Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 701-203-3 | 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- repeated dose toxicity: oral
- Remarks:
- combined repeated dose and carcinogenicity
- 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: Acceptable, well documented publication which meets basic scientific principles
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 992
Materials and methods
- Principles of method if other than guideline:
- Lifespan (2-year) repeated dose toxicity study in mice at dietary concentrations of 25000 and 50000 ppm
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Sorbitan monooleate, ethoxylated
- EC Number:
- 500-019-9
- EC Name:
- Sorbitan monooleate, ethoxylated
- Cas Number:
- 9005-65-6
- Molecular formula:
- Not applicable as UVCB
- IUPAC Name:
- Sorbitan, C18-unsat, fatty acid esters, ethoxylated (1 - 6.5 moles ethoxylated)
- Reference substance name:
- Tween 80
- IUPAC Name:
- Tween 80
- Details on test material:
- - Name of test material (as cited in study report): Polysorbate 80
- Physical state: translucent, pale yellow, viscous liquid
- Analytical purity: approx. 83- 85%
- Composition of test material, percentage of components: approx. 83-85% sorbitan polyethylene glycol fatty acid esters and approx. 15-17% sorbitan polyethylene glycols
- Lot/batch No.: 250-1 and 7230-C
- Storage condition of test material: protected from light
Constituent 1
Constituent 2
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Frederick Cancer Research Facility (Frederick, MD, USA)
- Age at study initiation: 57 days (males), 64 days (females)
- Weight at study initiation: group mean (males): 22.2-22.7 g, group mean (females): 16.4-16.8 g
- Housing: animals were housed in groups of five in solid-bottom polycarbonate cages (Lab Products, Inc., Garfield, NJ, USA), equipped with BetaChip® hardwood laboratory bedding (Northeastern Products Corp., Warrensburg, NY, USA), reemay spun-bonded polyester cage filters (Snow Filtration, Cincinnati, OH, USA) and stainless steel racks (Lab Products, Inc., Garfield, NY, USA).
- Diet: NIH-07 Open-Formula Mash (Zeigler Bros.,Inc., Gardners, PA, USA), ad libitum
- Water: tap water via automatic watering system (Edstrom Industries, Inc., Waterford, WI, USA), ad libitum
- Acclimation period: 20 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8-33.3
- Humidity (%): 18-82
- Air changes (per hr): min. 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 18 Aug 1982 To: 07 Aug 1984
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): the dose formulation were prepared weekly during the study period.
- Mixing appropriate amounts with (Type of food): NIH-07 Open-Formula Mash
- Storage temperature of food: at 5 °C in the dark - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Homogeneity and stability analyses of the dosed feed preparations were analysed using UV spectroscopy. Therefore, samples were extracted with solvent, evaporated to dryness, resuspended in methylene chloride and reacted with cobalt thiocyanate solution. The absorbance of the methylene chloride layer was determined at 320 nm using UV spectroscopy. Homogeneity of these formulations was confirmed, stability of the formulation was established for at least 2 weeks when stored in the dark at temperatures up to 5 °C. During the 2-year studies, the dose formulations were analysed at least once every 8 weeks. Concentration analysis of the dose formulations showed that 97% (84/87) dose formulations were within the specified ± 10% of the target concentrations.
- Duration of treatment / exposure:
- 103 weeks
interim sacrifice after 15 months - Frequency of treatment:
- daily (7 days/week)
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
25000 and 50000 ppm
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
5003 and 10811 mg/kg bw/day (male)
Basis:
other: based on the average reported body weight and food consumption (see Table 1 under “Any other information on results incl. tables")
- Remarks:
- Doses / Concentrations:
6487 and 13197 mg/kg bw/day (female)
Basis:
other: based on the average reported body weight and food consumption (see Table 2 under “Any other information on results incl. tables")
- No. of animals per sex per dose:
- 50 (main study control and treatment groups)
7-10 (interim sacrifice control and treatment groups) - Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: the dose levels were selected based on a previous 13-week toxicity study in mice, showing no adverse effects in mice up to the maximum dose of 50000 ppm. Thus, 50000 ppm was selected as the high dose and 25000 ppm was selected as the low dose for male and female mice in the 2-year study. Doses greater than 50000 ppm were not considered appropriate for the 2-year study, because diets containing more than 50000 ppm of the test substance could lead to nutritional deficiencies in the study animals.
- Rationale for animal assignment (if not random): animals were grouped by body weight and assigned to cages. Cages were assigned to treatment groups using a table of random numbers.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: animals were observed twice daily and at study termination and clinical observations were recorded once per week, then monthly or as necessary thereafter.
BODY WEIGHT: Yes
- Time schedule for examinations: animals were weighed at study initiation, weekly for 13 weeks, and monthly thereafter.
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes, monthly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, complete necropsy (all tissues and organs) was performed on all animals. Absolute and relative organ weights of brain, right kidney, and liver of all animals evaluated at 15 months (7-10 animals per each group) were determined at necropsy.
HISTOPATHOLOGY: Yes, complete histopathology was performed on all animals that died or were killed moribund prior to study termination, all animals from the 15-month interim evaluation that received 0 or 50000 ppm and all mice from the 0 and 50000 ppm dose groups that survived to study termination. Tissues examined included: adrenal gland, bone and bone marrow, brain (frontal cortex and basal ganglia, parietal cortex and thalamus, and cerebellum and pons), oesophagus, gallbladder, gross lesions and tissue masses, heart, kidney, large intestine (cecum, colon, and rectum), liver, lungs and mainstem bronchi, mammary gland, mandibular or mesenteric lymph nodes, nasal cavity and turbinates, ovary, pancreas, parathyroid gland, pituitary gland, prostate gland, salivary gland; seminal vesicle, skin, small intestine (duodenum, jejunum, and ileum), spleen, stomach, testis (with epididymis), thymus, thyroid gland, trachea, urinary bladder, and uterus. - Statistics:
- Statistical analyses for a possible dose-related effect on survival used the method of Cox (1972) for testing two groups for equality and Tarone's (1975) life table test to identify dose-related trends. Ball reported p values for the survival analyses were two sided. Organ and body weight data, which have approximately normal distributions, were analysed using the multiple comparison procedures of Williams (1971 and 1972) and Dunnett (1955). Jonckheere’s test (Jonckheere, 1954) was used to assess the significance of dose-response trends and to determine whether a trend-sensitive test (Williams’ test) was more appropriate for pairwise comparisons than a test that does not assume a monotonic dose-response (Dunnett’s test).
REFERENCES:
Cox, D.R. (1972). Regression models and life tables. J. R. Stat. Soc. B34: 187-220.
Tarone, R.E. (1975). Tests for trend in life table analysis. Biometrika 62: 679-682.
Williams, D.A (1971). A test for differences between treatment means when several dose levels are compared with a zero dose control. Biometrics 27: 103-117.
Williams, D.A. (1972). The comparison of several dose levels with a zero dose control. Biometrics 28: 519-531.
Dunnett, W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Am. Stat. Assoc. 50: 1095-1121.
Jonckheere, A. (1954). A distribution-free k-sample against ordered alternatives. Biometrika 41: 133-145
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 50000 ppm (females): reduction (-11% compared to controls) in final mean body weight
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Control group and 25000 ppm: increased incidence of squamous hyperplasia and inflammation of the forestomach (m/f); 50000 ppm: stat. signif. increase in the incidence of inflammation and squamous hyperplasia of the forestomach (m/f) as well as ulcers (f)
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Survival of male and female mice of both treatment groups was similar to that of the controls. Three control males, three males of the low dose group (25000 ppm) and one control female died prior to the 15-moth interim evaluations. As mortalities occurred only within the low dose group and also in the control group, they were not considered to be associated with treatment of the test substance.
No clinical findings associated with treatment of the test substance were observed in animals of both dose groups.
BODY WEIGHT AND WEIGHT GAIN
A slight reduction (-11%) in final mean body weights of females from the high dose group was observed compared to controls.
In contrast, no alterations in mean body weights and body weight gain were observed in treated males of both dose groups as well as treated females from the low dose group when compared to controls.
FOOD CONSUMPTION AND COMPOUND INTAKE
The average feed consumption of treated animals from both dose groups was similar to that of the controls. The average compound intake (determined over 101 weeks) for males and females of both dose groups is given in Table 1 and 2 under “Any other information on results incl. tables”.
ORGAN WEIGHTS
No changes in absolute and relative organ weights of brain, right kidney, and liver of all animals (7-10 per group) evaluated at 15 months were observed compared to the respective control group.
GROSS PATHOLOGY
No treatment-related gross pathological findings were observed in treated animals at the 15-month interim sacrifice and at the end of the 2-year study period.
HISTOPATHOLOGY: NON-NEOPLASTIC
During the 15-month interim evaluations, compound-related lesions occurred in 5 of 10 females from the high dose group. These lesions included mild hyperplasia of the forestomach epithelium and inflammation of the forestomach. No test substance-related non-neoplastic lesions were observed in treated males of both dose groups.
At the end of the 2-year study period, compound-related lesions of the forestomach occurred in mice of all dose groups (including controls) (see Table 3 under “Any other information on results incl. tables”). These included squamous hyperplasia of the epithelium, inflammation, and ulcers. The incidences and severity of hyperplasia of the forestomach epithelium (hyperplasia, squamous) and inflammation of the forestomach were significantly increased in males and females that received the highest concentration in the diet (50000 ppm). Hyperplasia of the forestomach was characterized by focal, broad-based lesions usually located near the limiting ridge between the forestomach and the glandular stomach. In the low dose group, minimal to mild hyperplasia consisted of slight thickening and folding of the epithelium; in marked lesions the thickened epithelium sometimes formed multiple projections into the lumen. Some hyperplasias were focal, elevated thickenings surrounding an ulcer. Hyperplasias were typically more extensive in high-dose than in low-dose animals. In a number of mice, aggregates of small to moderate numbers of neutrophils (inflammation, acute) were present in the forestomach wall. In several animals of the high dose group, chronic active inflammation, a scattering of small to moderate number of mixed Iymphocytes, macrophages, and neutrophils, often accompanied by varying amounts of fibrosis, were present in the forestomach wall beneath areas of hyperplasia. The forestomach squamous hyperplasia and inflammation in high-dose animals and the ulcers in high-dose females were considered to be related to treatment with the test substance.
HISTOPATHOLOGY: NEOPLASTIC
During the 15-month interim evaluations and at the end of the 2-year study period, no statistically significantly increased incidences of neoplasms occurred in treated mice of either sex. Although hyperplasia and inflammation was increased in animals of the high dose group, no neoplasms in the forestomach of these animals were noted. The only observed forestomach neoplasm, which were not considered to be of toxicological relevance, involved one squamous papilloma in a control male and one squamous cell carcinoma in a low-dose male.
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 50 000 ppm
- Based on:
- test mat.
- Remarks:
- corresponding to 10811 (m) and 13197 (f) mg/kg bw/day based on the average reported body weight and food consumption (over 102 weeks)
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Dose descriptor:
- NOAEL
- Effect level:
- 25 000 ppm
- Based on:
- test mat.
- Remarks:
- corresponding to 5003 (m) and 6487 (f) mg/kg bw/day based on the average reported body weight and food consumption (over 102 weeks)
- Sex:
- male/female
- Basis for effect level:
- other: slight, but not significant increase in the incidence of squamous hyperplasia (minimal to mild) and inflammation of the forestomach
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1. Calculation of doses in mg/kg bw/day (males) over the 2-year study period from the reported food and compound consumption
Week |
25000 ppm |
50000 ppm |
||||
Feed (g/day) |
Body weight (g) |
Dose (mg/kg bw/day) |
Feed (g/day) |
Body weight (g) |
Dose (mg/kg bw/day) |
|
1 |
7.5 |
22.7 |
8207 |
8.0 |
22.4 |
17860 |
2 |
6.0 |
25.6 |
5824 |
6.6 |
25.5 |
12889 |
4 |
4.7 |
27.5 |
4281 |
6.1 |
26.5 |
11481 |
5 |
7.6 |
28.0 |
6769 |
7.5 |
27.5 |
13641 |
9 |
8.3 |
30.5 |
6839 |
8.1 |
30.3 |
13316 |
13 |
8.5 |
31.8 |
6691 |
8.6 |
31.6 |
13553 |
16 |
10.2 |
33.5 |
7649 |
10.1 |
32.9 |
15365 |
20 |
9.7 |
34.6 |
7001 |
8.6 |
34.4 |
12513 |
25 |
8.8 |
35.7 |
6175 |
9.5 |
34.9 |
13637 |
29 |
9.5 |
35.5 |
6688 |
9.8 |
35.1 |
13984 |
33 |
9.4 |
36.8 |
6414 |
10.0 |
35.8 |
13952 |
37 |
8.2 |
35.4 |
5807 |
9.3 |
35.8 |
13039 |
41 |
10.2 |
37.4 |
6803 |
11.6 |
36.3 |
15936 |
45 |
11.3 |
36.8 |
7690 |
13.0 |
36.7 |
17724 |
49 |
10.6 |
38.4 |
6919 |
12.4 |
38.4 |
16166 |
53 |
9.3 |
38.3 |
6093 |
10.3 |
37.7 |
13637 |
58 |
4.3 |
37.4 |
2903 |
4.1 |
37.5 |
5509 |
62 |
4.5 |
36.2 |
3113 |
5.0 |
37.5 |
6614 |
66 |
4.7 |
38.4 |
3031 |
5.2 |
38.3 |
6851 |
70 |
5.0 |
36.8 |
3385 |
5.0 |
37.2 |
6718 |
74 |
4.3 |
38.5 |
2817 |
4.8 |
38.2 |
6339 |
78 |
4.0 |
38.3 |
2615 |
4.4 |
37.7 |
5859 |
82 |
4.3 |
37.5 |
2842 |
4.9 |
37.0 |
6564 |
86 |
3.9 |
36.1 |
2731 |
4.5 |
36.4 |
6119 |
90 |
3.8 |
31.7 |
2527 |
4.0 |
36.9 |
5364 |
94 |
4.3 |
36.4 |
2956 |
4.3 |
36.9 |
5761 |
98 |
3.8 |
36.5 |
2623 |
4.4 |
37.6 |
5915 |
102 |
3.9 |
36.2 |
2703 |
4.5 |
35.0 |
6399 |
Mean values over 102 weeks |
6.8 |
34.6 |
5003 |
7.3 |
34.6 |
10811 |
Table 2. Calculation of doses in mg/kg bw/day (females) over the 2-year study period from the reported food and compound consumption
Week |
25000 ppm |
50000 ppm |
||||
Feed (g/day) |
Body weight (g) |
Dose (mg/kg bw/day) |
Feed (g/day) |
Body weight (g) |
Dose (mg/kg bw/day) |
|
1 |
7.6 |
16.4 |
11624 |
7.9 |
16.5 |
24050 |
2 |
7.0 |
18.7 |
9354 |
6.5 |
18.9 |
17159 |
4 |
5.6 |
20.3 |
6838 |
5.1 |
20.3 |
12529 |
5 |
7.2 |
20.6 |
8787 |
7.1 |
20.3 |
17417 |
9 |
9.2 |
23.0 |
9980 |
8.8 |
22.8 |
19403 |
13 |
8.4 |
22.8 |
9208 |
9.3 |
22.8 |
20308 |
16 |
10.7 |
24.2 |
11094 |
10.7 |
24.7 |
21642 |
20 |
10.2 |
26.1 |
9816 |
9.7 |
25.3 |
19224 |
25 |
9.0 |
27.5 |
8173 |
10.2 |
26.6 |
19106 |
29 |
9.5 |
28.0 |
8498 |
8.4 |
27.7 |
15104 |
33 |
10.3 |
29.3 |
8763 |
10.0 |
28.1 |
17710 |
37 |
7.9 |
29.2 |
6772 |
7.8 |
28.2 |
13749 |
41 |
9.5 |
30.9 |
7696 |
10.0 |
29.4 |
17019 |
45 |
12.8 |
30.7 |
10429 |
11.0 |
28.8 |
19157 |
49 |
9.7 |
32.1 |
7543 |
9.7 |
30.7 |
15873 |
53 |
9.0 |
33.0 |
6835 |
7.6 |
30.8 |
12322 |
58 |
3.8 |
32.9 |
2864 |
3.5 |
31.3 |
5600 |
62 |
5.4 |
35.0 |
3880 |
5.8 |
32.9 |
8797 |
66 |
5.4 |
35.8 |
3746 |
5.8 |
33.1 |
8791 |
70 |
5.9 |
36.1 |
4076 |
5.4 |
33.5 |
8003 |
74 |
5.1 |
36.0 |
3542 |
5.0 |
34.2 |
7338 |
78 |
4.5 |
37.0 |
3045 |
4.8 |
34.4 |
6945 |
82 |
4.8 |
37.7 |
3211 |
4.9 |
34.4 |
7176 |
86 |
5.0 |
37.0 |
3407 |
6.0 |
34.7 |
8655 |
90 |
3.4 |
36.6 |
2337 |
3.7 |
34.4 |
5375 |
94 |
5.1 |
37.0 |
3439 |
5.3 |
35.1 |
7524 |
98 |
5.5 |
37.2 |
3689 |
4.9 |
34.7 |
7125 |
102 |
4.6 |
38.1 |
2993 |
4.6 |
35.6 |
6404 |
Mean values over 102 weeks |
7.2 |
30.3 |
6487 |
7.1 |
28.9 |
13197 |
Table 3. Incidences of selected forestomach lesions in mice in the 2-year feeding study
|
Control (0 ppm) |
25000 ppm |
50000 ppm |
Male |
|||
Hyperplasia, squamous |
3/48 (6%) |
4/50 (8%) |
19/50 (38%)** |
Inflammation, acute |
0/48 (0%) |
3/50 (6%) |
5/50 (10%)* |
Inflammation, chronic active |
0/48 (0%) |
1/50 (2%) |
7/50 (14%)** |
|
|||
Female |
|||
Hyperplasia, squamous |
4/49 (8%) |
8/50 (16%) |
26/49 (53%)** |
Inflammation, acute |
2/49 (4%) |
4/50 (8%) |
3/49 (6%) |
Inflammation, chronic active |
2/49 (4%) |
0/50 (0%) |
13/49 (27%)** |
Ulcer |
1/49 (2%) |
0/50 (0%) |
7/49 (14%)* |
* Significantly different (P<0.05) from the control group by the logistic regression tests ** P<0.01 |
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.