Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

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

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

Reference
Name:
Unnamed
Type:
Constituent
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:
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.