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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

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

Mammalian Erythrocyte Micronucleus Test (MNT / OECD guideline 474): negative

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

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 no study regarding genotoxicity available for C12-14 AS MIPA (CAS 85681-66-9). Therefore this endpoint is covered by read across to structurally related alkyl sulfates (AS) for weight-of-evidence approach, i.e. C12-14 AS Na (CAS 85586-07-8), C12 AS Na (CAS 151-21-3), C12-15 AS Na (CAS 68890-70-0) and C12-14 AS TEA (CAS 90583-18-9). 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 physicochemical, 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.

 

Mutagenicity in bacteria

Mutagenicity in bacteria was assessed in a study performed according to OECD Guideline 471. Tester strain TA 102 or E.coli were not used during the conduct of the study (KAO, 1996). In this study with C12-14 AS Na (CAS 85586-07-8), 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 5, 15, 50, 150, 500, and 1500 µg/plate without and 5, 15, 50, 150, 500, 1500 and 5000 µg/plate with metabolic activation in the first experiment as well as 5, 15, 50, 150, 500, and 1500 µg/plate (with and without S9 mix) in the second experiment. Results achieved with vehicle (DMSO) and positive controls were valid. Cytotoxicity was observed in presence and absence of metabolic activation at 1500 µg/plate while no genotoxicity was observed.

 

Mutagenicity in mammalian cells

The mutagenicity of C12 AS 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.

 

Clastogenicity in vivo

The potential of C12-14 AS TEA (CAS 90583-18-9, analytical purity approx. 41%) to induce micronuclei in vivo was assessed in a study conducted according to OECD guideline 474 with CFW-1 mouse (BASF, 1987c). 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 (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 C12-15 AS 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 (Unilever, 1976c). 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 read across substances 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 […].”

 

Influence of counter-ions on genotoxicity

The effects on health of isopropanolamine (MIPA) are dominated by its corrosive properties. MIPA is listed in Annex VI of EG 1272/2008 as Skin Corrosive Cat 1B, H314. Further information indicates MIPA to be moderately toxic after dermal application. During the registration process for 2010 MIPA was also classified as harmful in contact with skin (Acute Toxicity Cat 4, H312 according to Regulation 1272/2008/EC). There is no indication of genotoxicity by MIPA. Therefore, MIPA is not expected to be genotoxic and therefore will not contribute to the endpoint genotoxicity.

 

[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 classification or non-classification

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

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