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Administrative data

Description of key information

Skin irritation, rabbits, OECD 404, not irritating to the skin
Skin irritation, rabbits, not irritating to the skin
Eye irritation, rabbits, OECD 405, not irritating to eyes
Eye irritation, rabbits, OECD 405, not irritating to eyes

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Between 6 October 1999 and 14 October 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to guidelines and GLP and reported fully.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Agricultural Chemicals Laws & Regulations Testing Guidelines for Toxicology Studies (MAFF) [59 NohSan No. 4200 (1985)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products
- Age at study initiation: Young adult
- Weight at study initiation: 2071 to 2480 g
- Housing: Individual suspended wire mesh cages
- Diet (e.g. ad libitum): LabDiet 150 g/day
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C (68.3 - 68.8 °F)
- Humidity (%): 30.2-55%
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
60 minutes, 24h, 48h, 72h and 8 days
Number of animals:
3/sex
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: Gauze binder

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wiped with paper towels moistened with deionised water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Remarks:
Animal 1
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 6 days
Irritation parameter:
erythema score
Remarks:
Animal 2
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 6 days
Irritation parameter:
erythema score
Remarks:
Animal 3
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Remarks:
Animal 4
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
Animal 5
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 5 days
Irritation parameter:
erythema score
Remarks:
Animal 6
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Remarks:
Animal 1
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 days
Irritation parameter:
edema score
Remarks:
Animal 2
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
Animal 3
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Remarks:
Animal 4
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
Animal 5
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Remarks:
Animal 6
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Mean score calculated by average of results at 24h, 48h and 72h for each animal.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema

Oedema

Max. score: 2

Max. score: 1

24 h

1/1/1/2/1/1

1/0/1/0/1/0

48 h

1/1/1/2/1/1

1/0/0/0/0/0

72h

1/1/1/1/1/1

1/0/0/0/0/0

Average 24h, 48h, 72h

 1.2/1.2/1

 0.5/0.2/0.2

 Reversibility*)

 c

 c

 Average time (unit) for reversion

 7 days

 48h

 

*) Reversibility: c. = completely reversible;= not completely reversible; n. = not reversible

 

Mortality: There were no deaths during the study.

 

Dermal Observations (Table 2):

Very slight to slight erythema and desquamation were noted for all animals. Very slight edema was noted for three animals. All dermal irritation completely subsided

by day 8.

The Primary Irritation Index (PII) was calculated to be 1.4, using the 24-, 48- and 72 -hour observations. The test article received a descriptive rating classification of slightly irritating.

TABLE 2

PROJECT NO.WIL-168169

ACUTE DERMAL IRRITATION STUDY IN ALBINO RABBITS                                              
INDIVIDUAL DERMAL SCORES

SITE A: 0.5 ML/SITE

 

ERYTHEMA

EDEMA

ANIMAL

SEX

SITE

1H

24H

48H

72H

4D

5D

6D

7D

8D

SITE

1H

24H

48H

72H

4D

5D

60

7D

8D

29982

M

A

1s

1s

1

1

1

1

0d

-

-

A

0

1

1

1

0

0

0

-

-

29983

M

A

0s

1s

1

1

1

1

0d

-

-

A

0

0

0

0

0

0

0

-

-

29984

M

A

0s

1s

1

1d

1d

1d

1d

1d

0

A

0

1

0

0

0

0

0

0

0

29993

F

A

1

2

2

1d

1d

1d

1d

0d

-

A

0

0

0

0

0

0

0

0

-

29994

F

A

1

1

1

1d

1d

0d

-

-

-

A

1

1

0

0

0

0

-

-

-

29995

F

A

1

1

1

1

1

1d

0d

-

-

A

0

0

0

0

0

0

0

-

-

 

 

TOTAL

4

7

7

6

6

5

2

1

0

TOTAL

1

3

1

1

0

0

0

0

0

PII calculated using test periods: 24h, 48h, 72 h

Primary Irritaton Index (PII) = [(7+7+6)/18] + [(3+1+1)/18]

(PII) = [20/18] + [5/18]

(PII) = 1.1 + 0.3

PII  = 1.4 = SLIGHTLY IRRITATING

PII calculated using test periods: 24h, 72 h

Primary Irritaton Index (PII) = [(7+6)/12] + [(3+1)/12]

(PII) = [13/12] + [4/12]

(PII) = 1.1 + 0.3

PII  = 1.4 = SLIGHTLY IRRITATING

 

H = HOURS     

 D = DAYS 

F = FEMALE

M = MALE 

d = DESQUAMATION  

s = DOSE SITE STAINED YELLOW

 - = DERMAL IRRITATION PREVIOUSLY SUBSIDED; ANIMAL TERMINED FROM STUDY

 

Body Weights (Table 3):

There were no remarkable body weight changes during the study.

Table 3

Acute Dermal Irritation Study in Albino Rabbits

Individual Body Weights (Grams)

Initiation

Termination

Group

Number

Sex

(Day 0)

(Interval)

0.5 ml/site

29982

M

2480

2693 (Day 6)

29983

M

2218

2320 (Day 6)

29984

M

2329

2504 (Day 8)

29993

F

2071

2294 (Day 7)

29994

F

2213

2507 (Day 5)

29995

F

2311

2596 (Day 6)

M = Male

F = Female

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
Mean scores for each animal at 24h, 48h and 72 h for erythema and oedema, respectively, were 0. Therefore, this substance is not irritating to skin under the conditions of this test.
Executive summary:

The primary dermal irritation potential of the test material was evaluated in this study with New Zealand White rabbits. There was one group of six young adult albino rabbits that received a single, four-hour, semioccluded exposure. Each 0.5 ml dose of the test article was applied to the clipped, unabraded skin. At completion of exposure, the bandages were removed and the sites washed. Application sites were evaluated in accordance with the method of Draize at approximately 30-60 minutes and 24,48 and 72 hours after patch removal and daily through day 8, if irritation persisted. Very slight to slight erythema and desquamation were noted for all animals. Very slight edema was noted for three animals. All dermal irritation completely subsided by day 8. The Primary Irritation Index (PII) was calculated to be 1.4, using the 24-, 48- and 72 -hour observations. The calcium sulfonate read across substance (CAS 70024 -69 -0) received a descriptive rating classification of slightly irritating. The Primary Irritation Index (PII) was 1.4 (24, 48 and 72 hours) and 1.4 (24 and 72 hours). This is however, not considered to be irritating taking into account the classification criteria for skin irritation by the european global harmonised system (a dermal irritant is a substance which causes a primary irritation index of >2.3 < 4).

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1999-10-14 to 1999-10-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study to GLP.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products
- Age at study initiation: Young adult
- Weight at study initiation: 2141 to 2331 g
- Housing: Individual suspended wire mesh cages
- Diet (e.g. ad libitum): Certified Rabbit Lab diet 150 g/day
- Water (e.g. ad libitum): as libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C
- Humidity (%): 30.2 - 48.5%
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:
Eyelids of animals were held closed for one second after installation.
Observation period (in vivo):
1, 24, 48 and 72 hours following dosing and on day 4.
Number of animals or in vitro replicates:
3 male/3 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): unwashed exposure
SCORING SYSTEM: Draize
TOOL USED TO ASSESS SCORE: ophthalmoscope/ fluorescein
Irritation parameter:
cornea opacity score
Remarks:
Animal 1
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
Animal 2
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
Animal 3
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
Animal 4
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
Animal 5
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
Animal 6
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Remarks:
Animal 1
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Remarks:
Animal 2
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Remarks:
Animal 3
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Remarks:
Animal 4
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Remarks:
Animal 6
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
Animal 1
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
Animals 2 and 3 and 6
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
Animals 4 and 6
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Remarks:
Animal 1
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Remarks:
Animal 2
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Remarks:
Animal 3
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Remarks:
Animals 4 and 5
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Remarks:
Animal 6
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 days
Other effects:
One animal had clear discharge from the eye, one hour post dosing. There were no deaths or changes in bodyweight throughout the study.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis was 0 for all animals. Mean scores for conjuntival redness and oedema were less than 2 in all animals. Therefore, this substance is not irritating to rabbit eyes.
Executive summary:

In the key study, the eye irritation potential of the calcium sulfonate read across substance, (CAS 70024 -69 -0), was evaluated in accordance with EPA OPPTS 870.2400 (Kern, 1999b). A group of six albino rabbits (3 per sex) was used for the study. Each animal received a single, unwashed exposure of 0.1 mL of the test article instilled into the lower conjunctival sac of the right eye. The eyelid was held closed for approximately one second and released. The left eye was manipulated in a similar manner as the right eye and served as a contralateral control. Observations for eye irritation were made at 1, 24, 48 and 72 hours following dosing and on day 4 in accordance with the method of Draize.One animal had clear discharge from the eye, one hour post dosing. There were no deaths or changes in body weight throughout the study.Mean 24, 48, and 72 hour corneal and iris scores were 0 for all animals tested. The conjunctival erythema score were 1.3, 1, 1, 1, 1, and 1,respectively were all reversible within 7 days. The chemosis scores were 0.3, 1.3, 0.3, 0, 0 and 1, respectively.In this study, substance is not an eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

The key study was undertaken in 1999 (Kern, 1999a, according to OECD 404) to investigate the skin irritation potential of the calcium sulfonate read across substance (CAS 70024-69-0) in New Zealand White rabbits. 3 males and 3 females were treated semi-occlusively (type of cover: gauze binder) with 0.5 mL of the test material for 4 hours. After removal of the substance the animals were observed for 8 days. The test sites were then evaluated in accordance with the method of Draize at 60 min, 24, 48 and 72 hours and then daily if irritation persisted. The mean erythema score were 1, 1, 1, 1.7, 1 and 1 and were fully reversible by maximally 8 days. Mean oedema scores at 24, 48 and 72 hours were 1, 0, 0.3, 0, 0.3 and 0, and were fully reversible within 48 h or 4 days. Animals did not display any abnormal signs throughout the test period. Bodyweights did not significantly alter. Based on the results of this study this substance is not a skin irritant.

Furthermore, another key study also was conducted to evaluate the skin irritation potential of the calcium sulfonate read across substance (CAS 70024-69-0; Swan, 1972). In this primary dermal irritation study, a dose of 0.5 ml of the undiluted test substance was applied to the abraded an unabraded skin of 6 young adult albino rabbits for 24 hours. Animals then were observed at the end of the 24 hour exposure and at 72 hours. All scores for erythema and edema in abraded and unabraded skin at both the 24 hour and 48 hour observations were 0 using the method of Draize. Based on the absence of effects after 24 hour exposure, which is longer (more severe) than the current prescribed 4 hour exposure guidance, this substance is not a skin irritant.

In a supporting study with the calcium sulfonate read across substance CAS 70024-69-0 (Hoff, 2002a), New Zealand White rabbits (3 animals) were treated semi-occlusively (type of cover: plastic) with 0.5 mL of the test material for 4 hours. After removal of the substance (gently washing with distilled water) the animals were observed for 14 days. The test sites were then evaluated in accordance with the method of Draize at 24, 48 and 72 hours and then daily if irritation persisted. The mean erythema scores were 0.7, 0 and 1.7, and were fully reversible by 72 hours or 14 days for 1.7. Mean oedema scores at 24, 48 and 72 hours were 0, 0 and 1, and were fully reversible within 14 days. Animals did not display any abnormal signs throughout the test period. Bodyweights did not significantly alter. Based on the results of this study this substance is not a skin irritant.

In another supporting study, the dermal irritation potential of the same calcium sulfonate read across substance (CAS 70024-69-0) was tested (Hoff, 2002b). In this study, 3 young adult New Zealand White rabbits were dermally exposed (semi-occlusively) to 0.5 mL of the test item for 4 hours. After removal of the substance (gently mashing with distilled water), animals then were observed for 7 days. The test sites were then evaluated in accordance with the method of Draize at 24, 48 and 72 hours and then daily if irritation persisted. The mean erythema score were 1, 1 and 2, and were fully reversible within 7 days. Mean oedema scores at 24, 48 and 72 hours were 0, 0 and 1.3, and were fully reversible within 7 days. Animals did not display any abnormal signs throughout the test period. Bodyweight was reduced in one animal. Mean scores for each animal at 24, 48 and 72 hours for erythema and oedema were less than 2.3 and fully reversible by maximally 7 days, respectively. Based on the results of this study this substance is not a skin irritant.

In a disregarded skin irritation screening study (Buehler, 1990a) the calcium sulfonate read across substance, CAS 70024-69-0 was investigated in 2 rabbits (1 male and 1 female). A dose of 0.5 mL of the undiluted test material was placed on gauze, which was applied to the shaved skin and then covered with a semi-occlusive wrap. After 4 hours the wrap and gauze were removed and the skin of each animal was evaluated at 24 and 72 hours in accordance with the method of Draize. The mean erythema score were 2.5 in one animal and 2.0 in the other. In the former animal erythema decreased from a score of 3 at 24 hours to a score of 2 at 72 hours indicating the effects are reversible. While the overall mean scores for erythema and oedema (2.5 and 2.25, respectively, with evidence of reversibility) suggest that the substance is not a skin irritant, this study cannot be used to determine classification and labelling because only 2 animals were used and observations were terminated at 72 hours rather than the normal 14 days.

In another disregarded study of the calcium sulfonate read across substance, CAS 70024-69-0 that was conducted following the disregarded screening study of Buehler (1990a), six animals (3 male and 3 female animals) were used to more fully evaluate the skin irritation potential of the calcium sulfonate read across substance, CAS 70024-69-0 (Buehler, 1991a). A dose of 0.5 mL of four different concentrations (6.25 %, 12.5 %, 25 % and 50%). the test material was placed on gauze, which was applied to the shaved skin and then covered with a semi-occlusive wrap. After 4 hours the wrap and gauze were removed and the skin of each animal was evaluated at 24 and 72 hours in accordance with the method of Draize. The mean erythema score for 6.25 % were 1.5, 2, 2, 2, 2 and 1, and were not fully reversible within 72 hours. Mean oedema scores for 6.25 % at 24 and 72 hours were 0.5, 0.5, 0, 2, 0.5 and 1, and were mainly not fully reversible within 72 hours. The mean erythema score for 12.5 % were 1.5, 2, 2, 2, 2.5 and 2, and were not fully reversible within 72 hours. Mean oedema scores for 6.25 % at 24 and 72 hours were 0.5, 0.5, 0.5, 1, 1.5 and 0.5, and were mainly not fully reversible within 72 hours. The mean erythema score for 25 % were 2, 3, 3, 2.5, 2 and 2, and were not fully reversible within 72 hours. Mean oedema scores for 25 % at 24 and 72 hours were 2, 2.5, 1.5, 2.5, 0.5 and 2, and were mainly not fully reversible within 72 hours. Mean scores for each animal at 24 h, and 72 h for erythema and oedema (concentration ≤ 25%), respectively, were less than 2.3.The mean erythema score for 50 % at 24 and 72 hours were 2, 3, 3, 3, 2.5 and 1.5, and were not fully reversible within 72 hours. Mean oedema scores for 50 % at 24 and 72 hours were 2.5, 3, 2.5, 2.5, 2 and 0.5, and were mainly not fully reversible within 72 hours. However, the skin irritation response in this study, particularly at 50%, is disregarded because it is inconsistent with the skin irritation results from the key and supporting studies on the calcium sulfonate read across substances (CAS 70024-69-0 and CAS 61789-86-4.

In a supporting primary dermal irritation study, 6 albino rabbits were dermally exposed to the test article (as supplied, dose volume 0.5 mL) the calcium sulfonate read across substance (CAS 61789 -86 -4) for 4 hours (Costello, 1986b). The skin was clipped over a wide area on their backs approximately 24 hours prior to application. Animals then were observed for 72 hours. Irritation was scored by the method of Draize. The mean 24, 48, and 72 hour individual animal erythema and oedema scores were 1.33, 1.67, 1.0, 1.67, 1.67, and 1.67 and 0.33, 1.67, 1.33, 2.0, 2.33, and 2.0, respectively. The overall mean 24, 48, and 72 hour erythema and edema scores were 1.5 and 1.6, respectively. Scores of 1 for erythema and oedema were present in one or more animals at the end of the 14 day observation period. Based on the results of this study this substance is not a skin irritant.

In another supporting primary dermal irritation study, 6 albino rabbits were dermally exposed to the test article (as supplied, dose volume 0.5 mL) the calcium sulfonate read across substance (CAS 61789 -86 -4) for 24 hours (Ohees, 1968c). The test material was applied to two areas, one abraded area and one intact area. The animals were fitted with collars for a 24 hour period at which time the coverings were removed, the test material washed off and the degree of erythema and oedema were recorded. A second reading was taken at 72 hours. The mean 24 and 72 hour individual animal erythema and oedema scores for abraded skin were 0.5, 0.5, 0.5, 0.5, 0.5, and 0.5 and 0.0, 0.5, 0.0, 0.5, 0.5, and 0.0, respectively. The mean 24 and 72 hour individual animal erythema and oedema scores for unabraded skin were 0.5, 0.5, 0.5, 0.5, 0.5, and 0.5 and 1.67 and 0.0, 0.5, 0.0, 0.5, 0.5, and 0.0, respectively. The overall mean 24 and 72 hour erythema and edema scores for abraded and unabraded skin were 0.5 and 0.25, respectively. All erythema and oedema scores in abraded and unabraded skin were 0.0 at the final 72 hour observation period. Based on the results of this study this substance is not a skin irritant.

In another disregarded primary dermal irritation study, 6 albino rabbits were dermally exposed to the sulfonate read across substance (CAS 61789 -86 -4, as supplied, dose 0.5 g) for 24 hours (Gabriel, 1981). The test material was applied to two areas, one abraded area and one intact area. Gauze patches were placed over the treated area and an impervious material was wrapped snugly around the trunks of the animals to hold the patches in place. The skin of each animal was evaluated at 24 and 72 hours in accordance with the method of Draize. The mean erythema scores were 2 (intact skin) and 2 (abraded skin) after 24 hours and 1.83 (intact skin) and 1.67 (abraded skin) after 72 hours. Mean oedema scores at 24 and 72 hours were 1.5 and 0.67 referring to intact skin. In addition, scores of 1.5 and 0.67 were determined for abraded skin. However, this study cannot be used to determine classification and labelling because the exposure period was 24 hours rather than 4 hours and the study was terminated prior to 14 days post exposure. The observed skin irritation scores following 24 hours cannot be used to predict the scores following the shorter (less severe) 4 hour exposure prescribed under current guidance. 

The primary dermal irritation potential of the calcium sulfonate read across substance (CAS 61789-86-4) was evaluated in this study with New Zealand White rabbits (Kern, TG, 1999). There was one group of six albino rabbits that received a single, four-hour, semioccluded exposure. Each 0.5 mL dose of the test article was applied to the clipped, unabraded skin. At completion of exposure, the bandages were removed and the sites washed. Application sites were evaluated in accordance with the method of Draize at approximately 30-60 minutes and 24, 48 and 72 hours after patch removal and daily through day 13, if irritation persisted. The mean 24, 48, and 72 hour individual animal erythema and oedema scores were 1.0, 1.33, 0.33, 0.0, 0.0, and 0.67 and 0.0, 0.33, 0.0, 0.0, 0.0, and 0.5, respectively. The overall mean 24, 48, and 72 hour erythema and oedema scores were 0.5 and 0.05, respectively. All erythema and oedema was fully reversible by day 13 and 72 hours, respectively. Based on the results of this study this substance is not a skin irritant.

Based on the weight-of-evidence, the calcium sulfonate target substance (C15 -C36) is not classified as a skin irritant in accordance with EU CLP Regulation (EC) No. 1272/2008.

Eye irritation:

In the key study, the eye irritation potential of the calcium sulfonate read across substance, (CAS 70024-69-0), was evaluated in accordance with EPA OPPTS 870.2400 (Kern, 1999b). A group of six albino rabbits (3 per sex) was used for the study. Each animal received a single, unwashed exposure of 0.1 mL of the test article instilled into the lower conjunctival sac of the right eye. The eyelid was held closed for approximately one second and released. The left eye was manipulated in a similar manner as the right eye and served as a contralateral control. Observations for eye irritation were made at 1, 24, 48 and 72 hours following dosing and on day 4 in accordance with the method of Draize. One animal had clear discharge from the eye, one hour post dosing. There were no deaths or changes in bodyweight throughout the study. Mean 24, 48, and 72 hour corneal and iris scores were 0 for all animals tested. The conjunctival erythema score were 1.3, 1, 1, 1, 1, and 1,respectively and were all reversible within 7 days. The chemosis scores were 0.3, 1.3, 0.3, 0, 0 and 1, respectively. In this study, substance is not an eye irritant.

In the other key study, the eye irritation potential of the calcium sulfonate read across substance, (CAS 70024-69-0), was evaluated (Swan, 1972). Adult New Zealand white rabbits (3/sex) were administered 0.1 mL of test substance into one eye. The other eye served as a control. The test material was not washed from the eyes. Eyes were scored for corneal, iritis and conjunctival effects 24, 48 and 72 hours following exposure in accordance with the method of Draize. Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis was 0 for all animals. Mean scores for conjunctival redness were 2, 2, 1.3, 1.3, 1 and 1, respectively. Mean scores for chemosis were 2, 1.7, 0.7, 1, 0.3 and 1, respectively. As the scores for conjunctival redness and oedema were less than 2 in 4 animals, therefore, this substance is not irritating to rabbit eyes.

Moreover, data on calcium sulfonate read-across substance, (CAS 70024-69-0), in rabbits show that this substance is not irritating to the eyes.

In a supporting eye irritation screening study (Buehler, 1990b) the calcium sulfonate read across substance, CAS 70024-69-0 was investigated in 2 rabbits (1 male and 1 female). Each animal received a single, exposure of 0.1 ml of the test article instilled into one eye. The other eye served as a control. The test material was not washed from the eyes. Animals were observed at 1, 24, 48, 72 hours in accordance with the method of Draize. Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis were 0 for all animals. Mean scores for conjunctival redness was 2 in both animals. Conjunctival oedema scores were 2.0 in one animal and 2.33 for the other. In the latter animal the conjunctival oedema decreased from a score of 3 at 24 hours to a score of 2 at 72 hours indicating the effects being reversible. However, because only 2 animals were used and observations were terminated at 72 hours rather than the normal 21 days, this study cannot be used to determine classification and labelling.

In the definitive supporting study of the calcium sulfonate read across substance, CAS 70024-69-0, that was conducted following the screening study of Buehler (1990b), six animals (3 male and 3 female animals) were used to more fully evaluate the eye irritation potential of the calcium sulfonate read across substance, CAS 70024-69-0 (Buehler, 1991b). Each animal received a single, exposure of 0.1 mL of the test article instilled into one eye. The other eye served as a control. The test material was not washed from the eyes. Animals were observed at 1, 24, 48, 72 hours in accordance with the method of Draize. Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis was 0 for all animals. Mean scores for conjunctival redness were 1, 0.7, 0.7, 0.3, 0.3 and 1, respectively. Mean scores for chemosis were 1.3, 0.7, 0, 0.7, 0.7 and 1.7, respectively. With the exception of the 1.7 value for chemosis in animal 6, all other signs were fully reversible within 72 hours. The mean scores for all animals for conjunctival redness and oedema were less than 2. Therefore, this substance is not irritating to rabbit eyes.

In another supporting study the calcium sulfonate read across substance (CAS 61789-86-4) was investigated for its eye irritating potential (Ohees, 1968d). Adult albino rabbits of the New Zealand White variety (6) were placed in a collar such that the animals could not rub their eyes. One tenth of a millilitre of test substance was instilled in one eye, the other untreated eye served as a control. The reaction to the test material was read according to the scale of scoring for damage to the cornea, iris and the bulbar and palpebral conjunctivae at 24, 48 and 72 hours after eye instillation. Any residue of the test material and accumulated discharge are flushed from the eye each time they are scored.

Under the conditions specified the product has an eye irritating score of 0 and 0 and 0 at 24, 48 and 72 hours respectively. Therefore the substance is not irritating to the eye.

In a supporting study with the same calcium sulfonate read across substance, CAS 61789-86-4 (Gabriel, 1981c) was investigated for its eye irritating potential in rabbits. Six healthy young adult albino rabbits were used in this study. 0.1 gram of the experimental material was instilled into the right eyes of the test animals, while the other eye remained untreated to serve as a control. The test material was not washed from the eyes. The treated eyes were examined at one, two, three, five and seven days following instillation of the test material into the eyes. Interpretation of the results was made in accordance with the Draize Scale of Scoring Ocular Lesions. The test material is not a primary irritant and requires no cautionary labelling with respect to an eye irritating potential.

Based on these results the calcium sulfonate target substance (C15 -C36) is not classified as an eye irritating in accordance with EU CLP Regulation (EC) No. 1272/2008.

Justification for selection of skin irritation / corrosion endpoint:
best study available

Justification for selection of eye irritation endpoint:
best study available

Justification for classification or non-classification

In vivo studies with the calcium sulfonate read across substances showed the substances not to be irritating to the skin or the eyes. In detail, the calcium sulfonate read across substance (CAS 70024-69-0) was not irritating to the skin or eyes. Therefore, the calcium sulfonate target substance (C15 -C36) does not meet the criteria for classification and labelling for skin or eye irritation in accordance with European regulation (EC) No. 1272/2008.

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