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EC number: 217-775-8 | CAS number: 1951-97-9
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- fertility, other
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- Details not available
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- not specified
- Sex:
- female
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Details not available
- Frequency of treatment:
- Details not available
- Remarks:
- Doses / Concentrations:
100, 250 and 500 mg
Basis:
no data - No. of animals per sex per dose:
- 5 rabbits
- Control animals:
- yes
- Details on study design:
- A reproduction study using oral administration of doses 100, 250 and 500 mg piperazine phosphate per kg body weight by gavage.
- Parental animals: Observations and examinations:
- Study showed dose dependent maternal toxicity culminating at the highest dose in death of does (2), abortion (1) and increase of major abnormalities in pups (23% versus 1.7% in controls).
- Litter observations:
- The main abnormalities observed were cleft palate and umbilical hernia; otherwise rarely seen in the strains of rabbit used
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- dose dependent maternal toxicity culminating at the highest dose in death of does (2), abortion (1)
- Dose descriptor:
- dose level:
- Effect level:
- > 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Piperazine in doses higher than 100 mg/kg bw/daycould provoke maternotoxicity, which can contribute to teratological effects as a consequence (at high dose levels )
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The main abnormalities observed were cleft palate and umbilical hernia; otherwise rarely seen in the strains of rabbit used
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Conclusions:
- Piperazine in doses higher than 100 mg/kg bw/daycould provoke maternotoxicity, which can contribute to teratological effects as a consequence (at high dose levels )
- Executive summary:
In the study using 5 rabbits, a study on reproduction by oral administration of doses 100, 250 or 500 mg piperazine posphate /kg bw per gavage showed dose dependent maternal toxicity culminating at the highest dose in death, abortion and increases of major abnormalities in pups (23% versus 1.7% in controls). The main abnormalities observed were cleft palate and umbalical hernia , otherwise rarely seen in the strains of rabbits used. Piperazine in doses higher than 100 mg/kg bw/daycould provoke maternotoxicity, which can contribute to teratological effects as a consequence (at high dose levels ). Thus, it can be summarised that piperazine phosphate is likely to be reprotoxic substance at higher doses.
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rabbit
Additional information
The summary of the weight of evidence studies in support of piperazine phosphate being classified as a repro-toxic substance is furnished below
S. No |
Dose level |
Species |
Effect |
Source of data |
1 |
100 mg/kg bw/day (NOAEL) |
Rabbit |
Maternotoxicity |
The European Agency for the Evaluation of Medicinal Products Veterinary medicines and Inspections |
2 |
125 mg/kg bw/day (NOAEL) |
Sprague-Dawley Rat |
Parental toxicity |
European Union Risk Assessment Report : Piperazine |
Short description of key information:
In the study using 5 rabbits, a study on reproduction by oral administration of doses 100, 250 or 500 mg piperazine posphate /kg bw per gavage showed dose dependent maternal toxicity culminating at the highest dose in death, abortion and increases of major abnormalities in pups (23% versus 1.7% in controls). The main abnormalities observed were cleft palate and umbalical hernia , otherwise rarely seen in the strains of rabbits used. Piperazine in doses higher than 100 mg/kg bw/daycould provoke maternotoxicity, which can contribute to teratological effects as a consequence (at high dose levels ). Thus, it can be summarised that piperazine phosphate is likely to be reprotoxic substance at higher doses.
Justification for selection of Effect on fertility via oral route:
Data has been taken from published report of the European Agency for the evaluation of medicinal products veterinary medicines and Inspections
Effects on developmental toxicity
Description of key information
Piperazine phosphate does not appear to be teratogenic in rat. However, in rabbit teratogenic effects may be elicited at a dose level that is also toxic to the mother animal. Thus, the teratogenic effect of piperazine phosphate remains inconclusive and since there is no classification in the CLP inventory suggesting "teratogenicity" for piperazine phosphate, the chemical is not considered to be teratogenic.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- Data is from Report to Reckitt and Coleman from Toxicol Laboratories Ltd.,
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Route of administration:
- other: oral intubation
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: methyl cellulose
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- The females were treated from days 6 to 18 of pregnancy
- Frequency of treatment:
- females were treated from days 6 to 18 of pregnancy
- Duration of test:
- 28 days
- Remarks:
- Doses / Concentrations:
0, 100, 225, and 500 mg piperazine phosphate per kg bw
Basis:
no data - No. of animals per sex per dose:
- 16 animals
- Details on study design:
- At 210 mg/kg/day piperazine base overt signs of toxicity were observed in the treated dams including signs of neurotoxicity as demonstrated
by excessive salivation and nervousness noted in all treated animals. Other symptoms of adverse effects were anorexia, reduced or no faeces production, reduced food intake (e.g., by 85% days 6-14) coupled with body weight loss (high dose animals lost 9% of body weight whereas controls gained 6%).
Two females were killed in extremis and one female aborted.The sacrificed females were found to have intestinal abnormalities including erosion of the mucosa of the stomach or duodenum. At 94 mg/kg/day piperazine base, there were no effects on body weight, although food consumption (-39%) and body weight gain were transiently reduced during the 4 first days of dosing. One female aborted, and five females were observed with reduced faeces production for short periods. One female died, but this was ascribed to accidental dosing into the lungs. - Fetal examinations:
- The foetuses were subjected to detailed external, visceral and skeletal examination.
- Dose descriptor:
- NOAEL
- Effect level:
- 42 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Remarks on result:
- other: not specified
- Dose descriptor:
- LOAEL
- Effect level:
- 94 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Remarks on result:
- other: not specified
- Abnormalities:
- not specified
- Localisation:
- not specified
- Description (incidence and severity):
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes. Remark: Fetal weight reduced and feotuses exhibited major abnormalities like umbilical hernia and cleft palate
- Dose descriptor:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Abnormalities:
- not specified
- Localisation:
- other: not specified
- Description (incidence and severity):
- not specified
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Conclusions:
- In the New Zealand rabbit, embryotoxic as well as teratogenic effects were elicited at doses that also caused overt signs of toxicity in the mother animal (maternal LOAEL 94/ NOAEL 42 mg/kg/day).
No effects were observed at 42 mg/kg/day of piperazine base.Although borderline, 94 mg/kg/day piperazine base may be considered to constitute the maternal LOAEL in this study. - Executive summary:
In the New Zealand rabbit, embryotoxic as well as teratogenic effects were elicited at doses that also caused overt signs of toxicity in the mother animal (maternal LOAEL 94/ NOAEL 42 mg/kg/day).
No effects were observed at 42 mg/kg/day of piperazine base.Although borderline, 94 mg/kg/day piperazine base may be considered to constitute the
maternal LOAEL in this study.
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- Study duration:
- subacute
- Species:
- rat
Additional information
The summary of the weight of evidence studies in support of piperazine phosphate not being classified as a teratogenic substance is furnished below. Thus, the teratogenic effect of piperazine phosphate remains inconclusive and since there is no classification in the CLP inventory suggesting "teratogenicity" for piperazine phosphate, the chemical is not considered to be teratogenic.
S. No |
Dose level |
Species |
Effect |
Source of data |
1 |
42 mg/kg bw/day (NOAEL) |
Rabbit (New Zealand White) |
Developmental toxicity |
European Union Risk Assessment Report : Piperazine |
2 |
250 to < 5000 mg/kg bw/day (nominal) (LOAEL) |
Rat Crj: CD(SD) |
Lower foetal weight was recorded but no evidence of teratogenecity was reported at any dose level. |
Piperazine phosphate, Rat teratology study; Report to Reckitt and Coleman from Toxicol. Laboratory Limited |
3 |
94 mg/kg bw/day (LOAEL)
|
Rabbit (New Zealand White) |
No symptoms of teratogenecity, only maternal toxicity observed |
USEPA High volume program (HPV) report |
Justification for selection of Effect on developmental toxicity: via oral route:
Data has been published in the European Union Risk Assessment Report of Piperazine
Justification for classification or non-classification
Additional information
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.
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