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EC number: 248-502-0 | CAS number: 27503-81-7
- 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
Endpoint summary
Administrative data
Description of key information
Based on a 90-day oral toxicity study according to OECD 408 it is concluded that test article showed no treatment-related adverse effects in all test doses up to 1000 mg/kg bw/day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- September - December 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Experimental Animals and Housing Conditions
SPF rats (strain Wistar W, 74, bred by Winkelmann, Borchen) were used for this study.
At the start of study rats were about 42 to 49 days old. The mean initial weight of males was 93- 94 g, that of females 94 g.
The animals were housed individually, under conventional conditions, in Makrolon type II cages (SPIEGEL and GONNERT, 1961) on dustfree wood granules at a room temperature of 23 ±2 °C. During the study period the animals received fresh Altromin R- powder feed (manufactured by Altromin GmbH, Lage) and tap water ad libitum. - Route of administration:
- oral: gavage
- Vehicle:
- other: aqueous thylose suspension
- Details on oral exposure:
- Groups of 15 male and 15 female rats each received the test substance by gavage 7 times a week.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- for 3 months
- Frequency of treatment:
- daily (7 times a week)
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 330 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- The following doses were administered, 0 (control), 100, 330 and 1000 mg/kg bw/day.
The substance was applied in a 5% aqueous tylose suspension at a constant volume of 10 ml/kg. Control animals received the corresponding volume of tylose suspension.
At the start of study the rats were separated, by sex and three weight groups (light, medium, heavy) were established for each sex group. The animals were allocated to dose groups using a randomization list. Subsequently the animals were numbered chronologically. - Positive control:
- none
- Observations and examinations performed and frequency:
- 1,General Examinations
a.Inspection of Experimental Animals
The animals were inspected daily and occurring changes and signs were recorded.
b Determination of Body Weights and Feed Intake
Body weights were determined weekly. Male rats could not be weighed in the 9th week of study due to a defect of the scales. Weekly feed intake was determined by comparing the final weight of feed at the end of the week to the initial weight.
2, Clinical Laboratory Investigations
Clinical laboratory investigations were performed on 5 male and 5 female rats each per dose 6 weeks and 3 months after the start of feeding. Blood samples for the determination of blood sugar were taken from the caudal vein, for the other determinations from the retro-orbital venous plexus of animals under ether anesthesia (according to NOLLER, 1955).
a.Haematology
Erythrocyte count and leucocyte count using the Coulter-Counter, type ZF.
Thrombocyte count using the Coulter-Counter, type FN Reticulocyte count after staining with brilliant cresyl blue Haemoglobin content using the Coulter-Counter haemoglobinometer Haematocrit using the Heraeus-Christ micro-haematocrit centrifuge
Differential blood count using smears (staining according to Wright) at 630-fold magnification MCH and MCV calculation
Thromboplastin time at the end of study according to QUICK, 1951 using Metrolab clottimer
b. Clinical Chemistry
Enzymes
Alkaline phosphatase (ALP), Glutamic-oxalacetic-transaminase (GOT), Glutamic-pyruvic-transaminase (GPT)
Substrates
Creatinine, Blood sugar, Cholesterol ,Bilirubin, ,Total protein in serum
c.Urinalysis semiquantitative
Glucose, blood, protein and pH value, Ketone bodies, Bilirubin, Macroscopic examinations of sediment - Sacrifice and pathology:
- Gross Pathology
a, Necropsy of Rats Dvincr Intercurrently
Rats dying intercurrently were necropsied and macroscopically evaluated; organs and tissues deemed evaluable were fixed in 10% formaldehyde solution.
b. Necropsy of Rats Sacrificed at the End of Study
After a feeding period of 3 months all surviving animals were anesthetized with ether and exsanguinated. The animals were subsequently necropsied and macroscopically examined. The weights of the following organs were determined: thyroid gland, thymus, heart, lung, liver, spleen, kidneys, adrenals, testes or ovaries.
The following organ material from 5 male and 5 female rats each killed regularly at the end of study was fixed in Bouinian fluid (after about 30 hours decanted into 70% alcohol), adrenals, aorta brain, epididymides, esophagus, eyes, femur, heart. intestine (duodenum, jejunum, ileum, colon), kidneys, liver, lung, lymph nodes, ovaries, pancreas, pituitary, prostate, salivary gland, sciatic nerve, seminal vesicle, skeletal musculature, spleen, sternum, stomach, testes, thymus, thyroid gland, trachea, urinary bladder, uterus as well as all organs showing macroscopic lesions The organ material from the other animals was fixed in 10% formaldehyde solution and, in addition, parts of the liver from all animals were fixed in formol-calcium. - Statistics:
- The following parameters were calculated, arithmetic group means, standard deviation s, upper and lower confidence limits at the confidence level of l-a = 95 % and l-a= 99 %.
The values of the treated groups were compared to those of the control groups using the significance test (U-test) as described by Mann, Whitney and Wilcoxon at the significance level of a = 5 % and a = 1 %. An IBM-370/145 computer was used. - Clinical signs:
- no effects observed
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- During the entire study period one male of the control group and female each of the dose groups 330 and 1000 mg/kg bw/day died. Mortalities were not considered treatment related.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The protein content in serum, which, at the end of study, was significantly increased (P < 0.01) in females of the dose group 1000 mg/kg bw/day is not considered to be an indication of damage because all values were within the biological range (2s range 5.37 - 6.89 g/100 mL, measured in 100 female rats of that age).
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Details on results:
- During the entire study period one male of the control group and female each of the dose groups 330 and 1000 mg/kg bw/day died.
During the entire study period treated animals showed no treatment-related signs in any dose group. Growth, feed intake, water intake and mortality were not affected.
Haematological investigations performed during as well as at the end of study gave no indication of damage in any dose group,
Clinico-chemical analyses, gross pathology and histopathological investigations established no damage to the liver in the dose group of up to 1000 mg/kg bw/day.
The protein content in serum, which, at the end of study, was significantly increased (P < 0.01) in females of the dose group 1000 mg/kg bw/day is not considered to be an indication of damage because all values were within the biological range (2s range 5.37 - 6.89 g/100 mL, measured in 100 female rats of that age).
Urinalysis, urea and creatinine concentrations in serum as well as gross pathological, gravimetric and histopathological organ findings gave no indication of an effect on the kidneys.
No treatment-related organ changes were observed in any rat at necropsy.
Histopathological investigations of the other organs gave no indication of a damaging effect by test article. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Key result
- Critical effects observed:
- no
- Conclusions:
- In conclusion, the no-observed-adverse-effect-level (NOAEL) of the test article is considered to be 1000 mg/kg bw/day.
- Executive summary:
This study was performed following OECD guideline 408 with test article exposed in a 3-month toxicity test in female and male rats. The following dose levels of 0 (control), 100, 330 and 1000 mg/kg bw/day were used with application of gavage daily (7 times a week). During the entire study period one male of the control group and female each of the dose groups 330 and 1000 mg/kg bw/day died. There was no significant differences in Clinical chemistry, Blood sugar and cholesterol concentrations of rats, blood ,urinalysis, clinico-chemical analyses, necropsies and histopathological investigations, gross pathology and histopathology compared with controls in the parameters investigated of the dose groups of 100 to 1000 mg/kg bw/day. All vaules were within normal range. Therefore, it is concluded that test article showed no treatment-related adverse effects in all test doses up to 1000 mg/kg bw/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- very well document, conclusive guideline study
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
A subchronic oral toxicity study (gavage) was performed following OECD guideline 408 with test article exposed daily for 3 month to female and male rats. The following dose levels of 0 (control), 100, 330 and 1000 mg/kg bw/day were used. There was no significant differences in mortality, clinical chemistry, blood sugar and cholesterol concentrations of rats, blood, urinalysis, clinico-chemical analyses, necropsies and histopathological investigations, gross pathology and histopathology compared with controls in the parameters investigated of the dose groups of 100 to 1000 mg/kg bw/day. All values were within normal range. Therefore, it is concluded that test article showed no treatment-related adverse effects in all test doses up to 1000 mg/kg bw/day.
Justification for classification or non-classification
As no treatment related effects were observed in a subchronic oral toxicity study performed on rats with doses of 1000 mg/kg bw/day applied, no classification for Specific Target Organ Toxicity (STOT), Repeat Exposure (RE) is required according to CLP (Regulation (EC) No 1272/2008.
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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