Docosan-1-ol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

The Alkyl and Alk-1-enyl Glycerols in the Liver of the Rats Fed Long-Chain Alcohols or Alkyl Glycerols

Author:

Bandi, Z. L., Mangold, H. K., Hølmer, G., & Aaes-Jørgensen, E

Year:

1971

Bibliographic source:

FEBS letters, 12(4), 217-220

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The experiment was carried out to determine whether dietary monounsaturated and diunsaturated long-chain alcohols can be incorporated into the ionic alkoxylipids of
rat liver. Groups of rats were fed a basic diet and water plus supplements of cis-9-octadecenyl alcohol ((Z)-octadec-9-enol) and cis, cis-9,12-octadecadienyl alcohol ((Z)-octadec-9,12-dienol). The constituent alkyl, alk-1-enyl, and acyl moieties in the phosphoglycerides isolated from the liver of the rats were analysed to determine whether the dietary lipids had been incorporated into the tissue lipids of these animals.

GLP compliance:

no

Remarks:

pre-dates GLP

Test material

Test material information

Constituent 1

Reference substance name:

(Z)-octadec-9-enol

EC Number:

205-597-3

EC Name:

(Z)-octadec-9-enol

Cas Number:

143-28-2

Molecular formula:

C18H36O

IUPAC Name:

octadec-9-en-1-ol

Specific details on test material used for the study:

Test substances used: cis-9-octadecenyl alcohol ((Z)-octadec-9-enol) and cis, cis-9,12-octadecadienyl alcohol ((Z)-octadec-9,12-dienol)

Methyl esters, which were used as reference compounds, were purchased from the Hormel Institute Lipids Preparation Laboratory. Aldehydes, alkyl acetates, and isopropylidene derivatives of alkyl glycerols were prepared. Cis-9-octadecenyl alcohol (oleyl alcohol) and cis, cis-9,12-octadecadienyl alcohol, which were used as dietary supplements, were prepared by hydrogenolysis of the corresponding methyl esters, with lithium aluminum hydride.

Radiolabelling:

no

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4-5 week old
- Diet (e.g. ad libitum): basic diet consisting of 20% extracted casein, 68% sucrose, 5%
salt mixture, 0.5% vitamin mixture, 0.5% choline chloride and, as the sole source of lipids, 6% peanut oil, ad libitum
- Water (e.g. ad libitum): water, ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on exposure:

All of the supplements were fed by stomach tube.

Duration and frequency of treatment / exposure:

28 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (actual dose received)

Remarks:

Group A - control group, received basic diet only

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Remarks:

Group B - basic diet plus cis-9-octadecenyl alcohol ((Z)-octadec-9-enol)

Doses / concentrations 3

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Remarks:

Group C - basic diet plus cis,cis-9,12-octadecadienyl alcohol ((Z)-octadec-9,12-dienol)

No. of animals per sex per dose / concentration:

4 per group

Control animals:

yes, concurrent no treatment

Positive control reference chemical:

Not used

Details on dosing and sampling:

Sampling: The animals were killed 10 hour after the last feeding, their brain, heart, kidneys, liver, and testes were excised, weighed and inspected; the lipids were extracted with chloroform-methanol (2:1, v/v) and purified following established procedures.

Lipid analysis: Thin-layer chromatography of the total lipid extracts was carried out on Silica Gel H using hexanediethyl ether (60:40, v/v) as solvent, and the phosphoglycerides were eluted from the adsorbent with chloroform-methanol-water (30:50:20, v/v/v). The phosphoglycerides were subjected to hydrogenolysis, and the alkyl glycerols and alk-I-enyl glycerols formed were separated from the alcohols by thin-layer chromatography on Silica Gel G with the solvent hexane-diethyl ether (80:20, v/v). The mixture of alkyl and alk-I-enyl glycerols was treated with hydrochloric acid in diethyl ether and the resulting mixture of aldehydes and alkyl glycerols treated with lithium aluminum hydride in diethyl ether. The alcohols derived from alk-1-enyl glycerols, and the alkyl glycerols were resolved by thin-layer chromatography on Silica Gel H with hexane-diethyl ether (20:80, v/v) as solvent. Acetates of the alcohols and isopropylidene derivatives of the alkyl glycerols were prepared as described previously. The alkyl acetates were analysed by gas chromatography at 170°, on a column, 6 ft by 1/8 inch, filled with 20% diethyleneglycol succinate on Anakrom A, 80- 100 mesh, whereas the isopropylidene derivatives of alkyl glycerols were analyzed, at 200°, on the same column.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Remarks:

See tables 1 and 2

Details on metabolites:

The addition of long-chain alcohols to the basic diet did not markedly alter the distribution of lipid classes nor the fatty acid composition of the phosphoglycerides in the liver of the animals. In contrast, dietary long-chain alcohols effected pronounced changes in the composition of both the alkyl moieties and the alk-1-enyl moieties in the phosphoglycerides of rat liver.

Any other information on results incl. tables

The dietary long-chain alcohols did not produce any obvious ill effects in the rats.

Long-chain alcohols are not normally present in the diet of rats. The study results show that, if added to the diet, long-chain alcohols, including polyunsaturated ones, are incorporated into both the alkyl moieties of the alkyl acyl phosphoglycerides and the alk-1-enyl moieties of the alk-1-enyl acyl phosphoglycerides of rat liver. Although the lipids of the basic diet were rich in linoleic acid, neither the phosphoglycerides of the control animals nor those of rats fed monounsaturated alcohol contained diunsaturated alkyl or alk-1-enyl moieties.

Table 1: Composition of the alkyl glycerols derived from the total alkyl acryl phosphoglycerides in the liver of rats fer long-chain alcohols

Chain length: number of double bonds in alkyl chain*	Control animals (%)	18:1 alcohol (%)	18:2 alcohol (%)
16:0	51.5	46.0	48.0
16:1	2.5	3.0	-
18:0	7.5	8.0	4.5
18:1	37.5	43.0	42.0
18:2**	-	-	3.0

 *The following alkyl glycerols were found in trace amounts: 13:0, 17:0, 18:0 br(?), 20:0, 20:1

** Including an unidentified alkyl glycerol, possibly 19:0

Table 2: Composition of the alk-1-enyl glycerols derived from the total alk-1-enyl acryl phosphoglycerides in the liver of rats fer long-chain alcohols

Chain length: number of double bonds in alkyl chain*	Control animals (%)	18:1 alcohol (%)	18:2 alcohol (%)
16:0	36.0	37.0	21.5
16:1	Trace	1.6	1.7
18:0	31.0	21.7	38.4
18:1	32.8	39.7	35.9
18:2	Trace	Trace	2.5

 *The following alk-1-enyl glycerols were found in trace amounts: 13:0, 17:0, 18:0 br(?), 20:0, 20:1

** Including an unidentified alk-1-enyl gycerol, possibly 19:0

Applicant's summary and conclusion

Conclusions:

Groups of rats were fed a basal diet alone or a basal diet and supplements of (Z)-octadec-9-enol and (Z)-octadec-9,12-dienol. Phosphoglycerides were isolated from the livers of the rats, and the constituent alkyl, alk-1-enyl, and acyl moieties were analysed. It was determined that dietary long-chain alcohols and the unsaturated alcohols including (Z)-octadec-9-enol are incorporated into the alkyl and alkenyl moieties of phosohoglycerides.