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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
Carcinogenicity
Administrative data
Description of key information
Oral
Carcinogenicity, oral, rat, drinking study, non-GLP, non-Guideline: negative (Lijinsky and Taylor, 1977)
Carcinogenicity, oral, rat, drinking study, non-GLP, non-Guideline: negative (Garcia and Lijinsky, 1973)
Carcinogenicity, rat, implantation, non-GLP, non-Guideline: positive (Suzuki et al., 1984), no valid test system and thereofore disregarded for the evaluation.
There was no evidence of carcinogenicity when piperidine was administered to rats in drinking water with or without sodium nitrite.
Inhalative
No studies were available on the carcinogenicity of piperidine administered by inhalation exposure.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Rats were treated by chronic administration for 75 weeks of piperidine with and without sodium nitrite in the drinking water. The animals were kept until death and subjected to complete pathological examination.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): piperidine
- no further data - Species:
- rat
- Strain:
- other: MRC
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 8 - 10 weeks
- Housing: 5 rats per cage
ENVIRONMENTAL CONDITIONS
- no data - Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- - Animals were given 100 ml of solution containing piperidine and nitrite as drinking water.
- Treatment groups in detail:
• Piperidine (0.1 %)
• Piperidine (0.025 %) + sodium nitrite (0.05 %)
• Piperidine (0.1 %) + sodium nitrite (0.2 %)
• Sodium nitrite (0.2 %)
• Untreated Control - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 75 weeks
- Frequency of treatment:
- 5 days per week in the drinking water
- Post exposure period:
- life-time
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Remarks:
- total dose: 9375 mg/animal; calculation based on 375 days of treatment and an average water consumption of 25 mL/day/animal; 0.1% in the drinking water
- No. of animals per sex per dose:
- 15
- Control animals:
- yes, concurrent no treatment
- Observations and examinations performed and frequency:
- - Survival of the experimental rats and the distribution of tumors in the animals were determined.
- Sacrifice and pathology:
- - The animals were kept until death and subjected to complete pathological examination.
- Description (incidence):
- - There was no significant difference in animal survival in any of the groups (mean survival of 80 % of the rats).
- Description (incidence and severity):
- - No significant difference between untreated or nitrite treated animals and treated groups (piperidine, piperidine plus nitrite) was observed in number of tumour bearing animals and in types of tumours.
- Common (spontaneous) tumours observed in treated and control rats were mainly pituitary adenomas and tumours of breast, uterus or testis. - Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: max. dose level tested
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The possible formation of N-nitroso compounds in vivo from ingested secondary or tertiary amines and nitrite was determined by the incidence of tumour development. Thereby piperidine was administered to rats in the drinking water with or without sodium nitrite.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): piperidine
- no further data - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 8 - 10 weeks
- Housing: three animals per plastic cage
- Diet: Rockland rat diet ad libitum
- Water (e.g. ad libitum): tap water
ENVIRONMENTAL CONDITIONS
- no data - Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
- The test substance was dissolved in distilled water (pH 6.8-7.0).
VEHICLE
- Concentration in vehicle: 0.09 %
TREATMENT
- For administration the suspension was simply shaken before being put in the drinking-water bottles.
- On the five working days of the week each cage of rats was given 60 ml of the solution to drink and on the remaining 2 days tap-water was given.
- One group of animals was administered 0.09% piperidine in the drinking water without addition of sodium nitrite;
- Another group was administered 0.09% piperidine in the drinking water with 0.2% sodium nitrite. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 50 weeks
- Frequency of treatment:
- continuously in the drinking water (5 days per week)
- Post exposure period:
- From the end of the treatment, which lasted 50 weeks, the animaIs were kept until they died spontaneously or until they became moribund and were killed.
- Dose / conc.:
- 45 mg/kg bw/day (nominal)
- Remarks:
- corresponding to the original value 0.09 % in the drinking water, dased on a consumption of 25 mL/animal/day; total dose: 5625 mg/animal
- No. of animals per sex per dose:
- 15
- Control animals:
- other: The results from a historical control group receiving 0.2% sodium nitrite in the drinking water for 2 years (26 males and 30 females) served as control.
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: No data
CLINICAL CHEMISTRY: No data
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, each animal was subjected to a complete autopsy.
HISTOPATHOLOGY: Yes, the tissues were fixed for full histopathological examination. - Description (incidence):
- All animals in the two test groups survived for 20 weeks following cessation of exposure to the appropriate drinking water solution (i.e. through study week 70). Following is a list of survivors beginning on study week 90:
Test group 0.09% Piperidine: Males: Week 90: 10/15; Week 110: 4/15; Week 130: 0/15;
Test group 0.09% Piperidine: Females: Week 90: 11/15; Week 110: 7/15; Week 130: 1/15;
Test group 0.09% Piperidine with 0.2 % sodium nitrite: Males: Week 90: 11/15; Week 110: 2/15; Week 130: 0/15;
Test group 0.09% Piperidine with 0.2 % sodium nitrite: Females: Week 90: 10/15; Week 110: 3/15; Week 130: 1/15;
There was no significant difference in animal survival in any of the groups compared to the control. - Description (incidence and severity):
- - No data
- Description (incidence and severity):
- - No data
- Description (incidence and severity):
- - No data
- Description (incidence and severity):
- - Table 1: Incidence of tumours is given in the attachment.
- The tumour incidences were not significantly different in any of the groups compared to the control. - Description (incidence and severity):
- - No specific tumors from N-nitrosopiperidine were observed.
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 45 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: max. dose level tested
Referenceopen allclose all
Table 1 Tumours in Rats Treated with nitrosamino acids, amines and nitrite
Treatment |
Total dose (g) |
surviving animals at week |
No. TBA* (%) |
No. TF* |
Pitui-tary |
Breast |
Testis |
Uterus/Vagina |
Adrenal |
Pancreas |
Skin |
Other |
|||||
0 |
20 |
40 |
60 |
80 |
100 |
||||||||||||
Piperidine (0.1%) |
3.7 |
15♂
15♀ |
15
15 |
15
15 |
14
15 |
14
14 |
11
13 |
4 (27) 7 (57) |
11
8 |
1
4 |
0
1 |
2
0 |
0
1 |
0
0 |
1
0 |
1
0 |
1 brain 2 ovary, 1 thymus |
Piperidine (0.025%) + sodium nitrite (0.05%) |
1.8
3.7 |
15♂
15♀ |
15
15 |
15
15 |
12
14 |
11
13 |
11
10 |
2 (13) 9 (60) |
13
6 |
2
8 |
0
0 |
0
0 |
0
3 |
0
0 |
0
0 |
0
0 |
1 liver |
Piperidine (0.1%) + sodium nitrite (0.2%) |
3.7
7.5 |
15♂
15♀ |
15
15 |
15
15 |
15
15 |
15
14 |
12
11 |
7 (57) 7(57) |
8
8 |
2
4 |
0
1 |
3
0 |
0
0 |
0
0 |
1
0 |
2
0 |
1 brain, 1 salivary gland, 1 ovary |
Sodium nitrite (0.2%) |
15.0 |
15♂
15♀ |
15
15 |
15
15 |
15
14 |
15
13 |
13
12 |
9 (60) 10 (67) |
6
5 |
1
6 |
0
2 |
2
0 |
0
1 |
1
0 |
1
0 |
3
1 |
3 soft tissue, 1 stomach, 1 thymus |
Untreated control |
|
15♂
15♀ |
15
15 |
14
15 |
14
15 |
14
14 |
11
13 |
5 (33) 4 (27) |
10
11 |
0
3 |
0
1 |
3
0 |
0
1 |
0
0 |
1
0 |
0
0 |
1 soft tissue |
*TBA - Tumor bearing animals, TF = Tumor free
Table 1: Incidence of tumours after administration of Piperidine to rats in the drinking water with and without sodium nitrite.
Tumour location |
Control (0.2% sodium nitrite) |
0.09% Piperidine |
Piperidine with 0.2% Sodium Nitrite |
||||
F (30) |
M (26) |
F (15) |
M (15) |
F (15) |
M (15) |
||
Breast |
18 |
3 |
9 |
1 |
8 |
1 |
|
Pituitary |
20 |
6 |
8 |
0 |
9 |
6 |
|
Adrenal |
7 |
10 |
4 |
3 |
3 |
5 |
|
Uterus |
9 |
- |
5 |
- |
3 |
- |
|
Pancreas |
1 |
4 |
1 |
1 |
0 |
0 |
|
Liver |
0 |
1 |
0 |
0 |
1 |
1 |
|
Thyroid |
4 |
4 |
0 |
1 |
0 |
3 |
|
|
|
|
|
|
|
|
|
Type of tumor |
|
|
|
|
|
|
|
Duodenum |
0 |
3 |
1 |
0 |
0 |
0 |
|
Zimball gland |
1 |
1 |
1 |
1 |
0 |
0 |
|
Stomach |
0 |
1 |
0 |
0 |
0 |
0 |
|
Brain |
0 |
1 |
0 |
0 |
0 |
1 |
|
Ileum |
1 |
0 |
0 |
0 |
0 |
0 |
|
Thymus |
1 |
0 |
0 |
0 |
0 |
0 |
|
Myeloma |
1 |
0 |
0 |
0 |
0 |
0 |
|
Kidney |
0 |
0 |
1 |
0 |
0 |
0 |
|
Lymphosarcoma |
0 |
0 |
1 |
0 |
0 |
1 |
|
Skin |
Papilloma |
0 |
0 |
0 |
2 |
0 |
0 |
Sarcoma |
0 |
0 |
0 |
0 |
0 |
1 |
|
Jejunum |
0 |
0 |
0 |
1 |
0 |
0 |
|
Seminal vesicle |
- |
0 |
- |
1 |
- |
0 |
|
Osteosarcoma |
0 |
0 |
1 |
0 |
0 |
0 |
|
Heart myxoma |
0 |
0 |
0 |
1 |
0 |
0 |
|
Testis mesothelioma |
- |
0 |
- |
0 |
- |
1 |
|
Sarcoma |
0 |
0 |
0 |
0 |
0 |
1 |
|
Lung adenoma |
0 |
0 |
0 |
0 |
1 |
0 |
M: Male; F: Female
Number in patenthesis (number of animals)
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data for carcinogenicity are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. As a result, the substance is not warranted to be classified for carcinogenicity, under Regulation (EC) No.1272/2008.
Additional information
Oral
Lijinsky and Taylor (1977) performed a non-GLP, non-Guideline study in which groups of Sprague-Dawley rats (15/dose/sex), 8 – 10 weeks old, were administered 0.09 % piperidine (ca. 45 mg/kg bw/day) continuously in the drinking water with and without 0.2% sodium nitrite 5 days per week for 50 week. Each animal was subjected to gross pathology and histopathology. There was no significant difference in animal survival in the treatment groups compared to the control. No treatment related neoplasm developed during the lifetime of either test group. Thus the incidence of tumors for rats chronically exposed to 0.09% piperidine or 0.09% piperidine with 0.2% sodium nitrite was not significantly increased as compared to control rats receiving 0.2% sodium nitrite in drinking water. There was no untreated control.
In a non-GLP, non-Guideline drinking water study (Garcia and Lijinsky, 1973) simultaneous administration of nitrite and piperidine was proved to increase the incidence of tumor development. Thereby, groups of 15 female and 15 male MRC rats, 8 to 10 weeks old, received 5 days / week over 75 weeks each 100 ml of a solution as drinking water containing either 0.1% piperidine alone, 0.1 % (ca. 50 mg/kg bw/day) or 0.025% piperidine combined with 0.2 % or 0.05 % sodium nitrite, respectively. After treatment the animals were held until death and examined for tumor development. None of the treated groups showed significant differences in survival rate and the number and range of the incidence of tumors, compared with an untreated control.
Suzuki et al., 1984 detected a significant increase in the incidence of urinary bladder cancer by implanting cholesterol pellets containing piperidine into the bladder of mice and concurrent administration of sodium nitrite to the animals. In the non-GLP and non-Guideline study, groups of female mice of the ddy strain, about 18 g in weight, were administered 20 mg pellets consisting of cholesterol and 20% piperidine hydrochloride surgically into the bladder (total piperidine content 2.8 mg) with and without concurrent administration of 0.1 % sodium nitrite in the drinking water for 40 weeks. As controls, mice were implanted with cholesterol pellets without piperidine hydrochloride. The bladder of each animal was subjected to histopathological examination and incidence of urinary bladder cancer was determined. A significant increase in the incidence of bladder tumours of the animals by simultaneous administration of piperidine and nitrite was detected. No significant increase was observed following exposure to piperidine alone. The authors concluded that in the bladder of the animals N-Nitrosopiperidine was generated from piperidine and N-nitrite, leading to an enhanced incidence of bladder cancer.
Due to the special application form of the test substances as urinary bladder implantation, the biological relevance of this study is questionable.
Additionally, it has been demonstrated that in the stomach and the small intestine of the rat as well as in vitro in isolated gastric juice (Alam et al., 1971) sodium nitrite and piperidine react to form N-nitrosopiperidine. Thus, an indirect carcinogenic effect of piperidine following formation of N-nitrosopiperidine cannot be excluded.
Nevertheless, there was no evidence of carcinogenicity when piperidine was administered to rats in drinking water with or without sodium nitrite.
Inhalative
No studies are available on the carcinogenicity of piperidine administered by inhalation exposure.
Dermal
No data available
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