Hydroxyoctadecanoic acid, monoester with glycerol

Basic toxicokinetics

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Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2007

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1945

Materials and methods

Objective of study:

absorption

excretion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Interpretation of data from a guideline in vivo dietary rodent feeding/metabolism study of a structural analogue, castor oil

GLP compliance:

no

Remarks:

predates development of GLP

Test material

Test material information

Constituent 1

Test material form:

liquid: viscous

Details on test material:

Castor oil (CAS 8001-79-4), lot #L-5G30-01, was obtained from Cas Chemical, Inc., Bayonne, NJ. (now owned by Vertellus LLC). Purity analysis indicated that it was consistent with the USP specifications and the reported composition for castor oil: Analysis was conducted by Midwest Research Institute (MRI), in Kansas City, MO, utilizing infrared, UV/Vis and NMR spectroscopy, Karl Fischer water analysis, TLC and HPLC, and a battery of USP standard analyses for castor oil.

Specific details on test material used for the study:

no data

Radiolabelling:

no

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Adult rats

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Duration and frequency of treatment / exposure:

daily for 4-6 weeks

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: %

Remarks:

castor oil

Doses / concentrations 2

Dose / conc.:

48.4 other: %

Remarks:

castor oil

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.

Results and discussion

Preliminary studies:

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

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Ricinoleic acid was found in glycerides and cholesterol esters of the fat depots.

Main ADME results 2

Type:

excretion

Results:

Fatty acids were excreted

Toxicokinetic / pharmacokinetic studies

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 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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

Conclusions:

Castor oil, when given to adult rats as 48.4% of a stock feed for 4-6 weeks, ls absorbed and results in incorporation of ricinoleic acid in the glycerides of carcass fat depots. Approximately 7% of the total fatty acid content of depot fat glycerides was found to be ricinoleic acid. This fatty acid was not found in hepatic glycerides or in phospholipids of the liver, small intestine or skeletal muscle. Castor oil and rcinoleic acid are rapidly metabolized.