Fatty acids, rape-oil, mixed esters with 1,4:3,6-dianhydro-d-glucitol, sorbitan and sorbitol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no data on test substance purity)

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

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

yes

Remarks:

(analytical purity of test substance not given, limited documentation)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sorbitan stearate

EC Number:

215-664-9

EC Name:

Sorbitan stearate

Cas Number:

1338-41-6

Molecular formula:

C24H46O6

IUPAC Name:

1,4-anhydro-6-O-stearoyl-D-glucitol

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
- Analytical purity: not specified

Radiolabelling:

yes

Remarks:

C14

Test animals

Species:

rat

Strain:

other: Albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 190-210 g
- Fasting period before study: no fasting
- Diet: Purina Laboratory Chow
- Individual metabolism cages: yes

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, 48 h 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 (0.5-6.5 mg/kg bw)

No. of animals per sex per dose / concentration:

1/experiment

Control animals:

no

Details on study design:

11 different experiments were performed: In experiments 1 to 6 the polyol was labeled. For experiment 1 and 2, the test substance was emulsified in water, for 3 to 6 in corn oil. In experiments 7 to 11 the stearate was labeled. For experiment 7 to 9, the test substance was emulsified in water, for 10 and 11 in corn oil.

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:

When administerd in corn oil, 90% of the test substance is hydrolysed 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 C14 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 C14 as sorbitol anhydrids.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Stearic acid and anhydrids of sorbitol

Any other information on results incl. tables

Table 1: Percent distribution of radioactivity 48 hours after oral administration of C¹⁴ labeled sorbitan monostearate:

	Polyol labeled						Stearate labeled
Experiment number	1	2	3	4	5	6	7	8	9	10	11
Expired CO2	15	14	18	19	24	20	18	7	12	33	21
Urine	25	16	66	66	50	44	1	1	1	1	1
Stool
CHCl3 soluble	31	54	7	6	7	8	75	76	69	37	33
CHCL3 insoluble	17	12	12	8	10	12	3	5	4	2	2
Combined tissues	--	3	6	7	5	7	--	10	15	32	41
Total recovery	88	99	109	106	96	91	97	99	101	105	98

Exp. 1, 2, 7-9: test substance administered in water

Exp. 3 -6, 10, 11: test substance administered in corn oil

A small amount (3 -7%) of the ingested radioactivity was recovered in the tissues 48 hours after the feeding of the labeled polyol. Under similar conditions a 4- to 6 -fold increase in C¹⁴ deposition occured by feeding the stearate labeled compound when dissolved in corn oil. The percentage of the injected C¹⁴ in the crude fat was 0.76 and 0.46% (see Table 2):

Table 2: Percent distribution of radioactivity in tissues 48 hours after oral administration of C¹⁴ labeled sorbitan monostearate:

	Polyol labeled					Stearate labeled
Experiment number	2	3	4	5	6	8	9	10	11
Liver
CHCl3 soluble	0.06	0.08	0.09	0.1	0.11	1.38	1.45	4.3	4.7
CHCL3 insoluble	0.23	0.52	0.55	0.57	0.50	0.35	0.62	0.92	1.82
Kidneys
CHCl3 soluble	0.01	0.01	0.02	0.08	0.03	0.18	0.05	0.14	0.18
CHCL3 insoluble	0.02	0.05	0.05	0.05	0.05	0.05	0.14	0.09	0.49
Intestines
CHCl3 soluble	0.07	0.29	1.18	0.12	0.76	0.61	0.62	2.53	2.54
CHCL3 insoluble	0.18	0.98	0.77	0.59	1.64	0.18	0.23	0.73	0.85
Carcass
CHCl3 soluble	0.53	1.13	1.39	0.68	0.91	6.2	11.3	17.95	26.4
CHCL3 insoluble	1.44	2.58	2.85	2.84	2.80	1.45	1.07	5.65	3.9
Total recovery	2.54	5.64	6.9	5.03	6.8	10.4	15.48	32.31	40.88

Exp. 1, 2, 7-9: test substance administered in water

Exp. 3 -6, 10, 11: test substance administered in corn oil