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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 411-490-4 | CAS number: 7027-11-4 ISOPHORONENITRILE, IPN
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1991-07-09 to 1991-11-19
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 3-cyano-3,5,5-trimethylcyclohexanone
- EC Number:
- 411-490-4
- EC Name:
- 3-cyano-3,5,5-trimethylcyclohexanone
- Cas Number:
- 7027-11-4
- Molecular formula:
- C10H15NO
- IUPAC Name:
- 3-cyano-3,5,5-trimethylcyclohexanone
- Details on test material:
- Isophorne nirile from Degussa AG, purity: 99.6%, Batch No. 64 II/87/90
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS:
- Strain: Bor: WISW (SPF Cpb)
- Source: Winkelmann GmbH & Co. KG, Borchen (Germany)
- Age: males 7 weeks, females 8 weeks
- Weight at study initiation: males 186 - 225 g, females 141 - 175 g
- Housing: single housing
- Diet: ad libitum, special diet for rats, SSniff R
- Water: ad libitum, tab water
- Acclimation period: 3 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 40 - 70 % (for short periods down to 35% or up to 75 %)
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours dark
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: aqueous Tragant(R) (1 %) suspension
- Details on oral exposure:
- ADMINISTRATION:
- Preparation of test substance: daily preparation of suspension in vehicle immediately before dosing using Ultraturrax homogenizer
- Doses per time period: once daily, 7 days per week
VEHICLE
- Concentration in vehicle: 3.83, 8.25, 17.8/14.7 *mg/ml, * in test week 6 dose for group 4 were reduced because of severe clonoc convulsions
- Amount of vehicle (if gavage): 2,15 ml/kg
- Lot/batch no. (if required): Tragacanth, batch 821 V57 6905 (E. Merck) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations of isophorone nitrile in aqueous tragacanth suspensions were determined by gas chromatographic method (FID). Sodium chloride
and methanol were added to the suspension and treated in an ultrasonic bath, the phases were separated using a centrifuge. Internal standard was
added to methanolic phase and the solution were analyzed using gaschromatographie
Stability test demonstrate that the isophorone nitrile remeins stable during a shipping period of approximately 24 hours at ambient temperatrures - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- once daily a.m., 7 days per week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
8.25, 17.8, 38.3/31.6* mg/kg bw; * in test week 6 dose for group 4 were reduced because of severe clonoc convulsions
Basis:
other: in aqueous Tragant(R) (1 %) suspension
- No. of animals per sex per dose:
- control: 20 (including 10 recovery animals
low and mid test group: 10 animals
high testr group: 20 (including 10 recovery animals - Control animals:
- other: yes, 1% tragacanth suspension
- Details on study design:
- - Dose selection rationale: dose finding study at doses of 17.8, 26.1, 38.3, 56.2, 68.1, 82.5 mg/kg 4 weeks treatment. At Doses below 38.3 mg/kg
no symptoms appeared, at a dose of 38.3 mg/kg convulsions were observed and doses above this level caused mortality.
- Post-exposure period: 6 weeks, Rats of main groups were sacrified at the end of the 13-week treatment period. Additional animals
(10 rats/sex/group) were allocated to the control and high-level group that served as satellite rats which were subjected to a postexposure
observation period of approx. 6 weeks. - Positive control:
- no positive control
Examinations
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS AND FREQUENCY:
- Clinical signs: were observed daily for the occurence of toxicityc symptoms and their severity and duration
- Mortality: was checked twice daily, on Saturday, Sunday and business holidays only once daily
- Body weight: once per week , starting with pretest period
- Food consumption: once a week, starting with pretest period
- Reflexes: pain, pinna and corneal refexes were tested once a week, starting with pretest period
- Hearing and Teeth: prior to first substance administration and in test weeks 6 and 13
- Ophthalmoscopic examination: in pretest week 1 and in test week 6 and 13 eyes of all animals of groups 1 and 4 were examined by biomicroscopy
with slit lamp 30 SL/M (Carl Zeiss)
- Haematology and Clinical Chemistry: weeks 6 and 12 a.m. as well as in test week 19 from the recovery animals, blood was collected from the
retro orbital venous plexus of onr eye under CO2 anesthesia : hematocrit (Hct), hemoglobin (Hb), leukocytes (WBC), erythrocytes (RBC) ,mean
corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), reticulocytes, Leukocyze differential count,
aspartate aminotransferase (optimized, ASAT), alanine aminotransferase(optimized, ALAT), glutamate dehydrogenase (GLDH), gamma-
Glutamylaminotransferaase, alkaline phosphatase (AKP), albumin, total bilirubin, blood glucose, total protein, triglycerides, cholesterol, creatinine,
blood urea, sodium, potassium
- Urinalysis: in test week 13 with test strips COMBUR9 and photometer determination of pH, protein, glucose, hemoglobin/erythrocytes, bilirubin,
urobilinogen, ketones, nitrite, osmolality and leukocytes. Microscopical examinations of the urine sediment were done in animals whose urine
state showed pathological changes in hemoglobin/erythrocytes or protein
- Sacrifice and pathology:
- ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Sacrifice: at the end of the treatment or recovery period the survived animals were anesthetized with CO2 ans sacrificed by exsanguination
- Organ weights: Adrenals, brain, heart, kidneys, liver, ovaries, pituitary, prostate/seminal vesicles in toto, spleen, testes, thymus.
Organs weights were expressed as absolute and relative to body weight after exsanguination
- Gross Necropsy: all animals were subjected to full cross necroscopy which included examination of the external surface of the body, all orifices, and the cranial, thoracic and abdominal cavities and their contens.
Following organs or tissues were preserved: all gross lesions, adrenal glands, aorta, axillary lymph node, bone (femur, tibia, sternum), bone
marrow, bone marrow smear, brain, caecum, cervix, colon, duodenum, epididymides, eyes with optic nerve, Harderian glands, heart, jejunum,
ileum, kidneys, knee joint, liver, lungs, mammary gland, mesenteric lymph nodes, oesophagus, ovaries, pancreas, parathyroid glands,
peripheral nerve, pituitary gland, prostate, rectum, salivary glands, seminal vesicles, skeletal muscle, skin, spinal cord, spleen, stomach, testes,
thymus, thyroid glands, tongue, trachea, urinary bladder, uterus, vagina
- Microscopical: all slides prepared with exception of bone marrow smears (no respective changes in peripheral blood parameterers) were
examined microscoically - Other examinations:
- no other examinations
- Statistics:
- Mean values of all parameters and - where indicated- standard deviations were calculated separately for each group and sex.
For statistical evaluation of food consumption, body weights, and organ weights the DUNNETT-Test was used. For values of hematological and clinical chemistry examinations the DUNETT-Test was used in case of normal distribution, otherwise the STEEL-test was employed.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- effects observed, treatment-related
- 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:
- Mortality: no substance related mortality
Food consumtion/Body weight: neither food consumption nor body weight were affected.
Clinical signs /Neurobehaviour: dose related, temporary and reversible changes in the behaviour (hyperkinesia, hyperactivity, clonic/tonic convulsion, salivation, tremor). No changes in reflexes, teeth and hearing
Macroscopicaly: no substance related findings
Microscopicaly/Histopathology a dose related partial disappearance of glycogen deposits in liver cells of males, after 6-week recovery period the finding was
no longer detected.
Organ weights: slight increases in absolute organ weights in high dose group in males and females in week 14
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 8.25 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- clinical signs
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
no further remarks
Applicant's summary and conclusion
- Conclusions:
- In a 13 week oral subcronic toxicity study, conducted with rats, the test item Isophorone nitrile showed effects on central and/or motoric nervous system ( hyperkinesia, hyperactivity, clonic convulsion, salivation) as well as histopathological alterations in the liver of males. The non-toxic dose (NOAEL) of the test item Isophorone nitrile is determined to be 8.25 mg/kg bw under the conditions of this study.
- Executive summary:
The toxicity of Isophorone nitrile after repeated oral administration was examined in a 13 week subchronic toxicity study conducted in rats. Obvious changes in the behaviour of treated animals were the temporary and fully reversible increase of locomotor activity (hyperkinesia, hyperactivity), the occurence of clonic and tonic convulsions and tremor. These findings occured in a dose releated pattern and may be judged as expression of a stimulation of the central and/or the motoric nervous system. Regarding the observed salivation, this effect can be attributed to a stimulation of vegetative functions, so that different parts of the central nervous system and the vegetative nervous system must be considered as target regions for Isophorone nitrile.
In the microscopic examination of the preserved tissues the liver is noticed as an affected organ. The partial disappearance of glycogen deposits in liver cells is dose and in so far treatment related. As there was no functional correlate, e.g. reduction of serum glucose levels and degenerative changes were absent, this finding is considered to have an adaptive nature. After the 6 -week recovery period the finding was no longer detected. A final evaluation of this phenomen on the basis of this study is not feasible.
Because only two low dose animals showed slight hyperkinesia occasionally in week 4 and no other effects were noted in the low dose group the non toxic dose of isophorone nitrile is still considered to be 8.25 mg/kg bw.
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.