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Skin sensitisation: not sensitising

Conclusion based on data with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) and considering all available data on skin sensitisation in the Alkyl Ether Sulfate (AES) category in a Weight-of-Evidence approach.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
GPMT
Deviations:
yes
Remarks:
no positive or negative controls
GLP compliance:
no
Remarks:
Study was conducted prior to implementation of GLP.
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted prior to the introduction of the LLNA as an OECD test guideline.
Species:
guinea pig
Strain:
other: albino
Sex:
male
Route:
intradermal
Vehicle:
water
Concentration / amount:
5%
Adequacy of induction:
not specified
Route:
other: epicutaneous (not further specified)
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted test material (100%)
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
other: epicutaneous; no additional data
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted test material
Adequacy of challenge:
not specified
No. of animals per dose:
10
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
neat material
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
neat material
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
positive control
Remarks on result:
not measured/tested
Reading:
2nd reading
Group:
positive control
Remarks on result:
not measured/tested
Reading:
1st reading
Group:
negative control
Remarks on result:
not measured/tested
Reading:
2nd reading
Group:
negative control
Remarks on result:
not measured/tested
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In the present in vivo skin sensitisation study (GPMT), the test substance did not induce any sensitisation in the guinea pigs tested. It is concluded that the test substance is not a skin sensitiser.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer to the category justification provided in the category object.
Key result
Group:
negative control
Remarks on result:
other: No skin sensitisation potential identified for Alkyl Ether Sulfates (AES) based on all available relevant data in the category.
Key result
Group:
test chemical
Remarks on result:
other: No skin sensitisation potential identified for Alkyl Ether Sulfates (AES) based on all available relevant data in the category.
Key result
Group:
positive control
Remarks on result:
other: No skin sensitisation potential identified for Alkyl Ether Sulfates (AES) based on all available relevant data in the category.

For a detailed assessment of the skin sensitisation potential of the Alkyl Ether Sulfates (AES) category, please refer to the category justification attached to the category object.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
Applying read-across based on grouping of substances (category approach), no skin sensitisation potential is predicted for the target substance.
Executive summary:

The available data on skin sensitisation in the Alkyl Ether Sulfates (AES) category indicate no skin sensitisation potential for the target substance. As explained in the category justification, the differences in molecular structure and composition between the target substance and the members of the AES category are unlikely to lead to differences in the skin sensitisation potential.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation

Data on skin sensitisation are available for alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) as well as several member substances of the Alkyl Ether Sulfates (AES) category.

 

Study with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4)

A study was performed with the test substance to assess the skin sensitising potential. The study was performed according to the protocol described by Magnusson and Kligman (J. Invt. Derm. 1969; 52: 268 - 276), which is similar to the one published in the first version of OECD guideline 406 (Huntsman, 1977c). Ten male guinea pigs were included in the test group. No control groups were included in the study. The test substance (purity not reported) was suspended in deionised water for the intradermal induction. On Day 1 the intradermal induction was performed with 5% test substance. Freund’s complete adjuvant (FCA) was used as the adjuvant. Twenty-four hours before the topical induction 10% sodium lauryl sulphate was applied to the test site to induce skin irritation. The topical induction started on Day 7 with the undiluted test substance, lasting for 48 h under occlusive conditions. On Day 21 the animals of the treatment group were challenged with the undiluted test substance for 24 h under occlusive conditions. Skin reactions were scored 24 and 48 h after patch removal. The topical induction did not cause skin irritation in any negative control or test group animals. Following the challenge, no skin irritation was noted in any animal in the treatment group. Due to the significant methodological deficiencies, the study is not considered to be reliable.

 

Studies in the AES category

The available studies on skin sensitisation, including that performed with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4), are summarised in Table 1 below:

 

Table 1: Database on skin sensitisation in the Alkyl Ether Sulfates (AES) category

CAS / EC Nos.

Substance

Study or Report No.

Study protocol (adopted in)

Concentration in test material [%]

Hazard conclusion

‘Linear’ subgroup

1471312-55-6 / 939-523-2

Alcohols, C8-10, ethoxylated, sulfates, sodium salts

121487

OECD 406 (GPMT)

98.7

Not sensitising

68585-34-2 / 500-223-8

Alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts

247/8409

Similar OECD 406 (GPMT)

Not reported

Not sensitising

4301

OECD 406 (GPMT)

10

Not sensitising

11182

Similar OECD 406 (GPMT)

Not reported

Not sensitising

11182

Similar OECD 406 (Buehler)

Not reported

Not sensitising

16604

Similar OECD 406 (Buehler)

31.4

Not sensitising

4309

Similar OECD 406 (GPMT)

Not reported

Sensitising

4303

Similar OECD 406 (GPMT)

Not reported

Sensitising

4289

Similar OECD 406 (GPMT)

Not reported

Sensitising

4304

Similar OECD 406 (GPMT)

Not reported

Sensitising

9731

Similar OECD 406 (Buehler)

Not reported

Sensitising

30449

Human data (HRIPT), Good clinical practices guideline 21 CFR parts 50 and 56

Not reported

Not sensitising

07-009A

Human data (HRIPT), Good clinical practices guideline 21 CFR parts 50 and 56

Not reported

Not sensitising

68891-38-3 / 500-234-8

Alcohols, C12-14, ethoxylated, sulfates, sodium salts

R770036

OECD 406 (GMPT)

28

Not sensitising

3170

OECD 406 (GPMT)

28

Not sensitising

861041D/UGF 19/SS

OECD 406 (GPMT)

70

Not sensitising

90/8507

Similar OECD 406 (GPMT)

Not reported

Not sensitising

89.0241

OECD 406 (GPMT)

27

Not sensitising

SM880964

Similar OECD 406 (GPMT)

27

Sensitising

174450-50-1 / 605-725-1

Alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts

2399

OECD 406 (Buehler)

83.8

Not sensitising

‘Mixed branched & linear’ subgroup

160901-28-0 / 500-465-4

Alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts

221/7703

Similar OECD 406 (GPMT)

Not reported

Not sensitising

 

Evaluation of skin sensitisation as observed in studies

The available studies were performed with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2), alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8), alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) and alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1) from the ‘linear’ subgroup and with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) from the ‘mixed branched & linear’ subgroup. The concentration of the respective AES substances in the test material used in these studies varied from 10 - 98.7%, with water as the solvent in most test materials. For a number of studies no test material purity was reported. All in vivo animal studies followed the Buehler or GPMT protocol described in OECD guideline 406.

For a majority of the in vivo animal studies, no skin sensitising potential was reported. Mild to severe skin irritation effects (erythema and/or oedema) were observed following the epicutaneous and/or topical induction and were absent following the challenge phase.

Two studies of high quality were available within the category and are summarised below.

A study was performed with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) according to the guinea pig maximisation test protocol described in OECD guideline 406 and under GLP conditions (Z&S, 2013). Ten female guinea pigs were included in the test group. The pure test substance (98.7%) was suspended in physiological saline for the intradermal induction, and in vaseline for the topical induction and challenge phases, respectively. On Day 0 the intradermal induction was performed with 2.5% test substance. The topical induction started on Day 6 with a 1.5% suspension, lasting for 48 h under occlusive conditions. On Day 20 the animals of the test and negative control groups were challenged with 0.5% test substance for 24 h under occlusive conditions. Skin reactions were scored 24 and 48 h after patch removal. The concentrations used in the main study were selected based on the results of a range-finding test with 10 animals. In the positive control group, 5 female guinea pigs were treated according to the same protocol as the test group with mercaptobenzothiazole. The intradermal and topical induction concentrations were 2% and 25%, respectively, while the challenge was performed with a 15% suspension in vaseline.

Following the intradermal induction, skin irritation was noted at the test sites of all animals. The topical induction did not cause skin irritation in any negative control or test group animals. Following the challenge, no skin irritation was observed in the negative control and test group animals. No adverse systemic effects of the treatment or significant body weight changes were noted in any animals. The 5 animals in the negative control group did not show any skin reactions following the challenge, while 5/5 animals in the positive control group showed a positive indication of skin sensitisation, indicating the controls were valid. The test substance showed no sensitising potential under the study conditions.

The study with alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1) was performed according to the Buehler protocol described in OECD guideline 406 and under GLP conditions. Twenty female guinea pigs were included in the test group and ten in the negative control group. The pure test substance (83.8%) was suspended in deionised water for the topical induction and challenge phases. On Day 0 the first topical induction was performed with 50% test substance, lasting for 6 h under occlusive conditions. The second and third topical induction was performed on Day 7 and 14, respectively, with a 50% concentration. On Day 28 the animals of the test and negative control groups were challenged with 25% test substance for 6 h under occlusive conditions. Skin reactions were scored 24 and 48 h after patch removal. The concentrations used in the main study were selected based on the results of a range-finding test with 6 animals.

The dermal treatment during the first induction phase led to scarcely detectable skin irritation in 2/20 animals, 24 h after patch removal. After the second induction phase, 14/20 animals exhibited slight to well-defined erythema in combination with slight oedema 24 h after patch removal. Before the treatment in the third induction phase, these 14 animals, after shearing, still exhibited scaling in the administration area. The test substance was administered to intact skin. 24 h after the second induction phase, the administration area exhibited scarcely detectable erythema and oedema in 4/20 animals, well-defined erythema and oedema in 5/20 animals and moderate erythema and oedema in 2/20 animals, in 1 animal combined with necrotic spots on the skin. The control animals treated with the vehicle did not show irritation on the treated skin at any reading time point during the three induction phases. The challenge treatment did not cause any cutaneous reactions in the negative control and test group animals in the form of erythema or oedema 24 and 48 h after patch removal. No adverse systemic effects of the treatment or significant body weight changes were noted in any animals. A reliability check was performed regularly with 2-mercaptobenzothiazole. The test substance showed no sensitising potential under the conditions of the study.

In the in vivo studies 4309, 4303, 4289, 4304 and 9731 performed with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8), as well as study No. SM880964 performed with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8), it was concluded that the test material caused skin sensitisation. However, for all these studies the information on the irritating skin effect following epicutaneous and/or topical induction was missing. In most studies for which this information was reported, the induction application caused skin irritation. Therefore, the skin effects observed following the challenge phase in these studies are likely to have been skin irritation, rather than skin sensitisation.

Two Human Repeated Insult Patch Tests (study No. 30449 and 07-009A) were performed with alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts (CAS No. 68585-34-2, EC No. 500-223-8). Some skin irritation was noted during the induction phases in a majority of the volunteers. Both studies concluded that the test substance showed no skin sensitising potential in the human volunteers.

 

Data on counter ions

There is experimental data on substances with the counter ions sodium (Na+) and triisopropanolamine (TIPA), showing negative results for skin sensitisation. This indicates that these counter ions will not have a skin sensitising potential.

Magnesium (Mg2+) and ammonium (NH4+) are both considered not to show a skin sensitising potential based on the available data (primarily on their salts).

For a detailed evaluation of a potential effect of the counter ions on the toxicological profiles of the AES member substances, please refer to the category justification attached to the category object.

 

Conclusion on skin sensitisation potential of substances in the AES category

The WoE analysis based on the in vivo studies and HIRPTs indicates that AES substances in general do not show a skin sensitising potential. The conclusion is fully supported by the OECD QSAR Toolbox profiling results. This applies to all AES substances in the category, whether they belong to the ‘linear’, ‘unsaturated’ or ‘mixed branched & linear’ subgroups and regardless of their counter ion. The outcome of this WoE evaluation is used for the hazard assessment and to conclude on classification and labelling of all AES substances in the category. This evaluation is considered sufficient for the hazard assessment and classification and labelling of the AES substances. For a detailed evaluation of the skin sensitising potential of the substances in the AES category, please refer to the category justification attached to the category object.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation obtained with members of the Alkyl Ether Sulfates (AES) category do not meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification. Based on grouping of substances (category approach), alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts (CAS No. 160901-28-0, EC No. 500-465-4) is predicted not to fulfil the classification criteria and is consequently not classified for skin sensitisation.