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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No data on genotoxicity 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.

Bacterial reverse mutation assay (Ames test / OECD 471): negative

Read-across from structural analogue source substances Alcohols, C10-16, ethoxylated (1-2.5 EO), sulfates, mono (hydroxyethyl) ammonium salt (CAS 157627-92-4) and Alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3).


In vitro mammalian cell gene mutation assay (MLA / OECD 476): negative

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

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay
Target gene:
TK operon
Species / strain / cell type:
mouse lymphoma L5178Y cells
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
-S9: 2.44, 4.88, 9.76, 19.5, 39.1, 58.6 µg/mL
+S9: 2.44, 4.88, 9.76, 19.5, 39.1, 78.1, 117 µg/mL
Vehicle / solvent:
n.a.
Untreated negative controls:
yes
Remarks:
untreated cells
Negative solvent / vehicle controls:
no
Remarks:
no vehicle used
Positive controls:
yes
Positive control substance:
other: ethylmethanesulphonate, 7,12-dimethylbenzanthracene
Evaluation criteria:
According to Guideline.
Statistics:
yes
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not examined
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
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 471 (Bacterial Reverse Mutation Assay)
Deviations:
not applicable
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
His operon
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
0, 10, 100, 1000, 10000, 100000 µg/plate
Vehicle / solvent:
distilled water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
distilled water
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 9-aminoacridine, sodium azide, 2-nitrofluorene, 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)
Evaluation criteria:
According to Guideline.
Statistics:
yes
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
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 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
No E.coli strains tested.
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
His operon
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
0, 11, 56, 280, 1400, 7000 µg/plate
Vehicle / solvent:
water
Negative solvent / vehicle controls:
yes
Remarks:
destilled water
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 9-aminoacridine, sodium azide, 2-nitrofluorene, 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)
Evaluation criteria:
According to Guideline.
Statistics:
yes
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

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

Mammalian Bone Marrow Chromosome Aberration Test (CA / OECD 475): negative

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

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
chromosome aberration assay
Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
According to Guideline.
Route of administration:
oral: gavage
Vehicle:
Distilled water
Duration of treatment / exposure:
n.a.
Frequency of treatment:
Once
Post exposure period:
test group: 10, 24 and 48 h
positive control: 26 h
Remarks:
Doses / Concentrations:
0, 1000, 2000 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (50 mg/kg bw)
Tissues and cell types examined:
Femoral bone marrow cells
Details of tissue and slide preparation:
SAMPLING TIMES
test groups: 10, 24 and 48 h after treatment
positive control group: 26 h after treatment
Evaluation criteria:
According to Guideline.
Statistics:
Yes
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

No data on genetic toxicity 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 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.

Genetic toxicity

There is one study available addressing genetic toxicity for the analogue substance AES (C12-14; < 2.5 EO) (CAS No. 157627-92-4). Mutagenicity in bacteria was assessed in this key study performed similar to OECD Guideline 471. Tester strain E.coli was not used during the conduct of the study (Z&S, 1996). In this study, Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 1538 and TA 100 were treated using the plate incorporation method with and without the addition of a rat liver S9-mix. The dose range for the plate incorporation test was 0, 10, 100, 1000, 10000 and 100000 µg/plate. Results achieved with vehicle (distilled water) and positive controls were valid. Cytotoxicity was seen in presence and absence of metabolic activation while no genotoxicity was observed under both circumstances for AES (C12-14; < 2.5 EO) (CAS No. 157627-92-4).

There are two additional studies available addressing in vitro genotoxicity for the analogue substance AES (C12-14; 1-2.5EO) Na (CAS 68891-38-3).

Mutagenicity in bacteria was assessed in a key study performed similar to OECD Guideline 471. Tester strain TA 102 or E.coli were not used during the conduct of the study (Sasol, 1994). In this study, Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 1538 and TA 100 were treated using the plate incorporation method with and without the addition of a rat liver S9-mix. The dose range for the plate incorporation test was 11, 56, 280, 1400 and 7000 µg/plate. Results achieved with vehicle (distilled water) and positive controls were valid. Cytotoxicity was seen in the presence and absence of metabolic activation while no genotoxicity was observed under both circumstances for AES (C12-14; 1-2.5 EO) Na (CAS 68891-38-3).

The mutagenicity of AES (C12-14) Na (CAS 68891-38-3, analytical purity 27.6% a.i., no data on grade of ethoxylation) in a mammalian cell line was investigated according to OECD guideline 476 using the mouse lymphoma L5178Y cells with and without metabolic activation (BASF, 1995a). The test concentrations were 2.44, 4.88, 9.76, 19.5, 39.1 and 58.6 µg/mL without metabolic activation as well as 2.44, 4.88, 9.76, 19.5, 39.1, 78.1 and 117 µg/mL with metabolic activation. Results achieved with the negative (distilled water) and positive controls were valid. Cytotoxicity was seen in presence and absence of metabolic activation while no genotoxicity was observed under both circumstances for Na AES (C12-14, 1-2.5 EO) (CAS 68891-38-3).

Referring to in vivo genotoxicity, the in vivo clastogenic potential of the analogue compound AES (C12-14) Na (CAS 68891-38-3, analytical purity 27-29% a.i., no data on grade of ethoxylation) was assessed in a mammalian bone marrow chromosomal aberration test with CD-1 mouse according to OECD Guideline 475 (BASF, 1995b). The test substance was administered via gavage at doses of 1000 and 2000 mg/kg bw to five animals per sex per dose. Distilled water was used as vehicle. The post exposure period were 10, 24 and 48 h for the test group including the vehicle control and 26 h for the positive control group. Results achieved with the negative (distilled water) and positive controls were valid. No signs of toxicity and no increased number of chromosome aberration were seen at 1000 and 2000 mg/kg bw. Thus the test substance did not show clastogenicity at 1000 and 2000 mg/kg bw based on the test material and 270 to 290 and 540 to 580 mg/kg bw based on the active ingredient.

In conclusion, the test substance did not show any genotoxic potential. This is supported by the conclusions of the HERA (2003) report for AES were it is stated that: “In all available in vitro and in vivo genotoxicity assays, there is no indication of genetic toxicity of AES.”

Influence of counter ions on genotoxicity

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. Therefore, contribution of TEA to genotoxicity 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

The available data on genetic toxicity do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.