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EC number: 201-851-2 | CAS number: 88-68-6
- 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
In a 2 years (feed) oral repated dose toxicity study, effects for clinical pathology at ~6 and 12 months and for anatomic pathology (organ weights, gross and microscopic pathology) at the end of 12 months.
In a 15-day (gavag) and 28-day (feed) oral repeated dose toxicity study, effects were observed on the thyroid.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Information from public copy of a correspondance letter to US EPA, reliability not known but contributing to a weight of evidence assessment.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- A 2-year feeding study is being conducted in Crl:CD(SD) rats (SO/sex/concentration) with the test substance at dietary concentrations of 0, 20, 200, 2000, or 20000 ppm. This notification covers effects through the one-year interim sacrifice. The rats have been observed for mortality, clinical signs, body weight effects, and food consumption, and rats received an ophthalmologic examination after ~ 1 year of dosing. Ten rats/sex/concentration were designated for evaluation of chronic toxicity. These rats were evaluated for clinical pathology at ~6 and 12 months and for anatomic pathology (organ weights, gross and microscopic pathology) at the end of 12 months.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Route of administration:
- oral: feed
- Vehicle:
- not specified
- Duration of treatment / exposure:
- 12 months
- Dose / conc.:
- 20 ppm
- Dose / conc.:
- 200 ppm
- Dose / conc.:
- 2 000 ppm
- Dose / conc.:
- 20 000 ppm
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Observations and examinations performed and frequency:
- The rats have been observed for mortality, clinical signs, body weight effects, and food consumption, and rats received an ophthalmologic examination after ~ 1 year of dosing.
- Sacrifice and pathology:
- These rats were evaluated for clinical pathology at 6 and 12 months and for anatomic pathology (organ weights, gross and microscopic pathology) at the end of 12 months.
- Details on results:
- Mild reductions in mean body weight, body weight gain, food consumption, and food efficiency were observed in females in the 2000 ppm and 20000 ppm groups compared to control. Mild reductions in food efficiency were observed in the male 2000 ppm and 20000 ppm groups. Clinical observations included subdued behavior, ataxic gait, dragging hindlimbs, and tilted head.These were only observed in isolated cases involving 1 animal in any dose group throughthe one year time point, and did not exhibit a dose-response. The following clinical chemistry changes were observed in males (not all statistically significant or clear dose response and many differences of small magnitude) at 6 and/or 12 months: at 20000 ppm - HGB, MCRC, AST, bilirubin, ALKP, i Ca; at 2000 ppm - ! bilirubin, i hemoglobin distribution width, Ca, cholesterol, triglycerides, Na; At 200 ppm - ! RBC ghosts, i HGB, Na; and at 20 ppm - ! BUN.
The following clinical chemistry changes were observed in females (not all statistically significant) at 6 and/or 12 months: at 20000 ppm - ! prothrombin time (PT), triglycerides, AST,ALT, bilirubin, Cl, i red cell distribution width, cholesterol, Ca: at 2000 ppm - ! HGB, MCHC, RBC ghosts, prothrombin time (PT), AST, bilirubin, ired cell distribution width, activated partial thromboplastin time (APTT), cholesterol, Ca, total protein, globulin, CI; at 200 ppm - ! RBC ghosts, AST; and at 20 ppm i total protein, globulin. None of these differences was considered to be adverse or test substance related except the increased cholesterol in females at 2000 or 20000 ppm. No gross observations at necropsy were attributed to test substance exposure. Test substance-related increases in absolute and/or relative liver weights were observed in males and females at 2000 and 20000 ppm. Non-statistically significant elevations in liver weights were also observed in 20 and 200 ppm female groups. Correlative centrilobular hepatocellular hypertrophy (minimal or mild) was observed in 20000 ppm males and females and in 200 and 2000 ppm females. Minimal or mild vacuolar degeneration of the liver was also observed in 2000 and 20000 ppm males; however, no correlative clinical pathology effects were observed. Other statistically significant organ weight changes were increased relative kidney weight (2000 and 20000 ppm females), increased absoluteheart weight (2000 ppm males), and increased relative heart weigh (2000 ppm females). No microscopic pathology correlates were observed. Other microscopic pathology lesions attributed to test substance exposure were increased adrenal cortical microvesiculation (minimal) in 20000 ppm females and increased thyroid gland follicular cell hypertrophy (minimal) in 2000 and 20000 ppm females. Uterine squamous metaplasia (minimal) was observed in all dose groups, but not in controls. However, the incidence was highest in the 20 ppm group and did not display a doseresponse; therefore, the detennination of whether or not this lesion is test substance related will be made based on overall incidence at the end of the study. - Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Information from public copy of a correspondance letter to US EPA, reliability not known but contributing to a weight of evidence assessment.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- not specified
- Sex:
- male/female
- Route of administration:
- oral: feed
- Vehicle:
- not specified
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
- Concentration in vehicle: dietary concentrations of 0, 300, 1500, or 5000 ppm - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 4 weeks
- Remarks:
- Doses / Concentrations:
300, 1500, and 5000 ppm
Basis:
nominal in diet - No. of animals per sex per dose:
- 5 - 7
- Control animals:
- yes, plain diet
- Observations and examinations performed and frequency:
- Body weights, food consumption, and clinical signs were evaluated weekly.
- Sacrifice and pathology:
- Clinical pathology endpoints were evaluated during week 4. After 4 weeks of treatment all surviving rats were euthanized and given a gross and microscopic pathological examination.
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- Test substance-related mortality was observed in 3/7 high dose female rats on the first day of dosing. Following the first day of dosing no adverse clinical signs were observed in any dose group.
BODY WEIGHT AND WEIGHT GAIN
-Body weight gain was approximately 10 and 20% lower in male and female rats fed 5000 ppm, respectively, compared to the controls.
FOOD CONSUMPTION AND COMPOUND INTAKE
- Food consumption was 13 % lower in female rats fed 5000 ppm compared to the control rats.
FOOD EFFICIENCY
- Male and female food efficiency was 6 % lower in rats fed 5000 ppm compared to the control rats.
ORGAN WEIGHTS
- Absolute and relative liver weights were statistically higher in male and female rats fed 1500 and 5000 ppm compared to the control rats.
HAEMATOLOGY
- Prolongation of prothrombin time and activated partial thromboplastin time were observed in male rats fed 5000 ppm (30 and 33% prolongation compared to control group means, respectively). Increased clotting times were not observed in female rats at any dietary concentration.
HISTOPATHOLOGY: NON-NEOPLASTIC
- Hepatocellular hypertrophy was observed in male and female rats fed all dietary concentrations of test substance.
- Thyroid hypertrophy was observed in male and female rats fed 5000 ppm and also in male rats fed 1500 ppm. Colloid depletion was observed in male rats fed 5000 ppm. - Dose descriptor:
- NOAEL
- Effect level:
- 300 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Only effect observed at this dose level was hepatocellular hypertrophy, but this effect is considered to be an adaptive physiologic response to exposure to a xenobiotic and not biologically adverse.
- Critical effects observed:
- not specified
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Study duration:
- chronic
- Species:
- rat
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 2-year feeding study is being conducted in Crl:CD(SD) rats (8O/sex/concentration) with the test substance at dietary concentrations of 0, 20, 200, 2000, or 20000 ppm.he rats have been observed for mortality, clinical signs, body weight effects, and food consumption, and rats received an ophthalmologic examination after ~ 1 year of dosing. Ten rats/sex/concentration
were designated for evaluation of chronic toxicity. These rats were evaluated for clinical pathology at ~6 and 12 months and for anatomic pathology (organ weights, gross and microscopic pathology) at the end of 12 months.
In a repeated dose oral toxicity study similarly performed in accordance with OECD guideline 407, the test substance was administered to 4 groups of male and female rats (5-7 rats/sex/dose) at dietary concentrations of 0, 300, 1500, or 5000 ppm for 4 weeks. Body weights, food consumption, and clinical signs were evaluated weekly. Clinical pathology endpoints were evaluated and all surviving rats were euthanized for pathological examination. Mortality was observed in 3/7 high dose female rats on the first day of dosing. No adverse clinical signs were observed in any dose group. A decrease in body weight gain, food consumption, and food efficiency was observed in the 5000 ppm exposure groups. Prolongation of prothrombin time and activated partial thromboplastin time was observed in male rats fed 5000 ppm. Hepatocellular hypertrophy was observed in male and female rats at all concentrations, but this effect is considered to be an adaptive physiologic response to exposure to a xenobiotic and not biologically adverse. Thyroid hypertrophy was observed in male and female rats fed 5000 ppm and also in male rats fed 1500 ppm. Colloid depletion was observed in male rats fed 5000 ppm.
In a 15-day repeated dose oral toxicity study the test substance was administered by oral gavage to 3 groups of male rats at concentrations of 0, 50 or 250 mg/kg/day. Rats were dosed daily for 15 days and euthanized on the morning of test day 15. The liver, thyroid gland, adrenals, and reproductive organs were weighed, and the testes, epididymides, and thyroid gland were saved for histopathological evaluation. Blood was collected and serum was prepared for hormonal evaluation. Mortality was observed on the first day of dosing in 4/15 rats dosed with 250 mg/kg/day of the test substance. Throughout the remainder of the study, no adverse clinical signs were observed and there were no effects on final body weights or the incidence of clinical signs. At necropsy, relative liver weights were significantly higher in rats dosed with 50 and 250 mg/kg/day when compared to the control rats. Absolute thyroid weights were significantly higher in rats dosed with 250 mg/kg/day when compared to the control rats, although relative thyroid weights were not significantly higher. Serum thyroid stimulating hormone (TSH) concentrations were significantly higher in rats dosed with 50 and 250 mg/kg/day, compared to the controls. Serum thyroxine (T4) concentrations were significantly lower in rats dosed with 50 and 250 mg/kg/day when compared to the controls.
These two studies contradict the results observed in the acute toxicity study considering that the LD50 is 2200 mg/kg and in these two repeated dose toxicty studies animals already died at 250 mg/kg. Since these effects already occured on day 1, it can be excluded that mortality is based on cumulation of the test substance. Considering that the original study report is not available, but only a brief summary, the results of these studies are not considered for the evaluation of the hazardous properties of the test substance.
Justification for classification or non-classification
Based on the effects observed in the studies performed, classification in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification and labelling is not warranted.
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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