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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 700-258-0 | CAS number: 125971-95-1
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Report date:
- 2007
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- tert-butyl 2-[(4R,6R)-6-{2-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]ethyl}-2,2-dimethyl-1,3-dioxan-4-yl]acetate
- EC Number:
- 700-258-0
- Cas Number:
- 125971-95-1
- Molecular formula:
- C40H47FN2O5
- IUPAC Name:
- tert-butyl 2-[(4R,6R)-6-{2-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]ethyl}-2,2-dimethyl-1,3-dioxan-4-yl]acetate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5% methylcellulose in water for injections
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- analyses were performed by HPLC
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 mg/kg/day
Basis:
- Remarks:
- Doses / Concentrations:
250 mg/kg/day
Basis:
- Remarks:
- Doses / Concentrations:
500 mg/kg/day
Basis:
- Remarks:
- Doses / Concentrations:
1000 mg/kg/day
Basis:
- No. of animals per sex per dose:
- 6 females + 6 males
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- satellite control 6 females + 6 males
S 0mg/kg/day
S 1000 mg/kg/day
Examinations
- Observations and examinations performed and frequency:
- Experimental data collection
Body weight weekly
Food consumption weekly
Water consumption twice a week
Health condition daily
General clinical observation daily
Clinical observation battery weekly
Functional observations in the last week of administration
Haematological examination 29th (main groups) and 43 rd day of study (satellite groups)
Clinical biochemistry 29th and 43rd day of study
Urinalysis 28th and 42nd day of study
Biometry of organs 29th and 43rd day of study
Pathological examination 29th and 43rd day of study
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Haematological findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Details on results:
- Results
After completion of all examinations the following effects of test substance were
distinguished:
No treatment-related effects were detected in the following parameters:
- health condition
- behavioral assessment
- functional observation
- mortality
- fundamental histopathological findings of observed organs.
Treatment-related findings observed were as follows:
Dose level 1000 mg/kg/day
Reversible changes:
- increased value of lymphocytes in females - statistically significant
- increased count of platelets in both sexes — not statistically significant
- increased value of protrombin time in males — not statistically significant
- increased count of trachea inflammation in both sexes
- increased count of desquamation of urinary bladder
Irreversible changes:
- increased value of protrombin time in females — statistically significant
- decreased absolute weight of liver in females - statistically significant
- decrease of body weight in both sexes — not statistically significant
- decrease of food consumption in both sexes - not statistically significant
- decrease of food conversion in both sexes - not statistically significant
- decrease of water consumption in both sexes
- decreased value of tromboplastin time in males — not statistically significant
- increased value of tromboplastin time in females — not statistically significant
- decreased values of glucose in blood in females — not statistically significant decreased
-decreased absolute weight of testes and epidydimides in males — not statistically significant
- increase of relative weight of brain and heart in females — not statistically significant
Protracted changes (observed oniy after 14 day survival- recovery period):
- decreased value of monocytes in both sexes - statistically significant
- increased value of monocytes in satellite animals in both sexes — statistically significant
- decreased value of lymphocytes in satellite males - statistically significant
- increased value of granulocytes in satellite males - statistically significant
- decreased values of calcium and phosphorus in blood in satellite males — statistically significant
- increased relative weight of kidney in males—not statistically significant
- decreased relative weight of kidney in satellite males — not statistically significant
Dose level 500 mg/kg/day
Changes:
- increased value of granulocytes and monocytes in males - statistically significant
- decreased value of lymphocytes in males - statistically significant
- decreased value of lymphocytes in females — not statistically significant
- decreased value of granulocytes in females — not statistically significant
- decreased value of tromboplastin time in males — not statistically significant
- increased value of tromboplastin time in females — not statistically significant
- decreased value of protrombin time in both sexes — not statistically significant
- increased value of ALP in blood of males — not statistically significant
- decreased absolute weight of heart in males — not statistically significant
- decreased absolute weight of spleen in females — not statistically significant
- increased absolute weight of uterus in females — not statistically significant
- increased absolute weight of adrenal glands in females — not statistically significant
- increased relative weight of testes in males—not statistically significant
- increased relative weight of uterus in females — not statistically significant
- decreased relative weight of kidney in females — not statistically significant
- increased count of trachea inflammation in both sexes
- increased count of stomach inflammation in males.
Dose level 250 mg/kg/day
Changes:
- decrease of body weight in both sexes — not statistically significant
- decrease of weight increment in both sexes - not statistically significant
- increased value of total count of erythrocytes in both sexes — not statistical, significant
- increased value of total count of leucocytes in females — not statistically significant
- decreased value of tromboplastin time in males—not statistically significant
- increased value of tromboplastin time in females — not statistically significant
- increased value of protrombin time in both sexes — not statistically significant
- decreased values of cholesterol in blood in females — not statistically significant
- decreased volume of urine and increased of urine pH in both sexes
- decreased absolute and relative weight of liver in both sexes — not statistically significant
- decreased absolute weight of kidney and thyrnus in males — not statistically significant
- increased absolute weight of ovary in females — not statistically significant
- decreased relative weight of thymus in males — not statistically significant
- increased relative weight of testes and brain in males — not statistically significant
- increased relative weight of ovary in females — not statistically significant.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 125
- Sex:
- male/female
- Basis for effect level:
- other: overall effects clinical signs; mortality; body weight; food consumption; water consumption and compound intake; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Conclusion
Overall assessment of the effects of test substance, Acetonide Atorvastatine, after 28 day gavage administration revealed that the substance caused no toxicologically significant changes in observed health condition parameters (health condition control, clinical observations, behavioral assessment, functional observation) and did not cause mortality or fundamental histopathological changes of observed organs in both sexes.
The test substance decreased body weight with keeping standard food consumption. It decreased absolute weight of liver, value of glucose in blood was lowered without morphological changes in liver.
Haematological examination showed primarily negative effect on leucocyte differential - increase of a number of granulocytes and monocytes with normal rate of total number of white blood cells. This change could indicate general response of organism to the toxic noxa. It was not accompanied by inflammatory changes in organs. These effects detected in the highest dose level 1000 mg/kg/day and in middle dose level 500 mg/kg/day were statistically significant and irreversible. At a dose level of 250 mg/kg/day no change in examined organs or parameters was statistically significant but for instance in haematology parameters some toxicologically important effects were detected. So this lowest dose level can not be established as the NOAEL (No Observed Adverse Effect Level, dose without toxic effects).
According to diminishing trend of changes in dose levels 1000-500-250 mg/kg/day it is possible to deduce, that the dose without unfavorable effects will be somewhere between about 100- 150 mg/kg/day and we estimate it to 125 mg/kg/day.
The dose level about 125 mg/kg/day could be regarded as the NOAEL (No Observed Adverse Effect Level).
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.