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Toxicological information

Basic toxicokinetics

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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:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
(analytical purity of test substance not given, limited documentation)
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
- Analytical purity: not specified
Radiolabelling:
yes
Remarks:
C14

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
- 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:
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

Applicant's summary and conclusion