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Description of key information

Based on the experimental results it is concluded that the submission substance has to be classified as skin corrosive Cat. 1A and eye irritating Cat. 1 according to Regulation (EC) No. 1272/2008.

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:
January and February 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study based on national and scientific standards, basic data given, acceptable for assessment
Qualifier:
according to guideline
Guideline:
other: SOP No. CT20-137, version 01 (ICI)
Principles of method if other than guideline:
reduced exposure time, below 4 h
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
not specified
Preparation of test site:
other: shaved, intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Duration of treatment / exposure:
1 h and 3 min
Observation period:
1, 4, 24, 48, and 96 h (after 1-h exposure),
4, 24, 48, and 72 h (after 3-min exposure)
Number of animals:
6 each
Details on study design:
no data
Irritation parameter:
overall irritation score
Remarks:
necrosis
Basis:
other: 2/6 animals (1-h exposure)
Time point:
other: 4 h p.a.
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: corrosive: => not quantitively evaluable, descriptive rating: Scores are surrogates.
Irritation parameter:
overall irritation score
Remarks:
necrosis
Basis:
other: 6/6 animals (1-h exposure)
Time point:
other: 24, 48, and 96 h p.a.
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: corrosive: => not quantitively evaluable, descriptive rating: Scores are surrogates.
Irritation parameter:
overall irritation score
Remarks:
necrosis
Basis:
other: 5/6 animals (3-min exposure)
Time point:
other: 4 h p.a.
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: corrosive: => not quantitively evaluable, descriptive rating: Scores are surrogates.
Irritation parameter:
overall irritation score
Remarks:
necrosis
Basis:
other: 6/6 animals (3-min exposure)
Time point:
other: 24, 48, and 72 h p.a.
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: corrosive: => not quantitively evaluable, descriptive rating: Scores are surrogates.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no erythema score could be derived.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no erythema score could be derived.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no erythema score could be derived.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no erythema score could be derived.
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no erythema score could be derived.
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no erythema score could be derived.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no edema score could be derived.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no edema score could be derived.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no edema score could be derived.
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no edema score could be derived.
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no edema score could be derived.
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the corrosivity no edema score could be derived.
Irritant / corrosive response data:
After exposure of 1 h, tissue destruction was observed in 2/6 animals after 4 h post-application and in all animals at 24 through 96 h It was characterised by thickened, dark, necrotic skin with slight hardening and surrounded by an area of blanched skin edged with erythematous skin.
After exposure of 3 min, similar signs of tissue destruction were observed 4 h post-application.

Observations after 3 -minute application:

 Test Site              Ratio of 6 Rabbits
4 hr  24 hr  48 hr  96 hr 
 Abraded  5/6  6/6  6/6  6/6
 Intact 5/6  6/6  6/6 

 6/6

Observations after 1 -hour application:

    Test Site              Ratio of 6 Rabbits
 1 hr 4 hr  24 hr  48 hr  96 hr 
 Abraded  0/6  2/6  6/6  6/6  6/6
 Intact  0/6 2/6  6/6  6/6 

 6/6
Interpretation of results:
Category 1A (corrosive) based on GHS criteria
Conclusions:
The test item caused corrosive responses under the conditions of this test.
Executive summary:

The effect of the test item on rabbit skin was assesed in oder to classify the potential corrosivity according to standard operating procedure no. CT20 -137, Version 01.

In a first study, the test item was applied for one hour on abraded and intact skin of six rabbits, respectivetly. Tissue destruction was observed in two out of six animals at 4 hours and in all six animals at 24 hours after application. It was characterised by thickened, dark, necrotic skin with slight hardening and surrounded by an area of blanched skin edged with erythematous skin.

Similar signs of tissue destruction were observed 4 hours after a 3 -minute application of the test item.

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:
other: Study based on national and scientific standards, basic data given, acceptable for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
according to standard procedure, grading of effects based on the numerical scoring systems after Draize 1959
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Huntingdon
- Housing: individually in metal cages
- Diet: ad libitum
- Water: ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
not rinsed
Observation period (in vivo):
2 days
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: numerical scale according to Draize, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Appendix 2, 1959.
The results were interpreted using a modification of the method recommended by Kay and Calandra, Journal of the Society of Cosmetic Chemists, 13 (6), 281-9, Appendix 3, 1962.
Irritation parameter:
overall irritation score
Basis:
animal: 1, 2, 3
Time point:
other: day 1 and 2
Score:
110
Max. score:
110
Reversibility:
not reversible
Remarks on result:
other: not quantitively evaluable / descriptive rating: very to extremely severe irritant
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
Due to the severity of the reactions the animals were all sacrificed on day 2.
Irritant / corrosive response data:
Corneal damage in all animals, severe conjunctival swelling extending beyond the limits of the orbit, resulting in total eye closure.
No assessment of the degree of inflammation reaction possible.
All three animals had to be killed on day 2 for humane reasons.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
On instillation of the test item the animals showed moderate initial pain.
Corneal damage was produced in all three animal but assesment of the degree and extent was precluded by the severe conjuctival swelling. Considerable swelling of the conjuctivae extending well beyond the limits of the orbit resulting in complete closure of the eye was observed in all three rabbits. It was impossible to asses the degree of inflammation.
Due to the severity of the reactions the animals were all sacrificed on day 2.
Executive summary:

In an in vivo eye irritation study three albino rabbits of the New Zealand White strain were treated with 1 drop (0.1 mL) of the test substance per one eye.

The test item caused moderate to severe initial pain (3 -4 on a 5 point scale according to Kay and Calandra, 1962) which was followed by extremely severe irritation which was impossible to score. No readings could be taken if the iris and cornea due to swelling accomapnied by a great amount of discharge. Histopathological examination of sections of the eye 2 days after the installation showed the material to cause severe conjunctivitis, diffuse necrosis and inflammation of the anterior chamber.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In an in vivo study six rabbits were dermally exposed for 1 -hour towards the test item. In all animals 24 hours after application, the test item caused thickened, dark, necrotic skin with slight hardening surrounded by an area of blanched skin edged with erythematous skin. Similar signs were also observed by a 3 -minute application of the test item and already 4 hours after application.

Based on these results the substance would be considered as corrosive to skin (CLP: Cat. 1A).

The instillation of 1 mL test item in course of an in vivo eye irritation study on three rabbits caused moderate to severe initial pain followed by extremely severe irritation impossible to score. Due to the severity of the effects all animals were sacrified on day 2.

Based on these results the substance would be considered as eye irritating, Cat. 1 (CLP).

Justification for classification or non-classification

Based on the experimental results it is concluded that the submission substance has to be classified as skin corrosive Cat. 1A and eye irritating Cat. 1 according to Regulation (EC) No. 1272/2008.