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EC number: 411-380-6 | CAS number: 147315-50-2 CG 30-1577
- 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
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Endpoint summary
Administrative data
Description of key information
In a 28 d study performed in rat (according GLP and OECD guideline 407), the substance did not induce mortalities, signs of toxicity or any other changes or abnormalities. The NOAEL/NOEL is considered to be 1090 mg/kg bw/d in females and 1130 mg/kg bw/d in males.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1992 - 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Revised Chemical Substance Law (1987), Japan
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Sprague-Dawley derived
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: CIBA-GEIGY Limited, Stein, Switzerland
- Age at study initiation: approximately 4 weeks at delivery
- Weight at study initiation: 97.3 - 118.8 g in males; 91.6 - 115.4 g in females
- Housing: in groups of 5 in Macrolon cages (type 4) with wire mesh tops and standardised granulated soft wood bedding
- Diet: Pelleted, certified standard diet ad libitum
- Water: ad libitum
- Acclimation period: 10 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2 °C
- Humidity: 55 +/- 10 %
- Air changes (per hr): 16 - 20
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 1992-08-31 To: 1992-09-29 (treatment group); From: 1992-08-31 To: 1992-10-27 (recovery group) - Route of administration:
- oral: feed
- Vehicle:
- other: admixed to pelleted food
- Details on oral exposure:
- DIET PREPARATION
The test item was weighed on a balance. The pulverized food was then homogeneously mixed with the appropriate concentrations of the test substance and about 25% water was added before pelleting. The pellets were subsequently airdried. The diet was stored in stainless steel containers at room temperature. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Control analyses of the test item content were undertaken with diet used for treatment weeks 1 to 4.
Analytical method: KBB-284/1 (named in CIBA-GEIGY-Report "ANALYTICAL REPORT ON THE CONTENT OF TEST MATERIAL IN RAT FEED /28-DAYS STUDY") - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- regular
- Remarks:
- Doses / Concentrations:
0 ppm (= mg/kg food)
Basis:
other: analytically determined value in the diet - Remarks:
- Doses / Concentrations:
8.95, 59.1, 1130 mg/kg bw/day in males
Basis:
other: analytically determined value in the diet - Remarks:
- Doses / Concentrations:
8.62, 55.5, 1090 mg/kg bw/day in females
Basis:
other: analytically determined value in the diet - No. of animals per sex per dose:
- 5 males, 5 females per dose group; additionally 5 males, 5 females for recovery assessment in the control and high dose group
- Control animals:
- yes
- Details on study design:
- - Dose levels were based on the results of a 14-days range-finding study described elsewhere.
- Randomization: Computer-generated random algorithm
- Post-exposure recovery period in satellite groups: 28-day recovery period - Positive control:
- no
- Observations and examinations performed and frequency:
- MORTALITY: Yes
- Time schedule: evaluated on a daily basis
IN-LIFE OBSERVATIONS: Yes
- Time schedule: evaluated on a daily basis, observations were recorded at least weekly
- Observations performed to detect changes in state of health or behaviour
BODY WEIGHT: Yes
- Time schedule for examinations: recorded individually at weekly weighing sessions.
FOOD CONSUMPTION: Yes
- recorded weekly (cagewise) and calculated for periods of one week
- individual food consumption values: calculated from the food consumption per cage and the number of animals
- Food consumption ratios: weekly food consumption (g)/midweek bw (g) x (1000/7) [g food/kg bw per day]
- Test item intake: food consumption ratio x nominal dose (ppm)/1000 [mg test item/kg bw per day]
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the treatment period; additionally at the end of the recovery period
- Anaesthetic used for blood collection: Yes, ether anesthesia, blood samples were drawn from the retro-orbital plexus
- Animals fasted: Yes
- How many animals: all animals
- Parameters examined:
Red blood cells: Erythrocyte count, Hemoglobin, Hematocrit, Mean corpuscular volume, Red cell volume distribution width, Mean corpuscular haemoglobin, Mean corpuscular haemoglobin concentration, Hemoglobin concentration distribution width; Differential leukocyte count; Thrombocyte count; Prothrombin time; Methemoglobin
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the treatment period; additionally at the end of the recovery period
- Animals fasted: Yes
- How many animals: all animals
- Parameters examined: Glucose, Urea, Creatinine, Total Bilirubin, Total Protein, Albumin, Globulins, A/G Ratio, Cholesterol, Triglycerides, Sodium, Potassium, Calcium, Chloride, Phosphorus inorganic, Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Gamma-glutamyl transpeptidase
URINALYSIS: No
OPHTHALMOSCOPIC EXAMINATION: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY/NECROPSY: Yes
At the end of 28-day treatment and of additional 4-week recovery period all control and treated animals were bled under ether anesthesia and subjected to detailed autopsy. A complete autopsy with tissue preservation was performed also on one control animal, which died on day 9 of the study. The weights of body (exsanguinated) adrenals, liver, kidneys, ovaries, testes, thyroid with parathyroid gland, and mesenteric lymph node were recorded. Samples of the following tissues and organs were preserved in neutral buffered 4% formalin: Skin, mammary area, spleen, mesenteric lymph node, axillary lymph node, sternum with bone marrow, femur with joint, skeletal muscle, trachea, lung, heart, aorta, submandibular salivary gland (both), liver, pancreas, esophagus, stomach, small intestine, large intestine, kidney (both), urinary bladder, prostate, seminal vesicle, testis (both), epididymis (both), uterus, vagina, ovary (both), pituitary gland, adrenal gland (both), thyroid with parathyroid gland, thymus, peripheral nerve, brain, spinal cord, eye with optic nerve (both), orbital gland (both), extraorbital lacrimal gland (both), Zymbal gland (both), muzzle, tongue, and any tissue with gross lesions. All organ and tissue samples were processed, embedded, cut at a thickness of 3-5 micrometers, and stained with hematoxylin and eosin (only main group to evaluate toxicity).
HISTOPATHOLOGY: Yes
Spleen, heart, liver, kidney (both), adrenal gland (both), thyroid with parathyroid gland, and any organ with gross lesions - Statistics:
- For each time point and parameter an univariate statistical analysis was performed. Nonparametric methods were applied, to allow for non normal as well as normal data distribution. Each treated group was compared to the control group by Lepage's two-sample test and tested for increasing or decreasing trends from control up to the respective dose group by Jonekheere's test for ordered alternatives.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food efficiency:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Details on results:
- IN-LIFE OBSERVATIONS AND MORTALITY:
No relevant clinical signs were observed during the study.
No treatment-related death occurred during the study.
BODY WEIGHT:
Mean bodyweight development in both sexes was not affected by treatment.
FOOD CONSUMPTION AND FOOD CONSUMPTION RATIOS:
Mean food intake was not influenced by treatment.
Mean food consumption ratios were comparable to control values
HAEMATOLOGY:
The treatment had no influence on the hematological profile.
CLINICAL (BLOOD) CHEMISTRY:
The treatment had no influence on blood chemistry parameters.
ORGAN WEIGHTS:
All organ weights were considered not to be influenced by treatment.
GROSS PATHOLOGY:
No treatment-related changes were observed.
HISTOPATHOLOGY:
No treatment-related changes were observed. - Dose descriptor:
- NOEL
- Effect level:
- 1 130 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No treatment-related changes up to and including the highdose level.
- Dose descriptor:
- NOEL
- Effect level:
- 1 090 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No treatment-related changes up to and including the highdose level.
- Dose descriptor:
- NOAEL
- Effect level:
- 1 130 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No treatment-related changes up to and including the highdose level.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 090 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No treatment-related changes up to and including the highdose level.
- Key result
- Critical effects observed:
- no
- Executive summary:
In a repeated toxicity study the test item (as described in section 1.2) was administered to five rats/sex/dose level by feeding at dose levels of 0, 100, 650, and 12000 ppm for a period of 28 days. The analytically determined mean daily intake was 8.95, 59.1, and 1130 mg/kg bw in males, and 8.62, 55.5, and 1090 mg/kg bw in females. In addition, a 28-day recovery testing was performed with five male/female rats at dose levels of 0 and 12000 ppm. No test item-related effects in mortality, clinical signs, body weight, food consumption, hematology, clinical chemistry, organ weights, gross pathology, and histopathology were observed. However, one female from the control group died accidentally. No other death occurred during the study. The NO(A)EL is 1130 mg/kg bw/d in males and 1090 mg/kg bw/d in females. This repeated toxicity study in the rat is acceptable and satisfies the guideline requirement for a repeated dose 28-day oral toxicity study (OECD 407) in rodents.
Reference
In a previous subacute 14-day range-finding study the test item was administered in the diet for 2 weeks at doses of 0, 100, 1000 and 10000 ppm (= mg/kg food) to a total of 40 albino rats , 5 males and 5 females per dose group. Corrected for the analytically determined test item concentrations in the diet , the mean daily intakes were 16.2 , 98.1, and 1050 mg/kg bw in males, and 16.1, 93.3 , and 966 mg/kg bw in females, respectively. No clinical signs were observed and no animal died during the study. Neither mean bodyweight development nor food intake were affected by treatment. Treatment did not influence the hematological or blood chemistry profiles of the rats. Mean organ weights were not influenced by treatment and no treatment-related changes were detected at necropsy. This study is listed above as further reference (CIBA-GEIGY924087).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 090 mg/kg bw/day
- Study duration:
- subacute
- 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
Procedure and observations
A 28d study in rats (OECD guideline 407) was performed to evaluate the toxicity of the test substance after repeated application (Ciba 1993).
The test article was administered to rats (5 per sex and dose) by feeding at dose levels of 0, 100, 650, and 12000 ppm for a period of 28 days. The analytically determined mean daily intake was 8.95, 59.1, and 1130 mg/kg bw in males, and 8.62, 55.5, and 1090 mg/kg bw in females. Additional 5 rats per sex and group were used at 0 and 12000 ppm. These animals were treated for 28 days and then allowed a 14-day treatment-free recovery period after which they were sacrificed. Clinical signs, food consumption and body weights were recorded periodically during the treatment and recovery periods. Haematology, urinalysis as well as pathological and microscopic analysis were performed. One female from the control group died accidentally. No other death occurred during the study. There were no test article-related clinical signs in any group. Body weight and food consumption were unaffected by the test substance. There were no treatment-related effects on hematology, clinical biochemistry and urinalysis, neither at termination of the treatment nor at the end of the treatment free recovery period. All gross and microscopic lesions recorded in this study were considered to be spontaneous in origin. Their incidence and severity was similar in control and treated rats. Changes in organ weight were not observed.
In a previous subacute 14-day range-finding study the test item was administered in the diet for 2 weeks at doses of 0, 100, 1000 and 10000 ppm (= mg/kg food) to a total of 40 albino rats , 5 males and 5 females per dose group. Corrected for the analytically determined test item concentrations in the diet , the mean daily intakes were 16.2 , 98.1, and 1050 mg/kg bw in males, and 16.1, 93.3 , and 966 mg/kg bw in females, respectively. No clinical signs were observed and no animal died during the study. Neither mean bodyweight development nor food intake were affected by treatment. Treatment did not influence the hematological or blood chemistry profiles of the rats. Mean organ weights were not influenced by treatment and no treatment-related changes were detected at necropsy.
Discussion
In this subacute toxicity study, the test substance was administrated to rats (5 per sex and dose) by feeding at dose levels of 0, 100, 650, and 12000 ppm for a period of 28 days. Neither during treatment period nor during post-observation period of 14 days treatment related mortalities or any signs of toxicity occurred. The biochemical analyses did not reveal abnormalities. Also pathology, organ weighing and microscopic examination were without findings. The NO(A)EL is 1130 mg/kg bw/d in males and 1090 mg/kg bw/d in females.
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008 (CLP)
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for repeated dose toxicity under 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.
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.
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