Registration Dossier

Administrative data

Description of key information

Skin Irritation: BASF AG, 1981. Pruefung der Aetzwirkung von "Methylethanolamin" am Kaninchen nach 4stuendiger, 1stuendiger und 3minuetiger Einwirkungsdauer. Report No. 79/561. Comparable to the OECD guideline 404.
Eye irritation: BASF AG, 1965. Industrial hygiene orientating investigation. Report No. XV/126. Comparable to the OECD guideline 405.
Respiratory irritation: Ballantyne and Leung, 1996. Acute Toxicity and Primary Irritancy of Alkylalkanolamines. Rabbits, 0.005 mL

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 May 1980 - 16 May 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented report which meets the basic scientific principles.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
BASF-Test
Principles of method if other than guideline:
Method: BASF-Test. See further details in remarks on material and methods.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: M. Gaukler, Offenbach, Germany
- Weight at study initiation: 3.5 kg (mean)
- Diet: Ssniff K, standard diet for rabbits and guinea pigs, supplied by INTERMAST GmbH, Soest, Germany, ad libitum.
- Water: tap water ad libitum.

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
3 min, 1h or 4 h
Observation period:
8 days
Number of animals:
4 h application: 1 male and 1 female
1 h application: 2 females
3 min appliction: 2 males
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1:1).
- Time after start of exposure: 3 min, 1 h or 4 h.
Irritation parameter:
erythema score
Remarks:
; 3 min exposure
Basis:
mean
Time point:
other: 24 h - 48 h
Score:
1.25
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: 72 h reading is missing
Irritation parameter:
edema score
Remarks:
; 3 min exposure
Basis:
mean
Time point:
other: 24 h - 48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: 72 h reading is missing
Irritation parameter:
erythema score
Remarks:
; 1 h exposure
Basis:
mean
Time point:
other: 24 h - 48 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: 72 h reading is missing
Irritation parameter:
edema score
Remarks:
; 1 h exposure
Basis:
mean
Time point:
other: 24 h - 48 h
Score:
2.25
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: 72 h reading is missing
Irritation parameter:
erythema score
Remarks:
; 4 h exposure
Basis:
mean
Time point:
other: 24 h - 48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
; irreversible necrosis
Remarks on result:
other: 72 h reading is missing
Irritation parameter:
edema score
Remarks:
; 4 h exposure
Basis:
mean
Time point:
other: 24 h - 48 h
Score:
2.5
Max. score:
4
Reversibility:
not reversible
Remarks:
; irreversible necrosis
Remarks on result:
other: 72 h reading is missing

Mean erythema score after 24 and 48 (72 h reading is missing); (animal1/animal2)

   24 h  48 h  72 h  mean  
 3 min  1/2 1/1  -/-  1/1.5  
1 h   4/4 4/4   -/-  4/4  
 4 h  4/4 4/4 -/-   4/4  

Mean edema score after 24 and 48 (72 h reading is missing); (animal1/animal2)

   24 h  48 h 72 h  mean  
 3 min  0/2  0/0  -/-  0/1  
 1 h  2/3  2/2  -/-  2/2.5  
 4 h  3/2  2/2  -/-  2.5/2  

3 min exposure: 24 h after application slight erythema was observed and 1 animal showed distinct edema. At the end of the observation period of 8 days the irritations eased under scaling.

 

1 h exposure: immediately after exposure wide spanning erythema and distinct spanning edema were observed. After 24 h parchment-like necrosis was noted. At the end of the observation period of 8 days, persistent edema and leathery-like necrosis was observed. This is considered to be a full thickness necrosis.

 

4 h exposure: immediately after exposure necrosis and wide spanning edema was noted. At the end of the observation period of 8 days irreversible necrosis was observed. This is considered to be a full thickness necrosis.

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Test substance is corrosive
Executive summary:

Test substance is corrosive

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 Jun 1965 - 23 Jun 1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented report which meets basic scientific principles
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
BASF-Test
Principles of method if other than guideline:
Method: BASF-Test. See further details in remarks on materials and methods.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.8 and 3.0 kg
Vehicle:
unchanged (no vehicle)
Controls:
other: The adjacent eye served as control treated with 0.9 % NaCl (saline).
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µl
Duration of treatment / exposure:
single application
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h - 72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 48 h reading is missing
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h - 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 48 h reading is missing
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
other: 48 h reading is missing

Findings animal1/animal2:

 Time Opacity  Iritis  Erythema Chemosis              
1h 3/3 0/0 x/x  0/0              
24h 3/3 0/0 x/x 4/4              
48h  -/- -/- -/- -/-              
72h 3/3 0/0 x/x 4/4              
 8d  3/3 0/0 x/x 4/4              

-: The 48 h reading is missing.

x: a precise evaluation of erythema score was not possible.

Mean values over 24 h and 72 h (48 h reading is missing):

Animal1: Opacity: 3; Chemosis: 4; Erythema: x; Iritis: 0

Animal2: Opacity: 3; Chemosis: 4; Erythema: x; Iritis: 0

The application of the test substance caused within 10 minutes severe corneal opacity and corrosions of the mucous membrane. After 3 days purulent exsudate was noted. At the end of the observation period of 8 days symptoms were still persistent. Severe corneal opacity is considered to be irreversible effect to ophthalmic tissue.

 

The original BASF grading was converted into the numerical grading according to the OECD Draize system.

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is corrosive
Executive summary:

The test substance is corrosive

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

Skin irritation by MMEA has been tested in several studies.

In an irritation study (BASF, 1981), three animals were treated for 3 min, 1 h or 4 h using occlusive conditions. An application site of 2.5x2.5 cm was covered with the liquid test substance (0.5 ml). After the application time the skin was washed with Lutrol (conc.) and Lutrol/water (1:1). The animals were observed for 8 days and skin changes were recorded daily. The following outcomes were observed:
3 min exposure: 24 h after application slight erythema was observed and 1 animal showed distinct edema. At the end of the observation period of 8 days the irritations eased under scaling.
1-hour exposure: immediately after exposure wide spanning erythema and distinct spanning edema were observed. After 24 h parchment-like necrosis was noted. At the end of the observation period of 8 days, persistent edema and leathery-like necrosis was observed. This is considered to be a full thickness necrosis.
4-hour exposure: immediately after exposure necrosis and wide spanning edema was noted. At the end of the observation period of 8 days irreversible necrosis was observed. This is considered to be a full thickness necrosis.

Other dermal irritation studies confirmed these findings. MMEA was highly irritating to the skin after short dermal contact (1, 3 and 5 min) and corrosive after 15 min and longer ( BASF AG, 1966; Ballantyne and Leung, 1996).

Eye irritation

Eye irritation by MMEA has been tested in two studies. 50 µl of the test substance were applied to the conjunctival sac of one eye in 2 animals (BASF AG, 1966). The animals were observed after 10 min, 1 hour and 3 hours on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours as specified in OECD Guideline 405.
The application of the test substance caused within 10 minutes severe corneal opacity and corrosions of the mucous membrane. After 3 days purulent exudate was noted. At the end of the observation period of 8 days symptoms were still persistent. Severe corneal opacity is considered to be irreversible effect to ophthalmic tissue.
Ballantyne and Leung described MMEA as highly irritating to the rabbit eyes (Ballantyne and Leung, 1996). Severe eye irritating effects were produced by small volume (0.005 mL) contamination of the eye with MMEA. This agrees with that known irritating and corrosive effects on the skin. The conjunctivae became severely hyperemic and edematous within 1 hour of contaminating the eye with an associated profuse discharge. The effects remained unchanged until the end of inspection period (21 days). The cornea became moderately to severely opaque within 1 hour, affecting ¾ to the whole of the cornea. All corneas became severely opaque over the whole of their surface by 7 days and persisted as such up to the final inspection. Other effects were necrotic areas in the conjunctivae and nictitating membrane by 4hour post-application, corneal neovascularisation by 7 days and corneal ulceration by 14 days. The iris could not be inspected due to the marked keratitis.

Respiratory irritation

Based on the results of the acute toxicity and irritation studies and taken into account physical-chemical properties of MMEA (high pH value), there is sufficient reason to suppose that the test substance might exhibit a respiratory hazard. In the acute inhalation study, eye and nose discharge were observed in animals, inhaled by MMEA during 8 hours (BASF, 1965, XV/126). Ballantyne and Leung did not anticipate adverse effects from exposure to low vapour concentrations that may develop from MMEA (Ballantyne and Leung, 1996).


Justification for selection of skin irritation / corrosion endpoint:
The most reliable similar to OECD 404 study

Justification for selection of eye irritation endpoint:
The most reliable similar to OECD 405 study

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

The classification is 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.

DSD: C, R.34 Corrosive, causes burns

GHS: Skin Corr.1B