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Diss Factsheets

Administrative data

Description of key information

Irritation studies for skin and eye were conducted in rabbits with a test item containing 44 -46% active ingredient (for both endpoints) and with a 50% dilution of the product for eye irritation as well. Scoring according to Draize demonstrated that the test material was not a skin irritant for humans,  the overall  irritation scores  were 0.8 of max. 4 (24- 72 h), however the concentrated registered subsance was considered to be skin irritating based on the mono-ester group CLP 2 classification for irritation. Mean 24 -72h scores for cornea, conjuctiva and iris were 7.3/80, 7.3/20 and 1/10, respectively for the initial formulation and 11/80, 10.7/20 and 0/10 for the 50% formulation. The findings were not reversible within the observed 72 hours. This information in combination with category resuls for eye irritation resulted in classification for skin irritation and CLP category 1 classification for 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
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed with a +-45% active ingredient formulation, and not under GLP compliance. However, the study was conducted according to standards of that time, therefore the study is considered to be adequate, reliable and relevant.
Qualifier:
according to guideline
Guideline:
other: FHSA, 16cfr1500.41 CPSC
Principles of method if other than guideline:
FHSA: Federal Hazardous Substances Act
CPSC: Consumer Product Safety Commission
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
Not provided
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5g of the product, prepared as an aqueous paste
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
Both intact and abraded skin were tested.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: for intact areas
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
animal #4
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
animal #5
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
animal #6
Time point:
48 h
Remarks on result:
other: not specified
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h

Table1. Observations

Time,

Hours

Reaction

Rabbit number, Value

Mean

Value

1

2

3

4

5

6

 

Erythema

 

 

 

 

 

 

 

24

Intact

1

2

0

1

1

1

1.0

72

Intact

0

0

0

0

0

0

0.0

24

Abraded

2

2

1

1

2

2

1.7

72

Abraded

0

1

0

1

1

0

0.5

 

Edema

 

 

 

 

 

 

 

24

Intact

0

0

0

0

0

0

0.0

72

Intact

0

0

0

0

0

0

0.0

24

Abraded

0

0

0

0

0

0

0.0

72

Abraded

0

0

0

0

0

0

0.0

No structure of the tissue at the site of contact was destroyed or changed irreversible in 24 hours or less.

The scoring system used herein for skin irritation reactions is that of Draize, J.H.,Woodward, G., and Calvery, H.O.: J. Pharmacol. Exptl. Therap., B2; 377,1944. The maximum possible value for a skin reaction (excluding necrosis) is 4. The “primary irritation score” is the sum of the mean values divided by 4.

Primary irritation score 0.8

 

Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Primary irritation score of the test item containing 44-46% active ingredient in a Rabbit Skin Irritation Test with 0.5g in occlusive contact for 24 hours with shaved Skin was 0.8.This test item was only slightly irritating to rabbit skin. Therefore, it is not expected to produce significant skin irritation under conditions of ordinary industrial handling.
Executive summary:

6 Male albino rabbits underwent a covered application to the clipped intact and abraded skin of 0.5 g test item containing 44 -46% active ingredient as an aqueous paste. Scoring according to Draize et al. (1944) demonstrated a primary irritation score of 0.8, based on erythema which was reversible within 72 hours. It was concluded that the test item has no irritating potential under conditions of ordinary industrial handling.

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:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed with a +-45% active ingredient formulation, and not under GLP compliance. However, the study was conducted according to standards of that time, therefore the study is considered to be adequate, reliable and relevant.
Qualifier:
according to guideline
Guideline:
other: FHSA, 16cfr1500.42 CPSC
Principles of method if other than guideline:
FHSA: Federal Hazardous Substances Act
CPSC: Consumer Product Safety Commission
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Not provided
Vehicle:
unchanged (no vehicle)
Remarks:
part 1 ( in part 2: 50% w/v aqueous dispersion of the product)
Controls:
no
Amount / concentration applied:
Part 1: 0.1g of the product as received
Part 2: 0.1g of a 50% w/v aqueous dispersion of the product
Duration of treatment / exposure:
Not provided
Observation period (in vivo):
24, 48 and 72 hours
Number of animals or in vitro replicates:
6 (part 1)
3 (part 2)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
7.3
Max. score:
80
Reversibility:
not reversible
Remarks on result:
other: product as received
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
10
Reversibility:
not reversible
Remarks on result:
other: product as received
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
7.3
Max. score:
20
Reversibility:
not reversible
Remarks on result:
other: product as received
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
11
Max. score:
80
Reversibility:
not reversible
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24,48, 72 h
Score:
0
Max. score:
10
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
10.7
Max. score:
20
Reversibility:
not reversible
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
6.67
Max. score:
80
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.33
Max. score:
80
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
6.67
Max. score:
80
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
10
Max. score:
80
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
6.67
Max. score:
80
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: product as received
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
11.67
Max. score:
80
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: product as received
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: product as received
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: product as received
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: product as received
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: product as received
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
5
Max. score:
10
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
6.67
Max. score:
20
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
5.33
Max. score:
20
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
7.33
Max. score:
20
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.67
Max. score:
20
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
9.33
Max. score:
20
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: product as received
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
14.67
Max. score:
20
Reversibility:
not reversible
Remarks on result:
other: product as received
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: product as received
Remarks:
not specified
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: product as received
Remarks:
not specified
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: product as received
Remarks:
not specified
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Remarks on result:
other: product as received
Remarks:
not specified
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Remarks on result:
other: product as received
Remarks:
not specified
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Remarks on result:
other: product as received
Remarks:
not specified
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
6.67
Max. score:
80
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
18.3
Max. score:
80
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
10
Max. score:
80
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
10.67
Max. score:
20
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
10.67
Max. score:
20
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
11.33
Max. score:
20
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Remarks:
not specified
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Remarks:
not specified
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: 50% w/v aqueous dispersion of product
Remarks:
not specified

Table1. Scores part 1 (test material as such)

Time,

Hours

Reaction

Rabbit number, Value

Mean

Value

1

2

3

4

5

6

24

Cornea

10

5

10

15

20

15

12

Iris

0

0

0

0

0

5

1

Conjunctivae

10

10

10

4

14

14

10

48

Cornea

5

5

5

10

0

15

7

Iris

0

0

0

0

0

5

1

Conjunctivae

6

6

10

2

12

14

8

72

Cornea

5

0

5

5

0

5

3

Iris

0

0

0

0

0

5

1

Conjunctivae

4

0

2

2

2

16

4

At the readings made at 24, 48 and 72 hours, there was:

- discernible opacity or ulceration of the cornea other than a slight dulling of the normal luster.

- no inflammation of the iris other than slight deepening of the folds, or slight circumcorneal injection.

- a diffuse, deep-crimson red appearance of the conjunctivae with individual vessels, not easily discernible.

- an obvious swelling of the conjunctivae, excluding cornea and iris, with partial eversion of the lid.

- no destruction or irreversible change of any tissue in 24 hours or less.

Table 2. Scores part 2 (50% w/v aqueous dispersion of the product)

Time,

Hours

Reaction

Rabbit number, Value

Mean

Value

1

2

3

4

5

6

24

Cornea

10

20

20

-

-

-

17

Iris

0

0

0

-

-

-

0

Conjunctivae

12

12

12

-

-

-

12

48

Cornea

5

20

5

-

-

-

10

Iris

0

0

0

-

-

-

0

Conjunctivae

12

10

12

-

-

-

11

72

Cornea

5

15

5

-

-

-

8

Iris

0

0

0

-

-

-

0

Conjunctivae

8

10

10

-

-

-

9

At the readings made at 24, 48 and 72 hours, there was:

- discernible opacity or ulceration of the cornea other than a slight dulling of the normal luster.

- no Inflammation of the iris other than slight deepening of the folds, or slight circumcorneal injection.

- a diffuse, deep-crimson red appearance of the conjunctivae with individual vessels, not easily discernible.

- no obvious swelling of the conjunctivae, excluding cornea and iris, with partial eversion of the lids.

- no destruction or irreversible change of any tissue in 24 hours or less.

Interpretation of results:
irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
This test item is sufficiently irritating to the rabbit eye so that precautions should be observed to avoid its introduction into or near the eyes.
Executive summary:

An in vivo eye irritation study was conducted with a first phase where 6 rabbits received 0.1 g test item containing 44 -46% active ingredient in one eye as an aqueous paste. Scoring at 24, 48 and 72 hours demonstrated non-reversible scores for cornea and conjunctivae in all animals and iris changes in one animal, all not reversible within 72 hours. Mean 24 -72h scores for cornea, conjuctiva and iris were 7.3/80, 7.3/20 and 1/10, respectively. There was no destruction or irreversible change of any tissue in 24 hours,but discernible opacity or ulceration of the cornea, diffuse, deep-crimson red appearance of the conjunctivae and obvious swelling of the conjunctivae with partial eversion of the lid were observed. In a second part of the study, 3 rabbits received 0.1 g as a 50% dilution of the above test item (22 -23% active ingredient). Scoring at 24, 48 and 72 hours demonstrated non-reversible scores in all 3 animals for cornea and conjunctivae, not reversible within 72 hours. Mean 24 -72h scores for cornea, conjuctiva and iris were 11/80, 10.7/20 and 0/10, respectively.

There was no destruction or irreversible change of any tissue in 24 hours, but discernible opacity or ulceration of the cornea, and diffuse, deep-crimson red appearance of the conjunctivae were observed.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

A key in vivo skin irritation study with the registered substance was conducted (American Cyanamid Company, 1969), with 6 male albino rabbits receiving a covered application to the clipped intact and abraded skin of 0.5 g test item containing 44 -46% active ingredient. Scoring according to Draize demonstrated a primary irritation score of 0.8, based on erythema which was reversible within 72 hours. It was concluded that the test substance containing 44 -46% has no irritation potential under conditions of industrial handling.

In conclusion, the test item containing 44 -46% act.ingr. was not considered irritating for the skin.

Eye irritation

A key in vivo eye irritation study was conducted with the registered substance (American Cyanamid Company, 1969), with a first phase where 6 rabbits received 0.1 g in one eye as an aqueous formulation containing 44 -46% active ingredient. Scoring according to Draize at 24, 48 and 72 hours demonstrated non-reversible scores for cornea and conjunctivae in all animals and iris changes in one animal, all not reversible within 72 hours. Mean 24 -72h scores for cornea, conjuctiva and iris were 7.3/80, 7.3/20 and 1/10, respectively.

There was no destruction or irreversible change of any tissue in 24 hours, but discernible opacity or ulceration of the cornea, diffuse, deep-crimson red appearance of the conjunctivae and obvious swelling of the conjunctivae with partial eversion of the lid were observed. In a second part of the study, 3 rabbits received 0.1 g test item as a 50% dilution of the above test material (22 -23% active ingredient). Scoring at 24, 48 and 72 hours demonstrated non-reversible scores in all 3 animals for cornea and conjunctivae, not reversible within 72 hours.

Mean 24 -72h scores for cornea, conjuctiva and iris were 11/80, 10.7/20 and 0/10, respectively. There was no destruction or irreversible change of any tissue in 24 hours, but discernible opacity or ulceration of the cornea, and diffuse, deep-crimson red appearance of the conjunctivae were observed.

In conclusion, the the test item containing 44 -46% act.ingr. was considered irritating for the eye (CLP Cat. 2).

Conclusion

- As the substance tested for skin irritation only contained 44 -46% active ingredient, it is assumed that the registered substance as a concentrated substance might be irritating (CLP Category 2). A concentration limit of 44% might then be considered for non-classification.

- The test item containing 44 -46% act.ingr. was irritating (CLP Category 2); it is assumed that the registered substance as a concentrated substance might be irritating (CLP Category 12). A concentration limit of 44% might then be considered for the Cat. 2 classification.

-Further information supporting the classification is provided in the read across justification for the Di-ester category, showing that all substances in the group were group classified to cause skin irritation (CLP Category 2) and severe eye damage (CLP Category 1).


Justification for selection of skin irritation / corrosion endpoint:
Key study (44-46% active ingredient)
Further information supporting the classification is provided in the read across justification for the Di-ester category, showing that all substances in the group were classified to cause skin irritation (CLP category 2). A concentration limit can be applied for the test substance containing 44 -46% active ingredient, which is not classified.

Justification for selection of eye irritation endpoint:
Key study

Effects on eye irritation: irritating

Justification for classification or non-classification

The registered substance is classified for skin irritation according to CLP as Category 2, with signal word 'Warning' and hazard statement: H315 -Causes skin irritation. 


A concentration limit can be applied for the test substance containing 44 -46% active ingredient, which is not classified and has no obligatory labelling requirement for skin irritation according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008).


 


Based on the results and read across with category member(s), the registered test substance is classified to the Directive 67/548/EEC, Annex VI with symbol Xi and risk phrase R41- Risk of serious damage to eyes. According to CLP regulation (No. 1272/2008 of 16 December 2008), the substance is classified as Category 1, with signal word 'Danger' and hazard statement: H318 -Causes serious eye damage.