Registration Dossier

Administrative data

Description of key information

The available skin and eye irritation studies with rabbits, performed according to methods similar to OECD guidelines, indicate that MDEA is irritating to eyes, but not to skin.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.9 kg (mean)
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Duration of treatment / exposure:
1, 5, 15 min and 20 h
Observation period:
8 days
Number of animals:
2
Details on study design:
Two animals were treated for 1, 5, 15 min and 20 hours using occlusive conditions. An application site of 2.5x2.5 cm was covered with the liquid test substance. After the application time (1, 5, 15 min) the skin was washed with Lutrol (50%). The animals were observed for 8 days and skin changes were recorded daily. The report describes findings after 24 hours and at the end of the observation period (8 days). For a final evaluation, the findings after 48 and 72 hours from the raw data were taken into account.

TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 1, 5 and 15 min
Irritation parameter:
erythema score
Remarks:
1, 5 and 15 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
1, 5 and 15 min
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
1, 5 and 15 min
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Remarks:
1, 5 and 15 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Remarks:
1, 5 and 15 min
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Remarks:
1, 5 and 15 min
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
20 h exposure
Basis:
mean
Time point:
24/48/72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
erythema score
Remarks:
20 h exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Irritation parameter:
erythema score
Remarks:
20 h exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Irritation parameter:
edema score
Remarks:
20 h exposure
Basis:
mean
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
20 h exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Irritation parameter:
edema score
Remarks:
20 h exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Application of undiluted methyldiethanolamine to rabbit skin did not produce reactions after periods of 1 to 15 minutes but wide spanning reddening of the whole dorsal skin area and at the end of the observation period scale formation were reported in one animal after 20 hours contact with the substance.

Mean erythema score after 24, 48 h and 72 h (animal 1/animal 2):

   24 h  48 h  72 h  mean  
 1 min  0/0 0/0 0/0  0/0  
 5 min  0/0 0/0 0/0  0/0  
 15 min  0/0  0/0  0/0 0/0   
 20 h  3/2  3/2  3/2  3/2  

Mean edema score after 24, 48 h and 72 h (animal 1/animal 2):

   24 h  48 h  72 h  mean  
 1 min 0/0 0/0 0/0  0/0  
 5 min 0/0 0/0 0/0  0/0  
 15 min  0/0  0/0  0/0  0/0  
 20 h  3/0  3/0  2/0  2.6/0  

Application of undiluted methyldiethanolamine to rabbit skin did not produce reactions after periods of 1 to 15 minutes but wide spanning reddening of the whole dorsal skin area and at the end of the observation period scale formation were reported in one animal after 20 hours contact with the substance.

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

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5 kg (mean)
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: 50 µL
Duration of treatment / exposure:
single application - eyes were not washed out
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Details on study design:
50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3 h 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.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Irritant / corrosive response data:
In the rabbit eye, 50 μL undiluted methyldiethanolamine caused redness, swelling and clouding of the cornea as well as conjunctival bleeding. The symptoms had disappeared after 8 days.

Table 1: Findings animal1/animal2:

 Time     Conjunctiva   

Opacity 

Iritis

Erythema

Chemosis

1 h

3/3

0/0

2/2

2/2

24 h

1/1

0/0

2/2

1/1

48 h

1/1

0/0

2/2

1/1

72 h

1/1

0/0

1/1

0/0

8 days

 0/0

 0/0

 0/0

 0/0

Mean values over 24, 48, and 72 h:

Animal1: Opacity: 1; Iritis: 0; Erythema: 1.7; Chemosis: 0.7

Animal2: Opacity: 1; Iritis: 0; Erythema: 1.7; Chemosis: 0.7

In the rabbit eye, 50 μL undiluted methyldiethanolamine caused redness, swelling and clouding of the cornea as well as conjunctival bleeding. The symptoms had disappeared after 8 days.

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

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

A patch test with two rabbits treated with MDEA for 1, 5, 15 min or 20 h under occlusive conditions is available (similar to OECD 404, non-GLP). Application of undiluted MDEA to rabbit skin did not produce reactions after periods of 1 to 15 minutes but wide spanning reddening of the whole dorsal skin area and at the end of the observation period scale formation were reported in one animal after 20 hours contact with the substance (BASF AG, 1969). The mean erythema and edema scores after 20 hours contact for 24, 48 and 72 hours were 2.5 and 1.3, respectively. It should be noted that 20 hours exposure is relatively long compared to the prescribed 4 hours in the guideline. Furthermore, the observation period was only 8 days.

In another skin irritation study (Ballantyne and Leung, 1996b), also similar to OECD 404, erythema and edema mean scores (24, 48 and 72 hours) of 0.2 were observed after occlusive application for 4 hours. The effects were fully reversible within 72 hours.

Eye irritation

A study with 2 rabbits treated with MDEA is available for assessment (similar to OECD 405, non-GLP). A volume of 50 µL was instilled in the rabbit’s eyes and the animals were observed up to 8 days afterwards. Observations at 24, 48 and 72 h revealed redness, swelling and clouding of the cornea as well as conjunctival bleeding. The symptoms had disappeared after 8 days. Mean irritation scores over 24, 48, and 72 hours were 1 for opacity, 0 for iritis, 1.7 for erythema and 0.7 for chemosis (BASF AG, 1969).

 


Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The substance is not considered to be classified for skin irritation but has to be classified for eye irritation Cat.2 (H319: “ Causes serious eye damage”) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.