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EC number: 943-428-1 | 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:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key 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).
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- yes
- Remarks:
- (analytical purity of test substance not given)
- GLP compliance:
- yes
- Limit test:
- 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
- Details on test material:
- - Name of test material (as cited in study report): sorbitan monooctadecanoate
- Physical state: light yellow crystalline pellet
- Analytical purity: no data
- Storage condition of test material: stored in a sealed box under the room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc., Yokohama, Japan
- Age at study initiation: 10 weeks
- Weight at study initiation: males (g): 385.3 ± 18.2 - 386.6 ± 16.8, females (g): 220.4 ± 9.6 - 224.8 ± 7.8
- Housing: metal wire mesh cages (220x270x190 mm)
- Diet (ad libitum): CE-2, Clea Japan
- Water (ad libitum): tap water
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0 - 24.5
- Humidity (%): 55.0 - 65.5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: serial dilutions in water were prepared
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Prior to the main study, analytical measurements were performed (GC).
- Duration of treatment / exposure:
- females: 2 weeks before mating until day 4 of lactation ~42 days
males: 42 days - Frequency of treatment:
- once daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
40, 200, 1000 mg/kg bw/d
Basis:
nominal in water
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: preliminary range-finding study (pilot project number: R-04-004) 0, 500, 1000 and 2000 mg/kg bw/d
- Post-exposure recovery period in satellite groups: 14 days
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 1 time daily during the breeding and recovery period and twice daily during the treatment period before and after administration
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: day 7, 14, 21, 28, 35, 42 during treatment and day 7, 14 during recovery
[position, posture, spontaneous movement, noise, tremor, ease of retrieval, ease of handling, heart beat, body temperature, fur, skin, visible mucous membranes, tearing, bulging eyes, pupil diameter, Postural position, exploratory behavior, grooming, vocalizations, straub tail reaction, walking, stereotypic behavior, bizarre behavior, tremors, piloerection, eye fissure]
BODY WEIGHT: Yes
- Time schedule for examinations:
males: 1, 7, 14, 21, 28, 35, 42 during treatment and 1, 7, 14, 15 during recovery
pregnant females: 1, 7, 14, 21, 28 before the copulation, 0, 7, 14, 20 after the copulation and 0, 4, 5 after delivery,
females in satellite group: 1, 7, 14, 21, 28, 35, 42 during treatment and 1, 7, 14, 15 during recovery
FOOD CONSUMPTION:
males and satellite fimales: between days 1-2, 7-8, 14-15, 29-30, 35-36, 41-42 during treatment and 6-7, 13-14 during recovery
females: between days 1-2, 7-8, 14-15 before pregnancy, 0-1, 7-8, 14-15, 20-21 during pregancy and 3-4 during lactation
FOOD EFFICIENCY:
- Body weight gain in g: Yes
WATER CONSUMPTION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: male: one day after the end of dosing period, males and females in satellite groups: 15 day after the end of treatment, females: day 4 during lactation
- Animals fasted: 18 - 24 hours before anatomy
- How many animals: 5 per group
- Parameters checked: red blood cell count, white blood cell count, leukocyte classification, amount of hemoglobin, mean corpuscular volume, platelet count, hematocrit, mean corpuscular hemoglobin content, mean corpuscular hemoglobin concentration, prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: male: one day after the end of dosing period, males and females in satellite groups: 15 day after the end of treatment, females: day 4 during lactation
- Animals fasted: 18 - 24 hours before anatomy
- How many animals: 5 per group
- Parameters checked: total protein concentration, total cholesterol concentration, urea nitrogen level, AST (GOT), ALT (GPT), γ-GTP, inorganic phosphorus concentration, sodium ion concentration, potassium ion concentration, chloride ion concentration
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: males: at the end of dosing period, males and females in satellite groups: at the end of recovery period, females: day 4 during lactation
- Dose groups that were examined: 0, 40, 200, 1000 mg/kg
- Battery of functions tested: reaction function testing, pupillary reflex, visual orientation, surprised reaction, hind limb retraction reflex, experimental eye (blink) reflex, observed the presence or absence of righting reflex
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
brain, heart, thymus, liver, kidney, spleen tiles, adrenal gland, testis and epididymis were weighed (actual weight). Pituitary, spinal cord, heart, trachea, lung (including bronchus), liver, kidney, thymus, spleen tiles, adrenals, thyroid, stomach, duodenum, jejunum, cecum, colon, rectum, testis, epididymis, ventral prostate, seminal vesicles including coagulation glands, ovary, uterus,mandibular lymph node, mesenteric lymph nodes, sciatic nerve, and femoral bone marrow were preserved.
HISTOPATHOLOGY: Yes
brain, heart, thymus, liver, kidney, spleen tiles, adrenal gland, testis, epididymis, pituitary, spinal cord, heart, trachea, lung (including bronchus), liver, kidney, thymus, spleen tiles, adrenals, thyroid, stomach, duodenum, jejunum, cecum, colon, rectum, testis, epididymis, ventral prostate, seminal vesicles including coagulation glands, ovary, uterus,mandibular lymph node, mesenteric lymph nodes, sciatic nerve, and femoral bone marrow - Other examinations:
- sexual cycle, mating, pup delivery, external malformations offspring
- Statistics:
- Fisher´s exact test, Mann-Whitney U-grade test, Student´s t-test, Aspin-Welch test, Bartlett test, Dunnett multiple comparison method, Kruskal-Wallis test
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- non-adverse effects
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- non-adverse effects
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- non-adverse effects
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- non-adverse effects
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- non-adverse effects, as also observed in control group.
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No mortality was observed.
200 mg/kg bw/d: loss of fur with ulcer (between day 14 and day 41 during treatment) in one male animal
control group: loss of fur with ulcer (between day 14 and day 42) in one female animal
HAEMATOLOGY
200 mg/kg bw/d: increased mean corpuscular haemoglobin in females
CLINICAL CHEMISTRY
1000 mg/kg bw/d: reduced total protein and albumin in males
200 mg/kg bw/d: reduced albumin in males
40 mg/kg bw/d: increased triglycerides in females
1000 mg/kg bw/d (satellite group): increased ALP in females
NEUROBEHAVIOUR
No abnormal behaviour in all groups.
ORGAN WEIGHTS
1000 mg/kg bw/d: decreased relative weights of epididymis in males
200 mg/kg bw/d: decreased relative weight of brain in males
1000 mg/kg bw/d (satellite group): increased absolute epididymis weight in males and increased absolute brain weight in females
GROSS PATHOLOGY
200 mg/kg bw/d: spots in glandular stomach in females
HISTOPATHOLOGY: NON-NEOPLASTIC
In the control group and in the 40, 200, 1000 mg/kg bw/d dose groups, tubular atrophy and cell debris in the testes was observed.
- 1000 mg/kg bw/d: heart muscle degeneration, metaplasia in lungs, fat in the periportal hepatocytes, infiltration of lymphocytes in stomach, extramedullary hematopoiesis and brown pigment in spleen, basophilic tubules and mineral deposition in localized renal cortical and circumscribed cyst in kidney in male and female animals; neutrophil and lymphocyte infiltration in prostatic stroma and epithelium additionally in male animals
- Control group: heart muscle degeneration, neutrophil infiltration in lugs, fat in the periportal hepatocytes, subcapsule necrotic spot in liver, extramedullary hematopoiesis and brown pigment in spleen, basophilic tubules and mineral deposition in localized renal cortical and circumscribed lymphocytic infiltration in kidney, neutrophil and lymphocyte infiltration in prostatic stroma and epithelium in male animals and myocardial degeneration, periportal hepatocytes, extramedullary hematopoiesis and brown pigment in spleen, tubular basophilia in kidney in female animals Testes and epididymes and ovaries showed no abnormal findings at the end of the study period.
REPRODUCTIVE TOXICITY
No significant or dose-related effects on reproduction.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
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