Poly(oxy-1,2-ethanediyl), .alpha.-sulfo-.omega.-hydroxy-, C8-10-alkyl ethers, sodium salts

Endpoint summary

Description of key information

Skin sensitisation (in vivo, OECD 406): not sensitising

Conclusion based on data with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Aug - 25 Oct 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted in 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certifying authority: Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Erlangen, Germany

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

For the present test substance, the LLNA is not suitable. According to OECD TG 429 certain limitations may justify the use of TG 406 as an alternative, i.e. "false positive findings with certain skin irritants, such as some surfactant type chemicals". As the test substance is a skin irritant surfactant, the GPMT according to OECD test guideline 406 was chosen as the test for skin sensitization.

Species:

guinea pig

Strain:

other: Crl: HA (SPF)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: Approximately 6 weeks old
- Weight at study initiation: 396 - 492 g
- Housing: Animals were kept in groups in Terluran cages on Altromin saw fibre bedding.
- Diet: Autoclaved hay and Altromin 3122 maintenance diet for guinea pigs; ad libitum
- Water: tap water (drinking water, municipal residue control, microbiological controls at regular intervals); ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

2.5% (w/v)

Day(s)/duration:

Study Day 0 three injections

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

1.5%

Day(s)/duration:

Study Day 7 Exposure: 48 h

Adequacy of induction:

other: Highest applicable concentration shown to not cause any signs of skin irritation.

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline

Concentration / amount:

0.5%

Day(s)/duration:

Study Day 20 Exposure: 24 h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

test group: 10 animals
negative control group: 5 animals
positive control group 5 animals

Details on study design:

RANGE FINDING TESTS:
A range finding test was performed with 10 animals. The concentrations used in the main experiment based on the results of this test.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline 0.9% NaCl
Injection 2: a 2.5% concentration of the test item in physiological saline 0.9% NaCl
Injection 3: a 2.5% concentration of the test item formulated in a 1:1 mixture (v/v) FCA/physiological saline 0.9% NaCl
Epicutaneous: 1.5% in vaseline
- Negative control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline 0.9% NaCl
Injection 2: 100% physiological saline 0.9% NaCl
Injection 3: a 50% (v/v) formulation of physiological saline 0.9% NaCl in a 1:1 (v/v) mixture FCA/physiological saline 0.9% NaCl
Epicutaneous: pure vaseline
- Positive control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/physiological saline 0.9% NaCl
Injection 2: 2% mercaptobenzothiazole in cottonseed oil
Injection 3: a 50% (v/v) formulation of 2% mercaptobenzothiazole in a 1:1 (v/v) mixture FCA/physiological saline 0.9% NaCl
Epicutaneous: 25% mercaptobenzothiazole
- Site: shoulder (intradermal + epicutaneous)
- Frequency of applications: Intradermal Day 0, epicutaneous Day 7

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: day 20
- Exposure period: 24 hours
- Test groups: 0.5% of test item in vaseline
- Negative control group: 0.5% of test item in vaseline
- Positive control group: 15% mercaptobenzothiazole
- Site: flank
- Evaluation (hr after challenge): 24 and 48 h after removal of challenge patch.

Positive control substance(s):

yes

Remarks:

mercaptobenzothiazole

Positive control results:

The positive control substance induced positive reactions in 5/5 animals (100%), thereby validating the test system.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

induction: 0%; challenge: 0.5%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no effects observed

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

induction: 0%; challenge: 0.5%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no effects observed

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction: 2.5%; challenge: 0.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no effects observed

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction: 2.5%; challenge: 0.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no effects observed

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

induction: 2%; challenge: 15%

No. with + reactions:

5

Total no. in group:

5

Clinical observations:

erythema grade 2 in 5/% and oedema grade 1 in 1/5 animals

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

induction: 2%, challenge: 15%

No. with + reactions:

5

Total no. in group:

5

Clinical observations:

erythema grade 2 in 5/5 aniamls

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

Under the present test conditions, the test substance was assessed to have no skin sensitising potential. The test is valid as evidenced by the positive control substance's results. Therefore, the test substance does not meet the classification criteria and no classification is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation

Data on skin sensitisation are available foralcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) as well as several member substances of the Alkyl Ether Sulfates (AES) category.

 

Study with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2)

A study was performed with the substance 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 conditions of the study.

 

Studies in the AES category

The available studies on skin sensitisation, including those performed with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2), 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.

In addition to the study performed with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2), a second high-quality test was available.

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 with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) 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.