Saponification and oxidation product of carnauba wax with acidic sodium dichromate solution esterified with 1-methyl-1,3-propanediol and subsequent saponification with calcium dihydroxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Accetable, well-documented publication

Data source

Reference

Reference Type:

publication

Title:

CD36 mediates both cellular uptake of very long chain fatty acids and their intestinal absorption in mice

Author:

Drover VA, Nguyen DV, Bastie CC, Darlington YF, Abumrad NA, Pessin JE, London E, Sahoo D, Phillips MC

Year:

2008

Bibliographic source:

Journal of Biological Chemistry, 283: 13108-13115

Report date:

2008

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Study on gastrointestinal uptake of long chain fatty acids (C16-C26)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

very long-chain fatty acids

IUPAC Name:

very long-chain fatty acids

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

mouse

Strain:

other: C57BL6/J and derived knockout strain CD36-/-

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration and frequency of treatment / exposure:

single exposure

No. of animals per sex per dose / concentration:

5-8

Control animals:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Absorption efficiency in wild type animals: about 85% for hexadecanoic acid, about 50% for tetracosanoic acid (estimated from figure)
CD36-/- mice showed a comparable uptake of hexadecanoic acid, but only 1.3% uptake of tetracosanoic acid
The intestinal absorption was lower for the tetracosanoic acid (but not for hexadecanoic acid) in animals with a high fat, high cholesterol diet compared to standard chow.

Metabolite characterisation studies

Metabolites identified:

no

Applicant's summary and conclusion

Conclusions:

CD36 is a specific transport system in the mouse intestine, facilitating the uptake of very long chain fatty acids.

Executive summary:

Wild type mice, fed with a high fat, high cholesterol diet showed an absorption efficiency of about 85% for hexadecanoic acid and about 50% for tetracosanoic acid (estimated from figure). CD36-/- mice had a comparable uptake of hexadecanoic acid, but only 1.3% uptake of tetracosanoic acid.

The intestinal absorption was lower for the tetracosanoic acid (but not for hexadecanoic acid) in animals with a high fat, high cholesterol diet compared to standard chow.