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EC number: 201-818-2 | CAS number: 88-30-2
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
In a 90 day feeding study in rats similar to OECD guideline 408 (WARF Institute, 1971), a NOAEL of 162 mg/kg bw/day and a LOAEL of 292 mg/kg bw/day based on decrease in body weight was determined.
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:
- 1971-06-06 to 1971-10-04
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- 1998-09-21
- Deviations:
- yes
- Remarks:
- preserved tissues devergent from guideline
- GLP compliance:
- no
- Remarks:
- Pre-GLP study
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Sprague-Dawley, Madison, Wisconsin, USA
- Females: non-pregnant: yes
- Age at study initiation: ~3 - 4 weeks
- Weight at study initiation: 45 - 55 g
- Housing: individually in metal screen bottom cages.
- Diet: ad libitum, Purina Lab Chow
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2 - Route of administration:
- oral: feed
- Details on route of administration:
- Feed, mixed and presented fresh weekly. It was offered ad libitum from specially capped clean glass jars that limit spillage and contamination of feed.
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: The TFM (HB) was ground by mortar and pestle with lab chow to obtain a 10 % premix, then admixed dry with the basal diet to obtain the desired level. The amount of TFM (HB) used for each level was determined using a purity for this TFM (HB) of 90 %.
DIET PREPARATION
- Rate of preparation of diet: weekly
- Mixing appropriate amounts with: Purina Lab Chow - Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- continuously
- Dose / conc.:
- 500 ppm
- Remarks:
- = 50.0 mg/kg bw/day
- Dose / conc.:
- 900 ppm
- Remarks:
- = 90.0 mg/kg bw/day
- Dose / conc.:
- 1 620 ppm
- Remarks:
- = 162.0 mg/kg bw/day
- Dose / conc.:
- 2 916 ppm
- Remarks:
- = 292.0 mg/kg bw/day
- Dose / conc.:
- 5 248 ppm
- Remarks:
- = 525.0 mg/kg bw/day
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent no treatment
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: day 21 and day 90
BODY WEIGHT: Yes
- Time schedule for examinations: initially and weekly through 90 days.
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean weekly diet consumption.
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 21 and day 90
- Animals fasted: No
- How many animals: 5/group
- Parameters examined: RBC, WBC electronically by Coulter Counter; Hgb by the cyanomethemoglobin method; Hematocrit by centrifugation; Differential cell count - 100 white cells identified
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 21 and day 90
- How many animals: 5/group
- Parameters examined: SGOT, SAP by micro method on Eskalab system
URINALYSIS: Yes
- Time schedule for collection of urine: day 21 and day 90
- How many animals: 5/group
- Parameters examined: blood, biliruben, ketone, glucose, protein, pH - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, liver, heart, kidneys, adrenal glande, gonad, spleen,
HISTOPATHOLOGY: Yes, brain, pituitary, lymph nodes, salivary glands, thyroid & parathyroid, lungs, heart, spleen, liver, stomach, small intestine, colon, mesenteric lymph nodes, pancreas, adrenals, kidneys, gonads, urinary bladder, uterus or prostate, muscle (skeletal), bone marrow, bone - Statistics:
- Organ weight data were punched onto data cards and submitted with the appropriate program to a Univac 1108 for computing of organ to body weight ratios, averages, and comparisons of test group to controls by t-test. T-tests of body weights and feed consumptions were calculated on a Hewlett-Packard 9100 A Calculator, program 70809-modified, with reference to: Statistical Theory and Methodology for Science and Engineering, Second Edition, K. A. Brownlee, John Wiley & Sons, Inc. 1965,
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No abnormal behavior was observed in the animals nor signs of illness or other displays in any particular group which indicated a response to a specific stress.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The body weight data for males in dose group 3 - 6 showed a dose related depression of body weights in test groups when compared to the control group. Body weight curves for females did not show the marked differentiation seen in the male curves.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- No remarkable differences exist here for males or females with the exception of the 2 higher levels which show slightly poorer efficiencies.
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Though a strong dose response in male was not evident, tendencies for increased liver weights in the test groups and increased kidney weight in the high level test group were seen. Data and analyses for females revealed almost no significant difference's regarding organ weights and organ weight ratios for the organs measured. The single instance of notable differences was the increased liver weight and liver weight ratio of the high level group when compared to the control group.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Gross observations are minimal and of low incidence. Alterations observed are of a non-specific type and not related to administration of test compound. No gross alterations were observed in any other animals of all groups.
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Liver alterations of swelling, and cloudy swelling, were seen in both control and test animals and are believed to result from the cellular changes that occur from the time the animal was euthanized until the tissues were fixed. Vacuolation had a very low incidence and is believed to be due to the nutritional status of the animal at the time of death. Pigmentation was again seen in control and test animals and was usually the result of red blood cell destruction. The kidney alteration of congestion of the medulla was seen with a very high incidence in all groups of animals and was believed to be a result of the type of euthanasia. Other histopathological alterations observed had a very low incidence of occurrence. Since histologic observations noted were minimal, apparent in both test and control animals, and incidence was essentially the same in all groups, the alterations were considered spontaneous and not related to the administration of the test material.
- Histopathological findings: neoplastic:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 162 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- Dose descriptor:
- LOAEL
- Effect level:
- 292 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- Key result
- Critical effects observed:
- no
- Conclusions:
- In this 90 day feeding study in rats similar to OECD guideline 408, a NOAEL of 162 mg/kg bw and a LOAEL of 292 mg/kg bw was determined, which is based on the observed decrease in body weight
- Executive summary:
In a pre-GLP 90-day feeding study in rats similar to OECD guideline 408 (WARF Institue, 1971), groups of weanling SD rats (10/sex/group) were fed diets containing the test substance (90 %) at concentrations of 50.0, 90.0, 162.0, 292.0, or 525.0 mg/kg bw/day for 90 days. The control groups (20/sex) received the untreated diet. The results showed that body weights of the 292 and 525 mg/kg bw/day groups were consistently decreased (10 - 13 %) in males from week 3 to the end of the study. The decrease was statistically significant. Food consumption, and hematological parameters were similar to those of the controls. Clinical signs were not seen in the treated or control rats. There was a decrease in the aspartate aminotransferase (SGOT) activity in both males and females at 525.0 mg/kg bw/day on the 21 day examination period, but by 90 day examination period the SGOT values of 525.0 mg/kg bw/day animals were similar to those of the controls. The alkaline phosphatase level was slightly increased in both males and females of 525.0 mg/kg bw/day groups, but no statistical significance was found. At sacrifice, liver weights of the 292.0 and 525.0 mg/kg bw/day females were slightly increased. No gross pathology and histological changes were observed. The LOAEL of this study was 292 mg/kg bw/day which is based on decreased in body weights; the NOAEL was 162 mg/kg bw/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 162 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Klimisch code 2
Additional information
In a pre-GLP 90-day feeding study in rats similar to OECD guideline 408 (WARF Institute, 1971), groups of weanling SD rats (10/sex/group) were fed diets containing the test substance (90 %) at concentrations of 50.0, 90.0, 162.0, 291.6, or 524.8 mg/kg bw/day for 90 days. The control groups (20/sex) received the untreated diet. The results showed that body weights of the 291.6 and 524.8 mg/kg bw/day groups were consistently decreased (10 - 13 %) in males from week 3 to the end of the study. The decrease was statistically significant. Food consumption, and hematological parameters were similar to those of the controls. Clinical signs were not seen in the treated or control rats. There was a decrease in the aspartate aminotransferase (SGOT) activity in both males and females at 524.8 mg/kg bw/day on the 21 day examination period, but by 90 day examination period the SGOT values of 524.8 mg/kg bw/day animals were similar to those of the controls. The alkaline phosphatase level was slightly increased in both males and females of 524.8 mg/kg bw/day groups, but no statistical significance was found. At sacrifice, liver weights of the 291.6 and 524.8 mg/kg bw/day females were slightly increased. No gross pathology and histological changes were observed. The LOAEL of this study was 291.6 mg/kg bw/day (based on 1 ppm = 0.1 mg/kg bw/day) is based on decreased in body weights; the NOAEL was 162 mg/kg bw/day.
Regarding the mortality, the findings are supported by another subchonic repeated dose toxicity study in Sprague-Dawley rats (WARF Institute, 1971), since no mortality was observed up to the highest dose group (525.5 mg/kg bw/day).
Justification for classification or non-classification
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The NOAEL was 162 mg/kg bw/day. As a result the test substance is considered not to be classified for repeated dose oral toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.
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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