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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 603-522-2 | CAS number: 131819-23-3
- 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
- Study period:
- February 18, 2000 - November 12, 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The informtion for this endpoint study record was obtained from an experimental study. The OECD GLP criteria were met and the methods applied are fully compliant with OECD TG 407
Data source
Reference
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2001
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- only 6 animals per dose group, 4 dose groups, dose spacing increased to factor of 5, recovery in three groups
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 4-trans-Propyl-4-trans-(3,4,5-trifluorphenyl)-[1,1-bicyclohexyl]
- EC Number:
- 603-522-2
- Cas Number:
- 131819-23-3
- Molecular formula:
- C21H29F3
- IUPAC Name:
- 4-trans-Propyl-4-trans-(3,4,5-trifluorphenyl)-[1,1-bicyclohexyl]
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- lot No. E998833
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 5 weeks
- Weight at study initiation: 141- 161 g (m), 114-141 g (f)
- Fasting period before study: no
- Housing: grouped
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
DETAILS OF FOOD AND WATER QUALITY:
Pellet diet for experimental animals (MF, Oriental Yeast Co., Ltd.) and
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20" to 24" C
- Humidity (%): 40% to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 h
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on oral exposure:
- Tue test substance was suspended in a 0.5% CMC-Na aqueous solution mixed with 0.1 % Tween 80 (Tween 80: Tokyo Kasei Kogyo Co., Ltd., lot No. GEOl; CMC-Na: Iwai Chemicals Company, lot No. 041210). The dosing solutions were prepared once a week, and
were stored in a dark refrigerated place. They were used within 8 days. The dosing solutions were stirred just before administration. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The homogeneity and stability of the test substance in the dosing solution which is stored in a dark refrigerated place for 8 days were confirmed at the doses of 0.4 and 100 mg/mL by the HPLC method before the first administration. The dosing solutions for each dose group prepared at the first time were analyzed by the HPLC method and confirmed that the concentrations of the test substance were within ± 10% for each indicated concentration.
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 8 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 40 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 200 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- Group name (mg/mL) Main Male Main Female Recov. Male Recov. Female
Control 0 6 6 6 6
8 mg/kg 0.8 6 6
40 mg/kg 4.0 6 6
200 mg/kg 20 6 6 6 6
1000 mg/kg 100 6 6 6 6 - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on DRF study results
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: recovery animals
- Post-exposure recovery period in satellite groups: 14 days
- Section schedule rationale (if not random): random
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All rats were observed twice a day (before and after administration) during the treatment
period and once a day on every other day in the morning.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / Not specified
- Time schedule for examinations:
OPHTHALMOSCOPIC EXAMINATION: Yes / No / Not specified
- Time schedule for examinations:
- Dose groups that were examined:
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Days 29 and 43
- Anaesthetic used for blood collection: Yes (Ravonal)
- Animals fasted: No
- How many animals:
- Parameters checked in table [No.?] were examined.
CLINICAL CHEMISTRY: Yes / No / Not specified
- Time schedule for collection of blood:
- Animals fasted: Yes / No / Not specified
- How many animals: 6
URINALYSIS: Yes
- Time schedule for collection of urine: day 23
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: No
NEUROBEHAVIOURAL EXAMINATION: No
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:
IMMUNOLOGY: No
- Time schedule for examinations:
- How many animals:
- Dose groups that were examined:
- Parameters checked in table [No.?] were examined.
OTHER: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Tue following organs of all rats were weighed with an electronic balance (AEG-120,
Shimadzu Corp.). Tue relative organ weights (organ to body weight ratio) were calculated
from the body weight on the day of necropsy.
Brain, liver, kidneys, adrenals, thymus, spleen, testes, and ovaries.
HISTOPATHOLOGY: Yes
Tue following organs and tissues were removed from all rats and fixed in a 10% neutral
phosphate-buffered formalin, except for the eye and Harderian gland which were fixed in
Davidson's solution, and for testis and epididymis which were fixed in Bouin's fluid.
Brain, pituitary, eye and Harderian gland, thymus, lung, stomach, thyroid and parathyroid,
heart, liver, spieen, kidney, adrenal, urinary bladder, testis, epididymis, ovary, and hone
marrow (femur, unilateral).
Histopathological examination was perf orrned on the following organs and tissues of the
control and 1000 mg/kg groups at the end of the treatment period, along with all gross lesions
found in any group.
Histological specimens were stained with H.E. stain in accordance with
routine methods and examined. Additionally, the liver, adrenal, and Harderian gland of all
males and females of other doses at the end of the treatment period and all of the groups at the
end of the the recovery period were also examined histologically, since the change considered
to be caused by the administration of the test substance were found in these organs.
Further, since focal necrosis in the bone marrow was noted in one male of the 1000 mg/kg group,
to determine the incidence of this change, the bone marrow was also
examined in the rnales of other dose groups at the end of the treatment period.
Heart, liver, spieen, kidney, adrenal, Harderian gland, bone marrow. - Statistics:
- Standard statistical methods have been applied for data processing.
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
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the end of the treatment period, increased reticulocyte count was noted in the males of the 200 and 1000 mg/kg groups and shortened prothrombin time in the females of the 1000 mg/kg group. These changes were not observed at the end of the recovery period.
In addition, shortened prothrombin time was noted at the end of the recovery period in the females of the 200 mg/kg group. However, this change was slight and was not noted at the end of the recovery period in the 1000 mg/kg group, so it was considered unrelated to test substance adrninistration. - Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the end of the treatment tperiod, the absolute and relative weights of the liver were increased in the males of the 200 and 1000 mg/kg groups, the absolute weight of the adrenals was increased in the females of the 40 and 1000 mg/kg groups, and the relative weight of the adrenals was increased in the females of the 200 and 1000 mglkg groups. These changes were not observed at the end of the recovery period.
In addition, at the end of the treatment period, the absolute weight of the kidneys was increased in the males of the 200 mglkg group and at the end of the recovery period, the absolute weight of the spleen and the relative weight of the liver were decreased in the males
of the 200 mg/kg group. However, these changes were slight and any of them was not noted in the 1000 mg/kg group, so it was considered unrelated to test substance administration. - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At the end of the treatment period, enlargement of the liver was noted in the animals of both sexes of the 200 and 1000 mg/kg groups, enlargement of the adrenal in the females of the 1000 mg/kg group, and a brown change in the Harderian gland in the females of the 40 mg/kg bw/d group and the animals of both sexes of the 200 and 1000 mg/kg bw groups. At the end of the recovery period, only the brown change in the Harderian gland was still noted in the females of the 200 mg/kg bw/d group and the animals ofboth sexes of the 1000 mg/kg bw/dgroup.
In addition, in the test substance-treated groups, brown patch in the lung was noted at the end of the treatment period. However, since the incidence of this change showed no constant tendency, it was considered unrelated to test substance administration. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Liver Hypertrophy, hepatocyte, centrilobular
Adrenal Increase in lipid droplet, fascicular zone
Harderian gland Hypersecretion
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 8 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Total incidences of necropsy findings
Period |
End of treatment |
End of recovery |
|||||||||||||||
Organ |
Sex |
Male |
Female |
Male |
Female |
||||||||||||
Dose [mg/kg] |
0 |
8 |
40 |
200 |
1000 |
0 |
8 |
40 |
200 |
1000 |
0 |
200 |
1000 |
0 |
200 |
1000 |
|
Number of animals |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
|
Liver |
centrilobular hypertrophy grade 1 | 0 |
0 |
4 |
4 |
5 |
0 |
0 |
0 |
2 |
5 |
0 |
0 |
1 |
0 |
0 |
1 |
Adrenal | increase lipid droplet, fascilar zone grade 1 |
0 |
0 |
0 |
0 |
4 |
0 |
0 |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
Adrenal |
increase lipid droplet, fascilar zone grade 2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
Harderian gland |
hypersecretion |
0 |
0 |
0 |
1 |
4 |
0 |
0 |
2 |
4 |
4 |
0 |
0 |
1 |
0 |
3 |
4 |
Applicant's summary and conclusion
- Conclusions:
- A NOEL (no effect level) of 8 mg/kg bw/ for both sexes and the NOAEL (no observed adverse effect level) of 200 mg/kg bw/day are considered justified.
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.