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EC number: 203-813-0 | CAS number: 110-89-4
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- (First Addendum to the OECD Guideline for Testing of Chemicals, Section 4, No. 474, adopted May 26, 1983, "Micronucleus Test")
- Deviations:
- yes
- Remarks:
- Deviation to updated version of OECD TG 474 (1997): 1000 polychromatic erythrocytes analysed per animal (instead of 2000 PCEs)
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- Piperidine
- EC Number:
- 203-813-0
- EC Name:
- Piperidine
- Cas Number:
- 110-89-4
- Molecular formula:
- C5H11N
- IUPAC Name:
- piperidine
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Piperidin
- Physical state: liquid, colourless/yellowish
- Analytical purity: 99.3 %
- Lot/batch No.: 459-60 17 FA. 10000 GR 1 FA. GEZ
- Expiration date of the lot/batch: June 27, 1990
- Stability under test conditions: not indicated
- Storage condition of test material: 4°C, closed container
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: minimum 10 weeks
- Weight at study initiation: approximately 30 g
- Fasting period before study: 18 hours
- Housing: single, Makrolon Type I, with wire mesh top (EBECO, Castrop-Rauxel, Germany)
- Diet (ad libitum): pelleted standard diet (ALTROMIN, Lage/Lippe, Germany)
- Water (ad libitum): tap water
- Acclimation period: minimum 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): not regulated
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- VEHICLE
- Vehicle(s)/solvent(s) used: water
- Amount of vehicle (if gavage): 10 mL/kg body weight orally
- Justification for choice of vehicle: non-toxicity for the animals. - Duration of treatment / exposure:
- single dose
- Frequency of treatment:
- single dose
- Post exposure period:
- Bone marrow preparation intervals: 24, 48, 72 h
Doses / concentrationsopen allclose all
- Dose / conc.:
- 40 mg/kg bw/day (actual dose received)
- Remarks:
- 24 hours
- Dose / conc.:
- 120 mg/kg bw/day (actual dose received)
- Remarks:
- 24 hours
- Dose / conc.:
- 400 mg/kg bw/day (actual dose received)
- Remarks:
- 24 hours, 48 hours and 72 hours
- No. of animals per sex per dose:
- 6 animals/sex/dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamid
- Route of administration: gavage
- Doses / concentrations: 30 mg/kg bw in 10 mL physiological saline /kg bw
Examinations
- Tissues and cell types examined:
- Polychromatic erythrocytes (PCE) in the bone marrow of the mouse
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
A preliminary study on acute toxicity was performed with the same strain and under identical conditions as in the mutagenicity study.
The maximum tolerated dose level was determined to be the dose that caused toxic reactions without having major effects on survival within 72 hours.
Three adequate spaced dose levels extending over a single log range were applied at the central sampling interval 24 h after treatment. The highest dose level used was the maximum tolerated dose or that producing some indication of cytotoxicity. For this dose level additional samples were taken at 48 h and 72 h after treatment.
TREATMENT AND SAMPLING TIMES (in addition to information in specific fields):
Preparation of the Animals:
The animais were sacrificed by cervical dislocation. The femora were removed, the epiphyses were cut off and the marrow was flushed out with 2.0 mL fetal calf serum, using a 5 mL syringe, into 1 mL fetal calf serum. The cell suspension was centrifuged at 1000 rpm for 5 minutes and the supernatant was discarded. A small drop of the resuspended cell pellet was spread on a slide.
DETAILS OF SLIDE PREPARATION:
The smear was air-dried and then stained with May-Gruenwald/Giemsa. Cover slips were mounted with EUKITT (KINDLER, D-7800 Freiburg F.R.G.). At least one slide was made from each bone marrow sample.
METHOD OF ANALYSIS:
Evaluation of the slides was performed using NIKON microscopes with 100x oil immersion objectives. 1000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei. To describe a cytotoxic effect the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and expressed as normochromatic erythrocytes per 1000 PCEs. The analysis was performed with coded slides. - Evaluation criteria:
- A test article is classified as mutagenic if it induces either a statistically significant dose-related increase in the number of micronucleated polychromatic erythrocytes or a reproducible statistically significant positive response for at least one of the test points.
A test article producing neither a statistically significant dose-related increase in the number of micronucleated polychromatic erythrocytes nor a statistically significant and reproducible positive response at anyone of the test points is considered nonmutagenic in this system.
This can be confirmed by means of the nonparametric Mann-Whitney test. However, both biological and statistical significance was considered together. - Statistics:
- Statistical significance at the five per cent level (p < 0.05) was evaluated by means of the non-parametric Mann-Whitney test.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- After treatment with 400 mg/kg bw piperidine 5 out of 36 animals died in the micronucleus assay. One male and one female died at preparation intervals 24 and 48 h, respectively, and one male animal at preparation interval 72 h.
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
1. In a first pre-experiment 6 animals (3 males, 3 females) received orally a single dose of 500 mg/kg b.w. piperidine dissolved in aqua dest.. The volume administered was 10 mL/kg b.w..
All treated animals expressed toxic reactions: eyelid closure, apathy, tremor, dyspnoea.
Lethalities: one female within 24 hours, one male and one female within 48 hours.
2. In a second pre-experiment 6 animals (3 males, 3 females) per dose level received orally a single dose of 300 or 400 mg/kg b.w., respectively, piperidine dissolved in aqua dest.. The volume administered was 10 mL/kg b.w..
300 mg/kg b.w.:
All treated animals expressed toxic reactions: eyelid closure, apathy. None of the treated animals died.
400 mg/kg b.w.:
All treated animals expressed toxic reactions: eyelid closure, apathy. None of the treated animals died.
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei: In comparison with the corresponding negative controls there was no substantial enhancement in the freguency of the detected micronuclei at any preparation interval or dose level of the test article. The mean values of micronuclei observed after treatment with piperidine were in the same range as compared to the negative control groups.
- Ratio of PCE/NCE: As compared to the corresponding negative controls the mean number of normochromatic erythrocytes was enhanced after the treatment with highest dose of piperidine, indicating that the test article had cytotoxic properties.
- Positive control: 30 mg/kg b.w. cyclophosphamide administered per os was used as positive control which showed a distinct increase in induced micronucleus frequency.
Any other information on results incl. tables
Test group |
Dose [mg/kg bw] |
Sampling time [h] |
PCEs with micronuclei [%] |
Range |
PCE/NCE |
solvent |
0 |
24 |
0.12 |
0-3 |
1000/496 |
test article |
40 |
24 |
0.12 |
0-4 |
1000/441 |
test article |
120 |
24 |
0.08 |
0-3 |
1000/612 |
test article |
400 |
24 |
0.13 |
0-4 |
1000/1001 |
cyclophosphamide |
30 |
24 |
1.21 |
4-24 |
1000/769 |
|
|
|
|
|
|
solvent |
0 |
48 |
0.09 |
0-2 |
1000/630 |
test article |
400 |
48 |
0.14 |
0-3 |
1000/1181 |
|
|
|
|
|
|
solvent |
0 |
72 |
0.14 |
0-3 |
1000/605 |
test article |
400 |
72 |
0.14 |
0-3 |
1000/435 |
In conclusion, it can be stated that during the study described and under the experimental conditions reported, the test article did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: negative
Under the experimental conditions reported, the test article did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse. - Executive summary:
In a NMRI mouse bone marrow micronucleus assay, performed according to GLP and OECD 474, five animals per sex and per dose were treated orally at a single time point with the test item (99.3 % a.i.) at doses of 0, 40, 120, and 400 mg/kg bw (CCR/BG Chemie, 1989). Bone marrow cells were harvested at 24, 48 and 72 h post-treatment. The vehicle was aqua dest..
In the highest dose of 400 mg/kg bw all treated animals expressed toxic reactions such as eyelid closure and apathy. None of the treated animals died. The mean number of normochromatic erythrocytes was enhanced after the treatment with highest dose of the test item as compared to the corresponding negative control, indicating that the test article had cytotoxic properties. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time or dose level. The positive control induced the appropriate response. The study is classified as acceptable (reliability 1) and satisfies the requirement for Test Guideline OECD 474 for in vivo cytogenetic mutagenicity data.
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