Sulfuric acid, mono-C12-16-alkyl esters, sodium salts

Endpoint summary

Additional information

The lack of mutagenic activity for the alkyl sulfates 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. Alkyl sulfates with fully saturated carbon chains are not metabolized to reactive electrophiles. The consistent lack of mutagenic activity with alkyl sulfates is consistent with these mechanistic predictions.

There is only one bacterial mutagenicity test for C10-16AS Na (CAS 73296-89-6) available. Therefore this endpoint is further covered by read across to structurally related alkyl sulfates (AS), i.e. C12AS Na (CAS 151-21-3) and C12-15AS Na (CAS 68890-70-0). The possibility of a read-across to other alkyl sulfates in accordance with Regulation (EC) No 1907/2006 Annex XI 1.5. Grouping of substances and read-across approach was assessed. In Annex XI 1.5 it is given that a read-across approach is possible for substances, whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. The AS reported within the AS category show structural similarity. The most important common structural feature of the category members is the presence of a predominantly linear aliphatic hydrocarbon chain with a polar sulfate group, neutralized with a counter ion. This structural feature confers the surfactant properties of the alkyl sulfates. The surfactant property of the members of the AS category in turn represent the predominant attribute in mediating effects on mammalian health. Therefore, the AS of the AS category have similar physico-chemical, environmental and toxicological properties, validating the read across approach within the category. The approach of grouping different AS for the evaluation of their effects on human health and the environment was also made by the OECD in the SIDS initial assessment profile [1] and by a voluntary industry program carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS.

Mutagenicity in bacteria of C12-16AS Na (CAS 73296-89-6)

Mutagenicity in bacteria was assessed in a study performed according to OECD Guideline 471. Tester strains TA 102 or E.coli were not used during the conduct of the study (Banduhn, 1992). In this study with C12-16AS Na (CAS 73296-89-6), Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 1538 and TA 100 were treated with and without addition of a rat liver S9-mix. The dose range was 8, 40, 200, 1000, 5000 µg/plate with and without S9-mix in the first experiment and 2.2, 6.6, 20, 60, 180 µg/plate with and without metabolic activation in the second experiment. Results achieved with vehicle (medium), untreated cells and positive controls were valid. Cytotoxicity was observed in presence and absence of metabolic activation at concentrations of 180 µg/plate and higher while no genotoxicity was observed.

Mutagenicity in mammalian cells of C12AS Na (CAS 151-21-3)

The mutagenicity of C12AS Na (CAS 151-21-3) in a mammalian cell line was investigated similar to OECD guideline 476 using the mouse lymphoma L5178Y cells with and without metabolic activation (McGregor et al., 1988). The test concentrations were 3.125, 6.25, 10, 12.5, 20, 25, 30, 40, 50, 55, 60, 65, 70, 80 and 100 µg/mL without and 50, 55, 60, 65, 70, 75, 80, 85, 90 and 95 µg/mL with metabolic activation. Results achieved with the negative (untreated), vehicle (DMSO) and positive controls were valid. Cytotoxicity was observed in presence and absence of metabolic activation while no genotoxicity was observed under both circumstances.

In vivo clastogenicity of C12-15AS Na (CAS 68890-70-0)

The potential of C12-15AS Na (CAS 68890-70-0, analytical purity approx. 30%) to induce in vivo chromosomal aberration was assessed in a study conducted similar to OECD guideline 475 in rats (Hope, 1976). The test substance was administered via feed at a dose of 1.13% for a period of 90 days to 6 animals per sex and dose and bone marrow was sampled thereafter. Results achieved with the vehicle (DMSO) and positive controls were valid. No signs of toxicity were noted. As no enhanced chromosome aberrations were observed in this chromosomal aberration test the test substance was considered to be not clastogenic.

In conclusion, the alkyl sulfates did not show any genotoxic potential. This is supported by the conclusions of the HERA Draft report “AS are not genotoxic, mutagenic or carcinogenic…” and the conclusions of the SIDS initial assessment profile “Alkyl sulfates of different chain length and with different counter ions were not mutagenic in standard bacterial and mammalian cell systems [...]. There was also no indication for a genotoxic potential of alkyl sulfates in various in vivo studies on mice […].”

 

[1] SIDS initial assessment profile, (2007);
http://www.aciscience.org/docs/Alkyl_Sulfates_Final_SIAP.pdf

[2] (HERA Draft report, 2002);
http://www.heraproject.com/files/3-HH-04-%20HERA%20AS%20HH%20web%20wd.pdf

Justification for selection of genetic toxicity endpoint
No study selected as all 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 clastogenicity:
Mammalian Bone Marrow Chromosome Aberration Test (CA / OECD guideline 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.