Docosanoic acid, monoester with glycerol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews

Justification for type of information:

Data are available for docosanoic acid, monoester with glycerol (glycerol monobehenate). Because of the structural and functional similarities, data from other glyceryl monoesters are also included in this weight of evidence assessment as supporting data.

The following expert opinion (attached in section 13) will be used in the weight of evidence approach:

CIR 2016: Cosmetic Ingredient Review. Safety assessment of monoglyceryl monoesters as used in cosmetics. Final amended report, January 15, 2016.





 

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:

The results are based on a weight of evidence analysis from collection of data extracted from the literature/expert opinions. For more details please refer to the attached weight of evidence document as well as documents attached in section 13 identified as key references.

In relation to the data requirements of REACH Annex VII (1-10 t/y), data on acute oral 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.

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

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Any other information on results incl. tables

Docosanoic acid, monoester with glycerol 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. The acute oral toxicity was evaluated based on data on docosanoic acid, monoester with glycerol (Glycerol Monobehenate) as well as data from other glycerol monoesters.

The following was concluded from expert opinions:

Nine acute oral toxicity studies are described in the CIR (2016) for glycerol monobehenate and other monoglyceryl monoesters. The acute oral toxicity of monobehenate was reported to be >2 g/kg bw in mice. In the acute oral toxicity study, similar to OECD guideline 401, glycerol monobehenate was administered via gavage to five female Swiss mice at a limit dose of 2 g/kg bw (CIR 2016). No mortalities and no clinical signs were observed in the animals up to the end of the 14-day observation period. No effects on body weights were noted during the study. An oral LD50 value in female Swiss mice was set to> 2 g/kg bw.

For other glycerol monoesters, In two acute oral toxicity studies, glycerol ester of partially hydrogenated gum rosin, neat or in olive oil, was administered via gavage to five Sprague Dawley rats at a limited dose of 2 g/kg bw (CIR 2016). An oral LD50 value in male Sprague Dawley rats was set to > 2 g/kg bw. 

In four acute oral toxicity studies, glyceryl rosinate neat or in different solvents (vaselin oil, corn oil and 0.25% agar and 0.10% Tween 80) was administered via gavage to Sprague Dawley rats at limited doses of 2, 5, or 10 g/kg bw the LD50 were set to >2 g/kg bw, >5 g/kg bw and >10 kg/kg bw respectively.

Finally, in two studies with five mice exposed to glyceryl stearate by oral gavage resulted in no mortality at a dose of 5 g/kg bw (CIR 2016).

To summarize the CIR expert panel concluded based on the oral studies, LD50 values to be >2 g/kg glyceryl behenate, >2 g/kg glyceryl hydrogenated rosin, >5 g/kg glyceryl stearate, and >10 g/kg glyceryl rosinate. Furthermore, monoglyceryl monoesters are considered Generally Recognized as Safe (GRAS) for food use (CIR 2015; 2016).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the studies available for docosanoic acid, monoester with glycerol (Glycerol monobehenate), the relevant hydrolysis products as well as data from other glycerol monoesters, it can be concluded that glycerol monobehenate has low acute oral toxicity with LD50-values above the highest dose used for classification as acute toxicity (i.e. 2000- 5000 mg/kg). Thus, docosanoic acid, monoester with glycerol (glycerol monobehenate) is not to be classified for acute oral toxicity.

Executive summary:

Detailed study reports on acute oral toxicity is not available for docosanoic acid, monoester with glycerol (glycerol monobehenate), however data on glycerol monobehenate from a CIR expert review (2016) is available. Because of the structural and functional similarities, data from other glyceryl monoesters are also included in this weight of evidence assessment as supporting data.

The LD50 of glycerol monobehenate from acute oral toxicity studies performed in mice was set to >2 g/kg bw. Furthermore, the CIR expert panel concluded, based on the oral studies, LD50 values to be >2 g/kg glyceryl hydrogenated rosin, >5 g/kg glyceryl stearate, and >10 g/kg glyceryl rosinate. In all studies, no mortality is reported. The acute oral toxicity of glycerol monobehenate is therefore considered to have low toxicity and to be above the doses used for classification.

The overall conclusion is therefore that glycerol monobehenate has low acute oral toxicity with a LD50-value above 2000 mg/kg bw. Thus, classification for acute oral toxicity according to (EC) No 1272/2008 is not warranted.