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Key value for chemical safety assessment

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 are sufficient data on the genotoxicity of C12AS Na (CAS 151-21-3) available.

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, 1988). In the study with C12AS Na (CAS 151-21-3) 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 was 8, 40, 200, 1000, 5000 µg/plate for the first experiment (with and without S9 mix) as well as 5, 10, 20, 40, 80 µg/plate (-S9 mix) and 2.5, 10, 40, 160, 640 µg/plate (+S9 mix) for the second experiment. Results achieved with vehicle (water) and positive controls were valid. Cytotoxicity was observed in presence and absence of metabolic activation occasionally around 200 µg/plate while no genotoxicity was observed for C12AS Na (CAS 151-21-3) at all.

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, 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 for C12AS Na (CAS 151-21-3).

The potential of C12AS Na (CAS 151-21-3) to induce in vivo chromosomal aberration was assessed in a study comparable to the dominant lethal test with CD-1 mice (Unilever, 1976). The test substance was administered via gavage at doses of 120, 380 and 1200 mg/kg bw to a total of 225 males. Each male was caged with 2 virgin females for 7 days. Thereafter males were caged with another two virgin females for 7 days. This was repeated another 6 times. The males were not further examined. Females were sacrificed 13 days after the assumed date of fertilization, i.e.15 or 16 days after caging females with males and the frequency of early death, frequency of pregnancy and number of implantations was assessed. No adverse effects on the frequency of early death, frequency of pregnancy and number of implantations occurred. Thus the test substance did not show clastogenicity at doses of 120, 380 and 1200.

 

In conclusion, the substance 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 […].”

 

REFERENCES

[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:
In vivo study comparable to the dominant lethal test (DLA / OECD guideline 478): 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.