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EC number: 939-179-3 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Justification of read-across: Both chemicals are of comparable structures with minor deviations and can be characterized as an ester of sorbitan and a fatty acid. Justification of reliability of 2: scientifically well-performed study
Data source
Reference
- Reference Type:
- publication
- Title:
- The metabolism of sorbitan monostearate
- Author:
- Wick, A.N. and Joseph, L.
- Year:
- 1 953
- 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
- Principles of method if other than guideline:
- Rats were fed with C14 radiolabelled sorbitan monostearate and samples from the animals were collected for 48h and analysed.
- GLP compliance:
- no
Test material
- Reference substance name:
- Sorbitan stearate
- EC Number:
- 215-664-9
- EC Name:
- Sorbitan stearate
- Cas Number:
- 1338-41-6
- IUPAC Name:
- 1,4-anhydro-6-O-stearoyl-D-glucitol
- Reference substance name:
- Sorbitan monostearate
- IUPAC Name:
- Sorbitan monostearate
- Reference substance name:
- Span 60
- IUPAC Name:
- Span 60
- Test material form:
- solid: crystalline
- 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
Constituent 1
Constituent 2
Constituent 3
- 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
- Source: Purina Laboratory Chow
- Weight at study initiation: 90-210 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 / concentration:
- no data
- Control animals:
- no
- Details on study design:
- 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 - Details on dosing and sampling:
- See "any other information on materials and methods incl. talbles"
Results and discussion
- Preliminary studies:
- no
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:
- Distribution of the radioactivity 48 hours after the oral administration of sorbitan monostearate is shown in the Tables in the following ("any other information on results incl.tables".
A small amount (3-7%) of the ingested radioactivity was recovered in the tissues 48 hours after the feeding of the polyol labeled compound. Under similaconditions a 4- to 6-fold increase in C14 deposition occurred by feeding the stearate labeled compound when dissolved in oil.
The distribution of the C14 in the crude fat obtained from animal given 100 mg of sorbitan monostearate dissolved in 4 ml of corn oil is shown in the Table in the following. Three animals were sacrifieced after 2 and 7 days, respectively. In these experiments the carcasses included the kidneys and the liver, Although the crude fat obtained from each animal was saponified separately for the isolation of the fatty acids, the water soluble fractions were combined for the 2- and 7-day animals, respectively. by averaging the results from the 3 animals in each of the 2- and 7-day groups, the percentage of the injected C14 in the crude fat (excluding the intestinal tract) was 0.76 and 0.46%.
- Details on excretion:
- Expired CO2:
In all experiments a significant fraction of theadministered C14 was found in the expired CO2. The feeding of the polyol labeled ester resulted in recoveries of 14 to 24% of the administered radioactivity.
Urine:
When the polyol labeled substance was administered in water 25 and 16% of the C14 was recovered in the urine. when administered in oil 44 to 66% of the radioactivity was recovered. On the other hand, the feeding of the stearate labeled compound resulted, as expected from the stool analyses, in only a trace of C14 excretion.
Stool:
The feeding of the stearate labeled substance as a water emulsion resulted in an excrection of 69 to 76 of the fed C14 as CHCl3 soluble which is in line with results obtained by absorption studies on stearic acid. When the stearate labeled compound was fed in oil, lower values (33 to 37%) were obtained. Considerably lower results were obtained when feeding the polyol labeled compound. Hence the administration of the esters in oil in all experiments increased their intestinal absorption as indicated by the diminished C14 content of the stools.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Stearic acid and anhydrids of sorbitol
Any other information on results incl. tables
The analogue approach using sorbitan stearate as source chemical is justified:
Both chemicals are of comparable structures with minor deviations and can be characterized as an ester of sorbitan and a fatty acid. Compared to the source chemical, the target chemical has a shorter alkyl chains that affect its physicochemical properties. But based on the kinetic / metabolic investigations on both chemicals, the length of the alkyl chain is not considered to have significant impact on the metabolic pathway or toxicological mode of action. Oral gavage studies in rats administered C14 labeled sorbitan stearate in oil solutions have demonstrated that about 90% of the substance was absorbed and hydrolyzed to stearic acid and sorbitan. The metabolic fate of sorbitan caprylate was investigated using a lipase assay. The hydrolysis mediated by porcine pancreas lipase was quantitatively determined. The target chemical sorbitan caprylate is proved to be hydrolyzed and caprylic acid was formed . These findings suggest that metabolism of the sorbitan occur initially via enzymatic hydrolysis, leading to sorbitan and the corresponding natural acids.
Based on the above mentioned information, it is reasonable to consider that these two substances are comparable in their metabolic fate and thereby toxicological profiles. Hence, the source chemical is considered as “suitable with interpretation” analog.
According to the available toxicity studies, the findings are also comparable for target and source chemicals:
· The findings in acute toxicity studies are comparable. Both chemicals are of no acute toxicity.
· The findings in subacute dose toxicity studies are comparable. No treatment effects were observed in 28-day repeated toxicity studies in Wistar rats. The same NOEL of 1000 mg/kg bw/d was derived for both chemicals.
· The findings in genetic toxicity are comparable. Both chemicals did not induce gene mutations in Ames tests, but induced structural chromosomal aberrations in cell lines of Chinese Hamster.
· The findings in reproduction / developmental toxicity studies are comparable.
Percent distribution of radioactivity 48 hours after oral administration of carbon 14 labeled sorbitan stearate
Polyol labled | Stearate labeled | ||||||||||
Experiment No. | 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 |
Stool 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 |
Percent distribution of radioactivity in tissues 48 hours after oral administration of carbon 14 labeled sorbitan stearate
Polyol labeled | Stearate labeled | |||||||||
Experiment No. | 2 | 3 | 4 | 5 | 6 | 8 | 9 | 10 | 11 | |
Liver | CH3Cl3 soluble | 0.06 | 0.08 | 0.09 | 0.10 | 0.11 | 1.28 | 1.45 | 4.30 | 4.70 |
CH3Cl3 insoluble | 0.23 | 0.52 | 0.55 | 0.57 | 0.50 | 0.35 | 0.62 | 0.92 | 1.82 | |
Kidney | CH3Cl3 soluble | 0.01 | 0.01 | 0.02 | 0.08 | 0.03 | 0.18 | 0.05 | 0.14 | 0.18 |
CH3Cl3 insoluble | 0.02 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.14 | 0.09 | 0.49 | |
Intestines | CH3Cl3 soluble | 0.07 | 0.29 | 1.18 | 0.12 | 0.76 | 0.61 | 0.62 | 2.53 | 2.54 |
CH3Cl3 insoluble | 0.18 | 0.98 | 0.77 | 0.59 | 1.64 | 0.18 | 0.23 | 0.73 | 0.85 | |
Carcasse | CH3Cl3 soluble | 0.53 | 1.13 | 1.39 | 0.68 | 0.91 | 6.20 | 11.30 | 17.95 | 26.40 |
CH3Cl3 insoluble | 1.44 | 2.58 | 2.58 | 2.84 | 2.80 | 1.45 | 1.07 | 5.65 | 3.90 | |
Total recovery | 2.54 | 5.64 | 6.90 | 5.03 | 6.80 | 10.40 | 15.48 | 32.31 | 40.88 |
Rate of C14 excretion in expired CO2 after administration of polyol labeled sorbitan monostearate
Period (hours) | Experiment number | |||
3 | 4 | 4 | 6 | |
1 -6 | 3.2 | 2.1 | 3.2 | 1.8 |
7 -12 | 4.9 | 4.2 | 4.9 | 2.3 |
13 -18 | 4.8 | 3.8 | 4.1 | 2.6 |
19 -24 | 2.7 | 4.6 | 4.2 | 1.8 |
25 -30 | 1.1 | 2.5 | 2.5 | 4.5 |
31 -36 | 0.7 | 1.0 | 1.9 | 4.2 |
37 -42 | 0.6 | 0.7 | 2.1 | 1.4 |
43 -48 | 0.3 | 0.4 | 1.0 | 1.4 |
Total | 18 | 19 | 24 | 20 |
Vales expressed as % of fed ester
Percent distribution of radioactivity 48 hours after administration of urine and stool extracts
Stool from No.2 | Urine frome No.2 | Urine from No.12 | |
Experiment No. | 12 | 13 | 14 |
Expired CO2 | 28 | 23 | 24 |
Urine | 27 | 64 | 34 |
Stool CHCl3 soluble | 32 | 5 | 5 |
Stool CHCl3 insoluble | 17 | 24 | 31 |
Total | 104 | 116 | 94 |
Distribution of C14 in crude carcass fat
Time of sacrifice after feeding | 2 -day | 7 -day |
1. Fatty acids | 38 | 42 |
2. Glycerol | 27 | 43 |
3. Residue | 14 | 12 |
Total | 79 | 97 |
Values expressed as precent of the crude fat
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): other:
The target chemical sorbitan caprylate is considered to be hydrolyzed to caprylic acid and the anhydrides of sorbitol. - Executive summary:
The metabolism and toxicokinetics of sorbitan caprylate was assessed based on the analogue approach using sorbitan stearate as a read-across supporting substance.
Radioactive sorbitan monostearate has been fed to rats and the fate of the C14 has been studied. The distribution of the C14 shows that at least 90% of the polyol labeled emulsifier, when fed in oil solution, was hydrolyzed to stearic acid and the anhydrides of sorbitol. When fed as a water emulsion, about 50% of the ester is hydrolyzed.
The anhydrides of sorbitol which were liberated by the hydrolysis were largely excreted into the urine before they could be completely oxidized to CO2.
The amount of C14 found in the tissues 48 hours after feeding of polyol labeled sorbitan monostearate in oil was 5 to 7% of the administered C14. Fractionation of the crude fat extract of the 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.
Based on the results from the study of sorbitan monostearate, the target chemical sorbitan caprylate is considered to be hydrolyzed to caprylic acid and the anhydrides of sorbitol.
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