Alcohols, C9-11, branched and linear, ethoxylated, sulfates, ammonium 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.

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 (C9-11, 1-2.5 EO) NH4 (CAS 160901-27-9). Therefore this endpoint is covered by read across from structurally related AES, i.e. AES (C8-10, 1-2.5 EO) Na and 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. For further details on the suitability of the read-across please refer to the AES Category Approach Justification.

In general a lack of mutagenic activity for the AES category is predictable based on structural and mechanistic considerations. Mutagens are chemicals that either 1) contain highly reactive electrophilic centers capable of interacting with nucleophilic sites on DNA (direct acting agents) or 2) can be metabolized to highly reactive electrophiles. The chemical structures represented by this chemical class do not contain electrophilic functional groups or functional groups capable of being metabolized to electrophiles. AES are readily absorbed in the gastrointestinal tract in human and rat and excreted principally via the urine or faeces depending on the length of the ethoxylate chain but independently of the route of administration. Once absorbed, AES are extensively metabolized by beta- or omega oxidation. The EO-chain seems to be resistant to metabolism. Thus, AES with fully saturated carbon chains are not metabolized to reactive electrophiles.

 

There are two studies for the read-across substance AES (C8-10, 1-2.5 EO) Na and one study for the read-across substance AES (C12-14; 1-2.5 EO) Na (CAS 68891-38-3) addressing genetic toxicity available.

Mutagenicity of AES (C8-10, 2 EO) Na in bacteria was assessed in a study performed according to OECD Guideline 471 with Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 102 and TA 100 (Wallner, 2012). The tester strains were treated using the plate incorporation and the pre incubation method both with and without the addition of a rat liver S9-mix. The concentrations for both testing methods was 3.16, 10, 31.6, 100, 316, 1000, 2500 and 5000 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.

The mutagenicity of AES (C8-10, 2 EO) Na in a mammalian cell line was investigated according to OECD guideline 476 using the mouse lymphoma L5178Y cells with and without metabolic activation (Trenz, 2012). The test concentrations were 0.01, 0.02, 0.05, 0.10, 0.20, 0.24, 0.28, 0.32 mM without metabolic activation as well as 0.01, 0.05, 0.24, 0.28, 0.32, 0.36, 0.40, 0.44, 0.48 mM with metabolic activation in the first experiment (4 h incubation). In the second experiment the cells were incubated with concentrations of 0.15, 0.35, 0.39, 0.43, 0.45, 0.47, 0.49, 0.53 mM in the presence of metabolic activation for 4 h and at concentrations of 0.0005, 0.001, 0.005, 0.01, 0.05, 0.10, 0.15, 0.20, 0.25 mM in the absence of metabolic activation for 24 h. Results achieved with the vehicle (RPMI medium) and positive controls were valid. Cytotoxicity was seen in presence and absence of metabolic activation. No genotoxicity was observed, except for the highest dose level in experiment I with metabolic activation where a significantly increased number of mutants and a dose dependency were seen at 0.48 mM. In addition the Global Evaluation Factor of 126 was exceeded by the induced mutant frequency. This effect was observed in the highly cytotoxic range only (relative total growth below 10%) and was not verified in the verification experiment (experiment II with metabolic activation). Therefore this effect was considered to be of no biological relevance.

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, AES and their metabolites lack the structural moieties which confer mutagenic properties. This is reflected by the lack of reliable positive genotoxicity studies within the AES category. 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 outcome is negative.

Short description of key information:
In vitro bacterial reverse mutation assay (Ames test / OECD guideline 471): negative
In vitro mammalian cell gene muatation assay (MLA / OECD guideline 476): negative
In vivo mammalian chromosome aberration assay (CA / OECD guideline 475): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to the classification criteria of Directive 67/548/EEC and Regulation (EC) No 1272/2008 the substance does not need to be classified for genotoxicity.