Registration Dossier

Administrative data

Description of key information

No data are available for the target substance Alcohols, C12-14, ethoxylated (1-2.5 EO), sulfates, triethanolammonium salts (CAS 157627-94-6). Therefore, read-across from structural analogue substances has been applied.

skin irritation (OECD 404): irritating

Read-across from structural analogue source substances Alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) and C12-C14 fatty alcohol polyethylene glycol (2EO) ether suphate, triisopropanolammonium salt (CAS 174450-50-1).


eye irritation (OECD 405): highly irritating/corrosive

Read-across from structural analogue source substances Alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3).


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

>= 10% Eye damage Cat 1 H318
>=5% - <10% Eye Irrit. Cat.2
< 5% No Classification

SCLs have been derived using supporting studies with different contents of analogue source substances to investigate the effects of differenct AES concentrations on eye irritation / corrosion.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals and environmental conditions:
According to Guideline.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
14 days
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.8
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS).
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
According to Guideline.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 h
Observation period:
21 days
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
3.2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
3.2
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: Skin irrit. 2, H315. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
Study was conducted before implementation of GLP.
Species:
rabbit
Strain:
other: Kleine weiße Russen, Chbb-SPF
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: Eye damage 1, H318. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS).
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
5% a.s.
Controls:
yes, concurrent no treatment
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: Eye irrit. 2, H319. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS).
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Only limited data on test material are available.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
Study was conduced before implementation of GLP.
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.6
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Interpretation of results:
other: Eye damage 1, H318. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS).
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Only limited data on test material are available.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
Study was conduced before implementation of GLP.
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Amount: 0.1 mL
Concentration: 20% (5.4% a.i.)
Duration of treatment / exposure:
single administration without washing
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.2
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No data on skin and eye irritation/corrosion are available for AES (C12-14; 1-2.5 EO) C6H15NO3 (CAS 157627-94-6). Therefore, this endpoint is covered by read-across from structurally related AES. The AES reported within the AES category show similar structural, physico-chemical, environmental and toxicological properties. The approach of grouping different AES for the evaluation of their effects on human health and the environment was also made by the Danish EPA (2001) and HERA (2003), supporting the read-across approach between structurally related AES. Within the HERA report (2003) it was concluded that “The skin irritating properties of AES normally decrease with increasing level of ethoxylation.” 

Skin irritation

There are two studies available addressing skin irritation. Both studies are accounted for in a Weight-of-Evidence approach.

The study conducted with AES (C12-14) Na (CAS 68891-38-3, no data on ethoxylation grade) was performed according to OECD Guideline 404 under semi-occlusive conditions (BASF, 1994a). Each of three New Zealand White rabbits was exposed for 4 h to 0.5 g of the unchanged test item (analytical purity 70%) and was observed for a period of 21 days for erythema and edema. The mean erythema score (24, 48 and 72 h reading) and the mean edema score over all animals was 3.2, which fully reversed within the 21 days observation period. Thus the test substance was classified as skin irritating Category 2 according to the CLP Regulation (EC) No. 1272/2008.

The second study regarding skin irritation/corrosion was conducted on three Small White Russian rabbits with AES (C12-14; 2 EO) TIPA (CAS 174450-50-1) according to OECD Guideline 404 (Sasol, 1997c). Each of the rabbits was exposed for 4 h to 0.5 mL of the unchanged test item and was observed for a period of 14 days for erythema and edema. The mean erythema score (24, 48 and 72 h reading) over all animals was 2.3 and the mean edema score over all animals was 2.8, which fully reversed within the 14 days observation period. Thus, the test substance was classified as skin irritating Category 2 according to the CLP Regulation (EC) No. 1272/2008.

 

Eye irritation

Regarding eye irritation/corrosion there is one suitable key study available for the neat substance for the structural analogue substance AES (C12-14; 1-2.5 EO) Na (CAS 68891-38-3). In this study, 0.1 mL of unchanged test item (analytical purity 28%) was applied to one eye of each of three rabbits similar to OECD guideline 405 (Sasol, 1986). The observation period lasted 21 days. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 1.3, 0.8, 3 and 1. The corneal and the effects on the iris were not fully reversible within 21 days while conjunctival redness and chemosis fully reversed within the observation period. Thus the test substance produced severe eye damage at a concentration of 28%.

Derivation of SCL values

As corrosion and irritation depends on the concentration of the substance in a solvent, further studies with lower concentrations of the test substance were also considered to assess whether specific concentration limits can be set. For this purpose, three studies with the analogue substances (C12-14; 4 EO) Na (CAS 68891-38-3) and one study with the analogue substance (C10-16; 2 EO) Na (CAS68585-34-2) with a concentration range of 1 to 10% were evaluated.

One study was performed with 0.1 mL AES (C12-14; 4 EO) Na (CAS 68891-38-3, analytical purity 10%) similar to OECD guideline 405 (Stepan, 1980a) 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 1.6, 0.6, 2 and 1.6 representing an eye irritating effect of the test substance at a concentration of 10% . The effects were not fully reversed within the 7 days observation period. Therefore the test substance showed eye irritating potential.

The second study was performed with 0.1 mL AES (C12-14; 4 EO) Na (CAS 68891-38-3) similar to OECD guideline 405 (Stepan, 1980b) on three New Zealand White rabbits with an observation period of 7 days, however at an concentration of 5%. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 0.4, 0, 1 and 0.3. All effects reversed within the 7 days observation period. Thus, the test substance was not irritating to the eye at a concentration of 5%.

In a further supporting study with AES (C12-14; 2 EO) Na (CAS 68891-38-3) according to OECD guideline 405, 0.1 mL of the test substance was applied to the rabbits eye at a concentration of 20% resulting in an actual concentration of 5.4% (Z&S, 1997).The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 0, 0, 1.2 and 0. The conjunctival redness reversed within the 7 days observation period. Thus the test substance was not irritating to eyes at a concentration of 5.4%.

The supporting study with AES (C10-16) Na (CAS 68585-34-2, no data on grade of ethoxylation, analytical purity 58%) was performed similar to OECD guideline 405 (Unilever, 1980).The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 0.7, 1, 3 and 3.3. All findings were fully reversible within the observation period. Thus, the test substance showed eye irritating properties at a concentration of 5%.

Based on the above mentioned results with different concentrations of structurally related alkyl ethersulfates, a cut of value for classification as severe irritating to eyes is set at a concentration of 10% and for classification as irritating at a concentration of 5% for the AES of the category. No classification is warranted at concentrations below 5%.

Influence of counter ions on irritating potential

Since triethanolamine (TEA) in its protonated form (triethanolammonium) is the counter-ion present in Alcohols C12-14, ethoxylated (1-2,5 EO) sulphated, trieth salts (CAS 157627-94-6), TEA might have an impact on the toxicological properties of the registered substance. Therefore, the toxicological profile of TEA is considered. TEA is not listed in Annex VI of Regulation 1272/2008. In addition the effects of TEA on human health were assessed by the OECD in the SIDS initial assessment Report (2013). Despite of some local signs of irritation TEA gives no rise to concern of adverse effects on human health. Alkyl ether sulfates of the current Category are classified as skin irritating and corrosive to the eyes. Therefore contribution of TEA to the irritating potential of AES is not expected.

 

References:

Danish EPA - Environmental and Health Assessment of Substances in Household Detergents and Cosmetic Detergent Products (2001). Environmental Project No. 615, pp. 24-28

HERA (2003). Human & Environmental Risk Assessment on ingredients of European household cleaning products Alcohol Ethoxysulphates, Human Health Risk Assessment Draft, 2003. http: //www.heraproject.com.

SIDS initial assessment report, (2013); http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?key=8aefe41b-8499-4052-943f-f6dd6f8c5997&idx=0

Justification for classification or non-classification

According to the classification criteria of Regulation (EC) No. 1272/2008 (CLP) the test substance needs to be classified with Skin Irrit. 2, H315 and Eye Dam.1, H318, respectively.

Further, based on supporting data from analogue compounds, specific concentration limits could be assessed fo the present substance with respect to eye irritation. In fact, the supporting data revealed that at about 10% active substance only the classification Eye Irrit. Cat.2 remains and below 5% active substance no classification at all is necessary. Hence, the Generic Concentration Limits (GCLs) can be substituted by the following specific ones (SCLs):

SCLs according to CLP:

>= 10% Eye damage Cat 1 H318
>=5% - <10% Eye Irrit. Cat.2
< 5% No Classification