Sulfuric acid, mono-C8-18-alkyl esters, magnesium salts, compds. with triethanolamine

Endpoint summary

Additional information

The mutagenic potential on bacterial cells in vitro is assessed for C8-18AS TEA&Mg (CAS 85586-38-5). Therefore this endpoint is covered by direct data from an Ames study.  To assess the mutagenic potential on mammalian cells in vitro a read across from structurally related alkyl sulfate (AS), i.e. C8isoAS Na (CAS 126-92-1) and C12AS Na (CAS 151-21-3) was performed. In addition one study assessing the in vivo genotoxicity of C12AS Na (CAS 151-21-3) was used for read across. 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 programme carrying out Human and Environmental Risk Assessments (HERA [2]) further supporting the read across approach between structurally related AS. During data processing of all alkyl sulfates within the category it turned out that alkyl sulfates with a carbon chain length of C12 exert the most prominent effects on human health. Therefore C12AS Na (CAS 151-21-3) was additionally chosen for read across as worst case assumption as well.

There is a substantial data base on triethanolamine (TEA) online available. TEA is not listed in Annex VI of directive 1272/2008. In addition the effects of TEA on human health were assessed by the OECD in the SIDS initial assessment Report [3]. Despite of some local signs of irritation TEA gives no rise to concern of adverse effects on human health. Therefore a contribution of TEA to the effects on human health is considered to be negligible when assessing human health effects of C8-18AS Mg&TEA (CAS 85586-38-5). Magnesium is a metal occurring ubiquitously in the diet. A tolerable upper intake level (UL) was established by the US Food and Nutrition Board, adapted by the European Food Safety Authority and set to 250 mg/d for adults [4]. This equals 3.6 mg/kg bw/d for an adult of 70 kg bw. Correcting for the molecular weight of the C12AS Mg (approx. 290 g/mol) this corresponds to approx. 43 mg/kg bw/d. This UL is above the derived DNEL for the oral route and based on a slight and reversible laxative effect. Therefore, contribution of magnesium to adverse effects of C8-18AS Mg&TEA (CAS 85586-38-5) on human health is not expected. Therefore, read across to alkyl sulfates with other counter ions is considered to be valid and reliable. This approach was also followed by the OECD in the SIDS initial assessment profile [1] and by the voluntary industry programme carrying out Human and Environmental Risk Assessments (HERA [2]).

 

In vitro mutagenicity of C8-18AS TEA&Mg (CAS 85586-38-5)

The test substance Component in "confidential name" was tested for its mutagenic potential based on the ability to induce point mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium and Escherichia coli, in a reverse mutation assay according to OECD 471 (BASF SE 2019).
STRAINS: TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA
DOSE RANGE: 33 μg - 5300 μg/plate (SPT)
3.3 μg - 5300 μg/plate (PIT)
TEST CONDITIONS: Standard plate test (SPT) and preincubation test (PIT) both with and without metabolic activation (liver S9 mix from induced rats).
SOLUBILITY: No precipitation of the test substance was observed with and
without S9 mix.
TOXICITY: A bacteriotoxic effect was observed depending on the strain and
test conditions at and above 100 μg/plate 
MUTAGENICITY:
A relevant increase in the number of his+ or trp+ revertants (factor ≥ 2: TA 100, TA 98 and E.coli WP2 uvrA or factor ≥ 3: TA 1535 and TA 1537) was not observed in the standard plate test or in the preincubation test without S9 mix or after the addition of a metabolizing system.

 

In vitro mutagenicity of C8isoAS Na (CAS 126-92-1)

The potential of C8isoAS Na (CAS 126-92-1, no data on analytical purity) to induce genotoxicity in mammalian cells in vitro was assessed in a study conducted according to OECD guideline 476 using the mouse lymphoma L5178Y cells with and without metabolic activation (McGregor, 1991). The study comprised of 4 trials with and without metabolic activation. The concentrations tested in the absence of metabolic activation were 156.25, 312.5, 625, 1250, 2500 µg/mL (Trial 1); 200, 1000, 1800, 2600, 3400, 4200 µg/mL (Trial 2); 1000, 1800, 2600, 3400, 4200 µg/mL (Trial 3) and 1000, 1800, 2600, 3400, 4200, 5000 µg/mL (Trial 4). The concentrations tested in the presence of metabolic activation were 200, 1000, 1800, 2600, 3400, 4200 µg/mL (Trial 1), 1000, 1800, 2600, 3400, 4200 µg/mL (Trial 2&3) and 2600, 3000, 3400, 3800, 4200 µg/mL (Trial 4). No treatment related increased mutation frequencies were observed in three of four trials without S9 mix. However, in trial 3, all concentrations showing no marked cytotoxicity were associated with significantly increased mutation frequencies in the absence of metabolic activation. There was no reasonable explanation for this striking result of trial 3. In trial 1 without metabolic activation a statistically significant increased mutation frequency occurred at a single concentration level. At higher concentrations no increased mutation frequencies were observed within this trial. Taken together no increased mutation frequency was evidenced when L5178Y cells were exposed to the test substance without metabolic activation. In the presence of metabolic activation no increased mutation frequencies were observed. In two trials the top dose of 4200 µg/L produced marked cytotoxicity. Therefore also no increased mutation frequency was evidenced when L5178Y cells were exposed to the test substance with metabolic activation.

 

In vitro cytogenicity of C8isoAS Na (CAS 126-92-1)

The potential of C8isoAS Na (CAS 126-92-1, analytical purity 39.6%) to induce chromosomal aberration in a mammalian cell line was investigated similar to OECD guideline 473 using Chinese hamster Ovary cells with and without metabolic activation (Loveday, 1990). The test concentrations were 501, 1500 and 5010 µg/L. Results achieved with the vehicle (water) and positive controls were valid. No cytotoxicity was observed in presence and absence of metabolic activation however the test was conducted up to the limit concentration of 5000 µg/L. No enhanced chromosome aberration was observed under any conditions of the study.

 

In vitro mutagenicity of C12AS Na (CAS 151-21-3)

The mutagenicity of C12AS Na (CAS 151-21-3, no data on analytical purity) 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).

 

In vivo cytogenicity of 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 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 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 […].”

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

[3] SIDS initial assessment report, (1995);

http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?Key=5ca67317-5fcc-41ea-a429-53d1267be383&idx=0

[4] (EFSA, TOLERABLE UPPER INTAKE LEVELS FOR VITAMINS AND MINERALS, 2006)

http://www.efsa.europa.eu/en/ndatopics/docs/ndatolerableuil.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 chromosome aberration test (CA / OECD guideline 473): 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

According to the classification criteria of Directive 67/548/EEC and Regulation (EC) No 1272/2008 the substance does not need to be classified for genotoxicity.