Sulfuric acid, mono-C12-14(even numbered)-alkyl esters, ammonium salts

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No data are available for the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) regarding in vitro bacterial and in vitro mammalian cell gene mutation. Therefore, read-across from structural analogue substances has been applied.

Bacterial reverse mutation assay (Ames test / equivalent or similar OECD 471): negative with and without metabolic activation

Read-across from source substance sulfuric acid, mono-C12-16-alkyl esters, potassium salts (CAS 90583-12-3).

In vitro mammalian cell gene mutation assay (MLA / OECD 476): negative with and without metabolic activation

Read-across from source substance sodium dodecyl sulfate (CAS 151-21-3).

An in vitro cytogenicity study in mammalian cells or an in vitro micronucleus study was not conducted because adequate data from in vivo cytogenicity tests are available.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Refer to the Category Approach Justification document provided in IUCLID6 Section 13

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: Source, key, 90583-12-3, 1987d

Conclusions:

Interpretation of results: negative

Executive summary:

The potential to induce gene mutations in bacterial cells of the target substance is estimated based on an adequate and reliable in vitro bacterial reverse mutation assay of a structural analogue source substance. Experiments have been performed both in the presence as well as in the absence of metabolic activation. All results obtained are negative, i.e., no gene mutation in the tester strains was observed. Therefore, no hazard with regard to gene mutation in bacterial cells is identified for the target substance. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in gene mutation in bacterial cells.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Refer to the Category Approach Justification document provided in IUCLID6 Section 13

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

-S9: 70, 80 and 90 µg/mL; +S9: 95 µg/mL

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: Source, key, 151-21-3, 1988

Conclusions:

Interpretation of results: negative

Executive summary:

The potential of gene mutations in mammalian cells of the target substance is estimated based on an adequate and reliable in vitro gene mutation study in mouse lymphoma L5178Y cells of a structural analogue source substance. Experiments have been performed both in the presence as well as in the absence of metabolic activation. All results obtained are negative, i.e., no gene mutation in mouse lymphoma L5178Y cells was observed. Therefore, no hazard with regard to gene mutation in mammalian cells is identified for the target substance. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in gene mutation in mammalian cells.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No data are available for the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2). Therefore, read-across from structural analogue substances has been applied.

Mammalian Bone Marrow Chromosome Aberration Test (CA / equivalent or similar OECD 475): negative

Read-across from source substance sulfuric acid, mono-C12-15-alkyl esters, sodium salts (CAS 68890-70-0).

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

Read-across from source substance sulfuric acid, mono-C16-18-alkyl esters, sodium salts (CAS 68955-20-4).

Link to relevant study records

Reference

Endpoint:

genetic toxicity in vivo, other

Remarks:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration and erythrocyte micronucleus

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

weight of evidence

Justification for type of information:

Refer to the Category Approach Justification document provided in IUCLID6 Section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: Source, WoE, 68890-70-0, 1976c

The key result is further supported by an additional study accounted for in a Weight-of-Evidence approach:

Source, WoE, 90583 -18 -9, 1987d: mouse (m/f): negative for genotoxicity after oral gavage application of 400, 2000 and 4000 mg/kg bw

Conclusions:

Interpretation of results: negative

Executive summary:

The potential for in vivo mammalian chromosome aberration of the target substance is estimated based on two adequate and reliable in vivo studies of structural analogue source substances. Feeding of male and female rats with sulfuric acid, mono-C12-15-alkyl esters, sodium salts (CAS 68890-70-0) at 1.13% (nominal in diet) for 90 days did not induce chromosome aberrations in bone marrow. Moreover, a single oral exposure by gavage with 400, 2000 and 4000 mg/kg bw/day sulfuric acid, mono-C12-14-alkyl esters, compds. with triethanolamine (CAS 90583-18-9) did not induce erythrocyte micronuclei in male and female mice. Therefore, based on read-across no hazard with regard to in vivo mammalian chromosome aberration is identified for the target substance. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the genotoxic potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

General considerations

The lack of mutagenic activity for the alkyl sulfates (AS) category is predictable based on structural and mechanistic considerations. Mutagens are chemicals that either contain highly reactive electrophilic centers capable of interacting with nucleophilic sites on DNA (direct acting agents) or can be metabolised to highly reactive electrophiles. The chemical structures represented by the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) and AS in general, incl. the structural analogues used for read-across, do not contain electrophilic functional groups or functional groups capable of being metabolised to electrophiles. AS with fully saturated carbon chains are not metabolised to reactive electrophiles. The consistent lack of mutagenic activity observed for all AS is consistent with these mechanistic predictions.

Genetic toxicity in vitro

There are no genotoxicity data for the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) available. Therefore, these endpoints are covered by read-across from structurally related alkyl sulfates (AS). The possibility of a read-across from 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 physico-chemical, 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, neutralised 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 represents the predominant attribute in mediating effects on mammalian health. Therefore, the members 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 programme carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read-across approach between structurally related AS.

Ammonium sulfate is used to produce AS NH4 within the current AS category. There is a substantial data base on ammonium sulfate online available. Ammonium sulfate is not listed in Annex VI of Regulation (EC) No. 1272/2008 (CLP). In addition, the effects of ammonium sulfate on human health were assessed by the OECD in the SIDS initial assessment report [3]. Ammonium sulfate gives no rise to concern of adverse effects on human health. Therefore, a contribution of ammonium sulfate to the effects on human health is considered to be negligible when assessing human health effects of the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2).

 

Mutagenicity in bacteria

Mutagenicity in bacteria was assessed in a study performed according to OECD Guideline 471 with sulfuric acid, mono-C12-16-alkyl esters, potassium salts (CAS 90583-12-3, analytical purity 30%). 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. Tester strain TA 102 or E.coli were not used during the conduct of the study (BASF, 1987d). The dose range was from 8 to 5000 µg/plate for the first experiment (with and without S9 mix) and from 1.6 to 1000 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 while no genotoxicity was observed.

Cytogenicity / chromosome aberration / micronucleus study in mammalian cells

An in vitro cytogenicity study in mammalian cells or an in vitro micronucleus study was not conducted because adequate data from in vivo cytogenicity tests are available. The in vivo studies will be discussed further down.

 

Mutagenicity in mammalian cells

The mutagenicity of sodium dodecyl sulfate (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 the test item.

 

Genotoxicity in vivo

The potential of sulfuric acid, mono-C12-15-alkyl esters, sodium salts (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 test the test substance was considered to be not clastogenic.

 

The potential of sulfuric acid, mono-C12-14-alkyl esters, compds. with triethanolamine (CAS 90583-18-9, analytical purity ca. 41%) to induce micronuclei in vivo was assessed in a study conducted according to OECD Guideline 474 with CFW-1 mouse (BASF, 1987e). 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.

 

Conclusion

In conclusion, no structural analogue substances used for read-across showed any genotoxic potential in studies performed in vitro on bacterial and mammalian cells as well as in two independent in vivo studies. This is supported by the conclusions of the HERA Draft report on alkyl sulfates (AS) “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

[3] http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?Key=2c80d506-86bf-4719-be9b-d922022506ec&idx=0

Justification for classification or non-classification

The available in vitro and in vivo data on genetic toxicity obtainded with structurally analogue substances do not meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008 and are, therefore, conclusive but not sufficient for classification. Based on read-across the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) is also not classified for genetic toxicity.