Registration Dossier

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Description of key information

Irritation studies for skin and eye were conducted according to Draize method in rabbits with a test item containing 80% active ingredient. Scoring according to Draize demonstrated  a primary irritation score of 2.3/4 for skin irritation and mean 24-72h scores for cornea, conjunctiva and iris of 17.6/80, 14/20 and 5/10, respectively, for eye irritation. Based on the scores, the substance was considered irritating for skin (CLP category 2) and, in combination with various eye findings which were not reversible, causing severe eye damage (CLP category 1). 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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:
guideline study with acceptable restrictions
Remarks:
The study was not performed under GLP, however the study was conducted according to standards of that time, therefore the study is considered to be adequate, reliable and relevant.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive patch, 24h exposure period, test with 6 animals
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
Not provided
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the product, prepared as an aqueous paste

VEHICLE
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
Not provided
Irritation parameter:
other: primary irritation score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
2.3
Max. score:
8
Reversibility:
fully reversible within: 24 hours

Table1. Rabbit skin irritation

Conditions : 0.5 g of the product , prepared as an aqueous paste, was held under an impervious patch in continuous 24-hour contact with the shaved skin 

Time,

Hours

Reaction

Rabbit Number, Value

Mean

Value

1

2

3

4

5

6

 

ERYTHEMA

 

 

 

 

 

 

 

24

intact

2

1

2

2

2

2

1.8

72

intact

2

1

1

0

1

2

1.2

24

abraded

2

1

2

2

2

2

1.8

72

abraded

2

2

2

2

2

2

2.0

 

EDEMA

 

 

 

 

 

 

 

24

intact

0

0

0

0

4

0

0.7

72

intact

0

0

0

0

0

0

0.0

24

abraded

0

0

0

4

4

0

1.3

72

abraded

0

0

0

3

0

0

0.5

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

 

Interpretation of results:
Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The report states: "Although this product produces some irritation of rabbit skin, it is not expected to produce significant skin irritation under conditions of ordinary industrial handling." However, based on the primary irritation score of 2.3 and erythema still present at 72 hours, the product is considered irritating.
Executive summary:

Six rabbits underwent a covered application to the clipped intact and abraded skin of 0.5 g Butanedioic acid, sulfo-, 1,4 -dicyclohexyl ester, sodium salt as an aqueous paste containing 80% active ingredient. Scoring according to Draize et al. (1944) demonstrated a primary irritation score of 2.3. It was concluded that the test item produces some irritation of rabbit skin. Although the design of the study was different from current OECD methods, irritation Category 2 according to CLP is concluded.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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:
guideline study with acceptable restrictions
Remarks:
The study was not performed under GLP,however the study was conducted according to standards of that time, therefore the study is considered to be adequate, reliable and relevant.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
¨test with 6 animals, 72h observation period
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Not provided
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of the product as received was introduced into the conjunctival sac


Duration of treatment / exposure:
Not applicable
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Details on study design:
Not provided
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
17.6
Max. score:
80
Reversibility:
other: not fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
5
Max. score:
10
Reversibility:
other: not fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
14
Max. score:
20
Reversibility:
other: not fully reversible

Table 1.Rabbit eye irritation results

Time,

Hours

Structure

Rabbit Number, Value

Mean

Value

1

2

3

4

5

6

24

CORNEA

20

20

20

20

20

20

20

IRIS

5

5

5

5

5

5

5

CONJUNCTIVAE

14

20

14

20

8

12

15

48

CORNEA

20

20

20

20

20

5

18

IRIS

5

5

5

5

5

5

5

CONJUNCTIVAE

14

14

14

16

8

14

13

72

CORNEA

20

20

15

10

10

5

15

IRIS

5

5

5

5

5

5

5

CONJUNCTIVAE

14

14

16

8

8

14

14

         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.

- inflammation of the iris other than slight deepening of the folds, or slight circumcorneal injection.

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

- 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:
Category I
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
This test item is irritating to rabbit eyes. Therefore, precautions should be observed to avoid its introduction into or near the eyes.
Executive summary:

0.1 g Butanedioic acid, sulfo-, 1,4 -dicyclohexyl ester, sodium salt containing 80% active ingredient was introduced into the conjunctival sac of 6 rabbits. Scoring according to Draize et al. (1944) after 24, 48 and 72 hours demonstrated a mean cornea score of 17.6/80, a mean iris score of 5/10 and a mean conjuctivae score of 14/20. 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,inflammation of the iris other than slight deepening of the folds, or slight circumcorneal injection, diffuse, deep-crimson red appearance of the conjunctivae, with individual vessels not easily discernible and obvious swelling of the conjunctivae, excluding cornea and iris, with partial eversion of the lids. It was concluded that the test item produces irritation of rabbit eyes. Therefore, precaution should be observed to avoid its introduction into or near the eyes.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a key in vivo skin irritation study with the registered substance, 6 rabbits underwent a covered application to the clipped intact and abraded skin of 0.5 g test item containing 80% active ingredient (American Cyanamid Company, 1969). Scoring according to Draize method demonstrated a primary irritation score of 2.3. It was concluded that the test item produces irritation of rabbit skin.

Eye irritation

In a key in vivo eye irritation study with the registered substance, 0.1 g test item as received (80% active) was introduced into the conjunctival sac of 6 rabbits (American Cyanamid Company, 1969). Scoring according to Draize et al. (1944) after 24, 48 and 72 hours demonstrated a mean cornea score of 17.6/80, a mean iris score of 5/10 and a mean conjuctivae score of 14/20. 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, inflammation of the iris other than slight deepening of the folds, or slight circumcorneal injection, diffuse, deep-crimson red appearance of the conjunctivae, with individual vessels not easily discernible and obvious swelling of the conjunctivae, excluding cornea and iris, with partial eversion of the lids. Therefore, precaution should be taken to avoid its introduction into or near the eyes.

Further information supporting the classification is provided in the read across justification for the Diester category, showing that all substances in the group (except 1 which was not irritating) were irritating for skin and all were group classified to cause severe eye damage (justification with data matrix separately attached in Section 13).


Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the results the test item containing 80% active ingredient needs to be classified for skin irritation according to the Directive 67/548/EEC, Annex VI with symbol Xi and the indication of danger “irritant”; the following risk phrase shall be assigned: R38 - Irritating to skin.  For the eye, the substance containing 80% active ingredient is classified as irritating to eyes and risk phrase R41- Risk of serious damage to eyes shall be assigned.

According to CLP regulation (No. 1272/2008 of 16 December 2008), the substance containing 80% ingredient is classified as Category 2, with signal word 'Warning' and hazard statement: H315 - Causes skin irritation. For the eye irritation, the test item containing 80% active ingredient is classified as Category 1, with signal word 'Danger' and hazard statement: H319 -Causes serious eye damage.