Registration Dossier

Administrative data

Description of key information

In an dermal iritation study, no signs of irritation were evident at any time during the study and the test substance was not considered a dermal irritant.
The results from an eye irritation study in rabbits showed that the test item has potential for irreversible eye damage and is ths regarded as being corrosive to the eye.

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:
1997-10-28 until 1997-10-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
other: Hra:(NZW)SPF
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc. (Denver, PA)
- Age at study initiation: young adult (at least three month old')
- Weight at study initiation: at least 200 g grams at the start of the study
- Housing: singly, in suspended, stainless-steel mesh cages. Cages and racks were washed once a week.
- Diet: Certified High Fiber Rabbit Diet (PMI #5325) was available ad libitum
- Water: municipal drinking water, regularly assayed
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-21°C
- Humidity: 53-54 %
- Photoperiod: 12 hours of artificial light
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: test item as such (no vehicle)
Duration of treatment / exposure:
4 h
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approx 6 cm2
- Type of wrap if used: fiber pad and an occlusive wrap


REMOVAL OF TEST SUBSTANCE
- Washing: rinsed with running water


SCORING SYSTEM: OECD Draize - as described in OECD Guideline 405 (Annex V., Test B.4) (Grading of Skin Reaction)
- Body weights were measured on the day of initiation of the study.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: No irritant response noted
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: No irritant response noted
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24 -48 - 72 h
Score:
0
Max. score:
4
Reversibility:
other: No irritant response noted
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 - 48 - 72 h
Score:
0
Max. score:
4
Reversibility:
other: No irritant response noted
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24 -48 - 72 h
Score:
0
Max. score:
4
Reversibility:
other: No irritant response noted
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24 -48 - 72 h
Score:
0
Max. score:
4
Reversibility:
other: No irritant response noted
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24 -48 - 72 h
Score:
0
Max. score:
4
Reversibility:
other: No irritant response noted
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 -48 - 72 h
Score:
0
Max. score:
4
Reversibility:
other: No irritant response noted

Exposition:

4 h

Animal

Reading

Erythema

Edema

1

1 h

0

0

2

1 h

0

0

3

1 h

0

0

 

1

24 h

0

0

 

2

24 h

0

0

 

3

24 h

0

0

 

1

48 h

0

0

 

2

48 h

0

0

 

3

48 h

0

0

 

1

72 h

0

0

 

2

72 h

0

0

 

3

72 h

0

0

 

mean

24 - 72 h

0

0

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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
Study period:
1997-12-15 until 1998-01-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
other: Hra:(NZW)SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc. (Denver, PA)
- Age at study initiation: young adult (at least three month old)
- Weight at study initiation: at least 200g grams at the start of the study
- Housing: singly, in suspended, stainless-steel mesh cages. Cages and racks were washed once a week.
- Diet: Certified High Fiber Rabbit Diet (PMI #5325) was available ad libitum
- Water: municipal drinking water, regularly assayed
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-21°C
- Humidity: 41-55 %
- Photoperiod: 12 hours of artificial light
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied 0.1 mL of test item as such was pplaced into conjunctival sac of one eye (right)
Duration of treatment / exposure:
First animal: The treated eye of one animal was immediately washed after instillation.
Second animal: The treated eye of one animal was not washed after instillation.
Observation period (in vivo):
Observation: immediately after instillation of the test substance and at 1, 24, 48, 72 and 96 hours and at 7, 14 and 21 days after instillation of the test substance.
Number of animals or in vitro replicates:
2
Details on study design:
TREATMENT
The right eyes of two animals were treated. The left eyes were not treated.

REMOVAL OF TEST SUBSTANCE
- Washing:The treated eye of one animal was washed with runing water
- The treated eye of the second animal was not wahsed after exposure
- Time after start of exposure: Immediately after instillation

SCORING SYSTEM: OECD system as specified in OECD 405

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
Irritation parameter:
cornea opacity score
Remarks:
mean
Basis:
animal #1
Remarks:
(not irrigated)
Time point:
other: 24 - 48 -72 h
Score:
1.67
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Remarks:
mean
Basis:
animal #2
Remarks:
(irrigated)
Time point:
other: 24-48-72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Remarks:
mean
Basis:
animal #1
Remarks:
(not irrigated)
Time point:
other: 24 - 48 -72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Remarks:
mean
Basis:
animal #2
Remarks:
(irrigated)
Time point:
other: 24 - 48 -72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal #1
Remarks:
(not irrigated)
Time point:
other: 24 - 48 -72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Remarks:
mean
Basis:
animal #2
Remarks:
(irrigated)
Time point:
other: 24 - 48 -72 h
Score:
2.67
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal #1
Remarks:
(not irrigated)
Time point:
other: 24 - 48 -72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Remarks:
mean
Basis:
animal #2
Remarks:
(irrigated)
Time point:
other: 24 - 48 -72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days

Animal

 

Irrigated

Corneal Opacity, Iris Effects, Redness, Chemosis

1 h

24 h

48h

72h

96h

Day 7

Day 14

Day 21

1

No

0,0,2,3

1a,1,3,3

2a,1,3,3

2a,1,3,3

3a,x,3,3

3a,x,3,3

3a,X,2,2

2a,0,2,1

2

Yes

0,0,1,3

1a,1,2,3

1a,1,3,3

2a,1,3,3

1a,1,3,3

0,0,3,1

0,0,2,0

0,0,1,0

 

X) Due to opacity, iris details were obscured.

a) Greater than three-quarters up to the whole area of the cornea was involved

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin iritation/corrosion

A dermal irritation study was conducted accroding to OECD guideline 404 by administering single topical dose of 5 mL of the test substance to rabbits. The test substance was left in contact with the skin under an occlusive wrap for four hours. Skin lesions were graded according to OECD Guideline 404 (Annex V., Test B.4). No irritant response or serious lesion was noted during the 72-hour observation period. Furthermore, no toxic effects were noted during the study. Since no signs of irritation were evident at any time during the study, the test substance was not considered a dermal irritant.

Eye irritation

key study:

An eye irritation study was conducted with this test substance accroding to OECD guideline 405 using a total of two rabbits. A single dose of 0.1 mL of the test substance was administered into the conjunctival sac of one eye of each animal. Immediately after administration, the treated eye of one animal was washed with distilled water. The other treated eye was not irrigated. Ocular lesions were graded according to OECD Guideline 405 (Annex V Test B.5) (Grades for Ocular Lesions). Signs of irritation for the unwashed eye included redness (grade 3) and chemosis (grade 3) of the conjunctivae, corneal opacity (grade 3) involving greater than three-quarters up to the whole area of the cornea, injection of the iris (grade 1), severe discharges, and moderate parous. Signs of irritation evident at study termination (Day 21), consisted of redness (grade 2) and chemosis (grade 1) of the conjunctivae, corneal opacity (grade 2) involving greater than three-quarters up to the whole area of the cornea, a moderate discharge, and moderate pannus for the unwashed eye. Staining of the conjunctivae and cornea was apparent when fluorescein dye was applied at the 24-hour examination. Immediate irrigation of the eyes was palliative. Signs of irritation for the washed eye included redness (grade 3) and chemosis (grade 3) of the conjunctivae, corneal opacity (grade 2) involving greater than three-quarters up to the whole area cornea, injection of the iris (grade 1), and severe discharges. Signs of irritation evident at study termination (Day 21), consisted of redness (grade 1) for the washed eye. Staining of the conjunctivae and cornea was apparent when fluorescein dye was applied at the 24-hour examination. A decision not to conduct a full study (three unwashed and three washed) was based on the irritant effects observed in the unwashed and washed eyes following administration of the test substance. Based on the responses observed, the test substance is regarded as corrosive to the eye. Supporting studies: The results of the key study were supported by a second study conducted with this test substance accroding to OECD guideline 405 using rabbits. The in vitro Irritection™ Assay System was used to assess the potential ocular irritancy of the test substance. The Irritection™ reagent is a highly organized protein matrix which undergoes conformation and hydration changes when challenged with a test substance which is an irritant. These changes may be relevant to in vivo irritation since disturbance of protein conformation and hydration have been identified as components of corneal injury and ocular irritation. Changes in turbidity of the Irritection™ reagent are correlated with expected Draize scores by using calibrators standardized by the manufacturer. Based on a pH value of 3.364 for a 10% solution of the test substance, the Irritection™ protocol was followed for this assay. The results of the Irritection™ assay suggest that the test substance may have the potential to produce, at most, minimal eye irritation.

Justification for selection of skin irritation / corrosion endpoint:
GLP and guideline compliant study

Justification for selection of eye irritation endpoint:
GLP and guideline compliant study

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on availbale skin irritation data of the test substance, no classification and labelling is required according to Regulation No (EC) 1272/2008 (CLP) or Directive 67/548/EEC (DSD) criteria.

Based on the available eye irritation data, the test item is classified as severely eye damaging (R41) according to Directive 67/548/EEC (DSD) and as severely eye damaging cat. 1 (H318) according to Regulation (EC) No 1272/2008.