Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Glycerides, C16 -18 mono-, di- and tri-, hydrogenated citrates is not considered to have genetic toxicity, according to the in vitro gene mutation study in bacteria and mammalian cells.

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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

 

In vitro cell gene mutation test

No information on mutagenicity of Glycerides, C16-18 mono-, di- and tri-, hydrogenated, citrates was identified. However, a studiy from a structural analogue is available.

 

The test item Glycerides, C16-18 mono-, di and tri-, hydrogenated, citrates, potassium salts (CAS 91744-38-6) was assessed for its potential to induce gene mutations at the HPRT locus using V79 cells of the Chinese hamster. The study was performed in two independent experiments, using identical experimental procedures. In the first experiment the treatment period was 4 hours with and without metabolic activation. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. The maximum concentration was limited by the solubility of the test item in THF and aqueous medium. Precipitation of the test item at the end of treatment was noted at 75 and 150 µg/mL in the first experiment with and without metabolic activation. In the second experiment precipitation as described above occurred at 75 and 150 µg/mL with and at 37.5 µg/mL and above without metabolic activation. No relevant toxic effects occurred up to the maximum concentration with and without metabolic activation following 4 and 24 hours treatment.

No relevant and reproducible increase in mutant colony numbers/10E+6 cells was observed in the main experiments up to the maximum concentration. The induction factor exceeded the threshold of three times the corresponding solvent control and the range of the historical solvent control data in the second culture of the first experiment without metabolic activation at 18.8 and 150.0 µg/mL. However, the increase at 18.8 µg/mL was marginal (induction factor of 3.4) and was not reproduced in the parallel culture under identical conditions. The increase at 150 µg/mL was substantial (induction factor of 6.1) but again, not reproduced in the parallel culture under identical experimental conditions. Furthermore, the concentration of 150 µg/mL was the second precipitating concentration so, the irreproducible increase of the mutation frequency was judged as irrelevant precipitation artefact. The minor increase at 18.8 µg/mL was judged as biologically irrelevant fluctuation. A linear regression analysis (least squares) was performed to assess a possible dose dependent increase of mutant frequencies. A significant dose dependent trend of the mutation frequency indicated by a probability value of <0.05 was detected in both cultures of the first experiment without metabolic activation. The trend observed in culture I however, was judged as irrelevant as it actually was reciprocal, going down versus increasing concentrations. The trend observed in culture II was judged irrelevant as it was based on a precipitation artefact at 150 µg/mL as described above. In both  experiments of this study (with and without S9 mix) the range of the solvent controls was from 9.7 up to 35.2 mutants per 10E+6 cells; the range of the groups treated with the test item was from 2.6 up to 84.9 mutants per 10E+6 cells.EMS (150 µg/mL) and DMBA (1.1 µg/mL) were used as positive controls and showed a distinct increase in induced mutant colonies.

 

Bases on these results, it was concluded that the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, Glycerides, C16-18 mono-, di and tri-, hydrogenated, citrates, potassium salts is considered to be non-mutagenic in this HPRT assay.

In a Bacterial Reverse Mutation Assay according to OECD 471, strains TA 1535, TA 1537, TA 98 and TA 100 of S. typhimurium were exposed to the test substance (CAS 91744-23-9) in solvent tetrahydrofurane at concentrations of 50 / 160 / 500 / 1600 / 5000 µg/plate (plate incorporation) in the presence and absence of mammalian metabolic activation (aroclor 1254 induced liver S9 mix). 

Justification for classification or non-classification

Based on the available data, classification for genetic toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.