Registration Dossier

Administrative data

Endpoint:
mechanistic studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Very long chain fatty acids (policosanols) and phytosterols affect plasma lipid levels and cholesterol biosynthesis in hamsters
Author:
Wang Y, Ebine N, Jia X, Jones P, Fairow C, Jaeger R
Year:
2005
Bibliographic source:
Metabolism Clinical and Experimental, Vol. 54: 508-514

Materials and methods

Principles of method if other than guideline:
Oral repeated dose study examinating the alterations in plasma lipid levels and cholesterol biosynthesis
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Licowax (derived from Montanwax), very long chain fatty acids (VLCFA)
- Composition of test material, percentage of components: 69% VLCFA (8% C24; 13% C26; 18% C28, 18% C30, 7% C32, 3% C34, 1% C36, 1% > C36)

Test animals

Species:
hamster, Syrian
Strain:
not specified
Sex:
male

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
25, 50 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
15 males
Control animals:
yes, plain diet

Results and discussion

Details on results:
TC levels and non-HDL-C levels were slightly increased in the groups treated with solely 25 or 50 mg/kg bw/day VLCFA, but the alterations were not significant. HDL-C was increased in both dosed groups, and this was significant in the 50 mg/kg bw/day group. The ratio of TC to HDL-C was not altered. The trigylceride levels were not affected in the treated groups (results presented in figures).
The exposure to VLCFA increased the rate of biosynthesis of cholesterol significantly at both doses, but there was no dose-response relationship.

Any other information on results incl. tables

Effects on cholesterol biosynthesis:

   % newly synthesised cholesterol (2 h)
 control group  6.64 +/- 0.15
 25 mg/kg bw/day  6.85 +/- 0.25*

50 mg/kg bw/day

 6.86 +/- 0.22*

*: significantly different from control

There were no alterations in body weight or organ weights (liver, heart, kidneys, brain) due to exposure to the test substance.

Applicant's summary and conclusion

Conclusions:
Licowax (VLCFA) slightly increased the HDL-cholesterol and the cholesterol biosynthesis after repeated oral doses of 25 and 50 mg/kg bw/day. The alterations in cholestesterol biosynthesis were not dose-dependent. These effects are not considered to be adverse.
Executive summary:

Groups of Syrian hamsters (15 males per group) were fed diets delivering body doses of 0, 25 or 50 mg/kg bw/day of very long chain fatty acids (VLCFA, Licowax). Body weights and the weight of liver, heart, kidneys and brain were unaffected by the treatment. Both treatments produced no alterations in the levels of trigycerides. A slight, but not significant increase of total cholesterol and non-HDL cholesterol was observed. HDL-C was increased in both dosed groups, and this effect was significant in the 50 mg/kg bw/day group. The ratio of TC to HDL-C was not altered. The exposure to VLCFA increased the rate of biosynthesis of cholesterol significantly at both doses, but there was no dose-response relationship.Therefore the effects are not considered to be adverse, the NOAEL of this study was >50 mg/kg/day.