea pigs.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

no data

Justification for classification or non-classification

According to the criteria of Classification, Labelling and Packaging of Substances and Mixtures Regulation (EC) No 1272/2008 (CLP Regulation), classification is not warranted.

In the Guinea Pig Maximisation Test, a dermal response to MMEA was observed in 2 of 20 animals (10 %) after 24h but not 48h when challenged with 5 % MMEA, the highest non-irritant concentration determined in a range finding study.

According to tables 3.4.3 and 3.4.4 (section 3.4.2.2.3 of Annex I to CLP Regulation), classification as skin sensitizer is only warranted when at least 30 % of test animals show an allergic response to the test substance in the Guinea Pig Maximisation Test.

Besides the substance is classified as:

GHS:

- Acute toxicity - oral: Cat 4, H302:harmful if swallowed

- Acute toxicity -dermal: Cat 4, H312:harmful in contact with skin.

-Skin Corr.1B, H314:causes severe skin burns and eye damage

- Eye Damage 1:H318:causes serious eye damage.

- STOT SE Cat.3, H335:may cause respiratory irritation, C>=5%

- Repro 2, H361 F/D: Suspected of damaging fertility or the unborn child <state specific effect if known> <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

and

- STOT RE Cat 2,H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>; Affected organs: other: the kidney, testes, epidymides, ovaries, liver, and spleen).