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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
The metabolism of sorbitan monostearate
Author:
Wick, A., N.
Year:
1953
Bibliographic source:
Food research, 1953, 18:79-84
Report Date:
1952

Materials and methods

Objective of study:
distribution
excretion
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
analytical purity of test substance not given
Principles of method if other than guideline:
Rats were fed with radiolabelled sorbitan monostearate and samples from the animals were collected for 48h and analysed.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): sorbitan monostearate
- Locations of the label (if radiolabelling): polyol residue or stearic acid fraction
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
other: Albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 190-210 g
- Fasting period before study: no fasting

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water emulsion or corn oil because of different absorption properties
Details on exposure:
VEHICLE
- Justification for use and choice of vehicle (if other than water): absorption from the intestinal tract by itself is not necessarily identical with its route when dissolved in oil or in water
- Concentration in vehicle: dose dependent
- Amount of vehicle (if gavage): 4 mL corn oil or 8 mL water
Duration and frequency of treatment / exposure:
single exposure, 48h observation time
Doses / concentrations
Remarks:
Doses / Concentrations:
dependent on the experiment: 100, 240, 258, 263, 303, 307, 400 or 1293 mg in 4 or 8 mL vehicle
No. of animals per sex per dose:
no data
Control animals:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, plasma, serum or other tissues, cage washes, bile

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine, faeces, liver, kidneys, intestinal tract, hind lend muscle or entire carcas for fat, CO2
- Time and frequency of sampling: CO2 for 48h in 6h intervals, others after 48h
- From how many animals: (samples pooled or not) single samples
- Method type(s) for identification: by BaCO3 obtained directly or by dry combustion, or by direct counting

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
90% of the sorbitan monostearate when administerd in corn oil is hydrolyzed in the intestinal tract and after its absorption. The resulting anhydrid is poorly absorbed. When administered in water only 50% are hydrolyzed. The anhydrids of sorbitol were largly excreted into the urine before they could be completely oxidized to CO2.
Details on distribution in tissues:
5-7% of the administered 14C that was fed in corn oil was found in the tissue.
Fractionation of the crude fat extract of tissues excluding the intestinal tract indicated that less than 0.1% of the fed C14 may represent sorbitans derived from fed sorbitan monostearate or sorbitan esters synthesized from circulating sorbitan.
Details on excretion:
Urine contains 44-66% of the fed 14C as sorbitol anhydrids.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Stearic acid and anhydrids of sorbitol

Applicant's summary and conclusion