Docosanoic acid, monoester with glycerol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: weight of evidence assessment based 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:

Limited data are available fordocosanoic acid, monoester with glycerol The toxicokinetic properties of docosanoic acid, monoester with glycerol is assessed in the present weight of evidence analysis based on existing data on based on existing data on mono-, di- and triglycerides, fatty acids and glycerol.

The following expert opinions (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.
EFSA (2017a): Re-evaluation of fatty acids (E 570) as a food additive EFSA Journal 2017;15(5):4785
EFSA (2017b): Re-evaluation of glycerol (E 422) as a food additive EFSA Journal 2017;15(3):4720
EFSA (2017c). Re-evaluation of mono- and di-glycerides of fatty acids (E 471) as food additives EFSA Journal 2017;15(11):5045
OECD SIDS (2014). SIDS INITIAL ASSESSMENT PROFILE. Glycerides category. CoCAM 6, 30 - 03 October 2014

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:

As no specific data on toxicokinetics of docosanoic acid, monoester with glycerol is available, the weight of evidence assessment is based on toxicokinetic data on monoglycerides in general and on glycerol and fatty acids. The data is extracted from expert opinions (attached in section 13)

GLP compliance:

not specified

Remarks:

Data extracted from expert opinions

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

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Docosanoic acid, monoester with glycerol (CAS 30233-64-8) is ready absorbed (up to nearly 100%) in the gastrointestinal tract either as the monoester or as glycerol and docosanoic acid.

Glycerol is then subject to phosphorylation and oxidation and is used as an energy substrate via glycolysis or participates in gluconeogenesis and lipogenesis. Glycerol is extensively oxidised and exhaled as CO2, with only minor amounts excreted via urine or faeces.

Fatty acids are after absorption either metabolised or incorporated into chylomicrons, which enter the systemic circulation. Ultimately, fatty acids, either incorporated into glycerides and phospholipids, are catabolised via the b-oxidation pathway and the tricarboxylic acid cycle to carbon dioxide which is finally excreted via exhalation.

Details on distribution in tissues:

Docosanoic acid, monoester with glycerol (CAS 30233-64-8) is ready absorbed (up to nearly 100%) in the gastrointestinal tract either as the monoester or as glycerol and docosanoic acid.

Glycerol is then subject to phosphorylation and oxidation and is used as an energy substrate via glycolysis or participates in gluconeogenesis and lipogenesis. Glycerol is extensively oxidised and exhaled as CO2, with only minor amounts excreted via urine or faeces.

Fatty acids are after absorption either metabolised or incorporated into chylomicrons, which enter the systemic circulation. Ultimately, fatty acids, either incorporated into glycerides and phospholipids, are catabolised via the b-oxidation pathway and the tricarboxylic acid cycle to carbon dioxide which is finally excreted via exhalation.

Details on excretion:

Docosanoic acid, monoester with glycerol (CAS 30233-64-8) is ready absorbed (up to nearly 100%) in the gastrointestinal tract either as the monoester or as glycerol and docosanoic acid.

Glycerol is then subject to phosphorylation and oxidation and is used as an energy substrate via glycolysis or participates in gluconeogenesis and lipogenesis. Glycerol is extensively oxidised and exhaled as CO2, with only minor amounts excreted via urine or faeces.

Fatty acids are after absorption either metabolised or incorporated into chylomicrons, which enter the systemic circulation. Ultimately, fatty acids, either incorporated into glycerides and phospholipids, are catabolised via the b-oxidation pathway and the tricarboxylic acid cycle to carbon dioxide which is finally excreted via exhalation.

Metabolite characterisation studies

Details on metabolites:

Docosanoic acid, monoester with glycerol (CAS 30233-64-8) is ready absorbed (up to nearly 100%) in the gastrointestinal tract either as the monoester or as glycerol and docosanoic acid.

Glycerol is then subject to phosphorylation and oxidation and is used as an energy substrate via glycolysis or participates in gluconeogenesis and lipogenesis. Glycerol is extensively oxidised and exhaled as CO2, with only minor amounts excreted via urine or faeces.

Fatty acids are after absorption either metabolised or incorporated into chylomicrons, which enter the systemic circulation. Ultimately, fatty acids, either incorporated into glycerides and phospholipids, are catabolised via the b-oxidation pathway and the tricarboxylic acid cycle to carbon dioxide which is finally excreted via exhalation.

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 toxicokinetic properties/fate of this substance is assessed in the present as a weight of evidence analysis based on existing data on mono-, di- and triglycerides, fatty acids and glycerol.

The following was concluded from expert opinions:

According to OECD SIDS (2014) monoglycerides are readily absorbed through the duodenal mucosa and converted to triglycerides. Ingested triglycerides are in the small intestine split by pancreatic lipases into monoglycerides, free fatty acids, and glycerol, which can be absorbed by the intestinal mucosa. A small fraction of triglycerides is absorbed as free glycerol and as diglycerides. Once across the intestinal barrier, triglycerides are reformed.

According to CIR (2016), monoglycerides are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides.

EFSA (2017a) in its opinion on glycerol concluded that glycerol is rapidly and near completely absorbed from the gastrointestinal tract; distributed into the total body water space and is primarily metabolised in the liver. After phosphorylation and oxidation, glycerol is used as an energy substrate via glycolysis or participates in gluconeogenesis and lipogenesis. Glycerol is extensively oxidised and exhaled as CO₂, with only minor amounts excreted via urine or faeces.

EFSA (2017b) in its opinion on fatty acids concluded that caprylic-, capric-, oleic-, lauric-, palmitic-, myristic- or stearic acid like other fatty acids are readily and extensively absorbed from the gastrointestinal tract. After absorption, fatty acids are either metabolised or incorporated into chylomicrons, which enter the systemic circulation. Ultimately, fatty acids, either incorporated into glycerides and phospholipids, are catabolised via the b-oxidation pathway and the tricarboxylic acid cycle to carbon dioxide which is finally excreted via exhalation.

EFSA (2017c) noted that after exposure in rats to cottonseed oil monoglycerides, only traces were found in the faeces, indicating an oral absorption rate of 97.8±0.4%.

Applicant's summary and conclusion

Conclusions:

As no specific data on toxicokinetics of tocosanoic acid, monoester with glycerol is available the weight of evidence assessment is based on toxicokinetic data on monoglycerides in general and on glycerol and fatty acids. Form these data it can be concluded that docosanoic acid, monoester with glycerol is ready absorbed (up to nearly 100%) in the gastrointestinal tract either as the monoester or as glycerol and docosanoic acid as extensive hydrolysis in the gastrointestinal tract is to be expected.

Executive summary:

Docosanoic acid, monoester with glycerol (glycerol monobehenate) is a mono
constituent substance with a purity of 80-90%. As no specific data on
toxicokinetics of the substance is available, the assessment is based on
toxicokinetic data on monoglycerides in general and on glycerol and fatty acids.
From these data it can be concluded that docosanoic acid, monoester with
glycerol is ready absorbed (up to nearly 100%) in the gastrointestinal tract
either as the monoester or as glycerol and docosanoic acid as extensive
hydrolysis in the gastrointestinal tract is to be expected.
Glycerol is then subject to phosphorylation and oxidation and is used as an
energy substrate via glycolysis or participates in gluconeogenesis and
lipogenesis. Glycerol is extensively oxidised and exhaled as CO2, with only
minor amounts excreted via urine or faeces.
Fatty acids are after absorption either metabolised or incorporated into
chylomicrons, which enter the systemic circulation. Ultimately, fatty acids,
either incorporated into glycerides and phospholipids, are catabolised via the boxidation pathway and the tricarboxylic acid cycle to carbon dioxide which is
finally excreted via exhalation.
Data is lacking regarding dermal absorption and a default dermal absorption
ratio of 100% may be assumed.
The available information comprises adequate, reliable studies from reference
substances with similar structure and intrinsic properties. The weight-ofevidence approach is justified based on common functional group and common
precursors/breakdown products. The information from these independent
sources is consistent and provides sufficient weight of evidence leading to an
endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No
1907/2006