Registration Dossier

Administrative data

Description of key information

Based on several studies the test substance is not regarded as irritating to eyes and 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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
The test procedure was based on the description in the Code of Federal Regulations 16 (commercial practices) Chapter II, part 1500.41, January 1, 1977.
Six male albino rabbits were treated with test substance at two abraded and two intact sites of the skin. After 24 hours the occluded patch was removed and the first reading was done. After 72 hours the second reading was performed and the primary dermal irritation index was determined.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Weight: 2 - 2.5 kg
Individual housing.
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact
Vehicle:
water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
24 hour
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE:
Four areas, two on each side of the rabbit´s back, approximately 10 cm apart, were utilized for substance administration. The hair on the backs of the animals was removed with an electric clipper. Two of the four sites were abraded, two were left intact. Abrations were made with a 24-gauge hypodermic needle and consisted of three superficial incisions 1 cm long and 0.5 cm apart. Abrasions were made to the stratum corneum.

EXPOSURE:
0.5 g of solid test substance was applied directly to a coverlet, dissolved in water and applied using a surgical gauze pad (1"x1"). The entire trunk was wrapped with an impervious material for the 24-h exposure period.

READING:
After 24 h the patches were removed and remained off for the duration of the experiment. Readings were performed 1, 24 and 72h following the exposure period.

INTERPRETATION:
An average irritation score was calculated for intact and abraded skin by adding the total irritation scores at 24 and 72 divided by the number of values. The primary dermal irritation index was determined by averaging the average irritation scores of the intact and abraded skin.
Two negative (blank preparation and destilled water) and a positive control (5% sodium lauryl sulfate) were also tested.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 h
Score:
0.08
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
0.17
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
The PDII reveals a mild irritating effect of the test substance. The effect was only observed in abraded skin. However, a similar mildly irritating effect was observed in control animals on abraded skin.
The positive control (sodium lauryl sulfate) resulted in severe skin irritation on intact and abraded skin (PDII 6 or 5.5).

MDA did not cause dermal irritation on New Zeeland albino rabbits after topical application.

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
The procedure conforms to that described in the Code of Federal Regulations 16 Commercial practices Chapter II, part 1500.42, January 1, 1977. Six albino New Zealand rabbits were used for each test substance. One hour prior to instillation of the test substance, the ocular irritation grades were determined using a modified Draize grading system for ocular lesions. In addition both eyes of each rabbit were stained with 2% sodium fluorescein and examined to confirm the absence of corneal lesions. 0.1 mL of flake was placed in one eye of the animals. The eyes are examined at 24, 48, and 72 hours.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
the eyes remained unwashed
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no


SCORING SYSTEM: Draize scoring


TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No irritation responses were observed in the control eyes. Details on irritation responses in the exposed eyes are reported in table 1.

Table 1: Draize scoring of ocular irritation after treatment with test substance

Time point

 

Observations

 

Animal No

1

2

3

4

5

6

24 h

Cornea

0

0

2

2

1

1

Iris

0

0

0

0

0

0

Conjunctivae

2

2

2

2

2

2

Chemosis

1

1

1

1

1

1

48 h

 

 

 

Cornea

0

0

1

1

1

1

Iris

0

0

0

0

0

0

Conjunctivae

1

1

2

2

2

1

Chemosis

0

0

1

1

1

0

72 h

 

 

Cornea

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctivae

0

0

0

0

0

1

Chemosis

0

0

0

0

0

0

Mean

(24-48-72 h)

Cornea

0.0

0.0

1.0

1.0

0.67

0.67

Iris

0.0

0.0

0.0

0.0

0.0

0.0

Conjunctivae

1.0

1.0

1.33

1.33

1.33

1.33

Chemosis

0.33

0.33

0.67

0.67

0.67

0.67

Mean (24-48-72 h) for all 6 rabbits

Cornea

0.56

Iris

0.0

Conjunctivae

1.22

Chemosis

0.56

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In summary, the available animal data on irritation/corrosion is dated, and no full GLP/OECD guideline study is available. Nevertheless, taken together, the information is sufficient to conclude that classification for irritation is not warranted..

Skin irritation:

In the key study (performed according to CFR 16, II, 1500.41), MDA (0.5 g) did not cause erythema or edema on intact skin under occlusive conditions (Draize score = 0). Mild erythema was observed on abraded skin (draize score = 0.17) which was fully reversible within 72 h (Allied Chemical Corp, 1978). According to EU and GHS standards, no classification is required for skin irritation/corrosion.

Similar results were observed a supporting study with mean Draize scores of 0.5 for erythema on intact skin. This mild effect was fully reversible within 72 h (Huntsman, 1973).

Additionally, a short report is available in which MDA was estimated to be not irritating (Dow, 1954). Undiluted MDA was tested on intact and abraded skin in 1 animal each. Very slight scaliness was described on the intact skin, and slight reversible hyperemia was observed on the abraded skin. Furthermore, in an insufficiently reported study by BASF (1956), no more than slight reversible erythema was observed on the skin of rabbits exposed to various dilutions of MDA. The reported data were not sufficient to derive appropriate Draize scores.

 

In summary, animal data indicate that there is no need for classification of MDA as an irritant to the skin according to EU- and GHS-directives. Human data on irritating effects to skin are not available.

 

Eye irritation:

In a eye irritation study (performed according to CFR 16, II, 1500.41) only mild eye reaction was observed in rabbits following instillation of 100 mg MDA into the conjunctival sac. The effects were fully reversible within 72 hours in 5 out of 6 animals (Allied Chemical Corporation, 1978).

Similar mild eye reactions were observed in a supporting study with 100 mg MDA. Following application into the conjunctival sac mild irritation was reversible in 5 of 6 animals, in one animal reversion occurred between day 3 and 7 (Huntsman, 1973).

Additionally a short report is available in which MDA-instillation into the eye of rabbits resulted in a slight transient conjunctivitis (Dow Chemical Corporation, 1954).

BASF (1959) reported slight erythema (scale=1) and bleeding from nictating membrane in rabbit eyes within 48 h observation period. These signs were fully reversible within 7 days. No information was provided for 72 h, so draize scoring was not possible.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled for eye or skin irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.