Alcohols, C16-18 and C18-unsatd., ethoxylated, sulfates, sodium salts

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The assessment is based on the data currently available. New studies, based on the category review and the final decisions issued for some of the category substances, which are also relevant for this assessment, are currently being conducted. The hazard assessment with respect to genetic toxicity will be updated once all ongoing studies have been finalised.

Bacterial reverse mutation assay (Ames test / OECD guideline 471): negative
In vitro mammalian cell gene mutation assay (MLA / OECD guideline 476): negative

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to Guideline study with acceptable restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

No E.coli strains tested.

Qualifier:

according to guideline

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

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP Guideline study. 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.

Qualifier:

according to guideline

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

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

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

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP Guideline study. 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.

Qualifier:

according to guideline

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 or test system 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 (migrated information): negative

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

The assessment is based on the data currently available. New studies, based on the category review and the final decisions issued for some of the category substances, which are also relevant for this assessment, are currently being conducted. The hazard assessment with respect to genetic toxicity will be updated once all ongoing studies have been finalised.

No data on genetic toxicity are available for AES (C16-18/18:1, 2 EO) Na (CAS 157627-95-7). Therefore this endpoint is covered by read across to structurally related AES, i.e. AES (C12-14; 1-2.5 EO) Na (CAS 68891-38-3). 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.

There are three studies available addressing genetic toxicity for the read-across 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 (Schöberl, 1994). In the study with AES (C12-14; EO2)Na (CAS 68891-38-3, analytical purity 71.5%) 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 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%, 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 (Falezza, 1995). 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).

The in vivo clastogenic potential of AES (C12-14) Na (CAS 68891-38-3, analytical purity 27-29%, 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 (Ciliutti, 1995). 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 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.”

 

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.

Justification for selection of genetic toxicity endpoint
No study selected as all three studies were negative.

Short description of key information:
In vitro gene mutation:
Bacterial reverse mutation assay (Ames test / OECD guideline 471): negative
In vitro mammalian cell gene mutation assay (MLA / OECD guideline 476): negative
In vivo:
Mammalian Bone Marrow Chromosome Aberration Test (OECD 475): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.