Registration Dossier

Diss Factsheets

Administrative data

Description of key information

No data are available for the target substance Sulfuric acid, mono-C16-20 (even numbered)-alkyl esters, sodium salts (CAS 91648-55-4). Therefore, read-across from structural analogue substances has been applied.

Skin irritation (OECD 404), rabbit: irritating

Read-across from source substances Sulfuric acid, mono-C12-18-alkyl esters, sodium salts (CAS 68955-19-1)

Eye irritation (OECD 405), rabbit: highly irritating/corrosive

Read-across from source substance Sulfuric acid, mono-C12-16-alkyl esters, sodium salts (CAS 73296-89-6)

SCLs according to Regulation (EC) No. 1272/2008 (CLP):

≥ 10% < 20% Eye Irrit. Cat. 2, H319

< 10% no classification

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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive dressing
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrusse Chbb:HM
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Amount: 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
5
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.6
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive dressing
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrusse Chbb:HM
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
Concentration: 25% a.i.
Amount: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
21 days
Number of animals:
5
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
primary dermal irritation index (PDII)
Score:
2.33
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
According to Guideline.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 h
Observation period:
14 days
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS)
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Only a summary report is available where details on materials and methods were not provided.
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
GLP compliance:
no
Species:
human
Strain:
other: reconstructed human epidermal model
Type of coverage:
other: not applicable
Preparation of test site:
other: not applicable
Vehicle:
water
Controls:
other: Not applicable. Negative (de-ionized water (corrosion test) / PBS, steril (irritation test)) and positive control (8 N KOH (corrosion test) / 5% SDS in de-ionized water (irritation test)) included.
Amount / concentration applied:
25% suspension
Duration of treatment / exposure:
corrosion test: 3 min and 1 h
irritation test: 1 h
Observation period:
corrosion test: not applicable
irritation test: 42 h post incubation
Number of animals:
corrosion test: two tissue samples per treatment group, per time point
irritation test: three tissue samples per treatment group, per time point
Details on study design:
The test consists of a topical exposure of the test substance (25% aqueous suspension) to the surface of a human reconstituted epidermis model for 3 min and 1 h (corrosion test) or 1 h with 42 h postincubation (irritation test) followed by a cell viability test (MTT). The optical density of the extracts of test substance treated tissues is compared to negative control values from tissue treated with de-ionized water or PBS and is expressed as relative tissue viability.
Irritation / corrosion parameter:
% tissue viability
Remarks:
% of negative control
Run / experiment:
3 min (corrosion test)
Value:
103
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Remarks:
% of negative control
Run / experiment:
1 h (corrosion test)
Value:
107
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Remarks:
% of negative control
Run / experiment:
1 h (irritation test)
Value:
117
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
Based on the observed results it was concluded, that the test substance does not show a skin irritation potential in the EpiDerm skin corrosion/irritation test under the test conditions chosen.

Table 1: Cell viability of the corrosion test

Corrosion test

Exposure: 3 min

Exposure: 1 hour

Test substance

 

tissue 1

tissue 2

mean

tissue 1

tissue 2

mean

Negative control (NC)

mean OD570

1.938

1.874

1.906

1.671

1.658

1.664

viability (% of NC)

101.7

98.3

100

100.4

99.6

100

test substance

(25%)

mean OD570

1.977

1.961

1.969

1.756

1.808

1.782

viability (% of NC)

103.7

102.9

103

105.5

108.6

107

Positive control

(PC)

mean OD570

0.565

0.423

0.494

0.139

0.134

0.137

viability (% of NC)

29.7

22.2

26

8.4

8.1

8

Table 2: Cell viability of the irritation test

Test substance

 

tissue 1

tissue 2

tissue 3

mean

SD

Negative control (NC)

mean OD570

1.824

2.069

1.717

1.870

 

viability (% of NC)

97.5

110.7

91.8

100

9.67

test substance

(25%)

mean OD570

2.203

2.237

2.106

2.182

 

viability (% of NC)

117.8

119.6

112.6

117

3.65

Positive control

(PC)

mean OD570

0.165

0.168

0.171

0.168

 

viability (% of NC)

8.8

9.0

9.1

9

0.17

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Only 7 d recovery instead of 21 d, Some data not reported (e.g. environmental conditions)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Grade 1 in one animal
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Grade 1 in two animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: Eye irrit. 2, H319. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS)
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Only14 d recovery instead of 21 d, Some data not reported (e.g. environmental conditions)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.9
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Only 2 animals tested.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Only 2 animals.
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrusse Chbb:Hm
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Amount applied: 0.1 g
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
6 days
Number of animals or in vitro replicates:
2
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.8
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrusse Chbb:Hm
Vehicle:
water
Controls:
not required
Amount / concentration applied:
Concentration: 25% a.i.
Amount applied: 0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: Eye irrit. 2, H319. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS)
Endpoint:
eye irritation: in vivo
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Lack on details of test substance. However details were achieved from the sponsor.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
According to Guideline.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
2
Reversibility:
not fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.8
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.6
Max. score:
4
Reversibility:
fully reversible within: 21 days
Interpretation of results:
other: Eye damage 1, H318. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS)
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1977-12-15 to 1978-03-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Performed before GLP was set into force.
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Marland Breeding Farms, Inc
- Age at study initiation: Not available
- Weight at study initiation: Not available
- Housing: animals were individually housed
- Diet (e.g. ad libitum): Not available
- Water (e.g. ad libitum): Not available
- Acclimation period: Not available


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not available
- Humidity (%): Not available
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): Not available


IN-LIFE DATES: From: 1977-12-15 To: 1978-03-10
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (eye non rinsed /rinsed)
- Concentration (if solution): 50% w/w solution of test material in distilled water (22% a.i.)


VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable
Duration of treatment / exposure:
Six rabbits were divided into two treatment groups: 0.1 ml of a 50% w/w solution of the test material (B0010) in distilled water was instilled into one eye each of three rabbits (Group I); a second group of three rabbits received the same treatment as group I, followed at 4 seconds by a 20 ml lukewarm tap water rinse (Group II).
Observation period (in vivo):
1 hour , and on days 1, 2, 3, 4, 7 ,14, 21 and 28 following compound administration.
Number of animals or in vitro replicates:
Group I - 3 animals (50% w/w solution of test material B0010 in distilled water, non-rinsed)
Group II - 3 animals (50% w/w solution of test material B0010 in distilled water, rinsed)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Group I - Unwashed, Group II washing with 20 ml lukewarm tap water
- Time after start of exposure: 4 seconds in group II


SCORING SYSTEM: Draize Scoring System


TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Day 1-3
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Day 1-3
Score:
0.8
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: Day 1-3
Score:
2.1
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Day 1-3
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Group I (Unwashed eye)
Overall irritation score at 1 hour: 6
Overall irritation score at 1 day: 7.67
Overall irritation score at 2 days: 6.67
Overall irritation score at 3 days: 5.33
Overall irritation score at 4days: 5.33
Overall irritation score at 7 days: 3.33
Overall irritation score at 14 days: 0.33
Overall irritation score at 21 days: 0.66
Group II (Washed eyes)
Overall irritation score at 1 hour: 4.00
Overall irritation score at 1 day: 6.34
Overall irritation score at 2 days: 5.33
Overall irritation score at 3 days: 4.33
Overall irritation score at 4 days: 4.33
Overall irritation score at 7 days: 1.66
Overall irritation score at 14 days: 1.33
Overall irritation score at 21 days: 0
Overall irritation score at 28 days: 0
Other effects:
None

Irritation parameter   Basis  Time point    Max. score  Reversibility  Remarks
 overall irritation score  mean  14 and 21 days    0.66  not fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, non rinsed
 Cornea score and iris score  mean  14 and 21 days  0  0  othere: No corneal and iridal irritation was observed  0.1 ml of 50% w/w solution of test material in distilled water, non rinsed
 conjunctivae and chemosis score  mean one animal with grade 1, two animals with grade 0  14 and 21 days > = 0 -< = 1  1  not fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, non rinsed
  overall irritation score  mean  1 hour    4.00  fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, rinsed
 cornea score  mean three animals with grade 1  1 hour  1  1 fully reversible within: 21 days     0.1 ml of 50% w/w solution of test material in distilled water, rinsed
 Iris score  mean 1hour  0  0  other: no iridal irritation was observed   0.1 ml of 50% w/w solution of test material in distilled water, rinsed
 conjunctivae score  mean one animal with grade 1, two animals with grade 2  1 hour  > =1 -< =2  2  fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, rinsed 
 chemosis score  mean one animal with grade 2, two animals with grade 1  1 hour  > =1 -<=2  2  fully reversible within: 7 days    0.1 ml of 50% w/w solution of test material in distilled water, rinsed 
 overall irritation score  mean  1 days    6.34   fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, rinsed 
 cornea score  mean one animal with grade 1, two animals with grtade 2  1 days > = 1 - <=2  2   fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, rinsed 
 iris score  mean two animals with garde 1, one animal with grade 0  1, 2, 3 and 4 days  > =0 - <=1  1  fully reversible within: 7 days   0.1 ml of 50% w/w solution of test material in distilled water, rinsed
conjunctivae score  mean two animals with grade 2, one animal with grade 3  1 and 2 days  > =2 - <=3   3  fully reversible within: 21 days   0.1 ml of 50% w/w solution of test material in distilled water, rinsed 
 chemosis score  mean one animal grade 0, one animal with grade 2, one animal with grade 3  1 days  >=0 - <=3  3  fully reversible within: 7 days   0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 overall irritation score  mean  2 days    5.33  fully reversible within: 21 days   0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 cornea score  mean two animals with grade 2, one animal with grade 0  2, 3 and 4 days  >=0 -<=2  2  fully reversible within: 21 days   0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
chemosis score  mean one animal with grade 0, one animal with grade1, one animal with grade 2 2 and 3 days    >= 0- <=3  3  fully reversible within: 7 days   0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 overall irritation score  mean  3 and 4 days    4.33  fully reversible within: 21 days   0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 conjunctivae score  mean two animals with grade 2, one animal with grade 0 3 and 4 days   >= 0 -<=2  2   fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 overall irritation score  mean  7 days   1.66   fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 cornea score  mean one animal with grade 0, one animal with grade 1, one animal with grade 3  7 days  >= 0 -<=3  3   fully reversible within: 21 days  0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 iris score  mean  7 and 14 days  0  0    other : no iridal irritation was observed  0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 conjunctivae score  mean one animal with grade 1, two animals with grade 0  7 and 14 days >=0 -<=1   1    fully reversible within: 21 days   0.1 ml of 50% w/w solution of test material in distilled water, rinsed  
 chemosis score  mean  7 and 14 days  0  0 other : no conjunctival chemosis was observed   0.1 ml of 50% w/w solution of test material in distilled water, rinsed 
 overall irritation score  mean  14 days    1.33    fully reversible within: 21 days    0.1 ml of 50% w/w solution of test material in distilled water, rinsed 
 cornea score  mean one animal with grade 0, one animal with grade 1, one animal with grade 3  14 days  >=0 - <=3  3    fully reversible within: 21 days    0.1 ml of 50% w/w solution of test material in distilled water, rinsed 
 overall irritation, cornea, conjunctivae and chemosis score  mean  21 and 28 days  0  0 other : no ocular irritation was observed    0.1 ml of 50% w/w solution of test material in distilled water, rinsed 

GHS Rating and Calculations

 Animals no.  GHS Classification  What It means?  Cornea  Iris  Conjunctival redness  Conjunctival chemosis  Days to clear
 354  2a  Irritating to eyes  2  0.67  2  1.67  21 days
 355  2a  Irritating to eyes  2  0.67  2  1.33 21 days 
 356  2a  Irritating to eyes  2  1  2.33  2  21 days
Interpretation of results:
other: Eye irrit. 2, H319. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS)
Conclusions:
Regarding the fact that only one animal showed very slight effects on Day 28, a trigger for a classification as highly irritant is not justified. Hence, 22% a.s. potassium alkyl sulfates paste is irritating to the eyes.
Executive summary:

Six rabbits were divided into two treatment groups: 0.1 ml of a 50% w/w solution of the test material B0010 (44% KAS paste) in distilled water was instilled into one eye each of three rabbits (Group I); a second group of three rabbits received the same treatment as group I, followed at 4 seconds by a 20 ml lukewarm tap water rinse (Group II). The eyes were examined for corneal opacity, iritis and conjunctivitis at one hour and on days 1, 2, 3, 4, 7, 14, 21 and 28 following treatment and were graded using Draize ocular irritation grading system.

All three eyes in Group I were assigned positive scores for corneal opacity and ulceration, iritis, conjunctival redness and chemosis. Two eyes were clear on day 28 of the study and showed signs of eye irritation on day 21 of the study.

Three eyes in Group II were assigned positive scores for corneal opacity. Three eyes were observed to have positive scores for conjunctival redness and two for chemosis. In addition, two eyes were assigned positive score for iritis. One eye was clear on day 3 and two on day 21 of the study.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no study regarding skin and eye irritation/corrosion available for C16-20 AS Na (CAS 91648-55-4). Therefore this endpoint is covered by read across to structurally related alkyl sulfates (AS). The possibility of a read-across to other alkyl sulfates in accordance with Regulation (EC) No 1907/2006 Annex XI 1.5 “Grouping of substances and read-across approach” was assessed. In Annex XI 1.5 it is given that a read-across approach is possible for substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. The AS reported within the AS category show structural similarity. The most important common structural feature of the category members is the presence of a predominantly linear aliphatic hydrocarbon chain with a polar sulfate group, neutralized with a counter ion. This structural feature confers the surfactant properties of the alkyl sulfates. The surfactant property of the members of the AS category in turn represent the predominant attribute in mediating effects on mammalian health. Therefore, the AS of the AS category have similar physicochemical, environmental and toxicological properties, validating the read across approach within the category. The approach of grouping different AS for the evaluation of their effects on human health and the environment was also made by the OECD in the SIDS initial assessment profile [1] and by a voluntary industry program carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS.

 

Skin irritation

Regarding skin irritation one relevant key study is available for the read-across substance C12-18 AS Na (CAS 68955-19-1) and three supporting studies for C16-18 AS Na (CAS 68955-20-4).

One skin irritation study was conducted with C12-18 AS Na (CAS 68955-19-1, analytical purity 88.7%) according to OECD Guideline 404 under semi-occlusive conditions (BASF, 1994). Each of three New Zealand White rabbits was exposed for 4 h to 0.5 g of the unchanged test item and was observed for a period of 14 days for erythema and edema. The mean erythema score (24, 48 and 72 h reading) and the mean edema score were 3 and 2.3, respectively. Both effects were fully reversed within the 14 days observation period. Thus the test substance was classified as skin irritating, category 2, according to Regulation (EC) No. 1272/2008 (CLP) within this study.

A second study was conducted with C16-18 AS Na (CAS 68955-20-4, analytical purity 55%) according to OECD guideline 404 on 5 rabbits (strain: Kleinrusse Chbb:HM) (BASF, 1986a). 0.5 g of the unchanged test item was applied for 4 h under occlusive conditions and skin reactions were scored immediately, 24, 48 and 72 h after removal of the patch and on day 7. The mean erythema score (24, 48 and 72 h reading) and the mean edema score were 1.3 and 0.6, respectively. Both effects were fully reversed within the 7 days observation period. Based on the result of this study the test substance is not irritating at a concentration of 55% a.i.

Another study with C16-18 AS Na (CAS 68955-20-4, analytical purity 94.3%) was performed according to OECD guideline 404 on 5 rabbits (strain: Kleinrusse Chbb:HM) (BASF, 1987b) 0.5 mL of the diluted test item (25%) was applied for 4 h under occlusive conditions to the rabbit skin and skin reactions were scored immediately after removal of the patch, after 24, 48 and 72 h and on day 7, 10, 14, 17 and 21. The mean erythema score (24, 48 and 72 h reading) and the mean edema score were 1.6 and 0.7, respectively. Both effects were fully reversible during the observation period. Based on the result of this study the test substance is not irritating at a concentration of 25% a.i.

A combined OECD guideline 431 and OECD guideline 439 in vitro study with reconstructed human epidermis (RHE) was performed with 25% C16-18 AS Na (CAS 68955-20-4) (BASF, 2012b). When cells were exposed for 3 and 60 minutes without a post exposure period (corrosion test) the cell viabilities were 103% and 107%, respectively. The cell viability after a 60 min exposure and 42 h post exposure period (irritation test) was 117%. Thus, 25% C16-18 AS Na was neither corrosive nor irritating in this in vitro study.

 

Conclusion on the skin irritating properties of C16-20 AS Na (CAS 91648-55-4)

C12-18 AS Na (CAS 68955-19-1) contains in contrast to C16-20 AS Na (CAS 91648-55-4) up to 65 % C12 AS which represents the carbon chain length with the highest irritation potential of the members of the AS Category. However, no data within the category for C20 AS are available. Therefore, this read-across is conservative and the hazard of the target substance might be overestimated. According to Regulation (EC) No. 1272/2008 (CLP) ≥ 10% C16-20 AS Na (CAS 91648-55-4) needs to be classified as H315, Skin Irrit. 2. No classification is required below 10% C16-20 AS Na (CAS 91648-55-4).

 

Eye irritation

No data are available for the neat substance allowing a definitive classification of C16-20 AS Na (CAS 91648-55-4). Therefore, a read-across from C12-16 AS Na (CAS 73296-89-6).

An OECD guideline 405 study was performed with 0.1 mL pure C12-16 AS Na (CAS 73296-89-6, analytical purity 30%) on three New Zealand White rabbits (KAO, 1997). The observation period was 21 days. Eye reactions were scored 1, 24, 48 and 72 h after treatment. Further observations were performed on days 7, 14, and 21 after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 1, 0.2, 2.8 and 3.6. The iritic effects reversed within 72 h and chemosis within the 21 day observation period. The effects observed on cornea and the redness of the conjunctiva was not fully reversible within 21 days. Thus the substance produced irreversible effects on the eye at a concentration of 30% within this study.

 

Setting of SCLs for eye irritation

As corrosion and irritation depends on the concentration of the substance in a solvent, further studies with lower concentrations of the read across substances were also considered to assess whether specific concentration limits can be set. For this purpose, studies with C16-18 AS Na (CAS 68955-20-4), C12-13 AS K (CAS 91783-22-1) and C10-16 AS Na (CAS 68585-47-7) with a concentration range of 10 to 25% were evaluated.

In an OECD guideline 405 study 0.1 mL of a 25% aqueous solution of C16-18 AS Na (CAS 68955-20-4) was applied to one eye of each of four rabbits (BASF, 1987c). Eye reactions were scored 1, 6, 24, 48 and 72 h and 1, 10, 14, 17 and 21 days after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 0.8, 0, 2.3 and 0.4. All effects were fully reversible. The test substance meets the classification criteria of Regulation (EC) No 1272/2008 (Eye Irritating Cat 2). Thus, the results of this study indicate the concentration of 25% used within this study to be the borderline for classification purposes under CLP.

 

In the study with C12-13 AS K (CAS 91783-22-1, analytical purity 44%) 0.1 mL of the diluted test item (1:1 mixture with water) was applied to one eye of each of three New Zealand White rabbits according to OECD guideline 405 (P&G, 1978b) without rinsing. In a second experiment with additional 3 rabbits the procedure was repeated but the treated eye was rinsed with 20 mL of lukewarm tap water four seconds after application of the test item. The eye reactions were recorded 1, 24, 48, 72 h and 4, 7, 14, 21 and 28 days in both experiments. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores of experiment 1 were 2, 0.8, 2.1 and 1.7. The findings reversed in 2/3 animals within 14 days while 1/3 animals showed signs of irritation after 21 days. However, the signs of irritation show a clear tendency to decrease with time. No reading on Day 28 was possible. Findings in the experiment with rinsing of the eye were less pronounced but irritating properties were also observed. As the ocular findings clearly reversed within 21 days the result of the study indicate the concentration of 22% to be the turning point between classification as severe damage to the eye and eye damaging.

The first study with 0.1 mL undiluted C10-16 AS Na (CAS 68585-47-7, analytical purity 10%) was performed similar to OECD guideline 405 (Stephan, 1980a) on three New Zealand White rabbits with an observation period of seven days. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 1.4, 0.7, 2 and 1.6. Corneal opacity was still observed in 1/3 animals (scored 1) and conjunctival redness was still present in 2/3 animals (both scored 1) upon reading at Day 7. Depending on the classification requirements the test substance is not or only moderate irritating to the eye at a concentration of 10%.

The second study with C10-16 AS Na (CAS 68585-47-7, analytical purity 10%) was performed similar to OECD guideline 405 (Stephan, 1980b). 0.1 mL of the undiluted test item was instilled into one eye of each of three New Zealand White rabbits. Eye reactions were scored at least 24, 48 and 72 h and 14 days after application of the test item. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 0.9, 0.7, 1.9 and 1.6. All findings were fully reversible within the observation period. Thus, the test substance showed no eye irritating properties at a concentration of 10%.

 

Conclusion on the eye irritating properties of C16-20 AS Na (CAS 91648-55-4)

Based on the above mentioned results with different concentrations of structurally related alkyl sulfates a cut-off value for classification as severe irritating to eyes is set at a concentration of 20% and for classification as irritating at a concentration of 10%. Since the available data of the read-across substance C10-16 AS Na (CAS 68585-47-7) indicates no eye irritation potential at a concentration of 10%, no classification is required below 10% C16-20 AS Na (CAS 91648-55-4).

 

According to Regulation (EC) No. 1272/2008 (CLP) ≥ 20% C16-20 AS Na (CAS 91648-55-4) needs to be classified as H318, Eye Dam. 1. Based on a weight of evidence approach ≥ 10 % - < 20% C16-20 AS Na (CAS 91648-55-4) needs to be classified as H319, Eye Irrit. 2 according to CLP. Below 10% no classification at all is required.

 

No data on respiratory irritation are available. AS is mainly used in liquid media and due to its very low vapour pressure [2] inhalation is not viewed as a significant route of exposure. Inhalation of AS may occur by inhalation of aerosols generated by spray cleaners or by inhalation of detergent dusts (e.g. washing powder). In both cases the substance will be used in low concentrations. However in case the substance is available as neat powder the substance will also be classified as STOT Single exp. Cat 3 according to CLP at concentrations exceeding 20%

 

[1] SIDS initial assessment profile, (2007); http://www.aciscience.org/docs/Alkyl_Sulfates_Final_SIAP.pdf

[2] (HERA Draft report, 2002); http://www.heraproject.com/files/3-HH-04-%20HERA%20AS%20HH%20web%20wd.pdf

Justification for classification or non-classification

According to the classification criteria of Regulation (EC) No. 1272/2008 (CLP) the test substance needs to be classified with Skin Irritation Category 2, H315 and Eye Dam.1, H318, respectively. As the neat substance has to be classified as skin irritating, the substance will also be classified as “may cause respiratory irritation” (STOT SE3, H335, respectively) in case the substance is available as neat powder.

It could be shown with experimental data on eye irritation that at 10 to 20% active substance only the classification Eye Irritating Category 2 according to Regulation (EC) No. 1272/2008 remains. Below 10% active substance no classification at all is necessary. Hence, the Generic Concentration Limits (GCLs) can be substituted by the mentioned specific ones (SCLs).