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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
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 22- October 13, 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Reliable study according to currenty guidelines under GLP According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Justification for type of information:
This is a read-across study. See section 13 for detailed justification
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: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 application

ENVIRONMENTAL 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 item

VEHICLE
Minimally 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 AG

REMOVAL 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: 4h

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animal with equal erythema score of 3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
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:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
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 an amount of 0.5 g of the 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 conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no study on skin irritation of C10-12AS Na (CAS 85049-86-1) available. Therefore a read across to structurally related AS, i.e. C8AS Na (CAS 142-31-4) and C12AS Na (CAS 151-21-3) for skin irritation and C10-16 AS 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.

 

Skin irritation

The skin irritating property of C10-12AS Na (CAS 85049-86-1) is assessed via read-across to the structurally related alkyl sulfates, i.e. C8AS Na (CAS 142-31-4) and C12AS Na (CAS 151-21-3). 

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 after removal of the patch. The observation period was 14 d. Clinical observations comprised of scaling to severe scaling, incrustations, eczema like lesions, bloody, yellowish incrustations, yellowish discoloration 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 d. 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.

The relevant 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

 

Based on the available data C10-12 AS Na (CAS 85049-86-1) is assumed to be irritating to the skin.

 

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 AS, 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 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 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%.

[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 selection of skin irritation / corrosion endpoint:
The key study was selected.

Justification for selection of eye irritation endpoint:
worst case assumed

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

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.

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).