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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 423-860-2 | CAS number: 56309-94-5
- 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://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
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 07 January - 12 May 1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- 1995
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Version / remarks:
- 1996
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 423-860-2
- EC Name:
- -
- Cas Number:
- 56309-94-5
- Molecular formula:
- Hill formula: C14H22O3 CAS formula: C14H22O3
- IUPAC Name:
- 4-{1,4-dioxaspiro[4.5]decan-8-yl}cyclohexan-1-one
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Crl:(WI) BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: males 195 - 228 g, females 158 - 184 g
- Fasting period before study: not specified
- Housing: 5 animals/cage, individual housing during activity monitoring
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days
DETAILS OF FOOD AND WATER QUALITY: diet batches were analysed for nutrients and contaminants on a regular basis, for water certificates of analysis were performed quarterly
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark
IN-LIFE DATES: From: To: 12 February 1998 - 12 March 1998
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- using stainless steel stomach tube
- Vehicle:
- propylene glycol
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
formulations were prepared daily immediately prior to dosing, adjustment was made for specific gravity of vehicle
VEHICLE
- Justification for use and choice of vehicle: based on laboratory trial informations
- Concentration in vehicle: 10, 40 and 200 mg/mL
- Amount of vehicle: 5 mL/kg - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of week 1 formulations were analysed to check stability, homogeneity in vehicle (highest and lowest concentration) and accuracy of preparations.
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- 7 days/week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
based on 5-day dose range finding study
- Fasting period before blood sampling for clinical biochemistry: overnight fasting
- Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once prior to treatment, once daily thereafter
BODY WEIGHT: Yes
- Time schedule for examinations: days 1, 8, 15, 22 and 28
FOOD CONSUMPTION:
- weekly
WATER CONSUMPTION:
- subjective, no quantitative investigation
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: immediately prior to scheduled post mortem examination
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Yes
- How many animals: 5/sex/group
- Parameters checked: erythrocyte count, haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin concentration, platelet count, red cell distribution width, total leucocyte count, differential leucocyte count, prothrombin time, partial thromboplastin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: immediately prior to scheduled post mortem examination
- Animals fasted: Yes
- How many animals: 5/sex/group
- Parameters checked: alanine aminotransferase, aspartate aminotransferase, total bilirubin, total cholesterol, creatinine, glucose, urea, total protein, albumin, alkaline phosphatase, sodium, potassium, chloride, calcium, phosphorus
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: during week 4 of treatment
- Dose groups that were examined: all dose groups
- Battery of functions tested: sensory activity / grip strength / motor activity
IMMUNOLOGY: No, but endpoints addressing potential adverse effects on the immune system were assessed - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Tissues examined: adrenal glands, aorta, brain, caecum, colon, duodenum, epididymides, heart, ileum, jejunum, kidneys, liver, lung, lymph nodes, oesophagus, ovaries, pancreas, Peyer's patches, pituitary gland, prostate gland, rectum, sciatic nerve, spinal cord, spleen, sternum with bone marrow, stomach, testes, thymus, thyroid/parathyroid, trachea, urinary bladder, uterus, all gross lesions - Other examinations:
- Organ weights: adrenal glands, brain, epididymides, heart, kidneys, liver, spleen, testes, thymus
- Statistics:
- Univariate one-way analysis of variance was used to assess the significance of intergroup differences.
If the variables could be assumed to follow a normal distribution, the Dunnett-test (many-to-one t-test) based on a pooled variance estimate was applied for the comparison of the treated groups and the control groups for each sex.
The Steel-test (many-to-one rank test) was applied when the data could not be assumed to follow a normal distribution.
All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance.
Group means were calculated for continuous data and medians were calculated for discrete data (scores) in the summary tables.
Test statistics were calculated on the basis of exact values for means and pooled variances. Individual values, means and standard deviations may have been rounded off before printing. Therefore, two groups may display the same printed means for a given parameter, yet display different test statistics values.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Salivation was observed in control and treated animals. This sign is often noted in rats of this age and strain following oral gavage and considered to be related to multiple intra-oesophageal intubation and/or the taste of the test substance. Therefore, this finding was considered not to be a sign of systemic toxicity.
Other findings, including a wound, scabs, diarrhoea and red staining were considered not be treatment related. - Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred during the study period.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The increased body weight gain of females receiving 200 mg/kg bw/d on days 15, 22 and 28, when compared to controls, was considered to have arisen by chance. This finding was considered of no toxicological significance, based on the absence of a treatment-related distribution and any other corroborative findings in these females. Body weights and body weight gain of other dose groups and the male animals remained in the same range as controls over the study period.
- 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 specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A minor statistically significant difference for erythrocyte count arising between controls and animals receiving 50 mg/kg bw/d was considered to have arisen by chance and not to represent a change of biological significance.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Values in treated males or females achieving a level of statistical significance when compared to the controls, were considered to have arisen as a result of slightly high control values and in the absence of a treatment- related distribution or corroborative findings in the opposite sex, considered to be of no toxicological significance. Moreover, a decrease in the enzyme level of alanine aminotransferase is considered to be of no biological relevance.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- Any findings noted and the variation in motor activity did not indicate a relation with treatment.
- Immunological findings:
- not examined
- Description (incidence and severity):
- Endpoints addressing potential adverse effects on the immune system did not reveal any immunotoxic potential of the test item.
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A slightly increased relative liver weight, achieving a level of statistical significance when compared to controls, was found in females dosed with 1000 mg/kg bw/d. The increase in relative liver weight can reflect a higher metabolic activity in this organ and may thus simply represent an adaptive change related to high dose treatment rather than a toxic effect. There were no relevant findings in histopathology corresponding to the increased relative liver weight and this effect was not found in male animals.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Findings noted among treated animals were considered to be within the range of biological variation for rats of this age and strain and not to represent a change of toxicological significance.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- The small number of findings recorded are within the normal range of background alterations which may be seen in untreated rats of this age and strain.
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- The small number of findings recorded are within the normal range of background alterations which may be seen in untreated rats of this age and strain.
- Other effects:
- not examined
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Remarks on result:
- other: no adverse effects observed
- Dose descriptor:
- NOEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- organ weights and organ / body weight ratios
- Remarks on result:
- other: considered as adaptive change
Any other information on results incl. tables
Analysis of dose preparations:
Test item formulations in proylene glycol were noted as stable for at least 4 hours and formed a homogeneous suspension at the concentrations tested. Analysis of accuracy of dose preparations revealed mean values of 102%, 103% and 100% for the dose groups 50, 200 and 1000 mg/kg bw/d, respectively. This was considered to represent an acceptable level of accuracy for formulations of this type.
Applicant's summary and conclusion
- Conclusions:
- From the results of the study presented, 1000 mg/kg bw is considered to be the no-observed-adverse-effect-level (NOAEL) and 200 mg/kg bw/d the no-observed-effect-level (NOEL).
- Executive summary:
A subacute 28-day toxicity study (OECD 407) was performed with the test item at doses of 0, 50, 200 and 1000 mg/kg bw/d administered orally (gavage) to rats (5 animals/sex/group). The test item was administered daily for 28 days. The following parameters were evaluated: clinical signs and mortality daily, funtional observation tests, body weight and food consumption weekly, clinical pathology and macroscopy at termination, organ weights and histopathology on selected tissues.
Accuracy, stability and homogeneity of test item formulations in the vehicle were demonstrated by analyses. Up to 1000 mg/kg bw/d no treatment-related findings were observed for the parameters evaluated. An increased relative liver weight was observed in females only at the highest dose. This finding was considered to be an adaptive change of the liver related to treatment without toxicological significance (higher metabolic activity).
There were no changes in clinical appearance, functional observations, body weights, food consumption, clinical laboratory investigations, macrosopic and microscopic examination that were considered to be treatment related.
From the results of this study, a NOAEL of 1000 mg/kg bw/d and a NOEL of 200 mg/kg bw/d were concluded.
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)