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Key value for chemical safety assessment

Additional information

No data on genetic toxicity are available for C16-18 and C18 unsaturated AS Na (CAS 1394155-71-5). Therefore this endpoint is covered by read across to structurally related alkyl sulfates (AS) , i.e. C12-18AS Na (CAS 68955-19-1), C14-18 and C18 unsaturated AS Na (CAS 90583-31-6), C12AS Na (CAS 151-21-3), C16-18 AS Na (CAS 68955-20-4) 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.The AS of the AS category also 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 programme carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS.

There are overall six studies available addressing genetic toxicity for the read-across substances C12-18AS Na (CAS 68955-19-1), C14-18 and C18 unsaturated AS Na (CAS 90583-31-6), C12AS Na (CAS 151-21-3), C16-18AS Na (CAS 68955-20-4) and C12-15AS Na (CAS 68890-70-0).

Mutagenicity in bacteria

Two studies assessing the mutagenicity of AS in bacteria are available.

In the first study, performed according to OECD Guideline 471, Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 1538 and TA 100 were treated with C12-18AS Na (CAS 68955-19-1, analytical purity 39.4%) in presence and absence of metabolic activation according to the plate incorporation method. The tester strains TA 102 or E.coli were not used during the conduct of the study (Banduhn, 1991). In this study the dose range was 8, 40, 200, 1000, 5000 µg/plate in the first experiment and 11.1, 33.3, 100, 300, 600 µg/plate in a second experiment. Results achieved with negative control (untreated), vehicle (water) and positive controls were valid. Cytotoxicity was observed in presence and absence of metabolic activation at and above 200 µg/plate. No genotoxicity was observed.

The second bacterial mutagenicity study was performed according to OECD guideline 417 on Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 1538 and TA 100 with C14-18 and C18 unsaturated AS Na (CAS 90583-31-6, analytical purity 57-60%). The tester strains TA 102 or E.coli were not used during the conduct of the study (Banduhn, 1991). The test substance was applied at concentrations of 8, 40, 200, 1000 and 5000 µg/plate according to the plate incorporation method. Results achieved with negative control (untreated), vehicle (water) and positive controls were valid. Cytotoxicity was observed in presence and absence of metabolic activation at 5000 µg/plate. No genotoxicity was observed.

Mutagenicity in mammalian cells

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 C12ASNa (CAS 151-21-3).

Genotoxicity in mammalian cells 

The potential of C16-18AS Na (CAS 68955-20-4, analytical purity 55%) to induce in vivo micronuclei was assessed in a study conducted according to OECD guideline 474 with CFW-1 mouse (Wallat, 1986). The test substance was administered via gavage at doses of 400, 2000 and 4000 mg/kg bw to 7 animals per sex and dose. Bone marrow was sampled 24 h (400 and 2000 mg/kg bw) and 24, 48 and 72 h (4000 mg/kg bw) after gavage. Results achieved with the vehicle (water) and positive controls were valid. No signs of toxicity were noted. As no enhanced chromosome aberrations were observed in this micronucleus test the test substance was considered to be not clastogenic.

Genotoxicity in vivo

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 with rat (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 micronucleus test the test substance was considered to be not clastogenic.

The potential of C12AS Na (CAS 151-21-3) to induce micronuclei in vivo was assessed in a study comparable to the dominant lethal test with CD-1 mouse (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 male and the frequency of early death, frequency of pregnancy and number of implantations was assessed. No adverse effects on and 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…” [2] 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].

 

[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 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 muatation assay (MLA / OECD guideline 476): negative
In vivo clastogenicity:
Mammalian Erythrocyte Micronucleus Test: negative (MNT / OECD guideline 474)
Mammalian Bone Marrow Chromosome Aberration Test (CA / OECD guideline 475)
In vivo study comparable to the dominant lethal test: negative (DLA / OECD guideline 478)

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.