Esterification product of castor oil fatty acids and pentaerythritol

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

metabolism

Qualifier:

no guideline available

Principles of method if other than guideline:

in vitro metabolism using radiolabelled esters

GLP compliance:

no

Specific details on test material used for the study:

Radiolabelled product synthesized in house. TLC showed product to be homogeneous.

Radiolabelling:

yes

Remarks:

Sp activity of 4200 cpm/ µmole

Species:

rat

Strain:

other: not specified

Sex:

not specified

Route of administration:

other: in vitro

Type:

metabolism

Results:

Hydrolysis primarily by rat nonspecific lipase

Details on absorption:

No data

Details on distribution in tissues:

No data

Details on excretion:

No data

Metabolites identified:

yes

Remarks:

tetraester, triester, diester, monoester, and erythritol

Details on metabolites:

Erythritol tetraoleate was hydrolysed by nonspecific lipase (from rat), confirming is action only on esters of primary alcohols. The initial digestion product was 1,2,3-trioleate. Lipase then removes a fatty acid from the triester, forming erythritol-2,3-dioleate. The digestion continues in a stepwise manner from tetraester to triester to diester to monoester to erythritol. Hydrolysis of the tri- and diesters is rapid; the rate-limiting step is the hydrolysis of the tetraester.

Conclusions:

Hydrolysis of pentaerythritol tetraoleate was demonstrated in vitro by the combined action of rat pancreatic lipase and nonspecific lipase. The digestion occurs in a stepwise manner from tetraester to triester to diester to monoester to erythritol.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: Review of experimental data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientifically reliable and peer reviewed by CIR Expert Panel, USA

Justification for type of information:

Judged to be scientifically reliable and appropriate for risk assessment by the Expert Panel of dermatologists and scientists at the Cosmetics Ingredient Review, Washington, DC., U.S.A

Objective of study:

absorption

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

in vivo dietary feeding/metabolism study of castor oil in rats

GLP compliance:

no

Remarks:

predates development of GLP

Specific details on test material used for the study:

no data

Radiolabelling:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Adult rats

Route of administration:

oral: feed

Vehicle:

not specified

Duration and frequency of treatment / exposure:

daily for 4-6 weeks

Dose / conc.:

0 other: %

Dose / conc.:

48.4 other: %

No. of animals per sex per dose / concentration:

not specified. ≥ 3.

Control animals:

not specified

Details on study design:

Adult rats received a diet containing 48.4% castor oil for 4-6 weeks. Control rats received stock ration only. Feces were collected from 3 rats on the castor oil diet. At the end of the feeding period, excised organs/tissues were ground thoroughly and samples of phospholipid fatty acids were obtained from the liver, small intestine and muscle; glyceride fatty acids were obstained from the liver and fat depots.

Preliminary studies:

No evidence of catharsis in rats fed 48.4% castor oil in the diet (stock ration)

Type:

absorption

Results:

Metabolites but not parent substance are rapidly absorbed and found in glycerides and cholesterol esters of the fat depots.

Type:

excretion

Results:

Fatty acids were excreted

Details on absorption:

Ricinoleic acid was absorbed from dietary castor oil and was found as a component acid (up to 7%) of the fatty acids in glycerides in carcass fat depots. The feeding of castor oil did not lead to the appearance of significant amounts of ricinoleic acid in glycerides in the liver, nor in phospholipids of any organ tested (liver, small intestine and skeletal muscle). Total body fat in these three animals was also determined, and it was calculated that 1-2% of absorbed ricinoleic acid was deposited in the fat depots.

Details on distribution in tissues:

Metabolites (diglycerides and ricinoleic acid) are absorbed, distributed and measurable in fat depots.

Details on excretion:

The fatty acids excreted by each of three rats amount to 2.1, 2.2 and 3.6% of those ingested. It is assumed that this is in the animals fed castor oil and refers to ricinoleic acid.

Metabolites identified:

yes

Details on metabolites:

Metabolites are ricinoleic acid and its mono- or diglycerides.

Bioaccessibility (or Bioavailability) testing results:

Parent castor oil is not absorbed through the GI tract; metabolites are rapidly absorbed.

Ricinoleic Acid Content of Phospholipids

	Ricinoleic Acid content (%) in Control-fed rats	No. of analyses	Ricinoleic Acid content (%) in Castor Oil-fed rats	No. of analyses
Liver	1.7 ± 1.1	7	1.3 ± 0.6	9
Small intestine	6.0 ± 4.4	4	4.9 ± 1.7	8
Skeletal muscle	4.0 ± 1.7	7	3.6 ± 2.9	8

Ricinoleic Acid Content of Glycerides and Cholesterol Esters in Fat Depots

	Ricinoleic Acid content (%) in Control-fed rats	No. of analyses	Ricinoleic Acid content (%) in Castor Oil-fed rats	No. of analyses
Liver	5.6 ± 4.1	5	7.2 ± 2.4	8
Carcass Fat Depots	0.5 ± 0.5	7	6.8 ± 4.2	11

Conclusions:

Castor oil is rapidly hydrolysed by lipases into ricinoleic acid and di- and mono-glycerides, which are absorbed. Ricinoleic acid is found in carcass fat depots (comprising approximately 7% of the total fatty acid content) This fatty acid was not found in hepatic glycerides or in phospholipids of the liver, small intestine or skeletal muscle. These metabolites are rapidly processed and excreted or stored.

Description of key information

PE esters of castor oil are not absorbed orally, but are rapidly hydrolysed, processed in a similar manner as are triglycerides, and excreted or stored in fat.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

10

Additional information

Castor oil PE esters are poorly water soluble and may partition to lipid. They are not readily absorbed after oral exposure but are rapidly hydrolysed by lipases into ricinoleic acid and di- and mono-glycerides, which are absorbed. Parent substance is not absorbed by the oral, dermal or inhalation routes. The metabolite ricinoleic acid can be found in carcass fat depots (comprising approximately 7% of the total fatty acid content). This fatty acid was not found in hepatic glycerides or in phospholipids of the liver, small intestine or skeletal muscle. These metabolites are rapidly processed and excreted or stored. The polyols are not highly absorbed, but primarily excreted in urine unchanged.  PE, as well as TMP and glycerol, have low degrees of toxicity (U.S. EPA, 2010).

In a review by the Cosmetic Ingredient Review (CIR, Becker, et al., 2015) the pentaerythrityl tetraesters are not bioavailable by the dermal route. A study of fatty acids, C5 -9, penterythrityl tetraesters was reported to display 2 -6% skin absorption after repeated dose application in rats.