Registration Dossier

Administrative data

Description of key information

skin irritation (OECD 404): irritating
eye irritation (worst case assumption): highly irritating/corrosive
SCLs according to GHS:
>=10% - <20% Eye Irrit. Cat.2, R36
<10% No Classification

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source:Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany- Age at study initiation: Approx. 4 - 8 months- Weight at study initiation: 4.41 kg –5.01 kg- Housing: Stainless steel wire mesh cages with grating with shallow cage body; floor area: 4225 cm2. Fully air-conditioned rooms.- Diet: ad libitum- Water: ad libitum- Acclimation period: Acclimatization for at least 5 days before applicationENVIRONMENTAL CONDITIONS- Temperature (°C): 20°C +- 3°C- Humidity (%): 30 – 70% - Air changes (per hr): Approx. 10- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Remarks:
The solid test item was minimally moistened with a suitable amount of highly deionized water to guarantee skin contact immediately before test-item application
Controls:
not required
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 g of undiluted test itemVEHICLEMinimally moistened with highly deionized water
Duration of treatment / exposure:
4h
Observation period:
Immediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals maximally up to day 14.
Number of animals:
3
Details on study design:
TEST SITE- Area of exposure: 2.5 cm x 2.5 cm- Type of wrap if used: The test item was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AGREMOVAL OF TEST SUBSTANCE- Washing (if done): The test item was removed at the end of the exposure period with Lutrol®** and Lutrol® / water (1 : 1).- Time after start of exposure: 4hSCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animal with equal erythema score of 3
Time point:
other: mean of 24-72h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean of 24-72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean of 24-72h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean of 24-72h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritant / corrosive response data:
The following test item-related clinical observations were recorded during the course of the study:•Well-defined to moderate erythema (grade 2 to 3)•Very slight to severe edema (grade 1 to 4)•Scaling•Severe scaling•Incrustations•Eczema like skin lesions•Erythema and edema beyond the application site•Bloody, yellowish discolored incrustations•Yellowish discoloration of the application site•Plaque-like incrustations
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Testitem shows a skin irritating potential under the test conditions chosen.
Executive summary:

The potential of TI to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 g test item for 4 hours to the intact skin of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing one additional animal per step up to a maximum number of three animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off.

The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and in weekly intervals until Day 14.

 

The following test item-related clinical observations were recorded during the course of the study:

  • Well-defined to moderate erythema (Grade 2 to 3)
  • Very slight to severe edema (Grade 1 to 4)
  • Scaling
  • Severe scaling
  • Incrustations
  • Eczema like skin lesions
  • Erythema and edema beyond the application site
  • Bloody, yellowish discolored incrustations
  • Yellowish discoloration of the application site
  • Plaque-like incrustations

The cutaneous reactions were not reversible in all animals during the course of the study.

Mean scores over 24, 48 and 72 hours for each animal were 3.0, 3.0 and 3.0 for erythema and 2.0, 3.3 and 3.0 for edema.

 

Considering the described cutaneous reactions as well as the average score for irritation, TI shows a skin irritating potential under the test conditions chosen.

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24+72 h
Score:
2.2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+72 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
August 22 - October 13, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source:Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany- Age at study initiation: Approx. 4 - 8 months- Weight at study initiation: 4.41 kg –5.01 kg- Housing: Stainless steel wire mesh cages with grating with shallow cage body; floor area: 4225 cm2. Fully air-conditioned rooms.- Diet: ad libitum- Water: ad libitum- Acclimation period: Acclimatization for at least 5 days before applicationENVIRONMENTAL CONDITIONS- Temperature (°C): 20°C +- 3°C- Humidity (%): 30 – 70% - Air changes (per hr): Approx. 10- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Remarks:
The solid test item was minimally moistened with a suitable amount of highly deionized water to guarantee skin contact immediately before test-item application
Controls:
not required
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 g of undiluted test itemVEHICLEMinimally moistened with highly deionized water
Duration of treatment / exposure:
4h
Observation period:
Immediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals maximally up to day 14.
Number of animals:
3
Details on study design:
TEST SITE- Area of exposure: 2.5 cm x 2.5 cm- Type of wrap if used: The test item was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AGREMOVAL OF TEST SUBSTANCE- Washing (if done): The test item was removed at the end of the exposure period with Lutrol®** and Lutrol® / water (1 : 1).- Time after start of exposure: 4hSCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animal with equal erythema score of 3
Time point:
other: mean of 24-72h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean of 24-72h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean of 24-72h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean of 24-72h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritant / corrosive response data:
The following test item-related clinical observations were recorded during the course of the study:•Well-defined to moderate erythema (grade 2 to 3)•Very slight to severe edema (grade 1 to 4)•Scaling•Severe scaling•Incrustations•Eczema like skin lesions•Erythema and edema beyond the application site•Bloody, yellowish discolored incrustations•Yellowish discoloration of the application site•Plaque-like incrustations
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Testitem shows a skin irritating potential under the test conditions chosen.
Executive summary:

The potential of TI to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 g test item for 4 hours to the intact skin of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing one additional animal per step up to a maximum number of three animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off.

The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and in weekly intervals until Day 14.

 

The following test item-related clinical observations were recorded during the course of the study:

  • Well-defined to moderate erythema (Grade 2 to 3)
  • Very slight to severe edema (Grade 1 to 4)
  • Scaling
  • Severe scaling
  • Incrustations
  • Eczema like skin lesions
  • Erythema and edema beyond the application site
  • Bloody, yellowish discolored incrustations
  • Yellowish discoloration of the application site
  • Plaque-like incrustations

The cutaneous reactions were not reversible in all animals during the course of the study.

Mean scores over 24, 48 and 72 hours for each animal were 3.0, 3.0 and 3.0 for erythema and 2.0, 3.3 and 3.0 for edema.

 

Considering the described cutaneous reactions as well as the average score for irritation, TI shows a skin irritating potential under the test conditions chosen.

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
e.g. 24 h occluded exposure, 48 h scoring missing, observation period only 72 h
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24+72 h
Score:
2.2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+72 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Interpretation of results:
Category 2 (irritant) based on GHS criteria
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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
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 availableENVIRONMENTAL CONDITIONS- Temperature (°C): Not available- Humidity (%): Not available- Air changes (per hr): Not available- Photoperiod (hrs dark / hrs light): Not availableIN-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 IISCORING SYSTEM: Draize Scoring SystemTOOL 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: 6Overall irritation score at 1 day: 7.67Overall irritation score at 2 days: 6.67Overall irritation score at 3 days: 5.33Overall irritation score at 4days: 5.33Overall irritation score at 7 days: 3.33Overall irritation score at 14 days: 0.33Overall irritation score at 21 days: 0.66Group II (Washed eyes)Overall irritation score at 1 hour: 4.00Overall irritation score at 1 day: 6.34Overall irritation score at 2 days: 5.33Overall irritation score at 3 days: 4.33Overall irritation score at 4 days: 4.33Overall irritation score at 7 days: 1.66Overall irritation score at 14 days: 1.33Overall irritation score at 21 days: 0Overall 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:
Category 2 (irritating to eyes) based on GHS criteria
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 sec by a 20 mL lukewarm tap water rinse (Group II). The eyes were examined for corneal opacity, iritis and conjunctivitis at 1 h 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:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
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:
other: 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:
other: 24+48+72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 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:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: not irritating acc. DSD; Cat.2 acc. CLP
Remarks:
Criteria used for interpretation of results: EU
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
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:
other: 24+48+72 h
Score:
0.9
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.9
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
GHS criteria not met
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:
other: Guideline study performed before GLP was set into force.
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
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 availableENVIRONMENTAL CONDITIONS- Temperature (°C): Not available- Humidity (%): Not available- Air changes (per hr): Not available- Photoperiod (hrs dark / hrs light): Not availableIN-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 IISCORING SYSTEM: Draize Scoring SystemTOOL 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: 6Overall irritation score at 1 day: 7.67Overall irritation score at 2 days: 6.67Overall irritation score at 3 days: 5.33Overall irritation score at 4days: 5.33Overall irritation score at 7 days: 3.33Overall irritation score at 14 days: 0.33Overall irritation score at 21 days: 0.66Group II (Washed eyes)Overall irritation score at 1 hour: 4.00Overall irritation score at 1 day: 6.34Overall irritation score at 2 days: 5.33Overall irritation score at 3 days: 4.33Overall irritation score at 4 days: 4.33Overall irritation score at 7 days: 1.66Overall irritation score at 14 days: 1.33Overall irritation score at 21 days: 0Overall 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:
Category 2 (irritating to eyes) based on GHS criteria
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 sec by a 20 mL lukewarm tap water rinse (Group II). The eyes were examined for corneal opacity, iritis and conjunctivitis at 1 h 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:
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
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
equivalent or similar to
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:
other: 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:
other: 24+48+72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 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:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: not irritating acc. DSD; Cat.2 acc. CLP
Remarks:
Criteria used for interpretation of results: EU
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
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
equivalent or similar to
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:
other: 24+48+72 h
Score:
0.9
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.9
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are no reliable studies with C9-12AS Na (CAS n.a.) regarding skin and eye irritation available. Therefore a read-across to structurally related ASO4, i.e. C8AS Na (CAS 142-31-4) and C12AS Na (CAS 151-21-3) for skin irritation as well as C10-16AS Na (CAS 68585-47-7) and C12-13AS K (CAS 91783-22-1) for eye irritation was performed.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 physico-chemical, 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 programme carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS. During evaluation of the human health hazards of the alkyl sulfates within the AS category it turned out that alkyl sulfates with a carbon chain length of C12 bear the most concern for potential adverse effects on human health. This trend is seen among others for the irritating properties of alkyl sulfates. Therefore a read across to C12AS is considered to be a worst case assumption for C8-10AS Na (CAS 85338-42-7). The available in vivo and in vitro studies but also studies on human volunteers investigating the irritating potency of alkyl sulfates in dependency of their carbon chain length are summarised in the discussion below.

Skin irritation

There is one relevant study for the read-across substance C12AS Na (CAS 151-21-3) available addressing skin irritation.

The study conducted with C12AS Na (CAS 151-21-3) was performed similar to OECD Guideline 404 under occlusive conditions (Esposito, 1976). Each of six New Zealand White rabbits was exposed for 24 h to 0.5 mL of the unchanged test item and was observed for a period of 72 h for erythema and edema. The 48 reading time point was missing. The mean erythema and edema score after 24 and 72 h were 2.2 and 1.7. Both were not reversible within 72 h. When using the higher value of the 24 and 72 h reading time point as value for the 48 h value (per animal) the mean erythema and edema score of all animals were 2.4 and 2.2, respectively. Thus the test substance was classified as skin irritating Category 2 according to Regulation 1272/2008/EC and R38 according to Directive 67/548/EEC.

It can be expected from the available experimental results that alkyl sulfates with a shorter carbon chain length will be less irritating (see discussion below). That shorter chained alkyl sulfates are not corrosive has been evidenced in an available in vivo irritation study with C8AS Na (CAS 142-31-4). In the OECD guideline 404 study, C8AS Na (CAS 142-31-4) was applied to 3 New Zealand rabbits under semi-occlusive conditions for 4 h (BASF 2012). Skin reactions were scored 1, 24, 48 and 72 h. The observation period was 14 d. Clinical observations comprised of scaling to severe scaling, incrustations, eczema like lessions, bloody, yellowish incrustations, yellowish discolouration of application site and plaque like incrustations. The mean erythema score after 24, 48 and 72 h was 3 for each rabbit. The mean edema scores after 24, 48 and 72 h were 2, 3.3 and 3 for animals 1, 2 and 3, respectively. Erythema and edema were not fully reversible within 14 days. Thus the test substance was classified as skin irritating Category 2 according to Regulation 1272/2008/EC and R38 according to Directive 67/548/EEC.

Taken together, classification of C9-12AS Na (CAS n.a.) as Xi, R38 and Skin Irrit. 2, H315 can be considered as worst case assumption. 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 and R37, respectively) in case the substance is available as neat powder.

 

 

Eye irritation

There are several studies investigating the eye irritating potential of alkyl sulfates (AS) which have shown that AS concentrations of 10% and higher are moderately to strongly irritating to rabbit eyes and that formulations containing more than 20% AS can cause serious eye damage. Unless data are available that show absence of the irritating potential as defined by the EC criteria the classification Xi, R41 according to Directive 67/548/EEC and Eye Dam. 1, H318 according to Regulation (EC) 1272/2008 will be applied for the neat substance.

 

As corrosion and irritation depends on the concentration of the substance in a solvent, further studies with lower concentrations of the test substances were also considered to assess whether specific concentration limits can be set. For this purpose a read across to structurally related ASO4, i.e C12-13AS K (CAS 91783-22-1) and C10-16AS Na (CAS 68585-47-7)with a concentration range of 10 to 22%was performed.

 

In the study with C12-13AS 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 (Braun, 1978) 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 4 sec 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 reversible eye damaging.

The first study with 0.1 mL undiluted C10-16AS Na (CAS 68585-47-7, analytical purity 10%) was performed similar to OECD guideline 405 (Kukulinski, 1980) on three New Zealand White rabbits with an observation period of 7 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 C10-16AS Na (CAS 68585-47-7, analytical purity 10%)was performed similar to OECD guideline 405(Kukulinski, 1980).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%.

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%.

 

Influence of carbon chain length on the irritating properties of alkyl sulfates

In the following studies evaluating the influence of carbon chain length of alkyl sulfates on their irritating properties are summarised (for study summaries see IUCLID chapter 7.12 Additional toxicological information)

In an in vivo study with guinea pigs the dorsal skin was washed with 25 mM aqueous solutions of sodium alkyl sulfates with C9 - C15 chain lengths in a washing simulator. After washing, the wash liquors were analysed for soluble protein (Folin-Ciocalteu method) and total amino acids (spectrocolorimetric assay). The C12 alkyl sulphate was the most effective to remove soluble proteins and amino acids from the skin.

In addition to this in vivo study on guinea pigs there are three studies conducted on the skin of human volunteers available. The skin irritating effects of sodium alkyl sulfates of carbon chain lengths from C8 to C16 was assessed after application to the backs of 10 human volunteers in the scapular region (Kligman, 1967). The skin was exposed to a series of five concentrations under occlusive conditions and after 24 hours for each compound. The percentage of volunteers exhibiting a discernible erythema was determined. The percentage of volunteers showing erythema was plotted against the log of applied concentrations. The ID50 (concentration producing erythema in 50% of the volunteers) was calculated from the graph. ID50 values plotted against the carbon chain length of tested alkyl sulphate showed a maximum of irritancy at C12 followed by C10, C14, C16 and C8.

A further study with human volunteers assessing skin irritancy as a function of varying carbon chain lengths ranging from C8 to C18 was performed with sodium alkyl sulfates (Schulz, 1957). The skin of the inner forearms of 20-25 volunteers was exposed to 0.1% and 0.25% aqueous solutions of alkyl sulfate for 22-24 h under occlusive conditions and the number of volunteers exhibiting skin reactions was recorded. Irritating effects were observed in 17/25 human volunteers for C12, 10/25 human volunteers for C10, 10/25 human volunteers for C14 and 3/25 human volunteers for C8 chained alkyl sulfates. The alkyl sulfates of chain lengths C16 and C18 gave no reactions on any volunteer.

Another available study with human volunteers measured the transepidermal water loss (TEWL) and occurrence of erythema after application of sodium alkyl sulfates with variable carbon chain length from C8 to C16 (purity >99%; Wilhelm, 1993). 20 mM aqueous solutions of alkyl sulfates of varying chain lengths were applied for 24 hours under occlusive conditions to the volar forearm of volunteers. TEWL was measured with an evaporation meter and erythema was objectively quantitated by skin colour reflectance measurements with a chromameter. Increasing barrier damage (TEWL increase) and increasing erythema were observed with increasing alkyl chain length with maximum effects at C12.

The results of the human volunteer studies were confirmed by the results of two in vitro studies. The swelling of excised abdominal human skin discs in the presence of sodium alkyl sulfates at different concentrations was investigated by Choman (1961). Alkyl chain lengths from C8 to C18 (>99% purity) were used. Each skin disc was placed individually in a screw cap test tube containing 20 ml solution and was fully submerged. The discs were removed and thickness was assessed with a micrometre dial gauge. Change in thickness was calculated in terms of percentage difference between initial thickness and thickness following treatment. By plotting the percentage swelling versus log concentration, a straight line was observed. When the slopes of the swelling curves were plotted as a function of carbon chain length of each tested compound the greatest swelling response was observed for the C12 alkyl sulfate. Carbon chain lengths of C10 and C14 produced a lower swelling response followed by C8, C16 and C18.

In a second in vitro study discs of membrane tissue were set up in glass diffusion cells filled with 5 mM solutions of alkyl sulfates of various chain lengths from C8 to C16. Epidermal electrical conductance was measured by means of stainless steel electrodes (Dugard, 1973). A clear correlation between alkyl chain length and the rate of change of electrical conductance was established with a maximum at C12. This change in electrical conductance decreased from C14 to C16 and was absent at C8.

The same trend in the irritating properties of various carbon chain lengths was also observed in a study performed on rabbit eyes. In this in vivo study the effect of a series of sodium alkyl sulfates of chain lengths C8 to C18 on the conjunctivae of rabbit eyes was assessed according to Draize (Daweke, 1959).Upon instillation of 0.1 mL aqueous solutions into the conjunctival sac of the rabbit eye effects were recorded at regular time intervals and the mean Draize score of 18 parallel experiments was determined. Both at equimolar concentrations (86.5 mM) and 2.5% w/w a maximum of irritancy was observed for C12 alkyl sulfate.

 

[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 Directive 67/548/EEC and Regulation (EC) No 1272/2008 the test substance needs to be classified with Xi, R38/R41 and Skin Irrit. 2, H315 and Eye Dam.1, H318, respectively.

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 and according to Directive 67/548/EEC only the classification R36 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).