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EC number: 222-392-4 | CAS number: 3458-28-4
- 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
5 -Month drinking water study; mouse; NOAEL for systemic toxicity = 20% (highest dose tested); Reliability = 2
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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- The study was conducted for 5 months
- GLP compliance:
- no
- Limit test:
- no
- Species:
- mouse
- Strain:
- other: C57 Bl/6
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: not reported
- Housing: individual cages
- Diet: standard rat chow ad libitum
- Water: dosed with test item ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 ºC
- Humidity (%): 55 ± 5%
- Photoperiod (hrs dark / hrs light): 12/12 hours - Route of administration:
- oral: drinking water
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF TEST SUBSTANCE FORMULATION:
- Preparation frequency: drinking water was changed thrice a week - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 5 months
- Frequency of treatment:
- continuous
- Dose / conc.:
- 1 other: %
- Remarks:
- nominal in water
- Dose / conc.:
- 3 other: %
- Remarks:
- nominal in water
- Dose / conc.:
- 10 other: %
- Remarks:
- nominal in water
- Dose / conc.:
- 20 other: %
- Remarks:
- nominal in water
- No. of animals per sex per dose:
- 3 male, 3 female per dose group
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- During the 5 month treatment, females were impregnated twice. The pups were weaned at 21 days and maintained on the same test item dose as their mother for 9 days. Both mother and pups were monitored for ill health such as bloating, diarrhea and abnormal weight gain or loss. Behavior of these animals were also monitored.
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
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: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at 3 months
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all
CLINICAL CHEMISTRY: Yes
- Animals fasted: No data
- How many animals: all
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: Yes
- Dose groups that were examined: all
- Battery of functions tested: mode of drinking and eating, climbing on the bars, grooming, social behaviour, and locomotion
OTHER: For reproduction data see Sec. 7.8.1: DL.K2.5Mon.DW.1Gen.M.Pub.KD - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, organs were examined for size and weight
HISTOPATHOLOGY: Yes - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- reduced consumption at 20%
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- increased compound levels in blood
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- GPT increased slightly
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
-
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study):
- Water consumption in various groups was similar (4.5-6.0 mL/day), except for mice placed on 20% test item, where consumption was about half (2-2.5 mL/day) that of all others. Nevertheless, their average daily test item intake was still the highest. This reduction is presumably due to the bitter taste of the β-anomer of the test item.
HAEMATOLOGY:
- Oral test item intake lead to a dose-dependent increase in test item levels in the blood of males, females, and recently weaned pups. The test item also increased the level in the milk from nursing dams.
CLINICAL CHEMISTRY:
- Liver enzymes in plasma such as GOT and GPT were normal in both control and test item-fed mice (normal range: GOT, 40-50 IU/L; GPT, 15-25 IU/L)
except 10% test item-fed mice where GPT increased slightly, but was still within the normal range. Thus, there was no evidence of liver abnormalities.
OTHER FINDINGS:
- During 5 months of test item supplements, female mice were impregnated twice. Litter sizes (7-9 pups) and all pups were normal at birth. The dams continued on test item-supplemented water during nursing. Pups grew at a normal rate, were healthy, and all survived until weaning at 21 days. After that, the pups were placed on test item supplements for 9 days along with the mother. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 20 other: % in drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- water consumption and compound intake
- Remarks on result:
- other: % in drinking water
- Critical effects observed:
- not specified
- Conclusions:
- This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Test item did not show any adverse or pathological effects on growth, behaviour, organ size or weight, accumulation of glycated hemoglobin, liver glycogen, serum transaminases or the histological appearance of any major organs or tissues. - Executive summary:
Test item-supplemented water given to mice for 5 months did not show any adverse or pathological effects on growth, behaviour, organ size or weight, accumulation of glycated hemoglobin, liver glycogen, serum transaminases or the histological appearance of any major organs or tissues. Those receiving 20% test item drank only half as much water as the control or the other groups. Nevertheless, their average daily test item intake was still the highest. Oral test item intake lead to a dose-dependent increase in test item levels in the blood of males, females, and recently weaned pups. The test item also increased the level in the milk from nursing dams. No adverse effects were seen on reproduction.
Reference
To assess protein glycation, hemoglobin A1C (HbA1C) was measured in mice after 3 months. All groups showed nearly the same levels (2.9-3.1%) regardless of test item supplements, suggesting that glycated proteins do not accumulate in the blood in this animal.
All organ weights and their histological appearance were normal in all groups.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subchronic
- Species:
- mouse
- Quality of whole database:
- Comparable to guidleline study with acceptable restrictions
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
The test item was administered in the drinking water at dose levels of 1%, 3%, 10% and 20% to mice for 5 months. During the 5 month treatment, females were impregnated twice. The pups were weaned at 21 days and maintained on the same test item dose as their mother for 9 days. Both mother and pups were monitored for ill health such as bloating, diarrhea and abnormal weight gain or loss. Behavior of these animals were also monitored. Test item-supplemented water given to mice for 5 months did not show any adverse or pathological effects on growth, behaviour, organ size or weight, accumulation of glycated hemoglobin, liver glycogen, serum transaminases or the histological appearance of any major organs or tissues. Those receiving 20% test item drank only half as much water as the control or the other groups. Nevertheless, their average daily test item intake was still the highest. Oral test item intake lead to a dose-dependent increase in test item levels in the blood of males and females.
Justification for classification or non-classification
Based on no adverse test substance-related effects at 20% (highest dose tested) in a 5-month mouse drinking water study, the test substance does not need to be classified for repeat dose toxicity according to EU Classification and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
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