Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 227-579-4 | CAS number: 5895-46-5
- 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://www.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 16 July 2007 to 31 October 2008
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. These data have been read-across from a structurally similar compound.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Dicerium tricarbonate
- EC Number:
- 208-655-6
- EC Name:
- Dicerium tricarbonate
- Cas Number:
- 537-01-9
- IUPAC Name:
- dicerium tricarbonate
- Details on test material:
- dicerium tricarbonate (read across)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 10 weeks old at the beginning of the treatment period
- Weight at study initiation: at the beginning of the treatment period, the animals had a mean body weight of 419g (range: 392g to 442g) for the males and 263g (range: 239g to 283g) for the females
- Fasting period before study: no
- Housing: The males were individually housed, except during pairing, in wire-mesh cages (43.0 x 21.5 x 18.0 cm). The females were individually housed, except during pairing, until late gestation in wire-mesh cages (43.0 x 21.5 x 18.0 cm). The females were individually housed from late gestation, and with their litter during lactation, in polycarbonate cages (43.0 x 21.5 x 20.0 cm).
- Diet: free access to SSNIFF R/M-H pelleted maintenance diet
- Water: free access to bottles containing tap water (filtered with a 0.22 µm filter)
- Acclimation period: the animals were acclimated to the study conditions for a period of 7 days before the beginning of the treatment period.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5% aqueous solution
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item was administered as a suspension in the vehicle. The test item was ground to fine powder using a mortar and pestle, suspended in the vehicle in order to achieve the concentrations of 30, 90 and 200 mg/mL and then homogenized using a magnetic stirrer. The test item dosage forms were prepared at a frequency based on stability data (up to 9 days) and were stored at +4°C, protected from light, prior to use.
VEHICLE
- Justification for use and choice of vehicle (if other than water): aqueous suspension for a poorly hydrosoluble test substance, as recommended in the guideline
- Concentration in vehicle: 30, 90 and 200 mg/mL
- Amount of vehicle (if gavage): a constant volume of 5 mL/kg/day was used
- Lot/batch no. (if required): methylcellulose batch No. 017K0052, supplied by Sigma
- Purity: data not available - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- During a pre-study period, the homogeneity, stability and concentration of two dosage forms prepared at the lowest and highest concentrations of the present study (30 and 200 mg/mL) were checked using ICP-OES (Inductively Coupled Plasma/Optical Emission Spectrometry) after validation of the analytical method. The results showed acceptable homogeneity and stability of both concentrations over 9 days at +4°C.
During the study, the concentration of the test item and homogeneity of the dosage forms was determined in samples of each control and test item dosage form prepared for use in weeks 1, 3 and 6. The results showed acceptable homogeneity and concentration of all dosage forms analyzed. Precision (RSD =< 10%) and accuracy (100 +/- 10%) of the method were found to be satisfactory. - Duration of treatment / exposure:
- - In males: 15 days before mating, during the mating period (up to 3 weeks), until sacrifice (i.e. at least 4 weeks in total)
- In females: 15 days before mating, during the mating period (up to 3 weeks), during pregnancy (~ 3 weeks) , during lactation until day 5 post-partum inclusive (approximately 7-9 weeks total) - Frequency of treatment:
- Each animal was given the appropriate dosage form once a day, at approximately the same time each day, 7 days a week.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 150, 450, and 1000 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 10/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: on the basis of a previous 14-day toxicity study in the rat in which the dose-levels of 150, 450 and 1000 mg/kg/day elicited no significant treatment-related effects.
- Rationale for animal assignment: during the pre-treatment period, the required number of animals (40 males and 40 females) was selected according to body weight and clinical condition and allocated to the groups (by sex), according to a computerized stratification procedure, so that the average body weight of each group was similar. - Positive control:
- no data
Examinations
- Observations and examinations performed and frequency:
- Parental animals: Observations and examinations
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: From arrival, the animals were observed once a day as part of routine examinations. From the start of treatment period, each animal was observed once a day, at approximately the same time for the recording of clinical signs.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: on all animals outside the home cage, in a standard arena, once before the beginning of the treatment period and then once a week until the end of the study.
Observations included (but were not limited to) changes in the skin, fur, eyes, mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g. lachrymation, piloerection, pupil size, unusual respiratory pattern). Changes in gait, posture and response to handling as well as the presence of clonic or tonic movements, stereotypes (e.g. excessive grooming, repetitive circling) or bizarre behavior (e.g. self-mutilation, walking backwards) were also recorded.
BODY WEIGHT: Yes
- Time schedule for examinations: the body weight of each male was recorded on the first day of treatment (day 1), then once a week until sacrifice. The body weight of each female was recorded on the first day of treatment (day 1), then once a week until mated (or until sacrifice) and on days 0, 7, 14 and 20 post-coitum and days 1 and 5 post-partum.
FOOD CONSUMPTION: Yes
The quantity of food consumed by each male was recorded once a week, over a 7 day period, from the first day of treatment until sacrifice. The quantity of food consumed by each female was recorded once a week, over a 7 day period, from the first day of treatment through gestation (days 0-7, 7-14 and 14-20 post-coitum intervals) and lactation (days 1-5 post-partum intervals) until sacrifice. During the pairing period, food consumption was not recorded for males or females.
WATER CONSUMPTION: No
OTHER:
MORTALITY AND MORBIDITY: each animal was checked for mortality or signs of morbidity at least twice a day during the treatment period.
Functional Observation Battery (FOB): on the first five males and the first five females, once at the end of the treatment period. This included a detailed clinical examination, measurement of reactivity to manipulation or to different stimuli and motor activity.
HEMATOLOGY: peripheral blood
The following parameters were determined for the last five males and females of each group on the day of sacrifice: Erythrocytes, Hemoglobin, Mean cell volume, Packed cell volum, Mean cell hemoglobin concentration, Mean cell hemoglobin, Thrombocytes, Leucocytes, Differential white cell count with cell morphology (neutrophils, eosinophils, basophils, lymphocytes and Large Unstained Cells), Monocytes, Reticulocytes, Prothrombin time, Activated partial thromboplastin time, Fibrinogen.
BLOOD BIOCHEMISTRY:
The following parameters were determined for the last five males and females of each group on the day of sacrifice: Sodium, Potassium, Chloride, Calcium, Inorganic phosphorus, Glucose, Urea, Creatinine, Total bilirubin, Total proteins, Albumin, Albumin/globulin ratio, Total cholesterol, Triglycerides, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Bile acids.
ESTROUS CYCLICITY (Parental animals)
The pre-coital time was calculated for each female. The estrous cycle stage was determined from a fresh vaginal lavage (stained with methylene blue), each morning during the mating period, until the females are mated.
SPERM PARAMETERS (Parental animals)
The microscopic examination made special emphasis on stages of spermatogenesis in the male gonads and histopathology of interstitial testicular cell structure. - Sacrifice and pathology:
- SACRIFICE
After overnight fasting, at least 14 hours, all surviving F0 animals were deeply anesthetized by an intraperitoneal injection of sodium pentobarbital and sacrificed by exsanguination:
- males: after the end of the mating period (after at least 4 weeks of treatment),
- females: on day 6 post-partum,
GROSS NECROPSY
- A complete macroscopic post-mortem examination was performed on all animals. This included examination of the external surfaces, all orifices, the cranial cavity, the external surfaces of the brain, the thoracic, abdominal and pelvic cavities with their associated organs and tissues and the neck with its associated organs and tissues. Special attention was paid to the reproductive organs. The numbers of corpora lutea and implantation sites were also recorded.
HISTOPATHOLOGY / ORGAN WEIGHTS
A microscopic examination was performed on:
- all the tissues listed in the Table 1 for the first five males and females of the control and high-dose groups (groups 1 and 4) sacrificed as scheduled
- all macroscopic lesions
The microscopic examination made special emphasis on stages of spermatogenesis in the male gonads and histopathology of interstitial testicular cell structure. - Other examinations:
- Litter observations
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in offspring:
- Stillbirths, live births
- The total litter size and numbers of pups of each sex (sex ratio) was recorded as soon as possible after birth.
- Postnatal mortality: The litters were observed daily in order to note the number of live, dead and cannibalized pups.
- The pups were observed daily for clinical signs.
- Weight gain: The weight of each pup was recorded on days 1 and 5 post-partum.
GROSS EXAMINATION OF DEAD PUPS: yes
Reproductive indices
The following parameters were evaluated:
- Pre-implantation loss,
- Post-implantation loss,
- Mating index,
- Fertility index,
- Gestation index,
- Number of corpora lutea,
- Number of implantations,
- Number of pups delivered
Offspring viability indices
The following parameters were evaluated:
- Live birth index,
- Viability index on day 4 post-partum,
- Mean litter size,
- Pup sex ratios
Pups found dead, prematurely sacrificed and pups sacrificed on day 5 post-partum were carefully examined externally for gross external abnormalities and a macroscopic examination was performed. There was no preservation of tissues. - Statistics:
- Mean values were compared by one-way variance analysis and Dunnett test, (mean values being considered as normally distributed, variances being considered as homogeneous). Percentage values were compared by Fisher exact probability test.
Results and discussion
Results of examinations
- 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):
- no effects observed
- Description (incidence and severity):
- administration was via gavage
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- administration was via gavage
- Water consumption and compound intake (if drinking water study):
- not examined
- Description (incidence and severity):
- administration was via gavage
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Animals treated at 1000 mg/kg/day had lower white blood cell count
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Females treated at 1000 mg/kg/day had lower chloride concentration, higher glucose, potassium, inorganic phosphorus and urea levels
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY - no effects
BODY WEIGHT AND WEIGHT GAIN - Females treated at 450 or 1000 mg/kg bw/day had slightly lower mean bodyweight gains during pregnancy, which were not statistically significant and likely due to one or two dams, respectively, which had pre-implantation losses higher than the rest of females within their groups. Mean body weight gains of treated females were also slightly lower during the lactation period, again not attaining statistical significance and not affecting mean body weights at termionation on day 5 of lactation. No effects during premating period or on males.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study) - females had lower food consumption during lactation but this may be related to the higher number of fetuses/pups in the control group. No effects during premating period or on males.
HAEMATOLOGY - lower white blood cell counts in animals treated at 1000 mg/kg/day
CLINICAL CHEMISTRY - lower chloride concentration and higher glucose, potassium, inorganic phophorus and urea levels in females treated at 1000 mg/kg/day
ORGAN WEIGHTS - no changes at 450 or 150 mg/kg/day (no details provided on effects at 1000 mg/kg/day)
GROSS PATHOLOGY - no changes at 450 or 150 mg/kg/day (no details provided on effects at 1000 mg/kg/day)
HISTOPATHOLOGY: NON-NEOPLASTIC - Increased incidence of submucosal eosinophil infiltration and pyloric gland hyperplasia in rats from both sexes treated at1000 mg/kg/day and males at 450 mg/kg/day.
HISTOPATHOLOGY: NEOPLASTIC (if applicable) - (see non-neoplastic hyperplasia effects above)
HISTORICAL CONTROL DATA (if applicable) - none
OTHER FINDINGS - No effects in any group on mating, fertilitty or delivery, mean numbers of corpora lutea, implantations or pups; no effects on mean pup body weight, survival or sex;
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Remarks:
- parental toxicity
- Effect level:
- 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on increased incidence and or severity of submucousal eosinophil infiltration and pyloric gland hyperplasia in male rats at 450 mg/kg/day and both sexes at 1000 mg/kg/day.
- Dose descriptor:
- NOAEL
- Remarks:
- parental systemic toxicity
- Effect level:
- 450 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Haematological and clinical chemistry changes at 1000 mg/kg bw/day
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Data for reproductive and developmental parameters not listed here (see 7.8.1 and 7.8.2)
Applicant's summary and conclusion
- Conclusions:
- NOEL for parental toxicity in the combined repeated-dose/reproductive study was 150 mg/kg/day in male and female rats based on microscopic findings in the stomach that consisted of increased incidence and or severity of submucousal eosinophil infiltration and pyloric gland hyperplasia in male rats treated at 450 mg/kg bw/day, and in rats of both sexes treated at 1000 mg/kg/day. As the effects on stomach represent a portal-of-entry irritating effect, likely due to the high concentrations of the substance given as a bolus by gavage, a systemic NOAEL can be set at 450 mg/kg bw/day, based on changes on haematological and clinical chemistry parameters recorded at 1000 mg/kg bw/day.
- Executive summary:
The test item, Cerium carbonate, the read across compound, was administered daily by oral gavage to male and female Sprague-Dawley rats, for 2 weeks before mating, during mating, gestation and until day 5 post-partum, at dose-levels of 150, 450 or 1000 mg/kg/day. Dosages were chosen on the basis of a preliminary 14-day oral gavage study (data not available). There were no adverse effects of treatment at any dose-level on mortality, clinical signs, body weight or food consumption. Animals treated at 1000 mg/kg/day had lower white blood cell counts and females in this group had lower chloride concentration and higher glucose, potassium, inorganic phosphorus and urea levels. There were no effects in any group on mating, fertility or delivery and no treatment-related effects on the mean numbers of corpora lutea, implantations or pups. There were no effects on mean pup body weight, survival or sex. There were no treatment-related organ weights and macroscopic changes in rats treated at 1000 mg/kg/day. At 450 or 150 mg/kg/day, there were no treatment-related organ weights and macroscopic changes. There were microscopic treatment related findings in the stomach that consisted of increased incidence and/or severity of submucosal eosinophil infiltration and pyloric gland hyperplasia in rats of both sexes treated at 1000 mg/kg/day and males at 450 mg/kg/day. No microscopic treatment related changes were observed in the testes and ovaries.
Based on the experimental conditions of this study, the No Observed Effect Level (NOEL) for parental toxicity was considered to be 150 mg/kg/day in female and male rats, based on microscopic findings on stomach. As these effects represent a portal-of-entry irritating effect, and signs of systemic toxicity evidenced by changes in haematological and/or clinical chemistry parameters were recorded only in animals treated at 1000 mg/kg/day, the systemic NOAEL can be set at 450 mg/kg/day.
The NOEL for reproductive performance (mating and fertility) was considered to be 1000 mg/kg/day and the NOEL for toxic effects on progeny was 1000 mg/kg/day.
These data have been read-across from a structurally similar compound.
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)