Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1926
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Good publication

Data source

Reference
Reference Type:
publication
Title:
EXPERIMENTS WITH THE UNSATURATED HYDROCARBON, SQUALENE (SPINACENE).
Author:
Channon
Year:
1926
Bibliographic source:
From the Departments of Physiology and Biochemistry, University College, London.

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
The general plan of the experiment was to feed two groups of rats on a complete artificial diet, while one group received in addition a small quantity
of squalene each day.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material: squalene
- IUPAC name:(2E,6E,10E,14E,18E)-2,6,10,15,19,23-Hexamethyltetracosa-2,6,10,14,18,22-hexaene
- Molecular formula:C30H50
- Substance type:organic
- Physical state:liquid
- Analytical purity:no data
Radiolabelling:
no

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Diet : - Diet: complete artificial diet that described by Drummond and Coward [1920].

Administration / exposure

Route of administration:
other: dropped directly in mouths from a micro-burette.
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
Single daily administration for 42 days
Doses / concentrations
Remarks:
Doses / Concentrations:
660 mg
No. of animals per sex per dose:
test group: 10 rats
negative control: 9 rats
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: based on animal's weight

Results and discussion

Main ADME results
Type:
absorption
Results:
10%

Toxicokinetic / pharmacokinetic studies

Details on absorption:
About 10 g. have been absorbed during the course of 42 days and this absorption has resulted in a marked increase in the weight of unsaponifiable matter in the livers and also in the bodies of these animals, namely, from 0.3680 to 1.0774 g. in the case of the livers and from 1.8620 to 2 .9114 g. in that of the bodies. There is also a large increase in the amounts of cholesterol, from 0.2576 to 0.6189 g. in the livers and from 1.3000 to 2.1620 g. in the bodies.
Transfer into organs
Test no.:
#1
Transfer type:
secretion via gastric mucosa
Observation:
slight transfer
Details on excretion:
It is clear from the weight of unsaponifiable matter from the faeces of the latter animals, and from its iodine value, that much of the squalene administered has been excreted.

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

If we assume that that fraction of this unsaponifiable matter which is not squalene has an iodine value which is the same as that of the material from the control group, namely 80.4%, then we may calculate from the iodine value of the whole of this unsaponifiable matter (316), that the amount of squalene present is 81.41 %, i.e. 16 -79 g. (squalene has iodine value 371). This figure can only be approximate, but some rough check on it is obtained from the fact that, if we subtract the weight of material not sterol in the faeces of the control group from the corresponding figure for the faeces of the animals receiving squalene, we arrive at the figure 17-60 g. These figures 16.79 and 17.60 g. can only be approximate, but they would seem to show that about 17 g. of the 27.7 g. of squalene administered had been excreted.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
No obvious ill effects followed the administration of squalene and post mortem examination showed that the organs of the animals were very healthy. There appeared to be a greater deposition of fat in the animals which received squalene and on the whole they seemed to grow at a somewhat greater rate than those of the control groups, possibly because the laxative action of the squalene caused a greater food consumption.
The amount of squalene present in faeces is 81.41 % after 42 days of somministration
Executive summary:

Squalene has been tested in subchronic repeted study by oral administration. The general plan of the experiment was to feed two groups of rats on a complete artificial diet, while one group received in addition a small quantity of squalene each day. Immediately before feeding-time the animals were given approximately 660 mg of squalene dropped directly into their mouths from a micro-burette. Records were taken of the amount of squalene given each day. The faeces were collected throughout the experiment at weekly intervals and stored in alcohol. At the end of the experiment the animals were killed by chloroform and their livers removed as free from blood as possible. The experiment shows that when squalene is administered to the rat, it is in part absorbed and as a result of absorption there is a marked increase in the amounts of unsaponifiable matter and of cholesterol in the body and liver of the animal.