Potassium hexadecyl hydrogen phosphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1967

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1967

Materials and methods

Objective of study:

other: absorption, excretion, metabolism

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hexadecan-1-ol

EC Number:

253-149-0

EC Name:

Hexadecan-1-ol

Cas Number:

36653-82-4

Molecular formula:

C16H34O

IUPAC Name:

hexadecan-1-ol

Constituent 2

Reference substance name:

cetyl alcohol

IUPAC Name:

cetyl alcohol

Test material form:

other: solution

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 300 g
- Fasting period before study: no
- Diet, water: ad libitum a water solution of an acid hydrolysate of casein (2%), sucrose (7.6%), Wesson's salt mixture {0.4%), and water-soluble vitamins, starting the evening before the thoracic duct or the bile duct was cannulated
- Housing: During the lymph and bile collections, the rats were kept in restraining cages of the type described by BOLLMAN and supplied with the diet solution from an inverted bottle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- 0.2 mg [14C]cetyl alcohol and 300 mg [14C]cetyl alcohol. 0.2 mg and 300 mg [14C]cetyl alcohol were administered in 0.5 mL and 0.6 mL corn oil, respectively, by stomach tube . Each dose contained 1-1.5 µCi of 14C-radioactivity.

Duration and frequency of treatment / exposure:

24 or 48 hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.7 mg/kg bw (total dose)

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw (total dose)

No. of animals per sex per dose / concentration:

2 male rats. 1 rat per dose.

Control animals:

no

Positive control reference chemical:

No

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled : urine, faeces, lymph, bile, serum and various tissues
- Time and frequency of sampling:
- Other: Analytical methods: [I-14C]cetyl alcohol was obtained commercially and purified by thin-layer chromatography.

METABOLITE CHARACTERISATION STUDIES
- Method type(s) for identification: Thin layer chromatography of lipids

Results and discussion

Preliminary studies:

No

Main ADME results

Type:

absorption

Results:

Approximately 30-40 % of the [14C]-cetylalcohol administered dose are absorbed from the GIT after oral administration.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Systemically available.

Details on distribution in tissues:

About 30-40 % of the radioactivity were detected in urine, expired air, residual carcass, lymph and liver -> systemically distributed

Details on excretion:

60 - 70 % in feces

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Triglycerides

Any other information on results incl. tables

- Cetyl alcohol was extensively (85%) converted (during lymphatic absorption) to saponifiable material which migrated (after methylation) with the normal fatty acid methyl esters and was presumed to be palmitic acid. The cetyl alcohol that was absorbed in non-saponifiable form was present largely in a complex that migrated ahead of the triglycerides.

Applicant's summary and conclusion

Conclusions:

Approximately 30-40% of the administered dose are absorbed from the GIT after oral administration. No radioactivity was detected in urine. Small amount of radioactivity were found in expired air (1-2%). The majority of the radioactivity is recovered in feces and intestine. Cetyl alcohol is most likely present in the animal body and is metabolized into its corresponding fatty acid which is then incorporated into triglycerides.

Executive summary:

In the present study 14C-labeled cetyl alcohol (among other substances and mainly used for comparable measures) was administered by gastric intubation to rats in which the thoracic lymph duct had been cannulated. Radioactivity in the drained lymph and in the expired CO2 was determined periodically, and radioactivity (including radioactive metabolities) in the tissues was determined after 24 or 48 h. 14C-labelled cetyl alcohol was administered at a dose level of 0.7 and 1000 mg/kg bw in corn oil to rat and was found to be systemically available. About 30-40 % of the radioactivity were detected in urine, expired air, residual carcass, lymph and liver. Whereas the remaining 60-70 % were recovered from feces. Cetyl alcohol is most likely present in the animal body and is metabolized into its corresponding fatty acid which is then incorporated into triglycerides.