Docosanoic acid, monoester with glycerol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

other: weight of evidence analysis based on expert evaluated data on hydrolysis products and structural analogues

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

In relation to the data requirements of REACH Annex VIII (10-100 t/y), data on genotoxicity must be provided. Limited data on this endpoint is available for docosanoic acid, monoester with glycerol (glycerol monobehenate).

Glycerol monobehenate is a mono-constituent substance. The main component is docosanoic acid, monoester with glycerol which is present in the product at a concentration of 80 – 90%, the remaining compounds are mainly fatty acids and monoesters of fatty acid and glycerol. Glycerol can also be present in a low concentration. Glyceryl monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides.

The mutagenicity of this substance is therefore assessed in the present document as a weight of evidence analysis based on existing data on groups of mono-, di- and triglycerides, fatty acids, which are all components with similar properties. Hereby, a huge data set is available for deriving a conclusion on the genotoxicity toxicity of the substance.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Principles of method if other than guideline:

In relation to the data requirements of REACH VIII (10-100 t/y), data on genetic toxicity must be provided. Limited data on this endpoint is available for Docosanoic acid, monoester with glycerol (glycerol monobehenate). Glycerol monobehenate is a mono-constituent substance. The main component is docosanoic acid, monoester with glycerol, the remaining compounds are mainly fatty acids and monoesters of fatty acid and glycerol. Glycerol can also be present in a low concentration. Glyceryl monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides.

The possible genetic toxicity of this substance is therefore assessed in the present weight of evidence analysis based on Q(SAR) predictions using different QSAR models (OECD QSAR Toolbox, VEGA QSAR Tool, and The Danish EPA QSAR database), and data generated from similar chemicals

Expert group assessments of the substances are considered the most valid data for the assessment, an overall weight of evidence approach based on these expert evaluations is used for the assessment.

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Docosanoic acid, monoester with glycerol

EC Number:

250-097-0

EC Name:

Docosanoic acid, monoester with glycerol

Cas Number:

30233-64-8

Molecular formula:

C25H50O4

IUPAC Name:

2-hydroxy-1-(hydroxymethyl)ethyl docosanoate

Test material form:

solid

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Applicant's summary and conclusion

Conclusions:

Limited in vitro and in vivo genotoxicity data was identified for Docosanoic acid, monoester with glycerol (glycerol monobehenate). However, based on Q(SAR) predictions using different QSAR models (OECD QSAR Toolbox, VEGA QSAR Tool, The Danish EPA QSAR database) and data generated from similar chemicals it is concluded that the Docosanoic acid, monoester with glycerol (glycerol monobehenate) is considered not be a clastogenic substance as no chromosome aberrations was seen in an OECD 473 study.

Executive summary:

From the literature search, specific data on mutagenicity of mono-glyceryl monoesters were found in an assessment performed by the Cosmetic Ingredient Review (CIR) expert panel (CIR 2016, 2019). 

Undecylenic acid was tested for gene mutation both in vitro and in vivo test systems. Undecylenic acid was not genotoxic in a Chinese hamster lung fibroblast (V79), with and without metabolic activation; as well as not genotoxic in male and female CD-1 mice. Glycerol tested negative for gene mutation without metabolic activation in an HGPRT gene mutation assay performed on Chinese hamster ovary cells. One OECD 473 Guidelines test on chromosome aberration was identified for glyceryl rosinate. Glycerol rosinate is a monoester of glycerol and long chain fatty acids from rosin. Glyceryl rosinate was not genotoxic in the OECD 473 chromosome aberration test. Glyceryl acetate (89% pure) was also tested in an in vitro gene mutation chromosomal aberration test (guideline study not stated). Glyceryl acetate (89% pure) was not genotoxic in the tested system. Behenic acid tested negative for genotoxicity in a mammalian chromosome aberrations test at a concentration up to 3500 µg/mL; likewise at a similar concertation Behenic acid (85.9% pure) tested negative for genotoxicity in an OECD 473 guideline study. Furthermore, glycerol tested negative for genotoxicity in three independent in vitro mammalian chromosome aberration studies, and one in vivo bone marrow chromosomal aberration test performed on male rats (strain not specified). Glycerides, C16-18 and C18-hydroxy mono- and di- were tested in an in vivo micronucleus test, which gave negative results. Glycerol was tested negative for DNA damage in an unscheduled DNA synthesis assay and a sister chromatid exchange assay.

Further, EFSA 2020 concluded that glycerol monobehenate was found to be non-genotoxic based on QSAR predictions using the OECD QSAR ToolBox and QSAR VEGA Tool.

In summary, limited in vitro and in vivo genotoxicity data was identified for Docosanoic acid, monoester with glycerol (glycerol monobehenate). However, based on Q(SAR) predictions using different QSAR models (OECD QSAR Toolbox, VEGA QSAR Tool, The Danish EPA QSAR database) and data generated from similar chemicals it is concluded that the Docosanoic acid, monoester with glycerol (glycerol monobehenate) is considered not be genotoxic and not a clastogenic substance as no chromosome aberrations was seen in vitro and in vivo.