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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 MEA is corrosive to the skin and leads to irreversible eye damage.

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
Vienna White
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
1, 5, 15 min, 20 hrs
Observation period:
8 days
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 1, 5 and 15 min, respectively

SCORING SYSTEM: The original scoring system was converted into Draize scores
Irritation parameter:
erythema score
Remarks:
1 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
1 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
5 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
5 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
0.16
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Remarks:
15 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
1.83
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
15 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Remarks:
20 hr exposure
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Remarks:
20 hr exposure
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Other effects:
bleedings and necrosis of the skin

 

Readings

Animal

Exposure period: 1 min

Erythema

Edema

Additional findings

1 min

1

2

0

spotted appearance

2

0

0

 

24 h

1

2

0

spotted appearance

2

1

0

 

48 h

1

2

0

spotted appearance

2

1

0

 

72 h

1

2

0

spotted appearance

2

0

0

 

8 d

1

0

0

slight desquamation

2

0

0

 

Mean 24, 48, 72 h

1

2

0

 

2

0.66

0

 

Mean 24, 48, 72 h

1-2

1.33

0

 

 

Readings

Animal

Exposure period: 5 min

Erythema

Edema

Additional findings

5 min

1

2

0

pea-sized spotted erythema, bleedings

2

3

0

bleedings

24 h

1

2

0

spotted appearance

2

2

2

grey-brown appearance

48 h

1

2

0

spotted appearance

2

0

0

leather-like necrosis

72 h

1

2

0

spotted appearance

2

0

0

brown-red leather-like necrosis, partly anaemic

8 d

1

0

0

pea-sized crusts, desquamation

2

0

0

brown-red leather-like necrosis, partly anaemic

Mean 24, 48, 72 h

1

2

0

 

2

1

0.33

 

Mean 24, 48, 72 h

1-2

1.5

0.16

 

 

Readings

Animal

Exposure period: 15 min

Erythema

Edema

Additional findings

15 min

1

2

0

bleedings

2

3

0

bleedings

24 h

1

2

2

pea-sized brown erythema

2

2

0

grey-brown spotted appearance, bleedings

48 h

1

2

2

pea-sized brown erythema

2

0

0

leather-like anaemic necrosis exceeding area of exposure

72 h

1

3

0

pea-sized crusts, spotted appearance

2

0

0

brown-red leather-like necrosis, partly anaemic

8 d

1

0

0

pea-sized crusts, desquamation

2

0

0

brown-red leather-like necrosis, partly anaemic

Mean 24, 48, 72 h

1

2

1.33

 

2

1.66

0

 

Mean 24, 48, 72 h

1-2

1.83

0.66

 

 

Readings

Animal

Exposure period: 20 hours

Erythema

Edema

Additional findings

24 h

1

3

2

grey-brown, exceeding area of exposure

2

3

2

grey-brown anaemic necrosis,

48 h

1

3

2

grey-brown, exceeding area of exposure

2

3

0

black brown hard necrosis

72 h

1

3

2

black-brown slideable necrosis

2

3

0

black brown hard necrosis

8 d

1

3

2

black-brown slideable necrosis

2

3

0

black brown hard necrosis

Mean 24, 48, 72 h

1

3

2

 

2

3

0.66

 

Mean 24, 48, 72 h

1-2

3

1.33

 

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
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
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 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
BASF-Test
GLP compliance:
not specified
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.65-2.89 kg
- Diet: ad libitum
- Water: ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
other: adjacent eye (physiological NaCl-solution)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 mL
Duration of treatment / exposure:
not applicable (tests substance was not washed out)
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: none
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Irritant / corrosive response data:
Chemical burnings, scars on upper eyelid, purulent secretion, bloody discharge, conjunctival bleedings, iritis, staphyloma, ciliar injections.

 

Readings

Animal

Cornea

Iris

Conjunctiva

Additional findings

op

ar

red

ch

di

1 h

1

1

-

0

0

0

-

cornea black-red coloured, bloody secretion, constricted pupil, strong secretion

2

3

-

0

0

0

-

cornea black-grey coloured, bloody secretion, constricted pupil, strong secretion

3

3

-

0

0

0

-

cornea brown-red coloured, chemical burnings, brown-red secretion

24 h

1

3

-

0

2

1

-

chemical burnings

2

3

-

0

1

2

 

chemical burnings

3

3

-

0

0

2

-

cornea brown-red coloured, chemical burnings, brown-red secretion

48 h

1

3

-

2

2

1

-

crust formation (eyelids)

2

3

-

-

1

2

-

chemical burning of the eyeball and eyelid

3

3

-

2

0

2

-

purulent secretion

72 h

1

3

-

2

2

0

-

purulent secretion

2

3

-

0

0

0

-

purulent secretion, conjunctiva covered with purulent fur

3

3

-

2

0

2

-

purulent secretion,

8 d

1

3

-

2

2

0

-

purulent secretion

2

3

-

0

0

0

-

loss of hair

3

3

-

2

0

0

-

Staphyloma, ciliar injections, conjunctiva white and chemically burned, scar on upper eyelid

Mean

24 -72 h

1

3

-

1.33

2

0.66

-

 

2

3

-

0

0.66

1.33

-

 

3

3

-

1.33

0

2

-

 

Mean

24-72 h

1-3

3

-

0.88

0.89

1.33

-

 

- endpoint not addressed

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a skin irritation study, performed according to a BASF internal standard operating procedure, exposure to neat MEA under occlusive conditions for 1, 5 and 15 minutes and 20 hours resulted in necrosis (BASF, 1966). Severe damage to skin, including necrosis, was also reported in another study (BASF, 1967), using a similar application protocol.

In another skin irritation test with rabbits performed according to the method similar to OECD guideline 404 but using an occlusive application, after 4 hours application of 20% substance solution in water chemical burns were observed in the two tested animals and the study was terminated (Dow, 1997).

Available eye irritation studies performed according to methods similar to OECD guidelines indicated that the instillation of 5 or 50 μL of neat substance in rabbit eyes caused severe damage to eyes, including severe corneal injury, iritis, bloody discharge, severe conjunctival irritation and necrosis (Union Carbide Corporation, 1988; BASF, 1966). Severe damage to eyes was also observed in another BASF study (BASF, 1967), in which 50 μL of neat substance were instilled in the eyes of 2 rabbits. The instillation of 20% solution of MEA (1 drop/animal) into rabbit eye, with eyes flushed with tap water immediately after the instillation, led to moderate corneal opacity and marked conjunctival swelling and redness. All findings were reversible within 4 days after application (BASF, 1956).

In conclusion, MEA is corrosive to the skin and leads to irreversible eye damage.


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. Based on the results of skin and eye irritation studies with rabbits the test substance has to be classified as Category 1B (H314: "Causes severe skin burns and eye damage") according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.