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EC number: 943-011-4 | 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
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 29 Nov 2005 - 10 Mar 2006
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- GLP-Guideline study, tested with the source substance Fatty acids, C6-12, esters with propylene glycol (CAS 85883-73-4). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- no neurobehavioural examinations
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Reference substance 001
- Cas Number:
- 85883-73-4
- Test material form:
- liquid
- Remarks:
- colourless
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, Inc., Raleigh, NC, USA
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: 216 - 250 g (males) and 163 - 196 g (females)
- Housing: animals were housed individually in clean, stainless steel, wire-mesh cages suspended above cage-board
- Diet: certified Rodent LabDiet 5002 (meal) (PMI Nutrition International, LLC), ad libitum
- Water: municipal water, ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test article was administered neat. The dose volumes used to obtain the desired dose levels were based on the specific gravity of the test article (0.9450) at approximately 20°C.
The test and control articles were warmed to room temperature prior to administration and stirred continuously throughout the preparation and dose administration procedures. - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- once daily, 7 days/week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 500 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 2 500 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10 (treatment groups 1-4, toxicology groups)
3 (toxicokinetic group 1A)
9 (toxicokinetic groups 2A-4A) - Control animals:
- other: Yes, water at the highest dosage volume (2.65 mL/kg)
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked: mortality, moribundity, clinical signs
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly, beginning 1 week prior to test article administration and prior to the scheduled necrosy
BODY WEIGHT: Yes, mean body weights and mean body weight changes
- Time schedule for examinations: at least weekly
FOOD CONSUMPTION: Yes, g/animal/day
- Time schedule for examinations: weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to the initiation of dose administration and near the end of the treatment period
- Dose groups that were examined: toxicology groups
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the scheduled necropsy
- Anaesthetic used for blood collection: Yes, blood was collected for haematology and serum chemistry evaluations prior to necropsy from a retro-orbital sinus from animals anesthetised with isoflurane and from the vena cava from animals anesthetised with carbon dioxide for coagulation evaluations
- Animals fasted: Yes, overnight
- How many animals: toxicology groups
- Parameters checked: total leukocyte count, erythrocyte count, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelet count, prothrombin time, activated partial thromboplastin time, reticulocyte count percent and absolute, differential leukocyte count -percent and absolute -neutrophil -lymphocyte -monocyte -eosinophil -basophil -large unstained cell
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the scheduled necropsy
- Animals fasted: Yes, overnight
- How many animals: toxicology groups
- Parameters checked: albumin, total protein, globulin [by calculation], albumin/globulin ratio [by calculation], total bilirubin, urea nitrogen, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, glucose, total cholesterol, calcium, chloride, phosphorus, potassium, sodium, triglycerides
URINALYSIS: Yes
- Time schedule for collection of urine: at the scheduled necropsy
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes, overnight
- Parameters checked: specific gravity, pH, total volume, colour, clarity, protein, glucose, urobilinogen, ketones, bilirubin, occult blood, leukocytes, microscopy of sediment
TOXICOKINETICS: No
- Since there were no adverse effects at the high-dose level and no differences between clinical findings in the low- and high-dose levels, determination of plasma drug levels was not considered necessary. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, the necropsies included, but were not limited to, examination of the external surface, all orifices, and the cranial, thoracic, abdominal and pelvic cavities, including viscera
HISTOPATHOLOGY: Yes, adrenal glands (2), aorta, bone with marrow, femur, sternum, bone marrow smear, brain, cerebrum level 1, cerebrum level 2, cerebellum with medulla/pons, epididymides, exorbital lacrimal glands (2), eyes with optic nerve (2), gastrointestinal tract, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, harderian glands (2), heart, kidneys (2), liver (sections of 2 lobes), lungs (including bronchi, fixed by inflation with fixative), lymph nodes, mandibular (2), mesenteric, mammary glands (females only), ovaries with oviducts (2), pancreas, peripheral nerve (sciatic), pituitary, prostate, salivary glands, [submandibular (2)], seminal vesicles (2), skeletal muscle (rectus femoris), skin, spinal cord (cervical, midthoracic, lumbar), spleen, testes (2), thymus, thyroid [with parathyroids(2)], tongue, trachea, urinary bladder (inflated with fixative), uterus with cervix, vagina, all gross lesions - Other examinations:
- The following organs were weighed from all animals at the scheduled necropsy: adrenal glands, brain, epididymides, heart, kidneys, liver, ovaries with oviducts, pituitary, prostate, spleen, testes, thymus, thyroid with parathyroids, uterus, paired organs were weighed together
- Statistics:
- Body weight, body weight change, food consumption, clinical pathology and organ weight data were subjected to a parametric 1-way analysis of variance (ANOVA) (Snedecor and Cochran, 1980) to determine intergroup differences. If the ANOVA revealed statistically significant (p < 0.05) intergroup variance, Dunnett's test (Dunnett, 1964) was used to compare the test article-treated groups to the control group.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- excessive salivation in all treatment groups, non-adverse
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- excessive salivation in all treatment groups, non-adverse
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- 2500 mg/kg bw/day: lower mean food consumption during week 3-4, non-adverse
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 1500 and 2500 mg/kg bw/day (males): mean white blood cell counts and absolute lymphocytes significantly elevated, non-adverse
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 1500 and 2500 mg/kg bw/day (males): signifcantly increased mean triglyceride levels; all female groups: significantly higher mean phosphorus level, non-adverse
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- 2500 mg/kg bw/day (females): mean absolute thyroid/parathyroid weight was slightly lower, non-adverse
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Test article-related clinical observations were noted in the 500, 1500 and 2500 mg/kg/day groups. These findings consisted of evidence of excessive salivation including clear material noted around the mouth and yellow or red material around the mouth and nose and on the forelimbs, hindlimbs, ventral neck and ventral trunk. In general, the males and females within each test article-treated group were equally affected with the highest incidence for these findings occurring in the 2500 mg/kg/day group. In the absence of associated test article-related effects on body weight parameters and food consumption, the test article-related clinical observations noted at 500, 1500 and 2500 mg/kg/day were not considered adverse.
BODY WEIGHT AND WEIGHT GAIN
Body weights were unaffected by test article administration.
FOOD CONSUMPTION
Statistically significant lower mean food consumption was noted in the 2500 mg/kg/day group (males) during study Week 3 to 4 when compared to the control group. Because there were no other remarkable changes in food consumption for this group over the course of the dosing period and no concurrent effects on body weights were observed, the lower food consumption was not considered to be test article-related.
OPHTHALMOSCOPIC EXAMINATION
No ophthalmic lesions indicative of toxicity were observed.
HAEMATOLOGY
Mean white blood cell counts and absolute lymphocyte counts were slightly, but statistically significantly higher in the 1500 and 2500 mg/kg/day group in male animals when compared to the control group (see Table 1 under "Any other information on results incl. tables"). Because similar trends were not observed in females, the counts were within the historical control data range and no microscopic correlates were noted, the elevated white blood cell and lymphocyte counts in males were not considered to be test article-related.
CLINICAL CHEMISTRY
Mean triglyceride levels were slightly, but statistically significantly higher in the 1500 and 2500 mg/kg/day group in male animals, and mean phosphorus levels were slightly, but statistically significantly higher in all test article-treated female groups when compared to the control group. Triglyceride levels were not significantly increased in females and phosphorus levels were not significantly elevated in males at corresponding doses. Furthermore, triglyceride and phosphorus levels were within the historical control data range. Non-concordance of serum chemistry changes in the opposite sex along with the absence of microscopic correlates indicated that the mean triglyceride and phosphorus differences from the control group means were not test article-related. In addition, statistically significantly lower mean alkaline phosphatase in the 1500 mg/kg/day group males and mean alanine aminotransferase in the 2500 mg/kg/day group males were observed compared to the control group (see Table 2 and 3 under "Any other information on results incl. tables").. These lower values were not attributed to the test article because toxic insult almost invariably results in increased serum aminotransferase levels rather than reduced values.
URINALYSIS
Urinalysis parameters were unaffected by test article administration.
ORGAN WEIGHTS
Mean absolute thyroid/parathyroid weight in the 2500 mg/kg/day group females was slightly, but statistically significantly, lower than the control group value (-19.8% change in comparison to the control group). Because a similar trend was not observed in males, the weight was within the historical control data range and there were no microscopic correlates, this lower thyroid/parathyroid weight in the 2500 mg/kg/day group females was not considered to be test article-related.
GROSS PATHOLOGY
There were no test article-related macroscopic findings.
HISTOPATHOLOGY:
There were no test article-related microscopic findings. All findings were considered to represent common, spontaneous alterations in laboratory rats or minor changes associated with necropsy artifact or gavage procedures.
Effect levels
- Dose descriptor:
- NOAEL
- Remarks:
- systemic toxicity
- Effect level:
- >= 2 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed
Target system / organ toxicity
- Critical effects observed:
- no
Any other information on results incl. tables
Table 1. Results of haematology (males).
Parameter |
Dose group [mg/kg bw/day] |
|||
|
0 |
500 |
1500 |
2500 |
White cells, Week 4 (1000/µL) Mean % change S.D. N |
9,92
1,909 10 |
12,36 24,6 1,854 10 |
13,12** 32,3 2,614 10 |
12,71* 28,1 2,479 10 |
Lymphocytes absolute, Week 4 (1000/µL) Mean % change S.D. N |
8,10
1,892 10 |
10,43 28,8 1,968 10 |
11,05* 36,4 2,559 10 |
10,88* 34,3 2,110 10 |
*: Significantly different from the control group at 0.05 using Dunnett´s test.
**: Significantly different from the control group at 0.01 using Dunnett´s test.
Table 2. Results of clinical chemistry (males).
Parameter |
Dose group [mg/kg bw/day] |
|||
|
0 |
500 |
1500 |
2500 |
Alkaline phosphatase, Week 4 (U/L) Mean % change S.D. N |
208
47.7 10 |
189 -9.1 36.7 10 |
163* -21.6 29.8 10 |
173 -16.8 29.1 10 |
Alanine trasferase, Week 4 (U/L) Mean % change S.D. N |
48
5.8 10 |
44 -8.3 5.7 10 |
41 -14.6 6.3 10 |
40* -16.7 7.9 10 |
Triglycerides, Week 4 (U/L) Mean % change S.D. N |
50
11.3 10 |
52 4.0 9.1 10 |
68** 36.0 16.0 10 |
66* 32.0 11.4 10 |
*: Significantly different from the control group at 0.05 using Dunnett´s test.
**: Significantly different from the control group at 0.01 using Dunnett´s test.
Table 3. Results of clinical chemistry (females).
Parameter |
Dose group [mg/kg bw/day] |
|||
|
0 |
500 |
1500 |
2500 |
Phosphorus, Week 4 (mg/100 mL) Mean % change S.D. N |
7.2
0.57 10 |
8.2* 13.9 1.01 10 |
8.4* 16.7 0.78 10 |
8.6** 19.4 1.16 10 |
*: Significantly different from the control group at 0.05 using Dunnett´s test.
**: Significantly different from the control group at 0.01 using Dunnett´s test.
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.
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