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Description of key information

The submission substance showed corrosive effects when appplied to the skin of rabbits. When applied to the rabbits´eye the submission substance caused irreversible 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
Study period:
From 27 AUG 1986 to 29 AUG 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to standards
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
observation time: only up to 48 h
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hare Marland, Hewitt, New Jersey, USA
- Age at study initiation: young adult
- Housing: single in suspended, stainless steel, wire-mesh cages
- Diet: Purina certified Rabbit Chow (#5322), ad libitum
- Water, ad libitum
- Acclimation period: not mentioned

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-2
- Humidity (%): 50 +/-10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
not specified
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
3 min
Observation period:
3 min, 24 and 48 h after exposure
Number of animals:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing with warm water and dry patting
- Time after start of exposure: 3 min

SCORING SYSTEM: According to Draize Scale

Irritation parameter:
edema score
Basis:
animal #1
Remarks:
20323
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
20451
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
20452
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
20411
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
20419
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
20421
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
20323
Time point:
other: 3 min and 24/48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
20451
Time point:
other: 3 min, 24/48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
20452
Time point:
other: 3 min, 24/48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
20411
Time point:
other: 3 min, 24/48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
20419
Time point:
other: 3 min, 24/48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
20421
Time point:
other: 3 min, 24/48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
After 3 min, 24 and 48 h necrosis was visible in all six animals. In the 48 h reading blanching of the skin was also visible.
Edema scores in the 3 min reading were 0 for all animals.
Interpretation of results:
Category 1A (corrosive) based on GHS criteria
Conclusions:
Under the applied test conditions the test substance induced skin corrosion in all six animals.
Executive summary:

A skin irritation/corrosion test was performed with six rabbits. The animals were exposed to 0.5 ml of test substance on the clipped skin for 3 minutes. The skin reactions were observed for 48 h after the initial exposure. All six animals showed severe skin corrosion with necrosis and skin blanching. Severe erythema and necrosis already were visible at the first reading time (i.e. 3 minutes).

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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to standards
Principles of method if other than guideline:
Eye irritation/corrosion test
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Albino
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
at least 20 seconds
animal #1: eye washed after 20 sec for 1 min
animal #2: eye washed after 20 sec for 15 min
animal #3: no washing
Observation period (in vivo):
1 and 4 h and 1, 2, 3, 7, 10, 11 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tap water for 1 minute in animal #1 and for 15 minutes in animal #2, but not in animal #3
- Time after start of exposure: 20 seconds

SCORING SYSTEM: no data

TOOL USED TO ASSESS SCORE: hand-slit lamp at all examinations; Fluor-i-strip stain, Hemestix and a biomicroscope were used at examination after the day of treatment
Irritation parameter:
overall irritation score
Remarks:
(descrption of general effects)
Basis:
animal #1
Time point:
other: Eye washed for 1 min after 20 seconds of exposure
Remarks on result:
other: severe corneal irritation with large ulcer, moderate iritis, clouds of precipitate in the anterior chamber, and necrosis of the conjunctiva and outer lids. At ten days the eye appeared shriveled and at 11 days the animal was sacrificed.
Irritation parameter:
overall irritation score
Remarks:
(descrption of general effects)
Basis:
animal #2
Time point:
other: The eye of animal 2 was washed for 15 min after 20 seconds of exposure
Remarks on result:
other: Water washing for 15 min did not lessen the ocular effects. This eye was similar to the one washed for 1 minute.
Irritation parameter:
overall irritation score
Remarks:
(descrption of general effects)
Basis:
animal #3
Time point:
other: The eye of animal 3 was not washed after test item application
Remarks on result:
other: immediate, complete corneal opalescence and necrosis of the conjunctiva and outer lid of the eye. Effects on iris were not seen due to the severity of the corneal irritation; at 1-3 days eye did not react to light, rabbit sacrificed.
Irritant / corrosive response data:
- animal #1: In the eye washed for 1 min the test substance caused severe corneal irritation with large ulcer, moderate iritis, clouds of precipitate in the anterior chamber, and necrosis of the conjunctiva and outer lids. At ten days the eye appeared shriveled and at 11 days the animal was sacrificed.
- animal #2: Water washing for 15 min did not lessen the ocular effects. This eye was similar to the one washed for 1 minute.
- animal #3: test substance caused immediate, complete corneal opalescence and necrosis of the conjunctiva and outer lid in the unwashed rabbit eye. Effects on the iris were not seen due to the severity of the corneal irritation; however, at 1-3 days the eye did not react to light. The rabbit was sacrificed at three days because of the obvious corrosive nature of the test material.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the conditions of the test the test substance is corrosive to the rabbit eye.
Executive summary:

An eye irritation/corrosion test was performed with three rabbits. The animals were exposed to 0.1 ml of test substance. In the first animal (eye washed for 1 min after 20 seconds of exposure) the test substance caused severe corneal irritation with large ulcer, moderate iritis, clouds of precipitate in the anterior chamber, and necrosis of the conjunctiva and outer lids. At ten days the eye appeared shriveled and at 11 days the animal was sacrificed. The eye of animal 2 was washed for 15 min after 20 seconds of exposure, this did not lessen the ocular effects in comparison to animal 1. The eye of animal 3 was not washed after test item application. The test substance caused immediate, complete corneal opalescence and necrosis of the conjunctiva and outer lid. Effects on the iris were not seen due to the severity of the corneal irritation; however, at 1-3 days the eye did not react to light. The rabbit was sacrificed at three days because of the obvious corrosive nature of the test material.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation


Three skin irritation/corrosion tests were conducted each using six rabbits. In two studies the animals were exposed to 0.5 ml of MPMD on the clipped skin for 4 h (mostly under occlusive conditions), in the third for 3 min. In one reliable study (with restrictions) MPMD was washed from the skin already after three minutes. The skin reactions were observed for 48 h after the initial exposure. In all tests all of the tested animals showed skin corrosion at all reading times (even after reading time 3 minutes after the 3 minute exposure).


   


Eye irritation


An eye irritation/corrosion test was performed with three rabbits. The animals were exposed to 0.1 ml of MPMD. In the first animal (eye washed for 1 min after 20 seconds of exposure) the test substance caused severe corneal irritation with large ulcer, moderate iritis, clouds of precipitate in the anterior chamber, and necrosis of the conjunctiva and outer lids. At ten days the eye appeared shrivelled and at 11 days the animal was sacrificed. The eye of animal 2 was washed for 15 min after 20 seconds of exposure, this did not lessen the ocular effects in comparison to animal 1. The eye of animal 3 was not washed after test item application. The test substance caused immediate, complete corneal opalescence and necrosis of the conjunctiva and outer lid. Effects on the iris were not seen due to the severity of the corneal irritation; however, at 1-3 days the eye did not react to light. The rabbit was sacrificed at three days because of the obvious corrosive nature of the test material.

Justification for classification or non-classification

According to the results of available data for this substance as well as the knowledge about its very alkaline nature, the substance does fulfil the criteria to be classified as skin corrosive substance following criteria of Regulation (EC) No. 1272/2008 (CLP). Using the most conservative results reported, the substance has to be classified in subcategory 1A (CLP).


According to the results of available data the test item fulfils the criteria to be classified to cause irreversible damage to the eyes (Cat. 1) following the criteria of Regulation (EC) No. 1272/2008 (CLP).