Isotridecyl 3,5,5-trimethylhexanoate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

22 February 2018

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Data source

Reference

Reference Type:

publication

Title:

The safety of the use of ethyl oleate in food is supported by metabolism data in rats and clinical safety data in humans

Author:

Bookstaff, R.C., PaiBir, S., Bharaj, S.S., Kelm, G.R., Kulick, R.M., Balm, T.K. & Murray, J.V.

Year:

2003

Bibliographic source:

Regulatory Toxicology and Pharmacology Volume 37, Issue 1, February 2003, Pages 133-148

Materials and methods

Objective of study:

absorption

excretion

metabolism

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

The absorption, distribution, and excretion of radiolabeled ethyl oleate (EO) was studied in Sprague–Dawley rats after a single, peroral dose of 1.7 or 3.4 g/kg body weight and was compared with a radiolabeled triacylglycerol (TG) containing only oleic acid as the fatty acid (triolein).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl oleate

EC Number:

203-889-5

EC Name:

Ethyl oleate

Cas Number:

111-62-6

Molecular formula:

C20H38O2

IUPAC Name:

ethyl (Z)-octadec-9-enoate

Test material form:

liquid

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Duration and frequency of treatment / exposure:

single dose

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1.7 other: g/kg bw

Doses / concentrations 2

Dose / conc.:

3.4 other: g/kg bw

Details on study design:

The absorption, distribution, and excretion of radiolabeled ethyl oleate (EO) was studied in Sprague–Dawley rats after a single, peroral dose of 1.7 or 3.4 g/kg body weight and was compared with a radiolabeled triacylglycerol (TG) containing only oleic acid as the fatty acid (triolein).

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Both test materials were well absorbed with approximately 70–90% of the EO dose absorbed and approximately 90–100% of the TG dose absorbed.

Details on distribution in tissues:

At sacrifice (72 h post-dose), tissue distribution of EO-derived radioactivity and TG-derived radioactivity was similar. The tissue with the highest concentration of radioactivity in both groups was mesenteric fat. The other organs and tissues had very low concentrations of test material-derived radioactivity.

Details on excretion:

Both test materials were rapidly and extensively excreted as CO2 with no remarkable differences between their excretion profiles. Approximately 40–70% of the administered dose for both groups was excreted as CO2 within the first 12 h (consistent with β-oxidation of fatty acids). Fecal elimination of EO appeared to be dose-dependent. At the dose of 1.7 g/kg, 7–8% of the administered dose was eliminated in the feces. At the dose of 3.4 g/kg, approximately 20% of the administered dose was excreted in the feces. Excretion of TG-derived radiolabel in the feces was approximately 2–4% for both doses.

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

Overall, the results demonstrate that the absorption, distribution, and excretion of radiolabeled EO is similar to that of TG providing evidence that the oleic acid moiety of EO is utilized in the body as a normal dietary TG-derived fatty acid. To confirm the expected safety of EO in humans, a total of 235 subjects participated in a 12-week trial where two levels of ethyl oleate in a milk-based beverage were investigated: 8 g/day in a single serving (approximately 0.1 g/kg) and 16 g/day taken in two divided servings (approximately 0.2 g/kg). Adverse events (AEs) were recorded throughout the 12-week trial. In addition, a brief physical exam (including vital signs and body weight), ECGs, fasting serum chemistry profile, serum lipid profile, and urinalysis were performed at baseline and after study completion.

Applicant's summary and conclusion

Conclusions:

Results showed the incidence of reported adverse events was similar between the EO groups and the control groups. Analysis of comprehensive laboratory data revealed no EO exposure-related, clinically significant adverse changes in laboratory parameters. These studies demonstrated that EO has a highly favorable safety profile and is well tolerated in the diet.